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Sample records for presumed uveal melanomas

  1. Clinical Course of a Presumed Metastatic Uveal Melanoma to the Contralateral Choroid.

    Science.gov (United States)

    Caminal Mitjana, Josep M; Vilà Grané, Natàlia; Adán Civera, Alfredo; Sabater, Noelia; Arias Barquet, Lluis; Rubio Caso, Marcos J

    2015-01-01

    We present the ultrasound and optic coherence tomography follow-up of a presumed choroidal metastasis from a contralateral melanoma. A 53-year-old male was diagnosed with uveal melanoma with extraescleral extension in his left eye. A year later, the fundus examination revealed a flat, gray-green, pigmented choroidal lesion in the right eye. The ultrasonography showed a mass, almost flat, and all these findings were compatible with a choroidal melanocytic lesion with risk factors for growth. One month later, melanocytic skin lesions appeared on the scalp, as well as small tumors. Three months later, an ultrasonography on B scan showed a growth of the tumor size. The patient developed a progressive deterioration and died. Three possibilities can explain the occurrence of a choroidal pigmented tumor in the contralateral eye: first, bilateral primary choroidal melanomas; second, both choroidal tumors are metastatic in origin from an unknown primary melanoma; and third, the contralateral tumor is a metastatic tumor from the primary choroidal melanoma.

  2. Uveal Melanoma

    International Nuclear Information System (INIS)

    Papastefanou, V. P.; Cohen, V. M. L.; Cohen, V. M. L.

    2011-01-01

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

  3. Uveal melanoma: estimating prognosis.

    Science.gov (United States)

    Kaliki, Swathi; Shields, Carol L; Shields, Jerry A

    2015-02-01

    Uveal melanoma is the most common primary malignant tumor of the eye in adults, predominantly found in Caucasians. Local tumor control of uveal melanoma is excellent, yet this malignancy is associated with relatively high mortality secondary to metastasis. Various clinical, histopathological, cytogenetic features and gene expression features help in estimating the prognosis of uveal melanoma. The clinical features associated with poor prognosis in patients with uveal melanoma include older age at presentation, male gender, larger tumor basal diameter and thickness, ciliary body location, diffuse tumor configuration, association with ocular/oculodermal melanocytosis, extraocular tumor extension, and advanced tumor staging by American Joint Committee on Cancer classification. Histopathological features suggestive of poor prognosis include epithelioid cell type, high mitotic activity, higher values of mean diameter of ten largest nucleoli, higher microvascular density, extravascular matrix patterns, tumor-infiltrating lymphocytes, tumor-infiltrating macrophages, higher expression of insulin-like growth factor-1 receptor, and higher expression of human leukocyte antigen Class I and II. Monosomy 3, 1p loss, 6q loss, and 8q and those classified as Class II by gene expression are predictive of poor prognosis of uveal melanoma. In this review, we discuss the prognostic factors of uveal melanoma. A database search was performed on PubMed, using the terms "uvea," "iris," "ciliary body," "choroid," "melanoma," "uveal melanoma" and "prognosis," "metastasis," "genetic testing," "gene expression profiling." Relevant English language articles were extracted, reviewed, and referenced appropriately.

  4. Uveal melanoma: Estimating prognosis

    Directory of Open Access Journals (Sweden)

    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.

  5. 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.

  6. Tumor progression in uveal melanoma

    NARCIS (Netherlands)

    C.M. Mooij (Cornelia)

    1995-01-01

    textabstractOphthalmic melanomas can be divided in extra-ocular (conjunctiva, caruncle) and intraocular uveal melanomas (iris, ciliary body and choroid). Uveal melanomas account for 95% of ocular melanomas, while only 5% are conjunctival in origin. The extra-ocular and intra-ocular melanomas differ

  7. Congenital uveal melanoma?

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    Singh, Arun D; Schoenfield, Lynn A; Bastian, Boris C; Aziz, Hassan A; Marino, Meghan J; Biscotti, Charles V

    2016-01-01

    A 3-month-old infant with a white mother and Asian father presented with discoloration and prominence of the left eye since birth. Examination revealed a normal right eye. The left eye had hyperchromic heterochromia and an enlarged cornea (diameter, 13.0 mm) with intraocular pressure of 26 mm Hg. There were multiple areas of subconjunctival nodular pigmentation that extended posteriorly into the superior fornix. Fundus examination showed a large ciliochoroidal pigmented mass extending from 10:30 to 3:00 o'clock position involving the superior half of the choroid and adjacent ciliary body. The eye was enucleated, confirming the diagnosis of diffuse uveal melanoma with extraocular extension. Systemic surveillance (hepatic panel and ultrasonography of the liver) performed every 6 months for 5 years was has been negative for metastases. The tumor was investigated intensively for the panel of genes (BAP1, BRAF, NRAS12, NRAS61, GNAQ, Kit 9,11,13,17,18) implicated in pathogenesis of blue nevus, cutaneous melanoma, and mucosal melanomas with negative results. Moreover, germline BAP1 mutation could not be identified. This case possibly represents as yet unidentified uveal melanocytic proliferation rather than a true variant of uveal melanoma. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Angiogenic profile of uveal melanoma.

    NARCIS (Netherlands)

    Notting, I.C.; Missotten, G.S.; Sijmons, B.; Boonman, Z.F.; Keunen, J.E.E.; Pluijm, G. van der

    2006-01-01

    Uveal melanoma develops in one of the most capillary-rich tissues of the body and is disseminated hematogenously. Knowledge of the nature and the spatiotemporal expression of angiogenic factors in uveal melanoma is essential to the development of new treatment strategies, especially with regard to

  9. Genetic Abnormalities in Uveal Melanoma

    NARCIS (Netherlands)

    N.C. Naus (Nicole)

    2001-01-01

    textabstractMelanocytic tumours are believed to arise from the neural crest-derived melanocytes. Five to twelve percent of all melanomas are located in the eye, making it, after the skin, the second most common site of melanomas (Egan et al., 1988; Chang et al., 1998). Uveal melanoma is the most

  10. Prognostic Factors in Uveal Melanoma

    NARCIS (Netherlands)

    E. Kiliç (Emine)

    2006-01-01

    textabstractUveal melanoma is the most common intra-ocular tumour in the western world with an annual incidence of seven per million. Approximately 50% of the patients treated by enucleation dye eventually due to metastatic disease. Besides enucleation there are nowadays more conservative treatment

  11. UVEAL MELANOMA EXTENSION TO THE OPTIC CHIASM.

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    Abdellatief, Amro; Pulido, Jose S; Bartley, George B; Salomao, Diva R; Quinn, Timothy A

    2016-01-01

    Case report describing a patient who developed intracranial extension of a uveal melanoma through the optic nerve. We reviewed the patient's medical history and images. A 41-year-old woman who was blind in one eye had a uveal melanoma that extended through the optic nerve into the optic chiasm and involved the hypophysis. The patient then developed metastasis. The patient developed uveal melanoma extension into the optic chiasm through the optic nerve resulting in a visual field defect in the fellow eye. Uveal melanoma extension through the optic nerve is a devastating complication, which occurs anywhere from 0.6% to 3.7% in patients with uveal melanoma. If enucleation of the affected eye is performed, a representative portion of the optic nerve should be excised to decrease the risk of extension. Patients with phthisical eyes should undergo appropriate imaging techniques to prevent a missed diagnosis of optic nerve involvement.

  12. Epidemiology of uveal melanomas in Moscow

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    E. E. Grishina

    2017-01-01

    Full Text Available Rationale: Melanoma of the uveal tract of the eye is among the most prevalent malignant intraocular tumors.Aim: To identify epidemiological characteristics of uveal melanoma in Moscow.Materials and methods: We performed a retrospective analysis of out-patient files and follow-up charts of patients with uveal melanoma in the Ophthalmological Clinical Hospital of the Department of Healthcare, Moscow, from 1977 to 2012.Results: Within 36 years, 2547 patients with uveal melanoma have been registered, at the age of 16 to 92 years. The male to female ratio was 1:1.5. The rate of patient referrals with subsequent diagnosis of uveal melanoma has not changed from 1977 to 2000 and was on average 1.07 persons per 100,000 of the adult population. From 2001 to 2012, there was some decline in the number of referrals with uveal melanoma to the average of 0.9 persons per 100,000 of the adult population. We analyzed survival among 359 patients with uveal melanoma after enucleation surgery of the eye; 37% of them were men (63.2 ± 1.8 years and 63% women (69.5 ± 2.7 years. Their 5-year metastasis-free survival was 65 ± 3%, whereas the 7-year survival was 60 ± 4%. The mean time to death was 5.5 years. There were no association between the life longevity and patients gender, but their survival was associated with the age of patients. The risk of death from metastatic uveal melanoma among patients above 60 years of age was on average 10% higher. After the enucleation surgery, patients with Т4 melanoma lived significantly less than those with Т1-3 tumor (5 and 6.5 years, respectively; р = 0.05.Conclusion: The rates of diagnosis of uveal melanoma at referrals within 36 years did not increased. Epidemiology of uveal melanoma in Moscow is characterized by a high proportion of elderly women. Shorter overall and metastasis-free survival of patients with uveal melanoma after the enucleation surgery depends from a higher proportion

  13. Genetic prognostic factors in uveal melanoma

    NARCIS (Netherlands)

    Maat, Willem

    2012-01-01

    Uveal melanoma (UM) is the most common malignancy of the eye in adults and it is the second most common form of melanoma after cutaneous melanoma (CM). The identification of patients who have a high risk of developing metastases would allow the possibility of providing adjuvant therapies to prevent

  14. Glaucoma secundario a melanoma uveal

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    Nairovys Gómez Martínez

    2017-09-01

    Full Text Available Introducción: Los tumores localizados en iris y cuerpo ciliar son poco frecuentes y puede ser valorada su resección local como alternativa terapéutica. El melanoma uveal representa el 79-81% de los melanomas oculares y el 3-5% de todos los melanomas. Objetivo: Dar a conocer el caso de una patología infrecuente con pocos casos reportados en la literatura, enfatizar su importancia dentro de los diagnósticos diferenciales y del estudio histopatológico. Descripción del caso: Paciente femenina de 47 años de edad, quien acudió a la consulta de oftalmología, para valoración de una lesión pigmentada en endotelio corneal y en iris asociada a hipertensión ocular y pérdida de la agudeza visual en el ojo izquierdo de cuatro meses de evolución. La biomicroscopía ultrasónica confirmó la presencia de una masa iridiana, localizada en la periferia del iris. El estudio anatomopatológico mostró una proliferación de células névicas pleomórficas que reemplazaban el estroma normal del iris. Conclusiones: En pacientes que presentan una clínica de glaucoma unilateral refractario a tratamiento farmacológico junto con dispersión de pigmento es importante una exploración exhaustiva destacando el papel de la biomicroscopía ultrasónica.

  15. Identification of an Immunogenic Subset of Metastatic Uveal Melanoma.

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    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.

  16. Optic nerve invasion of uveal melanoma

    DEFF Research Database (Denmark)

    Lindegaard, Jens; Isager, Peter; Prause, Jan Ulrik

    2007-01-01

    The aim of the study was to identify the histopathological characteristics associated with the invasion of the optic nerve of uveal melanoma and to evaluate the association between invasion of the optic nerve and survival. In order to achieve this, all uveal melanomas with optic nerve invasion...... in Denmark between 1942 and 2001 were reviewed (n=157). Histopathological characteristics and depth of optic nerve invasion were recorded. The material was compared with a control material from the same period consisting of 85 cases randomly drawn from all choroidal/ciliary body melanomas without optic nerve...... invasion. Prelaminar/laminar optic nerve invasion was in multivariate analysis associated with focal retinal invasion, neovascularization of the chamber angle, and scleral invasion. Postlaminar invasion was further associated with non-spindle cell type and rupture of the inner limiting membrane...

  17. Uveal melanoma: relatively rare but deadly cancer

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    Kaliki, S; Shields, C L

    2017-01-01

    Although it is a relatively rare disease, primarily found in the Caucasian population, uveal melanoma is the most common primary intraocular tumor in adults with a mean age-adjusted incidence of 5.1 cases per million per year. Tumors are located either in iris (4%), ciliary body (6%), or choroid (90%). The host susceptibility factors for uveal melanoma include fair skin, light eye color, inability to tan, ocular or oculodermal melanocytosis, cutaneous or iris or choroidal nevus, and BRCA1-associated protein 1 mutation. Currently, the most widely used first-line treatment options for this malignancy are resection, radiation therapy, and enucleation. There are two main types of radiation therapy: plaque brachytherapy (iodine-125, ruthenium-106, or palladium-103, or cobalt-60) and teletherapy (proton beam, helium ion, or stereotactic radiosurgery using cyber knife, gamma knife, or linear accelerator). The alternative to radiation is enucleation. Although these therapies achieve satisfactory local disease control, long-term survival rate for patients with uveal melanoma remains guarded, with risk for liver metastasis. There have been advances in early diagnosis over the past few years, and with the hope survival rates could improve as smaller tumors are treated. As in many other cancer indications, both early detection and early treatment could be critical for a positive long-term survival outcome in uveal melanoma. These observations call attention to an unmet medical need for the early treatment of small melanocytic lesions or small melanomas in the eye to achieve local disease control and vision preservation with the possibility to prevent metastases and improve overall patient survival. PMID:27911450

  18. Tissue-Based Microarray Expression of Genes Predictive of Metastasis in Uveal Melanoma and Differentially Expressed in Metastatic Uveal Melanoma

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    Hakan Demirci

    2013-01-01

    Full Text Available Purpose: To screen the microarray expression of CDH1, ECM1, EIF1B, FXR1, HTR2B, ID2, LMCD1, LTA4H, MTUS1, RAB31, ROBO1, and SATB1 genes which are predictive of primary uveal melanoma metastasis, and NFKB2, PTPN18, MTSS1, GADD45B, SNCG, HHIP, IL12B, CDK4, RPLP0, RPS17, RPS12 genes that are differentially expressed in metastatic uveal melanoma in normal whole human blood and tissues prone to metastatic involvement by uveal melanoma. Methods: We screened the GeneNote and GNF BioGPS databases for microarray analysis of genes predictive of primary uveal melanoma metastasis and those differentially expressed in metastatic uveal melanoma in normal whole blood, liver, lung and skin. Results: Microarray analysis showed expression of all 22 genes in normal whole blood, liver, lung and skin, which are the most common sites of metastases. In the GNF BioGPS database, data for expression of the HHIP gene in normal whole blood and skin was not complete. Conclusions: Microarray analysis of genes predicting systemic metastasis of uveal melanoma and genes differentially expressed in metastatic uveal melanoma may not be used as a biomarker for metastasis in whole blood, liver, lung, and skin. Their expression in tissues prone to metastasis may suggest that they play a role in tropism of uveal melanoma metastasis to these tissues.

  19. Molecular Prognostic Markers in Uveal Melanoma: Expression Profiling and Genomic Studies

    NARCIS (Netherlands)

    W. Gils (Walter)

    2008-01-01

    textabstractUveal Melanomas (UMs) arise from melanocytes. This cell type originates from neural crest cells and thereby uveal melanomas share their origin with pheochromocytomas, neuroblastomas, paragangliomas and cutaneous melanomas, other tumors that develop from neural crest originating cells.

  20. Stages of Intraocular (Uveal) Melanoma

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    ... or tans poorly. Blue or green or other light-colored eyes. Older age. Being white. Signs of intraocular melanoma include blurred vision ... to treat small tumors. This is also called light coagulation. ... are being tested in clinical trials. Information about clinical trials ...

  1. Proteomics of Uveal Melanoma: A Minireview

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    Søren K. O. Abildgaard

    2013-01-01

    Full Text Available Uveal melanoma (UM continues to be associated with a high mortality rate of up to 50% due to metastatic spread primarily to the liver. Currently there are relatively effective treatments for the primary tumor, though the management of the metastatic disease remains inadequate. Conventional diagnostic tools have a low sensitivity for detecting metastasis, and early detection of metastatic spread would allow more treatment options that could ultimately increase survival of UM patients. Advanced proteomic methods have already helped to find potential biomarkers associated with UM pathogenesis and metastasis. In the present review we discuss the field of proteomics in relation to studies elucidating biomarkers of UM, where proteins such as S-100β, osteopontin (OPN, and melanoma inhibitory activity (MIA have been shown to be associated with metastasis.

  2. Metastatic disease from uveal melanoma: treatment options and future prospects.

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    Carvajal, Richard D; Schwartz, Gary K; Tezel, Tongalp; Marr, Brian; Francis, Jasmine H; Nathan, Paul D

    2017-01-01

    Uveal melanoma represents ∼85% of all ocular melanomas and up to 50% of patients develop metastatic disease. Metastases are most frequently localised to the liver and, as few patients are candidates for potentially curative surgery, this is associated with a poor prognosis. There is currently little published evidence for the optimal management and treatment of metastatic uveal melanoma and the lack of effective therapies in this setting has led to the widespread use of systemic treatments for patients with cutaneous melanoma. Uveal and cutaneous melanomas are intrinsically different diseases and so dedicated management strategies and therapies for uveal melanoma are much needed. This review explores the biology of uveal melanoma and how this relates to ongoing trials of targeted therapies in the metastatic disease setting. In addition, we consider the options to optimise patient management and care. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  3. Ruthenium-106 plaque brachytherapy for uveal melanoma.

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    Tarmann, Lisa; Wackernagel, Werner; Avian, Alexander; Mayer, Christoph; Schneider, Mona; Winkler, Peter; Langmann, Gerald

    2015-12-01

    To report on local tumour control, eye preservation and visual outcome after ruthenium-106 brachytherapy for uveal melanoma. Medical records of 143 eyes with uveal melanoma, treated by ruthenium-106 brachytherapy between 1997 and 2012 at one single centre, were included. Primary outcome measures were local tumour control, eye preservation and visual outcome. The influence of patient, tumour and treatment parameters on outcome was analysed by time to event analysis and competing risk regression. The median overall follow-up was 37.9 months. Tumour control: recurrent tumour growth was observed in 17 patients. The estimated local tumour recurrence rate at 12, 24 and 48 months after irradiation was 3%, 8.4% and 14.7%, respectively. The only significant risk factors for tumour recurrence were age (p=0.046) and reduced initial visual acuity (VA, p=0.045). No significant difference could be shown for tumour size or tumour category (T1-T2 vs T3-T4), and for any other tumour or treatment parameters (including combined transpupillary thermo-therapy (TTT)).Eye preservation: The likelihood of keeping the eye 12, 24 and 48 months after irradiation was 97.7%, 94.7% and 91.8%, respectively. Most significant risk factors for secondary enucleation were initial VA (peye preservation and visual function. Adjunct sandwich therapy resulted in worse visual outcome. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  4. Nestin expression in primary and metastatic uveal melanoma - possible biomarker for high-risk uveal melanoma.

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    Djirackor, Luna; Shakir, Dilem; Kalirai, Helen; Petrovski, Goran; Coupland, Sarah E

    2018-01-16

    Nestin, a member of the intermediate filament protein family, has been described as a putative cancer stem cell marker (CSC) in uveal melanoma and poor prognostic factor in a variety of tumours, including cutaneous melanoma. In this study, we examined the expression of nestin in primary (PUM) and metastatic uveal melanoma (MUM) samples, and correlated the findings with histological, clinical and survival data. Nestin expression was assessed by immunohistochemistry in 141 PUM and 26 MUM samples; 11 PUM cases were matched with their corresponding metastases. The percentage of tumour cells expressing nestin was scored by three independent observers. Statistical analysis of all data was performed with SPSS. Nestin expression was identified in both the cytoplasm and membrane of UM cells. Increased expression of nestin in PUM samples was associated with known poor prognostic parameters, including epithelioid cell morphology (p < 0.001), closed loops (p = 0.001), higher mitotic count (p < 0.001), monosomy 3 (p = 0.007) and chromosome 8q gain (p < 0.001). Primary uveal melanoma (PUM) with nestin expression levels above a cut-off value of 10% [as determined by receiver operating characteristic (ROC) analysis] was associated with a significantly reduced survival time (Log-rank, p = 0.002). In MUM, a higher percentage of nestin-positive tumour cells combined with poor prognostic markers in the PUM led to a shorter survival time following the development of metastases. In conclusion, increased nestin expression in PUM is a predictor of a tumour phenotype associated with metastatic progression and reduced survival time at onset of metastasis. © 2018 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  5. Treatment of uveal melanoma: where are we now?

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    Yang, Jessica; Manson, Daniel K.; Marr, Brian P.; Carvajal, Richard D.

    2018-01-01

    Uveal melanoma, a rare subset of melanoma, is the most common primary intraocular malignancy in adults. Despite effective primary therapy, nearly 50% of patients will develop metastatic disease. Outcomes for those with metastatic disease remain dismal due to a lack of effective therapies. The unique biology and immunology of uveal melanoma necessitates the development of dedicated management and treatment approaches. Ongoing efforts seek to optimize the efficacy of targeted therapy and immunotherapy in both the adjuvant and metastatic setting. This review provides a comprehensive, updated overview of disease biology and risk stratification, the management of primary disease, options for adjuvant therapy, and the current status of treatment strategies for metastatic disease. PMID:29497459

  6. 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.

  7. Fluorescence angiography of iris in malignant uveal melanoma

    International Nuclear Information System (INIS)

    Boguszakova, J.; Dubska, Z.

    1988-01-01

    Fluorescence angiography of the iris was performed in 12 eyes with malignant uveal melanoma. Tumors localized in front of the equator, without respect to their cellular types, caused secondary fluoroangiographic changes in the iris corresponding to the location of these tumors. The character and degree of changes corresponded to the mechanical effect of the malignant melanoma. (author). 8 figs., 3 tabs., 10 refs

  8. Regression of posterior uveal melanomas following cobalt-60 plaque radiotherapy

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    Cruess, A.F.; Augsburger, J.J.; Shields, J.A.; Brady, L.W.; Markoe, A.M.; Day, J.L.

    1984-12-01

    A method has been devised for evaluating the rate and extent of regression of the first 100 consecutive patients with a posterior uveal melanoma that had been managed by Cobalt-60 plaque radiotherapy at Wills Eye Hospital. It was found that the average posterior uveal melanoma in the series did not regress rapidly to a flat, depigmented scar but shrank slowly and persisted as a residual mass approximately 50% of the thickness of the original tumor at 54 months following Cobalt-60 plaque radiotherapy. The authors also found that the rate and extent of regression of the tumors in patients who subsequently developed metastatic melanoma were not appreciably different from the rate and extent of regression of the tumors in patients who remained well systemically. These observations indicate that the rate and extent of regression of posterior uveal melanomas following Cobalt-60 plaque radiotherapy are poor indicators of the prognosis of the affected patients for subsequent development of clinical metastatic disease.

  9. Prognosis of uveal melanoma based on race in 8100 patients: The 2015 Doyne Lecture

    Science.gov (United States)

    Shields, C L; Kaliki, S; Cohen, M N; Shields, P W; Furuta, M; Shields, J A

    2015-01-01

    A retrospective, nonrandomized, interventional case series of 8100 patients with uveal melanoma were evaluated for melanoma-related metastasis based on patient race. The patient race was Caucasian (n=7918, 98%), Hispanic (n=105, 1%), Asian (n=44, melanoma based on race. In summary, uveal melanoma showed similar prognosis for all races. PMID:26248525

  10. Uveal Melanoma: Current Trends in Diagnosis and Management

    Science.gov (United States)

    Tarlan, Berçin; Kıratlı, Hayyam

    2016-01-01

    Uveal melanoma, which is the most common primary intraocular malignancy in adults, arises from melanocytes within the iris, ciliary body and choroid. The diagnosis is based principally on clinical examination of the tumor with biomicroscopy and indirect ophthalmoscopy and confirmed by diagnostic techniques such as ultrasonography, fundus fluorescein angiography and optical coherence tomography. The clinical diagnosis of posterior uveal melanomas can be made when the classical appearance of a pigmented dome-shaped mass is detected on dilated fundus exam. Uveal melanomas classically show low to medium reflectivity on A-scan ultrasonography and on B-scan ultrasonography the tumor appears as a hyperechoic, acoustically hollow intraocular mass. Management of a suspicious pigmented lesion is determined by its risk factors of transforming into a choroidal melanoma, such as documentation of growth, thickness greater than 2 mm, presence of subretinal fluid, symptoms and orange pigment, margin within 3 mm of the optic disc, and absence of halo and drusen. Advances in the diagnosis and local and systemic treatment of uveal melanoma have caused a shift from enucleation to eye-conserving treatment modalities including transpupillary thermotherapy and radiotherapy over the past few decades. Prognosis can be most accurately predicted by genetic profiling of fine needle aspiration biopsy of the tumor before the treatment, and high-risk patients can now be identified for clinical trials that may lead to target-based therapies for metastatic disease and adjuvant therapy which aims to prevent metastatic disease. PMID:27800275

  11. Prognostic Implications of Acquired Genetic Changes in Uveal Melanoma

    NARCIS (Netherlands)

    A.E. Koopmans (Anna)

    2015-01-01

    markdownabstractIn the last decade, genetic research in uveal melanoma (UM) has shifted from primarily cytogenetic workups to extensive molecular genetic analyses. Despite progress that has been made in understanding the genetic framework of UM, this disease still carries high mortality and patient

  12. Insights in tumorigenesis and metastasis of uveal melanoma

    NARCIS (Netherlands)

    Notting, Irene Christa

    2009-01-01

    For a long time enucleation has been the treatment of choice for uveal melanoma. New treatment modalities have been developed e.g. transscleral thermotherapy (TTT), proton beam radiation, stereotactic radiotherapy and ruthenium application 1-3 . These treatment options offer a better chance to spare

  13. Using risk factors for detection and prognostication of uveal melanoma

    Science.gov (United States)

    Rishi, Pukhraj; Koundanya, Vikram V; Shields, Carol L

    2015-01-01

    The early detection of malignancy, particularly uveal melanoma, is crucial in protecting visual acuity, salvaging the eye, and preventing metastasis. Risk factors for early detection of uveal melanoma have been clearly delineated in the literature and allow identification of melanoma when it is tiny and simulates a nevus. These factors include thickness >2 mm, presence of subretinal fluid (SRF), symptoms, the orange pigment, margin near optic disc, acoustic hollowness, surrounding halo, and absence of drusen. The importance of early detection is realized when one considers melanoma thickness, as each millimeter increase in melanoma thickness imparts 5% increased risk for metastatic disease. Newer imaging modalities like enhanced depth imaging optical coherence tomography and fundus autoflouroscence facilitate in detection of SRF and orange pigment. Additional molecular biomarkers and cytological features have been identified which can predict the clinical behavior of a small melanocytic lesion. Features that suggest a poor prognosis include higher blood levels of tyrosinase m-RNA, vascular endothelial growth factor, insulin-like growth factor; monosomy 3 and gains in chromosome 8. Management of uveal melanoma includes enucleation (for large), local eye wall resection, brachytherapy, charged particle irradiation, and thermotherapy (for small to medium tumors). Although the role of a good clinical evaluation cannot be underestimated, it is advisable to evaluate the various radiological, molecular, and cytological features, to enhance the accuracy of early diagnosis and improved prognosis. PMID:25827540

  14. Using risk factors for detection and prognostication of uveal melanoma

    Directory of Open Access Journals (Sweden)

    Pukhraj Rishi

    2015-01-01

    Full Text Available The early detection of malignancy, particularly uveal melanoma, is crucial in protecting visual acuity, salvaging the eye, and preventing metastasis. Risk factors for early detection of uveal melanoma have been clearly delineated in the literature and allow identification of melanoma when it is tiny and simulates a nevus. These factors include thickness >2 mm, presence of subretinal fluid (SRF, symptoms, the orange pigment, margin near optic disc, acoustic hollowness, surrounding halo, and absence of drusen. The importance of early detection is realized when one considers melanoma thickness, as each millimeter increase in melanoma thickness imparts 5% increased risk for metastatic disease. Newer imaging modalities like enhanced depth imaging optical coherence tomography and fundus autoflouroscence facilitate in detection of SRF and orange pigment. Additional molecular biomarkers and cytological features have been identified which can predict the clinical behavior of a small melanocytic lesion. Features that suggest a poor prognosis include higher blood levels of tyrosinase m-RNA, vascular endothelial growth factor, insulin-like growth factor; monosomy 3 and gains in chromosome 8. Management of uveal melanoma includes enucleation (for large, local eye wall resection, brachytherapy, charged particle irradiation, and thermotherapy (for small to medium tumors. Although the role of a good clinical evaluation cannot be underestimated, it is advisable to evaluate the various radiological, molecular, and cytological features, to enhance the accuracy of early diagnosis and improved prognosis.

  15. Irreversible electroporation of human primary uveal melanoma in enucleated eyes.

    Directory of Open Access Journals (Sweden)

    Yossi Mandel

    Full Text Available Uveal melanoma (UM is the most common primary intraocular tumor in adults and is characterized by high rates of metastatic disease. Although brachytherapy is the most common globe-sparing treatment option for small- and medium-sized tumors, the treatment is associated with severe adverse reactions and does not lead to increased survival rates as compared to enucleation. The use of irreversible electroporation (IRE for tumor ablation has potential advantages in the treatment of tumors in complex organs such as the eye. Following previous theoretical work, herein we evaluate the use of IRE for uveal tumor ablation in human ex vivo eye model. Enucleated eyes of patients with uveal melanoma were treated with short electric pulses (50-100 µs, 1000-2000 V/cm using a customized electrode design. Tumor bioimpedance was measured before and after treatment and was followed by histopathological evaluation. We found that IRE caused tumor ablation characterized by cell membrane disruption while sparing the non-cellular sclera. Membrane disruption and loss of cellular capacitance were also associated with significant reduction in total tumor impedance and loss of impedance frequency dependence. The effect was more pronounced near the pulsing electrodes and was dependent on time from treatment to fixation. Future studies should further evaluate the potential of IRE as an alternative method of uveal melanoma treatment.

  16. Irreversible electroporation of human primary uveal melanoma in enucleated eyes.

    Science.gov (United States)

    Mandel, Yossi; Laufer, Shlomi; Belkin, Michael; Rubinsky, Boris; Pe'er, Jacob; Frenkel, Shahar

    2013-01-01

    Uveal melanoma (UM) is the most common primary intraocular tumor in adults and is characterized by high rates of metastatic disease. Although brachytherapy is the most common globe-sparing treatment option for small- and medium-sized tumors, the treatment is associated with severe adverse reactions and does not lead to increased survival rates as compared to enucleation. The use of irreversible electroporation (IRE) for tumor ablation has potential advantages in the treatment of tumors in complex organs such as the eye. Following previous theoretical work, herein we evaluate the use of IRE for uveal tumor ablation in human ex vivo eye model. Enucleated eyes of patients with uveal melanoma were treated with short electric pulses (50-100 µs, 1000-2000 V/cm) using a customized electrode design. Tumor bioimpedance was measured before and after treatment and was followed by histopathological evaluation. We found that IRE caused tumor ablation characterized by cell membrane disruption while sparing the non-cellular sclera. Membrane disruption and loss of cellular capacitance were also associated with significant reduction in total tumor impedance and loss of impedance frequency dependence. The effect was more pronounced near the pulsing electrodes and was dependent on time from treatment to fixation. Future studies should further evaluate the potential of IRE as an alternative method of uveal melanoma treatment.

  17. Clinical observation of local resection or enucleation for uveal melanoma.

    Science.gov (United States)

    Hong, Mei; Wei, Wenbin; Hua, Lin; Xu, Xiaoling; Shao, Lei

    2014-01-01

    Local resection is an effective method for treating the uveal melanoma. The aim of this study is to evaluate the survival and clinical outcomes of patients with uveal melanoma treated by local resection or enucleation. Totally, 167 consecutive patients with uveal melanoma were recruited for the study, of whom 57 patients were treated with local resection and 110 patients were treated with enucleation. The main outcome was measured by the visual acuity, local recurrence, eye retention, metastases, and melanoma-related mortality. There were statistically significant differences in the largest basal diameter of the tumor (t = -3.441), the tumor thickness (t = -4.140), the ciliary body infiltration (χ(2) = 8.391), and the duration of follow-up (Z = 3.995) between the two groups (P 0.05); the 5-year melanoma-related mortality was 16.27% for the group with local resection and 25.33% for enucleation (χ(2) = 1.304, P > 0.05). The 5-year local tumor recurrence rate was 29.50% and the 5-year accumulated eye retention rate was 69.00% after local resection. The visual acuity which light perception or better of 60 months after local resection was observed in 25 (92.60%) among persons retaining eye. The survival outcomes of the patients with local resection were not worse than that of the patients with enucleation, and local resection could make the patient retain eye and partial visual functions. Hence, local resection may be an effective method for patients with uveal melanoma eligible for operation.

  18. Uveal melanoma: From diagnosis to treatment and the science in between.

    Science.gov (United States)

    Chattopadhyay, Chandrani; Kim, Dae Won; Gombos, Dan S; Oba, Junna; Qin, Yong; Williams, Michelle D; Esmaeli, Bita; Grimm, Elizabeth A; Wargo, Jennifer A; Woodman, Scott E; Patel, Sapna P

    2016-08-01

    Melanomas of the choroid, ciliary body, and iris of the eye are collectively known as uveal melanomas. These cancers represent 5% of all melanoma diagnoses in the United States, and their age-adjusted risk is 5 per 1 million population. These less frequent melanomas are dissimilar to their more common cutaneous melanoma relative, with differing risk factors, primary treatment, anatomic spread, molecular changes, and responses to systemic therapy. Once uveal melanoma becomes metastatic, therapy options are limited and are often extrapolated from cutaneous melanoma therapies despite the routine exclusion of patients with uveal melanoma from clinical trials. Clinical trials directed at uveal melanoma have been completed or are in progress, and data from these well designed investigations will help guide future directions in this orphan disease. Cancer 2016;122:2299-2312. © 2016 American Cancer Society. © 2016 American Cancer Society.

  19. Long-term results of proton beam irradiated uveal melanomas

    International Nuclear Information System (INIS)

    Gragoudas, E.S.; Seddon, J.M.; Egan, K.

    1987-01-01

    The first 128 consecutive patients with uveal melanomas treated with proton beam irradiation were studied in order to evaluate survival and visual acuity status of patients with relatively long-term follow-up. The median follow-up was 5.4 years, and no patient was lost to follow-up. All tumors showed regression. The most recent visual acuity was 20/40 or better in 35% and 20/100 or better in 58%. Eight eyes were enucleated because of complications. Metastasis developed in 26 patients (20.5%) from 3 months to 7 years after treatment. Results indicate that proton irradiation is quite successful for achieving local control of uveal melanomas. A large proportion of the treated eyes maintained useful vision. Five-year follow-up data indicate that proton irradiation has no deleterious effect on the likelihood of the development of metastasis

  20. Salvage proton beam therapy in local recurrent uveal melanoma.

    Science.gov (United States)

    Riechardt, Aline I; Cordini, Dino; Dobner, Bianca; Seibel, Ira; Gundlach, Enken; Rehak, Matus; Hager, Annette; Stark, Roland; Moser, Lutz; Joussen, Antonia M

    2014-11-01

    To evaluate survival and ocular outcome in recurrent uveal melanoma treated with proton beam therapy as salvage therapy. Retrospective, interventional case series. We evaluated 48 patients with local recurrence of uveal melanoma after primary treatment with brachytherapy, transpupillary thermotherapy, proton beam therapy, laser photocoagulation, CyberKnife radiation, or photodynamic therapy. All patients received proton beam therapy as a salvage therapy at the Helmholtz Zentrum Berlin between July 2000 and December 2010. Kaplan-Meier analysis was used to obtain survival rates. The Kaplan-Meier estimator for local tumor control was 92.1% at 10 years after secondary treatment with proton beam therapy. Local recurrence developed in 3 patients; 1 of them underwent enucleation. During follow-up, 20.8% of the patients died (16.7% of metastasis, 4.1% of other causes or not specified). The most frequent surgical interventions were phacoemulsification (20.8%) and pars plana vitrectomy (10.4%). The Kaplan-Meier estimators were 77.4% for survival and 70.1% for the absence of metastasis 10 years after the primary treatment. Proton beam therapy as a salvage treatment resulted in high local tumor control rates in recurrent uveal melanoma, especially if the primary therapy was transpupillary thermotherapy or plaque brachytherapy. Preservation of the globe was possible in most patients. Enucleations were indicated only in case of re-recurrences of uveal melanoma, but not because of secondary complications like intractable pain or secondary glaucoma. Retreatment was associated with vision deterioration, but loss of vision remained exceptional. Further larger prospective studies are needed to confirm the presented results of our retrospective analysis. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Transarterial chemoembolization of liver metastases in patients with uveal melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Huppert, P.E., E-mail: huppert@klinikum-darmstadt.d [Department of Diagnostic and Interventional Radiology, Klinikum Darmstadt, Darmstadt (Germany); Fierlbeck, G., E-mail: gerhard.fierlbeck@med.uni-tuebingen.d [Department of Dermatology, University of Tuebingen, Liebermeisterstrasse 25, D-72076 Tuebingen (Germany); Pereira, P., E-mail: philippe.pereira@slk-kliniken.d [Department of Diagnostic Radiology, University of Tuebingen, Hoppe-Seyler-Strasse 3, D-72076 Tuebingen (Germany); Schanz, S., E-mail: stefan.schanz@med.uni-tuebingen.d [Department of Dermatology, University of Tuebingen, Liebermeisterstrasse 25, D-72076 Tuebingen (Germany); Duda, S.H., E-mail: stephan.duda@t-online.d [Department of Diagnostic Radiology, University of Tuebingen, Hoppe-Seyler-Strasse 3, D-72076 Tuebingen (Germany); Wietholtz, H., E-mail: hubertus.wietholtz@klinikum-darmstadt.d [Department of Internal Medicine II, Klinikum Darmstadt, Darmstadt (Germany); Rozeik, C., E-mail: rozeik.christoph@klinloe.d [Department of Diagnostic and Interventional Radiology, Klinikum Darmstadt, Darmstadt (Germany); Claussen, C.D., E-mail: claus.claussen@med.uni-tuebingen.d [Department of Diagnostic Radiology, University of Tuebingen, Hoppe-Seyler-Strasse 3, D-72076 Tuebingen (Germany)

    2010-06-15

    Summary: Metastases from uveal melanoma are often confined to the liver. Palliative hepatic chemoembolization has been considered to be a reasonable treatment approach. We enrolled 14 patients with hepatic metastases from uveal melanoma into a pilot trial of transarterial chemoembolization (TACE). All patients received additional systemic immuno-chemotherapy or best supportive care. In 31 procedures 100 mg/m{sup 2} of cisplatine was continuously infused by means of a power injector preceding embolization by manual injection of polyvinyl alcohol particles. In three procedures cisplatine was replaced by 200 mg/m{sup 2} carboplatine because of increased serum creatinine levels. Tumor response was evaluated using RECIST criteria. Fourteen patients received 34 TACE's (mean: 2.4 treatments). Eight patients (57%) achieved partial response (PR), four patients (29%) had stable disease and two patients (14%) tumor progression. Median time to progression was 8.5 months (5-35 months). Median survival after first TACE was 14.5 months in responders compared to 10 months in non-responders (p = 0.18, not significant) and 11.5 months (3-69 months) in all patients. In seven patients with metastases occupying less than 25% of liver volume median survival was 17 months compared to 11 months in seven patients with tumor involvement of more than 25% (p = 0.02) with partial response rate of 86% and 29%, respectively. TACE of liver metastases from uveal melanoma is well tolerated and may prolong survival in patients with limited tumor extension.

  2. Trabeculectomy in patients with uveal melanoma after proton beam therapy.

    Science.gov (United States)

    Riechardt, Aline I; Cordini, Dino; Rehak, Matus; Hager, Annette; Seibel, Ira; Böker, Alexander; Gundlach, Enken; Heufelder, Jens; Joussen, Antonia M

    2016-07-01

    Retrospective evaluation of intraocular pressure, use of topical and systemic anti-glaucoma medication, secondary complications, local tumor control and survival in patients treated with trabeculectomy for the regulation of the intraocular pressure (IOP) after proton beam therapy for uveal melanoma. In this retrospective clinical case series we evaluated the follow-up of 15 patients receiving a trabeculectomy as surgical treatment if the IOP could not be lowered adequately by medications or laser surgery. All patients had received proton beam therapy for uveal melanoma at the Helmholtz-Zentrum Berlin between 1998 and 2010. The median IOP decreased significantly from 35 mmHg ± 8.8 before TE to 16 mmHg ± 8.2 (=52.3 %) six months after TE (Wilcoxon-Mann-Whitney-U Test, p<0.01). None of the patients needed any glaucoma medication six months after trabeculectomy. Two patients developed local recurrence during follow-up, which were independent of the trabeculectomy. One patient had to be enucleated due to intractable pain and suspected remaining tumor activity. One patient died due to metastasis. Trabeculectomy is an option in intractable glaucoma in patients with uveal melanoma after proton beam therapy in single cases. Secondary interventions are common. Inoculation metastases are possible. Secure local tumor control must be a prerequisite for filtrating operations.

  3. Molecular prognostic testing and individualized patient care in uveal melanoma.

    Science.gov (United States)

    Harbour, J William

    2009-12-01

    To critically assess the status of molecular prognostic testing and its use for individualized patient care in uveal melanoma. Perspective, literature review, evidence assessment, and commentary. Evaluation of selected articles from the literature and the authors' clinical and laboratory studies. The most accurate molecular tests for predicting metastatic death in patients with uveal melanoma currently involve automated techniques for assessing deoxyribonucleic acid (DNA) copy number alterations and gene expression profiling. Most tests reported in the literature to date do not provide adequate scientific and statistical validation to be used outside of an ethically supervised investigational environment. Many cytogenetic and molecular prognostic tests for uveal melanoma have been reported, yet few have reached the standards required for routine clinical testing. Clinicians must understand the statistical and scientific limitations of the tests they are using, and appropriate ethical oversight is essential until such time that validated testing instruments are available that are performed in a standardized clinical testing environment. Well-controlled prospective studies are necessary to identify the most accurate, widely accessible, and affordable tests for routine clinical use.

  4. 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.

  5. Cellular radiosensitivity of primary and metastatic human uveal melanoma cell lines

    NARCIS (Netherlands)

    G.J.M.J. van den Aardweg (Gerard J. M.); N.C. Naus (Nicole); A.C. Verhoeven; J.E.M.M. de Klein (Annelies); G.P.M. Luyten (Gré)

    2002-01-01

    textabstractPURPOSE: To investigate the radiosensitivity of uveal melanoma cell lines by a clonogenic survival assay, to improve the efficiency of the radiation regimen. METHODS: Four primary and four metastatic human uveal melanoma cell lines were cultured in the presence of

  6. Changes in immunological markers and influx of macrophages following trans-scleral thermotherapy of uveal melanoma

    NARCIS (Netherlands)

    Dennaoui, J.; Bronkhorst, I.H.; Ly, L.V.; Wolff-Rouendaal, D. de; Keunen, J.E.E.; Schalij-Delfos, N.E.; Jager, M.J.

    2011-01-01

    PURPOSE: In trans-scleral thermotherapy (TSTT), heat is applied through the sclera in order to target an intraocular uveal melanoma. Previously, it had been shown that in uveal melanoma, hyperthermia and transpupillary thermotherapy influenced expression of immunologically relevant proteins, such as

  7. Occupational exposure to electromagnetic fields and sex-differential risk of uveal melanoma

    DEFF Research Database (Denmark)

    Behrens, Thomas Flensted; Lynge, Elsebeth; Cree, Ian

    2010-01-01

    The association between occupational exposure to electromagnetic fields (EMF) and the risk of uveal melanoma was investigated in a case-control study in nine European countries.......The association between occupational exposure to electromagnetic fields (EMF) and the risk of uveal melanoma was investigated in a case-control study in nine European countries....

  8. Noncontiguous local recurrence of posterior uveal melanoma after cobalt 60 episcleral plaque therapy

    International Nuclear Information System (INIS)

    Duker, J.S.; Augsburger, J.J.; Shields, J.A.

    1989-01-01

    Four patients with posterior uveal melanomas treated by cobalt 60 episcleral plaque therapy developed the intraocular recurrence of choroidal melanoma at a site distant from and noncontiguous to their original lesions. Three of the four patients died of metastatic melanoma. The proportion of eyes with posterior uveal melanoma treated with cobalt 60 brachytherapy who subsequently develop this type of local recurrence appears to be low (0.68%)

  9. Gamma knife radiosurgery for uveal melanoma ineligible for brachytherapy by the Collaborative Ocular Melanoma Study criteria

    Directory of Open Access Journals (Sweden)

    Nicola G Ghazi

    2008-09-01

    Full Text Available Nicola G Ghazi1, Christopher S Ketcherside1, Jason Sheehan2, Brian P Conway11Department of Ophthalmology and 2Neurosurgery, University of Virginia Health System, Charlottesville, VA, USAPurpose: To report outcomes of Gamma Knife radiosurgery (GKRS in treating uveal melanoma lesions ineligible for standard brachytherapy.Methods: A retrospective interventional case series of uveal melanoma patients treated with GKRS between 1996 and 2004 was performed. The main outcome measures were local tumor control, metastasis, and death.Results: Four patients with uveal melanoma treated with GKS were identified. Three tumors involved the ciliary body and one was macular with its border within 2 mm of the optic disc. Adequate globe stabilization was achieved by retrobulbar anesthesia in all cases. Pretreatment mean visual acuity was 20/30. Tumor volume as determined by magnetic resonance imaging ranged from 0.05 to 0.30 cc. Ultrasonographic greatest tumor diameter and height ranged from 11 to 18 mm (mean 14.5 mm and 2.9 to 4.5 mm (mean 3.6 mm, respectively. The peripheral dose varied from 16.5 to 30 Gray. Local tumor control was achieved in all cases over a follow up period of 6 to 96 months. Mean final visual acuity was 20/50. One eye was enucleated for neovascular glaucoma and one patient died from liver and lung metastasis.Conclusions: GKRS for uveal melanoma appears to be safe and effective. The metastasis and mortality rates appear to be comparable to those following brachytherapy and enucleation. Moreover, local tumor control and enucleation rates are similar to those following brachytherapy. The findings in this small series suggest a role for GKRS in the treatment of selected cases of uveal melanomas.Keywords: gamma knife radiosurgery, radiation therapy, uveal melanoma

  10. Neovascular glaucoma after helium ion irradiation for uveal melanoma

    International Nuclear Information System (INIS)

    Kim, M.K.; Char, D.H.; Castro, J.L.; Saunders, W.M.; Chen, G.T.; Stone, R.D.

    1986-01-01

    Neovascular glaucoma developed in 22 of 169 uveal melanoma patients treated with helium ion irradiation. Most patients had large melanomas; no eyes containing small melanomas developed anterior segment neovascularization. The mean onset of glaucoma was 14.1 months (range, 7-31 months). The incidence of anterior segment neovascularization increased with radiation dosage; there was an approximately three-fold increase at 80 GyE versus 60 GyE of helium ion radiation (23% vs. 8.5%) (P less than 0.05). Neovascular glaucoma occurred more commonly in larger tumors; the incidence was not affected by tumor location, presence of subretinal fluid, nor rate of tumor regression. Fifty-three percent of patients had some response with intraocular pressures of 21 mmHg or less to a combination of antiglaucoma treatments

  11. A BAP1 Mutation in a Danish Family Predisposes to Uveal Melanoma and Other Cancers

    DEFF Research Database (Denmark)

    Aoude, Lauren G; Wadt, Karin; Bojesen, Anders

    2013-01-01

    with predominantly uveal melanoma but also a range of other tumor types including lung, neuroendocrine, stomach, and breast cancer; as well as pigmented skin lesions. Whole-exome sequencing identified a BAP1 splice mutation located at c.581-2A>G, which leads to a premature truncation of BAP1 in an individual...... with uveal melanoma. This mutation was carried by several other family members with melanoma or various cancers. The finding expands on the growing profile of BAP1 as an important uveal and cutaneous melanoma tumor suppressor gene and implicates its involvement in the development of lung, and stomach cancer.......Truncating germline mutations in the tumor suppressor gene BRCA-1 associated protein-1 (BAP1) have been reported in families predisposed to developing a wide range of different cancer types including uveal melanoma and cutaneous melanoma. There has also been an association between amelanotic tumor...

  12. Reduced melanoma-related mortality in uveal melanoma by preenucleation radiotherapy

    NARCIS (Netherlands)

    Kilic, Emine; Stijnen, Theo; de Jong, Paulus T. V. M.; Mooy, Cornelia M.; Eijkenboom, Wilhelmina M. H.; Ringens, Peter J.; Luyten, Gre P. M.

    2005-01-01

    Radiotherapy of an eye before enucleation, so called preenucleation radiotherapy (PER), of patients with uveal melanoma was initiated to reduce enucleation-induced systemic metastasis. Earlier studies with a short follow-up period have not demonstrated a significant effect on survival. To study the

  13. Cellular radiosensitivity of primary and metastatic human uveal melanoma cell lines

    OpenAIRE

    Aardweg, Gerard J. M.; Naus, Nicole; Verhoeven, A.C.; Klein, Annelies; Luyten, Gré

    2002-01-01

    textabstractPURPOSE: To investigate the radiosensitivity of uveal melanoma cell lines by a clonogenic survival assay, to improve the efficiency of the radiation regimen. METHODS: Four primary and four metastatic human uveal melanoma cell lines were cultured in the presence of conditioned medium. After single-dose irradiation (0-12 Gy), colonies were allowed to form for 6 to 14 days. Two cutaneous melanomas cell lines were also tested for comparison. The survival curves were analyzed by the li...

  14. Clinicopathologic correlations in eyes enucleated after uveal melanoma resection with positive surgical margins

    Directory of Open Access Journals (Sweden)

    Khalifa Yousuf

    2007-01-01

    Full Text Available We identified three eyes that had undergone enucleation after transscleral resection of uveal melanoma. Two enucleated eyes with microscopically positive margins of resection exhibited no evidence of residual melanoma and these patients were alive without metastasis with at least four years′ follow-up. One eye with a transected melanoma contained residual melanoma and that patient died with metastatic melanoma to the liver three years after enucleation. There appear to be at least two general types of positive surgical margins of resection of uveal melanoma: microscopically positive margins and macroscopically positive (transected margins of resection.

  15. Regression patterns of uveal melanomas after proton beam irradiation

    International Nuclear Information System (INIS)

    Wilkes, S.R.; Gragoudas, E.S.

    1982-01-01

    Forty-four uveal melanomas were evaluated for patterns of tumor regression after proton beam irradiation. All tumors were followed for a minimum of ten months after treatment. Seven lesions completely disappeared, 33 have decreased in size, and 4 remained unchanged. Associated signs of tumor regression were: resolution of the secondary serous retinal detachments, central apical yellow discoloration of the tumor, destruction of the tumor's vasculature, and elimination of fluorescein leakage. This study demonstrated that regression after proton beam irradiation is a relatively slow process, and the effects of radiation could be observed in some cases more than a year after treatment

  16. Computed tomography and magnetic resonance imaging study of uveal melanoma

    International Nuclear Information System (INIS)

    Xian Junfang; Wang Zhenchang; Yan Fei

    1998-01-01

    Purpose: To study CT and MRI findings of uveal melanoma and detect the most appropriate MRI scanning sequences. Materials and methods: A series of MRI scanning sequences were performed in 15 cases, and CT was performed in 11 cases. MRI and CT findings were compared with pathologic, operative and clinical findings. Results: Of 11 cases receiving CT scanning, 9 displayed iso-density masses with respect to extraocular muscles. The other two tumors were too small to be demonstrated. Fourteen cases of melanoma showed characteristic MR appearances with hyperintense signal with respect to the vitreous on T 1 -weighted images and hypointense with respect to the vitreous on T 2 -weighted images. One case of iris melanoma only 3 mm in height was not demonstrated on T 1 -weighted images, but was displayed hypointense signal on T 2 -weighted images. Eleven cases associated with retinal detachment showed high intensity signal on T 1 - and T 2 -weighted images and could not be distinguished from melanoma. Postcontrast T 1 -weighted images with fat suppression technique were found to be the most helpful in detecting and delineating small melanomas less than 5 mm as well as distinguishing them from retinal detachment. Conclusion: MRI was superior to ultrasound or CT. Collaborative diagnosis including clinical, ultrasonographic, CT and MRI examinations is the best for ocular melanoma

  17. Metastasis of Ciliary Body Melanoma to the Contralateral Eye: A Case Report and Review of Uveal Melanoma Literature

    OpenAIRE

    Torossian, Nouritza M.; Wallace, Roy T.; Hwu, Wen-Jen; Bedikian, Agop Y.

    2015-01-01

    Many types of cancers metastasize to the eye. However, uveal melanoma metastasizing to the contralateral choroid is very rare. We report the case of a 68-year-old man with history of treated uveal melanoma of the right eye that developed metastasis to the liver and the choroid of the left eye. Ten years earlier, he was diagnosed to have uveal melanoma of the right eye and was initially treated with plaque radiotherapy. Two years later, upon progression of the disease in the right eye he had e...

  18. Treatment Options for Intraocular (Uveal) Melanoma

    Science.gov (United States)

    ... or tans poorly. Blue or green or other light-colored eyes. Older age. Being white. Signs of intraocular melanoma include blurred vision ... to treat small tumors. This is also called light coagulation. ... are being tested in clinical trials. Information about clinical trials ...

  19. Treatment Option Overview (Intraocular [Uveal] Melanoma)

    Science.gov (United States)

    ... or tans poorly. Blue or green or other light-colored eyes. Older age. Being white. Signs of intraocular melanoma include blurred vision ... to treat small tumors. This is also called light coagulation. ... are being tested in clinical trials. Information about clinical trials ...

  20. General Information about Intraocular (Uveal) Melanoma

    Science.gov (United States)

    ... or tans poorly. Blue or green or other light-colored eyes. Older age. Being white. Signs of intraocular melanoma include blurred vision ... to treat small tumors. This is also called light coagulation. ... are being tested in clinical trials. Information about clinical trials ...

  1. Iodine-125 radiation of posterior uveal melanoma

    International Nuclear Information System (INIS)

    Packer, S.

    1987-01-01

    Twenty-eight cases of posterior choroidal melanoma were treated with iodine-125 in gold eye plaques. Eleven cases were located within 3.0 mm of the optic nerve (group A), nine were within 3.0 mm of the fovea (group B), and eight were within 3.0 mm of the optic nerve and fovea (group C). The mean follow-up of group A was 46.3 months; group B, 25.5 months; and group C, 42.7 months. Complications included macular edema, cataract and tumor growth. Visual acuity remained within two lines of that tested preoperatively for 4 of 11 patients in group A, 4 of 9 in group B, and 5 of 8 in group C. These results with iodine-125 suggest it as an appropriate treatment for patients with choroidal melanoma located near optic nerve and/or macula

  2. Iodine-125 radiation of posterior uveal melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Packer, S.

    1987-12-01

    Twenty-eight cases of posterior choroidal melanoma were treated with iodine-125 in gold eye plaques. Eleven cases were located within 3.0 mm of the optic nerve (group A), nine were within 3.0 mm of the fovea (group B), and eight were within 3.0 mm of the optic nerve and fovea (group C). The mean follow-up of group A was 46.3 months; group B, 25.5 months; and group C, 42.7 months. Complications included macular edema, cataract and tumor growth. Visual acuity remained within two lines of that tested preoperatively for 4 of 11 patients in group A, 4 of 9 in group B, and 5 of 8 in group C. These results with iodine-125 suggest it as an appropriate treatment for patients with choroidal melanoma located near optic nerve and/or macula.

  3. Effectiveness of fractionated stereotactic radiotherapy for uveal melanoma

    International Nuclear Information System (INIS)

    Muller, Karin; Nowak, Peter; Pan, Connie de; Marijnissen, Johannes P.; Paridaens, Dion A.; Levendag, Peter; Luyten, Gre P.M.

    2005-01-01

    Purpose: To study the effectiveness and acute side effects of fractionated stereotactic radiation therapy (fSRT) for uveal melanoma. Methods and Materials: Between 1999 and 2003, 38 patients (21 male, 17 female) were included in a prospective, nonrandomized clinical trial (mean follow-up of 25 months). A total dose of 50 Gy was given in 5 consecutive days. A blinking light and a camera (to monitor the position of the diseased eye) were fixed to a noninvasive relocatable stereotactic frame. Primary end points were local control, best corrected visual acuity, and toxicity at 3, 6, 12, and 24 months, respectively. Results: After 3 months (38 patients), the local control was 100%; after 12 months (32 patients) and 24 months (15 patients), no recurrences were seen. The best corrected visual acuity declined from a mean of 0.21 at diagnosis to 0.06 2 years after therapy. The acute side effects after 3 months were as follows: conjunctival symptoms (10), loss of lashes or hair (6), visual symptoms (5), fatigue (5), dry eye (1), cataract (1), and pain (4). One eye was enucleated at 2 months after fSRT. Conclusions: Preliminary results demonstrate that fSRT is an effective and safe treatment modality for uveal melanoma with an excellent local control and mild acute side effects. The follow-up should be prolonged to study both long-term local control and late toxicity

  4. Metastasis of ciliary body melanoma to the contralateral eye: a case report and review of uveal melanoma literature.

    Science.gov (United States)

    Torossian, Nouritza M; Wallace, Roy T; Hwu, Wen-Jen; Bedikian, Agop Y

    2015-01-01

    Many types of cancers metastasize to the eye. However, uveal melanoma metastasizing to the contralateral choroid is very rare. We report the case of a 68-year-old man with history of treated uveal melanoma of the right eye that developed metastasis to the liver and the choroid of the left eye. Ten years earlier, he was diagnosed to have uveal melanoma of the right eye and was initially treated with plaque radiotherapy. Two years later, upon progression of the disease in the right eye he had enucleation of the eye. We describe the patient's clinical history, the diagnosis of recurrent disease in the contralateral eye, therapy of the left eye, and systemic metastasis. In addition, we reviewed the published medical literature and described the recent advances in the management of uveal melanoma.

  5. Metastasis of Ciliary Body Melanoma to the Contralateral Eye: A Case Report and Review of Uveal Melanoma Literature

    Directory of Open Access Journals (Sweden)

    Nouritza M. Torossian

    2015-01-01

    Full Text Available Many types of cancers metastasize to the eye. However, uveal melanoma metastasizing to the contralateral choroid is very rare. We report the case of a 68-year-old man with history of treated uveal melanoma of the right eye that developed metastasis to the liver and the choroid of the left eye. Ten years earlier, he was diagnosed to have uveal melanoma of the right eye and was initially treated with plaque radiotherapy. Two years later, upon progression of the disease in the right eye he had enucleation of the eye. We describe the patient’s clinical history, the diagnosis of recurrent disease in the contralateral eye, therapy of the left eye, and systemic metastasis. In addition, we reviewed the published medical literature and described the recent advances in the management of uveal melanoma.

  6. Paraneoplastic vitelliform retinopathy associated with cutaneous or uveal melanoma and metastases.

    NARCIS (Netherlands)

    Sotodeh, M.; Paridaens, D.; Keunen, J.E.E.; Schooneveld, M. van; Adamus, G.; Baarsma, S.

    2005-01-01

    PURPOSE: To report unusual vitelliform fundus findings in three cases of paraneoplastic retinopathy associated with metastasised cutaneous or uveal melanoma and in one case, a unique immunoreactivity response. PATIENTS AND METHODS: Observational case series. The histories of three patients with

  7. External Validation of the Liverpool Uveal Melanoma Prognosticator Online.

    Science.gov (United States)

    DeParis, Sarah W; Taktak, Azzam; Eleuteri, Antonio; Enanoria, Wayne; Heimann, Heinrich; Coupland, Sarah E; Damato, Bertil

    2016-11-01

    To validate the Liverpool Uveal Melanoma Prognosticator Online (LUMPO) in a cohort of patients treated at the University of California-San Francisco (UCSF). A retrospective chart review was performed of 390 patients treated between 2002 and 2007 for choroidal melanoma at UCSF. Similar patients (n = 1175) treated at the Liverpool Ocular Oncology Centre (LOOC) were included in the study. The data were analyzed using the model previously developed for LUMPO, an online prognostication tool combining multiple prognostic factors. Main outcome measures included all-cause mortality and melanoma-specific mortality. Reliability of the survival estimates in each group of patients was indicated by the C-indices of discrimination and Hosmer-Lemeshow test. Patients treated at UCSF tended to be younger with thicker tumors, and were more likely to receive proton beam radiotherapy as primary treatment compared to patients at LOOC. There were no significance differences with respect to ciliary body involvement, melanoma cytomorphology, and mitotic counts between the two groups. Death occurred in 140/390 (35%) patients from UCSF and 409/1175 (34%) patients from LOOC, with no difference in overall mortality by Kaplan-Meier analysis (log rank test, P = 0.503). For all-cause mortality and melanoma-specific mortality, the C-index of discrimination and Hosmer-Lemeshow test at 5 years after treatment indicated good discrimination performance of the model, with no statistically significant difference between observed and predicted survival. Despite differences between the two cohorts, external validation in patients treated at UCSF indicates that LUMPO estimated the all-cause and melanoma-specific mortality well.

  8. A linac-based stereotactic irradiation technique of uveal melanoma

    International Nuclear Information System (INIS)

    Dieckmann, Karin; Bogner, Joachim; Georg, Dietmar; Zehetmayer, Martin; Kren, Gerhard; Poetter, Richard

    2001-01-01

    Purpose: To describe a stereotactic irradiation technique for uveal melanomas performed at a linac, based on a non-invasive eye fixation and eye monitoring system. Methods: For eye immobilization a light source system is integrated in a standard stereotactic mask system in front of the healthy eye: During treatment preparation (computed tomography/magnetic resonance imaging) as well as for treatment delivery, patients are instructed to gaze at the fixation light source. A mini-video camera monitors the pupil center position of the diseased eye. For treatment planning and beam delivery standard stereotactic radiotherapy equipment is used. If the pupil center deviation from a predefined 'zero-position' exceeds 1 mm (for more than 2 s), treatment delivery is interrupted. Between 1996 and 1999 60 patients with uveal melanomas, where (i) tumor height exceeded 7 mm, or (ii) tumor height was more than 3 mm, and the central tumor distance to the optic disc and/or the macula was less than 3 mm, have been treated. A total dose of 60 or 70 Gy has been given in 5 fractions within 10 days. Results: The repositioning accuracy in the mask system is 0.47±0.36 mm in rostral-occipital direction, 0.75±0.52 mm laterally, and 1.12±0.96 mm in vertical direction. An eye movement analysis performed for 23 patients shows a pupil center deviation from the 'zero' position<1 mm in 91% of all cases investigated. In a theoretical analysis, pupil center deviations are correlated with GTV 'movements'. For a pupil center deviation of 1 mm (rotation of the globe of 5 degree sign ) the GTV is still encompassed by the 80% isodose in 94%. Conclusion: For treatments of uveal melanomas, linac-based stereotactic radiotherapy combined with a non-invasive eye immobilization and monitoring system represents a feasible, accurate and reproducible method. Besides considerable technical requirements, the complexity of the treatment technique demands an interdisciplinary team continuously dedicated to this

  9. Phantom Eye Syndrome: Patient Experiences after Enucleation for Uveal Melanoma.

    Science.gov (United States)

    Hope-Stone, Laura; Brown, Stephen L; Heimann, Heinrich; Damato, Bertil; Salmon, Peter

    2015-08-01

    Patients undergoing enucleation for uveal melanoma need to be informed of the possibility of phantom eye syndrome (PES). The number with uveal melanoma in PES studies has been small. Aims were to: (1) determine the prevalence, symptoms, and characteristics of PES and to test associations of PES symptoms with sociodemographic and clinical characteristics; (2) examine the interrelatedness of PES symptoms; and (3) explore the emotional valence of PES and the relationship to anxiety and depression. Cross-sectional questionnaire. Patients (n = 179) with uveal melanoma enucleated 4 to 52 months previously. Questionnaire on PES. Responses to a routine audit of mood obtained from clinical records. Patients were asked about 3 symptoms: pain, visual sensations, and a feeling of seeing through the removed eye. Mood was assessed by the Hospital Anxiety and Depression Scale. Of 179 respondents, 108 (60.3%) experienced symptoms: 86 reported (48%) visual sensations, 50 reported (28%) seeing, and 42 reported (23%) pain; 14 (7.8%) reported all 3 symptoms. At the time of the questionnaire, 31 (17%) experienced 1 or more symptoms daily. Women were more likely to report pain (odds ratio [OR], 2.18; 95% confidence interval [CI], 1.08-4.40). Younger patients at enucleation were more likely to report pain (t = 4.13; degrees of freedom (df), 177; P < 0.001) and visual sensations (t = 2.11; df, 177; P < 0.05). Patients studied sooner after enucleation were more likely to report seeing (Mann-Whitney U, 2343; P < 0.05). Pain and seeing were intercorrelated (chi-square, 5.47; Φ = 0.18; df, 1; P < 0.05), pain with visual sensations (chi-square, 3.91; Φ = 0.15; df, 1; P < 0.05) and seeing with visual sensations (chi-square, 34.22; Φ = 0.45; df, 1; P < 0.001). Twenty of 108 patients (18.5%) found symptoms disturbing, and 21 of 108 (19.4%) pleasurable. Patients reporting pain were more anxious (OR, 3.53; 95% CI, 1.38-9.03) and depressed (OR, 13.26; 95% CI, 3.87-46.21). Patients should be

  10. Proton therapy for uveal melanomas and other eye lesions

    International Nuclear Information System (INIS)

    Munzenrider, J.E.

    1999-01-01

    Charged particle beams are ideal for treating intra-ocular lesions, since they can be made to deposit their dose in the target, while significantly limiting dose received by non-involved ocular and orbital structures. Proton beam treatment of large numbers of uveal melanoma patients consistently achieves local control rates in excess of 95%, and eye retention rates of approximately 90%. Visual preservation is related to initial visual acuity, tumor size and location, and dose received by the macula, disc, and lens. The probability of distant metastasis is increased by larger tumor diameter, more anterior tumor location, and older patient age. Proton therapy is also effective treatment for patients with ocular angiomas, hemangiomas, metastatic tumors, and retinoblastomas, and may be beneficial for patients with exudative ('wet') age-related macular degeneration. (orig.)

  11. Proton therapy for uveal melanomas and other eye lesions

    Energy Technology Data Exchange (ETDEWEB)

    Munzenrider, J.E. [Dept. of Radiation Oncology, Harvard Univ. Medical School, Boston, MA (United States)

    1999-06-01

    Charged particle beams are ideal for treating intra-ocular lesions, since they can be made to deposit their dose in the target, while significantly limiting dose received by non-involved ocular and orbital structures. Proton beam treatment of large numbers of uveal melanoma patients consistently achieves local control rates in excess of 95%, and eye retention rates of approximately 90%. Visual preservation is related to initial visual acuity, tumor size and location, and dose received by the macula, disc, and lens. The probability of distant metastasis is increased by larger tumor diameter, more anterior tumor location, and older patient age. Proton therapy is also effective treatment for patients with ocular angiomas, hemangiomas, metastatic tumors, and retinoblastomas, and may be beneficial for patients with exudative (`wet`) age-related macular degeneration. (orig.)

  12. Use of the Chick Embryo Model in Uveal Melanoma

    Science.gov (United States)

    Kalirai, Helen; Shahidipour, Haleh; Coupland, Sarah E.; Luyten, Gregorius

    2015-01-01

    Animal models play a crucial role in basic and translational oncology research. Conventional rodent experiments, however, face ethical, practical and technical issues that limit their use. The chick embryo represents an accessible and economical in vivo model, which has long been used in developmental biology and for the study of angiogenesis. It is also a recognised xenograft model, and because of its lack of immune system in early development, the chick embryo has established itself as a key model system for cancer research, with which to study various steps in the metastatic process. In this chapter, we review the chick embryo model and the technical approaches adopted by cancer biologists, including advances in real-time imaging, and discuss how this has been or can be applied to improve our understanding of the biological events during uveal melanoma development and metastasis. PMID:27171889

  13. Late side effects of Ruthenium 106 therapy for uveal melanomas

    International Nuclear Information System (INIS)

    Langmann, G.; Faulborn, J.; Poier, E.

    1994-01-01

    When effectiveness is evaluated in brachytherapy with Ruthenium 106 special emphasis has to be put on tumor destruction and late side effects responsible for the definite functional results. We evaluated the late side effects of 22 uveal melanomas, which had been treated with 106 Ruthenium plaques. The tumor prominences ranged from 3 to 10 mm, the diameter from 4 to 9 disc diameters. In 4 patients the tumor involved the posterior pole, 14 melanomas were located in the midperiphery of the fundus, 4 tumors were ciliary body melanomas. The total radiation dose of the apex ranged from 100 to 240 Gy with a corresponding dose to the sclera between 540 to 1000 Gy. Because of the short half life of the plaque we have been using different dose rates (1.6-11 Gy/h). In 17/22 eyes adequate regression could be achieved by Ruthenium therapy alone. In one case additional laser treatment of the macular part of the melanoma had to be performed, Gamma Knife therapy was necessary in another melanoma with 10 mm tumor prominence. 3 recurrences led to enucleation. The mean follow up was 4.8 years ranging from 1 to 7 years. In 2/22 patients opticopathy caused severe visual impairment, in another 2 patients radiation maculopathy and opticopathy was observed. 7/22 developed vasculopathy with neovascularization treated by photocoagulation. In one case of focal radiation maculopathy laser treatment could prevent further visual impairment. The following factors are responsible for a higher incidence of late side effects: 1. High dose rate of the plaques in combination with a high radiation dose to the sclera 2. Location of the tumor within a minimum distance of 2 disc diameters to the optic nerve or macula 3. Tumor location at the ciliary body Laser treatment in case of neovascularization and focal radiation maculopathy is the only effective treatment with regard to late side effects. Ischemic maculopathy and radiation opticopathy are responsible for late visual impairment. (authors)

  14. Effect of hypoxic stress on migration and characteristics of monocytes in uveal melanoma.

    Science.gov (United States)

    Bronkhorst, Inge H G; Jehs, Tina M L; Dijkgraaf, Eveline M; Luyten, Gregorius P M; van der Velden, Pieter A; van der Burg, Sjoerd H; Jager, Martine J

    2014-05-01

    Among the characteristics of uveal melanoma that are associated with a poor prognosis are a large tumor size and the presence of increased numbers of lymphocytes and macrophages. In rapidly growing tumors, reduction in oxygen tension may occur with increased distance from blood vessels, which we hypothesize may lead to an inflammatory microenvironment, further stimulating tumor growth. To analyze whether hypoxia induces uveal melanoma cells to express proinflammatory cytokines and whether tumor supernatant (TSN) affects monocyte migration and differentiation. The expression of proinflammatory genes in freshly cultured uveal melanoma samples was studied in an in vitro 24-hour hypoxic culture system using quantitative polymerase chain reaction. In addition, cell lines cultured under normoxic and hypoxic conditions were used. The effect of TSN on monocyte chemotaxis was tested using a transwell migration system and by analyzing monocyte differentiation. The levels of the cytokines CCL2, IL6, and PGE2 in TSN were determined by enzyme-linked immunosorbent assay. Five cell lines (OCM8, 92.1, Mel270,Mel290 and OMM2.5) and 11 primary short-term cultures. Exposure of freshly cultured uveal melanoma cells to hypoxia led to an increased expression of the proinflammatory cytokines PLGF (OMIM 601121), TGFβ (OMIM 190180), END1 (OMIM +131240), and ICAM1 (OMIM 147840) and a lower expression of AIMP1 (OMIM 603605) (EMAP2), CCL2 (MCP-1) (OMIM +158105), and IL1b (OMIM *147720). The TSN from cultured melanoma cell lines induced chemotaxis of monocytes, but this was independent of the normoxic or hypoxic state. The TSN of 1 cell line and 2 primary uveal melanoma cultures inhibited the dendritic cell maturation and did not induce M2 macrophage polarization in vitro. Our results indicate that under hypoxic conditions, immune response genes are differentially expressed in cultured primary uveal melanoma cells. The TSN from uveal melanoma cell lines is capable of affecting the chemotactic

  15. Sex Disparity in Survival of Patients With Uveal Melanoma: Better Survival Rates in Women Than in Men in South Korea.

    Science.gov (United States)

    Park, San Jun; Oh, Chang-Mo; Yeon, Bora; Cho, Hyunsoon; Park, Kyu Hyung

    2017-03-01

    The purpose of this study was to determine the survival rate of patients with uveal melanoma and sex disparity in this rate in South Korea. We extracted incident uveal melanoma patients using the Korea Central Cancer Registry (KCCR) database, which covered the entire population from 1999 to 2012 in South Korea. We estimated all-cause survival probabilities and cancer-specific survival probabilities of patients with uveal melanoma and compared these probabilities between subgroups (sex, tumor site, age at diagnosis, etc.) using Kaplan-Meier methods and log-rank tests. We fitted the Cox-proportional hazards models for all-cause death and cancer death to determine sex disparities in survival. A total of 344 uveal melanoma patients (175 women, 51%) were ascertained. They comprised 283 patients with choroidal melanoma (82%) and 61 patients with ciliary body/iris melanoma (18%). The observed 5-year survival probability from all-cause death was 75% (95% confidence interval [CI]: 69%-79%); women with uveal melanoma showed higher survival probability (83% [95% CI: 76%-89%]) compared with men (66% [95% CI: 58%-73%], P women with uveal melanoma were lower than those in men (hazards ratio for cancer death = 0.50 [95% CI: 0.30-0.81]; hazards ratio for all-cause death = 0.39 [95% CI: 0.25-0.61]). Women with uveal melanoma have better survival probabilities relative to men with uveal melanoma. Our findings show a comprehensive picture of survival probability in uveal melanoma cancer patients in Korea, which requires further investigation of mechanism of the sex disparity in uveal melanoma.

  16. Reduction of Nodular Growth Pattern of Metastatic Uveal Melanoma after Radioembolization of Hepatic Metastases.

    Science.gov (United States)

    Halenda, Kevin M; Kudchadkar, Ragini R; Lawson, David H; Kies, Darren D; Zhelnin, Kristen E; Krasinskas, Alyssa M; Grossniklaus, Hans E

    2016-04-01

    The aim of this study was to report a case of metastatic uveal melanoma in which radioembolized nodular liver metastases decreased in size while infiltrative sinusoidal metastases progressed, leading to jaundice without obstruction of the biliary ducts. The relevant clinical features, imaging, and histopathologic findings of this case are reviewed. A 61-year-old Caucasian male with a history of uveal melanoma of the left eye status post plaque brachytherapy developed numerous liver metastases. After progression on systemic therapies, he underwent palliative radioembolization. Despite some radiographic improvement in the liver metastases, he developed hyperbilirubinemia without biliary tract obstruction or signs of liver failure. A biopsy of radiographically normal liver demonstrated extensive sinusoidal infiltration with melanoma. Distinct angiographic and histopathologic growth patterns of metastatic uveal melanoma differ in their amenability to radioembolization. Sinusoidal infiltration may lead to hyperbilirubinemia in the absence of overt obstruction or liver failure.

  17. Bimodal mortality dynamics for uveal melanoma: a cue for metastasis development traits?

    International Nuclear Information System (INIS)

    Demicheli, Romano; Fornili, Marco; Biganzoli, Elia

    2014-01-01

    The study estimates mortality dynamics (event-specific hazard rates over a follow-up time interval) for uveal melanoma. Three thousands six hundred seventy two patients undergoing radical or conservative treatment for unilateral uveal melanoma, whose yearly follow-up data were reported in three published datasets, were analysed. Mortality dynamics was studied by estimating with the life-table method the discrete hazard rate for death. Smoothed curves were obtained by a Kernel-like smoothing procedure and a piecewise exponential regression model. The ratio deaths/patients at risk per year was the main outcome measure. The three explored hazard rate curves display a common bimodal pattern, with a sudden increase peaking at about three years, followed by reduction until the sixth-seventh year and a second surge peaking at about nine years after treatment. The bimodal pattern of mortality indicates that uveal melanoma metastatic development cannot be explained by a continuous growth model. Similar metastasis dynamics have been reported for other tumours, including early breast cancer, for which it supported a paradigm shift to an interrupted growth model, the implications of which are episodes of ‘tumour dormancy’. We propose that the concepts of tumour homeostasis, tumour dormancy and enhancement of metastasis growth related to primary tumour removal, convincingly explaining the clinical behaviour of breast cancer, may be used for uveal melanoma as well. To confirm this proposition, a careful analysis of uveal melanoma metastasis dynamics is strongly warranted

  18. Case-control study on uveal melanoma (RIFA: rational and design

    Directory of Open Access Journals (Sweden)

    Schmidt-Pokrzywniak Andrea

    2004-08-01

    Full Text Available Abstract Background Although a rare disease, uveal melanoma is the most common primary intraocular malignancy in adults, with an incidence rate of up to 1.0 per 100,000 persons per year in Europe. Only a few consistent risk factors have been identified for this disease. We present the study design of an ongoing incident case-control study on uveal melanoma (acronym: RIFA study that focuses on radiofrequency radiation as transmitted by radio sets and wireless telephones, occupational risk factors, phenotypical characteristics, and UV radiation. Methods/Design We conduct a case-control study to identify the role of different exposures in the development of uveal melanoma. The cases of uveal melanoma were identified at the Division of Ophthalmology, University of Essen, a referral centre for tumours of the eye. We recruit three control groups: population controls, controls sampled from those ophthalmologists who referred cases to the Division of Ophthalmology, University of Duisburg-Essen, and sibling controls. For each case the controls are matched on sex and age (five year groups, except for sibling controls. The data are collected from the study participants by short self-administered questionnaire and by telephone interview. During and at the end of the field phase, the data are quality-checked. To estimate the effect of exposures on uveal melanoma risk, we will use conditional logistic regression that accounts for the matching factors and allows to control for potential confounding.

  19. Ultrasonic mirror image from ruthenium plaque facilitates calculation of uveal melanoma treatment dose

    DEFF Research Database (Denmark)

    Espensen, Charlotte Alfast; Jensen, Peter Koch; Fog, Lotte Stubkjær

    2017-01-01

    plaque brachytherapy to determine intraobserver reproducibility and interobserver agreement between two surgeons. 230 eyes with primary uveal melanoma were included in a retrospective analysis to determine the distance from the plaque to the tumour base using ultrasound. A phantom study was used......Background/aims To present a new method to determine dose depth and the distance from the concave side of the plaque to the tumour base in patients with uveal melanoma treated with ruthenium-106 based on ultrasonic mirror image. Methods We used the mirror image associated with ultrasound during...... was incorrectly determined. Conclusions The dose depth in patients with uveal melanoma must be measured accurately for correct calculation of the radiation dose to the apex of the tumour. Repeated in vivo and in vitro ultrasound measurements of dose depth showed higher variance than measurements using the mirror...

  20. A BAP1 mutation in a Danish family predisposes to uveal melanoma and other cancers.

    Directory of Open Access Journals (Sweden)

    Lauren G Aoude

    Full Text Available Truncating germline mutations in the tumor suppressor gene BRCA-1 associated protein-1 (BAP1 have been reported in families predisposed to developing a wide range of different cancer types including uveal melanoma and cutaneous melanoma. There has also been an association between amelanotic tumor development and germline BAP1 mutation suggesting a possible phenotypic characteristic of BAP1 mutation carriers. Though there have been many types of cancer associated with germline BAP1 mutation, the full spectrum of disease association is yet to be ascertained. Here we describe a Danish family with predominantly uveal melanoma but also a range of other tumor types including lung, neuroendocrine, stomach, and breast cancer; as well as pigmented skin lesions. Whole-exome sequencing identified a BAP1 splice mutation located at c.581-2A>G, which leads to a premature truncation of BAP1 in an individual with uveal melanoma. This mutation was carried by several other family members with melanoma or various cancers. The finding expands on the growing profile of BAP1 as an important uveal and cutaneous melanoma tumor suppressor gene and implicates its involvement in the development of lung, and stomach cancer.

  1. Substantial expression of luteinizing hormone-releasing hormone (LHRH) receptor type I in human uveal melanoma

    Science.gov (United States)

    Schally, Andrew V.; Block, Norman L; Dezso, Balazs; Olah, Gabor; Rozsa, Bernadett; Fodor, Klara; Buglyo, Armin; Gardi, Janos; Berta, Andras; Halmos, Gabor

    2013-01-01

    Uveal melanoma is the most common primary intraocular malignancy in adults, with a very high mortality rate due to frequent liver metastases. Consequently, the therapy of uveal melanoma remains a major clinical challenge and new treatment approaches are needed. For improving diagnosis and designing a rational and effective therapy, it is essential to elucidate molecular characteristics of this malignancy. The aim of this study therefore was to evaluate as a potential therapeutic target the expression of luteinizing hormone-releasing hormone (LHRH) receptor in human uveal melanoma. The expression of LHRH ligand and LHRH receptor transcript forms was studied in 39 human uveal melanoma specimens by RT-PCR using gene specific primers. The binding charachteristics of receptors for LHRH on 10 samples were determined by ligand competition assays. The presence of LHRH receptor protein was further evaluated by immunohistochemistry. The expression of mRNA for type I LHRH receptor was detected in 18 of 39 (46%) of tissue specimens. mRNA for LHRH-I ligand could be detected in 27 of 39 (69%) of the samples. Seven of 10 samples investigated showed high affinity LHRH-I receptors. The specific presence of full length LHRH receptor protein was further confirmed by immunohistochemistry. A high percentage of uveal melanomas express mRNA and protein for type-I LHRH receptors. Our results support the merit of further investigation of LHRH receptors in human ophthalmological tumors. Since diverse analogs of LHRH are in clinical trials or are already used for the treatment of various cancers, these analogs could be considered for the LHRH receptor-based treatment of uveal melanoma. PMID:24077773

  2. A case-control study: occupational cooking and the risk of uveal melanoma

    Directory of Open Access Journals (Sweden)

    Marr Anja

    2010-10-01

    Full Text Available Abstract Background A European-wide population based case-control study (European rare cancer study undertaken in nine European countries examined risk factors for uveal melanoma. They found a positive association between cooks and the risk of uveal melanoma. In our study we examine whether cooks or people who worked in cook related jobs have an increased uveal melanoma risk. Methods We conducted a case-control study during 2002 and 2005. Overall, 1653 eligible subjects (age range: 20-74 years, living in Germany participated. Interviews were conducted with 459 incident uveal melanoma cases, 827 population controls, 180 ophthalmologist controls and 187 sibling controls. Data on occupational exposure were obtained from a self-administered postal questionnaire and a computer-assisted telephone interview. We used conditional logistic regression to estimate odds ratios adjusting for the matching factors. Results Overall, we did not observe an increased risk of uveal melanoma among people who worked as cooks or who worked in cook related jobs. When we restricted the source population of our study to the population of the Federal State of Northrhine-Westphalia, we observed an increased risk among subjects who were categorized as cooks in the cases-control analysis. Conclusion Our results are in conflict with former results of the European rare cancer study. Considering the rarity of the disease laboratory in vitro studies of human uveal melanoma cell lines should be done to analyze potential exposure risk factors like radiation from microwaves, strong light from incandescent ovens, or infrared radiation.

  3. Precision, high dose radiotherapy: helium ion treatment of uveal melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Saunders, W.M.; Char, D.H.; Quivey, J.M.; Castro, J.R.; Chen, G.T.Y.; Collier, J.M.; Cartigny, A.; Blakely, E.A.; Lyman, J.T.; Zink, S.R.

    1985-02-01

    The authors report on 75 patients with uveal melanoma who were treated by placing the Bragg peak of a helium ion beam over the tumor volume. The technique localizes the high dose region very tightly around the tumor volume. This allows critical structures, such as the optic disc and the macula, to be excluded from the high dose region as long as they are 3 to 4 mm away from the edge of the tumor. Careful attention to tumor localization, treatment planning, patient immobilization and treatment verification is required. With a mean follow-up of 22 months (3 to 60 months) the authors have had only five patients with a local recurrence, all of whom were salvaged with another treatment. Pretreatment visual acuity has generally been preserved as long as the tumor edge is at least 4 mm away from the macula and optic disc. The only serious complication to date has been an 18% incidence of neovascular glaucoma in the patients treated at our highest dose level. Clinical results and details of the technique are presented to illustrate potential clinical precision in administering high dose radiotherapy with charged particles such as helium ions or protons.

  4. Precision, high dose radiotherapy: helium ion treatment of uveal melanoma

    International Nuclear Information System (INIS)

    Saunders, W.M.; Char, D.H.; Quivey, J.M.

    1985-01-01

    The authors report on 75 patients with uveal melanoma who were treated by placing the Bragg peak of a helium ion beam over the tumor volume. The technique localizes the high dose region very tightly around the tumor volume. This allows critical structures, such as the optic disc and the macula, to be excluded from the high dose region as long as they are 3 to 4 mm away from the edge of the tumor. Careful attention to tumor localization, treatment planning, patient immobilization and treatment verification is required. With a mean follow-up of 22 months (3 to 60 months) the authors have had only five patients with a local recurrence, all of whom were salvaged with another treatment. Pretreatment visual acuity has generally been preserved as long as the tumor edge is at least 4 mm away from the macula and optic disc. The only serious complication to date has been an 18% incidence of neovascular glaucoma in the patients treated at our highest dose level. Clinical results and details of the technique are presented to illustrate potential clinical precision in administering high dose radiotherapy with charged particles such as helium ions or protons

  5. 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.

  6. Establishment and characterization of human uveal malignant melanoma xenografts in nude mice

    DEFF Research Database (Denmark)

    Heegaard, S; Spang-Thomsen, M; Prause, J U

    2003-01-01

    model. Tumour tissue blocks (2 x 2 x 2 mm) from enucleated eyes with choroidal malignant melanoma were transplanted subcutaneously into the flanks of nude mice. The growing tumours were measured and serially transplanted. The tumour samples were investigated by histology, immunohistochemistry......The purpose of this study was to develop a suitable animal model for the investigation of the pathogenesis and therapy of uveal malignant melanoma. Eight choroidal malignant melanomas from eight patients were transplanted into nude mice in an attempt to establish a serially transplantable tumour...... the characteristic properties of malignant melanoma. However, the transplanted cells demonstrated vimentin reactivity, whereas the primary tumour cells were negative for vimentin. It can be concluded that a new experimental model of malignant uveal melanoma with tumours that were easy to observe and access...

  7. 15 years experience with helium ion radiotherapy for uveal melanoma

    International Nuclear Information System (INIS)

    Castro, Joseph R.; Char, Devron H.; Petti, Paula L.; Daftari, Inder K.; Quivey, Jeanne M.; Singh, Rajindar P.; Blakely, Eleanor A.; Phillips, Theodore L.

    1997-01-01

    Purpose: To review the long-term experience of helium ion therapy as a therapeutic alternative to enucleation for uveal melanoma, particularly with respect to survival, local control, and morbidity. Methods and Materials: 347 patients with uveal melanoma were treated with helium ion RT from 1978-1992. A nonrandomized dose-searching study was undertaken, with doses progressively reduced from 80 GyE in five fractions to 48 GyE in four fractions, given in 3-15 days, mean of 7 days. Results: Local control was achieved in 96% of patients, with no difference in the rate of local control being seen at 80, 70, 60, or 50 GyE in five fractions. At the lowest dose level of 48 GyE in four fractions, the local control rate fell to 87%. Fifteen of 347 patients (4%) had local regrowth in the eye requiring enucleation (12 patients), laser (1 patient) or reirradiation (2 patients). The time of appearance of local regrowth ranged from 4 months to 5 years posttreatment, with 85% occurring within 3 years. Of the 347 patients, 208 are alive as of May 1, 1997. The median follow up of all patients is 8.5 years, range 1-17 years. Kaplan-Maier (K-M) survival is 80% at 5 years, 76% at 10 years, and 72% at 15 years posttreatment. Patients with tumors not involving the ciliary body have a 15-year K-M survival of 80%. The results for patients whose tumors involved the ciliary body are poor, with a 15-year K-M survival of 43%. Seventy-five percent of patients with tumors at least 3.0 mm from the fovea and optic nerve, and initial ultrasound height less than 6.0 mm, retained vision of (20(200)) or better posttreatment. Patients with tumors larger than 6 mm in thickness, or with tumors lying close to the optic nerve or fovea, have a reduced chance of retaining useful vision. The enucleation rate is 19%, 3% for local failure and 16% because of complications of the helium RT, particularly neovascular glaucoma, which occurred in 35% of patients. Conclusions: Local control and retention of the eye

  8. Oral picropodophyllin (PPP) is well tolerated in vivo and inhibits IGF-1R expression and growth of uveal melanoma.

    Science.gov (United States)

    Economou, Mario A; Andersson, Sandra; Vasilcanu, Diana; All-Ericsson, Charlotta; Menu, Eline; Girnita, Ada; Girnita, Leonard; Axelson, Magnus; Seregard, Stefan; Larsson, Olle

    2008-11-01

    The cyclolignan picropodophyllin (PPP) efficiently blocks the activity of insulin-like growth factor-1 receptor (IGF-1R) and inhibits growth of uveal melanoma cells in vitro and in vivo. In this study, we aimed to investigate the efficiency of orally administered PPP on growth of uveal melanoma xenografts. Further, we focused on the effect of PPP on vascular endothelial growth factor (VEGF) in vivo and evaluated its effects in combination with other established anti-tumor agents in vitro. Four different uveal melanoma cell lines (OCM-1, OCM-3, OCM-8, 92-1) were treated with PPP alone and in combination with imatinib mesylate, cisplatin, 5-FU and doxorubicin. Cell viability was determined by XTT assay. SCID mice xenografted with uveal melanoma cells were used to determine anti-tumor efficacy of oral PPP in vivo. Tumor samples obtained from the in vivo experiments were analyzed for VEGF and IGF-1R expression by western blotting. PPP was found to be superior to the other anti-tumor agents in killing uveal melanoma cells. Oral PPP inhibited uveal melanoma growth in vivo and was well tolerated by the animals. PPP decreased VEGF expression in the tumors. Oral PPP is well tolerated in vivo and caused total growth inhibition of uveal melanoma xenografts as well as it decreased the levels of VEGF in the tumors.

  9. Stereotactic photon beam irradiation of uveal melanoma: indications and experience at the University of Vienna since 1997

    Energy Technology Data Exchange (ETDEWEB)

    Dieckmann, K.; Georg, D.; Rottenfusser, A.; Poetter, R. [Dept. of Radiotherapy, Univ. of Vienna (Austria); Zehetmayer, M. [Dept. of Ophthalmology, Univ. of Vienna (Austria)

    2007-12-15

    Most uveal melanomas are currently treated by eye-preserving radiotherapy. No advantage of enucleation of posterior uveal melanoma (< 12 mm) could be demonstrated in multiple studies (e.g.). Besides brachytherapy and highly conformal proton therapy advanced photon beam therapy techniques have been introduced during the last years. Since 1997, at the Medical University of Vienna, patients with uveal melanoma have been treated with 3D stereotactic photon beam radiotherapy. Special fixation- and eye-monitoring systems have been developed to perform a local treatment which provides high local tumor control with acceptable long term side effects. (orig.)

  10. Stereotactic photon beam irradiation of uveal melanoma: indications and experience at the University of Vienna since 1997

    International Nuclear Information System (INIS)

    Dieckmann, K.; Georg, D.; Rottenfusser, A.; Poetter, R.; Zehetmayer, M.

    2007-01-01

    Most uveal melanomas are currently treated by eye-preserving radiotherapy. No advantage of enucleation of posterior uveal melanoma (< 12 mm) could be demonstrated in multiple studies (e.g.). Besides brachytherapy and highly conformal proton therapy advanced photon beam therapy techniques have been introduced during the last years. Since 1997, at the Medical University of Vienna, patients with uveal melanoma have been treated with 3D stereotactic photon beam radiotherapy. Special fixation- and eye-monitoring systems have been developed to perform a local treatment which provides high local tumor control with acceptable long term side effects. (orig.)

  11. Effect of Genistein on vasculogenic mimicry formation by human uveal melanoma cells

    Directory of Open Access Journals (Sweden)

    Gu Haijuan

    2009-09-01

    Full Text Available Abstract Background Vasculogenic mimicry (VM was increasingly recognized as a form of aggressive melanoma acquiring blood supply. Genistein had attracted much attention as a potential anticancer agent. Therefore, we examined the effect of Genistein on VM in human uveal melanoma cells. Methods VM structure was detected by periodic acid-Schiff (PAS staining for uveal melanoma C918 cells cultured on the three-dimensional type I collagen gels after exposed to Genistein. We used reverse transcription polymerase chain reaction (RT-PCR and Western Blot analysis to examine the effect of Genistein on vascular endothelial cadherin (VE-cadherin mRNA and protein expression. The nude mice models of human uveal melanoma C918 cells were established to assess the number of VM using immunohistochemical and PAS double-staining. Results Genistein inhibited the survival of C918 cells in vitro. The ectopic model study showed that VM in tumor tissue sections were significantly reduced by Genistein in vivo. In vitro, the VM structure was found in control, 25 and 50 μM Genistein-treatment groups but not in 100 and 200 μM. RT-PCR and Western Blot showed that 100 and 200 μM concentration of Genistein could significantly decrease VE-cadherin mRNA and protein expression of C918 cells compared with control (P 0.05. Conclusion Genistein inhibits VM formation of uveal melanoma cells in vivo and in vitro. One possible underlying molecular mechanism by which Genistein could inhibit VM formation of uveal melanoma is related to down-regulation of VE-cadherin.

  12. 15 years experience with helium ion radiotherapy for uveal melanoma

    International Nuclear Information System (INIS)

    Castro, J.R.; Char, D.H.; Petti, P.L.; Daftari, I.K.; Quivey, J.M.; Singh, R.P.; Phillips, T.L.

    1996-01-01

    Purpose/Objective: In this study we review our long term experience with helium ion therapy in treating uveal melanoma. Materials and Methods: At UCSF-LBL, 347 patients with uveal melanoma were treated with helium ions from December 1978 - May 1992. A non randomized dose searching study was undertaken beginning with 80 GyE in 5 fractions and subsequently lowered through several levels to 48 GyE in 4 fractions. The treatment period ranged from 3 to 15 days, with a mean of 7 days. The various dose groups were similar in tumor characteristics and size. Results: An overall local control rate of 96% has been achieved, with no dose response being seen at 80, 70, 60 or 50 GyE in 5 fxs. At the lowest dose level of 48 GyE in 4 fxs, the local control rate fell to 87%. Fifteen patients (4%) had local failure in the eye requiring enucleation (12 pts), laser (1 pt) or reirradiation (2 pts). The time of appearance of local failures ranges from 4 to 64 months with most occurring within 2 years. Eight of the 15 patients with local failure are dead of distant metastases. Of the 347 patients, 308 had (20(200)) vision or better in the affected eye prior to treatment. Of these, 125 (41%) have retained at least(20(200)) vision in the treated eye. Patients with tumors greater than 5 mm in ultrasound height or close to the optic nerve or fovea have a reduced chance of retaining useful vision. The total enucleation rate is 15%, 1% for local failure and 14% because of complications of the helium RT, mostly secondary to severe glaucoma. Of the 347 patients, 230 are still alive. The median follow up is 75 months, range 3-206 months. Kaplan-Maier (K-M) survival for all 347 patients was 80% at 5 years, 77% at 10 years and 68% at 15 years post treatment. Results for patients whose tumor involves the ciliary body is much worse with a 15 year K-M survival of 42%, whereas patients not having ciliary involvement have a 15 year K-M survival of 75%. The K-M survival in patients with local failure in

  13. Inflammatory cell infiltrates in advanced metastatic uveal melanoma.

    Science.gov (United States)

    Krishna, Yamini; McCarthy, Conni; Kalirai, Helen; Coupland, Sarah E

    2017-08-01

    Current treatments for metastatic uveal melanoma (mUM) are limited and rarely prolong patient survival. Immunotherapy trials for mUM are few and to date have demonstrated only marginal success. High densities of tumor-associated macrophages (TAMs) and infiltrating T lymphocytes (TILs) in primary UM are associated with poor prognosis. Little is known about the immune microenvironment of mUM. Our aim was to examine the presence and distribution of TAMs and TILs in mUM within the liver. Whole-tissue sections of liver mUM (n=35) were examined by immunohistochemistry. For TAMs, monoclonal antibodies against CD68 and CD163 were used. Macrophage density and morphology were scored using previous established systems. Density and spatial distribution of TILs were highlighted using antibodies against CD3 (pan-lymphocyte marker), CD4 (T-helper cells), and CD8 (T-cytotoxic cells). CD68+ and CD163+ TAMs were seen within the tumor in all 35 specimens; their density was "moderate" in 50% of cases and "few" in 43%, and the majority showed an "indeterminate" phenotype. CD3+ TILs were noted both within mUMs and surrounding the tumor. Of these, CD8+ TILs were "few" in number within mUM but were predominantly seen peritumorally at the tumor/normal liver interface, whereas CD4+ TILs showed a high perivascular density within mUM. CD68+ and CD163+ TAMs of "indeterminate" morphology were observed in mUM, suggesting a tendency toward the protumorigenic M2 phenotype. CD4+ TILs were seen within the mUM, whereas CD8+ TILs tended to be peritumoral. The biological and functional roles of inflammatory cells in mUM require further investigation to determine if they represent potential targets for future therapies in mUM. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. In-depth proteomic profiling of the uveal melanoma secretome

    Science.gov (United States)

    Prendergast, Samuel; Simpson, Deborah; Hammond, Dean E.; Madigan, Michele C.; Beynon, Robert J.; Coupland, Sarah E.

    2016-01-01

    Uveal melanoma (UM), the most common primary intraocular tumour in adults, is characterised by a high frequency of metastases to the liver, typically with a fatal outcome. Proteins secreted from cancer cells (‘secretome’) are biologically important molecules thought to contribute to tumour progression. We examined the UM secretome by applying a label-free nanoLCMS/MS proteomic approach to profile proteins secreted into culture media by primary UM tumours with a high− (HR; n = 11) or low− (LR; n = 4) metastatic risk, compared to normal choroidal melanocytes (NCM) from unaffected post-mortem eyes. Across the three groups, 1843 proteins were identified at a 1% false discovery rate; 758 of these by at least 3 unique peptides, and quantified. The majority (539/758, 71%) of proteins were classified as secreted either by classical (144, 19%), non-classical (43, 6%) or exosomal (352, 46%) mechanisms. Bioinformatic analyzes showed that the secretome composition reflects biological differences and similarities of the samples. Ingenuity® pathway analysis of the secreted protein dataset identified abundant proteins involved in cell proliferation-, growth- and movement. Hepatic fibrosis/hepatic stellate cell activation and the mTORC1-S6K signalling axis were among the most differentially regulated biological processes in UM as compared with NCM. Further analysis of proteins upregulated ≥ 2 in HR-UM only, identified exosomal proteins involved in extracellular matrix remodelling and cancer cell migration/invasion; as well as classically secreted proteins, possibly representing novel biomarkers of metastatic disease. In conclusion, UM secretome analysis identifies novel proteins and pathways that may contribute to metastatic development at distant sites, particularly in the liver. PMID:27391064

  15. [Immunotherapy of uveal melanoma: vaccination against cancer. Multicenter adjuvant phase 3 vaccination study using dendritic cells laden with tumor RNA for large newly diagnosed uveal melanoma].

    Science.gov (United States)

    Schuler-Thurner, B; Bartz-Schmidt, K-U; Bornfeld, N; Cursiefen, C; Fuisting, B; Grisanti, S; Heindl, L M; Holbach, L; Keserü, M; Knorr, H; Koch, K; Kruse, F; Meiller, R; Metz, C; Meyer-ter-Vehn, T; Much, M; Reinsberg, M; Schliep, S; Seitz, B; Schuler, G; Süsskind, D; Viestenz, A; Wagenfeld, L; Zeschnigk, M

    2015-12-01

    Uveal melanomas are the most common malignant tumors of the eye. With modern molecular biological diagnostic methods, such as chromosome 3 typing and gene expression analysis, these tumors can be categorized into highly aggressive (monosomy 3, class II) and less aggressive forms. This molecular biological stratification is primarily important for determining the risk of these tumors as no therapy is currently available that is able to prevent or delay metastases. A randomized study of patients with a poor prognosis (monosomy 3) is currently being carried out in order to determine whether a cancer vaccine prepared from autologous (patient's own) dendritic cells and uveal melanoma RNA can prevent or delay progression and further metastases of this extremely aggressive form of cancer. Inclusion in the uveal melanoma study, which hopes to provide a potential therapeutic option for patients, is only possible if patients are referred to an institution that is able to manufacture and provide this vaccination before the patient is operated on or treated with radiation. Untreated tumor material is necessary for producing the vaccine on an individualized patient basis.

  16. Presence of a fluid-conducting meshwork in xenografted cutaneous and primary human uveal melanoma.

    NARCIS (Netherlands)

    Clarijs, Ruud; Otte-Holler, I.; Ruiter, D.J.; Waal, R.M.W. de

    2002-01-01

    PURPOSE: Recently, it was reported that tumor cells themselves generate channels and networks in three-dimensional culture and can be found lining channels (some containing red blood cells [RBCs]) in vivo, and they express endothelial or vascular genes in aggressive uveal melanoma. The implications

  17. Cytogenetic analysis of uveal melanoma. Consistent occurrence of monosomy 3 and trisomy 8q.

    Science.gov (United States)

    Horsman, D E; White, V A

    1993-02-01

    The genetic alterations associated with the pathogenesis of uveal melanoma have not been determined. To address this issue, the authors performed a prospective cytogenetic study of 35 uveal melanomas, including 23 primary untreated tumors and 12 tumors that were removed after local radiation therapy. Representative tumor tissue was processed by established methods for histopathologic and cytogenetic studies. Tumor cells were disaggregated and established in short-term culture; metaphases were prepared by standard methods for karyotypic analysis. Successful analyses were achieved in 27 of the tumor specimens, including 20 of 23 tumors not exposed to radiation and 7 of 12 tumors exposed to radiation. All of the tumors had an abnormal karyotype. Recurrent chromosomal abnormalities detected in the tumors not exposed to radiation included monosomy 3 (13 of 20), trisomy 8 or 8q (11 of 20), loss of a sex chromosome (10 of 20), and loss of 6q (8 of 20). The tumors previously exposed to radiation were characterized by more complex changes, with monosomy 3 and trisomy 8q detected in three cases each. Uveal melanoma is characterized by monosomy 3 and trisomy 8q in most cases. These findings, which are supported by data from other investigators, provide compelling evidence that loss of gene sequences on chromosome 3 and duplication of gene sequences on chromosome 8 are implicated in the genetic alterations associated with uveal melanoma and offer a basis for additional molecular genetic investigations.

  18. Circulating Tumor Cells Detection and Counting in Uveal Melanomas by a Filtration-Based Method

    International Nuclear Information System (INIS)

    Mazzini, Cinzia; Pinzani, Pamela; Salvianti, Francesca; Scatena, Cristian; Paglierani, Milena; Ucci, Francesca; Pazzagli, Mario; Massi, Daniela

    2014-01-01

    Uveal melanoma is one of the most deadly diseases in ophthalmology for which markers able to predict the appearance of metastasis are needed. The study investigates the role of circulating tumor cells (CTC) as a prognostic factor in this disease. We report the detection of circulating tumor cells by Isolation by Size of Epithelial Tumor cells (ISET) in a cohort of 31 uveal melanoma patients: we identified single CTCs or clusters of cells in 17 patients, while the control population, subjects with choroidal nevi, showed no CTC in peripheral blood. The presence of CTCs did not correlate with any clinical and pathological parameter, such as tumor larger basal diameter (LBD), tumor height and TNM. By stratifying patients in groups on the basis of the number of CTC (lower or higher than 10 CTC per 10 mL blood) and the presence of CTC clusters we found a significant difference in LBD (p = 0.019), Tumor height (p = 0.048), disease-free and overall survival (p < 0.05). In conclusion, we confirm the role of CTC as a negative prognostic marker in uveal melanoma patients after a long follow-up period. Further characterization of CTC will help understanding uveal melanoma metastasization and improve patient management

  19. CNS metastasis from malignant uveal melanoma: a clinical and histopathological characterisation

    DEFF Research Database (Denmark)

    Holfort, S K; Lindegaard, J; Isager, P

    2008-01-01

    was observed in two cases (14%). The amount of tumour infiltrating lymphocytes was pronounced in three cases (23%). CONCLUSION: The proportion of uveal melanoma patients having CNS metastasis was 0.7%. Eleven patients had multiple organ metastases, and the average time from the initial CNS symptoms to death...

  20. Heat shock protein expression in the eye and in uveal melanoma

    NARCIS (Netherlands)

    Missotten, Guy S.; Journée-de Korver, Johanna G.; de Wolff-Rouendaal, Didi; Keunen, Jan E.; Schlingemann, Reinier O.; Jager, Martine J.

    2003-01-01

    PURPOSE: Expression of heat shock proteins (HSPs) is of prognostic significance in several tumor types, whereas HSPs may also have clinical use as stimulators in tumor vaccination. HSP expression levels were determined in normal eyes and in uveal melanoma and tested whether HSPs expression was

  1. A cryptic BAP1 splice mutation in a family with uveal and cutaneous melanoma, and paraganglioma

    DEFF Research Database (Denmark)

    Wadt, K.; Choi, J.; Chung, J.Y.

    2012-01-01

    Inactivating germ line BRCA1-associated protein-1 (BAP1) mutations have recently been reported in families with uveal or cutaneous malignant melanoma (UMM, CMM), mesothelioma, and meningioma. Although apparently predisposing to a wide range of tumors, the exact tumor spectrum associated with germ...

  2. Expression of the SST receptor 2 in uveal melanoma is not a prognostic marker

    NARCIS (Netherlands)

    M. Kouch-el Filali (Mariam); E. Kiliç (Emine); M.L. Melis (Marleen); J.E.M.M. de Klein (Annelies); M. de Jong (Marion); G.P.M. Luyten (Gré)

    2008-01-01

    textabstractIntroduction: Uveal melanoma (UM) cells and neurohormone-producing cells both originate from the neural crest. Somatostatin receptors subtype 2 (SSTR2) are over-expressed in several tumors, often from neuroendocrine origin, and synthetic antagonists like octreotide and octreotate are

  3. Plaque Brachytherapy for Uveal Melanoma: A Vision Prognostication Model

    International Nuclear Information System (INIS)

    Khan, Niloufer; Khan, Mohammad K.; Bena, James; Macklis, Roger; Singh, Arun D.

    2012-01-01

    Purpose: To generate a vision prognostication model after plaque brachytherapy for uveal melanoma. Methods and Materials: All patients with primary single ciliary body or choroidal melanoma treated with iodine-125 or ruthenium-106 plaque brachytherapy between January 1, 2005, and June 30, 2010, were included. The primary endpoint was loss of visual acuity. Only patients with initial visual acuity better than or equal to 20/50 were used to evaluate visual acuity worse than 20/50 at the end of the study, and only patients with initial visual acuity better than or equal to 20/200 were used to evaluate visual acuity worse than 20/200 at the end of the study. Factors analyzed were sex, age, cataracts, diabetes, tumor size (basal dimension and apical height), tumor location, and radiation dose to the tumor apex, fovea, and optic disc. Univariate and multivariable Cox proportional hazards were used to determine the influence of baseline patient factors on vision loss. Kaplan-Meier curves (log rank analysis) were used to estimate freedom from vision loss. Results: Of 189 patients, 92% (174) were alive as of February 1, 2011. At presentation, visual acuity was better than or equal to 20/50 and better than or equal to 20/200 in 108 and 173 patients, respectively. Of these patients, 44.4% (48) had post-treatment visual acuity of worse than 20/50 and 25.4% (44) had post-treatment visual acuity worse than 20/200. By multivariable analysis, increased age (hazard ratio [HR] of 1.01 [1.00-1.03], P=.05), increase in tumor height (HR of 1.35 [1.22-1.48], P<.001), and a greater total dose to the fovea (HR of 1.01 [1.00-1.01], P<.001) were predictive of vision loss. This information was used to develop a nomogram predictive of vision loss. Conclusions: By providing a means to predict vision loss at 3 years after treatment, our vision prognostication model can be an important tool for patient selection and treatment counseling.

  4. Plaque Brachytherapy for Uveal Melanoma: A Vision Prognostication Model

    Energy Technology Data Exchange (ETDEWEB)

    Khan, Niloufer [Department of Radiation Oncology, Taussig Cancer Center, Cleveland Clinic, Cleveland, Ohio (United States); Khan, Mohammad K. [Department of Radiation Oncology, Emory University School of Medicine, Atlanta, Georgia (United States); Bena, James [Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio (United States); Macklis, Roger [Department of Radiation Oncology, Taussig Cancer Center, Cleveland Clinic, Cleveland, Ohio (United States); Singh, Arun D., E-mail: singha@ccf.org [Department of Ophthalmic Oncology, Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio (United States)

    2012-11-01

    Purpose: To generate a vision prognostication model after plaque brachytherapy for uveal melanoma. Methods and Materials: All patients with primary single ciliary body or choroidal melanoma treated with iodine-125 or ruthenium-106 plaque brachytherapy between January 1, 2005, and June 30, 2010, were included. The primary endpoint was loss of visual acuity. Only patients with initial visual acuity better than or equal to 20/50 were used to evaluate visual acuity worse than 20/50 at the end of the study, and only patients with initial visual acuity better than or equal to 20/200 were used to evaluate visual acuity worse than 20/200 at the end of the study. Factors analyzed were sex, age, cataracts, diabetes, tumor size (basal dimension and apical height), tumor location, and radiation dose to the tumor apex, fovea, and optic disc. Univariate and multivariable Cox proportional hazards were used to determine the influence of baseline patient factors on vision loss. Kaplan-Meier curves (log rank analysis) were used to estimate freedom from vision loss. Results: Of 189 patients, 92% (174) were alive as of February 1, 2011. At presentation, visual acuity was better than or equal to 20/50 and better than or equal to 20/200 in 108 and 173 patients, respectively. Of these patients, 44.4% (48) had post-treatment visual acuity of worse than 20/50 and 25.4% (44) had post-treatment visual acuity worse than 20/200. By multivariable analysis, increased age (hazard ratio [HR] of 1.01 [1.00-1.03], P=.05), increase in tumor height (HR of 1.35 [1.22-1.48], P<.001), and a greater total dose to the fovea (HR of 1.01 [1.00-1.01], P<.001) were predictive of vision loss. This information was used to develop a nomogram predictive of vision loss. Conclusions: By providing a means to predict vision loss at 3 years after treatment, our vision prognostication model can be an important tool for patient selection and treatment counseling.

  5. Effects of Zeaxanthin on Growth and Invasion of Human Uveal Melanoma in Nude Mouse Model

    Directory of Open Access Journals (Sweden)

    Xiaoliang L. Xu

    2015-01-01

    Full Text Available Uveal melanoma cells were inoculated into the choroid of nude mice and treated with or without intraocular injection of zeaxanthin. After 21 days, mice were sacrificed and the eyes enucleated. Histopathological analysis was performed in hematoxylin and eosin stained frozen sections. Melanoma developed rapidly in the control group (without treatment of zeaxanthin. Tumor-bearing eye mass and tumor mass in the control group were significantly greater than those in zeaxanthin treated group. Melanoma in the controlled eyes occupied a large part of the eye, was epithelioid in morphology, and was with numerous mitotic figures. Scleral perforation and extraocular extension were observed in half of the eyes. Melanomas in zeaxanthin treated eyes were significantly smaller with many necrosis and apoptosis areas and no extraocular extension could be found. Quantitative image analysis revealed that the tumor size was reduced by 56% in eyes treated with low dosages of zeaxanthin and 92% in eyes treatment with high dosages of zeaxanthin, as compared to the controls. This study demonstrated that zeaxanthin significantly inhibits the growth and invasion of human uveal melanoma in nude mice, suggesting that zeaxanthin may be a promising agent to be explored for the prevention and treatment of uveal melanoma.

  6. Atypical Presentation: Metastatic Uveal Melanoma in a Young Patient without Visual Complaints

    Directory of Open Access Journals (Sweden)

    Pedro Grachinski Buiar

    2017-05-01

    Full Text Available BackgroundUveal melanoma is a rare and aggressive subtype of melanoma, with singular characteristics that separate it from the most famous cutaneous melanoma. This uncommon condition becomes even rarer if we look at young population. Common chemotherapy regimens does not work with this aggressive disease in its metastatic scenario, and the new armament like targeted and immunotherapies are still looking for more robust evidence.Case presentationWe report a rare case of uveal melanoma in a patient younger than 20 years, with abdominal pain as his initial complaint. He did not present the typical visual symptoms of the primary site because of an auto accident suffered 4 months before the presentation, letting him blind of the eye affected by the tumor development.ConclusionThere is always a possibility of the diagnosis of uveal melanoma in cases with associated isolated hepatic metastases, even in a young population, where this hypothesis is often rejected by the epidemiological frequency of other tumors. This rare case is a useful example.

  7. Disease control and toxicity outcomes using ruthenium eye plaque brachytherapy in the treatment of uveal melanoma.

    Science.gov (United States)

    Takiar, Vinita; Gombos, Dan S; Mourtada, Firas; Rechner, Laura A; Lawyer, Ann A; Morrison, William H; Garden, Adam S; Beadle, Beth M

    2014-01-01

    Ruthenium-106 ((106)Ru) eye plaques have the potential to achieve excellent tumor control with acceptable radiation toxicity. We evaluated our experience in the management of uveal melanoma treated with (106)Ru brachytherapy. The records of 40 patients with uveal melanoma treated with brachytherapy using (106)Ru plaques from 2003 to 2007 at University of Texas MD Anderson Cancer Center were reviewed. Endpoints assessed included tumor control and toxicity. Median ophthalmologic follow-up was 67 months. Actuarial 5-year rates of local control (LC), progression-free survival (PFS), and overall survival (OS) were 97%, 94%, and 92%. There were 3 deaths, 2 related to melanoma. Fifteen patients experienced clinically significant visual loss; no patients were diagnosed with neovascular glaucoma, and 1 patient developed a clinically significant radiation-associated cataract. No patient required enucleation. We report the largest published US cohort of patients treated with (106)Ru plaque brachytherapy for uveal melanoma. Tumor control was excellent, and toxicity was acceptably low. These data support the reintroduction of (106)Ru into clinical practice for ocular melanoma. © 2014.

  8. Evidence for the Role of Blue Light in the Development of Uveal Melanoma

    Directory of Open Access Journals (Sweden)

    Patrick Logan

    2015-01-01

    Full Text Available Uveal melanoma is the most common malignancy of the adult eye. Although it is a relatively infrequent tumor, clinical prognosis is often poor owing to a high incidence of aggressive metastatic disease, for which there are limited treatment options. Little is known about the etiology of this condition, although several risk factors have been identified. Unlike cutaneous melanoma, however, ultraviolet radiation does not figure prominently among these risk factors. In this review, we focus on an associated form of visible electromagnetic radiation, high-energy short-wave (blue light, a causative agent in various forms of age-related retina damage, as a previously overlooked risk factor in uveal melanoma development and progression. Finally, we discuss the impact of these data on contemporary ocular therapy, particularly the debate surrounding the filtering capabilities of intraocular lenses used to replace dysfunctional crystalline lenses during cataract surgery.

  9. Clinical, Histopathological and Cytogenetic Prognosticators in Uveal Melanoma - A Comprehensive Review.

    Science.gov (United States)

    Berus, Tomasz; Halon, Agnieszka; Markiewicz, Anna; Orlowska-Heitzman, Jolanta; Romanowska-Dixon, Bozena; Donizy, Piotr

    2017-12-01

    Uveal melanoma is the most prevalent primary intraocular cancer in adults. Although it accounts for only 5% of all melanomas, it is responsible for 13% of deaths due to this type of cancer. A wide variety of therapeutic options of primary tumor is available and progress in its management is noticeable. The fact still remains, however, that almost half of patients develop metastases which may be due to practically undetectable cancer spread present as early as at diagnosis of the primary focus. Metastatic disease is uniformly fatal despite systemic therapy. Prediction of metastasis is crucial for prognosis. It also allows targeting of emerging new therapeutic methods to the appropriate group of patients. The Authors reviewed literature concerning epidemiology and etiopathogenesis of uveal melanoma, and its clinical, histopathological and cytogenetic prognosticators. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  10. Multiplex fluorescence in situ hybridization identifies novel rearrangements of chromosomes 6, 15, and 18 in primary uveal melanoma.

    Science.gov (United States)

    Sisley, Karen; Tattersall, Nicola; Dyson, Michael; Smith, Kath; Mudhar, Hardeep S; Rennie, Ian G

    2006-09-01

    Uveal melanomas are the commonest ocular tumour of adults and are characterized by reproducible alterations of chromosomes 1, 3, 6 and 8. These alterations are of prognostic relevance and have also be shown to correlate to high risk and low risk metastatic categories of uveal melanoma as defined by micro-array analysis. It is, however, possible that a catalogue of relevant genetic alterations, involving gene rearrangement rather than amplification, have as yet eluded identification. To address this point we examined 14 primary uveal melanomas, using 24 colour multiplex fluorescence in situ hybridization (M-FISH). All tumours were karyotyped following G-Banding, and M-FISH was performed to confirm and clarify the identity of abnormal chromosomes. M-FISH data were obtained from all tumours and was able to establish the nature of most abnormalities not fully characterized by cytogenetics. Abnormalities of chromosome 6 were far more frequent than previously indicated, in approximately 70% of cases, indicating they have been substantially underrepresented in past studies of uveal melanoma. Spindle melanomas were found to have novel rearrangements affecting in particular chromosomes 6, 15 and 18, suggesting that juxtaposition of genes through translocational events may play a role in the development of some uveal melanomas. In conclusion, this study is the largest of primary uveal melanoma analysed by M-FISH and indicates that alterations of chromosome 6 have previously been underestimated. Furthermore spindle melanomas are prone to rearrangements affecting chromosomes 6, 15 and 18, which may relate to early changes in uveal melanoma development or associate with those melanomas of a more differentiated status.

  11. [Uveal Melanoma Cell Under Oxidative Stress - Influence of VEGF and VEGF-Inhibitors].

    Science.gov (United States)

    Dithmer, M; Kirsch, A M; Gräfenstein, L; Wang, F; Schmidt, H; Coupland, S E; Fuchs, S; Roider, J; Klettner, A K

    2017-04-04

    Background The role of oxidative stress in cancer is complex. While the pathological alterations induced by oxidative stress may be involved in the induction of tumours, in the late stages of tumour development, it can facilitate the loss of tumour cells and might even prevent metastasis. Tumour cells show metabolic alterations, often inducing an increased production of reactive oxygen species, which makes these cells particularly vulnerable to additional oxidative stress. This is an important mode of action in the use of many chemotherapeutics and in the application of ionizing radiation. Uveal melanoma is the most frequent primary tumour in the adult eye. For metastasis of this tumour, which affects about 50 % of the patients, no appropriate treatment is currently available. However, the primary tumour can efficiently be treated with ionizing radiation. A frequent side effect of this treatment is radiation retinopathy, which is treated with vascular endothelial growth factor (VEGF) antagonists. A therapy of the primary tumour with VEGF antagonists is under discussion. So far, little data is available on this subject, however, a paradoxical worsening of the situation has been found in a mouse model of uveal melanoma treated with bevacizumab. Methods We have investigated the effect of VEGF and of the VEGF-antagonist bevacizumab on the survival of five different melanoma cell lines under oxidative stress treatment with hydrogen peroxide. In addition, we investigated the expression of relevant proteins and the effect of bevacizumab on the proliferation of the cells as well as its effect on the angiogenic behaviour of endothelial cells, co-cultured with uveal melanoma cells. Results Our study showed that not only VEGF but also, paradoxically, the VEGF-antagonist bevacizumab is able to protect uveal melanoma cells from oxidative stress-induced cell death. Bevacizumab did not influence the proliferation of the cells and showed only limited effectiveness to reduce

  12. The use of pembrolizumab for the treatment of metastatic uveal melanoma.

    Science.gov (United States)

    Kottschade, Lisa A; McWilliams, Robert R; Markovic, Svetomir N; Block, Matthew S; Villasboas Bisneto, Jose; Pham, Anthony Q; Esplin, Brandt L; Dronca, Roxana S

    2016-06-01

    Uveal melanoma is a rare type of melanoma, with only five to seven cases per one million persons diagnosed each year. Patients with metastatic melanoma of uveal origin tend to have lower response rates on traditional therapies. Herein we report our experience with 10 patients with metastatic uveal melanoma (MUM) who received pembrolizumab. Eligible patients were more than or equal to 18 years old, had unresectable MUM, progressed on prior ipilimumab therapy, had good performance status (Eastern Cooperative Oncology Group of 0 or 1), and adequate organ and marrow function. Patients could have central nervous system disease, but needed to be clinically stable. Patients were treated with 2 mg/kg pembrolizumab intravenously over 30 min every 3 weeks until disease progression, unacceptable toxicity, or for up to 2 years. Between April 2014 and October 2014, we treated a total of 10 patients with MUM with pembrolizumab. Median age was 65 years, with 70% being female. As of the data cutoff date of 14 May 2015, median progression-free survival was 18 weeks (range 3.14-49.3 weeks), with four patients still currently receiving therapy. Of eight evaluable patients, there was one complete response, two partial responses, and one patient with stable disease. Four patients had rapidly progressive disease. Toxicities were as expected and were usually grade 1/2 in nature. Although this cohort of patients was small, to our knowledge this is the first such report of outcomes in uveal melanoma patients being treated with anti-PD1 therapy. In the absence of a clinical trial, treatment with pembrolizumab appears to be a viable option for patients with MUM.

  13. Treatment considerations for primary uveal melanoma with choroidal metastasis to the fellow eye.

    Science.gov (United States)

    Bourla, Dan H; Young, Tara A

    2007-01-01

    We report two cases of primary uveal melanoma with metastatic involvement of the contralateral eye. Two female patients presented with primary choroidal melanoma. In the first case, primary enucleation of the affected eye was performed. Two years later, systemic tumor spread with contralateral choroidal melanoma was detected. A decision for observation of the ocular metastasis was made. In the second case, systemic tumor spread was already evident at time of initial diagnosis of the ocular melanoma. Six months later, a choroidal metastasis was detected in the fellow eye. Again, observation was recommended. In conclusion, systemic spread of primary choroidal melanoma may include a choroidal metastasis to the contralateral eye. Observation of the second affected eye may be prescribed.

  14. Hypoxia promotes uveal melanoma invasion through enhanced Notch and MAPK activation.

    Directory of Open Access Journals (Sweden)

    Laura Asnaghi

    Full Text Available The transcriptional response promoted by hypoxia-inducible factors has been associated with metastatic spread of uveal melanoma. We found expression of hypoxia-inducible factor 1α (HIF-1α protein in well-vascularized tumor regions as well as in four cell lines grown in normoxia, thus this pathway may be important even in well-oxygenated uveal melanoma cells. HIF-1α protein accumulation in normoxia was inhibited by rapamycin. As expected, hypoxia (1% pO2 further induced HIF-1α protein levels along with its target genes VEGF and LOX. Growth in hypoxia significantly increased cellular invasion of all 5 uveal melanoma lines tested, as did the introduction of an oxygen-insensitive HIF-1α mutant into Mel285 cells with low HIF-1α baseline levels. In contrast, HIF-1α knockdown using shRNA significantly decreased growth in hypoxia, and reduced by more than 50% tumor invasion in four lines with high HIF-1α baseline levels. Pharmacologic blockade of HIF-1α protein expression using digoxin dramatically suppressed cellular invasion both in normoxia and in hypoxia. We found that Notch pathway components, including Jag1-2 ligands, Hes1-Hey1 targets and the intracellular domain of Notch1, were increased in hypoxia, as well as the phosphorylation levels of Erk1-2 and Akt. Pharmacologic and genetic inhibition of Notch largely blocked the hypoxic induction of invasion as did the pharmacologic suppression of Erk1-2 activity. In addition, the increase in Erk1-2 and Akt phosphorylation by hypoxia was partially reduced by inhibiting Notch signaling. Our findings support the functional importance of HIF-1α signaling in promoting the invasive capacity of uveal melanoma cells in both hypoxia and normoxia, and suggest that pharmacologically targeting HIF-1α pathway directly or through blockade of Notch or Erk1-2 pathways can slow tumor spread.

  15. Charged Particle Radiation Therapy for Uveal Melanoma: A Systematic Review and Meta-Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Zhen, E-mail: Wang.Zhen@mayo.edu [Mayo Clinic, Rochester, Minnesota (United States); Nabhan, Mohammed [Mayo Clinic, Rochester, Minnesota (United States); Schild, Steven E. [Mayo Clinic, Scottsdale, Arizona (United States); Stafford, Scott L.; Petersen, Ivy A.; Foote, Robert L.; Murad, M. Hassan [Mayo Clinic, Rochester, Minnesota (United States)

    2013-05-01

    Charged particle therapy (CPT) delivered with either protons, helium ions, or carbon ions, has been used to treat uveal melanoma. The present analysis was performed to systematically evaluate the efficacy and adverse effects of CPT for uveal melanoma. We searched EMBASE, MEDLINE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and SciVerse Scopus and cross-referenced recent systematic reviews through January 2012. Two independent reviewers identified clinical trials and observational studies of CPT (protons, helium ions, and carbon ions). These reviewers extracted data and assessed study quality. Twenty-seven studies enrolling 8809 uveal melanoma patients met inclusion criteria. The rate of local recurrence was significantly less with CPT than with brachytherapy (odds ratio [OR] = 0.22, 95% confidence interval [CI], 0.21-0.23). There were no significant differences in mortality or enucleation rates. Results were robust in multiple sensitivity analyses. CPT was also associated with lower retinopathy and cataract formation rates. Data suggest better outcomes may be possible with charged particle therapy with respect to local recurrence, retinopathy, and cataract formation rates. The overall quality of the evidence is low, and higher quality comparative effectiveness studies are needed to provide better evidence.

  16. Charged Particle Radiation Therapy for Uveal Melanoma: A Systematic Review and Meta-Analysis

    International Nuclear Information System (INIS)

    Wang, Zhen; Nabhan, Mohammed; Schild, Steven E.; Stafford, Scott L.; Petersen, Ivy A.; Foote, Robert L.; Murad, M. Hassan

    2013-01-01

    Charged particle therapy (CPT) delivered with either protons, helium ions, or carbon ions, has been used to treat uveal melanoma. The present analysis was performed to systematically evaluate the efficacy and adverse effects of CPT for uveal melanoma. We searched EMBASE, MEDLINE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and SciVerse Scopus and cross-referenced recent systematic reviews through January 2012. Two independent reviewers identified clinical trials and observational studies of CPT (protons, helium ions, and carbon ions). These reviewers extracted data and assessed study quality. Twenty-seven studies enrolling 8809 uveal melanoma patients met inclusion criteria. The rate of local recurrence was significantly less with CPT than with brachytherapy (odds ratio [OR] = 0.22, 95% confidence interval [CI], 0.21-0.23). There were no significant differences in mortality or enucleation rates. Results were robust in multiple sensitivity analyses. CPT was also associated with lower retinopathy and cataract formation rates. Data suggest better outcomes may be possible with charged particle therapy with respect to local recurrence, retinopathy, and cataract formation rates. The overall quality of the evidence is low, and higher quality comparative effectiveness studies are needed to provide better evidence

  17. Pesticide exposure in farming and forestry and the risk of uveal melanoma.

    Science.gov (United States)

    Behrens, Thomas; Lynge, Elsebeth; Cree, Ian; Lutz, Jean-Michel; Eriksson, Mikael; Guénel, Pascal; Merletti, Franco; Morales-Suarez-Varela, Maria; Afonso, Noemia; Stengrevics, Aivars; Févotte, Joëlle; Sabroe, Svend; Llopis-González, Agustin; Gorini, Giuseppe; Hardell, Lennart; Stang, Andreas; Ahrens, Wolfgang

    2012-01-01

    Since pesticides are disputed risk factors for uveal melanoma, we studied the association between occupational pesticide exposure and uveal melanoma risk in a case-control study from nine European countries. Incident cases of uveal melanoma and population as well as hospital controls were included and frequency-matched by country, 5-year age groups and sex. Self-reported exposure was quantified with respect to duration of exposure and pesticide application method. We calculated the exposure intensity level based on application method and use of personal protective equipment. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated by unconditional logistic regression analyses and adjusted for several potential confounders. 293 case and 3,198 control subjects were interviewed. We did not identify positive associations with activities in farming or forestry, pesticide application or pesticide mixing. No consistent positive associations were seen with exposure intensity level scores either. The only statistically significantly raised association in this study was for exposure to chemical fertilizers in forestry (OR = 8.93; 95% CI 1.73-42.13), but this observation was based on only six exposed subjects. Results did not change when we restricted analyses to morphologically verified cases and excluded proxy interviews as well as cancer controls. We did not observe effect modification by sex or eye color. Risk estimates for pesticide exposures and occupational activities in agriculture and forestry were not increased and did not indicate a hormonal mechanism due to these exposures.

  18. Uveal Melanoma Cell Lines: Where do they come from? (An American Ophthalmological Society Thesis).

    Science.gov (United States)

    Jager, Martine J; Magner, J Antonio Bermudez; Ksander, Bruce R; Dubovy, Sander R

    2016-08-01

    To determine whether some of the most often used uveal melanoma cell lines resemble their original tumor. Analysis of the literature, patient charts, histopathology, mutations, chromosome status, HLA type, and expression of melanocyte markers on cell lines and their primary tumors. We examined five cell lines and the primary tumors from which they were derived. Four of the five examined primary tumors were unusual: one occupied the orbit, two were recurrences after prior irradiation, and one developed in an eye with a nevus of Ota. One cell line did not contain the GNA11 mutation, but it was present in the primary tumor. Three of the primary tumors had monosomy 3 (two of these lacked BAP1 expression); however, all five cell lines showed disomy 3 and BAP1 expression. All of the cell lines had gain of 8q. Two cell lines lacked expression of melanocyte markers, although these were present in the corresponding primary tumor. All cell lines could be traced back to their original uveal melanoma. Four of the five primary tumors were unusual. Cell lines often differed from their primary tumor in chromosome status and melanocyte markers. However, their specific chromosome aberrations and capacity to continue proliferation characterize them as uveal melanoma cell lines.

  19. Prognostic Factors and Decision Tree for Long-term Survival in Metastatic Uveal Melanoma.

    Science.gov (United States)

    Lorenzo, Daniel; Ochoa, María; Piulats, Josep Maria; Gutiérrez, Cristina; Arias, Luis; Català, Jaum; Grau, María; Peñafiel, Judith; Cobos, Estefanía; Garcia-Bru, Pere; Rubio, Marcos Javier; Padrón-Pérez, Noel; Dias, Bruno; Pera, Joan; Caminal, Josep Maria

    2017-12-04

    The purpose of this study was to demonstrate the existence of a bimodal survival pattern in metastatic uveal melanoma. Secondary aims were to identify the characteristics and prognostic factors associated with long-term survival and to develop a clinical decision tree. The medical records of 99 metastatic uveal melanoma patients were retrospectively reviewed. Patients were classified as either short (≤ 12 months) or long-term survivors (> 12 months) based on a graphical interpretation of the survival curve after diagnosis of the first metastatic lesion. Ophthalmic and oncological characteristics were assessed in both groups. Of the 99 patients, 62 (62.6%) were classified as short-term survivors, and 37 (37.4%) as long-term survivors. The multivariate analysis identified the following predictors of long-term survival: age ≤ 65 years (p=0.012) and unaltered serum lactate dehydrogenase levels (p=0.018); additionally, the size (smaller vs. larger) of the largest liver metastasis showed a trend towards significance (p=0.063). Based on the variables significantly associated with long-term survival, we developed a decision tree to facilitate clinical decision-making. The findings of this study demonstrate the existence of a bimodal survival pattern in patients with metastatic uveal melanoma. The presence of certain clinical characteristics at diagnosis of distant disease is associated with long-term survival. A decision tree was developed to facilitate clinical decision-making and to counsel patients about the expected course of disease.

  20. Monosomy 3 by chromogenic in situ hybridization (CISH) in Iranian patients with uveal melanoma.

    Science.gov (United States)

    Naseripour, Masood; Mehrazma, Mitra; Pourmatin, Rama; Kashkouli, Mohsen Bahmani; Sedaghat, Ahad; Gheytanchi, Elmira

    2015-01-01

    The aim of this study was to investigate the rate of monosomy 3 by CISH technique in Iranian patients with uveal melanoma (UM) and its correlation with clinical and histopathological features. Archival formalin fixed, paraffin-embedded material from 50 patients who had undergone enucleation for large uveal melanomas was obtained. Monosomy of chromosome 3 alteration by chromogenic in situ hybridization (CISH) was investigated. Clinical and histopathological features of tumors were collected. The patients had a mean age of 56.6±7.6 years. Mean basal diameter and thickness of tumors were 14.1 mm and 10.2 mm, respectively. Four patients (8%) were identified to harbor monosomy of chromosome 3. In the mean follow-up of 5.3 years (range, 3.2-9.5 y), only one case with monosomy 3 died of UM metastasis. The most common type of cellularity was mixed cell (86%). There was not any statistically significant correlation between monosomy of chromosome 3 and type of cellularity, ciliary body involvement, and largest basal diameter. The low rate of monosomy chromosome 3 and the consequent low rate of mortality may be indicative of good prognosis in Iranian patients with uveal melanoma.

  1. In vivo Confocal Microscopy in Differentiating Ipilimumab-Induced Anterior Uveitis from Metastatic Uveal Melanoma

    Directory of Open Access Journals (Sweden)

    Hayyam Kiratli

    2016-09-01

    Full Text Available This report aims to describe the facilitating role of in vivo confocal microscopy in differentiating inflammatory cells from a metastatic process in a patient with uveal melanoma and multiple systemic metastases who developed anterior uveitis while under ipilimumab treatment. A 43-year-old woman developed systemic metastases 11 months after treatment of amelanotic choroidal melanoma in her right eye with 30 Gy fractionated stereotactic radiotherapy. She first received temozolomide and then 4 cycles of ipilimumab 3 mg/kg/day. After the third cycle, severe anterior uveitis with coarse pigment clumps on the lens was seen in the left eye. Her left visual acuity declined from 20/20 to 20/80. Confocal microscopy revealed globular keratic precipitates with hyperreflective inclusions and endothelial blebs all suggestive of granulomatous uveitis. The uveitic reaction subsided after a 3-week course of topical corticosteroids, and her visual acuity was 20/20 again. Although uveal melanoma metastatic to the intraocular structures of the fellow eye is exceedingly rare and metastasis masquerading uveitis without any identifiable uveal lesion is even more unusual, it was still mandatory to rule out this distant possibility in our particular patient who already had widespread systemic metastases. Confocal microscopy was a useful complementary tool by identifying the inflammatory features of the keratic precipitates.

  2. Uveal Melanoma Cell Lines: Where do they come from? (An American Ophthalmological Society Thesis)

    Science.gov (United States)

    Jager, Martine J.; Magner, J. Antonio Bermudez; Ksander, Bruce R.; Dubovy, Sander R.

    2016-01-01

    Purpose To determine whether some of the most often used uveal melanoma cell lines resemble their original tumor. Methods Analysis of the literature, patient charts, histopathology, mutations, chromosome status, HLA type, and expression of melanocyte markers on cell lines and their primary tumors. We examined five cell lines and the primary tumors from which they were derived. Results Four of the five examined primary tumors were unusual: one occupied the orbit, two were recurrences after prior irradiation, and one developed in an eye with a nevus of Ota. One cell line did not contain the GNA11 mutation, but it was present in the primary tumor. Three of the primary tumors had monosomy 3 (two of these lacked BAP1 expression); however, all five cell lines showed disomy 3 and BAP1 expression. All of the cell lines had gain of 8q. Two cell lines lacked expression of melanocyte markers, although these were present in the corresponding primary tumor. Conclusions All cell lines could be traced back to their original uveal melanoma. Four of the five primary tumors were unusual. Cell lines often differed from their primary tumor in chromosome status and melanocyte markers. However, their specific chromosome aberrations and capacity to continue proliferation characterize them as uveal melanoma cell lines. PMID:28018010

  3. Uveal melanoma in the Saudi Arabian population: Two decades of management at the King Khaled Eye Specialist Hospital

    International Nuclear Information System (INIS)

    Alsuhaibani Adel H

    2009-01-01

    To present the experience of King Khaled Eye Specialist Hospital (KKESH) with uveal melanoma over the last two decades in a fashion similar to the result of the Collaborative Ocular Melanoma Study (COMS). Retrospective, non-comparative, interventional, case series. All patients were diagnosed with uveal melanoma at the King Khaled Eye Specialist Hospital (KKESH), Riyadh, Saudi Arabia from June 1983 to July 2005 and met the inclusion criteria of the COMS. A medical record review of clinical history, imaging studies, surgical procedures and treatment outcome was performed. Forty patients (24 males and 16 females) with uveal melanoma (average age 50 years; range 24-77 years) were included in the study; 28 (70%) were of Saudi Arabian descent and the remaining 12 (30%) patients were from neighboring Arab countries. Decreased vision was the main presenting complaint of 29 (72.5%) patients; the duration of this symptom was 3 months or more in 27 (67.5%) patients. The apical height of the tumor was 10 mm or more in nine (22.5%) of the affected eyes and the largest basal dimension was more than 16 mm in nine (22.5%) of the affected eyes. The posterior border of the tumor was 1-2 mmfrom the optic disc in three (7.5%) affected eyes. Primary enucleation was performed for 33 (82.5%) eyes, episcleral radiation plaque therapy for six (15%) of the eyes and endo resection of the uveal melanoma in one (2.5%) eye. Adjunct external beam radiation therapy was performed in two (5%) orbits for extrascleral extension. The histopathological diagnosis was available for 34 (84%) eyes in which surgery had been performed (33 patients underwent primary enucleation and one patient underwent endo resection of the uveal melanoma); 24 (70.6%) eyes had spindle cell and the remaining 10 (29.4%) had epithelioid or mixed cell types. Evidence of extraocular tumor extension was found in three eyes. The average follow-up was 33.7 months with a median of 19 months (range 0.5 months to 10 years). Two (5

  4. Assessment of the influence of one's education on early diagnosis of multiple primary cancer in patients with uveal melanoma.

    Science.gov (United States)

    Mierzwa-Dobranowska, Marzena; Romanowska-Dixon, Bozena

    2012-01-01

    This study will show a comparison of two groups of patients with uveal melanoma; one group with multiple primary cancer, and a second group with no identifiable second cancer, in terms of education and occupation. Study concerns 240 patients, who were isolated from patients being treated with uveal melanoma at the Department of Ophthalmology and Ocular Oncology Jagiellonian University Medical College in the period from 1998 to 2007. On the basis of medical history and medical records 97 patients were diagnosed with the one or more independent primary cancers. These patients were subjected to comparative analysis with a group of 143 patients with uveal melanoma as a control group. Analyzing the impact of education on the recognition of multiple primary cancer, there were significantly more frequent diagnoses of second primary cancers among patients with secondary and higher education than among those who had primary and vocational education. Among the obtained data on patients in the study group, the largest occupational group (according to the ISCO-88 (COM)) constituted "professionals". In the control group prevailed "craft and related trades workers". The results suggest the great importance of knowledge about risk factors for the development of cancer among patients with uveal melanoma and the ensuing more scrupulous search for succesive primary neoplasm and indicate the neccesity of organizing broad prophylactic actions. uveal melanoma, multiple primary cancer.

  5. First Experience on Laparoscopic Near-Infrared Fluorescence Imaging of Hepatic Uveal Melanoma Metastases using Indocyanine Green

    Science.gov (United States)

    Tummers, Quirijn R.J.G.; Verbeek, Floris P.R.; Prevoo, Hendrica A.J.M.; Braat, Andries E.; Baeten, Coen I.M.; Frangioni, John V.; van de Velde, Cornelis J.H.; Vahrmeijer, Alexander L.

    2014-01-01

    Background Uveal melanoma is the most common primary intraocular tumor in adults and up to 50% of patients will develop liver metastases. Complete surgical resection of these metastases can improve 5-year survival, but only a few patients are eligible for radical surgical treatment. The aim of this study was to introduce a near-infrared (NIR) fluorescence laparoscope during minimally-invasive surgery for intraoperative identification of uveal melanoma hepatic metastases and to use it to provide guidance during resection. Methods Three patients diagnosed with one solitary liver metastasis from uveal melanoma are presented. Patients received 10 mg indocyanine green (ICG) intravenously 24 h before surgery. A NIR fluorescence laparoscope was used to detect malignant liver lesions. Results In all 3 patients, laparoscopic NIR fluorescence imaging using ICG successfully identified uveal melanoma metastases. In 2 patients, multiple additional lesions were identified by inspection and NIR fluorescence imaging, which were not identified by preoperative conventional imaging. In one patient, one additional lesion, not identified by computed tomography, magnetic resonance imaging, laparoscopic ultrasonography and inspection, was observed with NIR fluorescence imaging only.. Importantly, NIR fluorescence imaging provided guidance during resection of these metastases. Conclusions We describe the successful use of laparoscopic identification and resection of uveal melanoma liver metastases using NIR fluorescence imaging and ICG. This procedure is minimally-invasive, and should be used as complementary to conventional techniques for the detection and resection of liver metastases. PMID:24902685

  6. Association between smoking and uveal melanoma: a systematic review

    Directory of Open Access Journals (Sweden)

    Gianpaolo Smaldone

    2014-06-01

    Full Text Available Background: The aim of this study is systematically review the scientific literature on the relationship between tobacco smoking exposure and UM. Methods: The search was performed on Medline and Scopus databases. For each database, we used the following query: “smok* AND (eye OR uveal melanoma”. Results: 3 observational studies were considered suitable, two case-control studies and one cohort study. There is no significant evidence in the scientific literature about the association between smoking and UM. Conclusions: More complete and multi-center studies are desirable, giving the importance of smoking as a risk factor in the development of cancers.

  7. Polyneoplasias in uveal melanoma patients detected by positron emission tomography combined with computed tomography (two clinical cases

    Directory of Open Access Journals (Sweden)

    K. V. Avakyan

    2017-01-01

    Full Text Available In addition to abdominal ultrasound and chest X-ray, positron emission tomography combined with computed tomography (PET/CT has been increasingly used to diagnose metastatic disease in patients with uveal melanoma. We present two clinical cases of the second malignancy (synchronous polyneoplasia, colon cancer that was eventually found during PET/CT in uveal melanoma patients performed to exclude dissemination of the neoplasm. It was shown that hybrid PET/CT is the most informative method in the diagnosis and monitoring of uveal melanoma patients. During one diagnostic procedure it enables to diagnose early stages of secondary malignancies, in addition to the assessment of metastatic dissemination.

  8. Optic nerve invasion of uveal melanoma: clinical characteristics and metastatic pattern

    DEFF Research Database (Denmark)

    Lindegaard, Jacob; Isager, Peter; Prause, Jan Ulrik

    2006-01-01

    PURPOSE: To determine the frequency of optic nerve invasion in uveal melanoma, to identify clinical factors associated with optic nerve invasion, and to analyze the metastatic pattern and the association with survival. METHODS: All iris, ciliary body, and choroidal melanomas (N = 2758) examined...... between 1942 and 2001 at the Eye Pathology Institute, University of Copenhagen, Denmark, and the Institute of Pathology, Aarhus University Hospital, Aarhus, Denmark, were reviewed. Cases with optic nerve invasion were identified and subdivided into prelaminar or laminar invasion and postlaminar invasion....... Clinical characteristics were compared with those from 85 cases randomly drawn from all ciliary body and choroidal melanomas without optic nerve invasion from the same period. Survival data were obtained by the Kaplan-Meier method, and the Mantel-Cox log-rank test was used to test differences in survival...

  9. MicroRNA expression analysis and Multiplex ligation-dependent probe amplification in metastatic and non-metastatic uveal melanoma

    DEFF Research Database (Denmark)

    Larsen, Ann-Cathrine; Holst, Line; Kaczkowski, Bogumil

    2014-01-01

    Purpose: To determine the association of microRNA expression and chromosomal changes with metastasis and survival in uveal melanoma (UM). Methods: Thirty-six patients with UM were selected based on the metastatic status, and clinicopathological data were collected. Multiplex ligation-dependent pr......Purpose: To determine the association of microRNA expression and chromosomal changes with metastasis and survival in uveal melanoma (UM). Methods: Thirty-six patients with UM were selected based on the metastatic status, and clinicopathological data were collected. Multiplex ligation...

  10. Stereotactic Radiosurgery and Fractionated Stereotactic Radiation Therapy for the Treatment of Uveal Melanoma

    International Nuclear Information System (INIS)

    Yazici, Gozde; Kiratli, Hayyam; Ozyigit, Gokhan; Sari, Sezin Yuce; Cengiz, Mustafa; Tarlan, Bercin; Mocan, Burce Ozgen; Zorlu, Faruk

    2017-01-01

    Purpose: To evaluate treatment results of stereotactic radiosurgery or fractionated stereotactic radiation therapy (SRS/FSRT) for uveal melanoma. Methods and Materials: We retrospectively evaluated 181 patients with 182 uveal melanomas receiving SRS/FSRT between 2007 and 2013. Treatment was administered with CyberKnife. Results: According to Collaborative Ocular Melanoma Study criteria, tumor size was small in 1%, medium in 49.5%, and large in 49.5% of the patients. Seventy-one tumors received <45 Gy, and 111 received ≥45 Gy. Median follow-up time was 24 months. Complete and partial response was observed in 8 and 104 eyes, respectively. The rate of 5-year overall survival was 98%, disease-free survival 57%, local recurrence-free survival 73%, distant metastasis-free survival 69%, and enucleation-free survival 73%. There was a significant correlation between tumor size and disease-free survival, SRS/FSRT dose and enucleation-free survival; and both were prognostic for local recurrence-free survival. Enucleation was performed in 41 eyes owing to progression in 26 and complications in 11. Conclusions: The radiation therapy dose is of great importance for local control and eye retention; the best treatment outcome was achieved using ≥45 Gy in 3 fractions.

  11. Stereotactic Radiosurgery and Fractionated Stereotactic Radiation Therapy for the Treatment of Uveal Melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Yazici, Gozde [Department of Radiation Oncology, Faculty of Medicine, Hacettepe University, Ankara (Turkey); Kiratli, Hayyam [Department of Ophthalmology, Faculty of Medicine, Hacettepe University, Ankara (Turkey); Ozyigit, Gokhan; Sari, Sezin Yuce; Cengiz, Mustafa [Department of Radiation Oncology, Faculty of Medicine, Hacettepe University, Ankara (Turkey); Tarlan, Bercin [Bascom Palmer Eye Institute, Miami, Florida (United States); Mocan, Burce Ozgen [Department of Radiology, Faculty of Medicine, Hacettepe University, Ankara (Turkey); Zorlu, Faruk, E-mail: fzorlu@hacettepe.edu.tr [Department of Radiation Oncology, Faculty of Medicine, Hacettepe University, Ankara (Turkey)

    2017-05-01

    Purpose: To evaluate treatment results of stereotactic radiosurgery or fractionated stereotactic radiation therapy (SRS/FSRT) for uveal melanoma. Methods and Materials: We retrospectively evaluated 181 patients with 182 uveal melanomas receiving SRS/FSRT between 2007 and 2013. Treatment was administered with CyberKnife. Results: According to Collaborative Ocular Melanoma Study criteria, tumor size was small in 1%, medium in 49.5%, and large in 49.5% of the patients. Seventy-one tumors received <45 Gy, and 111 received ≥45 Gy. Median follow-up time was 24 months. Complete and partial response was observed in 8 and 104 eyes, respectively. The rate of 5-year overall survival was 98%, disease-free survival 57%, local recurrence-free survival 73%, distant metastasis-free survival 69%, and enucleation-free survival 73%. There was a significant correlation between tumor size and disease-free survival, SRS/FSRT dose and enucleation-free survival; and both were prognostic for local recurrence-free survival. Enucleation was performed in 41 eyes owing to progression in 26 and complications in 11. Conclusions: The radiation therapy dose is of great importance for local control and eye retention; the best treatment outcome was achieved using ≥45 Gy in 3 fractions.

  12. Uveal Melanoma with Histopathologic Intratumoral Heterogeneity Associated with Gene Expression Profile Discordance.

    Science.gov (United States)

    Miller, Audra K; Benage, Matthew J; Wilson, David J; Skalet, Alison H

    2017-07-01

    To report a case of intratumoral gene expression profile discordance in a malignant uveal melanoma, associated with intratumoral heterogeneity based upon histopathologic features. The clinical history, fundus findings, imaging and histopathologic features, and DecisionDx-UM gene expression profile results (Castle Biosciences, Inc., Phoenix, AZ, USA) of the tumor were reviewed. A trans-retinal fine-needle aspiration biopsy was performed for a thin, pigmented choroidal tumor in a 33-year-old man. Cells obtained from this biopsy were tested using the DecisionDx-UM gene expression profile test and the tumor was classified as class 1A. Cytology confirmed melanoma. The patient subsequently elected to undergo enucleation. On microscopic examination of the globe, the tumor was composed primarily of spindle B cells, but had a focal area composed of epithelioid cells. This portion of the tumor was subsequently tested and demonstrated a class 1B gene expression profile. Intratumoral discordance in gene expression profile results has been described in uveal melanomas. Here we demonstrate that this discordance may be associated in some cases with intratumoral heterogeneity based upon histopathologic features.

  13. Proton Beam Radiotherapy for Uveal Melanomas at Nice Teaching Hospital: 16 Years' Experience

    International Nuclear Information System (INIS)

    Caujolle, Jean-Pierre; Mammar, Hamid; Chamorey, Emmanuel Phar; Pinon, Fabien; Herault, Joel; Gastaud, Pierre

    2010-01-01

    Purpose: To present the results of uveal melanomas treated at Nice Teaching Hospital. Methods and Materials: This retrospective study included 886 consecutive patients referred to our clinic for the treatment of uveal melanomas by proton beam radiotherapy from June 1991 to December 2007. Survival rates were determined by using Kaplan-Meier estimates, and prognostic factors were evaluated using the log-rank test or Cox model. Results: The number (percent total) of subjects staged according to the TNM classification system (6th edition) of malignant tumors included 39 stage T1 (4.4%), 420 stage T2 (47.40%), 409 stage T3 (46.16%), and 18 stage T4 (2.03%) patients. The median follow-up was 63.7 months. The Kaplan-Meier overall survival rate at 5 years according to the sixth edition TNM classification was 92% for T1, 89% for T2, 67% for T3, and 62% for T4; and at 10 years, 86% for T1, 78% for T2, 43% for T3, and 41% for T4. Five factors were found to be associated with an increased death rate: advanced age, tumor thickness, largest tumor basal diameter, tumor volume, and tumor volume-to-eyeball volume ratio. The metastasis-free survival rates were 88.3 % at 5 years and 76.4 % at 10 years. The local control rates were 93.9% at 5 years and 92.1% at 10 years. The ocular conservation rates were 91.1% at 5 years and 87.3% at 10 years. Conclusions: We report the results of a large series of patients treated for uveal melanomas with a very long follow-up. Despite the large tumor volume treated, our results were similar to previously published findings relating to proton beam therapy.

  14. Prognostic value of morphometric features and the callender classification in uveal melanomas.

    Science.gov (United States)

    Coleman, K; Baak, J P; van Diest, P J; Mullaney, J

    1996-10-01

    Cytomorphometric analysis of uveal melanoma has focused on nucleolar characteristics, although nuclear measurements are easier and more reproducible. In this study, we examine a restricted set of nuclear and nucleolar cytomorphometric variables in the search for the most quantifiable and reproducible prognostic parameter among these and discover a means of assessing the malignancy of tumors within the different Callender subgroups. Uveal melanomas from 94 patients with a minimum follow-up of 5 years underwent nuclear and nucleolar morphometric analysis using a digitized interactive video overlay system. Statistical analysis included univariate and multivariate survival analysis on morphometric variables and classic prognostic parameters (such as Callender cell type, size, etc.). Univariate analysis of cytomorphometric parameters showed the standard deviation of nuclear area (NASD) to be the most significant variable (P < 0.0001: Mantel-Cox, 15.2). This was followed by the difference between nuclear and nucleolar areas (P < 0.002; Mantel-Cox, 9.5), the standard deviation of nucleolar area (SDNA) (P < 0.01; Mantel-Cox, 6.4), and the standard deviation of the shortest nuclear axis (P < 0.02; Mantel-Cox, 6.4). There was a trend for significance with the mean of the ten largest nucleoli (P < 0.07). Multivariate analysis of clinical and cytomorphometric variables showed improvement of prognostic prediction with a combination of the NASD, largest tumor dimension, and glaucoma (P < 0.0001; Mantel-Cox, 26.3). Callender cell type was strongly correlated with the NASD (P < 0.0002), the mean axis ratio of the nuclear area (P < 0.0007), and the mean of the ten largest nucleoli (P < 0.0007). Cytomorphometric analysis of uveal melanoma should include nuclear area and may identify tumors of differing malignancy within the same Callender class.

  15. Predictive risk factors for radiation retinopathy and optic neuropathy after proton beam therapy for uveal melanoma.

    Science.gov (United States)

    Seibel, Ira; Cordini, Dino; Hager, Annette; Tillner, Johanna; Riechardt, Aline I; Heufelder, Jens; Davids, Anja M; Rehak, Matus; Joussen, Antonia M

    2016-09-01

    This study was performed in order to evaluate the incidence of radiation retinopathy and optic neuropathy occurring after proton beam therapy for uveal melanoma. Included in this study were all patients who had been treated with primary proton beam therapy for uveal melanoma at the oncology service between May 1998 and June 2014 with a minimum follow-up of 12 months. Excluded were all patients who underwent re-irradiation, or vitrectomy due to exudative retinal detachment or for tumor-resection. During this period, 1127 patients matched the inclusion criteria, of whom 768 (68.1 %) and 463 (41.0 %) developed radiation retinopathy and optic neuropathy after a median time of 18.9 months (2.0-99.84 months) and 19.8 months (0.2-170.4 months), respectively. Mean follow-up was 53.4 months (12-170.4 months). Included were 558 men (49.5 %) and 569 women (50.5 %). Mean age was 61 years (16-89 years). Visual acuity slightly decreased from initial levels of 0.3 logMAR-0.4 logMAR in patients without developing any radiation-induced complication but severely decreased to 1.0 logMAR or 1.5 logMAR in the case of developing radiation retinopathy only or optic neuropathy, respectively. Independent risk factors for radiation retinopathy were a centrally (<2.5 mm from sensitive structures) located tumor or a thick tumor located more than 2.5 mm from sensitive structures, while those for radiation optic neuropathy comprised a short distance and applied dose to the optic disk. The risk for radiation retinopathy is higher in central uveal melanoma. Mid-/peripheral tumors are at high risk for radiation retinopathy and maculopathy if presenting with increased thickness.

  16. Cataract development in patients treated with proton beam therapy for uveal melanoma.

    Science.gov (United States)

    Seibel, Ira; Cordini, Dino; Hager, Annette; Riechardt, Aline I; Rehak, Matus; Böker, Alexander; Böhmer, Dirk; Heufelder, Jens; Joussen, Antonia M

    2016-08-01

    To evaluate the incidence, risk factors, and dosages of proton beam therapy associated with cataract development, and long-term visual outcomes after treatment of uveal melanoma. All patients receiving primary proton beam therapy for uveal melanoma between 1998 and 2008 with no signs of cataract before irradiation were included. A minimum follow-up of 12 months was determined. Exclusion criteria included all applied adjuvant therapies such as intravitreal injections, laser photocoagulation, tumor resections, or re-irradiation. For subgroup analysis, we included all patients who underwent brachytherapy between 1998 and 2008 for uveal melanoma, considering the above mentioned inclusion and exclusion criteria. Two hundred and fifty-eight patients matched our inclusion criteria. Median follow-up was 72.6 months (12.0-167.4 months). Of these 258 patients, 71 patients (66.3 %) presented with cataract after 31.3 months (0.7-142.4 months), of whom 35 (20.4 %) required surgery after 24.2 (0.7-111.1 months) to ensure funduscopic tumor control. Kaplan-Meier estimates calculated a risk for cataract of 74.3 % after 5 years. There was no increase in metastasis or local recurrence in these patients. Patient's age was the sole independent statistically significant risk factor for cataract development. The probability of cataract occurrence significantly increased with doses to lens exceeding 15-20 CGE. Neither the appearance of cataract nor cataract surgery influenced long-term visual outcome. Cataract formation is the most frequent complication after irradiation. There is no benefit vis-a-vis brachytherapy with regard to cataract development. Data indicate a dose-effect threshold of 0.5 CGE for cataractogenesis, with significantly increasing risk above a dose of 15 CGE. Furthermore, cataract surgery can be performed without an increased risk for metastasis.

  17. Fucoidan Does Not Exert Anti-Tumorigenic Effects on Uveal Melanoma Cell Lines.

    Science.gov (United States)

    Dithmer, Michaela; Kirsch, Anna-Maria; Richert, Elisabeth; Fuchs, Sabine; Wang, Fanlu; Schmidt, Harald; Coupland, Sarah E; Roider, Johann; Klettner, Alexa

    2017-06-22

    The polysaccharide fucoidan is widely investigated as an anti-cancer agent. Here, we tested the effect of fucoidan on uveal melanoma cell lines. The effect of 100 µM fucoidan was investigated on five cell lines (92.1, Mel270 OMM1, OMM2.3, OMM2.5) and of 1 µg/mL-1 mg/mL fucoidan in two cell lines (OMM1, OMM2.3). Cell proliferation and viability were investigated with a WST-1 assay, migration in a wound healing (scratch) assay. Vascular Endothelial Growth Factor (VEGF) was measured in ELISA. Angiogenesis was evaluated in co-cultures with endothelial cells. Cell toxicity was induced by hydrogen-peroxide. Protein expression (Akt, ERK1/2, Bcl-2, Bax) was investigated in Western blot. Fucoidan increased proliferation in two and reduced it in one cell line. Migration was reduced in three cell lines. The effect of fucoidan on VEGF was cell type and concentration dependent. In endothelial co-culture with 92.1, fucoidan significantly increased tubular structures. Moreover, fucoidan significantly protected all tested uveal melanoma cell lines from hydrogen-peroxide induced cell death. Under oxidative stress, fucoidan did not alter the expression of Bcl-2, Bax or ERK1/2, while inducing Akt expression in 92.1 cells but not in any other cell line. Fucoidan did not show anti-tumorigenic effects but displayed protective and pro-angiogenic properties, rendering fucoidan unsuitable as a potential new drug for the treatment of uveal melanoma.

  18. Fucoidan Does Not Exert Anti-Tumorigenic Effects on Uveal Melanoma Cell Lines

    Directory of Open Access Journals (Sweden)

    Michaela Dithmer

    2017-06-01

    Full Text Available Background. The polysaccharide fucoidan is widely investigated as an anti-cancer agent. Here, we tested the effect of fucoidan on uveal melanoma cell lines. Methods. The effect of 100 µM fucoidan was investigated on five cell lines (92.1, Mel270 OMM1, OMM2.3, OMM2.5 and of 1 µg/mL–1 mg/mL fucoidan in two cell lines (OMM1, OMM2.3. Cell proliferation and viability were investigated with a WST-1 assay, migration in a wound healing (scratch assay. Vascular Endothelial Growth Factor (VEGF was measured in ELISA. Angiogenesis was evaluated in co-cultures with endothelial cells. Cell toxicity was induced by hydrogen-peroxide. Protein expression (Akt, ERK1/2, Bcl-2, Bax was investigated in Western blot. Results. Fucoidan increased proliferation in two and reduced it in one cell line. Migration was reduced in three cell lines. The effect of fucoidan on VEGF was cell type and concentration dependent. In endothelial co-culture with 92.1, fucoidan significantly increased tubular structures. Moreover, fucoidan significantly protected all tested uveal melanoma cell lines from hydrogen-peroxide induced cell death. Under oxidative stress, fucoidan did not alter the expression of Bcl-2, Bax or ERK1/2, while inducing Akt expression in 92.1 cells but not in any other cell line. Conclusion. Fucoidan did not show anti-tumorigenic effects but displayed protective and pro-angiogenic properties, rendering fucoidan unsuitable as a potential new drug for the treatment of uveal melanoma.

  19. Fucoidan Does Not Exert Anti-Tumorigenic Effects on Uveal Melanoma Cell Lines

    Science.gov (United States)

    Dithmer, Michaela; Kirsch, Anna-Maria; Richert, Elisabeth; Fuchs, Sabine; Wang, Fanlu; Schmidt, Harald; Coupland, Sarah E.; Roider, Johann; Klettner, Alexa

    2017-01-01

    Background. The polysaccharide fucoidan is widely investigated as an anti-cancer agent. Here, we tested the effect of fucoidan on uveal melanoma cell lines. Methods. The effect of 100 µM fucoidan was investigated on five cell lines (92.1, Mel270 OMM1, OMM2.3, OMM2.5) and of 1 µg/mL–1 mg/mL fucoidan in two cell lines (OMM1, OMM2.3). Cell proliferation and viability were investigated with a WST-1 assay, migration in a wound healing (scratch) assay. Vascular Endothelial Growth Factor (VEGF) was measured in ELISA. Angiogenesis was evaluated in co-cultures with endothelial cells. Cell toxicity was induced by hydrogen-peroxide. Protein expression (Akt, ERK1/2, Bcl-2, Bax) was investigated in Western blot. Results. Fucoidan increased proliferation in two and reduced it in one cell line. Migration was reduced in three cell lines. The effect of fucoidan on VEGF was cell type and concentration dependent. In endothelial co-culture with 92.1, fucoidan significantly increased tubular structures. Moreover, fucoidan significantly protected all tested uveal melanoma cell lines from hydrogen-peroxide induced cell death. Under oxidative stress, fucoidan did not alter the expression of Bcl-2, Bax or ERK1/2, while inducing Akt expression in 92.1 cells but not in any other cell line. Conclusion. Fucoidan did not show anti-tumorigenic effects but displayed protective and pro-angiogenic properties, rendering fucoidan unsuitable as a potential new drug for the treatment of uveal melanoma. PMID:28640204

  20. Prognostic impact of chromosomal aberrations and GNAQ, GNA11 and BAP1 mutations in uveal melanoma

    DEFF Research Database (Denmark)

    Staby, Kjersti M; Gravdal, Karsten; Mørk, Sverre J

    2018-01-01

    PURPOSE: To evaluate clinico-pathological and molecular prognostic factors in a well-defined series of posterior uveal melanoma (UM) with focus on chromosomal aberrations and mutations in the GNAQ, GNA11 and BRCA1-associated protein 1 (BAP1) genes. METHODS: Formalin-fixed paraffin-embedded (FFPE......) tissue samples were obtained from 50 consecutive eyes enucleated for UM between 1993 and 2005. The material was tested for loss of chromosome 3 and gain of chromosome 8q gene signatures by selective molecular gene markers using multiplex ligation-dependent probe amplification (MLPA), and for DNA...

  1. Inflammation-induced chemokine expression in uveal melanoma cell lines stimulates monocyte chemotaxis

    DEFF Research Database (Denmark)

    Jehs, Tina; Faber, Carsten; Juel, Helene B

    2014-01-01

    of activated T cells on the expression of chemotactic cytokines in UM cells. Furthermore, we examined the ability of stimulated UM cells to attract monocytes. METHODS: We used an in vitro coculture system in which UM cell lines and T cells were cultured together, but separated by a membrane. Uveal melanoma...... resulted in an upregulation of chemokines such as CXCL8, CXCL9, CXCL10, CXCL11, CCL2, CCL5, VEGF, intracellular adhesion molecule 1 (ICAM1), and granulocyte-macrophage colony-stimulating factor (GM-CSF). The upregulation of these molecules was confirmed at the protein level. This increase of chemokines...

  2. Uveal melanoma cell-based vaccines express MHC II molecules that traffic via the endocytic and secretory pathways and activate CD8+ cytotoxic, tumor-specific T cells.

    Science.gov (United States)

    Bosch, Jacobus J; Iheagwara, Uzoma K; Reid, Sarah; Srivastava, Minu K; Wolf, Julie; Lotem, Michal; Ksander, Bruce R; Ostrand-Rosenberg, Suzanne

    2010-01-01

    We are exploring cell-based vaccines as a treatment for the 50% of patients with large primary uveal melanomas who develop lethal metastatic disease. MHC II uveal melanoma vaccines are MHC class I(+) uveal melanoma cells transduced with CD80 genes and MHC II genes syngeneic to the recipient. Previous studies demonstrated that the vaccines activate tumor-specific CD4(+) T cells from patients with metastatic uveal melanoma. We have hypothesized that vaccine potency is due to the absence of the MHC II-associated invariant chain (Ii). In the absence of Ii, newly synthesized MHC II molecules traffic intracellularly via a non-traditional pathway where they encounter and bind novel tumor peptides. Using confocal microscopy, we now confirm this hypothesis and demonstrate that MHC II molecules are present in both the endosomal and secretory pathways in vaccine cells. We also demonstrate that uveal melanoma MHC II vaccines activate uveal melanoma-specific, cytolytic CD8(+) T cells that do not lyse normal fibroblasts or other tumor cells. Surprisingly, the CD8(+) T cells are cytolytic for HLA-A syngeneic and MHC I-mismatched uveal melanomas. Collectively, these studies demonstrate that MHC II uveal melanoma vaccines are potent activators of tumor-specific CD4(+) and CD8(+) T cells and suggest that the non-conventional intracellular trafficking pattern of MHC II may contribute to their enhanced immunogenicity. Since MHC I compatibility is unnecessary for the activation of cytolytic CD8(+) T cells, the vaccines could be used in uveal melanoma patients without regard to MHC I genotype.

  3. Whole-body bioluminescent imaging of human uveal melanoma in a new mouse model of local tumor growth and metastasis.

    NARCIS (Netherlands)

    Notting, I.C.; Buijs, J.; Que, I.; Mintardjo, R.E.; Horst, G. ter; Karperien, M.; Missotten, G.S.; Jager, M.J.; Schalij-Delfos, N.E.; Keunen, J.E.E.; Pluijm, G. van der

    2005-01-01

    PURPOSE: Human uveal melanoma develops in one of the most capillary-rich tissues of the body and has a pure hematogenous dissemination. Radiodiagnostic examinations, such as ultrasonic diagnostic resonance imaging and chest radiographs plus liver enzyme studies in blood, are methods used to detect

  4. RasGRP3 Mediates MAPK Pathway Activation in GNAQ Mutant Uveal Melanoma.

    Science.gov (United States)

    Chen, Xu; Wu, Qiuxia; Depeille, Philippe; Chen, Peirong; Thornton, Sophie; Kalirai, Helen; Coupland, Sarah E; Roose, Jeroen P; Bastian, Boris C

    2017-05-08

    Constitutive activation of Gαq signaling by mutations in GNAQ or GNA11 occurs in over 80% of uveal melanomas (UMs) and activates MAPK. Protein kinase C (PKC) has been implicated as a link, but the mechanistic details remained unclear. We identified PKC δ and ɛ as required and sufficient to activate MAPK in GNAQ mutant melanomas. MAPK activation depends on Ras and is caused by RasGRP3, which is significantly and selectively overexpressed in response to GNAQ/11 mutation in UM. RasGRP3 activation occurs via PKC δ- and ɛ-dependent phosphorylation and PKC-independent, DAG-mediated membrane recruitment, possibly explaining the limited effect of PKC inhibitors to durably suppress MAPK in UM. The findings nominate RasGRP3 as a therapeutic target for cancers driven by oncogenic GNAQ/11. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Transarterial hepatic chemoperfusion of uveal melanoma metastases. Survival and response to treatment

    Energy Technology Data Exchange (ETDEWEB)

    Heusner, T.A.; Wittkowski-Sterczewski, A.; Ladd, S.C.; Forsting, M.; Verhagen, R. [Universitaetsklinik Essen, Duisburg-Essen Univ. (Germany). Inst. fuer Diagnostische und Interventionelle Radiologie und Neuroradiologie; Antoch, G. [Duesseldorf Univ. (Germany). Inst. fuer Diagnostische und Interventionelle Radiologie; Scheulen, M. [Duisburg-Essen Univ., Essen (DE). Klinik fuer Innere Medizin (Tumorforschung)

    2011-12-15

    Purpose: To assess the survival of patients with hepatic uveal melanoma metastases undergoing sequential transarterial hepatic chemoperfusion. Materials and Methods: 61 patients (mean age, 60.3 {+-} 13.8y) underwent a total of 249 hepatic chemoperfusion procedures (mean: 4 chemoperfusion procedures; range, 1 - 7 chemoperfusion procedures; standard deviation, 2.3 chemoperfusion procedures). All patients started with melphalan. In the case of progressive disease, melphalan was replaced by a different chemoperfusion agent. 38 patients were treated with melphalan only, 23 patients were treated with a combination of melphalan and other drugs. The median overall survival time was calculated for the overall population and several sub-groups. Differences in the survival rate between the sub-groups were assessed for statistical significance. The complication rate was assessed. Results: The median overall survival of the entire population was 10 months. The patients in the subgroups with a maximum number of 9 hepatic metastases as well as the patients in the subgroup without extrahepatic metastases at the beginning of therapy survived significantly longer than patients with more than 9 metastases/extrahepatic metastases (p = 0.019, p = 0.008). One patient (0.4 %) died from liver failure after initial infusion of melphalan. Conclusion: Intraarterial sequential hepatic chemoperfusion offers a minimally invasive treatment in patients with hepatic uveal melanoma metastases with good survival times and an acceptable major complication rate. (orig.)

  6. Molecular genetic testing of uveal melanoma from routinely processed and stained cytology specimens

    Science.gov (United States)

    Christopher, Benjamin N.; Cebulla, Colleen M.; Wakely, Paul E.; Davidorf, Frederick H.; Abdel-Rahman, Mohamed H.

    2013-01-01

    In the following study we investigated the utility of molecular genetic testing of the DNA extracted from routinely stained and processed smears from uveal melanoma (UM). Smears from five uveal melanoma cell lines and 12 primary tumors were prepared and stained with Papanicolaou and Romanowsky stains. Genotyping was carried out utilizing 14 microsatellite markers on chromosomes 3, 6 and 8. Mutational screening for alterations in GNAQ and GNA11 genes was carried out by restriction fragment length polymorphism. The results were compared to those obtained through direct sequencing of frozen tumor tissues. High quality DNA was extracted from the stained slides with no difference in the efficiency of DNA extraction between the two staining techniques. The extracted DNA was of adequate quality for genotyping and mutational screening. DNA extracted from approximately 200 tumor cells is sufficient for reproducible testing of allelic imbalances and for studying the common somatic mutations in GNAQ and GNA11 genes. In conclusion, we presented the feasibility of utilizing routinely stained cytology smears from UM for molecular genetic testing. The DNA obtained is of sufficient quality to carry out genotyping for markers on chromosome 3, 6 and 8, as well as screening for somatic mutations in GNAQ and GNA11 genes. PMID:21945171

  7. Conservation treatment of the eye: Conformal proton reirradiation for recurrent uveal melanoma

    International Nuclear Information System (INIS)

    Marucci, Laura; Lane, Anne M.; Li Wenjun; Egan, Kathleen M.; Gragoudas, Evangelos S.; Adams, Judy; Collier, John M.; Munzenrider, John E.

    2006-01-01

    Purpose: To evaluate the outcomes of a second course of proton beam radiation therapy (PBRT) in patients with recurrent uveal melanoma. Methods and Materials: Thirty-one patients received a second course of PBRT. The mean interval between the first and the second PBRT course was 50.2 months (range, 8-165 months). Most patients (87%) received 70 cobalt Gray equivalent (CGE) for both courses. Visual acuity was 20/200 or better in 30 patients initially and in 22 patients at the second treatment. The mean follow-up time after the second treatment was 50 months (range, 6-164 months). Results: At the time of the last follow-up, 20 patients were classified as having no evidence of disease, defined as tumor regression or an absence of tumor progression. Nine eyes (29%) were enucleated because of local recurrence (n = 5) or intractable pain (n = 4). The 5-year eye retention rate was 55% (95% confidence interval: 25.2-77.4). Six of the 22 patients who retained the eye (27%) had useful vision (20/200 or better). Conclusions A second course of PBRT for recurrent uveal melanoma to total doses between 118 and 140 CGE was associated with a relatively good probability of local control and a low enucleation rate. Although most patients lost vision, the majority were able to retain the reirradiated eye. Further evaluation is needed to assess metastasis-free survival of additional proton irradiation vs. enucleation after local recurrence

  8. Deep sequencing of uveal melanoma identifies a recurrent mutation in PLCB4

    DEFF Research Database (Denmark)

    Johansson, Peter; Aoude, Lauren G; Wadt, Karin

    2016-01-01

    Next generation sequencing of uveal melanoma (UM) samples has identified a number of recurrent oncogenic or loss-of-function mutations in key driver genes including: GNAQ, GNA11, EIF1AX, SF3B1 and BAP1. To search for additional driver mutations in this tumor type we carried out whole-genome or wh......Next generation sequencing of uveal melanoma (UM) samples has identified a number of recurrent oncogenic or loss-of-function mutations in key driver genes including: GNAQ, GNA11, EIF1AX, SF3B1 and BAP1. To search for additional driver mutations in this tumor type we carried out whole......, instead, a BRCA mutation signature predominated. In addition to mutations in the known UM driver genes, we found a recurrent mutation in PLCB4 (c.G1888T, p.D630Y, NM_000933), which was validated using Sanger sequencing. The identical mutation was also found in published UM sequence data (1 of 56 tumors...

  9. Early experiences of planning stereotactic radiosurgery using 3D printed models of eyes with uveal melanomas

    Directory of Open Access Journals (Sweden)

    Furdová A

    2017-01-01

    Full Text Available Alena Furdová,1 Miron Sramka,2 Andrej Thurzo,3 Adriana Furdová3 1Department of Ophthalmology, Faculty of Medicine, Comenius University, 2Department of Stereotactic Radiosurgery, St Elisabeth Cancer Inst and St Elisabeth University College of Health and Social Work, 3Department of Simulation and Virtual Medical Education, Faculty of Medicine, Comenius University, Bratislava, Slovak Republic Objective: The objective of this study was to determine the use of 3D printed model of an eye with intraocular tumor for linear accelerator-based stereotactic radiosurgery.Methods: The software for segmentation (3D Slicer created virtual 3D model of eye globe with tumorous mass based on tissue density from computed tomography and magnetic resonance imaging data. A virtual model was then processed in the slicing software (Simplify3D® and printed on 3D printer using fused deposition modeling technology. The material that was used for printing was polylactic acid.Results: In 2015, stereotactic planning scheme was optimized with the help of 3D printed model of the patient’s eye with intraocular tumor. In the period 2001–2015, a group of 150 patients with uveal melanoma (139 choroidal melanoma and 11 ciliary body melanoma were treated. The median tumor volume was 0.5 cm3 (0.2–1.6 cm3. The radiation dose was 35.0 Gy by 99% of dose volume histogram.Conclusion: The 3D printed model of eye with tumor was helpful in planning the process to achieve the optimal scheme for irradiation which requires high accuracy of defining the targeted tumor mass and critical structures. Keywords: 3D printing, uveal melanoma, stereotactic radiosurgery, linear accelerator, intraocular tumor, stereotactic planning scheme

  10. Combined mutation and copy-number variation detection by targeted next-generation sequencing in uveal melanoma.

    Science.gov (United States)

    Smit, Kyra N; van Poppelen, Natasha M; Vaarwater, Jolanda; Verdijk, Robert; van Marion, Ronald; Kalirai, Helen; Coupland, Sarah E; Thornton, Sophie; Farquhar, Neil; Dubbink, Hendrikus-Jan; Paridaens, Dion; de Klein, Annelies; Kiliç, Emine

    2018-01-12

    Uveal melanoma is a highly aggressive cancer of the eye, in which nearly 50% of the patients die from metastasis. It is the most common type of primary eye cancer in adults. Chromosome and mutation status have been shown to correlate with the disease-free survival. Loss of chromosome 3 and inactivating mutations in BAP1, which is located on chromosome 3, are strongly associated with 'high-risk' tumors that metastasize early. Other genes often involved in uveal melanoma are SF3B1 and EIF1AX, which are found to be mutated in intermediate- and low-risk tumors, respectively. To obtain genetic information of all genes in one test, we developed a targeted sequencing method that can detect mutations in uveal melanoma genes and chromosomal anomalies in chromosome 1, 3, and 8. With as little as 10 ng DNA, we obtained enough coverage on all genes to detect mutations, such as substitutions, deletions, and insertions. These results were validated with Sanger sequencing in 28 samples. In >90% of the cases, the BAP1 mutation status corresponded to the BAP1 immunohistochemistry. The results obtained in the Ion Torrent single-nucleotide polymorphism assay were confirmed with several other techniques, such as fluorescence in situ hybridization, multiplex ligation-dependent probe amplification, and Illumina SNP array. By validating our assay in 27 formalin-fixed paraffin-embedded and 43 fresh uveal melanomas, we show that mutations and chromosome status can reliably be obtained using targeted next-generation sequencing. Implementing this technique as a diagnostic pathology application for uveal melanoma will allow prediction of the patients' metastatic risk and potentially assess eligibility for new therapies.Modern Pathology advance online publication, 12 January 2018; doi:10.1038/modpathol.2017.187.

  11. Vision Loss Following Episcleral Brachytherapy for Uveal Melanoma: Development of a Vision Prognostication Tool.

    Science.gov (United States)

    Aziz, Hassan A; Singh, Nakul; Bena, James; Wilkinson, Allan; Singh, Arun D

    2016-06-01

    Vision loss following episcleral brachytherapy for uveal melanoma is difficult to predict for individual patients. To generate a risk calculator for vision loss following episcleral brachytherapy for uveal melanoma. A retrospective review of data was conducted at a multispecialty tertiary care center in Cleveland, Ohio. All patients with primary ciliary body or choroidal melanoma treated with iodine 125 or ruthenium 106 episcleral brachytherapy between January 1, 2004, and December 30, 2013, were included. Univariate and multivariable Cox proportional hazards were used to determine the influence of baseline patient factors on vision loss. Kaplan-Meier curves (log-rank analyses) were used to estimate freedom from vision loss. Bootstrap resampling was performed to bias correct this estimate. Vision loss (to visual acuity [VA] worse than 20/50 and worse than 20/200). A total of 311 patients were included in the study, with a mean (SD) age of 62 (14.7) years at start of treatment and a median follow-up of 36 months (interquartile range, 18-60 months). At presentation, VA was better than or equal to 20/50 in 199 patients (64%) and better than or equal to 20/200 in 289 patients (93%). By Kaplan-Meier analysis, VA less than 20/200 at 3 years was not associated with sex, diabetes, systemic hypertension, or hypercholesterolemia but was associated with history of ocular comorbidities, type of isotope (ruthenium 106 or iodine 125), and initial VA ( >20/50 or radiation dose to the fovea (HR, 1.03; 95% CI, 1.01-1.04; P = .001) and optic disc (HR, 1.01; 95% CI, 1.00-1.01; P = .005), and initial VA worse than 20/50 (HR, 1.85; 95% CI, 1.20-2.85; P = .005) were predictive of vision loss to a VA of less than 20/200. The concordance index for the full data set was 0.77. Using these data, an online risk calculator was developed to predict vision loss following episcleral brachytherapy. The vision prognostication tool presented herein needs to be validated by

  12. A Rare Thyroid Metastasis from Uveal Melanoma and Response to Immunotherapy Agents

    Directory of Open Access Journals (Sweden)

    Dearbhaile Catherine Collins

    2016-01-01

    Full Text Available Thyroid metastasis is a rare occurrence with cutaneous melanoma and even more uncommon with uveal melanoma. The management of such metastasis is uncertain due to its infrequency and, in the era of immunotherapy, the effect of these novel drugs on uncommon metastasis, such as to the thyroid, is unknown. We report the rare case of a thyroid metastasis in a patient diagnosed with ocular melanoma initially managed with enucleation. Metastatic disease developed in the lung and thyroid gland. The case patient received the immunotherapy ipilimumab with stable disease in the thyroid and progressive disease elsewhere. The patient was then further treated with a second immunotherapy agent, pembrolizumab, and remains with stable disease one year later. We discuss the current literature on thyroid metastases from all causes and the optimal known management strategies. Furthermore, we provide an original report on the response of this disease to the novel immunomodulators, ipilimumab, and pembrolizumab with stable disease four years after initial diagnosis of ocular melanoma.

  13. Uveal melanoma: evaluation of extrascleral extension using thin-section MR of the eye with surface coils.

    Science.gov (United States)

    Tartaglione, Tommaso; Pagliara, Monica Maria; Sciandra, Mariacarmela; Caputo, Carmela Grazia; Calandrelli, Rosalinda; Fabrizi, Gina; Gaudino, Simona; Blasi, Maria Antonietta; Colosimo, Cesare

    2014-10-01

    This study was done to evaluate the role of high-resolution magnetic resonance (MR) imaging with special surface coils in selecting the correct therapeutic approach (eye enucleation or follow-up) in patients with suspected extrascleral extension of uveal melanoma. This prospective study involved 12 patients with suspected extrascleral extension of uveal melanoma on orbital ultrasonography. All patients were studied with thin-section MR imaging of the eye using surface coils. High-resolution MR imaging of the eye excluded extrascleral extension of disease in 8/12 patients: in 4/8 cases it revealed vascular ectasia and in the other 4/8 cases the linear hypointensity of the sclera was unbroken. Seven of these eight patients were followed up by ultrasound, which showed stability of melanoma for at least 2 years, while the last patient underwent enucleation, and the histological examination confirmed the MR diagnosis. In 4/12 patients, high-resolution MR suggested a diagnosis of extrascleral extension of melanoma, which was confirmed at histological examination after enucleation. High-resolution MR imaging of the eye with surface coils allowed us to evaluate extrascleral extension of uveal melanoma and choose the correct therapeutic approach, avoiding unnecessary enucleation in 7/12 patients.

  14. In vitro anti-uveal melanoma activity of phenolic compounds from the Egyptian medicinal plant Acacia nilotica.

    Science.gov (United States)

    Salem, Manar M; Davidorf, Frederick H; Abdel-Rahman, Mohamed H

    2011-12-01

    Anti-uveal melanoma activity-guided fractionation of the MeOH extract of Acacia nilotica pods resulted in the isolation of the new compound gallocatechin 5-O-gallate in addition to methyl gallate, gallic acid, catechin, catechin 5-O-gallate, 1-O-galloyl-β-D-glucose, 1,6-di-O-galloyl-β-D-glucose and digallic acid. The structures of the isolated compounds were elucidated on the basis of HRESIMS, NMR spectroscopy and CD data. In addition to uveal melanoma, the antiproliferative activities of the isolated compounds and the related compound epigallocatechin 3-O-gallate (EGCG) were evaluated against cutaneous melanoma, ovarian cancer, glioblastoma and normal retinal pigmented cells. Copyright © 2011 Elsevier B.V. All rights reserved.

  15. Visual Outcomes of Parapapillary Uveal Melanomas Following Proton Beam Therapy

    International Nuclear Information System (INIS)

    Thariat, Juliette; Grange, Jean-Daniel; Mosci, Carlo; Rosier, Laurence; Maschi, Celia; Lanza, Francesco; Nguyen, Anh Minh; Jaspart, Franck; Bacin, Franck; Bonnin, Nicolas; Gaucher, David; Sauerwein, Wolfgang; Angellier, Gaelle; Hérault, Joel; Caujolle, Jean-Pierre

    2016-01-01

    Purpose: In parapapillary melanoma patients, radiation-induced optic complications are frequent and visual acuity is often compromised. We investigated dose-effect relationships for the optic nerve with respect to visual acuity after proton therapy. Methods and Materials: Of 5205 patients treated between 1991 and 2014, those treated using computed tomography (CT)-based planning to 52 Gy (prescribed dose, not accounting for relative biologic effectiveness correction of 1.1) in 4 fractions, with minimal 6-month follow-up and documented initial and last visual acuity, were included. Deterioration of ≥0.3 logMAR between initial and last visual acuity results was reported. Results: A total of 865 consecutive patients were included. Median follow-up was 69 months, mean age was 61.7 years, tumor abutted the papilla in 35.1% of patients, and tumor-to-fovea distance was ≤3 mm in 74.2% of patients. Five-year relapse-free survival rate was 92.7%. Visual acuity was ≥20/200 in 72.6% of patients initially and 47.2% at last follow-up. A wedge filter was used in 47.8% of the patients, with a positive impact on vision and no impact on relapse. Glaucoma, radiation-induced optic neuropathy, maculopathy were reported in 17.9%, 47.5%, and 33.6% of patients, respectively. On multivariate analysis, age, diabetes, thickness, initial visual acuity and percentage of macula receiving 26 Gy were predictive of visual acuity. Furthermore, patients irradiated to ≥80% of their papilla had better visual acuity when limiting the 50% (30-Gy) and 20% (12-Gy) isodoses to ≤2 mm and 6 mm of optic nerve length, respectively. Conclusions: A personalized proton therapy plan with optic nerve and macular sparing can be used efficiently with good oncological and functional results in parapapillary melanoma patients.

  16. Visual Outcomes of Parapapillary Uveal Melanomas Following Proton Beam Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Thariat, Juliette, E-mail: jthariat@gmail.com [Department of Radiation Therapy, Cancer Center Antoine Lacassagne-Nice Sophia Antipolis University Hospital, Nice (France); Grange, Jean-Daniel [Department of Ophthalmology, Eye University Clinic la Croix Rousse, Lyon (France); Mosci, Carlo [Department of Ophthalmology, National Institute for Cancer Research, Mura Delle Cappucine, Genova (Italy); Rosier, Laurence [Eye Clinic, Centre d' Exploration et de Traitement de la Retine et de la Macula, Bordeaux (France); Maschi, Celia [Department of Ophthalmology, Eye University Clinic Pasteur 2, Nice (France); Lanza, Francesco [Department of Ophthalmology, National Institute for Cancer Research, Mura Delle Cappucine, Genova (Italy); Nguyen, Anh Minh [Department of Ophthalmology, Eye University Clinic la Croix Rousse, Lyon (France); Jaspart, Franck; Bacin, Franck; Bonnin, Nicolas [Department of Ophthalmology, Eye University Clinic Gabriel Montpied, Clermont Ferrand (France); Gaucher, David [Department of Ophthalmology, Eye University Clinic, Hopital Civil, Strasbourg (France); Sauerwein, Wolfgang [Department of Radiation Therapy, NCTeam, Strahlenklinik, Universitätsklinikum Essen, Essen (Germany); Angellier, Gaelle; Hérault, Joel [Department of Radiation Therapy, Cancer Center Antoine Lacassagne-Nice Sophia Antipolis University Hospital, Nice (France); Caujolle, Jean-Pierre [Department of Ophthalmology, Eye University Clinic Pasteur 2, Nice (France)

    2016-05-01

    Purpose: In parapapillary melanoma patients, radiation-induced optic complications are frequent and visual acuity is often compromised. We investigated dose-effect relationships for the optic nerve with respect to visual acuity after proton therapy. Methods and Materials: Of 5205 patients treated between 1991 and 2014, those treated using computed tomography (CT)-based planning to 52 Gy (prescribed dose, not accounting for relative biologic effectiveness correction of 1.1) in 4 fractions, with minimal 6-month follow-up and documented initial and last visual acuity, were included. Deterioration of ≥0.3 logMAR between initial and last visual acuity results was reported. Results: A total of 865 consecutive patients were included. Median follow-up was 69 months, mean age was 61.7 years, tumor abutted the papilla in 35.1% of patients, and tumor-to-fovea distance was ≤3 mm in 74.2% of patients. Five-year relapse-free survival rate was 92.7%. Visual acuity was ≥20/200 in 72.6% of patients initially and 47.2% at last follow-up. A wedge filter was used in 47.8% of the patients, with a positive impact on vision and no impact on relapse. Glaucoma, radiation-induced optic neuropathy, maculopathy were reported in 17.9%, 47.5%, and 33.6% of patients, respectively. On multivariate analysis, age, diabetes, thickness, initial visual acuity and percentage of macula receiving 26 Gy were predictive of visual acuity. Furthermore, patients irradiated to ≥80% of their papilla had better visual acuity when limiting the 50% (30-Gy) and 20% (12-Gy) isodoses to ≤2 mm and 6 mm of optic nerve length, respectively. Conclusions: A personalized proton therapy plan with optic nerve and macular sparing can be used efficiently with good oncological and functional results in parapapillary melanoma patients.

  17. Experience with Ruthenium 106-treatment of uveal malignant melanoma

    International Nuclear Information System (INIS)

    Laatikainen, L.; Tarkkanen, A.

    1987-01-01

    In 1981-1986, 25 eyes with malignant melanoma of the uvea were treated with beta irradiation using ruthenium 106 plaques. In 21 cases the tumour originated in the choriod, in 4 cases in the ciliary body. In 12 eyes it was within 3 mm from the optic disc or the fovea, and the mean height (±SEM) was 5.2±0.4 mm. Three eyes received two sets of irradiation with 1.1 - 1.7 years' interval. After a mean followup of 1.6 years (range 0,5 - 5.6) the tumour had decreased in size in 12, was unchanged in 6, and had progressed in 7 eyes, 4 of the latter were enucleated. In 3 patients metastases were diagnosed (2.0 -2.9 years after irradiation), and 1 patient has died (3.3 years after the first irradiation). Twelve eyes have retained useful vision (0.05 or better), but in some of them a tendency to deterioration was observed 3-5 years after treatment due to radiation maculopathy. Other causes of visual loss were the centrally located tumour itself, exudative detachment of the retina, and persistent vitreous haemorrhage. (author)

  18. Experience with Ruthenium /sup 106/-treatment of uveal malignant melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Laatikainen, L.; Tarkkanen, A.

    1987-01-01

    In 1981-1986, 25 eyes with malignant melanoma of the uvea were treated with beta irradiation using ruthenium/sup 106/ plaques. In 21 cases the tumour originated in the choriod, in 4 cases in the ciliary body. In 12 eyes it was within 3 mm from the optic disc or the fovea, and the mean height (+-SEM) was 5.2+-0.4 mm. Three eyes received two sets of irradiation with 1.1 - 1.7 years' interval. After a mean followup of 1.6 years (range 0,5 - 5.6) the tumour had decreased in size in 12, was unchanged in 6, and had progressed in 7 eyes, 4 of the latter were enucleated. In 3 patients metastases were diagnosed (2.0 -2.9 years after irradiation), and 1 patient has died (3.3 years after the first irradiation). Twelve eyes have retained useful vision (0.05 or better), but in some of them a tendency to deterioration was observed 3-5 years after treatment due to radiation maculopathy. Other causes of visual loss were the centrally located tumour itself, exudative detachment of the retina, and persistent vitreous haemorrhage.

  19. LINAC based stereotactic radiotherapy of uveal melanoma: 4 years clinical experience

    International Nuclear Information System (INIS)

    Dieckmann, Karin; Georg, Dietmar; Zehetmayer, Martin; Bogner, Joachim; Georgopoulos, Michael; Poetter, Richard

    2003-01-01

    Purpose: To study local tumor control and radiogenic side effects after fractionated LINAC based stereotactic radiotherapy for selected uveal melanoma. Patients and methods: Between June 1997 and March 2001, 90 patients suffering from uveal melanoma were treated at a LINAC with 6 MV. The head was immobilized with a modified stereotactic frame system (BrainLAB). For stabilization of the eye position a light source was integrated into the mask system in front of the healthy or the diseased eye. A mini-video camera was used for on-line eye movement control. Tumors included in the study were either located unfavorably with respect to macula and optical disc ( 7 mm. Median tumor volume was 305±234 mm 3 (range 70-1430 mm 3 ), and mean tumor height was 5.4±2.3 mm (range 2.7-15.9 mm). Total doses of 70 (single dose 14 Gy at 80% isodose) or 60 Gy (single dose 12 Gy at 80% isodose) were applied in five fractions within 10 days. The first fractionation results in total dose (TD) (2 Gy) of 175 Gy for tumor and 238 Gy for normal tissue, corresponding values for the second fractionation schedule are 135 and 180 Gy, respectively. Results: After a median follow-up of 20 months (range 1-48 months) local control was achieved in 98% (n=88). The mean relative tumor reductions were 24, 27, and 37% after 12, 24 and 36 months. Three patients (3.3%) developed metastases. Secondary enucleation was performed in seven patients (7.7%). Long term side effects were retinopathy (25.5%), cataract (18.9%), optic neuropathy (20%), and secondary neovascular glaucoma (8.8%). Conclusion: Fractionated LINAC based stereotactic photon beam therapy in conjunction with a dedicated eye movement control system is a highly effective method to treat unfavorably located uveal melanoma. Total doses of 60 Gy (single dose 12 Gy) are considered to be sufficient to achieve good local tumor control

  20. Kinome-wide transcriptional profiling of uveal melanoma reveals new vulnerabilities to targeted therapeutics.

    Science.gov (United States)

    Bailey, Fiona P; Clarke, Kim; Kalirai, Helen; Kenyani, Jenna; Shahidipour, Haleh; Falciani, Francesco; Coulson, Judy M; Sacco, Joseph J; Coupland, Sarah E; Eyers, Patrick A

    2018-03-01

    Metastatic uveal melanoma (UM) is invariably fatal, usually within a year of diagnosis. There are currently no effective therapies, and clinical studies employing kinase inhibitors have so far demonstrated limited success. This is despite common activating mutations in GNAQ/11 genes, which trigger signalling pathways that might predispose tumours to a variety of targeted drugs. In this study, we have profiled kinome expression network dynamics in various human ocular melanomas. We uncovered a shared transcriptional profile in human primary UM samples and across a variety of experimental cell-based models. The poor overall response of UM cells to FDA-approved kinase inhibitors contrasted with much higher sensitivity to the bromodomain inhibitor JQ1, a broad transcriptional repressor. Mechanistically, we identified a repressed FOXM1-dependent kinase subnetwork in JQ1-exposed cells that contained multiple cell cycle-regulated protein kinases. Consistently, we demonstrated vulnerability of UM cells to inhibitors of mitotic protein kinases within this network, including the investigational PLK1 inhibitor BI6727. We conclude that analysis of kinome-wide signalling network dynamics has the potential to reveal actionable drug targets and inhibitors of potential therapeutic benefit for UM patients. © 2017 The Authors. Pigment Cell & Melanoma Research Published by John Wiley & Sons.

  1. Local Recurrence After Uveal Melanoma Proton Beam Therapy: Recurrence Types and Prognostic Consequences

    International Nuclear Information System (INIS)

    Caujolle, Jean-Pierre; Paoli, Vincent; Chamorey, Emmanuel; Maschi, Celia; Baillif, Stéphanie; Herault, Joël; Gastaud, Pierre; Hannoun-Levi, Jean Michel

    2013-01-01

    Purpose: To study the prognosis of the different types of uveal melanoma recurrences treated by proton beam therapy (PBT). Methods and Materials: This retrospective study analyzed 61 cases of uveal melanoma local recurrences on a total of 1102 patients treated by PBT between June 1991 and December 2010. Survival rates have been determined by using Kaplan-Meier curves. Prognostic factors have been evaluated by using log-rank test or Cox model. Results: Our local recurrence rate was 6.1% at 5 years. These recurrences were divided into 25 patients with marginal recurrences, 18 global recurrences, 12 distant recurrences, and 6 extrascleral extensions. Five factors have been identified as statistically significant risk factors of local recurrence in the univariate analysis: large tumoral diameter, small tumoral volume, low ratio of tumoral volume over eyeball volume, iris root involvement, and safety margin inferior to 1 mm. In the local recurrence-free population, the overall survival rate was 68.7% at 10 years and the specific survival rate was 83.6% at 10 years. In the local recurrence population, the overall survival rate was 43.1% at 10 years and the specific survival rate was 55% at 10 years. The multivariate analysis of death risk factors has shown a better prognosis for marginal recurrences. Conclusion: Survival rate of marginal recurrences is superior to that of the other recurrences. The type of recurrence is a clinical prognostic value to take into account. The influence of local recurrence retreatment by proton beam therapy should be evaluated by novel studies

  2. Proton therapy of uveal melanomas. Intercomparison of MRI-based and conventional treatment planning

    International Nuclear Information System (INIS)

    Marnitz, S.; Hinkelbein, W.; Cordini, D.; Heufelder, J.; Simiantonakis, I.; Kluge, H.; Bendl, R.; Lemke, A.J.; Bechrakis, N.E.; Foerster, M.H.

    2006-01-01

    Background and purpose: proton therapy for uveal melanoma provides high-conformal dose application to the target volume and, thus, an optimal saving of the organs at risk nearby. Treatment planning is done with the model-based treatment-planning system eyeplan. Tumor reconstruction is based only on a fundus composite, which often leads to an overestimation of the clinical target volume (CTV). The purpose was to exploit MRI on trial in a proton therapy-planning system by using the novel image-based treatment-planning system octopus. Patients and methods: ten patients with uveal melanomas received both a high-resolution planning CT and MRI of the eye. MR examinations were made with an eye coil. Eyeplan requires eye geometry data for modeling, and tantalum marker clips for submillimeter positioning and additional information from ultrasound and 3-D imaging. By contrast, octopus provides the full integration of 3-D imaging (e.g., CT, MRI). CTVs were delineated in each slice. For all patients, CTVs (eyeplan vs. octopus) were compared intraindividually. Results: octopus planning led to a mean reduction of the target volume by a factor of 1.7 (T1-weighted [T1w]) and 2.2 (T2w) without compromising safety. The corresponding field size could be scaled down on average by a factor of 1.2 (T1w) and 1.4 (T2w), respectively. Conclusion: compared with the conventional eyeplan, MRI-based treatment planning of ocular tumors with octopus could be a powerful tool for reducing the CTV and, consequently, the treatment volume and the field size. This might be translated into a better patient compliance during treatment and a decreased late toxicity. (orig.)

  3. Local Recurrence After Primary Proton Beam Therapy in Uveal Melanoma: Risk Factors, Retreatment Approaches, and Outcome.

    Science.gov (United States)

    Seibel, Ira; Cordini, Dino; Rehak, Matus; Hager, Annette; Riechardt, Aline I; Böker, Alexander; Heufelder, Jens; Weber, Andreas; Gollrad, Johannes; Besserer, Angela; Joussen, Antonia M

    2015-10-01

    To evaluate the risk factors, recurrence rates, retreatments, and long-term patient outcomes following proton beam therapy for uveal melanoma. Retrospective interventional case series. All patients treated with primary proton beam therapy for uveal melanoma at the oncology service at Charité-Berlin and Helmholtz-Zentrum-Berlin between May 1998 and December 2008 were reviewed for local recurrence. Of 982 patients, 982 eyes matched the inclusion criteria. The data were obtained from electronic health records, operative reports, discharge letters, and radiation planning. Comparisons of fundus photographs and ultrasound measurements were performed to assess the growth pattern of the tumor and to determine the success of retreatment, in the case that a globe-retaining therapy was undertaken. Of 982 patients, 35 patients (3.6%) developed local recurrence. The median follow-up was 60.7 months (6.0-170.4 months). Local control rate was 96.4% and the overall eye retention rate was 95.0% in this cohort. Local recurrence was correlated with a higher risk for metastasis and reduced survival. Largest tumor diameter was identified as the sole statistically significant risk factor for local recurrence (P = .00001). All globe-retaining retreatment approaches for local recurrence, including proton beam therapy, brachytherapy, and transpupillary thermotherapy used for recurrences at the tumor margins, showed good local tumor control and similar metastasis-free survivals. This study showed that each globe-retaining retreatment approach can result in satisfying local tumor control. In case of early detection of local recurrence, preservation of the globe can be warranted. Therefore, regularly performed follow-ups should be ensured. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Outcomes of Iodine-125 Plaque Brachytherapy for Uveal Melanoma With Intraoperative Ultrasonography and Supplemental Transpupillary Thermotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Badiyan, Shahed N. [Department of Radiation Oncology, Mallinckrodt Institute of Radiology, St. Louis, Missouri (United States); Rao, Rajesh C. [Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri (United States); Apicelli, Anthony J.; Acharya, Sahaja; Verma, Vivek; Garsa, Adam A.; DeWees, Todd; Speirs, Christina K.; Garcia-Ramirez, Jose; Esthappan, Jacqueline; Grigsby, Perry W. [Department of Radiation Oncology, Mallinckrodt Institute of Radiology, St. Louis, Missouri (United States); Harbour, J. William, E-mail: JWHarbour@med.miami.edu [Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri (United States); Ocular Oncology Service, Department of Ophthalmology, Bascom Palmer Eye Institute and Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida (United States)

    2014-03-15

    Purpose: To assess the impact on local tumor control of intraoperative ultrasonographic plaque visualization and selective application of transpupillary thermotherapy (TTT) in the treatment of posterior uveal melanoma with iodine-125 (I-125) episcleral plaque brachytherapy (EPB). Methods and Materials: Retrospective analysis of 526 patients treated with I-125 EPB for posterior uveal melanoma. Clinical features, dosimetric parameters, TTT treatments, and local tumor control outcomes were recorded. Statistical analysis was performed using Cox proportional hazards and Kaplan-Meier life table method. Results: The study included 270 men (51%) and 256 women (49%), with a median age of 63 years (mean, 62 years; range, 16-91 years). Median dose to the tumor apex was 94.4 Gy (mean, 97.8; range, 43.9-183.9) and to the tumor base was 257.9 Gy (mean, 275.6; range, 124.2-729.8). Plaque tilt >1 mm away from the sclera at plaque removal was detected in 142 cases (27%). Supplemental TTT was performed in 72 patients (13.7%). One or 2 TTT sessions were required in 71 TTT cases (98.6%). After a median follow-up of 45.9 months (mean, 53.4 months; range, 6-175 months), local tumor recurrence was detected in 19 patients (3.6%). Local tumor recurrence was associated with lower dose to the tumor base (P=.02). Conclusions: Ultrasound-guided plaque localization of I-125 EPB is associated with excellent local tumor control. Detection of plaque tilt by ultrasonography at plaque removal allows supplemental TTT to be used in patients at potentially higher risk for local recurrence while sparing the majority of patients who are at low risk. Most patients require only 1 or 2 TTT sessions.

  5. Proton therapy of uveal melanomas. Intercomparison of MRI-based and conventional treatment planning

    Energy Technology Data Exchange (ETDEWEB)

    Marnitz, S.; Hinkelbein, W. [Dept. of Radiooncology, Charite Univ. Medicine, Berlin (Germany); Cordini, D.; Heufelder, J.; Simiantonakis, I.; Kluge, H. [Eye Tumor Therapy, Hahn-Meitner Inst., Berlin (Germany); Bendl, R. [Dept. of Medical Physics, German Cancer Research Center (DKFZ), Heidelberg (Germany); Lemke, A.J. [Dept. of Diagnostic Radiology, Charite Univ. Medicine, Berlin (Germany); Bechrakis, N.E.; Foerster, M.H. [Dept. of Ophthalmology, Charite Univ. Medicine, Berlin (Germany)

    2006-07-15

    Background and purpose: proton therapy for uveal melanoma provides high-conformal dose application to the target volume and, thus, an optimal saving of the organs at risk nearby. Treatment planning is done with the model-based treatment-planning system eyeplan. Tumor reconstruction is based only on a fundus composite, which often leads to an overestimation of the clinical target volume (CTV). The purpose was to exploit MRI on trial in a proton therapy-planning system by using the novel image-based treatment-planning system octopus. Patients and methods: ten patients with uveal melanomas received both a high-resolution planning CT and MRI of the eye. MR examinations were made with an eye coil. Eyeplan requires eye geometry data for modeling, and tantalum marker clips for submillimeter positioning and additional information from ultrasound and 3-D imaging. By contrast, octopus provides the full integration of 3-D imaging (e.g., CT, MRI). CTVs were delineated in each slice. For all patients, CTVs (eyeplan vs. octopus) were compared intraindividually. Results: octopus planning led to a mean reduction of the target volume by a factor of 1.7 (T1-weighted [T1w]) and 2.2 (T2w) without compromising safety. The corresponding field size could be scaled down on average by a factor of 1.2 (T1w) and 1.4 (T2w), respectively. Conclusion: compared with the conventional eyeplan, MRI-based treatment planning of ocular tumors with octopus could be a powerful tool for reducing the CTV and, consequently, the treatment volume and the field size. This might be translated into a better patient compliance during treatment and a decreased late toxicity. (orig.)

  6. Proton beam radiotherapy for uveal melanoma: Results of Curie Institut-Orsay Proton Therapy Center (ICPO)

    International Nuclear Information System (INIS)

    Dendale, Remi; Lumbroso-Le Rouic, Livia; Noel, Georges; Feuvret, Loic; Levy, Christine; Delacroix, Sabine; Meyer, Anne; Nauraye, Catherine; Mazal, Alejandro; Mammar, Hamid; Garcia, Paul; D'Hermies, Francois; Frau, Eric; Plancher, Corine; Asselain, Bernard; Schlienger, Pierre; Mazeron, Jean Jacques; Desjardins, Laurence

    2006-01-01

    Purpose: This study reports the results of proton beam radiotherapy based on a retrospective series of patients treated for uveal melanoma at the Orsay Center. Methods and Materials: Between September 1991 and September 2001, 1,406 patients with uveal melanoma were treated by proton beam radiotherapy. A total dose of 60 cobalt Gray equivalent (CGE) was delivered in 4 fractions on 4 days. Survival rates were determined using Kaplan-Meier estimates. Prognostic factors were determined by multivariate analysis using the Cox model. Results: The median follow-up was 73 months (range, 24-142 months). The 5-year overall survival and metastasis-free survival rates were 79% and 80.6%, respectively. The 5-year local control rate was 96%. The 5-year enucleation for complications rate was 7.7%. Independent prognostic factors for overall survival were age (p < 0.0001), gender (p < 0.0003), tumor site (p < 0.0001), tumor thickness (p = 0.02), tumor diameter (p < 0.0001), and retinal area receiving at least 30 CGE (p = 0.003). Independent prognostic factors for metastasis-free survival were age (p = 0.0042), retinal detachment (p = 0.01), tumor site (p < 0.0001), tumor volume (p < 0.0001), local recurrence (p < 0.0001), and retinal area receiving at least 30 CGE (p = 0.002). Independent prognostic factors for local control were tumor diameter (p = 0.003) and macular area receiving at least 30 CGE (p = 0.01). Independent prognostic factors for enucleation for complications were tumor thickness (p < 0.0001) and lens volume receiving at least 30 CGE (p = 0.0002). Conclusion: This retrospective study confirms that proton beam radiotherapy ensures an excellent local control rate. Further clinical studies are required to decrease the incidence of postirradiation ocular complications

  7. Expression and migratory analysis of 5 human uveal melanoma cell lines for CXCL12, CXCL8, CXCL1, and HGF

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    Di Cesare Sebastian

    2007-01-01

    Full Text Available Abstract Background The aim of this study was to characterize the presence and roles of CXCL12, CXCL8, CXCL1, and HGF in five human uveal melanoma cell lines, using different methods, in order to ascertain their significance in this disease. Methods Five human uveal melanoma cell lines (92.1, SP6.5, MKT-BR, OCM-1, and UW-1 of known proliferative, invasive, and metastatic potential were used in this experiment. A migration assay was used in order to assess the responsiveness of each cell line towards the four chosen chemotactic factors. Immunohistochemistry was then performed for all five cell lines (cytospins using antibodies directed toward CXCL1, CXCL8 and their receptors CXCR2 and CXCR1 respectively. Quantitative real-time PCR was then performed on all five cell lines in order to establish the presence of these four chemotactic factors. Results All five human uveal melanoma cell lines migrated towards the four chosen chemotactic factors at a level greater than that of the negative control. Chemokines CXCL1 and CXCL8 resulted in the greatest number of migrating cells in all five of our cell lines. Immunohistochemistry confirmed the expression of CXCL1, CXCL8, and their receptors CXCR2 and CXCR1 in all five of the cell lines. Quantitative real-time PCR results established expression of CXCL8, CXCL1, and HGF in all 5 cell lines tested. CXCL1 and CXCL8 are highly expressed in SP6.5 and UW-1. None of the five cell lines expressed any detectable levels of CXCL12. Conclusion The migratory ability of the 5 human uveal melanoma cell lines was positively influenced by the four chemotactic factors tested, namely CXCL12, CXCL8, CXCL1, and HGF. Self-expression of chemotactic factors CXCL8, CXCL1, and HGF may indicate an autocrine system, which perhaps contributes to the cells' metastatic ability in vivo.

  8. Management of posterior uveal melanoma: past, present, and future: the 2014 Charles L. Schepens lecture.

    Science.gov (United States)

    Shields, Jerry A; Shields, Carol L

    2015-02-01

    To review the management of ciliary body and choroidal melanoma (posterior uveal melanoma [PUM]) over the last century with an emphasis on changing concepts. Retrospective review. Review of personal experience over 40 years and pertinent literature on management of PUM. Diagnosis and therapy for PUM. Patient survival. In the early 1900s, most patients presented with a large symptomatic melanoma that necessitated enucleation, and the systemic prognosis was poor. In the 1970s, controversy erupted regarding the role of enucleation for PUM. Some authorities advocated prompt enucleation, and others proposed that enucleation promoted metastasis, known as the "Zimmerman hypothesis." Others recommended observation, withholding treatment until tumor growth was documented. During the 1970s, there was a trend toward eye-saving procedures, including laser photocoagulation, surgical removal of tumor, and techniques of radiotherapy. Despite local treatment success, systemic prognosis remained guarded with approximately 40% mortality overall. However, there was convincing evidence that smaller tumors offered a significantly better prognosis. Currently, there is a movement toward earlier identification and treatment of small melanomas using clinical factors predictive of malignant potential, in keeping with similar philosophy regarding other cancers. Further understanding of melanoma cytogenetics and molecular pathways have helped to recognize patients at risk for metastasis. At-risk patients are offered systemic therapeutic trials to prevent metastasis. We anticipate that the future management of PUM will focus on detection of clinical and imaging clues for earliest diagnosis, prompt local tumor treatment, and systemic targeted therapies for microscopic metastasis or prevention of metastasis. Personalized evaluation of patient-specific melanoma molecular pathway signature could allow for therapeutic intervention at a site specific to the pathway abnormality that leads to the

  9. Ruthenium-106 eye plaque brachytherapy in the conservative treatment of uveal melanoma: a mono-institutional experience.

    Science.gov (United States)

    Perri, P; Fiorica, F; D'Angelo, S; Lamberti, G; Parmeggiani, F; Martini, A; Carpenteri, F; Colosimo, C; Micucci, M; Perazzini, L; De Gugliemo, E; Berretta, M; Sebastiani, A; Cartei, F

    2012-12-01

    Traditional treatment for uveal melanoma is the enucleation of the eye with outcomes cosmetically unacceptable and loss of useful vision. Plaque brachytherapy, compared to enucleation, had the advantage to preserve the eye with outcomes cosmetically acceptable and preservation of vision. From July 1990 to December 2009 one hundred forty-two (142) patients (51 males and 91 females) with small to medium uveal melanoma were treated with 106Ru plaque brachytherapy. The patients underwent a complete staging before brachytherapy with indirect ophthalmoscopy and ultrasounds. Mean tumour thickness was 3.26 mm (1.6-6 mm). The dose scheduled was 80-100 Gy to the apex with a maximum dose of 800 Gy to the sclera. One hundred forty-two have been treated, nine patients had lost the follow-up and drop out; 133 patients were assessed. Mean follow-up was 7.7 years (6 months-18 years). The overall survival at 5, 10 and 15 years was 92%, 85% and 78% respectively. Cancer fee survival was 95%, 90% and 83%, respectively at 5, 10 and 15 year. Radiation-induced toxicity was represented in 47 patients with a 5 year actuarial survival rate free from complications of 54%. 106Ru plaque brachytherapy is a valid approach for treatment of uveal melanoma. This technique is efficacy and safe, with a low toxicity profile.

  10. Nonlethal Levels of Zeaxanthin Inhibit Cell Migration, Invasion, and Secretion of MMP-2 via NF-κB Pathway in Cultured Human Uveal Melanoma Cells

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    Ming-Chao Bi

    2016-01-01

    Full Text Available Zeaxanthin at nonlethal dosages (3–10 μM significantly inhibited the cell migration of cultured uveal melanoma cells (C918 cell line as determined by wound healing assay and Boyden chamber assay. Matrigel invasion assay showed that cell invasion of uveal melanoma cells could be significantly inhibited by zeaxanthin. Secretion of MMP-2 by melanoma cells was significantly inhibited by zeaxanthin in a dose-dependent manner as measured by ELISA kit. Zeaxanthin also significantly inhibited the NF-κB levels in nuclear extracts of the UM cells, which is the upstream of the MMP-2 secretion. These results suggest that zeaxanthin might be a potentially therapeutic approach in the prevention of metastasis in uveal melanoma.

  11. Selumetinib in Combination With Dacarbazine in Patients With Metastatic Uveal Melanoma: A Phase III, Multicenter, Randomized Trial (SUMIT).

    Science.gov (United States)

    Carvajal, Richard D; Piperno-Neumann, Sophie; Kapiteijn, Ellen; Chapman, Paul B; Frank, Stephen; Joshua, Anthony M; Piulats, Josep M; Wolter, Pascal; Cocquyt, Veronique; Chmielowski, Bartosz; Evans, T R Jeffry; Gastaud, Lauris; Linette, Gerald; Berking, Carola; Schachter, Jacob; Rodrigues, Manuel J; Shoushtari, Alexander N; Clemett, Delyth; Ghiorghiu, Dana; Mariani, Gabriella; Spratt, Shirley; Lovick, Susan; Barker, Peter; Kilgour, Elaine; Lai, Zhongwu; Schwartz, Gary K; Nathan, Paul

    2018-04-20

    Purpose Uveal melanoma is the most common primary intraocular malignancy in adults with no effective systemic treatment option in the metastatic setting. Selumetinib (AZD6244, ARRY-142886) is an oral, potent, and selective MEK1/2 inhibitor with a short half-life, which demonstrated single-agent activity in patients with metastatic uveal melanoma in a randomized phase II trial. Methods The Selumetinib (AZD6244: ARRY-142886) (Hyd-Sulfate) in Metastatic Uveal Melanoma (SUMIT) study was a phase III, double-blind trial ( ClinicalTrial.gov identifier: NCT01974752) in which patients with metastatic uveal melanoma and no prior systemic therapy were randomly assigned (3:1) to selumetinib (75 mg twice daily) plus dacarbazine (1,000 mg/m 2 intravenously on day 1 of every 21-day cycle) or placebo plus dacarbazine. The primary end point was progression-free survival (PFS) by blinded independent central radiologic review. Secondary end points included overall survival and objective response rate. Results A total of 129 patients were randomly assigned to receive selumetinib plus dacarbazine (n = 97) or placebo plus dacarbazine (n = 32). In the selumetinib plus dacarbazine group, 82 patients (85%) experienced a PFS event, compared with 24 (75%) in the placebo plus dacarbazine group (median, 2.8 v 1.8 months); the hazard ratio for PFS was 0.78 (95% CI, 0.48 to 1.27; two-sided P = .32). The objective response rate was 3% with selumetinib plus dacarbazine and 0% with placebo plus dacarbazine (two-sided P = .36). At 37% maturity (n = 48 deaths), analysis of overall survival gave a hazard ratio of 0.75 (95% CI, 0.39 to 1.46; two-sided P = .40). The most frequently reported adverse events (selumetinib plus dacarbazine v placebo plus dacarbazine) were nausea (62% v 19%), rash (57% v 6%), fatigue (44% v 47%), diarrhea (44% v 22%), and peripheral edema (43% v 6%). Conclusion In patients with metastatic uveal melanoma, the combination of selumetinib plus dacarbazine had a tolerable safety

  12. Ruthenium-106 brachytherapy for uveal melanomas. Preliminary results: a single institutional experience; Braquiterapia com rutenio-106 em melanomas uveais. Resultados preliminares: experiencia uni-instuticional

    Energy Technology Data Exchange (ETDEWEB)

    Dias, Rodrigo Souza; Giordani, Adelmo Jose; Segreto, Helena Regina Comodo; Segreto, Roberto Araujo [Universidade Federal de Sao Paulo/Escola Paulista de Medicina (Unifesp/EPM), Sao Paulo, SP (Brazil). Departamento de Medicina. Setor de Radioterapia ; Erwenne, Clelia Maria; Teixeira, Luiz Fernando [Universidade Federal de Sao Paulo/Escola Paulista de Medicina (UNIFESP/EPM), Sao Paulo, SP (Brazil). Dept. de Oftalmologia]. E-mail: segreto. dmed@epm.br

    2007-03-15

    Objective: To analyze the early response of uveal melanomas in patients treated with ruthenium-106 brachytherapy. Materials And Methods: In the period between April 2002 and July 2003, 20 patients diagnosed with uveal melanoma were submitted to ruthenium-106 brachytherapy. The calculated dose delivered at the apex of the tumor ranged between 55 Gy and 100 Gy. Patients with lesions greater than 5 mm were submitted to transpupillary thermotherapy concomitantly with ophthalmic plaque insertion. Results: As regards the lesions site, 75% of the lesions were located in the choroid, 15% in the iris, and the remainder 10% in the ciliary body. In a median 19-month-follow-up, the progression-free survival for brachytherapy was 69%, and 87% for associated brachytherapy and transpupillary thermotherapy. A significant tumor height reduction was observed after treatment. No patient was submitted to enucleation. Conclusion: Our preliminary results show that ruthenium-106 brachytherapy is an appropriate method for conservative treatment of patients with uveal melanomas in terms of local management, ocular and visual acuity preservation with an acceptable complications incidence rate. (author)

  13. Exome sequencing identifies recurrent somatic mutations in EIF1AX and SF3B1 in uveal melanoma with disomy 3

    Science.gov (United States)

    Martin, Marcel; Maßhöfer, Lars; Temming, Petra; Rahmann, Sven; Metz, Claudia; Bornfeld, Norbert; van de Nes, Johannes; Klein-Hitpass, Ludger; Hinnebusch, Alan G; Horsthemke, Bernhard; Lohmann, Dietmar R; Zeschnigk, Michael

    2014-01-01

    Gene expression profiles and chromosome 3 copy number divide uveal melanomas into two distinct classes correlating with prognosis1–3. Using exome sequencing, we identified recurrent somatic mutations in EIF1AX and SF3B1, specifically occurring in uveal melanomas with disomy 3, which rarely metastasize. Targeted resequencing showed that 24 of 31 tumors with disomy 3 (77%) had mutations in either EIF1AX (15; 48%) or SF3B1 (9; 29%). Mutations were infrequent (2/35; 5.7%) in uveal melanomas with monosomy 3, which are associated with poor prognosis2. Resequencing of 13 uveal melanomas with partial monosomy 3 identified 8 tumors with a mutation in either SF3B1 (7; 54%) or EIF1AX (1; 8%). All EIF1AX mutations caused in-frame changes affecting the N terminus of the protein, whereas 17 of 19 SF3B1 mutations encoded an alteration of Arg625. Resequencing of ten uveal melanomas with disomy 3 that developed metastases identified SF3B1 mutations in three tumors, none of which targeted Arg625. PMID:23793026

  14. Automatic real-time surveillance of eye position and gating for stereotactic radiotherapy of uveal melanoma

    International Nuclear Information System (INIS)

    Petersch, Bernhard; Bogner, Joachim; Dieckmann, Karin; Poetter, Richard; Georg, Dietmar

    2004-01-01

    A new prototype (hardware and software) for monitoring eye movements using a noninvasive technique for gated linac-based stereotactic radiotherapy (SRT) of uveal melanoma was developed. The prototype was tested within the scope of a study for 11 patients. Eye immobilization was achieved by having the patient fixate a light source integrated into the system. The system is used in conjunction with a Head and Neck mask system for immobilization, and uses infrared tracking technology for positioning (both BrainLAB AG Heimstetten/Germany). It was used during CT and MR image acquisition as well as during all of five treatment fractions (6 MeV, 5x12 Gy to 80% isodose) to guarantee identical patient setup and eye rotational state during treatment planning and treatment delivery. Maximum temporal and angular deviations tolerated during treatment delivery can be chosen by the physician, the radiation then being interrupted automatically and instantaneously if those criteria are being exceeded during irradiation. A graphical user interface displays life video images of the treated eye and information about the current and previous rotational deviation of the eye from its reference treatment position. The physician thus has online access to data directly linked to the success of the treatment and possible side effects. Mean angular deviations during CT/MR scans and treatment deliveries ranged from 1.61 deg. to 3.64 deg. (standard deviations 0.87 deg. to 2.09 deg.) which is in accordance with precision requirements for SRT. Typical situations when preset deviation criteria were exceeded are slow drifts (fatigue), sudden large eye movements (irritation), or if patients closed their eyes (fatigue). In these cases radiation was reliably interrupted by the gating system. In our clinical setup the novel system for computer-controlled eye movement gated treatments was well tolerated by all patients. The system yields quantitative real-time information about the eye's rotational state

  15. Anterior segment sparing to reduce charged particle radiotherapy complications in uveal melanoma

    International Nuclear Information System (INIS)

    Daftari, Inder K.; Char, Devron H.; Verhey, Lynn J.; Castro, Joseph R.; Petti, Paula L.; Meecham, William J.; Kroll, Stewart; Blakely, Eleanor A.

    1997-01-01

    Purpose: The purpose of this investigation is to delineate the risk factors in the development of neovascular glaucoma (NVG) after helium-ion irradiation of uveal melanoma patients and to propose treatment technique that may reduce this risk. Methods and Materials: 347 uveal melanoma patients were treated with helium-ions using a single-port treatment technique. Using univariate and multivariate statistics, the NVG complication rate was analyzed according to the percent of anterior chamber in the radiation field, tumor size, tumor location, sex, age, dose, and other risk factors. Several University of California San Francisco-Lawrence Berkeley National Laboratory (LBNL) patients in each size category (medium, large, and extralarge) were retrospectively replanned using two ports instead of a single port. By using appropriate polar and azimuthal gaze angles or by treating patients with two ports, the maximum dose to the anterior segment of the eye can often be reduced. Although a larger volume of anterior chamber may receive a lower dose by using two ports than a single port treatment. We hypothesize that this could reduce the level of complications that result from the irradiation of the anterior chamber of the eye. Dose-volume histograms were calculated for the lens, and compared for the single and two-port techniques. Results: NVG developed in 121 (35%) patients. The risk of NVG peaked between 1 and 2.5 years posttreatment. By univariate and multivariate analysis, the percent of lens in the field was strongly correlated with the development of NVG. Other contributing factors were tumor height, history of diabetes, and vitreous hemorrhage. Dose-volume histogram analysis of single-port vs. two-port techniques demonstrate that for some patients in the medium and large category tumor groups, a significant decrease in dose to the structures in the anterior segment of the eye could have been achieved with the use of two ports. Conclusion: The development of NVG after

  16. The effects of a cyclooxygenase-2 (COX-2 expression and inhibition on human uveal melanoma cell proliferation and macrophage nitric oxide production

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    Marshall Jean-Claude

    2007-01-01

    Full Text Available Abstract Background Cyclooxygenase-2 (COX-2 expression has previously been identified in uveal melanoma although the biological role of COX-2 in this intraocular malignancy has not been elucidated. This study aimed to investigate the effect of a COX-2 inhibitor on the proliferation rate of human uveal melanoma cells, as well as its effect on the cytotoxic response of macrophages. Methods Human uveal melanoma cell lines were transfected to constitutively express COX-2 and the proliferative rate of these cells using two different methods, with and without the addition of Amfenac, was measured. Nitric oxide production by macrophages was measured after exposure to melanoma-conditioned medium from both groups of cells as well as with and without Amfenac, the active metabolite of Nepafenac. Results Cells transfected to express COX-2 had a higher proliferation rate than those that did not. The addition of Amfenac significantly decreased the proliferation rate of all cell lines. Nitric oxide production by macrophages was inhibited by the addition of melanoma conditioned medium, the addition of Amfenac partially overcame this inhibition. Conclusion Amfenac affected both COX-2 transfected and non-transfected uveal melanoma cells in terms of their proliferation rates as well as their suppressive effects on macrophage cytotoxic activity.

  17. The Long Non-Coding RNA RHPN1-AS1 Promotes Uveal Melanoma Progression

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    Linna Lu

    2017-01-01

    Full Text Available Increasing evidence suggests that aberrant long non-coding RNAs (lncRNAs are significantly correlated with the pathogenesis, development and metastasis of cancers. RHPN1 antisense RNA 1 (RHPN1-AS1 is a 2030-bp transcript originating from human chromosome 8q24. However, the role of RHPN1-AS1 in uveal melanoma (UM remains to be clarified. In this study, we aimed to elucidate the molecular function of RHPN1-AS1 in UM. The RNA levels of RHPN1-AS1 in UM cell lines were examined using the quantitative real-time polymerase chain reaction (qRT-PCR. Short interfering RNAs (siRNAs were designed to quench RHPN1-AS1 expression, and UM cells stably expressing short hairpin (sh RHPN1-AS1 were established. Next, the cell proliferation and migration abilities were determined using a colony formation assay and a transwell migration/invasion assay. A tumor xenograft model in nude mice was established to confirm the function of RHPN1-AS1 in vivo. RHPN1-AS1 was significantly upregulated in a number of UM cell lines compared with the normal human retinal pigment epithelium (RPE cell line. RHPN1-AS1 knockdown significantly inhibited UM cell proliferation and migration in vitro and in vivo. Our data suggest that RHPN1-AS1 could be an oncoRNA in UM, which may serve as a candidate prognostic biomarker and target for new therapies in malignant UM.

  18. Ion therapy for uveal melanoma in new human eye phantom based on GEANT4 toolkit

    International Nuclear Information System (INIS)

    Mahdipour, Seyed Ali; Mowlavi, Ali Asghar

    2016-01-01

    Radiotherapy with ion beams like proton and carbon has been used for treatment of eye uveal melanoma for many years. In this research, we have developed a new phantom of human eye for Monte Carlo simulation of tumors treatment to use in GEANT4 toolkit. Total depth−dose profiles for the proton, alpha, and carbon incident beams with the same ranges have been calculated in the phantom. Moreover, the deposited energy of the secondary particles for each of the primary beams is calculated. The dose curves are compared for 47.8 MeV proton, 190.1 MeV alpha, and 1060 MeV carbon ions that have the same range in the target region reaching to the center of tumor. The passively scattered spread-out Bragg peak (SOBP) for each incident beam as well as the flux curves of the secondary particles including neutron, gamma, and positron has been calculated and compared for the primary beams. The high sharpness of carbon beam's Bragg peak with low lateral broadening is the benefit of this beam in hadrontherapy but it has disadvantages of dose leakage in the tail after its Bragg peak and high intensity of neutron production. However, proton beam, which has a good conformation with tumor shape owing to the beam broadening caused by scattering, can be a good choice for the large-size tumors.

  19. Posterior uveal malignant melanoma: temporal stability and ethnic variation in rates in Israel.

    Science.gov (United States)

    Iscovich, J; Abdulrazik, M; Pe'Er, J

    2001-01-01

    In a population-based study of posterior uveal malignant melanoma (755 incidence cases), the authors found a stabilized incidence in Israel from 1961-1996. Overall, Jewish immigrants to Israel had a relative rate (RR) of 2.2 [95% confidence interval [1.5-2.6] as compared to the reference population (Israeli-born Jews with Israel-born parents, i.e. third generation). Whereas individuals born in Eastern Europe or the Americas experienced the highest age adjusted incidence rates per million [for example; from 1972-1996, 8.3 for those from Poland, 8.2 from Romania, 6.4 from the former Union of Soviet Socialist Republics, 7.6 from the Americas], the lowest incidence rates were observed among immigrants from Algeria-Morocco-Tunisia (rate of 2.8), Iraq (1.7), Iran (3.2). Jews born in Israel exhibited incidence patterns similar to those individuals from the place of their parent's birth; high rates were observed among individuals born of American- or European-born parents (rate of 7.2), and low rates among offspring of parents who migrated from Africa or Asia (2.6). A low incidence was found among Israeli-born Arabs (2.6 in men, and 2.0 in women). The stable differences in incidence rates, according to populations of Jews, and the persistence of these variations within the descendants of these populations suggest that underlying susceptibility states are related to an individual's origin.

  20. Ion therapy for uveal melanoma in new human eye phantom based on GEANT4 toolkit.

    Science.gov (United States)

    Mahdipour, Seyed Ali; Mowlavi, Ali Asghar

    2016-01-01

    Radiotherapy with ion beams like proton and carbon has been used for treatment of eye uveal melanoma for many years. In this research, we have developed a new phantom of human eye for Monte Carlo simulation of tumors treatment to use in GEANT4 toolkit. Total depth-dose profiles for the proton, alpha, and carbon incident beams with the same ranges have been calculated in the phantom. Moreover, the deposited energy of the secondary particles for each of the primary beams is calculated. The dose curves are compared for 47.8MeV proton, 190.1MeV alpha, and 1060MeV carbon ions that have the same range in the target region reaching to the center of tumor. The passively scattered spread-out Bragg peak (SOBP) for each incident beam as well as the flux curves of the secondary particles including neutron, gamma, and positron has been calculated and compared for the primary beams. The high sharpness of carbon beam׳s Bragg peak with low lateral broadening is the benefit of this beam in hadrontherapy but it has disadvantages of dose leakage in the tail after its Bragg peak and high intensity of neutron production. However, proton beam, which has a good conformation with tumor shape owing to the beam broadening caused by scattering, can be a good choice for the large-size tumors. Copyright © 2016 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

  1. Ion therapy for uveal melanoma in new human eye phantom based on GEANT4 toolkit

    Energy Technology Data Exchange (ETDEWEB)

    Mahdipour, Seyed Ali [Physics Department, Hakim Sabzevari University, Sabzevar (Iran, Islamic Republic of); Mowlavi, Ali Asghar, E-mail: amowlavi@hsu.ac.ir [Physics Department, Hakim Sabzevari University, Sabzevar (Iran, Islamic Republic of); ICTP, Associate Federation Scheme, Medical Physics Field, Trieste (Italy)

    2016-07-01

    Radiotherapy with ion beams like proton and carbon has been used for treatment of eye uveal melanoma for many years. In this research, we have developed a new phantom of human eye for Monte Carlo simulation of tumors treatment to use in GEANT4 toolkit. Total depth−dose profiles for the proton, alpha, and carbon incident beams with the same ranges have been calculated in the phantom. Moreover, the deposited energy of the secondary particles for each of the primary beams is calculated. The dose curves are compared for 47.8 MeV proton, 190.1 MeV alpha, and 1060 MeV carbon ions that have the same range in the target region reaching to the center of tumor. The passively scattered spread-out Bragg peak (SOBP) for each incident beam as well as the flux curves of the secondary particles including neutron, gamma, and positron has been calculated and compared for the primary beams. The high sharpness of carbon beam's Bragg peak with low lateral broadening is the benefit of this beam in hadrontherapy but it has disadvantages of dose leakage in the tail after its Bragg peak and high intensity of neutron production. However, proton beam, which has a good conformation with tumor shape owing to the beam broadening caused by scattering, can be a good choice for the large-size tumors.

  2. Fractionated stereotactic radiotherapy with linear accelerator for uveal melanoma - preliminary Vienna results

    International Nuclear Information System (INIS)

    Zehetmayer, M.; Ruhswurm, I.; Georgopoulos, M.; Dieckmann, K.; Kren, G.; Poetter, R.; Kitz, K.

    1999-01-01

    Between June 1997 and February 1998, 21 patients suffering from uveal melanomas have been treated with a sterotactic 6 MeV LINAC (Saturne 43 trademark , General Electric, France) in conjunction with a stereotactic frame system (BrainLAB trademark , Germany). Immobilization of the eye was ensured with an optical fixation system which was proven reliable. During radiotherapy, movements of the irradiated eye were controlled on a monitor and documented by video recording. All patients co-operated very well with the optical fixation system. In 1164 measurements, the median value of horizontal deviation of the diseased eye during treatment was 0.3 mm (range: 0 to 1.3 mm). Median vertical deviation was 0.2 mm (range: 0 to 1.2 mm). For all patients, mean tumor prominence before treatment was 6.0±2.2 mm. In 20 patients, the total dose of 70 Gy (at 80%) was delivered in 5 fractions within 10 days. In one patient with a ciliary body tumor, the total dose of 70 Gy was divided into 7 fractions for better sparing of the anterior eye segment. Results: After a follow-up of at least 6 months, local tumor control was seen in all eyes. Mean tumor thickness reduction after 3, 6 and 9 months was 7%, 13% and 31%, respectively. Up to now, only mild subacute side-effects located in the anterior eye segment have been noticed. (orig.)

  3. The risk of enucleation after proton beam irradiation of uveal melanoma

    International Nuclear Information System (INIS)

    Egan, K.M.; Gragoudas, E.S.; Seddon, J.M.; Glynn, R.J.; Munzenreider, J.E.; Goitein, M.; Verhey, L.; Urie, M.; Koehler, A.

    1989-01-01

    Enucleation after proton beam irradiation of uveal melanomas occurred in 64 (6.4%) of 994 eyes with a median follow-up time of 2.7 years. The median time between irradiation and enucleation in the 64 enucleated eyes was 13 months. The probability of retaining the eye was 95 and 90%, 2 and 5 years postirradiation, respectively. Three percent of eyes were enucleated during posttreatment year 1, and the yearly rate was 1% by the fourth year. No patient had enucleation later than 5 1/2 years posttreatment. The complication most likely to result in enucleation was neovascular glaucoma although this was frequently managed without enucleation. Other common reasons for enucleation were documented or suspected tumor growth and complete retinal detachment with associated loss of vision. The leading risk factors for enucleation were anterior tumor margin involving the ciliary body, tumor height greater than 8 mm, and proximity of the tumor to the fovea. Based on the presence or absence of these factors, 5-year eye retention rates were 99, 92, and 76% for low-, moderate-, and high-risk groups, respectively. Thus, the probability of eye retention after proton beam irradiation is high even among those at greatest risk of enucleation

  4. Local tumor control and morbidity after one to three fractions of stereotactic external beam irradiation for uveal melanoma.

    Science.gov (United States)

    Zehetmayer, M; Kitz, K; Menapace, R; Ertl, A; Heinzl, H; Ruhswurm, I; Georgopoulos, M; Dieckmann, K; Pötter, R

    2000-05-01

    To evaluate prospectively local tumor control and morbidity after 1-3 fractions of stereotactic external beam irradiation (SEBI) in patients with uveal melanoma, unsuitable for ruthenium-106 brachytherapy or local resection. This phase I/II study includes 62 selected patients with uveal melanoma. The mean initial tumor height was 7.8+/-2.8 mm. With the Leskell gamma knife SEBI, 41 patients (66%) were irradiated with two equal fractions of 35, 30 or 25 Gy/fraction, 14 patients (22%) were treated with three fractions of 15 Gy each, and seven patients (11%) with small tumor volumes below 400 mm(3) were treated with one fraction of 45 Gy. The mean total dose was 54+/-8 Gy. The minimal follow-up period was 12 months, and the median follow-up was 28.3 months. Data on radiation-induced side-effects were analyzed with the Cox proportional hazards model for possible risk factors. Local tumor control was achieved in 98% and tumor height reduction in 97%. The mean relative tumor volume reductions were 44, 60 and 72% after 12, 24 and 36 months, respectively. Seven patients developed metastases (11%). Secondary enucleation was performed in eight eyes (13%). Morbidity was significant in tumors exceeding 8 mm in initial height; it was comparable and acceptable in those smaller. In the stepwise multiple Cox model, tumor localization, height and volume, planning target volume (PTV), total dose and patient age were identified as the strongest risk factors for radiation-induced lens opacities, secondary glaucoma, uveitis, eyelash loss and exudative retinal detachment. In this model, the high-dose volume irradiated with more than 10 Gy/fraction was the strongest risk factor for radiation-induced uveitis. Stereotactic external photon beam irradiation and a total dose of 45-70 Gy delivered in one to three fractions are highly effective at achieving local tumor control in uveal melanoma. Further clinical studies using smaller fraction doses, and consequent smaller high-dose volumes, are

  5. Antitumor effects of the investigational selective MEK inhibitor TAK733 against cutaneous and uveal melanoma cell lines

    Directory of Open Access Journals (Sweden)

    von Euw Erika

    2012-04-01

    Full Text Available Abstract Background TAK733 is a novel allosteric, non-ATP-binding, inhibitor of the BRAF substrates MEK-1/2. Methods The growth inhibitory effects of TAK733 were assessed in a panel of 27 cutaneous and five uveal melanoma cell lines genotyped for driver oncogenic mutations. Flow cytometry, Western blots and metabolic tracer uptake assays were used to characterize the changes induced by exposure to TAK733. Results Fourteen cutaneous melanoma cell lines with different driver mutations were sensitive to the antiproliferative effects of TAK733, with a higher proportion of BRAFV600E mutant cell lines being highly sensitive with IC50s below 1 nM. The five uveal melanoma cell lines had GNAQ or GNA11 mutations and were either moderately or highly sensitive to TAK733. The tested cell lines wild type for NRAS, BRAF, GNAQ and GNA11 driver mutations were moderately to highly resistant to TAK733. TAK733 led to a decrease in pERK and G1 arrest in most of these melanoma cell lines regardless of their origin, driver oncogenic mutations and in vitro sensitivity to TAK733. MEK inhibition resulted in increase in pMEK more prominently in NRASQ61L mutant and GNAQ mutant cell lines than in BRAFV600E mutant cell lines. Uptake of the metabolic tracers FDG and FLT was inhibited by TAK733 in a manner that closely paralleled the in vitro sensitivity assays. Conclusions The MEK inhibitor TAK733 has antitumor properties in melanoma cell lines with different oncogenic mutations and these effects could be detectable by differential metabolic tracer uptake.

  6. Uveal Melanoma Risk Factors: A Systematic Review of Meta-Analyses.

    Science.gov (United States)

    Nayman, Taylor; Bostan, Cristina; Logan, Patrick; Burnier, Miguel N

    2017-08-01

    There is currently no clinical risk-assessment tool allowing identification of patients at risk for developing uveal melanoma (UM) who might benefit from regular screening. As a first step toward the elaboration of such a tool, we systematically reviewed UM risk factors already established by meta-analysis. Two reviewers independently screened Pubmed, Medline, Embase, and Web of Science from their respective inception dates until July 2016 using a combination of keywords and MeSH terms. Eligible studies were meta-analyses or systematic reviews providing pooled odds ratios (ORs) of risk factors for UM development or sufficient information to calculate them. Methodological quality was evaluated using the Assessment of Multiple Systematic Reviews tool. Four meta-analyses with a mean methodological quality score of 65.9% (min: 54.5%; max: 72.7%) were included. The following significant risk factors were identified: atypical cutaneous nevi (OR 2.82, 95% CI 1.10-7.26), welding (OR 2.05, 95% CI 1.20-3.51), occupational cooking (OR 1.81, 95% CI 1.33-2.46), fair skin color (OR 1.80, 95% CI 1.31-2.47), light eye color (OR 1.75, 95% CI 1.31-2.34), common cutaneous nevi (OR 1.74, 95% CI 1.27-2.39), propensity to sunburn (OR 1.64, 95% CI 1.29-2.09), iris nevi (OR 1.53, 95% CI 1.03-2.27), and cutaneous freckles (OR 1.27, 95% CI 1.09-1.49). Non-significant factors included outdoor leisure activity, occupational sunlight exposure, latitude of birth, and hair color. Moderate quality of evidence determined nine significant risk factors for developing UM. Knowledge of these variables will assist researchers in the elaboration of a formal risk-assessment tool allowing clinicians to estimate susceptibility to the disease and necessity of regular screening.

  7. The protein kinase C inhibitor enzastaurin exhibits antitumor activity against uveal melanoma.

    Directory of Open Access Journals (Sweden)

    Xinqi Wu

    Full Text Available GNAQ mutations at codon 209 have been recently identified in approximately 50% of uveal melanomas (UM and are reported to be oncogenic through activating the MAPK/Erk1/2 pathway. Protein kinase C (PKC is a component of signaling from GNAQ to Erk1/2. Inhibition of PKC might regulate GNAQ mutation-induced Erk1/2 activation, resulting in growth inhibition of UM cells carrying GNAQ mutations. UM cells carrying wild type or mutant GNAQ were treated with the PKC inhibitor enzastaurin. Effects on proliferation, apoptosis, and signaling events were evaluated. Enzastaurin downregulated the expression of several PKC isoforms including PKCβII PKCθ, PKCε and/or their phosphorylation in GNAQ mutated cells. Downregulation of these PKC isoforms in GNAQ mutated cells by shRNA resulted in reduced viability. Enzastaurin exhibited greater antiproliferative effect on GNAQ mutant cells than wild type cells through induction of G1 arrest and apoptosis. Enzastaurin-induced G1 arrest was associated with inhibition of Erk1/2 phosphorylation, downregulation of cyclin D1, and accumulation of cyclin dependent kinase inhibitor p27(Kip1. Furthermore, enzastaurin reduced the expression of antiapoptotic Bcl-2 and survivin in GNAQ mutant cells. Inhibition of Erk1/2 phosphorylation with a MEK specific inhibitor enhanced the sensitivity of GNAQ wild type cells to enzastaurin, accompanied by p27(Kip1 accumulation and/or inhibition of enzastaurin-induced survivin and Bcl-2 upregulation. PKC inhibitors such as enzastaurin have activity against UM cells carrying GNAQ mutations through inhibition of the PKC/Erk1/2 pathway and induction of G1 arrest and apoptosis. Inhibition of the PKC pathway provides a basis for clinical investigation in patients with UM.

  8. Mechanisms of resistance to imatinib mesylate in KIT-positive metastatic uveal melanoma.

    Science.gov (United States)

    Calipel, Armelle; Landreville, Solange; De La Fouchardière, Arnaud; Mascarelli, Frédéric; Rivoire, Michel; Penel, Nicolas; Mouriaux, Frédéric

    2014-06-01

    Imatinib mesylate is used in targeted therapy of cancer to inhibit type III tyrosine kinase receptors, such as KIT and platelet-derived growth factor receptors (PDGFRs). Expression of KIT in uveal melanoma (UM) suggests that this receptor may be the target of imatinib mesylate therapy. However, phase II multicenter clinical studies have shown no effect of imatinib mesylate in patients with unresectable liver metastases of UM. We therefore investigated which molecular mechanisms promote imatinib mesylate-resistance in metastatic UM. Expression of KIT, stem cell factor (SCF), PDGFRα and PDGFRβ, was analyzed by RT-PCR, immunostaining, and Western blot in twenty-four samples of UM liver metastases, as well as UM primary tumor and metastatic cell lines. Soluble SCF was quantified in UM cell lines using enzyme-linked immunosorbent assay. Cell viability of UM cell lines treated with imatinib mesylate and grown in SCF-supplemented medium or in microvascular endothelial cells-conditioned medium was studied by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assays. UM liver metastases and cell lines expressed KIT and SCF, but not the PDGFRs. Ninety-five percent of liver metastases expressed KIT at the protein level, but PDGFRs were not detected in these samples. Imatinib mesylate reduced the viability of UM metastatic cell lines in a concentration-dependent manner, but an increased resistance to this drug was observed when cells were incubated in SCF-supplemented or microvascular endothelial cells-conditioned medium. This study provides evidence that tumor microenvironment cytokines such as SCF may promote resistance to imatinib mesylate in metastatic UM.

  9. The occurrence and proposed significance of Schnabel cavernous degeneration in uveal melanoma.

    Science.gov (United States)

    Kanavi, Mozhgan Rezaei; Azari, Amir A; Potter, Heather D; Lee, Vivian; Albert, Daniel M

    2014-05-01

    Schnabel cavernous degeneration (SCD) has been observed in eyes with uveal melanoma (UM), but, to our knowledge, a definitive study establishing the association between SCD and UM has not been conducted. To explore an association between SCD and UM. A historical cohort analysis was performed using histologic slides and related clinical records of cases from the Collaborative Ocular Melanoma Study and Eye Pathology Laboratory at the University of Wisconsin, including 1985 UM eyes, 517 eye bank eyes, and 155 enucleated glaucomatous eyes. The prevalence of SCD was calculated and compared between each group; subgroup analysis was also conducted of eyes with and without SCD for the prevalence of glaucoma. Schnabel cavernous degeneration was seen in 17 (0.9%) UM eyes, 9 (1.7%) eye bank eyes, and 2 (1.3%) enucleated glaucomatous eyes. No difference was detected between the prevalence of SCD in UM eyes and eye bank eyes (odds ratio [OR], 0.49; 95% CI, 0.22-1.10) or enucleated glaucomatous eyes (OR, 0.66; 95% CI, 0.15-2.89). Subgroup analysis, performed on 421 UM eyes, provided sufficient clinical information to definitively establish the presence or absence of glaucoma. Of the 95 (22.6%) eyes with glaucoma, 11 (11.6%) revealed histopathologic evidence of SCD. Compared with enucleated end-stage glaucoma eyes, this represents a 10-fold increase in SCD in UM eyes with glaucoma (OR, 10.10; 95% CI, 2.17-46.26). The prevalence of glaucoma in UM eyes with SCD, however, was respectively 7- and 15-fold higher than the prevalence of glaucoma in SCD-negative UM eyes (OR, 6.98; 95% CI, 2.51-19.43) and SCD-positive eye bank eyes (OR, 14.67; 95% CI, 1.46-146.97). Although an association between SCD and UM was not confirmed, subgroup analysis did reveal an increased incidence of SCD in eyes with both UM and glaucoma. This suggests that the occurrence of glaucoma may increase the risk of SCD in eyes with UM.

  10. Sigma-1 and Sigma-2 receptor ligands induce apoptosis and autophagy but have opposite effect on cell proliferation in uveal melanoma.

    Science.gov (United States)

    Longhitano, Lucia; Castracani, Carlo Castruccio; Tibullo, Daniele; Avola, Roberto; Viola, Maria; Russo, Giuliano; Prezzavento, Orazio; Marrazzo, Agostino; Amata, Emanuele; Reibaldi, Michele; Longo, Antonio; Russo, Andrea; Parrinello, Nunziatina Laura; Volti, Giovanni Li

    2017-10-31

    Uveal melanoma is the most common primary intraocular tumor in adults, with about 1200-1500 new cases occurring per year in the United States. Metastasis is a frequent occurrence in uveal melanoma, and outcomes are poor once distant spread occurs and no clinically significant chemotherapeutic protocol is so far available. The aim of the present study was to test the effect of various σ 1 and σ 2 receptor ligands as a possible pharmacological strategy for this rare tumor. Human uveal melanoma cells (92.1) were treated with various concentrations of different σ 2 ligands (haloperidol and haloperidol metabolite II) and σ 1 ligand ((+)-pentazocine) at various concentrations (1, 10 and 25 μM) and time points (0, 4 h, 8 h, 24 h and 48 h). Cell proliferation and migration were evaluated respectively by continuous cell monitoring by xCELLigence analysis, clonogenic assay and wound healing. Apoptosis and autophagy were also measured by cytofluorimetric and microscopy analysis. Our results showed that σ 2 receptor ligands significantly reduced cell proliferation whereas (+)-pentazocine exhibited opposite results. All tested ligands showed significant decrease in cell migration. Interestingly, both σ 1 and σ 2 receptor ligands showed significant increase of autophagy and apoptosis at all concentrations. Taken all together these results suggest that sigma receptors mediates opposite biological effects but they also share common pharmacological effect on apoptosis and autophagy in uveal melanoma. In conclusion, these data provide the first evidence that sigma receptors may represent a "druggable" target to develop new chemotherapic agent for uveal melanoma.

  11. Intravitreal bevacizumab for neovascular glaucoma in uveal melanoma treated by proton beam therapy.

    Science.gov (United States)

    Mahdjoubi, Amir; Najean, Marie; Lemaitre, Stéphanie; Dureau, Sylvain; Dendale, Rémi; Levy, Christine; Rouic, Livia Lumbroso-Le; Desjardins, Laurence; Cassoux, Nathalie

    2018-02-01

    To evaluate the efficacy of bevacizumab on reduction of the enucleation rate and control of intraocular pressure (IOP) in neovascular glaucoma (NVG)-complicating proton beam therapy for UM and to identify the determinants of the efficacy of bevacizumab. Retrospective comparative study of patients with rubeosis following proton therapy for uveal melanoma. Patients were divided into two groups: a bevacizumab group and a control group which comprised two subgroups: panretinal photocoagulation (PRP)/cryotherapy and observation subgroups. Bevacizumab was administered by three intravitreal injections at 1-month intervals. A second series of injections was administered when necessary. Data concerning IOP and the secondary enucleation rate were collected and compared between the two groups. Univariate and multivariate analyses were performed to determine predictive factors of response to bevacizumab. A total of 169 patients who developed rubeosis following proton therapy between 2006 and 2016 were included: 44 patients in the bevacizumab group and 125 in the control group (38 in the PRP/cryotherapy subgroup and 87 in the observation subgroup). The two groups presented the same baseline characteristics apart from hypertension, retro-equatorial site, and proximity of the optic disk, which were more frequent in the control group, while initial retinal detachment and larger tumor volume were more frequent in the bevacizumab group. After a mean follow-up of 31 months, IOP was less than 21 mmHg in 54.54% of patients after IVB versus 72.7% before treatment (p = 0.06). Statistical analysis did not reveal any statistically significant reduction of the enucleation rate in the bevacizumab group compared to the observational group, whereas the PRP/cryotherapy group showed better eye retention rate (p = 0.15). No enucleation was performed when IOP was bevacizumab. Despite the improvement of IOP level, intravitreal bevacizumab (IVB) did not reduce the overall enucleation rate in

  12. Characterization of melanoma associated spongiform scleropathy

    DEFF Research Database (Denmark)

    Alyahya, Ghassan Ayish Jabur; Heegaard, Steffen; Prause, J.U.

    2002-01-01

    ophthalmology, melanoma associated spongiform scleropathy (MASS), MASS, malignant uveal melanoma, sclera, ciliary body, choroid, histopathology......ophthalmology, melanoma associated spongiform scleropathy (MASS), MASS, malignant uveal melanoma, sclera, ciliary body, choroid, histopathology...

  13. Complications after proton beam therapy for uveal malignant melanoma. A clinical and histopathologic study of five cases

    International Nuclear Information System (INIS)

    Kincaid, M.C.; Folberg, R.; Torczynski, E.; Zakov, Z.N.; Shore, J.W.; Liu, S.J.; Planchard, T.A.; Weingeist, T.A.

    1988-01-01

    Proton beam therapy for uveal malignant melanoma has been advocated as effective therapy because of documented reduction in tumor size and few clinical complications. However, some eyes have been removed because of adverse effects. The authors report the clinical courses and pathologic findings of five eyes enucleated after proton beam irradiation. Neovascular glaucoma had developed in three eyes, two eyes had vitreous hemorrhage, and two had extraocular extension. The tumors in the radiation treatment field showed continued postirradiation growth clinically in four of the five eyes, and mitotic activity histologically in all five cases. Two and one half years after irradiation, and nearly 2 years after subsequent enucleation, one of those two patients had biopsy-proven liver metastases, and later died. Despite the considerable success rate of proton beam irradiation, the potential for clinical complications and subsequent tumor growth remains

  14. The prognostic value of AJCC staging in uveal melanoma is enhanced by adding chromosome 3 and 8q status

    DEFF Research Database (Denmark)

    Dogrusöz, Mehmet; Bagger, Mette; Van Duinen, Sjoerd G.

    2017-01-01

    PURPOSE. The American Joint Committee on Cancer (AJCC) staging system has been validated for use as a prognostic parameter in uveal melanoma (UM). We studied whether adding information regarding chromosome 3 and 8q status further enhances the prognostic value of this staging system. METHODS. We...... retrospectively studied a cohort of 522 patients who had been treated for UM in two different centers between 1999 and 2015. The mean follow-up time was 47.7 months. Cumulative incidence curves were generated and regression analyses were performed for different combinations of AJCC staging and chromosome status....... Multivariable regression analyses demonstrated that AJCC staging and chromosome 3 and 8q status contain independent information about survival status. CONCLUSIONS. Combining information on AJCC staging and chromosome 3 and 8q status allows a more accurate prognostication in UM. We conclude that the prognostic...

  15. Brachytherapy treatment simulation of strontium-90 and ruthenium-106 plaques on small size posterior uveal melanoma using MCNPX code

    Science.gov (United States)

    Barbosa, N. A.; da Rosa, L. A. R.; Facure, A.; Braz, D.

    2014-02-01

    Concave eye applicators with 90Sr/90Y and 106Ru/106Rh beta-ray sources are usually used in brachytherapy for the treatment of superficial intraocular tumors as uveal melanoma with thickness up to 5 mm. The aim of this work consisted in using the Monte Carlo code MCNPX to calculate the 3D dose distribution on a mathematical model of the human eye, considering 90Sr/90Y and 160Ru/160Rh beta-ray eye applicators, in order to treat a posterior uveal melanoma with a thickness 3.8 mm from the choroid surface. Mathematical models were developed for the two ophthalmic applicators, CGD produced by BEBIG Company and SIA.6 produced by the Amersham Company, with activities 1 mCi and 4.23 mCi respectively. They have a concave form. These applicators' mathematical models were attached to the eye model and the dose distributions were calculated using the MCNPX *F8 tally. The average doses rates were determined in all regions of the eye model. The *F8 tally results showed that the deposited energy due to the applicator with the radionuclide 106Ru/106Rh is higher in all eye regions, including tumor. However the average dose rate in the tumor region is higher for the applicator with 90Sr/90Y, due to its high activity. Due to the dosimetric characteristics of these applicators, the PDD value for 3 mm water is 73% for the 106Ru/106Rh applicator and 60% for 90Sr/90Y applicator. For a better choice of the applicator type and radionuclide it is important to know the thickness of the tumor and its location.

  16. Uveal Melanoma Treated With Iodine-125 Episcleral Plaque: An Analysis of Dose on Disease Control and Visual Outcomes

    Energy Technology Data Exchange (ETDEWEB)

    Perez, Bradford A. [Department of Radiation Oncology, Duke University, Durham, North Carolina (United States); Mettu, Pradeep; Vajzovic, Lejla [Department of Ophthalmology, Duke University, Durham, North Carolina (United States); Rivera, Douglas [Austin Cancer Centers, Austin, Texas (United States); Alkaissi, Ali; Steffey, Beverly A.; Cai, Jing [Department of Radiation Oncology, Duke University, Durham, North Carolina (United States); Stinnett, Sandra [Department of Biostatistics and Informatics, Duke University, Durham, North Carolina (United States); Dutton, Jonathan J. [Department of Ophthalmology, University of North Carolina, Chapel Hill, North Carolina (United States); Buckley, Edward G. [Department of Ophthalmology, Duke University, Durham, North Carolina (United States); Halperin, Edward [Department of Radiation Oncology, New York Medical College, Valhalla, New York (United States); Marks, Lawrence B. [Department of Radiation Oncology, University of North Carolina, Chapel Hill, North Carolina (United States); Mruthyunjaya, Prithvi [Department of Radiation Oncology, Duke University, Durham, North Carolina (United States); Department of Ophthalmology, Duke University, Durham, North Carolina (United States); Kirsch, David G., E-mail: david.kirsch@duke.edu [Department of Radiation Oncology, Duke University, Durham, North Carolina (United States); Department of Pharmacology and Cancer Biology, Duke University, Durham, North Carolina (United States)

    2014-05-01

    Purpose: To investigate, in the treatment of uveal melanomas, how tumor control, radiation toxicity, and visual outcomes are affected by the radiation dose at the tumor apex. Methods and Materials: A retrospective review was performed to evaluate patients treated for uveal melanoma with {sup 125}I plaques between 1988 and 2010. Radiation dose is reported as dose to tumor apex and dose to 5 mm. Primary endpoints included time to local failure, distant failure, and death. Secondary endpoints included eye preservation, visual acuity, and radiation-related complications. Univariate and multivariate analyses were performed to determine associations between radiation dose and the endpoint variables. Results: One hundred ninety patients with sufficient data to evaluate the endpoints were included. The 5-year local control rate was 91%. The 5-year distant metastases rate was 10%. The 5-year overall survival rate was 84%. There were no differences in outcome (local control, distant metastases, overall survival) when dose was stratified by apex dose quartile (<69 Gy, 69-81 Gy, 81-89 Gy, >89 Gy). However, increasing apex dose and dose to 5-mm depth were correlated with greater visual acuity loss (P=.02, P=.0006), worse final visual acuity (P=.02, P<.0001), and radiation complications (P<.0001, P=.0009). In addition, enucleation rates were worse with increasing quartiles of dose to 5 mm (P=.0001). Conclusions: Doses at least as low as 69 Gy prescribed to the tumor apex achieve rates of local control, distant metastasis–free survival, and overall survival that are similar to radiation doses of 85 Gy to the tumor apex, but with improved visual outcomes.

  17. Bone morphogenetic protein 7 inhibits tumor growth of human uveal melanoma in vivo.

    NARCIS (Netherlands)

    Notting, I.C.; Buijs, J.; Mintardjo, R.E.; Horst, G. ter; Vukicevic, S.; Lowik, C.W.G.M.; Schalij-Delfos, N.E.; Keunen, J.E.E.; Pluijm, G. van der

    2007-01-01

    PURPOSE: Bone morphogenetic protein-7 (BMP7), a member of the TGF-beta superfamily, is essential for early ocular morphogenesis, and lack of BMP7 causes epithelial development disturbances in the eye. In the present study, the association of tumorigenicity and malignant behavior of human uveal

  18. Temporal Evolution and Dose-Volume Histogram Predictors of Visual Acuity After Proton Beam Radiation Therapy of Uveal Melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Polishchuk, Alexei L. [Department of Radiation Oncology, University of California, San Francisco, San Francisco, California (United States); Mishra, Kavita K., E-mail: Kavita.Mishra@ucsf.edu [Department of Radiation Oncology, University of California, San Francisco, San Francisco, California (United States); Weinberg, Vivian; Daftari, Inder K. [Department of Radiation Oncology, University of California, San Francisco, San Francisco, California (United States); Nguyen, Jacqueline M.; Cole, Tia B. [Tumori Foundation, San Francisco, California (United States); Quivey, Jeanne M.; Phillips, Theodore L. [Department of Radiation Oncology, University of California, San Francisco, San Francisco, California (United States); Char, Devron H. [Tumori Foundation, San Francisco, California (United States)

    2017-01-01

    Purpose: To perform an in-depth temporal analysis of visual acuity (VA) outcomes after proton beam radiation therapy (PBRT) in a large, uniformly treated cohort of uveal melanoma (UM) patients, to determine trends in VA evolution depending on pretreatment and temporally defined posttreatment VA measurements; and to investigate the relevance of specific patient, tumor and dose-volume parameters to posttreatment vision loss. Methods and Materials: Uveal melanoma patients receiving PBRT were identified from a prospectively maintained database. Included patients (n=645) received 56 GyE in 4 fractions, had pretreatment best corrected VA (BCVA) in the affected eye of count fingers (CF) or better, with posttreatment VA assessment at specified post-PBRT time point(s). Patients were grouped according to the pretreatment BCVA into favorable (≥20/40) or unfavorable (20/50-20/400) and poor (CF) strata. Temporal analysis of BCVA changes was described, and univariate and forward stepwise multivariate logistic regression analyses were performed to identify predictors for VA loss. Results: Median VA follow-up was 53 months (range, 3-213 months). At 60-month follow up, among evaluable treated eyes with favorable pretreatment BCVA, 45% retained BCVA ≥20/40, whereas among evaluable treated eyes with initially unfavorable/poor BCVA, 21% had vision ≥20/100. Among those with a favorable initial BCVA, attaining BCVA of ≥20/40 at any posttreatment time point was associated with subsequent maintenance of excellent BCVA. Multivariate analysis identified volume of the macula receiving 28GyE (P<.0001) and optic nerve (P=.0004) as independent dose-volume histogram predictors of 48-month post-PBRT vision loss among initially favorable treated eyes. Conclusions: Approximately half of PBRT-treated UM eyes with excellent pretreatment BCVA assessed at 5 years after treatment will retain excellent long-term vision. 28GyE macula and optic nerve dose-volume histogram parameters allow for

  19. Minimal contribution of ERK1/2-MAPK signalling towards the maintenance of oncogenic GNAQQ209P-driven uveal melanomas in zebrafish

    Science.gov (United States)

    Mouti, Mai Abdel; Dee, Christopher; Coupland, Sarah E.; Hurlstone, Adam F.L.

    2016-01-01

    Mutations affecting Gαq proteins are pervasive in uveal melanoma (UM), suggesting they ‘drive’ UM pathogenesis. The ERK1/2-MAPK pathway is critical for cutaneous melanoma development and consequently an important therapeutic target. Defining the contribution of ERK1/2-MAPK signalling to UM development has been hampered by the lack of an informative animal model that spontaneously develops UM. Towards this end, we engineered transgenic zebrafish to express oncogenic GNAQQ209P in the melanocyte lineage. This resulted in hyperplasia of uveal melanocytes, but with no evidence of malignant progression, nor perturbation of skin melanocytes. Combining expression of oncogenic GNAQQ209P with p53 inactivation resulted in earlier onset and even more extensive hyperplasia of uveal melanocytes that progressed to UM. Immunohistochemistry revealed only weak immunoreactivity to phosphorylated (p)ERK1/2 in established uveal tumours—in contrast to strong immunoreactivity in oncogenic RAS-driven skin lesions—but ubiquitous positive staining for nuclear Yes-associated protein (YAP). Moreover, no changes were observed in pERK1/2 levels upon transient knockdown of GNAQ or phospholipase C-beta (PLC-β) inhibition in the majority of human UM cell lines we tested harbouring GNAQ mutations. In summary, our findings demonstrate a weak correlation between oncogenic GNAQQ209P mutation and sustained ERK1/2-MAPK activation, implying that ERK1/2 signalling is unlikely to be instrumental in the maintenance of GNAQQ209P-driven UMs. PMID:27166257

  20. Sorafenib in metastatic uveal melanoma: efficacy, toxicity and health-related quality of life in a multicentre phase II study

    Science.gov (United States)

    Mouriaux, F; Servois, V; Parienti, J J; Lesimple, T; Thyss, A; Dutriaux, C; Neidhart-Berard, E M; Penel, N; Delcambre, C; Peyro Saint Paul, L; Pham, A D; Heutte, N; Piperno-Neumann, S; Joly, F

    2016-01-01

    Background: The aim of the study was to analyse efficacy, safety, and health-related quality of life (HRQoL) for sorafenib treatment in patients with metastatic uveal melanoma. Methods: A multicentre, single-arm phase II trial was conducted. The primary objective was to determine the non-progression rate (RECIST) at 24 weeks for patients receiving sorafenib at a dose of 800 mg per day. Secondary endpoints included progression-free survival (PFS), overall survival (OS), toxicity, and HRQoL. Results: Thirty-two patients were included. Ten patients showed non-progression at 24 weeks (31.2%) without objective tumour responses. The estimated 24-week PFS was 31.2% (95% CI: 14.8%–47.6%) and the estimated 24-week OS was 62.5% (95% CI: 45.4%–79.6%). Ten patients (34.3%) had at least one grade 3 or 4 adverse reaction and 12 patients (41.4%) required dose modifications due to toxicity. At 24 weeks, no patient had an improvement in global HRQoL and 87.5% experienced a permanent increase in physical fatigue. Conclusions: Sorafenib demonstrated non-progression at 24 weeks in 31.2% of patients. However, 41.4% of patients required dose modifications due to toxicity and no improvement in HRQoL was demonstrated. PMID:27253171

  1. Surgery vs. radiotherapy in patients with uveal melanoma : Analysis of the SEER database using propensity score matching and weighting.

    Science.gov (United States)

    Jang, Bum-Sup; Chang, Ji Hyun; Oh, Sohee; Lim, Yu Jin; Kim, Il Han

    2017-11-01

    The treatment modalities for uveal melanoma (UM) include surgery and radiotherapy (RT). The utilization of RT as a strategy for organ preservation has been increasing, but the survival difference between the two aforementioned treatment modalities has not been reported. An observational and cohort study was performed using a propensity score with an already existing public database. Patients diagnosed with UM within the period from 2004-2013 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. One-to-one matching and inverse probability of treatment weighting (IPTW) using the propensity score were used to estimate and compare survival rates. Overall, 3291 patients were treated: 2503 received RT only (RT group) and 788 received surgical resection only (surgery group). The RT group had an improved crude 5‑year overall survival (OS) rate compared with the surgery group (76% vs. 60%, P melanoma-specific survival (MSS) rate (89% vs. 73%, P < 0.001). Compared to the surgery group, the RT group was associated with improved OS (hazard ratio [HR] 0.52, 95% confidence interval [CI] 0.38-0.73, P < 0.001) and MSS (HR 0.48, 95% CI 0.35-0.65, P < 0.001) in the matched cohort. The survival benefit of the RT group maintained after adjustment with IPTW, both in OS and MSS. To our knowledge, the present study was the first to demonstrate the survival difference between the two treatment modalities for UM using both the propensity score matching and weighting methods with the SEER database. The current study suggests that RT may provide a survival advantage over surgery in the treatment of UM.

  2. Clinicopathological Characteristics and Prognosis for Survival after Enucleation of Uveal Melanoma in Chinese Patients: Long-term Follow-up.

    Science.gov (United States)

    Yue, Han; Qian, Jiang; Yuan, Yifei; Zhang, Rui; Bi, Yingwen; Meng, Fengxi; Xuan, Yi

    2017-05-01

    To summarize the clinicopathological characteristics and prognosis of uveal melanoma (UM) after enucleation in Chinese patients. Between 2003 and 2012, a series of 171 patients with UM received enucleation at the Eye & ENT Hospital of Fudan University in Shanghai. Patient clinical information was collected. Pathological examination and BAP1 staining of the enucleated eyes were conducted. Univariate and multivariate Cox proportional hazard regressions were conducted to determine the risk factors, and the survival rates were calculated and compared. The study included 83 (49%) men and 88 (51%) women, with a mean age of 48.6 years. The mean largest basal tumor diameter and mean largest tumor thickness were 11.8 and 8.6 mm, respectively. Ciliary body involvement was observed in 19 tumors (11%). Spindle and nonspindle patterns were observed in 100 (58%) and 71 eyes (42%), respectively. Extrascleral extension was observed in three eyes (2%). BAP1 staining was negative in 34% (53/156) of all tumors and 53% (19/36) of the cases with melanoma-related metastasis. The mean follow-up period was 63.4 months for all patients with the exception of 11 patients, who were excluded because they were lost during follow-up. A large basal tumor diameter, ciliary body involvement, nonspindle cell type, extrascleral extension, and negative BAP1 staining were associated with a worse prognosis. The survival curves significantly differed between the BAP1-negative and BAP1-positive groups (P = 0.004). According to Kaplan-Meier analysis, the 5- and 10-year metastasis-free survival rates were 80% and 70%, respectively. A large basal tumor diameter, ciliary body involvement, nonspindle cell type, extrascleral extension, and negative BAP1 staining may be risk factors for the prediction of the UM prognosis. A younger age at diagnosis and a similar prognosis between genders may be unique features in Asian patients compared to the Caucasian population.

  3. Percutaneous Isolated Hepatic Perfusion as a Treatment for Isolated Hepatic Metastases of Uveal Melanoma: Patient Outcome and Safety in a Multi-centre Study.

    Science.gov (United States)

    Vogl, Thomas J; Koch, Silvia A; Lotz, Gösta; Gebauer, Bernhard; Willinek, Winfried; Engelke, Christoph; Brüning, Roland; Zeile, Martin; Wacker, Frank; Vogel, Arndt; Radeleff, Boris; Scholtz, Jan-Erik

    2017-06-01

    Percutaneous isolated hepatic perfusion (PIHP) with Melphalan has been developed as a treatment for patients with isolated hepatic metastases of uveal melanoma. We discuss patient outcome and safety in a retrospective multi-centre study. Between 2012 and 2016 18 patients with un-resectable isolated hepatic metastases of uveal melanoma received single or repeated PIHP with Melphalan (n = 35) at seven sites. Progression-free time, overall survival time (OS) and tumour response by means of RECIST 1.1 criteria were evaluated. Peri- and post-procedural adverse events (AE) were registered. Patients' life quality was assessed using four-point scale questionnaires. Of 18 patients, initial PIHP treatment resulted in partial response (PR) in eight, stable disease (SD) in seven and progressive disease (PD) in three cases. Nine patients underwent second PIHP with PR in eight cases and PD in one case. Six patients were evaluated after third PIHP with PR in five patients and SD in one patient. Two patients received fourth PIHP with PD in both cases. Median OS was 9.6 months (range 1.6-41.0 months). Median progression-free survival time was 12.4 months (range 0.9-41.0 months) with 1-year survival of 44%. Most common post-procedural AE grade 3 and 4 were temporary leukopenia (n = 11) and thrombocytopenia (n = 8). Patients' self-assessments showed good ratings for overall health and quality of life with only slight changes after PIHP, and a high degree of satisfaction with PIHP treatment. PIHP with Melphalan proved to be a relatively safe, minimal-invasive and repeatable treatment for patients with non-resectable hepatic metastases of uveal melanoma.

  4. Percutaneous Isolated Hepatic Perfusion as a Treatment for Isolated Hepatic Metastases of Uveal Melanoma: Patient Outcome and Safety in a Multi-centre Study

    International Nuclear Information System (INIS)

    Vogl, Thomas J.; Koch, Silvia A.; Lotz, Gösta; Gebauer, Bernhard; Willinek, Winfried; Engelke, Christoph; Brüning, Roland; Zeile, Martin; Wacker, Frank; Vogel, Arndt; Radeleff, Boris; Scholtz, Jan-Erik

    2017-01-01

    PurposePercutaneous isolated hepatic perfusion (PIHP) with Melphalan has been developed as a treatment for patients with isolated hepatic metastases of uveal melanoma. We discuss patient outcome and safety in a retrospective multi-centre study.Materials and MethodsBetween 2012 and 2016 18 patients with un-resectable isolated hepatic metastases of uveal melanoma received single or repeated PIHP with Melphalan (n = 35) at seven sites. Progression-free time, overall survival time (OS) and tumour response by means of RECIST 1.1 criteria were evaluated. Peri- and post-procedural adverse events (AE) were registered. Patients’ life quality was assessed using four-point scale questionnaires.ResultsOf 18 patients, initial PIHP treatment resulted in partial response (PR) in eight, stable disease (SD) in seven and progressive disease (PD) in three cases. Nine patients underwent second PIHP with PR in eight cases and PD in one case. Six patients were evaluated after third PIHP with PR in five patients and SD in one patient. Two patients received fourth PIHP with PD in both cases. Median OS was 9.6 months (range 1.6–41.0 months). Median progression-free survival time was 12.4 months (range 0.9–41.0 months) with 1-year survival of 44%. Most common post-procedural AE grade 3 and 4 were temporary leukopenia (n = 11) and thrombocytopenia (n = 8). Patients’ self-assessments showed good ratings for overall health and quality of life with only slight changes after PIHP, and a high degree of satisfaction with PIHP treatment.ConclusionPIHP with Melphalan proved to be a relatively safe, minimal-invasive and repeatable treatment for patients with non-resectable hepatic metastases of uveal melanoma.

  5. Percutaneous Isolated Hepatic Perfusion as a Treatment for Isolated Hepatic Metastases of Uveal Melanoma: Patient Outcome and Safety in a Multi-centre Study

    Energy Technology Data Exchange (ETDEWEB)

    Vogl, Thomas J., E-mail: t.vogl@em.uni-frankfurt.de; Koch, Silvia A., E-mail: silvia.koch@web.de [University Hospital Frankfurt, Department of Diagnostic and Interventional Radiology (Germany); Lotz, Gösta, E-mail: goesta.lotz@kgu.de [University Hospital Frankfurt, Department of Anesthesiology, Intensive-Care Medicine and Pain Therapy (Germany); Gebauer, Bernhard, E-mail: bernhard.gebauer@charite.de [Universitätsmedizin Berlin, Department of Diagnostic and Interventional Radiology, Campus Charité Mitte (Germany); Willinek, Winfried, E-mail: w.willinek@bk-trier.de [Brüderkrankenhaus Trier, Department of Diagnostic and Interventional Radiology (Germany); Engelke, Christoph, E-mail: engelke@ekweende.de [Evangelisches Krankenhaus Göttingen-Weende gGmbH, Department of Diagnostic and Interventional Radiology (Germany); Brüning, Roland, E-mail: r.bruening@asklepios.com; Zeile, Martin, E-mail: m.zeile@asklepios.com [Asklepios Klinik Barmbek, Department of Diagnostic and Interventional Radiology (Germany); Wacker, Frank, E-mail: wacker.frank@mh-hannover.de [Medizinische Hochschule Hannover, Department of Diagnostic and Interventional Radiology (Germany); Vogel, Arndt, E-mail: vogel.arndt@mh-hannover.de [Medizinische Hochschule Hannover, Department of Gastroenterology, Hepatology and Endocrinology (Germany); Radeleff, Boris, E-mail: boris.radeleff@med.uni-heidelberg.de [Heidelberg University Hospital, Department of Diagnostic and Interventional Radiology (Germany); Scholtz, Jan-Erik, E-mail: janerikscholtz@gmail.com [University Hospital Frankfurt, Department of Diagnostic and Interventional Radiology (Germany)

    2017-06-15

    PurposePercutaneous isolated hepatic perfusion (PIHP) with Melphalan has been developed as a treatment for patients with isolated hepatic metastases of uveal melanoma. We discuss patient outcome and safety in a retrospective multi-centre study.Materials and MethodsBetween 2012 and 2016 18 patients with un-resectable isolated hepatic metastases of uveal melanoma received single or repeated PIHP with Melphalan (n = 35) at seven sites. Progression-free time, overall survival time (OS) and tumour response by means of RECIST 1.1 criteria were evaluated. Peri- and post-procedural adverse events (AE) were registered. Patients’ life quality was assessed using four-point scale questionnaires.ResultsOf 18 patients, initial PIHP treatment resulted in partial response (PR) in eight, stable disease (SD) in seven and progressive disease (PD) in three cases. Nine patients underwent second PIHP with PR in eight cases and PD in one case. Six patients were evaluated after third PIHP with PR in five patients and SD in one patient. Two patients received fourth PIHP with PD in both cases. Median OS was 9.6 months (range 1.6–41.0 months). Median progression-free survival time was 12.4 months (range 0.9–41.0 months) with 1-year survival of 44%. Most common post-procedural AE grade 3 and 4 were temporary leukopenia (n = 11) and thrombocytopenia (n = 8). Patients’ self-assessments showed good ratings for overall health and quality of life with only slight changes after PIHP, and a high degree of satisfaction with PIHP treatment.ConclusionPIHP with Melphalan proved to be a relatively safe, minimal-invasive and repeatable treatment for patients with non-resectable hepatic metastases of uveal melanoma.

  6. Yttrium-90 Microsphere Brachytherapy for Liver Metastases From Uveal Melanoma: Clinical Outcomes and the Predictive Value of Fluorodeoxyglucose Positron Emission Tomography.

    Science.gov (United States)

    Eldredge-Hindy, Harriet; Ohri, Nitin; Anne, Pramila R; Eschelman, David; Gonsalves, Carin; Intenzo, Charles; Bar-Ad, Voichita; Dicker, Adam; Doyle, Laura; Li, Jun; Sato, Takami

    2016-04-01

    To report outcomes after yttrium-90 microsphere brachytherapy for unresectable liver metastases from uveal melanoma and to evaluate factors predictive for overall survival (OS) and hepatic progression-free survival (PFS). A total of 71 patients were consecutively treated with microsphere brachytherapy for unresectable liver metastases from uveal melanoma between 2007 and 2012. Clinical, radiographic, and positron emission tomography-derived, functional tumor parameters were evaluated by log-rank test in univariate analysis and backwards stepwise multivariate Cox proportional hazards regression. OS and hepatic PFS were estimated by Kaplan-Meier analysis. A total of 134 procedures were performed in 71 patients with a median age of 63 years (range, 23 to 91 y). Fifty-eight patients (82%) received microsphere brachytherapy as a salvage therapy. Median hepatic PFS and OS after microsphere brachytherapy were 5.9 months (range, 1.3 to 19.1 mo) and 12.3 months (range, 1.9 to 49.3 mo), respectively. Median OS times after diagnosis of liver metastases was 23.9 months (range, 6.2 to 69.0 mo). In univariate analysis, female sex, pretreatment metabolic tumor volume, and total glycolic activity (TGA) were significantly correlated with hepatic PFS and OS. In multivariate analysis, female sex and TGA retained significance as independent predictors of hepatic PFS and OS. A low pretreatment TGA (Yttrium-90 microsphere brachytherapy provided favorable survival times in patients with unresectable liver metastases from uveal melanoma. Metabolic tumor volume and TGA are predictive functional tumor parameters, which may aid patient selection and risk stratification.

  7. Positive interaction between light iris color and ultraviolet radiation in relation to the risk of uveal melanoma: a case-control study.

    Science.gov (United States)

    Schmidt-Pokrzywniak, Andrea; Jöckel, Karl-Heinz; Bornfeld, Norbert; Sauerwein, Wolfgang; Stang, Andreas

    2009-02-01

    To examine the association among phenotypic characteristics, chronic and intermittent ultraviolet (UV) radiation, and the risk of uveal melanoma. Case-control study. Overall, between September of 2002 and March of 2005, 1677 eligible subjects (age range: 20-74 years, living in Germany) participated. Interviews were conducted with 459 incident uveal melanoma cases (response proportion 94%), 827 population controls (55%), 180 ophthalmologist controls (52%), and 187 sibling controls (57%). Data on phenotypic characteristics and chronic and intermittent UV radiation exposure were obtained from a self-administered postal questionnaire and computer-assisted telephone interview. We used conditional logistic regression to estimate odds ratios adjusting for the matching factors. Furthermore, we studied the presence of synergy (super additive of risk or relative excess risk due to interaction) between light iris color and several UV radiation exposures. Hair color at age 20 years, eye color, untanned skin color, ability to tan, propensity to burn on exposure, freckling, occupational sun exposure, artificial UV radiation, burns to the eyes. In all 3 control groups, fair skin color, freckling as a child, nevi on the upper arms, burns to the eyes, use of sunlamps, and ever worked outside for 4 or more hours per day were positively associated with uveal melanoma. The association with eye color was apparent only in population controls (odds ratio = 1.9; 95% confidence interval [CI], 1.4-5.2), resulting in a relative excess risk due to interaction of 0.9 (95% CI, -0.6-2.3) for light iris color and more than 5 eye burns (UV-related keratitis) and 0.6 (95% CI, -0.3 to 1.5) for light iris color and eye protection. Our interaction analyses suggest that there is an etiologic synergism between light iris color and the exposure of UV radiation. People with light iris color may have an especially increased risk for uveal melanoma if they are exposed to UV radiation. The author(s) have no

  8. Treatment of metastatic uveal melanoma with adoptive transfer of tumour-infiltrating lymphocytes: a single-centre, two-stage, single-arm, phase 2 study.

    Science.gov (United States)

    Chandran, Smita S; Somerville, Robert P T; Yang, James C; Sherry, Richard M; Klebanoff, Christopher A; Goff, Stephanie L; Wunderlich, John R; Danforth, David N; Zlott, Daniel; Paria, Biman C; Sabesan, Arvind C; Srivastava, Abhishek K; Xi, Liqiang; Pham, Trinh H; Raffeld, Mark; White, Donald E; Toomey, Mary Ann; Rosenberg, Steven A; Kammula, Udai S

    2017-06-01

    Uveal melanoma is a rare tumour with no established treatments once metastases develop. Although a variety of immune-based therapies have shown efficacy in metastatic cutaneous melanoma, their use in ocular variants has been disappointing. Recently, adoptive T-cell therapy has shown salvage responses in multiple refractory solid tumours. Thus, we sought to determine if adoptive transfer of autologous tumour-infiltrating lymphocytes (TILs) could mediate regression of metastatic uveal melanoma. In this ongoing single-centre, two-stage, phase 2, single-arm trial, patients (aged ≥16 years) with histologically confirmed metastatic ocular melanoma were enrolled. Key eligibility criteria were an Eastern Cooperative Oncology Group performance status of 0 or 1, progressive metastatic disease, and adequate haematological, renal, and hepatic function. Metastasectomies were done to procure tumour tissue to generate autologous TIL cultures, which then underwent large scale ex-vivo expansion. Patients were treated with lymphodepleting conditioning chemotherapy (intravenous cyclophosphamide [60 mg/kg] daily for 2 days followed by fludarabine [25 mg/m 2 ] daily for 5 days, followed by a single intravenous infusion of autologous TILs and high-dose interleukin-2 [720 000 IU/kg] every 8 h). The primary endpoint was objective tumour response in evaluable patients per protocol using Response to Evaluation Criteria in Solid Tumors, version 1.0. An interim analysis of this trial is reported here. The trial is registered at ClinicalTrials.gov, number NCT01814046. From the completed first stage and ongoing expansion stage of this trial, a total of 21 consecutive patients with metastatic uveal melanoma were enrolled between June 7, 2013, and Sept 9, 2016, and received TIL therapy. Seven (35%, 95% CI 16-59) of 20 evaluable patients had objective tumour regression. Among the responders, six patients achieved a partial response, two of which are ongoing and have not reached maximum

  9. Radiotherapy of uveal melanomas experiences with proton beam irradiation of high risk parapapillary, paramaculary tumors

    International Nuclear Information System (INIS)

    Hideghety, K.; Sauerwein, W.; Fluehs, D.; Sack, H.; Quast

    1999-01-01

    The role of the radiotherapy in the treatment of malignant chorioidal melanomas has been established by means of 106 Ru or 125 I applicators and proton therapy. The rationale of the indication to utilize brachytherapy or proton therapy is presented on the basis of the clinical situation and physical characteristic of the different radiation modalities. (author)

  10. Braquiterapia com rutênio-106 em melanomas uveais - resultados preliminares: experiência uni-institucional Ruthenium-106 brachytherapy for uveal melanomas - preliminary results: a single institutional experience

    Directory of Open Access Journals (Sweden)

    Rodrigo Souza Dias

    2007-04-01

    Full Text Available OBJETIVO: Analisar os resultados preliminares da braquiterapia com rutênio-106 em pacientes portadores de melanomas uveais. MATERIAIS E MÉTODOS: No período de abril de 2002 a julho de 2003, 20 pacientes com diagnóstico de melanoma uveal foram tratados com braquiterapia com rutênio-106. A dose calculada no ápice tumoral variou de 55 Gy a 100 Gy. Pacientes com lesões com altura maior que 5 mm foram submetidos a termoterapia transpupilar concomitante à colocação da placa oftálmica. RESULTADOS: Quanto à localização da lesão, esta se encontrava na coróide em 75% dos casos, na íris em 15% e no corpo ciliar em 10% dos pacientes. Com seguimento mediano de 19 meses, a sobrevida livre de progressão para a braquiterapia e para a associação com a termoterapia transpupilar foi de 69% e 87%, respectivamente. Observou-se redução significante da altura tumoral após o tratamento. Nenhum dos pacientes foi submetido a enucleação. CONCLUSÃO: Nossos resultados preliminares mostram que a braquiterapia com rutênio-106 é uma opção adequada para o tratamento conservador de melanomas uveais em termos de controle local, manutenção do globo ocular e visão útil, com índice aceitável de complicações.OBJECTIVE: To analyze the early response of uveal melanomas in patients treated with ruthenium-106 brachytherapy. MATERIALS AND METHODS: In the period between April 2002 and July 2003, 20 patients diagnosed with uveal melanoma were submitted to ruthenium-106 brachytherapy. The calculated dose delivered at the apex of the tumor ranged between 55 Gy and 100 Gy. Patients with lesions greater than 5 mm were submitted to transpupillary thermotherapy concomitantly with ophthalmic plaque insertion. RESULTS: As regards the lesions site, 75% of the lesions were located in the choroid, 15% in the iris, and the remainder 10% in the ciliary body. In a median 19-month-follow-up, the progression-free survival for brachytherapy was 69%, and 87% for

  11. In vitro characterization and inhibition of the CXCR4/CXCL12 chemokine axis in human uveal melanoma cell lines

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    Antecka Emilia

    2007-11-01

    Full Text Available Abstract Purpose The CXCR4/CXCL12 chemokine axis may play a critical role in guiding CXCR4+ circulating malignant cells to organ specific locations that actively secrete its ligand CXCL12 (SDF-1 such as bone, brain, liver, and lungs. We sought to characterize the presence of the CXCR4/CXCL12 axis in five uveal melanoma (UM cell lines in vitro. The ability of TN14003, a synthetic peptide inhibitor that targets the CXCR4 receptor complex, to inhibit this axis was also assessed. Methods Immunocytochemistry was performed against CXCR4 to confirm expression of this chemokine receptor in all five UM cell lines. Flow cytometry was preformed to evaluate CXCR4 cell surface expression on all five UM cell lines. A proliferation assay was also used to test effects TN14003 would have on cellular proliferation. Inhibition of cellular migration by specifically inhibiting the CXCR4/CXCL12 axis with TN14003 was also investigated. The binding efficacy of TN14003 to the CXCR4 receptor was assessed through flow cytometric methods. Results The CXCR4 receptor was present on all five UM cell lines. All five cell lines expressed different relative levels of surface CXCR4. TN14003 did not affect the proliferation of the five cell lines (p > 0.05. All cell lines migrated towards the chemokine CXCL12 at a level greater than the negative control (p Conclusion Interfering with the CXCR4/CXCL12 axis, using TN14003 was shown to effectively down regulate UM cell migration in vitro. Knowing that UM expresses the CXCR4 receptor, these CXCR4+ cells may be less likely to colonize distant organs that secrete the CXCL12 ligand, if treated with an inhibitor that binds CXCR4. Further studies should be pursued in order to test TN14003 efficacy in vivo.

  12. Expression of focal adhesion kinase in uveal melanoma and the effects of Hsp90 inhibition by 17-AAG.

    Science.gov (United States)

    Faingold, Dana; Filho, Vasco Bravo; Fernandes, Bruno; Jagan, Lisa; de Barros, Alexandre M; Orellana, Maria Eugenia; Antecka, Emilia; Burnier, Miguel N

    2014-11-01

    Focal adhesion kinase (FAK) is implicated in tumor progression and metastatic cascade, and has been shown to be overexpressed in a variety of human cancers. However, the role of FAK in human uveal melanoma (UM) is not well defined. The purpose of this study was to evaluate the expression of FAK in UM tumors and normal eyes, and to determine the effect of Hsp90 inhibition on FAK expression in UM cells. FAK expression was assessed in 39 UM specimens, FAK[pY397] expression was assessed in 51 UM specimens, and both FAK and FAK[pY397] expression were assessed in 20 normal eyes. The expression of FAK and FAK[pY397] was detected by Western blot in five UM cell lines after treatment with 10 μmol/L of 17-AAG. FAK was positive in 87.2% and FAK[pY397] in 90% of UM specimens. Low FAK expression was detected in non-tumor structures and in normal eyes. The cell lines with the most proliferative, invasive phenotype (92.1, SP6.5 and MKT-BR) displayed high expression of FAK[pY397], and the levels of FAK and FAK[pY397] were decreased in the presence of 17-AAG starting with 24 h of exposure. FAK and FAK[pY397] were overexpressed in human UM tumors compared to normal ocular tissue and high levels of FAK[pY397] were seen in the most aggressive UM cell lines. Hsp90 inhibition led to downregulation of FAK expression. We propose a role for FAK in the pathogenesis of UM. Future studies are needed to explore the use of Hsp90 inhibitors as a feasible approach for modulating FAK in UM. Copyright © 2014 Elsevier GmbH. All rights reserved.

  13. Monte Carlo calculations and measurements of absorbed dose per monitor unit for the treatment of uveal melanoma with proton therapy

    Energy Technology Data Exchange (ETDEWEB)

    Koch, Nicholas; Newhauser, Wayne D; Titt, Uwe; Starkschall, George [Department of Radiation Physics, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030 (United States); Gombos, Dan [Section of Ophthalmology, Department of Head and Neck Surgery MDACC Unit 441 (United States); Coombes, Kevin [Graduate School of Biomedical Sciences, University of Texas Health Science Center, 6767 Bertner Avenue, Houston, TX 77030 (United States)], E-mail: kochn@musc.edu

    2008-03-21

    The treatment of uveal melanoma with proton radiotherapy has provided excellent clinical outcomes. However, contemporary treatment planning systems use simplistic dose algorithms that limit the accuracy of relative dose distributions. Further, absolute predictions of absorbed dose per monitor unit are not yet available in these systems. The purpose of this study was to determine if Monte Carlo methods could predict dose per monitor unit (D/MU) value at the center of a proton spread-out Bragg peak (SOBP) to within 1% on measured values for a variety of treatment fields relevant to ocular proton therapy. The MCNPX Monte Carlo transport code, in combination with realistic models for the ocular beam delivery apparatus and a water phantom, was used to calculate dose distributions and D/MU values, which were verified by the measurements. Measured proton beam data included central-axis depth dose profiles, relative cross-field profiles and absolute D/MU measurements under several combinations of beam penetration ranges and range-modulation widths. The Monte Carlo method predicted D/MU values that agreed with measurement to within 1% and dose profiles that agreed with measurement to within 3% of peak dose or within 0.5 mm distance-to-agreement. Lastly, a demonstration of the clinical utility of this technique included calculations of dose distributions and D/MU values in a realistic model of the human eye. It is possible to predict D/MU values accurately for clinical relevant range-modulated proton beams for ocular therapy using the Monte Carlo method. It is thus feasible to use the Monte Carlo method as a routine absolute dose algorithm for ocular proton therapy.

  14. Electrochemotherapy with bleomycin and cisplatin enhances cytotoxicity in primary and metastatic uveal melanoma cell lines in vitro.

    Science.gov (United States)

    Fiorentzis, M; Kalirai, H; Katopodis, P; Seitz, B; Viestenz, A; Coupland, S E

    2018-01-01

    Electrochemotherapy (ECT) enhances responsiveness to cytotoxic drugs in numerous cell lines in vitro. Clinically ECT is widely applied for skin tumor ablation and has shown efficacy in treating non-resectable colorectal liver metastases. There is limited experience of ECT for ocular tumor therapy. We investigated the cytotoxic effect of bleomycin and cisplatin in combination with electroporation on chemoresistant human uveal melanoma (UM) cell lines in vitro. Four UM cell lines (Mel 270, 92-1, OMM-1, OMM-2.5) were treated with electroporation (pulse amplitude 300-1000 V/cm, 8-80 pulses, 100 μs, 5 Hz) and increasing concentrations of bleomycin and cisplatin (0-7.5 μg/ml). Cell survival was analyzed by MTT viability assay after 36 hours. UM cell lines were resistant to both bleomycin and cisplatin. In combination with electro- poration, the effects of bleomycin and cisplatin were increased 8-70 fold and 3-15 fold, respectively, in all UM cell lines. At the lowest concentration of bleomycin tested (1 μg/ml), viability was maximally reduced in all UM cell lines by ≥69% with electroporation conditions of 750 V/cm and 20 pulses. All UM cell lines were more resistant to cisplatin; however, electro- poration of 1000 V/cm and 8 pulses resulted in similar reductions in cell viability of 92-1, Mel270 with 2.5 μg/ml cisplatin, OMM2-5 cells with 5 μg/ml cisplatin and OMM1 cells with 1 μg/ml cisplatin. In vitro ECT with bleomycin or cisplatin is more effective than the highest concentration of the antineoplastic drug or electroporation alone, opening new perspectives in primary and metastatic UM treatment.

  15. Eye imaging with a 3.0-T MRI using a surface coil - a study on volunteers and initial patients with uveal melanoma

    International Nuclear Information System (INIS)

    Lemke, Arne-Joern; Hengst, Susanne Anja; Kazi, Iris; Felix, Roland; Alai-Omid, Minouche

    2006-01-01

    MRI of uveal melanoma using 1.5-T technology and surface coils has developed into a standard procedure. The purpose of the study was to evaluate the feasibility of 3.0-T technology in eye imaging. To optimize the MRI sequences for clinical eye imaging with 3.0-T, six healthy volunteers were conducted using a 4.0-cm surface coil. Evaluation criteria were the signal-to-noise-ratio (SNR), contrast-to-noise-ratio (CNR) and image quality. A further six patients with uveal melanoma were examined with 1.5- and 3.0-T under retrobulbar anesthesia. During 3.0-T examinations of volunteers, eye movements caused significant artifacts. On the contrary, excellent imaging quality was reached in examinations of patients under retrobulbar anesthesia at 3.0 T. Subjective assessment showed no significant difference between 1.5 and 3.0 T in patients. Due to the increased SNR, the 3.0-T technique has the potential to improve eye imaging, but the higher susceptibility to motion artifacts limits the clinical use of this technique to patients receiving retrobulbar anesthesia. (orig.)

  16. Clinical evaluation of ultra-high-field MRI for three-dimensional visualisation of tumour size in uveal melanoma patients, with direct relevance to treatment planning.

    Science.gov (United States)

    Beenakker, Jan-Willem M; Ferreira, Teresa A; Soemarwoto, Karina P; Genders, Stijn W; Teeuwisse, Wouter M; Webb, Andrew G; Luyten, Gregorius P M

    2016-06-01

    To assess the tumour dimensions in uveal melanoma patients using 7-T ocular MRI and compare these values with conventional ultrasound imaging to provide improved information for treatment options. Ten uveal melanoma patients were examined on a 7-T MRI system using a custom-built eye coil and dedicated 3D scan sequences to minimise eye-motion-induced image artefacts. The maximum tumour prominence was estimated from the three-dimensional images and compared with the standard clinical evaluation from 2D ultrasound images. The MRI protocols resulted in high-resolution motion-free images of the eye in which the tumour and surrounding tissues could clearly be discriminated. For eight of the ten patients the MR images showed a slightly different value of tumour prominence (average 1.0 mm difference) compared to the ultrasound measurements, which can be attributed to the oblique cuts through the tumour made by the ultrasound. For two of these patients the more accurate results from the MR images changed the treatment plan, with the smaller tumour dimensions making them eligible for eye-preserving therapy. High-field ocular MRI can yield a more accurate measurement of the tumour dimensions than conventional ultrasound, which can result in significant changes in the prescribed treatment.

  17. Eye imaging with a 3.0-T MRI using a surface coil - a study on volunteers and initial patients with uveal melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Lemke, Arne-Joern; Hengst, Susanne Anja; Kazi, Iris; Felix, Roland [Klinik fuer Strahlenheilkunde, Universitaetsklinikum Charite, Campus Virchow-Klinikum, Medizinische Fakultaet der Humboldt-Universitaet zu Berlin, Berlin (Germany); Alai-Omid, Minouche [Nuklearmedizin und Strahlentherapie, Klinikum Spandau, Vivantes-Netzwerk fuer Gesundheit, Institut fuer Radiologie, Berlin (Germany)

    2006-05-15

    MRI of uveal melanoma using 1.5-T technology and surface coils has developed into a standard procedure. The purpose of the study was to evaluate the feasibility of 3.0-T technology in eye imaging. To optimize the MRI sequences for clinical eye imaging with 3.0-T, six healthy volunteers were conducted using a 4.0-cm surface coil. Evaluation criteria were the signal-to-noise-ratio (SNR), contrast-to-noise-ratio (CNR) and image quality. A further six patients with uveal melanoma were examined with 1.5- and 3.0-T under retrobulbar anesthesia. During 3.0-T examinations of volunteers, eye movements caused significant artifacts. On the contrary, excellent imaging quality was reached in examinations of patients under retrobulbar anesthesia at 3.0 T. Subjective assessment showed no significant difference between 1.5 and 3.0 T in patients. Due to the increased SNR, the 3.0-T technique has the potential to improve eye imaging, but the higher susceptibility to motion artifacts limits the clinical use of this technique to patients receiving retrobulbar anesthesia. (orig.)

  18. Patterns of care and survival outcomes after treatment for uveal melanoma in the post-coms era (2004-2013: a surveillance, epidemiology, and end results analysis

    Directory of Open Access Journals (Sweden)

    Yuan James Rao

    2017-10-01

    Full Text Available Purpose : The Collaborative Ocular Melanoma Study (COMS established modern treatment recommendations for uveal melanoma. We aim to evaluate patterns of care and survival outcomes in the time after COMS. Material and methods : The retrospective study population includes 2,611 patients in the SEER database treated for uveal melanoma between 2004-2013. Patients stage were T1-4N0M0. Data analyzed included age, clinical stage, tumor size, race, and treatment. Treatments included enucleation (EN and globe preserving therapy (GPT, which consisted of limited surgical resection or ablation (LSRA, external beam radiation (EBRT, or brachytherapy (BT. Patients treated with radiation may receive radiation therapy alone (RTA or radiation therapy and supplemental laser therapy (RT+SLT. We evaluated disease specific survival (DSS and overall survival (OS using log-rank statistics, and Cox univariate and multivariate analysis. Results : The median follow-up was 44 months. Treatment strategy was EN in 538 (20.6% patients, LSRA in 80 (3.1%, EBRT in 609 (23.3%, and BT in 1,384 (53.0%. 1,876 patients received RTA and 117 received RT+SLT. Enucleation was associated with inferior DSS and OS compared to GPT in multivariate analysis (MVA (p < 0.01. Limited surgical resection or ablation and radiation had similar DSS and OS. Brachytherapy and EBRT had similar DSS and OS. Radiation therapy and supplemental laser therapy was associated with improved DSS compared to RTA in UVA (p = 0.03, but not MVA. The 5-year DSS for enucleation, RTA, and RT+SLT were 66.7%, 87.0%, and 94.7% (p < 0.01, respectively. Conclusions : Globe preserving treatments such as limited surgery or radiation are commonly utilized alternatives to enucleation, and resulted in favorable survival outcomes. Additional research is required to compare the outcomes of the various globe preserving treatment strategies.

  19. Clinico-Pathological Association of Delineated miRNAs in Uveal Melanoma with Monosomy 3/Disomy 3 Chromosomal Aberrations.

    Directory of Open Access Journals (Sweden)

    Nalini Venkatesan

    Full Text Available To correlate the differentially expressed miRNAs with clinico-pathological features in uveal melanoma (UM tumors harbouring chromosomal 3 aberrations among South Asian Indian cohort.Based on chromosomal 3 aberration, UM (n = 86 were grouped into monosomy 3 (M3; n = 51 and disomy 3 (D3; n = 35 by chromogenic in-situ hybridisation (CISH. The clinico-pathological features were recorded. miRNA profiling was performed in formalin fixed paraffin embedded (FFPE UM samples (n = 6 using Agilent, Human miRNA microarray, 8x15KV3 arrays. The association between miRNAs and clinico-pathological features were studied using univariate and multivariate analysis. miRNA-gene targets were predicted using Target-scan and MiRanda database. Significantly dys-regulated miRNAs were validated in FFPE UM (n = 86 and mRNAs were validated in frozen UM (n = 10 by qRT-PCR. Metastasis free-survival and miRNA expressions were analysed by Kaplen-Meier analysis in UM tissues (n = 52.Unsupervised analysis revealed 585 differentially expressed miRNAs while supervised analysis demonstrated 82 miRNAs (FDR; Q = 0.0. Differential expression of 8 miRNAs: miR-214, miR-149*, miR-143, miR-146b, miR-199a, let7b, miR-1238 and miR-134 were studied. Gene target prediction revealed SMAD4, WISP1, HIPK1, HDAC8 and C-KIT as the post-transcriptional regulators of miR-146b, miR-199a, miR-1238 and miR-134. Five miRNAs (miR-214, miR146b, miR-143, miR-199a and miR-134 were found to be differentially expressed in M3/ D3 UM tumors. In UM patients with liver metastasis, miR-149* and miR-134 expressions were strongly correlated.UM can be stratified using miRNAs from FFPE sections. miRNAs predicting liver metastasis and survival have been identified. Mechanistic linkage of de-regulated miRNA/mRNA expressions provide new insights on their role in UM progression and aggressiveness.

  20. Patterns of BAP1 protein expression provide insights into prognostic significance and the biology of uveal melanoma.

    Science.gov (United States)

    Farquhar, Neil; Thornton, Sophie; Coupland, Sarah E; Coulson, Judy M; Sacco, Joseph J; Krishna, Yamini; Heimann, Heinrich; Taktak, Azzam; Cebulla, Colleen M; Abdel-Rahman, Mohamed H; Kalirai, Helen

    2018-01-01

    Uveal melanoma (UM) is a rare aggressive intraocular tumour with a propensity for liver metastases, occurring in ∼50% of patients. The tumour suppressor BAP1 is considered to be key in UM progression. Herein, we present the largest study to date investigating cellular expression patterns of BAP1 protein in 165 UMs, correlating these patterns to prognosis. Full clinical, histological, genetic, and follow-up data were available for all patients. BAP1 gene sequencing was performed on a subset of 26 cases. An independent cohort of 14 UMs was examined for comparison. Loss of nuclear BAP1 (nBAP1) protein expression was observed in 54% (88/165) UMs. nBAP1 expression proved to be a significant independent prognostic parameter: it identified two subgroups within monosomy 3 (M3) UM, which are known to have a high risk of metastasis. Strikingly, nBAP1-positiveM3 UMs were associated with prolonged survival compared to nBAP1-negative M3 UMs (Log rank, p  = 0.014). nBAP1 protein loss did not correlate with a BAP1 mutation in 23% (6/26) of the UMs analysed. Cytoplasmic BAP1 protein (cBAP1) expression was also observed in UM: although appearing 'predominantly diffuse' in most nBAP1-negative UM, a distinct 'focal perinuclear' expression pattern - localized immediately adjacent to the cis Golgi - was seen in 31% (18/59). These tumours tended to carry loss-of-function BAP1 mutations. Our study demonstrates loss of nBAP1 expression to be the strongest prognostic marker in UM, confirming its importance in UM progression. Our data suggest that non-genetic mechanisms account for nBAP1 loss in a small number of UMs. In addition, we describe a subset of nBAP1-negative UM, in which BAP1 is sequestered in perinuclear bodies, most likely within Golgi, warranting further mechanistic investigation.

  1. Surgery vs. radiotherapy in patients with uveal melanoma. Analysis of the SEER database using propensity score matching and weighting

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Bum-Sup [Seoul National University Hospital, Department of Radiation Oncology, Seoul (Korea, Republic of); Chang, Ji Hyun [SMG-SNU Boramae Medical Center, Department of Radiation Oncology, Seoul (Korea, Republic of); Oh, Sohee [SMG-SNU Boramae Medical Center, Department of Biostatistics, Seoul (Korea, Republic of); Lim, Yu Jin [Kyunghee University Hospital, Department of Radiation Oncology, Seoul (Korea, Republic of); Kim, Il Han [Seoul National University College of Medicine, Department of Radiation Oncology, Seoul (Korea, Republic of)

    2017-11-15

    The treatment modalities for uveal melanoma (UM) include surgery and radiotherapy (RT). The utilization of RT as a strategy for organ preservation has been increasing, but the survival difference between the two aforementioned treatment modalities has not been reported. An observational and cohort study was performed using a propensity score with an already existing public database. Patients diagnosed with UM within the period from 2004-2013 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. One-to-one matching and inverse probability of treatment weighting (IPTW) using the propensity score were used to estimate and compare survival rates. Overall, 3291 patients were treated: 2503 received RT only (RT group) and 788 received surgical resection only (surgery group). The RT group had an improved crude 5-year overall survival (OS) rate compared with the surgery group (76% vs. 60%, P < 0.001), and an improved 5-year melanoma-specific survival (MSS) rate (89% vs. 73%, P < 0.001). Compared to the surgery group, the RT group was associated with improved OS (hazard ratio [HR] 0.52, 95% confidence interval [CI] 0.38-0.73, P < 0.001) and MSS (HR 0.48, 95% CI 0.35-0.65, P < 0.001) in the matched cohort. The survival benefit of the RT group maintained after adjustment with IPTW, both in OS and MSS. To our knowledge, the present study was the first to demonstrate the survival difference between the two treatment modalities for UM using both the propensity score matching and weighting methods with the SEER database. The current study suggests that RT may provide a survival advantage over surgery in the treatment of UM. (orig.) [German] Die Behandlungsmodalitaeten fuer das Uveamelanom (UM) sind die Chirurgie und Strahlentherapie (RT). Die Nutzung der RT als Strategie zum Organerhalt hat zugenommen, aber der Unterschied in der Ueberlebensrate zwischen den beiden zuvor genannten Behandlungsmodalitaeten wurde nicht berichtet. Beobachtungs- und

  2. Use of the Toric Surgical Marker to Aid in Intraoperative Plaque Placement for the USC Eye Physics Plaques to Treat Uveal Melanoma: A New Surgical Technique.

    Science.gov (United States)

    Berry, Jesse L; Kim, Jonathan W; Jennelle, Richard; Astrahan, Melvin

    2015-09-01

    To describe a new surgical technique for intraoperative placement of Eye Physics (EP) plaques for uveal melanoma using a toric marker. A toric marker is designed for cataract surgery to align the axis of astigmatism; its use was modified in this protocol to mark the axis of suture coordinates as calculated by Plaque Simulator (PS) software. The toric marker can be used to localize suture coordinates, in degrees, during intraoperative plaque placement. Linear marking using the toric marker decreases potential inaccuracies associated with the surgeon estimating 'clock-hours' by dot placement. Use of the toric marker aided surgical placement of EP plaques. The EP planning protocol is now designed to display the suture coordinates either by clock-hours or degrees, per surgeon preference. Future research is necessary to determine whether routine use of the toric marker improves operative efficiency. [Ophthalmic Surg Lasers Imaging Retina. 2015;46:866-870.]. Copyright 2015, SLACK Incorporated.

  3. Risk Factors for Neovascular Glaucoma After Proton Beam Therapy of Uveal Melanoma: A Detailed Analysis of Tumor and Dose–Volume Parameters

    International Nuclear Information System (INIS)

    Mishra, Kavita K.; Daftari, Inder K.; Weinberg, Vivian; Cole, Tia; Quivey, Jeanne M.; Castro, Joseph R.; Phillips, Theodore L.; Char, Devron H.

    2013-01-01

    Purpose: To determine neovascular glaucoma (NVG) incidence and identify contributing tumor and dosing factors in uveal melanoma patients treated with proton beam radiation therapy (PBRT). Methods and Materials: A total of 704 PBRT patients treated by a single surgeon (DHC) for uveal melanoma (1996-2010) were reviewed for NVG in our prospectively maintained database. All patients received 56 GyE in 4 fractions. Median follow-up was 58.3 months. Analyses included the Kaplan-Meier method to estimate NVG distributions, univariate log–rank tests, and Cox's proportional hazards multivariate analysis using likelihood ratio tests to identify independent risk factors of NVG among patient, tumor, and dose–volume histogram parameters. Results: The 5-year PBRT NVG rate was 12.7% (95% confidence interval [CI] 10.2%-15.9%). The 5-year rate of enucleation due to NVG was 4.9% (95% CI 3.4%-7.2%). Univariately, the NVG rate increased significantly with larger tumor diameter (P 30% of the lens or ciliary body received ≥50% dose (≥28 GyE), there was a higher probability of NVG (P 0%-30% vs >30%) (P=.01), and optic nerve length treated to ≥90% Dose (≤1 mm vs >1 mm) (P=.02). Conclusions: Our current PBRT patients experience a low rate of NVG and resultant enucleation compared with historical data. The present analysis shows that tumor height, diameter, and anterior as well as posterior critical structure dose–volume parameters may be used to predict NVG risk

  4. Screening for metastatic malignant melanoma of the uvea revisited

    DEFF Research Database (Denmark)

    Eskelin, Sebastian; Pyrhönen, Seppo; Summanen, Paula

    1999-01-01

    ophthalmology, malignant uveal melanoma, metastasis, liver, screening, ultrasonography, X-ray, lactate dehydrogenase, alkaline phosphatase, aminotransferases......ophthalmology, malignant uveal melanoma, metastasis, liver, screening, ultrasonography, X-ray, lactate dehydrogenase, alkaline phosphatase, aminotransferases...

  5. [Ocular melanomas : An update].

    Science.gov (United States)

    Kalirai, H; Müller, P L; Jaehne, D; Coupland, S E

    2017-11-01

    Melanoma is the most common type of primary cancer to affect the adult eye. Approximately 95% of ocular melanomas are intraocular and arise from the uvea (i. e. iris, ciliary body, and choroid), while the remaining 5% are located in the conjunctiva. Although both uveal and conjunctival melanomas are thought to derive from malignantly transformed melanocytes, uveal melanoma is clinically and biologically distinct from conjunctival melanoma, and indeed from its more common cutaneous counterpart. Intense efforts have been recently made to understand the molecular biology involved in the development of ocular melanomas, and in their progression. Molecular advances, particularly for uveal melanoma, have enhanced prognostication and the identification of rational therapeutic targets for disseminated disease. In this review, recent advances in the molecular characterisation of both uveal and conjunctival melanomas are discussed, and how these may be used to develop personalised therapeutic strategies.

  6. Phase II DeCOG-study of ipilimumab in pretreated and treatment-naïve patients with metastatic uveal melanoma.

    Directory of Open Access Journals (Sweden)

    Lisa Zimmer

    Full Text Available Up to 50% of patients with uveal melanoma (UM develop metastatic disease with limited treatment options. The immunomodulating agent ipilimumab has shown an overall survival (OS benefit in patients with cutaneous metastatic melanoma in two phase III trials. As patients with UM were excluded in these studies, the Dermatologic Cooperative Oncology Group (DeCOG conducted a phase II to assess the efficacy and safety of ipilimumab in patients with metastatic UM.We undertook a multicenter phase II study in patients with different subtypes of metastatic melanoma. Here we present data on patients with metastatic UM (pretreated and treatment-naïve who received up to four cycles of ipilimumab administered at a dose of 3 mg/kg in 3 week intervals. Tumor assessments were conducted at baseline, weeks 12, 24, 36 and 48 according to RECIST 1.1 criteria. Adverse events (AEs, including immune-related AEs were graded according to National Cancer Institute Common Toxicity Criteria (CTC v.4.0. Primary endpoint was the OS rate at 12 months.Forty five pretreated (85% and eight treatment-naïve (15% patients received at least one dose of ipilimumab. 1-year and 2-year OS rates were 22% and 7%, respectively. Median OS was 6.8 months (95% CI 3.7-8.1, median progression-free survival 2.8 months (95% CI 2.5-2.9. The disease control rate at weeks 12 and 24 was 47% and 21%, respectively. Sixteen patients had stable disease (47%, none experienced partial or complete response. Treatment-related AEs were observed in 35 patients (66%, including 19 grade 3-4 events (36%. One drug-related death due to pancytopenia was observed.Ipilimumab has very limited clinical activity in patients with metastatic UM. Toxicity was manageable when treated as per protocol-specific guidelines.ClinicalTrials.gov NCT01355120.

  7. Phase II DeCOG-Study of Ipilimumab in Pretreated and Treatment-Naïve Patients with Metastatic Uveal Melanoma

    Science.gov (United States)

    Zimmer, Lisa; Vaubel, Julia; Mohr, Peter; Hauschild, Axel; Utikal, Jochen; Simon, Jan; Garbe, Claus; Herbst, Rudolf; Enk, Alexander; Kämpgen, Eckhart; Livingstone, Elisabeth; Bluhm, Leonie; Rompel, Rainer; Griewank, Klaus G.; Fluck, Michael; Schilling, Bastian; Schadendorf, Dirk

    2015-01-01

    Purpose Up to 50% of patients with uveal melanoma (UM) develop metastatic disease with limited treatment options. The immunomodulating agent ipilimumab has shown an overall survival (OS) benefit in patients with cutaneous metastatic melanoma in two phase III trials. As patients with UM were excluded in these studies, the Dermatologic Cooperative Oncology Group (DeCOG) conducted a phase II to assess the efficacy and safety of ipilimumab in patients with metastatic UM. Patients and Methods We undertook a multicenter phase II study in patients with different subtypes of metastatic melanoma. Here we present data on patients with metastatic UM (pretreated and treatment-naïve) who received up to four cycles of ipilimumab administered at a dose of 3 mg/kg in 3 week intervals. Tumor assessments were conducted at baseline, weeks 12, 24, 36 and 48 according to RECIST 1.1 criteria. Adverse events (AEs), including immune-related AEs were graded according to National Cancer Institute Common Toxicity Criteria (CTC) v.4.0. Primary endpoint was the OS rate at 12 months. Results Forty five pretreated (85%) and eight treatment-naïve (15%) patients received at least one dose of ipilimumab. 1-year and 2-year OS rates were 22% and 7%, respectively. Median OS was 6.8 months (95% CI 3.7–8.1), median progression-free survival 2.8 months (95% CI 2.5–2.9). The disease control rate at weeks 12 and 24 was 47% and 21%, respectively. Sixteen patients had stable disease (47%), none experienced partial or complete response. Treatment-related AEs were observed in 35 patients (66%), including 19 grade 3–4 events (36%). One drug-related death due to pancytopenia was observed. Conclusions Ipilimumab has very limited clinical activity in patients with metastatic UM. Toxicity was manageable when treated as per protocol-specific guidelines. Trial Registration ClinicalTrials.gov NCT01355120 PMID:25761109

  8. Iodine 125 Brachytherapy With Vitrectomy and Silicone Oil in the Treatment of Uveal Melanoma: 1-to-1 Matched Case-Control Series

    Energy Technology Data Exchange (ETDEWEB)

    McCannel, Tara A., E-mail: TMcCannel@jsei.ucla.edu; McCannel, Colin A.

    2014-06-01

    Purpose: We initially reported the radiation-attenuating effect of silicone oil 1000 centistokes for iodine 125. The purpose of this report was to compare the clinical outcomes in case patients who had iodine 125 brachytherapy with vitrectomy and silicone oil 1000 centistokes with the outcomes in matched control patients who underwent brachytherapy alone. Methods and Materials: Consecutive patients with uveal melanoma who were treated with iodine 125 plaque brachytherapy and vitrectomy with silicone oil with minimum 1-year follow-up were included. Control patients who underwent brachytherapy alone were matched for tumor size, location, and sex. Baseline patient and tumor characteristics and tumor response to radiation, final visual acuity, macular status, central macular thickness by ocular coherence tomography (OCT), cataract progression, and metastasis at last follow-up visit were compared. Surgical complications were also determined. Results: Twenty case patients met the inclusion criteria. The average follow-up time was 22.1 months in case patients and 19.4 months in control patients. The final logMAR vision was 0.81 in case patients and 1.1 in control patients (P=.071); 8 case patients and 16 control patients had abnormal macular findings (P=.011); and the average central macular thickness by OCT was 293.2 μm in case patients and 408.5 μm in control patients (P=.016). Eleven case patients (55%) and 1 control patient (5%) had required cataract surgery at last follow-up (P=.002). Four patients in the case group and 1 patient in the control group experienced metastasis (P=.18). Among the cases, intraoperative retinal tear occurred in 3 patients; total serous retinal detachment and macular hole developed in 1 case patient each. There was no case of rhegmatogenous retinal detachment, treatment failure, or local tumor dissemination in case patients or control patients. Conclusions: With up to 3 years of clinical follow-up, silicone oil during brachytherapy

  9. Risk Factors for Neovascular Glaucoma After Proton Beam Therapy of Uveal Melanoma: A Detailed Analysis of Tumor and Dose–Volume Parameters

    Energy Technology Data Exchange (ETDEWEB)

    Mishra, Kavita K., E-mail: kmishra@radonc.ucsf.edu [Department of Radiation Oncology, University of California, San Francisco, San Francisco, California (United States); Daftari, Inder K.; Weinberg, Vivian [Department of Radiation Oncology, University of California, San Francisco, San Francisco, California (United States); Cole, Tia [The Tumori Foundation, San Francisco, California (United States); Quivey, Jeanne M.; Castro, Joseph R.; Phillips, Theodore L. [Department of Radiation Oncology, University of California, San Francisco, San Francisco, California (United States); Char, Devron H. [The Tumori Foundation, San Francisco, California (United States)

    2013-10-01

    Purpose: To determine neovascular glaucoma (NVG) incidence and identify contributing tumor and dosing factors in uveal melanoma patients treated with proton beam radiation therapy (PBRT). Methods and Materials: A total of 704 PBRT patients treated by a single surgeon (DHC) for uveal melanoma (1996-2010) were reviewed for NVG in our prospectively maintained database. All patients received 56 GyE in 4 fractions. Median follow-up was 58.3 months. Analyses included the Kaplan-Meier method to estimate NVG distributions, univariate log–rank tests, and Cox's proportional hazards multivariate analysis using likelihood ratio tests to identify independent risk factors of NVG among patient, tumor, and dose–volume histogram parameters. Results: The 5-year PBRT NVG rate was 12.7% (95% confidence interval [CI] 10.2%-15.9%). The 5-year rate of enucleation due to NVG was 4.9% (95% CI 3.4%-7.2%). Univariately, the NVG rate increased significantly with larger tumor diameter (P<.0001), greater height (P<.0001), higher T stage (P<.0001), and closer proximity to the disc (P=.002). Dose–volume histogram analysis revealed that if >30% of the lens or ciliary body received ≥50% dose (≥28 GyE), there was a higher probability of NVG (P<.0001 for both). Furthermore, if 100% of the disc or macula received ≥28 GyE, the NVG rate was higher (P<.0001 and P=.03, respectively). If both anterior and posterior doses were above specified cut points, NVG risk was highest (P<.0001). Multivariate analysis confirmed significant independent risk factors to include tumor height (P<.0001), age (P<.0001), %disc treated to ≥50% Dose (<100% vs 100%) (P=.0007), larger tumor diameter (P=.01), %lens treated to ≥90% Dose (0 vs >0%-30% vs >30%) (P=.01), and optic nerve length treated to ≥90% Dose (≤1 mm vs >1 mm) (P=.02). Conclusions: Our current PBRT patients experience a low rate of NVG and resultant enucleation compared with historical data. The present analysis shows that tumor height

  10. Iodine 125 Brachytherapy With Vitrectomy and Silicone Oil in the Treatment of Uveal Melanoma: 1-to-1 Matched Case-Control Series

    International Nuclear Information System (INIS)

    McCannel, Tara A.; McCannel, Colin A.

    2014-01-01

    Purpose: We initially reported the radiation-attenuating effect of silicone oil 1000 centistokes for iodine 125. The purpose of this report was to compare the clinical outcomes in case patients who had iodine 125 brachytherapy with vitrectomy and silicone oil 1000 centistokes with the outcomes in matched control patients who underwent brachytherapy alone. Methods and Materials: Consecutive patients with uveal melanoma who were treated with iodine 125 plaque brachytherapy and vitrectomy with silicone oil with minimum 1-year follow-up were included. Control patients who underwent brachytherapy alone were matched for tumor size, location, and sex. Baseline patient and tumor characteristics and tumor response to radiation, final visual acuity, macular status, central macular thickness by ocular coherence tomography (OCT), cataract progression, and metastasis at last follow-up visit were compared. Surgical complications were also determined. Results: Twenty case patients met the inclusion criteria. The average follow-up time was 22.1 months in case patients and 19.4 months in control patients. The final logMAR vision was 0.81 in case patients and 1.1 in control patients (P=.071); 8 case patients and 16 control patients had abnormal macular findings (P=.011); and the average central macular thickness by OCT was 293.2 μm in case patients and 408.5 μm in control patients (P=.016). Eleven case patients (55%) and 1 control patient (5%) had required cataract surgery at last follow-up (P=.002). Four patients in the case group and 1 patient in the control group experienced metastasis (P=.18). Among the cases, intraoperative retinal tear occurred in 3 patients; total serous retinal detachment and macular hole developed in 1 case patient each. There was no case of rhegmatogenous retinal detachment, treatment failure, or local tumor dissemination in case patients or control patients. Conclusions: With up to 3 years of clinical follow-up, silicone oil during brachytherapy

  11. Braquiterapia com Cobalto 60 para o tratamento do melanoma da úvea: análise dos fatores prognósticos para melhor resposta local Cobalt - 60 brachytherapy for uveal melanoma: analysis of prognostic factors for local response

    Directory of Open Access Journals (Sweden)

    Martha Motono Chojniak

    2002-03-01

    Full Text Available Objetivo: Determinar fatores prognósticos para resposta tumoral local ao tratamento do melanoma uveal por braquiterapia com cobalto 60, segundo parâmetros clínicos e próprios deste método. Métodos: Avaliamos os índices de controle tumoral, complicações, doença metastática e sobrevida global em 69 portadores de melanoma uveal tratados por braquiterapia com cobalto 60 de novembro de 1988 a outubro de 1994, no Hospital do Câncer - A.C.Camargo de São Paulo. Confrontamos estes índices com diferentes características tumorais e da técnica de braquiterapia para determinação dos melhores fatores prognósticos. Resultados: Após o tratamento, 79,9% das lesões demonstraram diminuição da altura, 66,7% do diâmetro basal, e 37,2% da acuidade visual. Foram realizadas 16 (23,2% enucleações, em média 21,1meses após o tratamento, 10 (62,5% por falha no controle tumoral e 6 (37,5% devido a complicações. O índice de doença metastática foi de 11,6% e o de sobrevida para 5 anos de 89,1%. O índice de complicação foi 76,8% e o de conservação do globo ocular foi 76,8%. Fatores prognósticos para maior índice de conservação associado a menor índice de complicações foram: tratamento de lesões com até 5mm de altura e 10 mm de diâmetro basal; dose apical maior que 12.000 cGy; taxa de dose apical maior que 45 cGy/h; dose basal menor que 25.000 cGy; taxa de dose basal menor que 120 cGy/h e atividade da placa menor que 2 mCi. O tempo de seguimento médio foi de 44,3 meses (10,1-114,3 m. Conclusão: Tamanho tumoral, atividade da placa, dose e taxa de dose devem ser cuidadosamente estudados no planejamento braquiterápico, para otimização do método.Purpose: To determine prognostic factors for local control of uveal melanoma treated by brachytherapy with cobalt 60. Methods: We evaluated indexes of local tumor control, complications, metastatic disease and global survival in 69 uveal melanoma patients treated with brachytherapy with

  12. Melanoma

    Science.gov (United States)

    ... Lentigo maligna melanoma; Melanoma in situ; Superficial spreading melanoma; Nodular melanoma; Acral lentiginous melanoma ... and brown. It is most common in Caucasians. Nodular melanoma usually starts as a raised area that is ...

  13. Tumour thickness, diameter, area or volume? The prognostic significance of conventional versus digital image analysis-based size estimation methods in uveal melanoma.

    Science.gov (United States)

    Arnljots, Thorsteinn Snaebjörnsson; Al-Sharbaty, Zaid; Lardner, Emma; All-Eriksson, Charlotta; Seregard, Stefan; Stålhammar, Gustav

    2018-01-16

    The aim of this study was to compare conventional and novel size estimation methods' ability to predict survival in uveal melanoma (UM). The study was designed as a retrospective consecutive chart review of patients with UM, enucleated between the years 1984 and 1993. Area and volume were estimated based on the largest histopathological cross-section, the second centroid theorem of Pappus and digital image analysis, correlated to overall and relative survival. Of 168 patients analysed, 20 (12%) of tumours were categorized as T1, 47 (28%) as T2, 67 (40%) as T3 and 19 (11%) as T4 (15 N/a). A total of 91 tumours with complete survival and measurement data were included and recategorized into small, medium and large volume groups. Increased separation of overall survival was seen compared with current American Joint Committee on Cancer T categories. Difference between the large and small volume groups was 8.6 years (p = 0.001), compared to a difference of 5.6 years (p = 0.091) between T1 and T4. Hazard ratio for all-cause mortality in the large versus small volume group was 2.6 compared to 1.9 for T4 versus T1. Relative survival rates for small, medium and large volumes were 62, 44 and 31% at 10 years, versus 50, 45, 56 and 0% for T1, T2, T3 and T4. This study provides evidence that a novel UM volume estimation method might offer a practical and cost-efficient alternative to improve the prognostic value intrinsic to a tumour's size. © 2018 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  14. Características ecográficas de melanomas uveales en población mexicana (serie de casos

    Directory of Open Access Journals (Sweden)

    Ariel Prado Serrano

    2014-10-01

    Full Text Available El melanoma coroideo es el tumor intraocular maligno más frecuente. Es más frecuente en la raza blanca. El melanoma es asintomático, se puede hallar incidentalmente durante la exploración oftalmológica. Tiene características ultrasonográficas especiales, por lo que el ultrasonido en modo A/B y la ultrabiomicroscopia son técnicas de diagnóstico estándar en este tipo de patología, llegando al 95% de exactitud en la mayoría de los casos. En este estudio, se analizaron 8 casos de pacientes con este tipo de tumor, valorando principalmente los hallazgos ecográficos, colocando así a estas técnicas como una herramienta fundamental para el diagnóstico, la observación y la determinación del tratamiento del melanoma coroideo.

  15. WE-FG-BRA-10: Radiodosimetry of a Novel Alpha Particle Therapy Targeted to Uveal Melanoma: Absorbed Dose to Organs in Mice

    Energy Technology Data Exchange (ETDEWEB)

    Tichacek, Christopher J.; Tafreshi, Narges K.; Budzevich, Mikalai M.; Ruiz, Epifanio [Small Animal Imaging Core, Tampa, FL (United States); Wadas, Thaddeus J. [Wake Forest School of Medicine, Departments of Radiology and Cancer Biology, Winston-Salem, NC (United States); McLaughlin, Mark L. [Department of Chemistry, Tampa, FL (United States); H. Lee Moffitt Cancer Center & Research Institute (United States); Modulation Therapeutics, Inc., Tampa, FL (United States); Moros, Eduardo G.; Morse, David L.

    2016-06-15

    Purpose: The melanocortin-1 receptor (MC1R) is expressed in 94% of uveal melanomas and is described as an ideal target for this untreatable disease. MC1RL is a high affinity MC1R specific peptidomimetic ligand that can serve as a scaffold for therapeutic conjugates such as alpha particle emitting isotopes. The purpose of this study was to assess normal tissue distribution and risk as a result of using the DOTA chelator conjugated to MC1RL to deliver {sup 225}Ac: MC1RL-DOTA-{sup 225}Ac. Methods: 17 non-tumor bearing BALB/c mice were intravenously injected with the novel MC1RL-DOTA-{sup 225}Ac radiopharmaceutical with an average initial administered activity of 2.5 µCi. After the injection, three groups of animals (6, 6, and 5 per group) were euthanized at 24, 48, and 96 hour time points. A total of 11 organs of interest were harvested at each time point including kidneys and liver. Since the emitted alpha particles from {sup 225}Ac and its daughter products are not easy to detect directly, the isomeric gamma spectra were measured instead in the tissue samples using a modified Atomlab™ Gamma Counter (Biodex Medical Systems, Inc) and converted using factors for gamma ray abundance per alpha decay. Dosimetry was performed using measured radioactivity distribution in organs and the generalized internal dosimetry schema of MIRD pamphlet #21. Results: Our calculations have shown that the maximum absorbed dose was delivered to the liver with a total of 47 cGy per 96 hour period. The average dose per kidney was calculated to be 21 cGy. Heart, brain, lung, spleen, skin doses ranged from 0.01 to 1 cGy over the same time period. All animals gained weight over the 110 day decay period and no organ damage was observed by pathology. Conclusion: Based on our results, the risk of using the MC1RL-DOTA-{sup 225}Ac compound is relatively small in terms of deterministic radiation effects. Funding Support: NIH/NCI P50CA168536-03 Skin SPORE; NIH/NCI Phase I SBIR Contract #HHSN

  16. Melanoma

    Science.gov (United States)

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

  17. Reconciling the principle of patient autonomy with the practice of informed consent: decision-making about prognostication in uveal melanoma.

    Science.gov (United States)

    Cook, Sharon A; Damato, Bertil; Marshall, Ernie; Salmon, Peter

    2011-12-01

    Influential views on how to protect patient autonomy in clinical care have been greatly shaped by rational and deliberative models of decision-making. Our aim was to understand how the general principle of respecting autonomy can be reconciled with the local reality of obtaining consent in a clinical situation that precludes extended deliberation. We interviewed 22 patients with intraocular melanoma who had been offered cytogenetic tumour typing to indicate whether the tumour was likely to shorten life considerably. They were interviewed before and/or up to 36 months after receiving cytogenetic results. Patients described their decision-making about the test and how they anticipated and used the results. Their accounts were analysed qualitatively, using inconsistencies at a descriptive level to guide interpretative analysis. Patients did not see a decision to be made. For those who accepted testing, their choice reflected trust of what the clinicians offered them. Patients anticipated that a good prognosis would be reassuring, but this response was not evident. Although they anticipated that a poor prognosis would enable end-of-life planning, adverse results were interpreted hopefully. In general, the meaning of the test for patients was not separable from ongoing care. Models of decision-making and associated consent procedures that emphasize patients' active consideration of isolated decision-making opportunities are invalid for clinical situations such as this. Hence, responsibility for ensuring that a procedure protects patients' interests rests with practitioners who offer it and cannot be delegated to patients. © 2010 Blackwell Publishing Ltd.

  18. Characterization of luteinizing hormone-releasing hormone receptor type I (LH-RH-I) as a potential molecular target in OCM-1 and OCM-3 human uveal melanoma cell lines.

    Science.gov (United States)

    Sipos, Eva; Dobos, Nikoletta; Rozsa, David; Fodor, Klara; Olah, Gabor; Szabo, Zsuzsanna; Szekvolgyi, Lorant; Schally, Andrew V; Halmos, Gabor

    2018-01-01

    Uveal melanoma (UM) is the most common primary intraocular malignancy with very poor prognosis. Conventional chemotherapy only rarely prolongs the survival, therefore patients require novel treatment modalities. The discovery of specific receptors for hypothalamic hormones on cancer cells has led to the development of radiolabeled and cytotoxic hormone analogs. In the present study, our aim was to investigate the expression of mRNA for receptors of luteinizing hormone-releasing hormone type I (LH-RH-I) and LH-RH ligand in OCM-1 and OCM-3 human uveal melanoma cell lines. The presence and binding characteristics of LH-RH-I receptor protein was further studied by Western blot, immunocytochemistry and ligand competition assay. The expression of mRNA and protein for LH-RH-I receptors has been also studied using tumor samples originating from nude mice xenografted with OCM-1 or OCM-3 cells. The mRNA for LH-RH-I receptor has been detected in OCM-1 and OCM-3 cell lines and was found markedly higher in OCM-3 cells. The mRNA for LH-RH-I receptors was also observed in both UM xenograft models in vivo with higher levels in OCM-3. The presence of LH-RH-I receptor protein was found in both cell lines in vitro by immunocytochemistry and Western blot, and also in tumor tissue samples grown in nude mice by Western blot. Both human uveal melanoma models investigated showed specific high affinity receptors for LH-RH-I using ligand competition assay. The mRNA for LH-RH ligand has also been detected in OCM-1 and OCM-3 cell lines and cancer tissues. The demonstration of the expression of LH-RH-I receptors in OCM-1 and OCM-3 human UM cell lines suggests that they could serve as potential molecular target for therapy. Our findings support the development of new therapeutic approaches based on cytotoxic LH-RH analogs or modern powerful antagonistic analogs of LH-RH targeting LH-RH-I receptors in UM.

  19. Bilateral choroidal melanoma--case analysis and literature review.

    Science.gov (United States)

    Kowal, Joanna; Strzałka, Anna; Markiewicz, Anna; Romanowska-Dixon, Bożena; Bogdali, Anna

    2015-01-01

    Uveal melanoma is the most common primary intraocular neoplasm in adults. Its bilateral localization is extremely rare. The aim of the paper is analysis of the cases of bilateral uveal melanoma. Five bilateral uveal melanoma patients were diagnosed in the Department of Ophtalmology and Ocular Oncology beetwen 1980 and 2014. Both eyes of four patients were threated with brachytherapy. Final enulcleation of the one eye was performed in three patients. It was the primary treatment in one patient. The presence of uveal melanoma was confirmed by pathological examination in all cases after surgical removal of eyeball and in one after local resection of iris tumor. Metastatic lesions were diagnosed in lungs and liver in two patients. Three patients are still followed-up at our institution. The possibility of bilateral uveal melanoma should considered although it is extremely rare. bilateral uveal melanoma, brachytherapy, enucleation.

  20. Aspectos psicológicos e qualidade de vida em pacientes com melanoma uveal durante o processo de tratamento por remoção do bulbo ocular Psychological aspects and quality of life in uveal melanoma patients during the treatment process by ocular bulb remotion

    Directory of Open Access Journals (Sweden)

    Terezinha Aparecida Carvalho Amaro

    2006-12-01

    Full Text Available OBJETIVO: Avaliar prospectivamente as repercussões emocionais no indivíduo com melanoma uveal e indicação cirúrgica em três momentos: diagnóstico e pré-cirúrgico, pós-cirúrgico e pós-cirúrgico tardio. MÉTODOS: Trata-se de estudo clínico-qualitativo, no qual se utilizaram os seguintes instrumentos: Inventário de Ansiedade Traço/Estado - IDATE; Inventário de Depressão Beck e o Questionário de Qualidade de Vida SF-36. RESULTADOS: Participaram do estudo, inicialmente, 20 pacientes, 13 homens e sete mulheres, com idade média de 52 anos e, num segundo momento, 16 estavam disponíveis. No momento pré-cirúrgico, o Estado de Ansiedade está aumentado em relação ao Traço. O índice de Depressão indica um estado mínimo a leve e a Qualidade de Vida revela que os aspectos físicos e emocionais são os mais afetados. No pós-cirúrgico de três meses, o Traço de Ansiedade está consideravelmente elevado, o índice de Depressão mostra um estado leve a grave e na Qualidade de Vida os aspectos mais atingidos são os físicos, sociais e emocionais, além da vitalidade e da saúde mental. No pós-cirúrgico de um ano, o Traço de Ansiedade se mantém semelhante ao da primeira avaliação, o Estado de Ansiedade diminui consideravelmente, a Depressão cai para um índice mínimo e a Qualidade de vida mostra a maioria dos aspectos equilibrados. CONCLUSÕES: Após três meses da cirurgia, os pacientes se mostram mais frágeis, com dificuldade de adaptação, com aumento do grau de depressão e ansiedade. Esse foi o pior período para os pacientes. Após um ano da cirurgia, mostram-se mais estruturados e com os aspectos de Qualidade de Vida mais equilibrados.PURPOSE: To evaluate prospectively the emotional repercussions in the individual with uveal melanoma and surgical indication in three phases: diagnosis and preoperative, postsurgery and late postsurgery. METHODS: Clinical qualitative study based on the following instruments: STAI

  1. Characterization of luteinizing hormone-releasing hormone receptor type I (LH-RH-I as a potential molecular target in OCM-1 and OCM-3 human uveal melanoma cell lines

    Directory of Open Access Journals (Sweden)

    Sipos E

    2018-02-01

    Full Text Available Eva Sipos,1 Nikoletta Dobos,1 David Rozsa,1 Klara Fodor,1 Gabor Olah,1 Zsuzsanna Szabo,1 Lorant Szekvolgyi,2,3 Andrew V Schally,4–7 Gabor Halmos1,4 1Department of Biopharmacy, School of Pharmacy, University of Debrecen, Debrecen, Hungary; 2MTA-DE Momentum, Genome Architecture and Recombination Research Group, Debrecen, Hungary; 3Research Centre for Molecular Medicine; Department of Biochemistry and Molecular Biology, Debrecen, Hungary; 4Endocrine, Polypeptide and Cancer Institute, Veterans Affairs Medical Center, Miami, FL, USA; 5Department of Pathology, Miller School of Medicine, University of Miami, Miami, FL, USA; 6Department of Medicine, Divisions of Hematology–Oncology and Endocrinology, Miller School of Medicine, University of Miami, Miami, FL, USA; 7Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA Introduction: Uveal melanoma (UM is the most common primary intraocular malignancy with very poor prognosis. Conventional chemotherapy only rarely prolongs the survival, therefore patients require novel treatment modalities. The discovery of specific receptors for hypothalamic hormones on cancer cells has led to the development of radiolabeled and cytotoxic hormone analogs. Materials and methods: In the present study, our aim was to investigate the expression of mRNA for receptors of luteinizing hormone-releasing hormone type I (LH-RH-I and LH-RH ligand in OCM-1 and OCM-3 human uveal melanoma cell lines. The presence and binding characteristics of LH-RH-I receptor protein was further studied by Western blot, immunocytochemistry and ligand competition assay. The expression of mRNA and protein for LH-RH-I receptors has been also studied using tumor samples originating from nude mice xenografted with OCM-1 or OCM-3 cells. Results: The mRNA for LH-RH-I receptor has been detected in OCM-1 and OCM-3 cell lines and was found markedly higher in OCM-3 cells. The mRNA for LH-RH-I receptors was also observed in both UM

  2. Trends in incidence, survival, and management of uveal melanoma: a population-based study of 7,516 patients from the Surveillance, Epidemiology, and End Results database (1973–2012

    Directory of Open Access Journals (Sweden)

    Mahendraraj K

    2016-10-01

    Full Text Available Krishnaraj Mahendraraj,1 Christine SM Lau,1,2 Injoon Lee,2 Ronald S Chamberlain1–3 1Department of Surgery, Saint Barnabas Medical Center, Livingston, NJ, USA; 2St George’s University School of Medicine, Grenada, West Indies; 3Department of Surgery, New Jersey Medical School, Rutgers University, Newark, NJ, USA Introduction: Uveal melanoma (UM is the most common primary intraocular malignancy, despite comprising <5% of all melanomas. To date, relatively few case series of UM have been published. Moreover, the factors influencing survival remain largely unknown. This study sought to analyze the impact of demographics, histology, clinical presentation, and treatments on the clinical outcomes of UM in a large modern nationwide patient cohort.Methods: Demographics and clinical data were abstracted on 277,120 histologically confirmed melanoma patients from the Surveillance, Epidemiology, and End Results database between 1973 and 2012.Results: A total of 7,516 cases of UM represented 3.2% of all recorded cases of melanoma. The mean age-adjusted incidence was 5.1 per million (95% CI 4.2–6.1 and was higher in males (5.9, CI =4.4–7.6 compared to females (4.5, CI =3.3–5.8, P<0.001. UM occurred most commonly in the sixth decade of life (61.4±15 and among Caucasians (94.7%. A total of 52.3% of cases were reported in the Western US (35.7% in California. The initial diagnoses in 65.2% of cases were by histopathology, followed by clinical diagnosis (18.8% and radiographic imaging (16.0%. The percentage of UM cases managed by surgery alone decreased by 69.4% between the 1973–1977 and 2006–2012 time periods, concomitant with a 62% increase in primary radiotherapy, P<0.001. The UM mean overall and cancer-specific 5-year relative survival rates were 79.8%±5.8% and 76%±5.3%, respectively. The mean 5-year cancer-specific survival rate (76% remained stable during the study period between 1973 and 2012. The mean survival for patients treated with

  3. Surgical Treatment in Uveal Tumors

    Directory of Open Access Journals (Sweden)

    Kaan Gündüz

    2014-09-01

    Full Text Available Surgical treatment in uveal tumors can be done via iridectomy, partial lamellar sclerouvectomy (PLSU and endoresection. Iridectomy is done in iris tumors without angle and ciliary body involvement. PLSU is performed in tumors with ciliary body and choroidal involvement. For this operation, a partial thickness scleral flap is dissected, the intraocular tumor is excised, and the flap is sutured back in position. PLSU surgery is done in iridociliary and ciliary body tumors with less than 3 clock hours of iris and ciliary body involvement and in choroidal tumors with a base diameter less than 15 mm. However, it can be employed in any size tumor for biopsy purposes. Potential complications of PLSU surgery include vitreous hemorrhage, cataract, retinal detachment, and endophthalmitis. Endoresection is a technique whereby the intraocular tumor is excised using vitrectomy techniques. The rationale for performing endoresection is based on the fact that irradiated uveal melanomas may be associated with exudation and neovascular glaucoma and removing the dead tumor tissue may contribute to better visual outcome. There are some centers where endoresection is done without prior radiotherapy. Allegedly, avoidance of radiation retinopathy and papillopathy are the main advantages of using endoresection without prior radiotherapy. (Turk J Ophthalmol 2014; 44: Supplement 29-34

  4. Uveal neovascularization at the ora serrata and pars plana.

    Science.gov (United States)

    Kaba, F; el Baba, F; Green, W R

    1987-03-01

    Thirty-two eyes with uveal neovascularization at the ora serrata and pars plana were studied histopathologically. Chronic retinal detachment of various etiologies was the most frequently associated feature, present in 65% of the patients. In three eyes, the neovascularization took the form of an angiomatous lesion, whereas in the others, capillaries, arterioles, and venules were present. A history of glaucoma was found in 60% of the patients. Other associated findings included choroidal rupture, vitreous hemorrhage, and a history of cryotherapy. Uveal neovascularization at the ora serrata should be considered in the differential diagnosis of retinal angiomas, retinal telangiectasia, malignant melanoma, adult Coats's disease, peripheral proliferative retinopathies, and vitreous hemorrhage.

  5. Malignant Melanoma of the Choroid in the Eye With Oculodermal Melanocytosis of a Chinese Woman

    OpenAIRE

    Ya-Chi Chen; Cheng-Hsien Chang; Shiuh-Liang Hsu; Min-Wen Hsu; Chia-Ling Lee

    2010-01-01

    In this study, we report a rare case of choroidal melanoma in an eye with oculodermal melanocytosis (Nevus of Ota). A 56-year-old Taiwanese woman with oculodermal melanocytosis in the right eye was found to have an ipsilateral uveal melanoma. Histopathology of the enucleated eye confirmed the diagnosis of malignant choroidal melanoma of mixed cell type. A search of the literature revealed strong evidence that oculodermal melanocytosis can predispose to the development of uveal melanoma in Cau...

  6. Melanoma

    Science.gov (United States)

    ... if they're dark skinned, young, and have no family history. Even for them, behaviors like too much sun exposure and not enough skin protection are important risk factors. How Do People Know They Have It? Many melanomas start out as a mole or a bump ...

  7. 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

  8. Ocular melanoma: an overview of the current status

    Science.gov (United States)

    Jovanovic, Predrag; Mihajlovic, Marija; Djordjevic-Jocic, Jasmina; Vlajkovic, Slobodan; Cekic, Sonja; Stefanovic, Vladisav

    2013-01-01

    Ocular melanoma is the second most common type of melanoma after cutaneous and the most common primary intraocular malignant tumor in adults. Large majority of ocular melanomas originate from uvea, while conjunctival melanomas are far less frequent. Incidence of uveal melanoma has remained stable over last three decades. Diagnosis is in most cases established by clinical examination with great accuracy. Local treatment of uveal melanoma has improved, with increased use of conservative methods and preservation of the eye, but survival rates have remained unchanged. Recent advances in cytogenetics and genetics enhanced prognostication and enabled to determine tumors with high metastatic potential. However, due to lack of effective systemic therapy, prognosis of patients with metastasis remains poor and metastatic disease remains the leading cause of death among patients with uveal melanoma. Conjunctival melanoma is rare, but its incidence is increasing. It mostly occurs among white adults. In majority of cases it originates from preceding primary acquired melanosis. Current standard treatment for conjunctival melanoma is wide local excision with adjuvant therapy, including brachytherapy, cryotherapy and topical application of chemotherapeutic agent. Rarity of this tumor limits conduction of controlled trials to define the best treatment modality. As well as for uveal melanoma, prognosis of patients with metastasis is poor because there is no effective systemic therapy. Better understanding of underlying genetic and molecular abnormalities implicated in development and progression of ocular melanomas provides a great opportunity for development of targeted therapy, which will hopefully improve prognosis of patients with metastatic disease. PMID:23826405

  9. Solitary Secondary Malignant Melanoma of Clavicle Two Years after Enuclation for Ocular Melanoma

    Directory of Open Access Journals (Sweden)

    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.

  10. Choroidal melanoma of left eye with very early liver metastasis.

    Science.gov (United States)

    Mandal, Sanchayan; Chaudhuri, Tamohan; Devleena, M; Sil, Subhra

    2015-01-01

    Uveal melanoma is a cancer (melanoma) of the eye involving the iris, ciliary body, or choroid (collectively referred to as the uvea). The liver is a frequent site for metastasis in patients with uveal melanoma. The interval between the diagnosis of the uveal melanoma and the diagnosis of the metastatic lesion can vary. Despite therapy, the median survival of those with liver metastasis is 5-7 months. We report here a rare case of choroidal melanoma in a 45-year-old male smoker presented with liver metastasis within just 8 months after completion of initial treatments consists of enucleation of eye and 3 Dimensional conformal radiation therapy (3D-CRT). The metastasis is an incidental finding on imaging after having some vague symptoms. This type of very early metastasis after completing initial treatment is very rare and proves the aggressiveness of the disease.

  11. Choroidal melanoma of left eye with very early liver metastasis

    Directory of Open Access Journals (Sweden)

    Sanchayan Mandal

    2015-01-01

    Full Text Available Uveal melanoma is a cancer (melanoma of the eye involving the iris, ciliary body, or choroid (collectively referred to as the uvea. The liver is a frequent site for metastasis in patients with uveal melanoma. The interval between the diagnosis of the uveal melanoma and the diagnosis of the metastatic lesion can vary. Despite therapy, the median survival of those with liver metastasis is 5-7 months. We report here a rare case of choriodal melanoma in a 45-year-old male smoker presented with liver metastasis within just 8 months after completion of initial treatments consists of enucleation of eye and 3 Dimensional conformal radiation therapy (3D-CRT. The metastasis is an incidental finding on imaging after having some vague symptoms. This type of very early metastasis after completing initial treatment is very rare and proves the aggressiveness of the disease.

  12. What is presumed when we presume consent?

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    Pierscionek Barbara K

    2008-04-01

    Full Text Available Abstract Background The organ donor shortfall in the UK has prompted calls to introduce legislation to allow for presumed consent: if there is no explicit objection to donation of an organ, consent should be presumed. The current debate has not taken in account accepted meanings of presumption in law and science and the consequences for rights of ownership that would arise should presumed consent become law. In addition, arguments revolve around the rights of the competent autonomous adult but do not always consider the more serious implications for children or the disabled. Discussion Any action or decision made on a presumption is accepted in law and science as one based on judgement of a provisional situation. It should therefore allow the possibility of reversing the action or decision. Presumed consent to organ donation will not permit such reversal. Placing prime importance on the functionality of body organs and their capacity to sustain life rather than on explicit consent of the individual will lead to further debate about rights of ownership and potentially to questions about financial incentives and to whom benefits should accrue. Factors that influence donor rates are not fully understood and attitudes of the public to presumed consent require further investigation. Presuming consent will also necessitate considering how such a measure would be applied in situations involving children and mentally incompetent adults. Summary The presumption of consent to organ donation cannot be understood in the same way as is presumption when applied to science or law. Consideration should be given to the consequences of presuming consent and to the questions of ownership and organ monetary value as these questions are likely to arise should presumed consent be permitted. In addition, the implications of presumed consent on children and adults who are unable to object to organ donation, requires serious contemplation if these most vulnerable

  13. Melanoma de corpo ciliar e coróide: relato de caso Choroidal and ciliary body melanoma: case report

    Directory of Open Access Journals (Sweden)

    Aline Amaral Fulgêncio da Cunha

    2010-04-01

    Full Text Available Melanomas oculares correspondem a 5% de todos os melanomas e 85% deles têm origem no trato uveal. Melanoma uveal é o tumor maligno intraocular primário mais comum no adulto. Relatamos neste artigo um caso de melanoma uveal em paciente, sexo feminino, 31 anos, com quadro de fotopsia, hiperemia e baixa da acuidade visual no olho esquerdo com evolução de quatro meses. Apresentava ao exame oftalmológico acuidade visual menor que 20/400, grande massa tumoral na região nasal retroiriana, com deslocamento anterior do cristalino, estreitamento da câmara anterior e descolamento seroso da retina. A ecografia sugeriu tratar-se de grande massa tumoral suspeita de melanoma de coróide com invasão do corpo ciliar. A confirmação diagnóstica foi possível por meio do exame anatomopatológico.Ocular melanomas correspond to 5% of all melanomas and 85% of them have its origin in the uveal tract. Uveal melanoma is the most commom primary intraocular malignant tumor in the adult. In this article, a case of uveal melanoma in a 31 year-old female patient, with photopsia, hyperemia and low visual acuity in the left eye with evolution of 4 months is presented. In the ophthalmologic examination, visual acuity was lower than 20/400, a large tumoral mass was noted at the nasal region behind the iris with anterior lens displacement, anterior chamber narrowing and serous retinal detachment. The ocular echography suggested a large tumoral mass as a choroidal melanoma extending to the ciliary body. The confirmation diagnosis was possible through the histopathologic examination.

  14. Uveal effusion syndrome.

    Science.gov (United States)

    Elagouz, Mohammed; Stanescu-Segall, Dinu; Jackson, Timothy L

    2010-01-01

    The terms uveal effusion, choroidal effusion, ciliochoroidal effusion, ciliochoroidal detachment, and choroidal detachment have been used interchangeably in the literature. These labels all describe an abnormal collection of fluid that expands the suprachoroidal space, producing internal elevation of the choroidal. There are various inflammatory and hydrostatic conditions that can cause uveal effusion, but in some cases no obvious cause exists. In this setting, patients are thought to have a distinct, primary abnormality of the choroid or sclera, called uveal effusion syndrome (UES). UES may be idiopathic, or associated with hypermetropia, and should be considered a diagnosis of exclusion. Histological studies show amorphous glycosaminoglycan-like material filling the interfibrillary spaces of excised scleral tissue, with disruption of collagen fibers. In some patients there may be reduced macromolecular diffusion that interferes with the normal transscleral egress of albumin out of the eye, perhaps causing choroidal fluid retention due to altered osmotic forces. An alternative, and perhaps complementary hypothesis, is that swollen sclera compresses the transscleral vessels with resulting fluid retention. Patients with UES are most typically middle-aged men who have a relapsing remitting clinical course. There is often co-existing, shifting subretinal fluid that may involve the macula. Chronic disease may lead to secondary retinal pigment epithelial (leopard spot) changes and permanently reduced visual acuity. Treatment with systemic steroids does not appear to be effective. Surgical decompression of the vortex veins as they pass through the sclera has been described, but the most common treatment is full-thickness sclerectomies to provide an exit for choroidal fluid. The largest case series suggests that this produces an anatomic improvement in approximately 83% of treated eyes after a single procedure and in about 96% after one or two procedures. Final visual

  15. A subconjunctival foreign body confused with uveal prolapse

    Directory of Open Access Journals (Sweden)

    Young Min Park

    2014-01-01

    Full Text Available There are cases in which the presence of a foreign body (FB is difficult to diagnose based on history taking or clinical examination. We report a case of subconjunctival FB confused with uveal prolapse. A 68-year-old man, who had the history of pterygium excision in his right eye, complained of irritation and congestion in that same eye. He also had the history of growing vegetables in a plastic greenhouse. It seemed to be a suspected uveal mass bulging through a focal scleral thinning site. On the basis of slit-lamp magnification, the lesion was presumed to be a hard and black keratinized mass embedded under the conjunctiva. Histopathologically, the removed mass was revealed to be a seed of the dicotyledones. Patients who show signs of prolapsed uvea or scleral thinning, possibility of a subconjunctival FB should be considered as differential diagnosis. In addition, a removed unknown FB should be examined histopathologically.

  16. Bilateral diffuse uveal melanocytic proliferation

    DEFF Research Database (Denmark)

    Klemp, Kristian; Kiilgaard, Jens Folke; Heegaard, Steffen

    2017-01-01

    Bilateral diffuse uveal melanocytic proliferation (BDUMP) is a rare paraneoplastic intraocular disease that causes progressive visual loss in patients driven by an IgG factor associated with an underlying malignancy. Characteristic ocular findings include exudative retinal detachment, rapid...... cataract formation and uveal melanocytic tumours. The awareness and documentation of BDUMP has increased during the past decade, and the increasing amount of data collected demonstrates the effect of treatment with plasmapheresis and the value of diagnostic tools in BDUMP such as genetic and immunologic...

  17. MALIGNANT TRANSFORMATION OF A CHOROIDAL NEVUS IN AN EYE TREATED FOR CHOROIDAL MELANOMA.

    Science.gov (United States)

    Fabian, Ido D; Arora, Amit K; Cohen, Victoria M L

    2017-01-01

    To report a case of a choroidal melanoma and a discrete choroidal nevus that has transformed into a malignant melanoma 5 years after initial diagnosis. Retrospective case report. A diffuse macular choroidal melanoma and a discrete choroidal nevus located superonasal to the optic disk were diagnosed in the right eye of a 63-year-old woman in 2009. The patient was treated by ruthenium plaque radiotherapy for the choroidal melanoma, which consequently flattened and scarred. On a routine eye check in 2014, the nevus was found to have been transformed into a choroidal melanoma. It was treated with ruthenium plaque radiotherapy. Although extremely rare, patients with a uveal melanoma can develop an additional discrete uveal melanoma. This case highlights the importance of monitoring benign choroidal nevi in patients with a history of choroidal melanoma.

  18. [Orbital Exenteration in Patient with Metastatic Choroidal Melanoma - a Case Report].

    Science.gov (United States)

    Justusová, P; Štubňa, M; Veselovský, M; Lipková, B

    Uveal melanoma is the most common primary intraocular tumour in adults in Caucasians and in 75% is arising from choroid. It threatens not only the patients loss of vision and eye, but also 50% of patients after 5-year interval after therapy die due to distant metastases. The treatment of small and medium-sized melanoma are methods preserving eye globe. Almost half of the total number of patients is still unavoidable enucleation. Considerably rarer is indicated exenteration of an orbit. These tumors metastasize only hematogenous, while the most frequent place of localization of distant metastases is the liver. Generalized disease prognosis is poor, and our current treatment options in this stage are ineffective. Case report of 59 years old patient with choroidal melanoma stage T4 N1 M1 massively infiltrating the orbit. At the time of diagnosis of the primary tumor distant metastases were present. The patient underwent exenteration of the orbit and systemic chemotherapy. Although choroidal melanomas with extrascleral extension and infiltration into the orbit have no better prognosis after exenteration of the orbit, surgery is providing us local tumour control. Good cosmetic effect after this mutilating procedure is offered by individually made prosthesis (epithesis). All patients with uveal melanoma require lifelong dispensation, distant metastases may occur even after many years. In the treatment of generalized disease is available systemic chemotherapy and immunotherapy only palliative. The best effect on survival has complete surgical resection of single metastasis. Uveal melanoma has a different genetic profile as cutaneous melanoma. The biological nature of uveal melanoma seems to be the key to determining risk patients, as well as the development of targeted systemic therapy. Treatment of patients with generalized large uveal melanoma with extrascleral extension is difficult. A better understanding of biological interest may be the key to the detection of

  19. [Uveal effusion induced by escitalopram].

    Science.gov (United States)

    Arias Palomero, A; Infantes Molina, E J; López Arroquia, E; Riveira Villalobos, L; López Mondéjar, E; González del Valle, F

    2015-07-01

    A 73 year-old woman with depression treated with escitalopram developed acute secondary angle closure glaucoma related to uveal effusion after duplicating the drug dose 3 days before. She evolved favorably once the antidepressant treatment was suspended and a new treatment with topical hypotensive therapy and oral prednisone was used. The uveal effusion syndrome associated to medicines is rare; it may be associated with acute myopic shift and acute angle closure glaucoma. The correct diagnosis and discontinuation of the drug lead to the resolution of this nosology. Copyright © 2014 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

  20. Iris melanoma invading the camerular angle

    International Nuclear Information System (INIS)

    Verona Ugando, Leticia; Landrian Iglesias, Beatriz; Padierne Gonzalez, Naysa

    2011-01-01

    Uveal melanomas are the most frequent primary uveal tumors, having an incidence of 8/1 000 000 a year in Caucasian people. Specifically, iris Melanoma represents 5 to 7 % of the uveal malignant melanomas and they may be amelanic or pigmented, generally very vascularized. An eighteen years old male patient with a history of health problems was presented, who had been seen at the Ophthalmological Emergency Service because of eye pain and sudden visual reduction in his right eye. In the physical exam, a marked ocular hypertension was confirmed as well as a 2 mm hyphema and corneal edema. These conditions were overcome with treatment and afterwards, there was observed iris tumoration invading the iridocorneal angle. Some complementary studies were carried out to search further tumors at other levels and finally a fine needle aspiration biopsy was performed. The diagnosis was amelanic Iris Melanoma invading the ciliary body. The patient was referred for surgical treatment at the National Institute of Oncology and Radiology

  1. Uveal cysts in domestic cats: a retrospective evaluation of thirty-six cases.

    Science.gov (United States)

    Blacklock, Benjamin T; Grundon, Rachael A; Meehan, Melissa; Tetas Pont, Roser; Hartley, Claudia

    2016-07-01

    The aim of this retrospective study was to investigate uveal cysts in domestic cats by identifying prevalence, predispositions, location, presumed etiologies, and sequelae. The clinical databases of two referral hospitals (The Animal Health Trust in the UK and Animal Eye Care in Australia) were searched to identify cats that had been diagnosed with uveal cysts, either as an incidental finding or as the reason for referral. Thirty-six cases were found. The signalment of the patients was recorded, along with any relevant previous clinical history, treatment, follow-up, and sequela. The data were compared with the unaffected feline populations examined by ophthalmologists in the two hospitals over the same 10-year time period. Thirty-six cats were affected, from a total examined population of 5017 (prevalence 0.72%). Twenty-one of the 36 cats were Burmese. The two centers examined 516 Burmese cats in the same time period, giving an incidence in Burmese cats of 4.1%. The mean age of affected cats at presentation was 10.25 years (SD = 4.12 years), and female cats accounted for 23 of 36 of the cases. Only 2 of 36 cats had concurrent intraocular disease. Uveal cysts in domestic cats are rare ophthalmic findings, and in most cases, they do not cause any clinical problems The Burmese breed is overrepresented in the data, with a relatively high prevalence of uveal cysts. © 2016 American College of Veterinary Ophthalmologists.

  2. Recurrent Uveal Effusion after Laser Iridotomy

    Directory of Open Access Journals (Sweden)

    Hiroshi Sakai

    2017-01-01

    Full Text Available A 59-year-old woman was seen by an ophthalmologist for blurred vision, ocular pain, headache, and nausea. She was diagnosed with acute primary angle closure (APAC and successfully treated with medications. Using ultrasound biomicroscopy (UBM, engorged episcleral vein was observed and small uveal effusion was diagnosed after laser peripheral iridotomy (LPI. The uveal effusion disappeared and was again diagnosed by UBM together with anterior segment inflammation with ocular pain. Iritis caused by LPI after APAC might be a cause of uveal effusion in this specific case.

  3. Diffuse iris melanoma: Report of a case with review of the literature

    OpenAIRE

    Skalicky, Simon E; Giblin, Michael; Conway, R Max

    2007-01-01

    Diffuse iris melanoma is an uncommon variant of anterior uveal melanoma. It is characterized by heterochromia and unilateral glaucoma secondary to angle invasion, and can be difficult to diagnose. We present a patient who had been managed for left-sided raised intraocular pressure with latanoprost eye drops for 12-months and pigmentary changes were subsequently noted. On referral to the Ocular Oncology Unit, Sydney, iris melanoma was suspected and confirmed on iridectomy, and the eye was even...

  4. Diffuse iris melanoma: Report of a case with review of the literature

    Science.gov (United States)

    Skalicky, Simon E; Giblin, Michael; Conway, R Max

    2007-01-01

    Diffuse iris melanoma is an uncommon variant of anterior uveal melanoma. It is characterized by heterochromia and unilateral glaucoma secondary to angle invasion, and can be difficult to diagnose. We present a patient who had been managed for left-sided raised intraocular pressure with latanoprost eye drops for 12-months and pigmentary changes were subsequently noted. On referral to the Ocular Oncology Unit, Sydney, iris melanoma was suspected and confirmed on iridectomy, and the eye was eventually enucleated. PMID:19668492

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

    Directory of Open Access Journals (Sweden)

    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.

  6. [Novel Adjuvant Therapy for Ocular Melanoma].

    Science.gov (United States)

    Bosch, Jacobus J; Heindl, Ludwig M

    2017-05-01

    Background Malignant melanoma is the most common cancer of the eye in adults that originates either in the intra-ocular uveal tract or extra-ocular conjunctiva. Although the primary tumor can be treated successfully, no effective therapy for both metastatic conjunctival and uveal melanoma currently exits. Tumor-associated lymphangiogenesis and immune cell infiltration play a pivotal role in the development and therapeutic targeting of metastases. Project description Here, we provide an overview of current translational research on lymphangiogenesis and its therapeutic inhibition as well as modulation of immune cell infiltration by passive and active immunotherapy in melanoma of the eye. Specifically, our previous and ongoing work on lymphangiogenesis and immune cells in ocular melanoma within the clinical research unit FOR 2240 "(Lymph)Angiogenesis and Cellular Immunity in Inflammatory Diseases of the Eye" is summarized. Conclusions Translational research on the modulation of tumor-associated lymphangiogenesis and immune cell infiltration could provide novel targets for adjuvant therapy in melanoma of the eye. Georg Thieme Verlag KG Stuttgart · New York.

  7. Ocular surface foreign bodies: novel findings mimicking ocular malignant melanoma.

    Science.gov (United States)

    Maudgil, A; Wagner, B E; Rundle, P; Rennie, I G; Mudhar, H S

    2014-11-01

    Malignant melanoma of the eye is an uncommon condition that is important to recognise. We describe three cases in which ocular foreign bodies have masqueraded as ocular malignant melanoma. Interventional case reports. Case 1 describes diathermy-induced carbon particle implantation, during plaque therapy for the treatment of uveal melanoma, mimicking recurrence with extra-scleral invasion. Case 2 shows a foreign body called 'mullite' mimicking conjunctival melanoma. Case 3 demonstrates a conjunctival foreign body called 'illite' that mimicked a limbal melanocytic lesion, clinically thought to be either melanocytoma or melanoma. This report highlights the importance of careful history taking, examination, and appropriate biopsy in cases of suspected malignant melanoma, to prevent unnecessary and potentially radical treatment.

  8. Melanoma of the eye: revealing hidden secrets, one at a time.

    Science.gov (United States)

    Shields, Carol L; Kels, Jane Grant; Shields, Jerry A

    2015-01-01

    Melanoma of the eye can involve the uveal tract with iris, ciliary body, or choroid involvement or it can involve the conjunctiva, eyelid, or orbit. Uveal involvement with choroidal melanoma is the most common, found in light complexion Caucasians with an age-adjusted incidence of 4.3 per million persons. Early detection of uveal melanoma is critical. The ABCDEF guide helps to differentiate iris nevus from iris melanoma. The letters represent: A, age young (≤40 years); B, blood in anterior chamber; C, clock hour of mass inferiorly; D, diffuse configuration; E, ectropion; and F, feathery margins. The mnemonic of TFSOM-UHHD (To Find Small Ocular Melanoma-Using Helpful Hints Daily) helps to differentiate choroidal nevus from small melanoma and represents: T, thickness over 2 mm; F, fluid; S, symptoms; O, orange pigment; M, margin within 3 mm of the optic disc; UH, ultrasound hollow; H, halo absent; and D, drusen absent. Patients with 3 or more of these factors are likely to have melanoma. These key clinical features help to identify small melanoma at a time when therapy could be life-saving. Conjunctival melanoma usually arises from primary acquired melanosis, a flat pigmentation that can lead to melanoma. Wide excision using no touch strategy is important to tumor control. Ocular examination is advised annually for all persons for detection of refractive error, cataract, glaucoma, and other conditions, but also for the detection of asymptomatic malignancies like melanoma. One at a time, we have uncovered the secrets of ocular melanoma and we forge ahead with the goal to solve the riddle of this challenging disease. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Malignant melanoma of the choroid in the eye with oculodermal melanocytosis of a Chinese woman.

    Science.gov (United States)

    Chen, Ya-Chi; Chang, Cheng-Hsien; Hsu, Shiuh-Liang; Hsu, Min-Wen; Lee, Chia-Ling

    2010-12-01

    In this study, we report a rare case of choroidal melanoma in an eye with oculodermal melanocytosis (Nevus of Ota). A 56-year-old Taiwanese woman with oculodermal melanocytosis in the right eye was found to have an ipsilateral uveal melanoma. Histopathology of the enucleated eye confirmed the diagnosis of malignant choroidal melanoma of mixed cell type. A search of the literature revealed strong evidence that oculodermal melanocytosis can predispose to the development of uveal melanoma in Caucasians. Only seven such cases have been reported in the East Asian population. This is believed to be the first such reported case in a patient of Chinese descent. Copyright © 2010 Elsevier. Published by Elsevier B.V. All rights reserved.

  10. Metastatic ocular melanoma to the liver exhibits infiltrative and nodular growth patterns

    DEFF Research Database (Denmark)

    Grossniklaus, Hans E; Zhang, Qing; You, Shuo

    2016-01-01

    We examined liver specimens from 15 patients with uveal melanoma (UM) who had died of their disseminated disease. We found 2 distinct growth patterns of UM metastasis: infiltrative (n = 12) and nodular (n = 3). In the infiltrative pattern, individual UM cells with a CD133+ cancer stem cell-like p...

  11. Efficient adenovector CD40 ligand immunotherapy of canine malignant melanoma.

    Science.gov (United States)

    von Euler, Henrik; Sadeghi, Arian; Carlsson, Björn; Rivera, Patricio; Loskog, Angelica; Segall, Thomas; Korsgren, Olle; Tötterman, Thomas H

    2008-05-01

    Cutaneous canine melanomas are usually benign in contrast to human malignant melanoma. However, the canine oropharyngeal, uveal, and mucocutaneous neoplasms are aggressive and have metastatic potential. Surgery and to a lesser extent radiotherapy and chemotherapy are widely adopted treatments but are seldom curative in advanced stages. The similarities between human and canine melanoma make spontaneous canine melanoma an excellent disease model for exploring novel therapies. Herein, we report the first 2 adenovector CD40L immunogene (AdCD40L) treatments of aggressive canine malignant melanoma. Case no. 1 was an advanced stage III oral melanoma that was cured from malignant melanoma with 2 intratumor AdCD40L injections before cytoreductive surgery. After treatment, the tumor tissue was infiltrated with T lymphocytes and B lymphocytes suggesting immune activation. This dog survived 401 days after the first round of gene therapy and was free of melanoma at autopsy. Case no. 2 had a conjunctival malignant melanoma with a rapid progression. This case was treated with 6 AdCD40L injections over 60 days. One hundred and twenty days after start of gene therapy and 60 days after the last injection, the tumor had regressed dramatically, and the dog had a minimal tumor mass and no signs of progression or metastasis. Our results indicate that AdCD40L immunogene therapy is beneficial in canine malignant melanoma and could be considered for human malignant melanoma as well.

  12. Conjunctivitis presumably due to Acanthamoeba

    OpenAIRE

    Ruthes, Ana Cristina de Carvalho; Wahab, Sâmia; Wahab, Najua; Moreira, Hamilton; Moreira, Luciane

    2004-01-01

    OBJETIVO: Abordar quatro casos de conjuntivite presumível por Acanthamoeba, descrevendo o diagnóstico, considerando sinais e sintomas e o tratamento instituído. MÉTODOS: Foram estudados casos de conjuntivite presumível por Acanthamoeba diagnosticados no Hospital de Olhos do Paraná (HOP), no período de setembro/1998 a janeiro/2002. Todos os olhos estudados foram submetidos a um protocolo de investigação que incluía exame oftalmológico completo, microbiologia e cultura de secreções conjuntivais...

  13. Uveal effusion in Hunter's syndrome. Evidence that abnormal sclera is responsible for the uveal effusion syndrome.

    Science.gov (United States)

    Vine, A K

    1986-01-01

    A patient with Hunter's Syndrome (systemic mucopolysaccharidosis type II) was evaluated for bilateral uveal effusion syndrome. The right eye showed a circular peripheral choroidal detachment for 360 degrees. The left eye showed a larger circular peripheral choroidal detachment and an exudative retinal detachment. Evaluation of the sclera during combined sclerectomies and sclerostomies of the left eye revealed markedly thickening sclera and a reduced number of vortex veins. The surgery resulted in complete resolution of the choroidal detachment and exudative retinal detachment of the left eye. The presence of uveal effusion in Hunter's Syndrome, in which the sclera has been histologically demonstrated to be abnormally thickened, supports the recently proposed pathophysiology of the uveal effusion syndrome.

  14. Isolated posterior uveal effusion: expanding the spectrum of the uveal effusion syndrome

    Directory of Open Access Journals (Sweden)

    Pautler SE

    2014-12-01

    Full Text Available Scott E Pautler,1 David J Browning2 1Department of Ophthalmology, University of South Florida, Morsani College of Medicine, Tampa, FL, USA; 2Charlotte Ear Eye Nose and Throat Associates, Charlotte, NC, USA Abstract: Uveal effusion syndrome usually causes peripheral chorioretinal detachment, but posterior effusion may present as isolated macular edema with serous macular detachment in the setting of hyperopia and a thickened posterior choroid. Carbonic anhydrase inhibitors may be effective to treat this condition. Keywords: uveal effusion, serous, macular detachment, macular edema

  15. Complications of presumed ocular tuberculosis.

    Science.gov (United States)

    Hamade, Issam H; Tabbara, Khalid F

    2010-12-01

    To determine the effect of steroid treatment on visual outcome and ocular complications in patients with presumed ocular tuberculosis. Retrospective review of patients with presumptive ocular tuberculosis. The clinical diagnosis was made based on ocular findings, positive purified protein derivative (PPD) testing of more than 15 mm induration, exclusion of other causes of uveitis and positive ocular response to anti-tuberculous therapy (ATT) within 4 weeks. Group 1 included patients who had received oral prednisone or subtenon injection of triamcinolone acetonide prior to ATT. Group 2 included patients who did not receive corticosteroid therapy prior to administration of ATT.   Among 500 consecutive new cases of uveitis encountered in 1997-2007 there were 49 (10%) patients with presumed ocular tuberculosis. These comprised 28 (57%) male and 21 (43%) female patients with a mean age of 45 years (range 12-76 years). Four (20%) patients in group 1 had initial visual acuity of 20/40 or better, in comparison to eight (28%) patients in group 2. At 1-year follow-up, six (30%) patients in group 1 had a visual acuity of 20/40 or better compared with 20 (69%) patients in group 2 (p = 0.007). Of 20 eyes (26%) in group 1 that had visual acuity of < 20/50 at 1-year follow up, 14 (70%) eyes developed severe chorioretinal lesion (p = 0.019). Early administration of corticosteroids without anti-tuberculous therapy in presumed ocular tuberculosis may lead to poor visual outcome compared with patients who did not receive corticosteroids prior to presentation. Furthermore, the severity of chorioretinitis lesion in the group of patients given corticosteroid prior to ATT may account for the poor visual outcome. © 2009 The Authors. Journal compilation © 2009 Acta Ophthalmol.

  16. 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...

  17. Bilateral uveal effusion associated with scleral thickening due to amyloidosis.

    Science.gov (United States)

    Liew, S C; McCluskey, P J; Parker, G; Taylor, R F

    2000-09-01

    A 45-year-old man with primary systemic amyloidosis was found to have bilateral uveal effusions secondary to thickened sclera according to magnetic resonance imaging of the orbits. The patient was treated with bilateral sclerectomies and vortex vein decompression, and had an excellent outcome. Light microscopy of excised sclera revealed severe infiltration of the tissue by amyloid. To our knowledge, this is the first report of amyloid infiltration of the sclera leading to uveal effusion. Arch Ophthalmol. 2000;118:1293-1295

  18. MULTIFOCAL CHOROIDAL MELANOMA IN A PATIENT WITH GERM LINE BRCA-ASSOCIATED PROTEIN 1 MUTATION.

    Science.gov (United States)

    Rao, Raksha; Pointdujour-Lim, Renelle; Ganguly, Arupa; Shields, Carol L

    2018-01-01

    To report a case of unilateral multifocal melanoma in a patient with germ line BRCA-associated protein 1 mutation. Case report. A 67-year-old white woman with a family history of lung and liver cancers developed blurred visual acuity of 20/30 in the left eye. She was discovered to have two independent pigmented choroidal melanomas in the macula and superotemporally, both demonstrating overlying subretinal fluid and orange pigment. Both melanomas were treated with a single custom-designed Iodine 125 brachytherapy device. Upon systemic evaluation, asymptomatic renal cell carcinoma was found, and blood lymphocyte testing for germ line BRCA-associated protein 1 mutation was positive. Multifocal choroidal melanoma is exceedingly rare. Patients with uveal melanoma, especially if multifocal, and those with other systemic malignancy or family history of cancers should be tested for germ line BRCA-associated protein 1 mutation. Lifelong monitoring for other systemic malignancies is advised.

  19. Exome sequencing identifies recurrent somatic RAC1 mutations in melanoma.

    Science.gov (United States)

    Krauthammer, Michael; Kong, Yong; Ha, Byung Hak; Evans, Perry; Bacchiocchi, Antonella; McCusker, James P; Cheng, Elaine; Davis, Matthew J; Goh, Gerald; Choi, Murim; Ariyan, Stephan; Narayan, Deepak; Dutton-Regester, Ken; Capatana, Ana; Holman, Edna C; Bosenberg, Marcus; Sznol, Mario; Kluger, Harriet M; Brash, Douglas E; Stern, David F; Materin, Miguel A; Lo, Roger S; Mane, Shrikant; Ma, Shuangge; Kidd, Kenneth K; Hayward, Nicholas K; Lifton, Richard P; Schlessinger, Joseph; Boggon, Titus J; Halaban, Ruth

    2012-09-01

    We characterized the mutational landscape of melanoma, the form of skin cancer with the highest mortality rate, by sequencing the exomes of 147 melanomas. Sun-exposed melanomas had markedly more ultraviolet (UV)-like C>T somatic mutations compared to sun-shielded acral, mucosal and uveal melanomas. Among the newly identified cancer genes was PPP6C, encoding a serine/threonine phosphatase, which harbored mutations that clustered in the active site in 12% of sun-exposed melanomas, exclusively in tumors with mutations in BRAF or NRAS. Notably, we identified a recurrent UV-signature, an activating mutation in RAC1 in 9.2% of sun-exposed melanomas. This activating mutation, the third most frequent in our cohort of sun-exposed melanoma after those of BRAF and NRAS, changes Pro29 to serine (RAC1(P29S)) in the highly conserved switch I domain. Crystal structures, and biochemical and functional studies of RAC1(P29S) showed that the alteration releases the conformational restraint conferred by the conserved proline, causes an increased binding of the protein to downstream effectors, and promotes melanocyte proliferation and migration. These findings raise the possibility that pharmacological inhibition of downstream effectors of RAC1 signaling could be of therapeutic benefit.

  20. Exome sequencing identifies recurrent somatic RAC1 mutations in melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Krauthammer, Michael; Kong, Yong; Ha, Byung Hak; Evans, Perry; Bacchiocchi, Antonella; McCusker, James P.; Cheng, Elaine; Davis, Matthew J.; Goh, Gerald; Choi, Murim; Ariyan, Stephan; Narayan, Deepak; Dutton-Regester, Ken; Capatana, Ana; Holman, Edna C.; Bosenberg, Marcus; Sznol, Mario; Kluger, Harriet M.; Brash, Douglas E.; Stern, David F.; Materin, Miguel A.; Lo, Roger S.; Mane, Shrikant; Ma, Shuangge; Kidd, Kenneth K.; Hayward, Nicholas K.; Lifton, Richard P.; Schlessinger, Joseph; Boggon, Titus J.; Halaban, Ruth (Yale-MED); (UCLA); (Queens)

    2012-10-11

    We characterized the mutational landscape of melanoma, the form of skin cancer with the highest mortality rate, by sequencing the exomes of 147 melanomas. Sun-exposed melanomas had markedly more ultraviolet (UV)-like C>T somatic mutations compared to sun-shielded acral, mucosal and uveal melanomas. Among the newly identified cancer genes was PPP6C, encoding a serine/threonine phosphatase, which harbored mutations that clustered in the active site in 12% of sun-exposed melanomas, exclusively in tumors with mutations in BRAF or NRAS. Notably, we identified a recurrent UV-signature, an activating mutation in RAC1 in 9.2% of sun-exposed melanomas. This activating mutation, the third most frequent in our cohort of sun-exposed melanoma after those of BRAF and NRAS, changes Pro29 to serine (RAC1{sup P29S}) in the highly conserved switch I domain. Crystal structures, and biochemical and functional studies of RAC1{sup P29S} showed that the alteration releases the conformational restraint conferred by the conserved proline, causes an increased binding of the protein to downstream effectors, and promotes melanocyte proliferation and migration. These findings raise the possibility that pharmacological inhibition of downstream effectors of RAC1 signaling could be of therapeutic benefit.

  1. Histopathology of enucleated intraocular melanomas irradiated with cobalt and ruthenium plaques

    International Nuclear Information System (INIS)

    Fuchs, U.; Kivelae, T.; Tarkkanen, A.; Laatikainen, L.

    1988-01-01

    Eight malignant uveal melanomas irradiated with Stallard's 60 Co applicator or Lommatzsch's 106 Ru/ 10 6 Rh applicator were studied by light microscopy and immunohistochemistry to analyse tumour cell morphology, antigenic expression and inflammatory cell infiltration in relation to radiation dose. The tumours were enucleated 1 to 24 months after irradiation because they did not regress or continued to grow. One patient has later died of metastatic disease. Eight uveal melanomas that were not irradiated were studied for comparative purposes. Radiation necrosis was found only in two cases. In four irradiated and in one control melanoma conspicuous collagen fibres were present in the basal part of the tumour. No difference was noted between the two groups in the number of mitotic figures or in the morphology of tumour cells. In all cases but one, more than half of the tumour cells were variably positive for S-100 protein. Neutron-specific enolase-positive melanoma cells were few in number and occurred in small clusters, and were somewhat more common in irradiated cases. A few lymphocytes and macrophages, which were preferentially found near the choroid, infiltrated every melanoma, but only single cells were associated with radiation necrosis. A mild scleritis near the tumour was present irrespective of irradiation. Although the melanomas were quite large for irradiation, the lack of necrosis in optimally irradiated basal parts of the tumour additionally indicates substantial radioresistance. (author)

  2. Histopathology of enucleated intraocular melanomas irradiated with cobalt and ruthenium plaques

    Energy Technology Data Exchange (ETDEWEB)

    Fuchs, U.; Kivelae, T.; Tarkkanen, A.; Laatikainen, L.

    1988-01-01

    Eight malignant uveal melanomas irradiated with Stallard's /sup 60/Co applicator or Lommatzsch's /sup 106/Ru//sup 10/ /sup 6/Rh applicator were studied by light microscopy and immunohistochemistry to analyse tumour cell morphology, antigenic expression and inflammatory cell infiltration in relation to radiation dose. The tumours were enucleated 1 to 24 months after irradiation because they did not regress or continued to grow. One patient has later died of metastatic disease. Eight uveal melanomas that were not irradiated were studied for comparative purposes. Radiation necrosis was found only in two cases. In four irradiated and in one control melanoma conspicuous collagen fibres were present in the basal part of the tumour. No difference was noted between the two groups in the number of mitotic figures or in the morphology of tumour cells. In all cases but one, more than half of the tumour cells were variably positive for S-100 protein. Neutron-specific enolase-positive melanoma cells were few in number and occurred in small clusters, and were somewhat more common in irradiated cases. A few lymphocytes and macrophages, which were preferentially found near the choroid, infiltrated every melanoma, but only single cells were associated with radiation necrosis. A mild scleritis near the tumour was present irrespective of irradiation. Although the melanomas were quite large for irradiation, the lack of necrosis in optimally irradiated basal parts of the tumour additionally indicates substantial radioresistance.

  3. Molecular Characterization of Melanoma Cases in Denmark Suspected of Genetic Predisposition

    DEFF Research Database (Denmark)

    Wadt, Karin A. W.; Aoude, Lauren G.; Krogh, Lotte

    2015-01-01

    Both environmental and host factors influence risk of cutaneousmelanoma (CM), and worldwide, the incidence varies depending on constitutional determinants of skin type and pigmentation, latitude, and patterns of sun exposure. We performed genetic analysis of CDKN2A, CDK4, BAP1, MC1R, and MITFp.E3...... cases of CM. In addition, we recommend that testing of BAP1 should not be conducted routinely in CM families but should be reserved for families with CM and uveal melanoma, or mesothelioma....

  4. Outcomes of Proton Therapy for the Treatment of Uveal Metastases

    Energy Technology Data Exchange (ETDEWEB)

    Kamran, Sophia C. [Harvard Medical School, Boston, Massachusetts (United States); Collier, John M. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Lane, Anne Marie; Kim, Ivana [Retina Service, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts (United States); Niemierko, Andrzej [Division of Biostatistics, Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Chen, Yen-Lin E.; MacDonald, Shannon M.; Munzenrider, John E. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Gragoudas, Evangelos [Retina Service, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts (United States); Shih, Helen A., E-mail: hshih@partners.org [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States)

    2014-12-01

    Purpose/Objective(s): Radiation therapy can be used to treat uveal metastases with the goal of local control and improvement of quality of life. Proton therapy can be used to treat uveal tumors efficiently and with expectant minimization of normal tissue injury. Here, we report the use of proton beam therapy for the management of uveal metastases. Methods and Materials: A retrospective chart review was made of all patients with uveal metastases treated at our institution with proton therapy between June 2002 and June 2012. Patient and tumor characteristics, fractionation and dose schemes, local control, and toxicities are reported. Results: Ninety patients were identified. Of those, 13 were excluded because of missing information. We report on 77 patients with 99 affected eyes with available data. Patients were 68% female, and the most common primary tumor was breast carcinoma (49%). The median age at diagnosis of uveal metastasis was 57.9 years. Serous retinal detachment was seen in 38% of treated eyes. The median follow-up time was 7.7 months. The median dose delivered to either eye was 20 Gy(relative biological effectiveness [RBE]) in 2 fractions. Local control was 94%. The median survival after diagnosis of uveal metastases was 12.3 months (95% confidence interval, 7.7-16.8). Death in all cases was secondary to systemic disease. Radiation vasculopathy, measured decreased visual acuity, or both was observed in 50% of evaluable treated eyes. The actuarial rate of radiation vasculopathy, measured decreased visual acuity, or both was 46% at 6 months and 73% at 1 year. The 6 eyes with documented local failure were successfully salvaged with retreatment. Conclusions: Proton therapy is an effective and efficient means of treating uveal metastases. Acutely, the majority of patients experience minor adverse effects. For longer-term survivors, the risk of retinal injury with vision loss increases significantly over the first year.

  5. Outcomes of Proton Therapy for the Treatment of Uveal Metastases

    International Nuclear Information System (INIS)

    Kamran, Sophia C.; Collier, John M.; Lane, Anne Marie; Kim, Ivana; Niemierko, Andrzej; Chen, Yen-Lin E.; MacDonald, Shannon M.; Munzenrider, John E.; Gragoudas, Evangelos; Shih, Helen A.

    2014-01-01

    Purpose/Objective(s): Radiation therapy can be used to treat uveal metastases with the goal of local control and improvement of quality of life. Proton therapy can be used to treat uveal tumors efficiently and with expectant minimization of normal tissue injury. Here, we report the use of proton beam therapy for the management of uveal metastases. Methods and Materials: A retrospective chart review was made of all patients with uveal metastases treated at our institution with proton therapy between June 2002 and June 2012. Patient and tumor characteristics, fractionation and dose schemes, local control, and toxicities are reported. Results: Ninety patients were identified. Of those, 13 were excluded because of missing information. We report on 77 patients with 99 affected eyes with available data. Patients were 68% female, and the most common primary tumor was breast carcinoma (49%). The median age at diagnosis of uveal metastasis was 57.9 years. Serous retinal detachment was seen in 38% of treated eyes. The median follow-up time was 7.7 months. The median dose delivered to either eye was 20 Gy(relative biological effectiveness [RBE]) in 2 fractions. Local control was 94%. The median survival after diagnosis of uveal metastases was 12.3 months (95% confidence interval, 7.7-16.8). Death in all cases was secondary to systemic disease. Radiation vasculopathy, measured decreased visual acuity, or both was observed in 50% of evaluable treated eyes. The actuarial rate of radiation vasculopathy, measured decreased visual acuity, or both was 46% at 6 months and 73% at 1 year. The 6 eyes with documented local failure were successfully salvaged with retreatment. Conclusions: Proton therapy is an effective and efficient means of treating uveal metastases. Acutely, the majority of patients experience minor adverse effects. For longer-term survivors, the risk of retinal injury with vision loss increases significantly over the first year

  6. Melanoma: Genetic Abnormalities, Tumor Progression, Clonal Evolution and Tumor Initiating Cells

    Science.gov (United States)

    Castelli, Germana; Pelosi, Elvira

    2017-01-01

    Melanoma is an aggressive neoplasia issued from the malignant transformation of melanocytes, the pigment-generating cells of the skin. It is responsible for about 75% of deaths due to skin cancers. Melanoma is a phenotypically and molecularly heterogeneous disease: cutaneous, uveal, acral, and mucosal melanomas have different clinical courses, are associated with different mutational profiles, and possess distinct risk factors. The discovery of the molecular abnormalities underlying melanomas has led to the promising improvement of therapy, and further progress is expected in the near future. The study of melanoma precursor lesions has led to the suggestion that the pathway of tumor evolution implies the progression from benign naevi, to dysplastic naevi, to melanoma in situ and then to invasive and metastatic melanoma. The gene alterations characterizing melanomas tend to accumulate in these precursor lesions in a sequential order. Studies carried out in recent years have, in part, elucidated the great tumorigenic potential of melanoma tumor cells. These findings have led to speculation that the cancer stem cell model cannot be applied to melanoma because, in this malignancy, tumor cells possess an intrinsic plasticity, conferring the capacity to initiate and maintain the neoplastic process to phenotypically different tumor cells. PMID:29156643

  7. Melanoma: Genetic Abnormalities, Tumor Progression, Clonal Evolution and Tumor Initiating Cells

    Directory of Open Access Journals (Sweden)

    Ugo Testa

    2017-11-01

    Full Text Available Melanoma is an aggressive neoplasia issued from the malignant transformation of melanocytes, the pigment-generating cells of the skin. It is responsible for about 75% of deaths due to skin cancers. Melanoma is a phenotypically and molecularly heterogeneous disease: cutaneous, uveal, acral, and mucosal melanomas have different clinical courses, are associated with different mutational profiles, and possess distinct risk factors. The discovery of the molecular abnormalities underlying melanomas has led to the promising improvement of therapy, and further progress is expected in the near future. The study of melanoma precursor lesions has led to the suggestion that the pathway of tumor evolution implies the progression from benign naevi, to dysplastic naevi, to melanoma in situ and then to invasive and metastatic melanoma. The gene alterations characterizing melanomas tend to accumulate in these precursor lesions in a sequential order. Studies carried out in recent years have, in part, elucidated the great tumorigenic potential of melanoma tumor cells. These findings have led to speculation that the cancer stem cell model cannot be applied to melanoma because, in this malignancy, tumor cells possess an intrinsic plasticity, conferring the capacity to initiate and maintain the neoplastic process to phenotypically different tumor cells.

  8. Thin melanoma.

    Science.gov (United States)

    Elder, David E

    2011-03-01

    The incidence of malignant melanoma is increasing and a preponderance of the melanomas diagnosed today are "thin in terms of Breslow criteria. Although thin melanomas, as a group, are associated with a very good prognosis, a subset of these tumors may metastasize and cause death. These cases can be identified by using prognostic models, including the "standard" American Joint Committee on Cancer criteria, and other attributes identified in follow-up studies. To review the history of concepts of prognostic modeling in melanoma, focusing on thin melanomas. Selected literature. About 40 years ago, it was realized that malignant melanoma, once almost uniformly fatal, could be divided into categories with better or worse prognosis through the use of prognostic models. The first simple models, Clark levels of invasion and Breslow thickness, are still in use. Thickness remains the single most useful variable. Breslow recognized that melanomas less than 0.76 mm in thickness were associated with a very good prognosis, with no metastases in his limited initial study. The American Joint Committee on Cancer selected a cutoff of 1.0 mm, which achieves a similar result, with stage modifiers, although some metastases and deaths do occur with stage I lesions. Clark demonstrated an almost equally good prognosis for his level II invasive melanomas and recognized that most of these lesions, although invasive, lacked the ability to form tumors or to undergo mitosis in the dermis and were therefore "nontumorigenic" and "nonmitogenic" and lacked competence for metastasis. Studies of these low-risk melanomas have led to the development of criteria for earlier diagnosis and a steady, but still inadequate, improvement in prognosis for melanoma overall. Multivariable models currently can identify groups of patients within the "thin melanoma" category whose prognosis varies, from a disease-free survival of close to 100% to about 70%. Prognosis declines more or less linearly with increasing

  9. Ocular Melanoma

    Science.gov (United States)

    ... also occur on the conjunctiva . Because most eye melanomas form in the part of the eye you can’t see when looking in a mirror, they can be difficult to detect. Also, eye melanoma typically doesn’t cause early signs or symptoms . ...

  10. Malignant melanoma

    NARCIS (Netherlands)

    de Braud, Filippo; Khayat, David; Kroon, Bin B. R.; Valdagni, Riccardo; Bruzzi, Paolo; Cascinelli, Natale

    2003-01-01

    In the European Community cutaneous melanoma accounts for 1 and 1.8% of cancers occurring in men and women, respectively. The incidence rate is increasing faster than that of any other tumour. Sun exposure, patient's phenotype, family history, and history of a previous melanoma are the major risk

  11. CHOROIDAL MELANOMA IN PHAKOMATOSIS PIGMENTOVASCULARIS WITH KLIPPEL-TRENAUNAY SYNDROME.

    Science.gov (United States)

    Shields, Carol L; Di Nicola, Maura; Pellegrini, Marco; Shields, Jerry A

    2017-09-20

    To describe the relationship of choroidal melanoma with phakomatosis pigmentovascularis in patients with Klippel-Trenaunay syndrome. Retrospective review of 5 patients. In all 5 cases, the patient was white and the cutaneous port-wine stain was congenital. The port-wine stain involved the chin (n = 1), jawline (n = 2), lower cheek (n = 1), thorax (n = 5), abdomen (n = 4), upper (n = 4), and lower (n = 3) limb(s). The ocular melanocytosis involved the sclera (n = 5), iris (n = 2) and choroid (n = 4). At diagnosis of choroidal melanoma, mean patient age was 57 years (median 61, range 17-83 years). The melanoma demonstrated mean basal diameter of 11.6 mm (median 12, range 5-16 mm) and mean thickness of 5.7 mm (median 6.1, range 2-9), revealing intrinsic tumor pigment and subretinal fluid in all cases. Melanoma management included plaque radiotherapy (n = 3), thermotherapy (n = 1), or enucleation (n = 1). At mean follow-up of 4 years, one patient demonstrated melanoma-related metastasis with death. Phakomatosis pigmentovascularis represents coexistence of Klippel-Trenaunay syndrome (or Sturge-Weber syndrome) and oculo(dermal) melanocytosis, promoting risk for life-threatening uveal melanoma. The authors suggest that all patients with Klippel-Trenaunay syndrome be evaluated for phakomatosis pigmentovascularis and affected patients have dilated fundus examination once or twice a year.

  12. Intraocular malignant melanoma of the choroid presenting as orbital cellulitis.

    Science.gov (United States)

    Nair, Akshay Gopinathan; Kaliki, Swathi; Ali, Mohammed Javed; Naik, Milind N; Vemuganti, Geeta K

    2014-06-01

    We report a case of choroidal melanoma with features suggestive of orbital cellulitis. A 24-year-old Asian Indian male presented with a 20-day history of sudden loss of vision in the right eye. Edematous eyelids with complete mechanical ptosis, complete ophthalmoplegia, gross proptosis accompanied by massive chemosis, and prolapse of the inferior forniceal conjunctiva were noted. He denied perception of light in the right eye. The left eye was unremarkable. B-scan ultrasonography of the right eye showed a large dome-shaped mass filling the posterior segment suggestive of choroidal melanoma. Computed tomography confirmed those findings and showed no extraocular tumor extension. The patient was conservatively treated with systemic steroids following which the inflammation subsided. He underwent enucleation of the right eye and a diagnosis of spindle A cell choroidal melanoma was confirmed by histopathological examination. Although rare, orbital cellulitis is one of the presenting features of choroidal melanoma. Uveal melanoma-associated orbital cellulitis can be well controlled with systemic steroids, does not always indicate extraocular tumor extension, and can occur in spindle A cell melanomas.

  13. Multimodal Imaging and Clinicopathologic Correlation in Primary Uveal Lymphoma

    Directory of Open Access Journals (Sweden)

    Brandon Erickson

    2016-01-01

    Full Text Available Purpose: We report a rare case of primary uveal lymphoma and characterize it using histopathology and multimodal imaging. Patient and Methods: A 41-year-old male presented with a 2-year history of increasingly blurry vision in his right eye and no systemic symptoms. Examination revealed a retinal detachment and mass lesion in the right eye. Radiologic and histologic testing was performed. Results: Multimodal imaging localized the lesion to the choroid, and fine needle aspiration biopsy diagnosed the lesion as a low-grade B-cell lymphoma. The patient was treated with external beam radiation, resulting in regression of the mass and resolution of the retinal detachment. Conclusions: Primary uveal lymphoma is a rare, usually indolent tumor that carries a good prognosis. In this case, we show that primary uveal lymphoma has distinct findings via histopathology and multimodal imaging, and that imaging after radiation treatment documents disease regression.

  14. Prognostic value of nucleolar size and size pleomorphism in choroidal melanomas

    DEFF Research Database (Denmark)

    Sørensen, Flemming Brandt; Gamel, J W; Jensen, O A

    1993-01-01

    treated solely by enucleation of the melanoma-bearing eye in the period from 1977 to 1979. The independent prognostic value of the quantitative histopathological variables was evaluated using multivariate Cox analysis. Apart from patient data and information about tumor extent, histological type......Morphometric estimates of nucleolar size have been shown to possess a high prognostic value in patients with uveal melanomas. The authors investigated various quantitative estimators of the mean size and pleomorphism of nucleoli in choroidal melanomas from a consecutive series of 95 Danish patients...... of melanoma, and largest macroscopic tumor dimension (LTD), the following histomorphometric estimates were obtained: mean diameter of the 10 largest nucleoli (MLN), point-sampled mean nucleolar profile area (nucleolar ao) and the associated standard deviation of nucleolar ao, the volume-weighted mean...

  15. Cutaneous malignant melanoma metastatic to the eye, lids, and orbit.

    Science.gov (United States)

    Rosenberg, Caroline; Finger, Paul T

    2008-01-01

    The incidence of malignant cutaneous melanoma is increasing faster than any other cancer. Thus, it will become an increasingly common source of metastatic disease to the eye, lids, and orbit. Herein, we have performed a systematic review of previously published cases including patient characteristics, clinical presentation, diagnostic techniques, current treatments, and outcomes. At the time of ocular diagnosis, nearly all reported patients had a known history of cutaneous melanoma and synchronous non-ocular metastases. Several aspects help in differentiating the tumors from primary uveal melanomas such as the presence of symptoms, rapidly growing multifocal tumors, vitreous seeding, and histopathological findings. Intraocular metastases (uvea, vitreous, retina, and anterior-segment) are more common and occur in younger patients than extraocular metastases (eyelids, orbit, and extraocular muscles). Palliative radiation therapy is often used for intraocular disease. Orbital metastases from cutaneous melanoma commonly involve the extraocular muscles resulting in diplopia and exophthalmos. The mainstays of extraocular treatment are surgical resection and radiation therapy. Unfortunately, there are few good options for systemic treatment of diffusely metastatic melanoma. Therefore, patients with ocular metastasis should be managed to prevent loss of vision or loss of the eye, and to maximize their quality of life.

  16. Conjuntivite presumível por Acanthamoeba

    OpenAIRE

    Ruthes,Ana Cristina de Carvalho; Wahab,Sâmia; Wahab,Najua; Moreira,Hamilton; Moreira,Luciane

    2004-01-01

    OBJETIVO: Abordar quatro casos de conjuntivite presumível por Acanthamoeba, descrevendo o diagnóstico, considerando sinais e sintomas e o tratamento instituído. MÉTODOS: Foram estudados casos de conjuntivite presumível por Acanthamoeba diagnosticados no Hospital de Olhos do Paraná (HOP), no período de setembro/1998 a janeiro/2002. Todos os olhos estudados foram submetidos a um protocolo de investigação que incluía exame oftalmológico completo, microbiologia e cultura de secreções conjuntivais...

  17. Ring melanoma of the anterior chamber angle as a mimicker of pigmentary glaucoma.

    Science.gov (United States)

    Stadigh, Anni; Puska, Päivi; Vesti, Eija; Ristimäki, Ari; Turunen, Joni A; Kivelä, Tero T

    A 19-year-old man noticed blurred vision in his right eye. He had an intraocular pressure of 60 versus 12 mmHg in the fellow eye. He was initially diagnosed with an atypical, advanced pigmentary glaucoma. The intraocular pressure did not respond to maximal medication, deep sclerectomy, goniopuncture, and 2 cyclophotocoagulations. Sixteen months after presentation, malignancy was first suspected, and the eye was enucleated. A ring melanoma of the anterior chamber angle was confirmed by the histopathologic examination. Normal nuclear staining for breast cancer 1 gene (BRCA1)-associated protein 1 suggested that the tumor was likely of disomy 3 type with a favorable prognosis. No local or systemic recurrence has developed within 4 years. A literature review of this rare type of minimal volume diffuse uveal melanoma identified 18 additional patients. The initial diagnosis in 18 of the 19 patients with a ring melanoma of the anterior chamber angle was unilateral glaucoma with a median intraocular pressure of 40 mmHg and an age range of 16-76 years. Liver metastasis developed in 5 of 12 patients older than 45 years. This rare subtype is estimated to account for 0.05%-0.16% of all uveal melanomas. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Mutational dichotomy in desmoplastic malignant melanoma corroborated by multigene panel analysis.

    Science.gov (United States)

    Jahn, Stephan W; Kashofer, Karl; Halbwedl, Iris; Winter, Gerlinde; El-Shabrawi-Caelen, Laila; Mentzel, Thomas; Hoefler, Gerald; Liegl-Atzwanger, Bernadette

    2015-07-01

    Desmoplastic malignant melanoma is a distinct melanoma entity histologically subtyped into mixed and pure forms due to significantly reduced lymph node metastases in the pure form. Recent reports investigating common actionable driver mutations have demonstrated a lack of BRAF, NRAS, and KIT mutation in pure desmoplastic melanoma. In search for alternative driver mutations next generation amplicon sequencing for hotspot mutations in 50 genes cardinal to tumorigenesis was performed and in addition the RET G691S polymorphism was investigated. Data from 21 desmoplastic melanomas (12 pure and 9 mixed) were retrieved. Pure desmoplastic melanomas were either devoid of mutations (50%) or displayed mutations in tumor suppressor genes (TP53, CDKN2A, and SMAD4) singularly or in combination with the exception of a PIK3CA double-mutation lacking established biological relevance. Mixed desmoplastic melanomas on the contrary were frequently mutated (89%), and 67% exhibited activating mutations similar to common-type cutaneous malignant melanomas (BRAF, NRAS, FGFR2, and ERBB2). Separate analysis of morphologically heterogeneous tumor areas in four mixed desmoplastic malignant melanomas displayed no difference in mutation status and RET G691 status. GNAQ and GNA11, two oncogenes in BRAF and NRAS wild-type uveal melanomas, were not mutated in our cohort. The RET G691S polymorphism was found in 25% of pure and 38% of mixed desmoplastic melanomas. Apart from RET G691S our findings demonstrate absence of activating driver mutations in pure desmoplastic melanoma beyond previously investigated oncogenes (BRAF, NRAS, and KIT). The findings underline the therapeutic dichotomy of mixed versus pure desmoplastic melanoma with regard to activating mutations primarily of the mitogen-activated protein kinase pathway.

  19. Malignant Melanoma

    Directory of Open Access Journals (Sweden)

    Eshini Perera

    2013-12-01

    Full Text Available Melanomas are a major cause of premature death from cancer. The gradual decrease in rates of morbidity and mortality has occurred as a result of public health campaigns and improved rates of early diagnosis. Survival of melanoma has increased to over 90%. Management of melanoma involves a number of components: excision, tumor staging, re-excision with negative margins, adjuvant therapies (chemo, radiation or surgery, treatment of stage IV disease, follow-up examination for metastasis, lifestyle modification and counseling. Sentinel lymph node status is an important prognostic factor for survival in patients with a melanoma >1 mm. However, sentinel lymph node biopsies have received partial support due to the limited data regarding the survival advantage of complete lymph node dissection when a micrometastasis is detected in the lymph nodes. Functional mutations in the mitogen-activated pathways are commonly detected in melanomas and these influence the growth control. Therapies that target these pathways are rapidly emerging, and are being shown to increase survival rates in patients. Access to these newer agents can be gained by participation in clinical trials after referral to a multidisciplinary team for staging and re-excision of the scar.

  20. Presumed hereditary retinal degenerations: Ibadan experience ...

    African Journals Online (AJOL)

    This study describes the clinical presentation of RP, the prevalence of associated treatable disorders and the characteristics of patients with severe visual impairment and blindness. Method: A retrospective review of 52 cases presumed and diagnosed to have RP was performed on patients who presented at the Eye Clinic, ...

  1. A case report of a patient with metastatic ocular melanoma who experienced a response to treatment with the BRAF inhibitor vemurafenib.

    Science.gov (United States)

    Maleka, A; Åström, G; Byström, P; Ullenhag, G J

    2016-08-12

    Conjunctival malignant melanoma (CMM) is a rare malignancy and in the advanced setting there is no effective treatment. In contrast, half of cutaneous melanomas have BRAF mutations and treatment with BRAF inhibitors is established for patients with disseminated disease. The most common form of ocular melanoma, uveal melanoma, lacks these mutations, however, their presence has been reported for CMM. We used the BRAF inhibitor vemurafenib to treat a 53 year-old female suffering from a BRAF(V600E) mutated metastatic CMM. The patient benefited from the treatment, a response was evident within a week and she experienced a progression free survival of four months. To our knowledge, this is the first described case of response to vemurafenib treatment in a patient with ocular melanoma.

  2. Malignant Melanoma of the Foot

    Science.gov (United States)

    ... Javascript in your browser. Malignant Melanoma of the Foot What Is Malignant Melanoma? Melanoma is a cancer ... age groups, even the young. Melanoma in the Foot Melanoma that occurs in the foot or ankle ...

  3. Prognostic value of nucleolar size and size pleomorphism in choroidal melanomas

    DEFF Research Database (Denmark)

    Sørensen, Flemming Brandt; Gamel, J W; Jensen, O A

    1993-01-01

    Morphometric estimates of nucleolar size have been shown to possess a high prognostic value in patients with uveal melanomas. The authors investigated various quantitative estimators of the mean size and pleomorphism of nucleoli in choroidal melanomas from a consecutive series of 95 Danish patients...... of melanoma, and largest macroscopic tumor dimension (LTD), the following histomorphometric estimates were obtained: mean diameter of the 10 largest nucleoli (MLN), point-sampled mean nucleolar profile area (nucleolar ao) and the associated standard deviation of nucleolar ao, the volume-weighted mean...... nucleolar volume (nucleolar vv), and associated variance and relative variance of nucleolar volume (nucleolar Varv(v) and nucleolar CVv(v), respectively). The intra-observer reproducibility of estimates of nucleolar vv was tested in 20 cases and found acceptable (r = 0.84, 2p = 3.6.10(-6)). Correlation...

  4. The Prognostic Effect of American Joint Committee on Cancer Staging and Genetic Status in Patients With Choroidal and Ciliary Body Melanoma

    DEFF Research Database (Denmark)

    Bagger, Mette; Andersen, Morten T; Andersen, Klaus K

    2015-01-01

    PURPOSE: To evaluate the prognostic effect of a combination of American Joint Committee on Cancer (AJCC) staging (7th edition) and genetic status in patients with posterior uveal melanoma. METHODS: A consecutive cohort of 153 patients with posterior uveal melanoma treated at Copenhagen University...... prognostic effects of AJCC staging and cytogenetic changes were evaluated by cumulative incidence curves and Cox proportional hazard models. RESULTS: An overall 5-year survival rate of 62% (95% confidence interval [CI]: 0.50-0.73) was observed. A normal genetic status of chromosomes 3 and 8, as found in 42...... patients (30%), minimized the additional prognostic effect of AJCC staging. The frequency of tumors with normal genetic status decreased with increasing AJCC stage. Both AJCC stage III (hazard ratio [HR]: 11.0, 95% CI: 1.4-85.6) and abnormal copy number of chromosomes 3 (HR: 6.3, 95% CI: 1.4-28.3) and 8...

  5. 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

  6. Does escalation of the apical dose change treatment outcome in β-radiation of posterior choroidal melanomas with 106Ru plaques?

    International Nuclear Information System (INIS)

    Hermann, Robert Michael; Pradier, Olivier; Lauritzen, Katharina; Ott, Marcel; Schmidberger, Heinz; Hess, Clemens F.

    2002-01-01

    Purpose: To show the results of treating posterior uveal melanomas with 106 Ru plaque β-ray radiotherapy and to review and discuss the literature concerning the optimal apical dose prescription (100 vs. 160 Gy). Methods and Materials: Forty-eight patients with uveal melanomas (median height 3.85 mm + 1 mm sclera) were treated with ruthenium plaques. The median apical dose was 120 Gy, the median scleral dose 546 Gy. Results: After 5.8 years of follow-up, the overall 5-year survival rate was 90%, the disease specific 5-year survival rate was 92% (3 patients alive with metastasis). Six percent received a second ruthenium application, 10% of the eyes had to be enucleated. Local control was achieved in 90% of the patients with conservative therapy alone. Central or paracentral tumors showed 50% of the pretherapeutic vision after 4 years, and 80% of the vision was preserved in those with peripheral tumors. The main side effects were mostly an uncomplicated retinopathy (30%); macular degeneration or scarring led to poor central vision in 30% of cases. Conclusion: Brachytherapy with ruthenium applicators is an effective therapy for small- and medium-size posterior uveal melanomas. Our results are comparable to other series. The treatment outcome does not seem to be capable of improvement by increasing the apical dose. An internationally accepted model for defining the dosage in brachytherapy is needed

  7. Targeting SRPK1 to control VEGF-mediated tumour angiogenesis in metastatic melanoma.

    Science.gov (United States)

    Gammons, M V; Lucas, R; Dean, R; Coupland, S E; Oltean, S; Bates, D O

    2014-07-29

    Current therapies for metastatic melanoma are targeted either at cancer mutations driving growth (e.g., vemurafenib) or immune-based therapies (e.g., ipilimumab). Tumour progression also requires angiogenesis, which is regulated by VEGF-A, itself alternatively spliced to form two families of isoforms, pro- and anti-angiogenic. Metastatic melanoma is associated with a splicing switch to pro-angiogenic VEGF-A, previously shown to be regulated by SRSF1 phosphorylation by SRPK1. Here, we show a novel approach to preventing angiogenesis-targeting splicing factor kinases that are highly expressed in melanomas. We used RT-PCR, western blotting and immunohistochemistry to investigate SRPK1, SRSF1 and VEGF expression in tumour cells, and in vivo xenograft assays to investigate SRPK1 knockdown and inhibition in vivo. In both uveal and cutaneous melanoma cell lines, SRPK1 was highly expressed, and inhibition of SRPK1 by knockdown or with pharmacological inhibitors reduced pro-angiogenic VEGF expression maintaining the production of anti-angiogenic VEGF isoforms. Both pharmacological SRPK1 inhibitors and SRPK1 knockdown reduced growth of human melanomas in vivo, but neither affected cell proliferation in vitro. These results suggest that selective blocking of pro-angiogenic isoforms by inhibiting splice-site selection with SRPK1 inhibitors reduces melanoma growth. SRPK1 inhibitors may be used as therapeutic agents.

  8. A Comprehensive Patient-Derived Xenograft Collection Representing the Heterogeneity of Melanoma

    Directory of Open Access Journals (Sweden)

    Clemens Krepler

    2017-11-01

    Full Text Available Summary: Therapy of advanced melanoma is changing dramatically. Following mutational and biological subclassification of this heterogeneous cancer, several targeted and immune therapies were approved and increased survival significantly. To facilitate further advancements through pre-clinical in vivo modeling, we have established 459 patient-derived xenografts (PDX and live tissue samples from 384 patients representing the full spectrum of clinical, therapeutic, mutational, and biological heterogeneity of melanoma. PDX have been characterized using targeted sequencing and protein arrays and are clinically annotated. This exhaustive live tissue resource includes PDX from 57 samples resistant to targeted therapy, 61 samples from responders and non-responders to immune checkpoint blockade, and 31 samples from brain metastasis. Uveal, mucosal, and acral subtypes are represented as well. We show examples of pre-clinical trials that highlight how the PDX collection can be used to develop and optimize precision therapies, biomarkers of response, and the targeting of rare genetic subgroups. : Krepler et al. have established a collection of melanoma patient-derived xenografts (PDX. Melanoma is a very heterogeneous cancer, and this large collection includes even rare subtypes and genetic aberrations in sufficient numbers. Multiple PDX from therapy-resistant patients are characterized and tested in pre-clinical trials for second line therapies. Keywords: melanoma, patient-derived xenografts, targeted therapy, immune checkpoint blockade, melanoma brain metastasis, in vivo models, BRAF inhibitor resistance, ERK inhibitor, MDM2 inhibitor, PI3K beta inhibitor

  9. Immunohistochemical Expression of FXR1 in Canine Normal Tissues and Melanomas.

    Science.gov (United States)

    Nordio, Laura; Marques, Andreia T; Lecchi, Cristina; Luciano, Alberto M; Stefanello, Damiano; Giudice, Chiara

    2018-04-01

    Fragile X mental retardation-related protein 1 (FXR1) is a cytoplasmic RNA-binding protein highly conserved among vertebrates. It has been studied for its role in muscle development, inflammation, and tumorigenesis, being related, for example, to metastasizing behavior in human and canine uveal melanoma. Anti-FXR1 antibodies have never been validated in the canine species. To investigate FXR1 expression in canine melanocytic tumors, the present study tested two commercially available polyclonal anti-human FXR1 antibodies, raised in goat and rabbit, respectively. The cross-reactivity of the anti-FXR1 antibodies was assessed by Western blot analysis, and the protein was localized by IHC in a set of normal canine tissues and in canine melanocytic tumors (10 uveal and 10 oral). Western blot results demonstrated that the antibody raised in rabbit specifically recognized the canine FXR1, while the antibody raised in goat did not cross-react with this canine protein. FXR1 protein was immunodetected using rabbit anti-FXR1 antibody, in canine normal tissues with different levels of intensity and distribution. It was also detected in 10/10 uveal and 9/10 oral melanocytic tumors. The present study validated for the first time the use of anti-FXR1 antibody in dogs and highlighted different FXR1 protein expression in canine melanocytic tumors, the significance of which is undergoing further investigations.

  10. Presumed oculoglandular syndrome from Bartonella quintana.

    Science.gov (United States)

    Borboli, Sheila; Afshari, Natalie A; Watkins, Lynnette; Foster, C Stephen

    2007-01-01

    To describe a case of clinically diagnosed oculoglandular syndrome in a 17-year-old patient that was presumed to be due to Bartonella quintana, as suggested by a positive serologic titer. The patient presented to the Massachusetts Eye and Ear Infirmary emergency room with signs and symptoms suggestive of oculoglandular syndrome. He had a follicular conjunctivitis with a conjunctival granuloma of the right eye and an ipsilateral large, tender submandibular lymph node. He had recently acquired a kitten and a clinical diagnosis of cat-scratch disease was made. A laboratory workup was initiated to determine the cause of this clinical presentation and empirical treatment with antibiotics was started. All laboratory results were negative or normal except for the IgM titer to Bartonella quintana, which was elevated. The patient responded well to treatment and his symptoms resolved within a few weeks. Bartonella quintana infection, a pathogen prevalent in HIV-infected, homeless, or alcoholic patients, is a possible etiologic agent of cat-scratch disease and the associated condition of oculoglandular syndrome.

  11. Cixutumumab in Treating Patients With Metastatic Melanoma of the Eye

    Science.gov (United States)

    2015-06-25

    Ciliary Body and Choroid Melanoma, Medium/Large Size; Ciliary Body and Choroid Melanoma, Small Size; Iris Melanoma; Metastatic Intraocular Melanoma; Recurrent Intraocular Melanoma; Stage IV Intraocular Melanoma

  12. PRL-3/PTP4A3 phosphatase regulates integrin β1 in adhesion structures during migration of human ocular melanoma cells.

    Science.gov (United States)

    Foy, Malika; Anézo, Océane; Saule, Simon; Planque, Nathalie

    2017-04-15

    In a previous transcriptomic analysis of 63 ocular melanomas of the uvea, we found that expression of the PRL-3/PTP4A3 gene, encoding a phosphatase that is anchored to the plasma membrane, was associated with the risk of metastasis, and a poor prognosis. We also showed that PRL-3 overexpression in OCM-1 ocular melanoma cells significantly increased cell migration in vitro and invasiveness in vivo, suggesting a direct role for PRL-3 in the metastatic spreading of uveal melanoma. Here, we aimed to identify PRL-3 substrates at the plasma membrane involved in adhesion to the extracellular matrix. We focused on integrin β1, which is the most highly expressed integrin in our cohort of uveal melanomas. We show that preventing PRL-3 anchorage to the plasma membrane i) abolishes PRL-3-induced migration in OCM-1 cells, ii) specifically enhances the spreading of OCM-1 cells overexpressing PRL-3, and iii) favors the maturation of large focal adhesions (FAs) containing integrin β1 on collagen I. Knockdown experiments confirmed integrin β1 involvement in PRL3-induced migration. We identified interactions between PRL-3 and integrin β1, as well as with FAK P-Y397, an auto-activated form of Focal Adhesion Kinase found in FAs. We also show that integrin β1 may be dephosphorylated by PRL-3 in its intracytoplasmic S/T region, an important motif for integrin-mediated cell adhesion. Finally, we observed that PRL-3 regulated the clustering of integrin β1 in FAs on collagen I but not on fibronectin. This work identifies PRL-3 as a new regulator of cell adhesion structures to the extracellular matrix, and further supports PRL-3 as a key actor of metastasis in uveal melanoma, of which molecular mechanisms are still poorly understood. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Stereologic estimation of nucleolar volume in ocular melanoma

    DEFF Research Database (Denmark)

    Sørensen, Flemming Brandt; Gamel, J W; McCurdy, J

    1993-01-01

    The aim of this study was to investigate the relationships between one-, two-, and three-dimensional histomorphometric estimators of nucleolar size in ordinary histologic sections of uveal melanomas from 144 patients. In addition, the prognostic value of the various size parameters was studied...... covariates at the chosen level of significance (5%). Unbiased, shape-independent estimates of the nucleolar vv offered superior prediction of clinical outcome, as compared with lower-dimensional, shape-dependent histomorphometric estimators of nucleolar size........ The following estimates were obtained: the mean diameter of the 10 largest nucleoli, the mean nucleolar profile area and associated standard deviation of the nucleolar profile area, the volume-weighted mean nucleolar volume (nucleolar vv), and the macroscopic, largest tumor dimension. All histomorphometric...

  14. Skin cancer and melanoma

    International Nuclear Information System (INIS)

    Moylan, D.J.

    1991-01-01

    In this chapter, the author discusses various types of non-melanoma malignant skin cancer, as well as malignant melanoma. Non-melanoma skin cancer, such as basal cell and squamous cell carcinomas, occasionally metastasize, but only late in the course of the disease. On the other hand, even relatively small primary melanomas tend to disseminate to regional lymph nodes and to distant sites. The author presents various treatment plans, including radiation therapy. Cutaneous melanomas have been considered relatively radioresistant. This is the rationale for the use of large fraction radiation therapy in the treatment of melanomas with the fraction sizes varying from 4--8 Gy

  15. The influence of silicone oil used in ophthalmology on the proton therapy of uveal melanomas

    Science.gov (United States)

    Weber, A.; Cordini, D.; Stark, R.; Heufelder, J.

    2012-12-01

    In ocular proton therapy the important parameters range and modulation of the proton field are calculated by a simple geometric ray tracking. Due to the assumed homogeneous eye tissue, the relative-to-water proton stopping power is nearly constant within the radiation field. In cases when silicone oil tamponades are used, this will no longer hold. CT-data which are necessary to estimate the path length of protons within the oil show bigger attenuation of x-rays then in eye tissue. The use of a CT-calibration curve to deduce the relative-to-water electron density for proton stopping power calculation would be misleading giving a value of 1.05 and thus a higher proton stopping power. In reality the relative-to-water electron density is smaller, namely 0.95, leading to a proton range prolonged by about 11% of the path length within the silicone oil, if the demand for the range adjustment would not be recognized (missing information from ophthalmologists or no CT data). This finding is congruent in analytical and Monte Carlo calculations as well as in experimental investigations, being presented here. The misleading result of the CT calibration curve is explained and therapeutic consequences are demonstrated. Multiple Coulomb scattering in silicone oil does not affect the size of the planed irradiation field.

  16. Normal HLA class I, II, and MICA gene distribution in uveal melanoma.

    NARCIS (Netherlands)

    Metzelaar-Blok, J.A.; Hurks, H.M.; Naipal, A.; Lange, P. de; Keunen, J.E.E.; Claas, F.; Doxiadis, I.I.; Jager, M.J.

    2005-01-01

    PURPOSE: The molecules of the HLA class I and II molecules as well as the MHC class I chain-related gene A (MICA), a polymorphic and stress-induced cell surface molecule, are involved in T-cell and natural killer-cell (NK-cell) mediated immune responses. In this study we looked for any genetic

  17. Simulation and dosimetric analysis of proton and carbon ion therapy in the treatment of uveal melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Christovao, Marilia Tavares, E-mail: marilia@cdtn.br [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil); Campos, Tarcisio Passos Ribeiro de; Trindade, Bruno Machado [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Dept. de Engenharia Nuclear

    2011-11-15

    The present paper addresses the dosimetric evaluation of carbon ion radiotherapy as compared with proton therapy. Materials and methods: computer simulations were undertaken with the Geant4 (GEometry ANd Tracking) code. An eye model discretized into voxels and implemented in the Siscodes system (computer system for dosimetry in radiation therapy) was utilized to generate and superimpose depth dose profiles and isodose curves. Different values for beam energy were adopted in the simulations of carbon ion beams, while in the simulation with proton beams irradiation line devices were included with different absorbing material thicknesses. Results: the simulations outputs were processed and integrated into the Siscodes to generate the spatial dose distribution in the eye model, considering changes in the beam entrance position. The dose rates were normalized as a function of the maximum dose for a beam at a specific entrance position, incident particle energy and number of incident carbon ions and protons. Conclusion: the described benefits together with the presented results contribute to the development of clinical applications and researches on carbon ion and proton therapy. (author)

  18. Adoptive T cell immunotherapy of human uveal melanoma targeting gp100

    NARCIS (Netherlands)

    Sutmuller, R. P.; Schurmans, L. R.; van Duivenvoorde, L. M.; Tine, J. A.; van der Voort, E. I.; Toes, R. E.; Melief, C. J.; Jager, M. J.; Offringa, R.

    2000-01-01

    HLA-A*0201-restricted CTL against human gp100 were isolated from HLA-A*0201/K(b) (A2/K(b))-transgenic mice immunized with recombinant canarypox virus (ALVAC-gp100). These CTL strongly responded to the gp100(154-162) epitope, in the context of both the chimeric A2/K(b) and the wild-type HLA-A*0201-

  19. Isolated hepatic perfusion as a treatment for uveal melanoma liver metastases (the SCANDIUM trial)

    DEFF Research Database (Denmark)

    Olofsson, Roger; Ny, Lars; Eilard, Malin Sternby

    2014-01-01

    for patients with liver metastases is between 6 and 12 months, and no treatment has in randomized trials ever been shown to prolong survival. A previous phase II trial using isolated hepatic perfusion (IHP) has suggested a 14-month increase in overall survival compared with a historic control group consisting...... metastases (verified by biopsy) and no evidence of extra-hepatic tumor manifestations by positron emission tomography-computed tomography (PET-CT). The primary endpoint is overall survival at 24 months, with secondary endpoints including response rate, progression-free survival, and quality of life...... survival being the primary endpoint. TRIAL REGISTRATION: ClinicalTrials.gov registration number: NCT01785316 (registered 1 February 2013). EudraCT registration number: 2013-000564-29....

  20. Occupational exposure to endocrine-disrupting chemicals and the risk of uveal melanoma

    DEFF Research Database (Denmark)

    Behrens, Thomas; Lynge, Elsebeth; Cree, Ian

    2012-01-01

    -disrupting agents. We constructed several exposure scores, taking into account intensity of exposure, use of personal protective equipment, and exposure duration. We calculated unconditional logistic regression analyses, adjusting for country, age, sex, eye color and a history of ocular damage due to intense...

  1. Treatment Option Overview (Melanoma)

    Science.gov (United States)

    ... Reporting & Auditing Grant Transfer Grant Closeout Contracts & Small Business Training Cancer Training at NCI (Intramural) Funding for ... the skin far away from where it first started. Recurrent Melanoma Recurrent melanoma is cancer that has ...

  2. General Information about Melanoma

    Science.gov (United States)

    ... Reporting & Auditing Grant Transfer Grant Closeout Contracts & Small Business Training Cancer Training at NCI (Intramural) Funding for ... the skin far away from where it first started. Recurrent Melanoma Recurrent melanoma is cancer that has ...

  3. Stages of Melanoma

    Science.gov (United States)

    ... Reporting & Auditing Grant Transfer Grant Closeout Contracts & Small Business Training Cancer Training at NCI (Intramural) Funding for ... the skin far away from where it first started. Recurrent Melanoma Recurrent melanoma is cancer that has ...

  4. Melanoma - neck (image)

    Science.gov (United States)

    This melanoma on the neck is variously colored with a very darkly pigmented area found centrally. It has irregular ... be larger than 0.5 cm. Prognosis in melanoma is best defined by its depth on resection.

  5. 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.

  6. 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.

  7. Melanoma International Foundation

    Science.gov (United States)

    ... the state of Pennsylvania, certificate #29498 © 2013 Melanoma International Foundation. All Rights Reserved. Privacy Policy | Terms of Use Toll-free: 866-463-6663 International: 610-942-3432 Melanoma International Foundation 250 Mapleflower ...

  8. Conjuntivite presumível por Acanthamoeba Conjunctivitis presumably due to Acanthamoeba

    Directory of Open Access Journals (Sweden)

    Ana Cristina de Carvalho Ruthes

    2004-12-01

    Full Text Available OBJETIVO: Abordar quatro casos de conjuntivite presumível por Acanthamoeba, descrevendo o diagnóstico, considerando sinais e sintomas e o tratamento instituído. MÉTODOS: Foram estudados casos de conjuntivite presumível por Acanthamoeba diagnosticados no Hospital de Olhos do Paraná (HOP, no período de setembro/1998 a janeiro/2002. Todos os olhos estudados foram submetidos a um protocolo de investigação que incluía exame oftalmológico completo, microbiologia e cultura de secreções conjuntivais. RESULTADOS: Os exames laboratoriais de microscopia e cultura do material colhido estes pacientes revelaram o diagnóstico de Acanthamoeba. A maioria dos pacientes referia olhos vermelhos e irritação ocular de longa data. Os autores encontraram correlação entre a cultura e o exame direto, em que se evidenciou a presença de cistos e trofozoítas do protozoário. CONCLUSÃO: Este é o primeiro relato de conjuntivite provavelmente por Acanthamoeba de acordo com a literatura revisada. Pacientes selecionados e refratários ao tratamento habitual de infecção ocular externa devem ser considerados para estudo laboratorial adequado à procura etiológica da doença.PURPOSE: To describe four cases of conjunctivitis presumably due to Acanthamoeba considering diagnosis, signs, symptoms and treatment. METHODS: We reviewed the medical records of all patients who presented a clinical diagnosis of Acanthamoeba conjunctivitis between September/1998 to January/2001 at the "Hospital de Olhos do Paraná (HOP". All eyes were submitted to a protocol of investigation that included ophthalmologic examination, microscopic examination and culture exams of conjunctival smears for adequate treatment. RESULTS: The laboratorial results of conjunctival smears revealed contamination with Acanthamoeba by direct examination and thereafter, confirmed by culture. The authors observed cysts and trophozoites of Acanthamoeba. CONCLUSION: This is the first report of

  9. Drug effects on melanoma

    NARCIS (Netherlands)

    Koomen, Elsje Rosalie

    2010-01-01

    Cutaneous melanoma is the most aggressive form of skin cancer and its incidence among Caucasian populations has increased whereas mortality rates are stabilizing or decreasing. The total burden of melanoma is expected to be increasing. As effective treatment options for advanced melanoma are

  10. 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.

  11. 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...

  12. Cutaneous melanoma in women

    Directory of Open Access Journals (Sweden)

    Mi Ryung Roh, MD

    2017-03-01

    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.

  13. Cutaneous melanoma in women

    Directory of Open Access Journals (Sweden)

    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.

  14. Ultrasound Biomicroscopic Evaluation of Uveal Effusion in Acute Primary Angle Closure.

    Science.gov (United States)

    You, Yi-an; Zhu, Le-ru; Wen, Ji-quan; Liu, Yin-he

    2015-12-01

    The aim of this study was to determine the prevalence of uveal effusion in acute primary angle closure (APAC), chronic primary angle-closure glaucoma (PACG), and primary open-angle glaucoma (POAG). A total of 152 consecutive patients (287 eyes) with APAC, PACG, and POAG were enrolled in this prospective and observational case series study. Intraocular pressure-lowering medications were used and ultrasound biomicroscopy examination was undertaken to determine the presence of uveal effusion and measure anterior chamber parameters. Overall, uveal effusion was evident in 40 of 194 affected eyes (20.6%) and no uveal effusion was seen in their fellow eyes. The prevalence of uveal effusion in APAC, chronic PACG, and POAG was 29.3%, 10.9%, and 3.1%, respectively (χ=226.63, PAPAC eyes had the highest prevalence of effusion and no effusion in their fellow eyes. In 40 eyes with uveal effusion, grade 1 effusion was seen in 17 eyes (42.5%), grade 2 in 15 eyes (37.5%), and grade 3 in 8 eyes (20%). In APAC eyes, the difference in the mean anterior chamber depth (ACD) among effusion grades 3, 2, and 1 was significant (F=5.425, P=0.017), and the eyes with grade 3 effusion had shallower ACD compared with grade 1 (P=0.031), but the difference was not significant compared with grade 2 (P=0.368). The eyes with APAC are associated with a higher prevalence of uveal effusion compared with PACG and POAG and probably as a result of rapid reduction in intraocular pressure with aggressive hypotensive therapy and inflammatory response to the process of acute attack.

  15. Apparent absence of a benign precursor lesion: Implications for the pathogenesis of malignant melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Ross, P.M. (Rockefeller Univ., New York, NY (USA))

    1989-09-01

    This review relates concepts derived from the study of chemically induced skin cancer in animal models to the pathogenesis of malignant melanoma in humans. Most chemically induced experimental cancers in animals, including melanomas in rodents, arise within a benign precursor lesion. The initiation-promotion-progression sequence is a central concept in animal models for carcinogenesis. Many human melanomas appear to arise from epidermal melanocytes, with no associated precursor lesion. This article considers why there is no apparent precursor in many human melanomas and the consequences of this absence. Melanocyte physiology and factors that govern escape from defenses such as DNA repair, local tissue environment, and immunity presumably influence melanocyte conversion to melanoma. These factors may determine the absence of a precursor lesion in primary melanomas. In addition, it is possible that some human melanomas arise by cellular mechanisms different from those causing cancer in rodent models. Both molecular and prospective clinical studies will be required to explain this apparent paradox in the pathogenesis of melanoma. A similar approach may help to explain the origin of basal cell carcinoma and perhaps other human cancers that appear to arise directly from normal cells. From a clinical point of view, the absence of an identifiable, benign precursor lesion requires even greater emphasis on melanoma prevention. Research on mechanisms of ultraviolet carcinogenesis indicates that appropriate postexposure treatments may be useful in preventing long-term consequences of sunburn, including melanoma. 69 references.

  16. Gamma-Secretase/Notch Signalling Pathway Inhibitor RO4929097 in Treating Patients With Stage IV Melanoma

    Science.gov (United States)

    2016-05-06

    Acral Lentiginous Malignant Melanoma; Lentigo Maligna Malignant Melanoma; Nodular Malignant Melanoma; Recurrent Melanoma; Solar Radiation-related Skin Melanoma; Stage IV Melanoma; Superficial Spreading Malignant Melanoma

  17. Molecular Characteristics of Conjunctival Melanoma Using Whole-Exome Sequencing.

    Science.gov (United States)

    Swaminathan, Swarup S; Field, Matthew G; Sant, David; Wang, Gaofeng; Galor, Anat; Dubovy, Sander R; Harbour, J William; Karp, Carol L

    2017-12-01

    Conjunctival melanoma (CM) is a highly aggressive ocular cancer for which treatment options are limited; the molecular pathogenesis is poorly understood. To identify the molecular characteristics of CM using next-generation whole-exome sequencing (WES). Whole-exome sequencing was performed on tumor DNA extracted from the archived specimens of 5 patients with CM who had been treated with surgical excision between 2006 and 2011. These samples were analyzed at a tertiary academic ocular oncology referral center using a customized bioinformatic pipeline. Sample analyses were designed to detect driver mutations, chromosome copy number aberrations, and mutation signatures. The study’s 5 patients ranged in age from 51 to 77 years. Four of the 5 were female, and all were white. Mutations were detected in known oncogenes, including BRAF, NRAS, NF1, EGFR, ALK, TERT, and APC. None of the mutations associated with uveal melanoma were found. All samples demonstrated a C→T mutation signature typical of UV-induced DNA damage. The most common CNA was a gain in chromosome 6p. In these 5 patients, WES allowed identification of mutations that can be targeted with therapy and supported the role of UV light in CM pathogenesis. These findings indicate a need for larger studies to evaluate the diagnostic, prognostic, and therapeutic value of WES for CM.

  18. Decoding Melanoma Metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Damsky, William E. Jr. [Department of Dermatology, Yale School of Medicine, New Haven, Connecticut (United States); Department of Pathology, University of Vermont College of Medicine, Burlington, Vermont (United States); Rosenbaum, Lara E.; Bosenberg, Marcus, E-mail: Marcus.Bosenberg@yale.edu [Department of Dermatology, Yale School of Medicine, New Haven, Connecticut (United States)

    2010-12-30

    Metastasis accounts for the vast majority of morbidity and mortality associated with melanoma. Evidence suggests melanoma has a predilection for metastasis to particular organs. Experimental analyses have begun to shed light on the mechanisms regulating melanoma metastasis and organ specificity, but these analyses are complicated by observations of metastatic dormancy and dissemination of melanocytes that are not yet fully malignant. Additionally, tumor extrinsic factors in the microenvironment, both at the site of the primary tumor and the site of metastasis, play important roles in mediating the metastatic process. As metastasis research moves forward, paradigms explaining melanoma metastasis as a step-wise process must also reflect the temporal complexity and heterogeneity in progression of this disease. Genetic drivers of melanoma as well as extrinsic regulators of disease spread, particularly those that mediate metastasis to specific organs, must also be incorporated into newer models of melanoma metastasis.

  19. 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.

  20. Radioactive phosphorus uptake test: an in vitro analysis of choroidal melanoma and ocular tissues

    International Nuclear Information System (INIS)

    Packer, S.; Shields, J.A.; Christman, D.R.; Wolf, A.P.; Atkins, H.L.

    1980-01-01

    The concentration of radioactive phosphorus in uveal melanoma and normal parts of the eye was determined in vitro in 14 eyes. The eyes were enucleated after a positive 32 P uptake test. Portions of the melanoma as well as normal choroid, retina, sclera, lens, and vitreous were analyzed. The 32 P uptake test had been performed at various intervals after intravenous administration of 32 P from 24 to 556 hr. The in vitro uptake of 32 P was compared to cell type, tumor volume, time of testing, percent uptake measured clinically, and specific activity. The only positive correlation was between percent uptake measured clinically and 32 P concentration (dpm/gm). A higher concentration of phosphorus in melanoma resulted when carrier-free 32 P was used. A negative correlation existed between number of hours from injection to clinical measurement of percent uptake, although melanoma to normal choroid ratios did not change from 24 to 72 hr. No correlation was found between uptake and tumor volume. The sample was small; however, we saw no correlation between 32 P uptake and degree of malignancy

  1. Molecular characterization of melanoma cases in Denmark suspected of genetic predisposition.

    Directory of Open Access Journals (Sweden)

    Karin A W Wadt

    Full Text Available Both environmental and host factors influence risk of cutaneous melanoma (CM, and worldwide, the incidence varies depending on constitutional determinants of skin type and pigmentation, latitude, and patterns of sun exposure. We performed genetic analysis of CDKN2A, CDK4, BAP1, MC1R, and MITFp.E318K in Danish high-risk melanoma cases and found CDKN2A germline mutations in 11.3% of CM families with three or more affected individuals, including four previously undescribed mutations. Rare mutations were also seen in CDK4 and BAP1, while MC1R variants were common, occurring at more than twice the frequency compared to Danish controls. The MITF p.E318K variant similarly occurred at an approximately three-fold higher frequency in melanoma cases than controls. To conclude, we propose that mutation screening of CDKN2A and CDK4 in Denmark should predominantly be performed in families with at least 3 cases of CM. In addition, we recommend that testing of BAP1 should not be conducted routinely in CM families but should be reserved for families with CM and uveal melanoma, or mesothelioma.

  2. CASE REPORT: NODULAR MELANOMA

    Directory of Open Access Journals (Sweden)

    Tina Zupančič

    2015-05-01

    Full Text Available Nodular melanoma is a rare type of cutaneous melanoma with an increased risk of death. It often mimics benign cutaneous tumors and inflammatory lesions. It has pronounced vertical growth phase and greater thickness at the time of diagnosis which caries ominous prognostic value. Nodular melanoma quickly develops metastases which are often present before the disease is clinically recognised. Here, we report a case of nodular melanoma clinically mimicking seborrheic keratosis. Therapy and 36 months follow-up after primal excision are also presented.

  3. Staging of cutaneous melanoma

    NARCIS (Netherlands)

    P. Mohr (P.); A.M.M. Eggermont (Alexander); A. Hauschild (Axel); A. Buzaid (A.)

    2009-01-01

    textabstractThe American Joint Committee on Cancer (AJCC) staging of cutaneous melanoma is a continuously evolving system. The identification of increasingly more accurate prognostic factors has led to major changes in melanoma staging over the years, and the current system described in this review

  4. 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.

  5. Bronchial malignant melanoma.

    Science.gov (United States)

    Weshler, Z; Sulkes, A; Kopolovitch, J; Leviatan, A; Shifrin, E

    1980-01-01

    We describe a case of malignant melanoma presenting initially as an endobronchial lesion located in the left main bronchus causing total atelectasis. This resolved with radiation therapy. Widespread metastases developed shortly thereafter. The differential diagnosis of primary and metastatic bronchial malignant melanoma is discussed. Other isolated case reports are reviewed.

  6. Melanoma do aparelho ungueal Nail apparatus melanoma

    Directory of Open Access Journals (Sweden)

    Ignez Regina dos Santos Muri Mendonça

    2004-10-01

    Full Text Available O melanoma do aparelho ungueal é apresentação relativamente rara dessa neoplasia, muitas vezes diagnosticada como nevo juncional, hematoma subungueal ou mesmo onicomicose. Esse fato leva a um atraso no diagnóstico e, conseqüentemente, na instituição da terapêutica específica, contribuindo para agravar o prognóstico de uma doença que por si só já é muito agressiva. Os autores relatam um caso de melanoma no primeiro quirodáctilo esquerdo de uma paciente negra com evolução de um ano, ressaltando a importância de avaliar certos critérios clínicos para obter o diagnóstico em fases mais precoces da doença.Nail apparatus melanoma is a rare presentation of melanoma and may be misdiagnosed as junctional nevus, subungual hematoma or onychomycosis. This fact often leads initially to inappropriate treatment and significant delays in appropriately managing such an aggressive disease. The authors report a case of melanoma on the left thumb of a black patient evolving for a year. Emphasis was placed on the importance of assessing certain clinical characteristics in order to reach an early diagnosis.

  7. 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...

  8. Cutaneous manifestations associated with melanoma.

    Science.gov (United States)

    Vyas, Ritva; Selph, Jacqueline; Gerstenblith, Meg R

    2016-06-01

    Melanoma is a malignancy most commonly arising from the skin; therefore, primary melanoma characteristics are usually the first cutaneous manifestations of melanoma. Cutaneous metastases, which can occur locally or diffusely, are important to detect in a timely manner as treatments for advanced melanoma that impact survival are now available. Melanoma can be associated with local or diffuse pigmentation changes, including depigmentation associated with the leukodermas and hyperpigmentation associated with diffuse melanosis cutis. The leukodermas occur frequently, illustrate the immunogenic nature of melanoma, and may impact prognosis. Paraneoplastic syndromes in association with melanoma are rare, though can occur. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Management of Melanoma Families

    Directory of Open Access Journals (Sweden)

    Wilma Bergman

    2010-04-01

    Full Text Available In this review we have aimed to focus on the clinical management of familial melanoma patients and their relatives. Along this line three major topics will be discussed: (1 management/screening of familial melanoma families: what is advised and what is the evidence thereof; (2 variability of families worldwide with regard to clinical phenotype, including cancer spectrum and likelihood of finding germline mutations and (3 background information for clinicians on the molecular biology of familial melanoma and recent developments in this field.

  10. Intravital Microscopy for Identifying Tumor Vessels in Patients With Stage IA-IV Melanoma That is Being Removed by Surgery

    Science.gov (United States)

    2017-06-05

    Recurrent Melanoma; Stage IA Skin Melanoma; Stage IB Skin Melanoma; Stage IIA Skin Melanoma; Stage IIB Skin Melanoma; Stage IIC Skin Melanoma; Stage IIIA Skin Melanoma; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma; Stage IV Skin Melanoma

  11. Ciliary body and choroidal melanomas treated by proton beam irradiation. Histopathologic study of eyes

    International Nuclear Information System (INIS)

    Seddon, J.M.; Gragoudas, E.S.; Albert, D.M.

    1983-01-01

    Proton beam irradiation resulted in clinical and/or histopathological regression of large ciliary body and choroidal melanomas in three eyes. Enucleations were performed 6 1/2 weeks, five months, and 11 months after irradiation for angle-closure glaucoma from total retinal detachment, increase in retinal detachment, and neovascular glaucoma, respectively. A direct relationship was found between the length of the interval from irradiation to enucleation and the degree of histologic changes. Vascular changes in the tumors included endothelial cell swelling and decreased lumen size, basement membrane thickening, collapse of sinusoidal vessels, and thrombosis of vessels. Although apparently unaltered tumor cells remained, degenerative changes occurred in some melanoma cells, including lipid vacuoles in cytoplasm, pyknotic nuclei, and balloon cell formation. Patchy areas of necrosis and proteinaceous exudate were present. Pigment-laden macrophages were found near tumor vessels and all had a substantial chronic inflammatory infiltrate. The effect of proton beam irradiation on tumor vessels probably plays an important role in uveal melanoma regression

  12. Ciliary body and choroidal melanomas treated by proton beam irradiation. Histopathologic study of eyes

    Energy Technology Data Exchange (ETDEWEB)

    Seddon, J.M.; Gragoudas, E.S.; Albert, D.M.

    1983-09-01

    Proton beam irradiation resulted in clinical and/or histopathological regression of large ciliary body and choroidal melanomas in three eyes. Enucleations were performed 6 1/2 weeks, five months, and 11 months after irradiation for angle-closure glaucoma from total retinal detachment, increase in retinal detachment, and neovascular glaucoma, respectively. A direct relationship was found between the length of the interval from irradiation to enucleation and the degree of histologic changes. Vascular changes in the tumors included endothelial cell swelling and decreased lumen size, basement membrane thickening, collapse of sinusoidal vessels, and thrombosis of vessels. Although apparently unaltered tumor cells remained, degenerative changes occurred in some melanoma cells, including lipid vacuoles in cytoplasm, pyknotic nuclei, and balloon cell formation. Patchy areas of necrosis and proteinaceous exudate were present. Pigment-laden macrophages were found near tumor vessels and all had a substantial chronic inflammatory infiltrate. The effect of proton beam irradiation on tumor vessels probably plays an important role in uveal melanoma regression.

  13. The Danish Melanoma Database

    DEFF Research Database (Denmark)

    Hölmich, Lisbet Rosenkrantz; Klausen, Siri; Spaun, Eva

    2016-01-01

    AIM OF DATABASE: The aim of the database is to monitor and improve the treatment and survival of melanoma patients. STUDY POPULATION: All Danish patients with cutaneous melanoma and in situ melanomas must be registered in the Danish Melanoma Database (DMD). In 2014, 2,525 patients with invasive......-node-metastasis stage. Information about the date of diagnosis, treatment, type of surgery, including safety margins, results of lymphoscintigraphy in patients for whom this was indicated (tumors > T1a), results of sentinel node biopsy, pathological evaluation hereof, and follow-up information, including recurrence......, nature, and treatment hereof is registered. In case of death, the cause and date are included. Currently, all data are entered manually; however, data catchment from the existing registries is planned to be included shortly. DESCRIPTIVE DATA: The DMD is an old research database, but new as a clinical...

  14. Primary leptomeningeal melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Aichner, F.; Schuler, G.

    1982-11-01

    A case of primary leptomeningeal melanoma is presented in which the diagnosis was made by ultrastructural demonstration of melanoma cells from the cerebrospinal fluid (CSF) at a time when cranial computed tomography (CT) still gave negative results. Later CT examinations documented the emergence of a tumor mass of the left temporoparietal lobe. This case clearly illustrates the complementary role of these investigational procedures for the diagnosis of cerebrospinal melanoma: leptomeningeal involvement, characterized by two-dimensional diffuse spread of melanoma tissue (''leptomeningeal melanomatosis''), is invisible with CT, but easily recognisable by CSF cytology; in contrast, nodular parenchymal tumor deposits can be readily detected by CT. Identification of pigmented cells recovered from the CSF requires ultrastructural confirmation.

  15. Distribution of CD163-positive cell and MHC class II-positive cell in the normal equine uveal tract.

    Science.gov (United States)

    Sano, Yuto; Matsuda, Kazuya; Okamoto, Minoru; Takehana, Kazushige; Hirayama, Kazuko; Taniyama, Hiroyuki

    2016-02-01

    Antigen-presenting cells (APCs) in the uveal tract participate in ocular immunity including immune homeostasis and the pathogenesis of uveitis. In horses, although uveitis is the most common ocular disorder, little is known about ocular immunity, such as the distribution of APCs. In this study, we investigated the distribution of CD163-positive and MHC II-positive cells in the normal equine uveal tract using an immunofluorescence technique. Eleven eyes from 10 Thoroughbred horses aged 1 to 24 years old were used. Indirect immunofluorescence was performed using the primary antibodies CD163, MHC class II (MHC II) and CD20. To demonstrate the site of their greatest distribution, positive cells were manually counted in 3 different parts of the uveal tract (ciliary body, iris and choroid), and their average number was assessed by statistical analysis. The distribution of pleomorphic CD163- and MHC II-expressed cells was detected throughout the equine uveal tract, but no CD20-expressed cells were detected. The statistical analysis demonstrated the distribution of CD163- and MHC II-positive cells focusing on the ciliary body. These results demonstrated that the ciliary body is the largest site of their distribution in the normal equine uveal tract, and the ciliary body is considered to play important roles in uveal and/or ocular immune homeostasis. The data provided in this study will help further understanding of equine ocular immunity in the normal state and might be beneficial for understanding of mechanisms of ocular disorders, such as equine uveitis.

  16. Primary Anorectal Melanoma: An Update

    Directory of Open Access Journals (Sweden)

    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.

  17. Genetics of Melanoma

    Directory of Open Access Journals (Sweden)

    Janet eWangari-Talbot

    2013-01-01

    Full Text Available Genomic variation is a trend observed in various human diseases including cancer. Genetic studies have set out to understand how and why these variations result in cancer, why some populations are predisposed to the disease, and also how genetics affect drug responses. The melanoma incidence has been increasing at an alarming rate worldwide. The burden posed by melanoma has made it a necessity to understand the fundamental signaling pathways involved in this deadly disease. Signaling cascades such as MAPK and PI3K/AKT have been shown to be crucial in the regulation of processes that are commonly dysregulated during cancer development such as aberrant proliferation, loss of cell cycle control, impaired apoptosis and altered drug metabolism. Understanding how these and other oncogenic pathways are regulated has been integral in our challenge to develop potent anti-melanoma drugs. With advances in technology and especially in next generation sequencing, we have been able to explore melanoma genomes and exomes leading to the identification of previously unknown genes with functions in melanomagenesis such as GRIN2A and PREX2. The therapeutic potential of these novel candidate genes is actively being pursued with some presenting as druggable targets while others serve as indicators of therapeutic responses. In addition, the analysis of the mutational signatures of melanoma tumors continues to cement the causative role of UV exposure in melanoma pathogenesis. It has become distinctly clear that melanomas from sun exposed skin areas have distinct mutational signatures including C to T transitions indicative of UV-induced damage. It is thus necessary to continue spreading awareness on how to decrease the risk factors of developing the disease while at the same time working for a cure. Given the large amount of information gained from these sequencing studies, it is likely that in the future, treatment of melanoma will follow a highly personalized route

  18. Perforating metastatic melanoma

    Directory of Open Access Journals (Sweden)

    Takenobu Ohashi

    2015-01-01

    Full Text Available We describe a case of metastatic malignant melanoma on the thigh with comedo-like appearance, which histologically showed elimination of tumor cells. A 70 year-old man was diagnosed with a nodular type malignant melanoma involving the lower back with satellite lesions (stage IIIB, T4b N2c M0, Breslow’s tumor thickness; 10.3 mm, Clark’s level; IV.

  19. Disseminated malignant melanoma

    Directory of Open Access Journals (Sweden)

    Verma Kaushal

    1999-01-01

    Full Text Available A 25-year-old man had multiple asymptomatic, nodular lesions on the trunk, extremities and the face for 3 months. He also had left facial palsy with severe headache and vomiting. There were no other systemic or constitutional symptoms. Skin biopsy from a nodular lesion showed features of malignant melanoma, confirmed by Fontana Masson and S-100 protein staining. A diagnosis of disseminated malignant melanoma was made and the patient was treated symptomatically. The patient died in 4 months.

  20. Radioimmunoscintigraphy in ocular melanoma

    International Nuclear Information System (INIS)

    Kovacs, J.; Chatterton, B.E.; Muecke, J.; Penglis, S.

    1999-01-01

    Full text: Malignant choroidal melanoma is one of the most common primary intraocular neoplasms. Despite significant advances in indirect ophthalmology, ultrasound, computed tomography (CT), magnetic resonance imaging (MRI) and fluoroescein angiography, choroidal melanomas may be difficult to distinguish from other malignant and non-malignant eye lesions. Radioimmunoscintigraphy (RIS) with 99 Tc m -labelled monoclonal antibody F(ab')2 fragments was performed on three patients (2 females, 1 male) who were suspected of having a choroidal melanoma. Patients were injected with 240-420 MBq Technemab-K-1 and scanned 6 and 22 h post-injection. Both planar and single photon emission tomographic (SPET) imaging were performed. RIS was faintly positive in one patient in whom the diagnosis of choroidal melanoma was confirmed by enucleation of the left eye. In the other two patients, immunoscintigraphy was negative. One patient had a benign choroidal haemangioma and the other an amelanotic melanoma. This was confirmed on clinical follow-up. These preliminary results indicate that this procedure may have utility for choroidal melanoma

  1. Oculocardiac reflex in a dog caused by a choroidal melanoma with orbital extension.

    Science.gov (United States)

    Steinmetz, Andrea; Ellenberger, Kristin; März, Imke; Ludewig, Eberhard; Oechtering, Gerhard

    2012-01-01

    A 7 yr old mixed-breed dog was presented with a choroidal melanoma of the left eye that had penetrated the sclera, producing an orbital mass. Bradycardia was detected on auscultation. The bradycardia resolved after exenteration of the orbit and was therefore presumed to be associated with the oculocardiac reflex.

  2. The Danish Melanoma Database

    Directory of Open Access Journals (Sweden)

    Hölmich Lr

    2016-10-01

    Full Text Available Lisbet Rosenkrantz Hölmich,1 Siri Klausen,2 Eva Spaun,3 Grethe Schmidt,4 Dorte Gad,5 Inge Marie Svane,6,7 Henrik Schmidt,8 Henrik Frank Lorentzen,9 Else Helene Ibfelt10 1Department of Plastic Surgery, 2Department of Pathology, Herlev-Gentofte Hospital, University of Copenhagen, Herlev, 3Institute of Pathology, Aarhus University Hospital, Aarhus, 4Department of Plastic and Reconstructive Surgery, Breast Surgery and Burns, Rigshospitalet – Glostrup, University of Copenhagen, Copenhagen, 5Department of Plastic Surgery, Odense University Hospital, Odense, 6Center for Cancer Immune Therapy, Department of Hematology, 7Department of Oncology, Herlev-Gentofte Hospital, University of Copenhagen, Herlev, 8Department of Oncology, 9Department of Dermatology, Aarhus University Hospital, Aarhus, 10Registry Support Centre (East – Epidemiology and Biostatistics, Research Centre for Prevention and Health, Glostrup – Rigshospitalet, University of Copenhagen, Glostrup, Denmark Aim of database: The aim of the database is to monitor and improve the treatment and survival of melanoma patients.Study population: All Danish patients with cutaneous melanoma and in situ melanomas must be registered in the Danish Melanoma Database (DMD. In 2014, 2,525 patients with invasive melanoma and 780 with in situ tumors were registered. The coverage is currently 93% compared with the Danish Pathology Register.Main variables: The main variables include demographic, clinical, and pathological characteristics, including Breslow’s tumor thickness, ± ulceration, mitoses, and tumor–node–metastasis stage. Information about the date of diagnosis, treatment, type of surgery, including safety margins, results of lymphoscintigraphy in patients for whom this was indicated (tumors > T1a, results of sentinel node biopsy, pathological evaluation hereof, and follow-up information, including recurrence, nature, and treatment hereof is registered. In case of death, the cause and date

  3. Treatment Options by Stage (Melanoma)

    Science.gov (United States)

    ... Reporting & Auditing Grant Transfer Grant Closeout Contracts & Small Business Training Cancer Training at NCI (Intramural) Funding for ... the skin far away from where it first started. Recurrent Melanoma Recurrent melanoma is cancer that has ...

  4. Intracerebral metastases from ocular melanoma.

    OpenAIRE

    Jones, D. R.; Scobie, I. N.; Sarkies, N. J.

    1988-01-01

    A blind painful eye may harbour an unsuspected malignant melanoma. We report a case of ocular melanoma that presented with confusion owing to direct extension via the optic nerve into the anterior cranial fossa.

  5. 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

  6. 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.

  7. Leptospirosis in a dog with uveitis and presumed cholecystitis.

    Science.gov (United States)

    Gallagher, Alexander

    2011-01-01

    A 7 yr old castrated male Australian shepherd dog was examined for acute change in iris color, lethargy, and anorexia. Uveitis, acute renal failure, and presumed cholecystitis were diagnosed. Based on clinical findings, leptosporosis was suspected, and the dog was treated with antibiotics and supportive care. The dog made a complete recovery, and leptospirosis was confirmed on convalescent titers. Due to the zoonotic potential, leptospirosis should be considered in cases of uveitis, as well as possible cholecystitis.

  8. Presumed Group B Streptococcal Meningitis After Epidural Blood Patch.

    Science.gov (United States)

    Beilin, Yaakov; Spitzer, Yelena

    2015-06-15

    Bacterial meningitis after epidural catheter placement is rare. We describe a case in which a parturient received labor epidural analgesia for vaginal delivery complicated by dural puncture. The patient developed postdural puncture headache and underwent 2 separate epidural blood patch procedures. She subsequently developed a headache with fever and focal neurologic deficits. She was treated with broad spectrum antibiotics for presumed meningitis, and she made a full recovery. Blood cultures subsequently grew group B streptococcus.

  9. ORAL AMELANOTIC MELANOMA FEATURE ARTICLE

    African Journals Online (AJOL)

    hard palate (more than 40%) and the gingiva2. Melanomas arise from the uninhibited proliferation ... Malignant melanomas of the mucosal regions of the head and neck are extremely rare neoplasms accounting for less than 1% of .... head and neck region reported that amelanotic melanomas had a 20% survival at 3 years, ...

  10. Uveal effusion syndrome: a new hypothesis concerning pathogenesis and technique of surgical treatment.

    Science.gov (United States)

    Gass, J D

    1983-01-01

    It is hypothesized that the primary underlying cause of the idiopathic uveal effusion syndrome is a congenital anomaly of the sclera, and in some cases, the vortex veins. Superimposed aging and hormonal changes in the sclera and its emissary channels impair its permeability to protein and predispose the eye to vortex vein obstruction. The inability of the eye to transport extravascular protein across the abnormal sclera is probably the cause of prolonged exudative detachment of the uvea and retina in these patients. Partial thickness sclerectomies and sclerostomies without choroidal puncture in each quadrant near the equator caused prompt resolution of long-standing uveal and bullous retinal detachment in two eyes. Images FIGURE 1 A FIGURE 1 B FIGURE 1 C FIGURE 3 A FIGURE 3 B PMID:6676971

  11. Bilateral Diffuse Uveal Melanocytic Proliferation: Molecular Genetic Analysis of a Case and Review of the Literature

    Science.gov (United States)

    Mittal, Ruchi; Cherepanoff, Svetlana; Thornton, Sophie; Kalirai, Helen; Damato, Bertil; Coupland, Sarah E.

    2015-01-01

    Purpose of the Study To describe the clinicopathological features, mutational and chromosomal copy number analysis, and 8-year follow-up of a case of bilateral diffuse uveal melanocytic proliferation (BDUMP) associated with clear-cell carcinoma of the endometrium. Methods Histological evaluation, multiplex ligation-dependent probe amplification (MLPA) analysis and GNAQ/11 mutational analysis were performed in a 67-year-old female patient with the diagnosis of BDUMP. Results Histological evaluation revealed proliferation of bland spindle cells, diffusely replacing the uveal tract, which showed a proliferation index of less than 1%. There was absence of mutations involving the codon 209 and 183 of GNAQ, and of GNA11. MLPA analysis showed disomy 3 with polysomy 8q for both eyes. The patient died 8 years later of an unrelated condition. Conclusions Although BDUMP is considered to be a benign proliferative disease, copy number alterations of unknown significance may occur in these lesions. PMID:27171825

  12. 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 212Pb/203 Pb radiolabeled melanoma targeting peptide DOTA-ReCCMSH. The radiolabeled alpha-melanocyte stimulating hormone (α-MSH) peptide analog DOTA-Re(Arg 11 )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 212 Pb labeled DOTA-Re(Arg 11 )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 212 Pb. 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.

  13. 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.

  14. Uveal effusion syndrome: a new hypothesis concerning pathogenesis and technique of surgical treatment.

    OpenAIRE

    Gass, J D

    1983-01-01

    It is hypothesized that the primary underlying cause of the idiopathic uveal effusion syndrome is a congenital anomaly of the sclera, and in some cases, the vortex veins. Superimposed aging and hormonal changes in the sclera and its emissary channels impair its permeability to protein and predispose the eye to vortex vein obstruction. The inability of the eye to transport extravascular protein across the abnormal sclera is probably the cause of prolonged exudative detachment of the uvea and r...

  15. Metástase de coróide simulando síndrome de efusão uveal: relato de caso Choroidal metastasis simulating uveal effusion syndrome: case report

    Directory of Open Access Journals (Sweden)

    Carlos Eduardo Cury Júnior

    2008-04-01

    Full Text Available Descrição de um caso de efusão uveal secundária a metástase de coróide e revisão dos principais diagnósticos diferenciais. Uma paciente com baixa da acuidade visual, no olho esquerdo, apresentou nódulos ao nível da coróide, dispersão pigmentar retiniana e descolamento seroso da retina. O exame angiofluoresceinográfico demonstrou padrão "leopard spots", semelhante ao encontrado nos casos de efusão uveal. A ecografia ocular demonstrou a presença do descolamento seroso da retina, presença de espessamento e nódulos na coróide e a tomografia de coerência óptica evidenciou ruptura do epitélio pigmentado da retina, presença de nodulações coroidianas hiperrefletivas e áreas de descolamento de retina seroso. Após ser submetido a exames diagnósticos de imagem, constatou-se a presença de nódulo único no ápice pulmonar esquerdo. As metástases de coróide podem levar a um quadro similar à síndrome de efusão uveal. Esta possibilidade deve sempre ser pensada diante de um quadro de efusão uveal atípica e avaliação sistêmica para pesquisa de carcinoma deverá ser solicitada.We report a case of choroidal metastasis simulating uveal effusion syndrome. This patient with uveal metastasis from lung carcinoma presented with decreased vision in the left eye. Fundoscopic examination revealed pigmentary clumping, multiple choroidal nodules and serous retinal detachment. Fluorescein angioraphy revealed a leopard spots pattern similar to uveal effusion syndrome. Ultrasound revealed the presence of choroidal nodules with moderate internal reflectivity, choroidal thickening and serous retinal detachment. Optical coherence tomography showed retinal pigment epithelium tear and hyper-reflective nodules within the choroid and areas of serous retinal detachment. Image investigation demonstrated the presence of a solitary pulmonary nodule at the left apical lung. Choroidal metastasis can lead to a scenario that simulates uveal effusion

  16. Chemoprevention of Melanoma

    Science.gov (United States)

    Madhunapantula, SubbaRao V.; Robertson, Gavin P.

    2013-01-01

    Despite advances in drug discovery programs and molecular approaches for identifying the drug targets, incidence and mortality rates due to melanoma continues to rise at an alarming rate. Existing preventive strategies generally involve mole screening followed by surgical removal of the benign nevi and abnormal moles. However, due to lack of effective programs for screening and disease recurrence after surgical resection there is a need for better chemopreventive agents. Although sunscreens have been used extensively for protecting from UV-induced skin cancer, results of correlative population based studies are controversial, requiring further authentication to conclusively confirm the chemoprotective efficacy of sunscreens. Certain studies suggest increased skin-cancer rates in sunscreen users. Therefore, effective chemopreventive agents for preventing melanoma are urgently required. This book-chapter, reviews the current understanding regarding melanoma chemoprevention and the various strategies used to accomplish this objective. PMID:22959032

  17. The Immunology of Melanoma.

    Science.gov (United States)

    Ko, Jennifer S

    2017-09-01

    The relatively high DNA mutational burden in melanoma allows for the creation of potentially "foreign," immune-stimulating neoantigens, and leads to its exceptional immunogenicity. Brisk tumor-infiltrating lymphocytes, a marker of immune editing, confer improved overall survival in melanoma, possibly due to reduced sentinel lymph node spread. Meanwhile, T-cell-stimulating drugs, so-called T-cell checkpoint inhibitors, which reverse peripheral tolerance-dependent tumor escape, have demonstrated unparalleled clinical success in metastatic melanoma. Markers to predict response to immunotherapy are currently imperfect, and the subject of intense research, which will guide the future of ancillary pathologic testing in this setting. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Angiogenesis and Melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Ribatti, Domenico, E-mail: ribatti@anatomia.uniba.it; Annese, Tiziana; Longo, Vito [Department of Human Anatomy and Histology, University of Bari Medical School, Piazza G. Cesare, 11, Policlinico 70124, Bari (Italy)

    2010-02-25

    Angiogenesis occurs in pathological conditions, such as tumors, where a specific critical point in tumor progression is the transition from the avascular to the vascular phase. Tumor angiogenesis depends mainly on the release by neoplastic cells of growth factors specific for endothelial cells, which are able to stimulate the growth of the host’s blood vessels. This article summarizes the literature concerning the relationship between angiogenesis and human melanoma progression. The recent applications of antiangiogenic agents which interfere with melanoma progression are also described.

  19. Confirmation of the presence of uveal effusion in Asian eyes with primary angle closure glaucoma: an ultrasound biomicroscopy study.

    Science.gov (United States)

    Kumar, Rajesh S; Quek, Desmond; Lee, Kelvin Y; Oen, Francis T; Sakai, Hiroshi; Koh, Victor T; Mohanram, Lakshmana S; Baskaran, Mani; Wong, Tina T; Aung, Tin

    2008-12-01

    To confirm the presence of uveal effusion in the eyes of Asian patients with primary angle closure glaucoma (PACG) using ultrasound biomicroscopy (UBM). In this observational case series, 70 patients with PACG (28 untreated patients with newly diagnosed PACG and 42 patients who had undergone previous laser iridotomy and were being monitored) and 12 patients with acute primary angle closure (APAC) were recruited. Eyes of patients with newly diagnosed PACG and APAC underwent UBM before and after laser iridotomy, whereas eyes of patients with treated PACG underwent UBM at enrollment. Uveal effusion was defined as a clear space between the choroid and sclera and was graded as follows: grade 0, none; grade 1, slitlike; grade 2, bandlike; and grade 3, obvious. Overall, uveal effusion was found in 11 of 70 eyes with PACG (15.7%; 95% confidence interval, 8.8%-26.2%) and in 3 of 12 eyes with APAC (25%; 95% confidence interval, 8.0%-53.4%). For patients with newly diagnosed PACG, uveal effusion was found in 4 of 28 eyes (14.2%; 95% confidence interval, 5.1%-32.1%) before laser iridotomy; 2 eyes had effusion after laser iridotomy. When present, the effusion was grade 1 in PACG eyes and grade 2 or 3 in APAC eyes. Uveal effusion was present in a significant proportion of Asian eyes with PACG and APAC, confirming a recent report of this finding.

  20. Visual Loss from Choroidal Melanoma Mimicking Neurological Syndromes

    Directory of Open Access Journals (Sweden)

    Karim Hammamji

    2017-03-01

    Full Text Available Melanoma of the eye is rare, but can mimic a range of disorders. This report highlights 2 cases of choroidal melanoma with vision loss mimicking neurological diagnoses. The first patient is a 41-year-old white male with a known history of multiple sclerosis and a previous episode of optic neuritis in the right eye, who presented with a 6-month history of decreased vision in the same eye, and occasional photopsiae. He was treated with 2 courses of oral steroids for presumed recurrent optic neuritis. After a temporary improvement in his symptoms, his vision worsened, following which he had a head MRI, which revealed a solid intraocular mass. He was subsequently diagnosed with a choroidal melanoma for which he was treated successfully with ruthenium-106 plaque brachytherapy. The second patient is a 57-year-old female, who presented with a progressive cerebellar syndrome under investigation by the neurology service, as well as decreased vision in the right eye. Her visual acuity gradually deteriorated and her neurological assessment, which included a PET-CT, revealed uptake in the right eye. The diagnosis of a choroidal melanoma was made, and following conservative treatment with proton beam radiotherapy, she had an enucleation of the eye. Intraocular tumours can masquerade as many different entities. Unexplained unilateral visual loss, especially if it is atypical for a neurological syndrome, should prompt dilated fundoscopy and referral to an ophthalmologist.

  1. Presumed consent for organ donation: is Romania prepared for it?

    Science.gov (United States)

    Grigoras, I; Condac, C; Cartes, C; Blaj, M; Florin, G

    2010-01-01

    In November 2007, a legislative initiative regarding the presumed consent for organ donation was proposed for parliamentary debate in Romania and was followed by public debate. The study aimed to asses public opinions expressed in the Romanian media. An Internet search was made. The pro and con reasons, the affiliation of parts involved in the debate and suggested future direction of action were identified. The Internet search had 8572 results. The parts involved in the pro and con debate consisted of governmental structures, physicians, ethicists, politicians, media, religious authorities, nongovernmental associations, and lay persons. The main pros were the low rate of organ donation and the long waiting lists, enhancement of organ procurement, avoidance of wasting valuable organs, avoiding responsibility, and the stress imposed to the family in giving the donation consent, humanitarian purposes (saving lives), going along with the scientific progress, and less bureaucracy. The main cons were an unethical issue, violation of human rights, denial of brain death, unethical advantage of public ignorance, unethical use of underprivileged people, little results in terms of organ procurement, but huge negative effects on public opinion, public mistrust in transplant programs and impossibility of refusal identification due to particularities of the Romanian medical system. The con opinions prevailed. For the moment, Romania seems to be unprepared to accept presumed consent. A future change in public perception regarding organ transplantation may modify the terms of a public debate.

  2. Melanoma Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing melanoma cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  3. Interleukin-6 and melanoma

    DEFF Research Database (Denmark)

    Hoejberg, Lise; Bastholt, Lars; Schmidt, Henrik

    2012-01-01

    Interleukin-6 (IL-6) is a pleiotropic immunomodulatory cytokine produced by various types of cells, including melanoma cells. IL-6 plays a major role in the pathogenesis and development of malignancies. It promotes tumour growth by inhibition of apoptosis and induces tumour angiogenesis. IL-6...

  4. Melanoma risk prediction models

    Directory of Open Access Journals (Sweden)

    Nikolić Jelena

    2014-01-01

    Full Text Available Background/Aim. The lack of effective therapy for advanced stages of melanoma emphasizes the importance of preventive measures and screenings of population at risk. Identifying individuals at high risk should allow targeted screenings and follow-up involving those who would benefit most. The aim of this study was to identify most significant factors for melanoma prediction in our population and to create prognostic models for identification and differentiation of individuals at risk. Methods. This case-control study included 697 participants (341 patients and 356 controls that underwent extensive interview and skin examination in order to check risk factors for melanoma. Pairwise univariate statistical comparison was used for the coarse selection of the most significant risk factors. These factors were fed into logistic regression (LR and alternating decision trees (ADT prognostic models that were assessed for their usefulness in identification of patients at risk to develop melanoma. Validation of the LR model was done by Hosmer and Lemeshow test, whereas the ADT was validated by 10-fold cross-validation. The achieved sensitivity, specificity, accuracy and AUC for both models were calculated. The melanoma risk score (MRS based on the outcome of the LR model was presented. Results. The LR model showed that the following risk factors were associated with melanoma: sunbeds (OR = 4.018; 95% CI 1.724- 9.366 for those that sometimes used sunbeds, solar damage of the skin (OR = 8.274; 95% CI 2.661-25.730 for those with severe solar damage, hair color (OR = 3.222; 95% CI 1.984-5.231 for light brown/blond hair, the number of common naevi (over 100 naevi had OR = 3.57; 95% CI 1.427-8.931, the number of dysplastic naevi (from 1 to 10 dysplastic naevi OR was 2.672; 95% CI 1.572-4.540; for more than 10 naevi OR was 6.487; 95%; CI 1.993-21.119, Fitzpatricks phototype and the presence of congenital naevi. Red hair, phototype I and large congenital naevi were

  5. RARE METASTASES OF MALIGNANT MELANOMA

    Directory of Open Access Journals (Sweden)

    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.

  6. 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.

  7. Conjunctival malignant melanoma in Denmark: epidemiology, treatment and prognosis with special emphasis on tumorigenesis and genetic profile.

    Science.gov (United States)

    Larsen, Ann-Cathrine

    2016-05-01

    Conjunctival malignant melanoma is a rare disease associated with considerable mortality. Most published data have been based on case reports or series of referred patients. In addition, very little is known about the genetic and epigenetic profile of conjunctival melanoma and the resemblance to uveal, cutaneous and mucosal melanoma. The aim was to determine the incidence rate of conjunctival melanoma, and to relate clinicopathological features and treatment to prognosis. A further aim was to determine the prevalence of BRAF mutations in conjunctival melanoma, to determine whether BRAF mutations are early events in pathogenesis, and relate clinicopathological features and prognosis to BRAF-mutation status. Finally, we wanted to identify tumour-specific and prognostic microRNAs in conjunctival melanoma, and to compare these with the microRNA expression of other melanoma subtypes. In order to investigate these rare tumours, we studied all the conjunctival melanomas that had been surgically removed in Denmark over a period of 52 years (1960-2012). Tissue samples, clinical files, pathology reports and follow-up data were collected and re-evaluated. Using droplet digital polymerase chain reaction and immunohistochemistry, we investigated BRAF mutations; and using microRNA expression profiling, we investigated differentially expressed microRNAs. The overall incidence of conjunctival melanoma was 0.5/1 000 000/year, and it increased in Denmark over 52 years. The increase was mainly caused by an increase in older patients (>65 years) and bulbar lesions. Clinicopathological features significantly associated with a poor prognosis were extrabulbar location, involvement of adjacent tissue structures, tumour thickness exceeding 2 mm and local tumour recurrence. Patients undergoing incisional biopsy and/or treatment involving excision without adjuvant therapy fared worse than patients treated with excision and any type of adjuvant treatment. We found that 35% (39/110) of

  8. Presumed symbolic use of diurnal raptors by Neanderthals.

    Directory of Open Access Journals (Sweden)

    Eugène Morin

    Full Text Available In Africa and western Eurasia, occurrences of burials and utilized ocher fragments during the late Middle and early Late Pleistocene are often considered evidence for the emergence of symbolically-mediated behavior. Perhaps less controversial for the study of human cognitive evolution are finds of marine shell beads and complex designs on organic and mineral artifacts in early modern human (EMH assemblages conservatively dated to ≈ 100-60 kilo-years (ka ago. Here we show that, in France, Neanderthals used skeletal parts of large diurnal raptors presumably for symbolic purposes at Combe-Grenal in a layer dated to marine isotope stage (MIS 5b (≈ 90 ka and at Les Fieux in stratigraphic units dated to the early/middle phase of MIS 3 (60-40 ka. The presence of similar objects in other Middle Paleolithic contexts in France and Italy suggest that raptors were used as means of symbolic expression by Neanderthals in these regions.

  9. Reactivation of presumed adenoviral keratitis after laser in situ keratomileusis.

    Science.gov (United States)

    Safak, Nilgün; Bilgihan, Kamil; Gürelik, Gökhan; Ozdek, Sengül; Hasanreisoğlu, Berati

    2002-04-01

    We report a patient with reactivation of presumed adenoviral keratoconjunctivitis after laser in situ keratomileusis (LASIK) to correct high myopia. The preoperative refraction was -13.00 diopters (D) in the right eye and -14.00 D in the left eye, and the best corrected visual acuity was 20/20 in both eyes. On the first postoperative day, mild conjunctival hyperemia and multiple subepithelial infiltrations localized in the flap zone consistent with adenoviral keratoconjunctivitis were seen. After prompt treatment, the lesions resolved. As a consequence, LASIK successfully corrected the high myopia. Adenoviral keratoconjunctivitis can be reactivated after LASIK, unlike after photorefractive keratectomy, despite the absence of symptomatic and clinical findings before the procedure.

  10. Presumed pseudobacteremia outbreak resulting from contamination of proportional disinfectant dispenser.

    Science.gov (United States)

    Siebor, E; Llanes, C; Lafon, I; Ogier-Desserrey, A; Duez, J M; Pechinot, A; Caillot, D; Grandjean, M; Sixt, N; Neuwirth, C

    2007-03-01

    Reported here are the microbiological and epidemiological details of a presumed outbreak of aerobic gram-negative bacilli infections affecting 19 hematological patients, which was traced to contaminated disinfectant. Over a 5-month period, the following organisms were isolated from the blood cultures of 19 neutropenic patients: Pseudomonas fluorescens (n = 13), Achromobacter xylosoxidans (n = 12), Comamonas testosteroni (n = 2) or Stenotrophomonas maltophilia (n = 1). The affected patients were all treated with an expensive regimen of broad-spectrum antibiotic therapy. The same bacteria were recovered from environmental samples as well as from the water pipes of an apparatus for dispensing disinfectant (didecyldimethylammonium chloride). Genotyping results indicated that many of the clinical strains were identical to strains isolated from the apparatus. It was eventually discovered that the night staff was in the habit of disinfecting the blood-culture bottles before use, thereby contaminating the bottles with bacteria contained in the disinfectant. Contamination of the apparatus resulted from faulty maintenance.

  11. The spectrum of presumed tubercular uveitis in Tunisia, North Africa.

    Science.gov (United States)

    Khochtali, Sana; Gargouri, Salma; Abroug, Nesrine; Ksiaa, Imen; Attia, Sonia; Sellami, Dorra; Feki, Jamel; Khairallah, Moncef

    2015-10-01

    The purpose of this study was to analyze the spectrum of presumed tubercular uveitis in Tunisia, North Africa. We retrospectively reviewed the clinical records of 38 patients (65 eyes) diagnosed with presumed tubercular uveitis at two referral centers in Tunisia, between January 2009 and December 2011. Mean age at presentation was 42.7 years. Twenty-four patients were women (63.2%) and 14 (36.8%) were men. Twenty-three eyes (35.4%) had posterior uveitis, 21 eyes (32.3%) had intermediate uveitis, 13 eyes (20%) had panuveitis, and 8 eyes (12.3%) had anterior uveitis. Ocular findings included vitritis in 67.7% of eyes, posterior synechiae in 47.7%, multifocal non-serpiginoid choroiditis in 23.1%, multifocal serpiginoid choroiditis in 21.5%, periphlebitis in 21.5%, and mutton-fat keratic precipitates in 20%. Anti-tubercular treatment was prescribed in 33 patients (86.8%) and was associated with systemic corticosteroids in 20 patients (52.6%) and periocular injections of corticosteroids in four patients (10.5%). After a mean follow-up of 14.2 months (range, 10-58), inflammation was controlled, with a significant improvement in visual acuity (VA) (p = 0.028). However, recurrences developed in two patients (5.3%). Final VA was better than 20/40 in 27 eyes (41.5%) and less than 20/200 in five eyes (7.7%). In Tunisia, all anatomic types are possible in tuberculosis-associated uveitis, but posterior and intermediate uveitis are more frequent. Vitritis, posterior synechiae, multifocal serpiginoid or non-serpiginoid choroiditis, and periphlebitis are the most common manifestations.

  12. Metastatic ocular melanoma to the liver exhibits infiltrative and nodular growth patterns.

    Science.gov (United States)

    Grossniklaus, Hans E; Zhang, Qing; You, Shuo; McCarthy, Conni; Heegaard, Steffen; Coupland, Sarah E

    2016-11-01

    We examined liver specimens from 15 patients with uveal melanoma (UM) who had died of their disseminated disease. We found 2 distinct growth patterns of UM metastasis: infiltrative (n = 12) and nodular (n = 3). In the infiltrative pattern, individual UM cells with a CD133+ cancer stem cell-like phenotype were present and formed aggregates of stage I 500μm-diameter metastases, which were encapsulated by collagenized fibrous septae. In the nodular growth pattern, CD133+ melanoma cells aggregated adjacent to portal venules and subsequently appeared to grow and efface the adjacent hepatocytes to form stage II 51- to 500-μm-diameter nodules that surrounded the portal venule. These avascular nodules appeared to further expand to form stage III >500-μm-diameter nodules that exhibited vascularization with minimal fibrosis. The tumor stem cell-like phenotype seen in individual UM cells was lost as the tumors progressed. There were CD56+ natural killer cells in sinusoidal spaces and CD3+ lymphocytes in periportal areas. The nodular growth pattern showed UM cells expressing MMP9 and VEGF. UM cells in both above-described growth patterns exhibited variable BAP1 expression. We propose that changes in the liver microenvironment are related to metastatic UM growth. We hypothesize that these changes include immune regulation within the sinusoidal space for the infiltrative pattern and changes in the VEGF/PEDF ratio for the nodular pattern. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Ciliary body melanoma with limited nodular extrascleral extension and diffuse iris-angle infiltration treated by whole anterior segment plaque radiotherapy.

    Science.gov (United States)

    Gray, Michael E; Corrêa, Zélia M; Augsburger, James J; Barrett, William

    2007-08-01

    Primary uveal malignant melanoma of the ciliary body associated with nodular extrascleral extension, diffuse iris-angle infiltration, and secondary glaucoma is usually treated by prompt enucleation. We report a patient with ciliary body melanoma associated with nodular extrascleral extension and diffuse infiltration of the iris and angle treated conservatively because the fellow eye was blind. The clinical features and surgical management of a melanoma of the ciliary body with extrascleral extension and diffuse infiltration of the iris and angle are presented. The tumor was treated with focal I-125 plaque radiotherapy followed by supplemental whole anterior segment I-125 plaque radiotherapy. The patient has been followed for over 2.5 years since the initial plaque radiotherapy and over 1.5 years since the supplemental whole anterior segment radiotherapy. His visual acuity is correctable to 20/40 OD and there is no evidence of metastatic disease. His glaucoma is well controlled following trabeculectomy and tube shunt procedure. Whole anterior segment plaque radiotherapy for ciliary body melanoma with diffuse iris-angle infiltration provided palliative local tumor control without significant local complications through available follow-up.

  14. Melanoma Epidemiology and Public Health

    Science.gov (United States)

    Berwick, Marianne; Erdei, Esther; Hay, Jennifer

    2013-01-01

    Melanoma has presented a conundrum to physicians and prevention researchers. We should be able to reduce incidence and mortality rather easily because evolving melanoma lesions are observable on the surface of the skin. However, melanoma has not proved tractable. The incidence and mortality have risen in all developed countries during the past 50 years. However, mortality appears to be abating among younger cohorts even though the reason for this is not clear. PMID:19254665

  15. Melanoma and immunotherapy bridge 2015

    OpenAIRE

    Nanda, Vashisht G. Y.; Peng, Weiyi; Hwu, Patrick; Davies, Michael A.; Ciliberto, Gennaro; Fattore, Luigi; Malpicci, Debora; Aurisicchio, Luigi; Ascierto, Paolo Antonio; Croce, Carlo M.; Mancini, Rita; Spranger, Stefani; Gajewski, Thomas F.; Wang, Yangyang; Ferrone, Soldano

    2016-01-01

    Table of contents MELANOMA BRIDGE 2015 KEYNOTE SPEAKER PRESENTATIONS Molecular and immuno-advances K1 Immunologic and metabolic consequences of PI3K/AKT/mTOR activation in melanoma Vashisht G. Y. Nanda, Weiyi Peng, Patrick Hwu, Michael A. Davies K2 Non-mutational adaptive changes in melanoma cells exposed to BRAF and MEK inhibitors help the establishment of drug resistance Gennaro Ciliberto, Luigi Fattore, Debora Malpicci, Luigi Aurisicchio, Paolo Antonio Ascierto, Carlo M. Croce, Rita Mancin...

  16. Nodular amelanotic melanoma

    Directory of Open Access Journals (Sweden)

    Nalamwar Rashmi

    2010-01-01

    Full Text Available We report a case of 65-year-old male patient who presented with multiple erythematous papules coalescing to form a nodular mass over posterior aspect of right thigh of six months duration. His general and systemic examinations were within normal range except for right inguinal lymphadenopathy. Biopsy from the lesion was done, which showed diffuse infiltrate of nests of atypical melanocytes extending upto reticular dermis. Malignant cells were positive for S100 and human melanin black 45(HMB 45. Hence, a diagnosis of amelanotic melanoma (AM - Clarke level IV and TNM stage III was reached. MRI of involved leg showed fungating soft tissue mass in the posterolateral aspect of right thigh and metastatic right inguinal adenopathy. Fine needle aspiration cytology (FNAC from the right inguinal nodes confirmed metastasis of melanoma. The patient was referred to oncosurgery department for further management.

  17. Dermoscopy of difficult-to-diagnose Melanomas

    Directory of Open Access Journals (Sweden)

    Papageorgiou Chrysoula

    2016-09-01

    Full Text Available Dermoscopy is a non-invasive procedure that allows the evaluation of cutaneous lesions, and is considered to be a useful tool that improves the diagnostic accuracy of melanoma. Many dermoscopic criteria of melanoma have been established and several algorithms have been created for melanoma detection. However, the recognition of some melanomas remains challenging. Melanomas on specific body sites, melanomas in patients with multiple atypical moles, and nodular melanomas represent the most difficult-to-recognize melanoma subtypes, since they typically lack the “classic” melanoma-specific criteria. This paper provides an update on dermoscopy of difficult-to-diagnose melanomas by summarizing the newest data. Lastly, we highlight the importance of digital dermoscopy in the follow-up of melanocytic lesions for the detection of incipient melanomas while maintaining a low excision rate.

  18. Circulating melanoma cells and survival in metastatic melanoma

    NARCIS (Netherlands)

    Rao, C.; Bui, T.; Connelly, M.; Doyle, G.; Karydis, I.; Middleton, M. R.; Clack, G.; Malone, M.; Coumans, F. A. W.; Terstappen, L. W. M. M.

    2011-01-01

    A validated assay for the enumeration of circulating melanoma cells (CMCs) may facilitate the development of more effective therapies for metastatic melanoma patients. In this study CD146(+) cells were immunomagnetically enriched from 7.5 ml of blood. Isolated cells were fluorescently stained with

  19. Infectious endotheliitis: a rare case of presumed mycotic origin

    Science.gov (United States)

    Zapata, Luis Fernando; Paulo, José David; Restrepo, Carlos A; Velásquez, Luis Fernando; Montoya, Andrés E Toro; Zapata, Melissa A

    2013-01-01

    Purpose To report an interesting case of infectious endotheliitis of presumed mycotic origin. Methods A case report of a 56-year-old male farmer who sought medical attention after a month-long evolution of irritative symptoms in his right eye, accompanied by visual acuity (VA) impairment. The patient received topical and oral broad-spectrum antibiotic treatment with no improvement before being referred to a cornea specialist, where he was found to have VA of 20/150 and was noted on biomicroscopy to have endothelial feathery coalescent lesions. The patient was admitted to the hospital for an aqueous humor sample and intravenous voriconazole. Results The microbiological studies did not isolate any micro-organisms. However, clinical evidence of improvement was confirmed after 5 days of antimycotic intravenous therapy. Complete clinical resolution was achieved at 1 month after treatment completion with oral voriconazole, as evidenced by VA of 20/20 and disappearance of endothelial lesions. Conclusion Endothelial involvement by fungi is a rare condition. In this case, no microbes were isolated, but the characteristic morphology of the lesions, the history of onychomycosis, and the spectacular response to voriconazole turn this case into a valid presumptive diagnosis. PMID:23901253

  20. Outbreak of keratitis presumed to be caused by Acanthamoeba.

    Science.gov (United States)

    Mathers, W D; Sutphin, J E; Folberg, R; Meier, P A; Wenzel, R P; Elgin, R G

    1996-02-01

    A sharp increase of Acanthamoeba keratitis from two cases per year to 30 cases per year at our institution prompted this study to determine whether there was a change in the clinical characteristics, basic epidemiology, and outcome of this disease. We reviewed all cases of Acanthamoeba keratitis diagnosed at the University of Iowa Hospitals and Clinics from mid-1993 through 1994. We screened 217 patients with keratitis by tandem scanning confocal microscopy and suspected Acanthamoeba in 51 patients. Diagnosis was confirmed by cytology in 43 patients (48 eyes). There were no positive cultures. Patients examined within four weeks of onset of symptoms were younger (mean age, 32.6 +/- 15.4 years) and wore contact lenses (11 of 18 patients), and infrequently herpes simplex keratitis (four of 18 patients) was diagnosed. Patients examined after four weeks were older (mean age, 54.0 +/- 19.5 years), infrequently wore contact lenses (six of 25 patients), and often had herpes simplex keratitis (12 of 25 patients). Corneal examination with tandem scanning confocal microscopy was associated with a marked increase in the detection of Acanthamoeba, strongly suggesting that the disease is more prevalent than suspected. Acanthamoeba may account for many cases of clinically presumed herpes simplex keratitis, the leading cause of corneal blindness in the United States. Acanthamoeba should be considered in the differential diagnosis of any unexplained keratitis, even those of short duration.

  1. 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.

  2. 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.

  3. NKT cells act through third party bone marrow-derived cells to suppress NK cell activity in the liver and exacerbate hepatic melanoma metastases.

    Science.gov (United States)

    Sadegh, Leila; Chen, Peter W; Brown, Joseph R; Han, Zhiqiang; Niederkorn, Jerry Y

    2015-09-01

    Uveal melanoma (UM) is the most common intraocular tumor in adults and liver metastasis is the leading cause of death in UM patients. We have previously shown that NKT cell-deficient mice develop significantly fewer liver metastases from intraocular melanomas than do wild-type (WT) mice. Here, we examine the interplay between liver NKT cells and NK cells in resistance to liver metastases from intraocular melanomas. NKT cell-deficient CD1d(-/-) mice and WT C57BL/6 mice treated with anti-CD1d antibody developed significantly fewer liver metastases than WT mice following either intraocular or intrasplenic injection of B16LS9 melanoma cells. The increased number of metastases in WT mice was associated with reduced liver NK cytotoxicity and decreased production of IFN-γ. However, liver NK cell-mediated cytotoxic activity was identical in non-tumor bearing NKT cell-deficient mice and WT mice, indicating that liver metastases were crucial for the suppression of liver NK cells. Depressed liver NK cytotoxicity in WT mice was associated with production of IL-10 by bone marrow-derived liver cells that were neither Kupffer cells nor myeloid-derived suppressor cells and by increased IL-10 receptor expression on liver NK cells. IL-10(-/-) mice had significantly fewer liver metastases than WT mice, but were not significantly different from NKT cell-deficient mice. Thus, development of melanoma liver metastases is associated with upregulation of IL-10 in the liver and an elevated expression of IL-10 receptor on liver NK cells. This impairment of liver NK activity is NKT cell-dependent and only occurs in hosts with melanoma liver metastases. © 2015 UICC.

  4. 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.

  5. Histopathological findings concerning ocular melanomas.

    Science.gov (United States)

    Costache, Mariana; Pătraşcu, Oana Maria; Dumitru, Adrian; Costache, Diana; Voinea, Liliana Mary; Simionescu, Olga; Sajin, Maria

    2014-01-01

    Ocular melanoma is rare in clinical practice. In this study, we present three cases of ocular melanoma surgically removed in the Department of Ophthalmology of the Emergency University Hospital of Bucharest, Romania, and diagnosed in the Department of Pathology of the same hospital using conventional histopathological techniques and immunohistochemical tests.

  6. Clinical characteristics and management of melanoma families

    NARCIS (Netherlands)

    Rhee, Jasper Immanuel van der

    2013-01-01

    Being a member of a melanoma family is a major risk factor for cutaneous malignant melanoma. In this thesis clinical characteristics and management of melanoma families are discussed. In the first part of the thesis clinical and histological characteristics of melanoma (patients) from families with

  7. Comparative Aspects of Canine Melanoma

    Directory of Open Access Journals (Sweden)

    Adriana Tomoko Nishiya

    2016-02-01

    Full Text Available Melanomas are malignant neoplasms originating from melanocytes. They occur in most animal species, but the dog is considered the best animal model for the disease. Melanomas in dogs are most frequently found in the buccal cavity, but the skin, eyes, and digits are other common locations for these neoplasms. The aim of this review is to report etiological, epidemiological, pathological, and molecular aspects of melanomas in dogs. Furthermore, the particular biological behaviors of these tumors in the different body locations are shown. Insights into the therapeutic approaches are described. Surgery, chemotherapy, radiotherapy, immunotherapy, and the outcomes after these treatments are presented. New therapeutic perspectives are also depicted. All efforts are geared toward better characterization and control of malignant melanomas in dogs, for the benefit of these companion animals, and also in an attempt to benefit the treatment of human melanomas.

  8. Infectious endotheliitis: a rare case of presumed mycotic origin

    Directory of Open Access Journals (Sweden)

    Zapata LF

    2013-07-01

    Full Text Available Luis Fernando Zapata,1 José David Paulo,1 Carlos A Restrepo,1 Luis Fernando Velásquez,2 Andrés E Toro Montoya,2 Melissa A Zapata21Department of Ophthalmology Hospital Pablo Tobón Uribe; 2School of Medicine, Universidad Pontificia Bolivariana, Medellín, ColombiaPurpose: To report an interesting case of infectious endotheliitis of presumed mycotic origin.Methods: A case report of a 56-year-old male farmer who sought medical attention after a month-long evolution of irritative symptoms in his right eye, accompanied by visual acuity (VA impairment. The patient received topical and oral broad-spectrum antibiotic treatment with no improvement before being referred to a cornea specialist, where he was found to have VA of 20/150 and was noted on biomicroscopy to have endothelial feathery coalescent lesions. The patient was admitted to the hospital for an aqueous humor sample and intravenous voriconazole.Results: The microbiological studies did not isolate any micro-organisms. However, clinical evidence of improvement was confirmed after 5 days of antimycotic intravenous therapy. Complete clinical resolution was achieved at 1 month after treatment completion with oral voriconazole, as evidenced by VA of 20/20 and disappearance of endothelial lesions.Conclusion: Endothelial involvement by fungi is a rare condition. In this case, no microbes were isolated, but the characteristic morphology of the lesions, the history of onychomycosis, and the spectacular response to voriconazole turn this case into a valid presumptive diagnosis.Keywords: endotheliitis, mycotic, keratitis, voriconazole

  9. Whole-body 18F FDG positron emission tomography/computed tomography evaluation of patients with uveal metastasis.

    Science.gov (United States)

    Patel, Payal; Finger, Paul T

    2012-04-01

    To investigate the value of whole-body positron emission tomography/computed tomography (PET/CT) as a screening tool for patients with uveal metastasis. Retrospective observational case series. setting: Clinical practice. study population: Eighteen patients with uveal metastatic tumors were evaluated. Patients had no history of malignancy or a past medical history of malignancy without known active metastasis or known systemic cancer. intervention: Whole-body PET/CT was used as a screening tool to evaluate the intraocular tumor, to evaluate for multi-organ metastatic disease, and for cancer staging. main outcome measures: Detection and PET/CT uptake of primary tumors and metastatic disease. PET/CT imaging uncovered previously occult primary nonocular cancers (11/18, 61%), revealed progression of known primary systemic cancer (7/18, 39%), and confirmed multi-organ metastases in all cases (18/18, 100%). PET/CT findings were used to direct nonocular, confirmatory biopsy in 67% of cases (12/18). No uveal biopsies were required. PET/CT revealed lymph nodes and bone as the most common metastatic sites. The intraocular tumor was detectable in 28% of cases. Small, non-avid tumors and those within the hypermetabolic, PET-avid brain were falsely negative. This study suggests that whole-body PET/CT can be useful for clinical evaluation of patients with uveal metastases. It allowed for screening of the entire body and directed extraocular biopsy. Commonly used for tumor staging, PET/CT aided in the detection of the primary cancer in patients with metastatic uveal tumors. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. The frequency of secondary glaucoma in patients with iridocorneal endothelial syndrome in correlation to the presence of uveal ectropion

    Directory of Open Access Journals (Sweden)

    Marković Vujica

    2017-01-01

    Full Text Available Introduction/Objective. Iridocorneal endothelial (ICE syndrome incudes 3 clinical forms: progressive iris atrophy, Chandler’s syndrome, and Cogan–Reese syndrome. It is characterized by various degrees of iris atrophy, corneal endothelial changes, uveal ectropion, corectopia, peripheral anterior synechiae (PAS and secondary glaucoma. The aim of the study was to illustrate forms of ICE syndrome, determine frequency of secondary glaucoma with emphasis on cases with uveal ectropion, analyze response to medicament treatment and the need for surgical treatment in intraocular pressure (IOP control. Methods. Patients underwent slit lamp examination, applanation tonometry, gonioscopy, ophthalmoscopy, Humphrey visual field testing and Heidelberg retina tomography. Patients were divided into two groups: group I, without uveal ectropion (22 patients and group II, with uveal ectropion (14 patients. Results. A total of 36 patients were examined in a 10-year period. The average age was 38 years, male to female ratio 1:2. Secondary glaucoma was confirmed in 26 (72.2% patients, out of which 12 (54.5% in group I and 14 (100% in group II. PAS were more frequent in group II. In group I, mean initial IOP was 37 mmHg, and after medicament treatment 26 mmHg. Secondary glaucoma was controlled in 50% and remaining 50% underwent surgical treatment. In group II, mean initial IOP was 49 mmHg, and after medicament treatment 32 mmHg. All 14 patients (100% underwent surgical treatment in order to achieve IOP control. Conclusion. ICE syndrome is a rare, progressive disease, with high incidence of secondary glaucoma, which is more frequent in cases with uveal ectropion. In these cases, medicament treatment is not effective and trabeculectomy with antimetabolite application is necessary.

  11. Interactive Tailored Website to Promote Sun Protection and Skin Self-Check Behaviors in Patients With Stage 0-III Melanoma

    Science.gov (United States)

    2017-11-15

    Stage 0 Skin Melanoma; Stage I Skin Melanoma; Stage IA Skin Melanoma; Stage IB Skin Melanoma; Stage II Skin Melanoma; Stage IIA Skin Melanoma; Stage IIB Skin Melanoma; Stage IIC Skin Melanoma; Stage III Skin Melanoma; Stage IIIA Skin Melanoma; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma

  12. Electrochemotherapy by pulsed electromagnetic field treatment (PEMF) in mouse melanoma B16F10 in vivo

    OpenAIRE

    Kranjc Simona; Kranjc Matej; Scancar Janez; Jelenc Jure; Sersa Gregor; Miklavcic Damijan

    2016-01-01

    Introduction Pulsed electromagnetic field (PEMF) induces pulsed electric field, which presumably increases membrane permeabilization of the exposed cells, similar to the conventional electroporation. Thus, contactless PEMF could represent a promising approach for drug delivery. Materials and methods Noninvasive electroporation was performed by magnetic field pulse generator connected to an applicator consisting of round coil. Subcutaneous mouse B16F10 melanoma tumors were treated with intrave...

  13. Histological Types of Polypoid Cutaneous Melanoma II

    OpenAIRE

    Knežević, Fabijan; Duančić, Vjekoslav; Šitić, Sanda; Horvat-Knežević, Anica; Benković, Vesna; Ramić, Snježana; Kostović, Krešimir; Ramljak, Vesna; Velemir Vrdoljak, Danko; Stanec, Mladen; Božović, Angelina

    2007-01-01

    The aim of this study was to ascertain which histological types of melanoma can clinically and morphologically appear as polypoid melanomas. In 645 cases of primary cutaneous melanoma we have analyzed criteria for diagnosis of polypoid cutaneous melanoma and afterwards we have analyzed growth phase in each polypoid melanoma, histological type of atypical melanocytes, the number of epidermal ridges which are occupied by atypical melanocytes, and distribution according to age, sex a...

  14. Brachytherapy of choroidal melanomas

    International Nuclear Information System (INIS)

    Brady, L.W.; Hernandez, J.C.

    1992-01-01

    In a compilation of nine reported series consisting of 2,024 enucleations, the five- and ten-year survivals following surgery were 63% and 43%, respectively. The 25-year survival has been reported to be 40%. In 1974 at Wills Eye Hospital and Hahnemann University, the cobalt-60 plaques technique was introduced. During the following years, other radioactive isotopes were introduced including irridium-192, iodine-125, ruthenium-106/rhodium-106 and more recently palladium-103. At the present time, iodine-125 is the most widely used radionuclide. Until now, 302 patients treated with plaque brachytherapy showed an actuarial survival of 77% and 67.8% at five and eight years, respectively. There was no significant survival difference when compared with a similar group of patients undergoing enucleation. Other retrospective studies show similar excellent results. In spite of these convincing results, the decision making process in management melanoma remains unsettled primarily due to the absence of prospective randomized trials. Because of this, the Collaborative Ocular Melanoma Study was initiated. From the standpoint of toxicity, the data are available on ocular radiation toxicity. In an analysis of 77 patients from the Wills Eye Hospital with pretreatment visual acuities of 20/25 or better, it was noted that 90% of patients who had received less than 500 Gy to the fovea retained visual acuity of 20/200 or better while only 52% of patients receiving more than 5,000 Gy to the fovea had vision of 20/200 or better. A serious late effect of radioactivity plaque treatment is scleral necrosis which may require repair or enucleation even in the absence of tumor progression. Enucleation may be necessary in approximately 10% of patients. We conclude that malignant melanoma of the uvea can be safely treated with radioactive plaques. (orig./MG) [de

  15. Preventing Melanoma PSA (:60)

    Centers for Disease Control (CDC) Podcasts

    2015-06-02

    This 60 second public service announcement is based on the June 2015 CDC Vital Signs report. Skin cancer is the most common form of cancer in the U.S. In 2011, there were more than 65,000 cases of melanoma, the most deadly form of skin cancer. Learn how everyone can help prevent skin cancer.  Created: 6/2/2015 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 6/2/2015.

  16. Dermoscopy of melanoma and non-melanoma skin cancer.

    Science.gov (United States)

    Babino, G; Lallas, A; Longo, C; Moscarella, E; Alfano, R; Argenziano, G

    2015-10-01

    Skin cancer is a major health problem because of its high incidence in white populations, as well as its related potential morbidity and mortality. Dermoscopy is a noninvasive tool that allows the identification of specific morphological features in different skin tumors, improving significantly the early diagnosis of melanoma and non-melanoma skin cancer (NMSC). This tool has also gained increased interest in the management of NMSC therapy and in the post-treatment follow-up. In this article, we provide a review of the dermoscopic patterns and criteria for the diagnosis of melanoma and NMSC described until now in the literature.

  17. Prognostic biopsy of choroidal melanoma: an optimised surgical and laboratory approach.

    Science.gov (United States)

    Angi, Martina; Kalirai, Helen; Taktak, Azzam; Hussain, Rumana; Groenewald, Carl; Damato, Bertil E; Heimann, Heinrich; Coupland, Sarah E

    2017-08-01

    Accurate survival prognostication for patients with uveal melanoma (UM) enables effective patient counselling and permits personalised systemic surveillance for the early detection of metastases and, in high-risk patients, enrolment in any trials of systemic adjuvant therapy. The aim of this work is to determine the success of prognostic UM tumour biopsy using an improved surgical approach and optimised sample handling workflow. Patients with UM treated by primary radiotherapy between 2011 and 2013 and who underwent a prognostic biopsy with cytology, multiplex ligation-dependent probe amplification and/or microsatellite analysis were included. The main outcomes and measures were success of cytology and genetic studies, and surgical complications. The cohort comprised 232 patients with UM having a median age of 59 years (range, 25-82) at treatment. The median largest basal diameter was 11.4 mm (range, 4.1-20.8) and tumour height was 3.4 mm (range, 0.7-10.3). Ciliary body involvement was noted in 42 cases. Treatment consisted of Ru-106 brachytherapy in 151 cases (65%) and proton beam radiotherapy in 81 cases (35%). With improvements in surgical techniques and laboratory methods over time, cytology success increased from 92% (131/142) to 99% (89/90) and the numbers of samples with sufficient DNA for genetic testing increased from 79% (104/131) to 93% (83/89). Overall, chromosome 3 loss was noted in 64/187 (34%) cases. Surgical complications, including transient localised bleeding, vitreous haemorrhage and retinal perforation, decreased over time. Eight patients required additional surgery. Improved surgical techniques and laboratory methods yielded successful cytology and genetic information in the majority of cases. Analysis of data from 232 patients with uveal melanoma undergoing prognostic tumour biopsy demonstrated that improved surgical techniques and laboratory methods yielded successful cytology and genetic information in 99% and 89% of cases, respectively

  18. 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.

  19. Superficial melanomas of oral mucous membranes.

    Science.gov (United States)

    Regezi, J A; Hayward, J R; Pickens, T N

    1978-05-01

    In accordance with microscopic and clinical criteria established for superficial melanomas of the skin (superficial spreading melanoma, lentigo maligna melanoma, acral-lentiginous melanoma), three oral lesions have been evaluated. The literature on oral melanomas has also been reviewed, with special attention given to those cases that had pre-existing melanosis. One patient with a diagnosis of superficial spreading melanoma eventually died of his untreated lesion 11 years after its first appearance. Two patients had lesions diagnosed as acral-lentiginous melanoma (a group which also includes volar and subungual melanomas) that exhibited aggressive, recurrent behavior. These lesions had microsocpic features similar to lentigo maligna melanoma but did not behave in a manner consistent with that diagnosis. Electron microscopic study of one acral-lentiginous melanoma demonstrated malenosomes and premelanosomes that were like those seen in normal melanocytes and nevus cells. The superficial or radial growth phase of many oral melanomas has apparently gone unrecognized. Melanosis has been reported to be a common feature of invasive oral melanomas but has not generally been related to the natural history of these lesions. Oral lesions with a prolonged intra-epithelial or radial growth phase would be expected to have a better prognosis than nodular melanomas, but meaningful survival data are not available because of the infrequency with which oral melanomas have been subclassified.

  20. Primary dermal melanoma: a West Australian cohort.

    Science.gov (United States)

    Teow, James; Chin, Olivia; Hanikeri, Mark; Wood, Benjamin A

    2015-09-01

    The objectives of this study were to identify a subgroup of patients with putative primary dermal melanoma after thorough multidisciplinary clinical and histological evaluation, and to describe the clinical, histological and selected molecular features of these lesions. The records of the Western Australian Melanoma Advisory Service were searched for potential cases of primary dermal melanoma. The clinical and histological features were reviewed, immunohistochemical assessment was performed and clinical outcomes recorded. Eighteen cases of putative primary dermal melanoma with available clinical data were identified. Two of 12 cases in which further histological sections could be obtained were excluded because of the presence of findings suggesting an epidermal origin on these further sections. In one additional case, such origin could not be histologically excluded. Median follow-up period for the remaining cases was 68 months. Confirmed primary dermal melanoma accounts for 0.87% of cases of melanoma referred to a subspecialist melanoma advisory service. These cases show significant histological overlap with dermal/subcutaneous metastases of melanoma, but display a relatively good prognosis, with a 5-year survival of 87.5%. Our results support the recognition of a distinct group of melanoma that mimics metastatic melanoma, but is associated with a relatively favourable outcome. The group of putative primary dermal melanoma is likely to be heterogenous, including cases of primary nodular melanoma in which epidermal connection has not been identified, metastatic melanoma with an occult primary lesion and true primary dermal melanoma. © 2015 Royal Australasian College of Surgeons.

  1. 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

    BACKGROUND: 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. METHODS: 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. RESULTS: The PPVs of melanoma in the Cancer Registry and the Melanoma Database were 97% (95% CI, 94-99) and 100...

  2. 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...... 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...

  3. 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.

  4. Use of iodine-125 brachytherapy in treatment of choroidal melanomas, technic and preliminary analysis of 78 patients

    International Nuclear Information System (INIS)

    Quetin, P.; Schumacher, C.; Schraub, S.; Meyer, L.; Polto, F.; Sahel, J.; Magnenet, P.; Andres, E.

    2001-01-01

    Purpose. - Iodine 125 curietherapy is one of the conservative treatments of uveal melanoma. The technique used to achieve these results was simplified through the physical characteristics of the radioelement and the optimized-dosimetry program employed. Patients and methods. - 78 patients with choroidal melanoma were treated with iodine 125. About 100 Gy were delivered to the superior pole of the tumour. The minimal length of follow-up was 17 months and the average, 67 months. Results. -There was 88% local control, leading to lowered visual acuity in 76 % of the cases. Radiation retinopathy, directly related to proximity to the macula, is the principle etiology. Seven patients died of hepatic metastasis, five patients were enucleated. Four patients were further treated with proton-therapy to make up for non-control locally. Conclusion. -One dose of 100 Gy to the superior pole of the tumor seemed to lead to good local control, with the exception of complications related to proximity to the macula and the optic nerve. In this attempt to optimize irradiation, the time lapse between any benefit in local control derived from irradiation and post-therapeutic complications observed remains insufficient to evaluate any relationship. (authors)

  5. Podoplanin Expression in Canine Melanoma

    OpenAIRE

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

    2016-01-01

    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 immunohistochemistr...

  6. Case studies of skin melanoma

    Directory of Open Access Journals (Sweden)

    A. V. Kozlova

    2015-01-01

    Full Text Available Skin melanoma is a malignant tumor originating in the cells of the melanocytic system, which is characterized by an aggressive clinical course, significant metastatic potential and unfavorable prognosis. These features of the tumor stipulate the need to improve measures to optimize early diagnosis of tumors. The article presents cases of pigmented skin melanoma to demonstrate the variability of clinical manifestations of this tumor requiring dermatologist skills in the differential diagnostics of neoplasms.

  7. [Choroidal melanoma - evolution and prognosis].

    Science.gov (United States)

    Chiruţa, Daria; Stan, Cristina

    2014-01-01

    Choroidal melanoma is the most common primary intraocular malignant tumor. We present the case of a 62 year old patient who was diagnosed with intraocular tumor in his right eye, for about three years. Regarding the fact that the patient refused any kind of treatment during this period, we just had the opportunity to monitor this case. Finally, the diagnosis was choroidal melanoma, confirmed by the histopathological exam.

  8. Umbilicus reconstruction after melanoma excision

    Directory of Open Access Journals (Sweden)

    Miguel Costa-Silva

    2017-01-01

    Full Text Available An 81-year-old woman was admitted with a nodular cutaneous melanoma of the abdominal wall involving the umbilicus. After performing wide excision with 2 cm margin of the melanoma, umbilical reconstruction and defect closure were planned. After careful consideration, we decided to use an island pedicle flap which allowed closure of the defect and reconstruction of the umbilicus.

  9. Ubiquitination in melanoma pathogenesis and treatment.

    Science.gov (United States)

    Ma, Jinyuan; Guo, Weinan; Li, Chunying

    2017-06-01

    Melanoma is one of the most aggressive skin cancers with fiercely increasing incidence and mortality. Since the progressive understanding of the mutational landscape and immunologic pathogenic factors in melanoma, the targeted therapy and immunotherapy have been recently established and gained unprecedented improvements for melanoma treatment. However, the prognosis of melanoma patients remains unoptimistic mainly due to the resistance and nonresponse to current available drugs. Ubiquitination is a posttranslational modification which plays crucial roles in diverse cellular biological activities and participates in the pathogenesis of various cancers, including melanoma. Through the regulation of multiple tumor promoters and suppressors, ubiquitination is emerging as the key contributor and therefore a potential therapeutic target for melanoma. Herein, we summarize the current understanding of ubiquitination in melanoma, from mechanistic insights to clinical progress, and discuss the prospect of ubiquitination modification in melanoma treatment. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  10. The role of nitric oxide in melanoma.

    Science.gov (United States)

    Yarlagadda, Keerthi; Hassani, John; Foote, Isaac P; Markowitz, Joseph

    2017-12-01

    Nitric oxide (NO) is a small gaseous signaling molecule that mediates its effects in melanoma through free radical formation and enzymatic processes. Investigations have demonstrated multiple roles for NO in melanoma pathology via immune surveillance, apoptosis, angiogenesis, melanogenesis, and on the melanoma cell itself. In general, elevated levels of NO prognosticate a poor outcome for melanoma patients. However, there are processes where the relative concentration of NO in different environments may also serve to limit melanoma proliferation. This review serves to outline the roles of NO in melanoma development and proliferation. As demonstrated by multiple in vivo murine models and observations from human tissue, NO may promote melanoma formation and proliferation through its interaction via inhibitory immune cells, inhibition of apoptosis, stimulation of pro-tumorigenic cytokines, activation of tumor associated macrophages, alteration of angiogenic processes, and stimulation of melanoma formation itself. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Tool to Distinguish Moles from Melanoma

    Science.gov (United States)

    “Moles to Melanoma: Recognizing the ABCDE Features” presents photos that show changes in individual pigmented lesions over time, and describes the different appearances of moles, dysplastic nevi, and melanomas.

  12. Primary tumor sites in relation to ultraviolet radiation exposure and skin visibility correlate with survival in cutaneous melanoma.

    Science.gov (United States)

    Gordon, Daniela; Hansson, Johan; Eloranta, Sandra; Gordon, Max; Gillgren, Peter; Smedby, Karin E

    2017-10-01

    The prognostic value of detailed anatomic site and ultraviolet radiation (UVR) exposure patterns has not been fully determined in cutaneous melanoma. Thus, we reviewed medical records for detailed site in a population-based retrospective Swedish patient cohort diagnosed with primary invasive melanoma 1976-2003 (n = 5,973). We followed the patients from date of diagnosis until death, emigration or December 31 st 2013, and evaluated melanoma-specific survival by subsite in a multivariable regression model adjusting for established prognostic factors. We found that melanoma on chronic UVR exposure sites (face, dorsum of hands; adjusted HR 0.6; CI 0.4-0.7) and moderately intermittent UVR sites (lateral arms, lower legs, dorsum of feet; HR 0.7; CI 0.6-0.8) were associated with a favorable prognosis compared with highly intermittent sites (chest, back, neck, shoulders and thighs). Further, melanoma on poorly visible skin sites upon self-examination (scalp, retroauricular area, back, posterior upper arms and thighs, buttocks, pubic area; HR 1.3; CI 1.1-1.5) had a worse prognosis than those on easily visible sites (face, chest, abdomen, anterior upper arms and thighs, lower arms and legs, dorsum of hands and feet, palms). In conclusion, highly intermittent UVR exposure sites and poor skin visibility presumably correlate with reduced melanoma survival, independent of established tumor characteristics. A limitation of the study was the lack of information on actual individual UVR exposure. © 2017 UICC.

  13. Large melanoma metastases to the gastrointestinal tract.

    OpenAIRE

    Silverman, J M; Hamlin, J A

    1989-01-01

    It is well known that malignant melanoma can metastasize widely. Although these metastases in the gastrointestinal tract usually appear as small 'bull's-eye' or 'target' lesions, there are a few reports of relatively large melanoma metastases. We report five cases of large melanoma lesions metastatic to the alimentary canal. We also emphasise the consideration of a thorough gastrointestinal tract evaluation in patients with malignant melanoma especially if they are symptomatic.

  14. Unusual presentations of melanoma: melanoma of unknown primary site, melanoma arising in childhood, and melanoma arising in the eye and on mucosal surfaces.

    Science.gov (United States)

    Sondak, Vernon K; Messina, Jane L

    2014-10-01

    Most melanomas present as primary tumors on the skin surface in adults; however, melanomas also arise in the eye and on the mucosal surfaces or present as apparently metastatic disease without any known history of a cutaneous primary. Melanoma is also being diagnosed during childhood more frequently than ever. Surgeons need to be aware of and understand these unusual presentations of melanoma to optimally manage their patients. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Aetiological study of the presumed ocular histoplasmosis syndrome in the Netherlands

    NARCIS (Netherlands)

    Ongkosuwito, J.V.; Kortbeek, L.M.; Lelij, van der A.; Molicka, E.; Kijlstra, A.; Smet, de M.D.; Suttrop-Schulten, M.S.A.

    1999-01-01

    Aim. To investigate whether presumed ocular histoplasmosis syndrome in the Netherlands is caused by Histoplasma capsulatum and whether other risk factors might play a role in the pathogenesis of this syndrome. Methods. 23 patients were clinically diagnosed as having presumed ocular histoplasmosis

  16. Pregnancy and early-stage melanoma

    NARCIS (Netherlands)

    Daryanani, D; Plukker, JT; De Hullu, JA; Kuiper, H; Nap, RE; Hoekstra, HJ

    2003-01-01

    BACKGROUND. Cutaneous melanomas are aggressive tumors with an unpredictable biologic behavior. It has been suggested that women who present with melanoma during pregnancy have a worse prognosis due to more aggressive behavior of the melanoma. The objective of the current study was to evaluate the

  17. Clinicopathological and molecular aspects of cutaneous Melanoma

    NARCIS (Netherlands)

    Bogenrieder, T.

    2009-01-01

    Clinicopathological and molecular aspects of cutaneous melanoma. Melanoma arises form the transformation of neural crest-derived melanocytes, the pigment cells of the skin, which reside in the basal layer of the epidermis. Melanoma is the deadliest form of skin cancer and one of the most aggressive

  18. Melanoma continues to rise throughout the world

    African Journals Online (AJOL)

    Review Article: Melanoma continues to rise throughout the world. 530 ... of melanoma. The radiation in the ultraviolet B range is said to be the critical component. Generally, worldwide, the incidence of melanoma in white people4,5 correlates inversely with .... lymphocytes, mitotic rate, regression, angiolymphatic invasion ...

  19. Decreased tumor-infiltrating lymphocytes in nodular melanomas compared with matched superficial spreading melanomas.

    Science.gov (United States)

    Lin, Richard L; Wang, Thomas J; Joyce, Cara J; Mihm, Martin C; Murphy, George F; Lian, Christine G; Lin, Jennifer Y

    2016-10-01

    Melanoma causes over 9000 deaths annually in the USA. Among its subtypes, nodular melanoma leads to a disproportionate number of fatalities compared with superficial spreading melanoma, the most common subtype. Recent breakthroughs in melanoma research have indicated a strong connection between melanoma virulence and the immune system. We hypothesize that the aggression of nodular melanoma may, in part, be because of decreased recognition by the immune system, as represented by a decreased presence of tumor-infiltrating lymphocytes (TILs), compared with its superficial spreading counterpart. Indeed, TILs on a primary melanoma have been used as a marker for immune response and have prognostic value for survival and sentinel lymph node status. After matching melanoma cases by age, sex, and Breslow thickness, we found significantly fewer TILs in nodular melanomas than in superficial spreading melanomas. This association was prominent in thin (≤2 mm) melanomas and was no longer significant in thick (>2 mm) melanomas. In addition, this difference in TILs was only present in men and not in women. Our finding suggests that nodular melanomas are more frequently associated with absent TILs, providing an avenue for further investigation into differences in immunogenicity of the primary melanoma and whether they underlie the unique virulence of nodular melanoma.

  20. Emerging targeted therapies for melanoma.

    Science.gov (United States)

    Johnson, Douglas B; Pollack, Megan H; Sosman, Jeffrey A

    2016-06-01

    Melanoma is an aggressive cutaneous malignancy associated with poor response to traditional therapies. Recent regulatory approval for immune checkpoint inhibitors and agents targeting mutated BRAF has led to a tremendous expansion of effective treatment options for patients with advanced melanoma. Unfortunately, primary or acquired resistance develops in most patients, highlighting the need for additional therapies. Numerous genetic and other molecular features of this disease may provide effective targets for therapy development. This article reviews available melanoma treatments, including immune and molecularly-targeted therapies. We then discuss agents in development, with a focus on targeted (rather than immune) therapies. In particular, we discuss agents that block mitogen-activated protein kinase (MAPK) signaling, as well as other emerging approaches such as antibody-drug conjugates, cell-cycle targeting, and novel genetically-informed clinical trials. Despite the incredible advances in melanoma therapeutics over the last several years, a clear need to develop more effective therapies remains. Molecularly-targeted therapy approaches will likely remain a cornerstone of melanoma treatment in parallel to immune therapy strategies.

  1. Current systemic therapies for melanoma.

    Science.gov (United States)

    Palathinkal, Darren M; Sharma, Timmie R; Koon, Henry B; Bordeaux, Jeremy S

    2014-09-01

    Systemic agents are used in melanoma for adjuvant therapy and to treat metastatic disease. Currently, interferon-α is the only agent approved for adjuvant therapy. Six drugs are FDA approved for metastatic disease: dacarbazine, interleukin-2 (IL-2), vemurafenib, ipilimumab, dabrafenib, and trametinib. Vemurafenib and ipilimumab were approved in 2011, whereas dabrafenib and trametinib were approved in 2013. This review will update the practicing dermatologist on the differences in efficacy, adverse events, and cost of systemic therapies available for the treatment of melanoma. This article is a review of the current literature on systemic therapies for advanced melanoma. Key search words included "advanced melanoma," "systemic therapy," and "adjuvant therapy" with particular focus on the past 20 years. Before 2011, dacarbazine and IL-2 were the only FDA approved therapies for metastatic melanoma, and IFN-α is the only approved agent for adjuvant therapy. The new agents vemurafenib, ipilimumab, dabrafenib, and trametinib are the first to have improved overall survival in Phase III studies in comparison with other systemic therapies. Despite new developments, there remains a significant need for better therapies with improved long-term efficacy and decreased toxicity.

  2. Other targeted drugs in melanoma.

    Science.gov (United States)

    González-Cao, María; Rodón, Jordi; Karachaliou, Niki; Sánchez, Jesús; Santarpia, Mariacarmela; Viteri, Santiago; Pilotto, Sara; Teixidó, Cristina; Riso, Aldo; Rosell, Rafael

    2015-10-01

    Targeted therapy drugs are developed against specific molecular alterations on cancer cells. Because they are "targeted" to the tumor, these therapies are more effective and better tolerated than conventional therapies such as chemotherapy. In the last decade, great advances have been made in understanding of melanoma biology and identification of molecular mechanisms involved in malignant transformation of cells. The identification of oncogenic mutated kinases involved in this process provides an opportunity for development of new target therapies. The dependence of melanoma on BRAF-mutant kinase has provided an opportunity for development of mutation-specific inhibitors with high activity and excellent tolerance that are now being used in clinical practice. This marked a new era in the treatment of metastatic melanoma and much research is now ongoing to identify other "druggable" kinases and transduction signaling networking. It is expected that in the near future the spectrum of target drugs for melanoma treatment will increase. Herein, we review the most relevant potential novel drugs for melanoma treatment based on preclinical data and the results of early clinical trials.

  3. 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

  4. 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.

  5. Ipilimumab in the real world: the UK expanded access programme experience in previously treated advanced melanoma patients.

    Science.gov (United States)

    Ahmad, Saif S; Qian, Wendi; Ellis, Sarah; Mason, Elaine; Khattak, Muhammad A; Gupta, Avinash; Shaw, Heather; Quinton, Amy; Kovarikova, Jarmila; Thillai, Kiruthikah; Rao, Ankit; Board, Ruth; Nobes, Jenny; Dalgleish, Angus; Grumett, Simon; Maraveyas, Anthony; Danson, Sarah; Talbot, Toby; Harries, Mark; Marples, Maria; Plummer, Ruth; Kumar, Satish; Nathan, Paul; Middleton, Mark R; Larkin, James; Lorigan, Paul; Wheater, Matthew; Ottensmeier, Christian H; Corrie, Pippa G

    2015-10-01

    Before licensing, ipilimumab was first made available to previously treated advanced melanoma patients through an expanded access programme (EAP) across Europe. We interrogated data from UK EAP patients to inform future clinical practice. Clinicians registered in the UK EAP provided anonymized patient data using a prespecified variable fields datasheet. Data collected were baseline patient characteristics, treatment delivered, toxicity, response, progression-free survival and overall survival (OS). Data were received for 193 previously treated metastatic melanoma patients, whose primary sites were cutaneous (82%), uveal (8%), mucosal (2%), acral (3%) or unknown (5%). At baseline, 88% of patients had a performance status (PS) of 0-1 and 20% had brain metastases. Of the patients, 53% received all four planned cycles of ipilimumab; the most common reason for stopping early was disease progression, including death from melanoma. Toxicity was recorded for 171 patients, 30% of whom experienced an adverse event of grade 3 or higher, the most common being diarrhoea (13%) and fatigue (9%). At a median follow-up of 23 months, the median progression-free survival and OS were 2.8 and 6.1 months, respectively; the 1-year and 2-year OS rates were 31 and 14.8%, respectively. The 2-year OS was significantly lower for patients with poorer PS (P<0.0001), low albumin concentrations (P<0.0001), the presence of brain metastases (P=0.007) and lactate dehydrogenase levels more than two times the upper limit of normal (P<0.0001) at baseline. These baseline characteristics are negative predictors of benefit from ipilimumab and should be taken into consideration before prescription.

  6. Clear cells in acral melanoma.

    Science.gov (United States)

    Schmuth, M; Spötl, L; Zelger, B; Weinlich, G; Zelger, B

    2001-01-01

    Acral melanoma may present clinically and histologically with atypical features causing a delay in proper diagnosis. The aim of the present study was to assess the frequency of a histological variant with clear cell changes. Clinical information, hematoxylin & eosin stained paraffin sections and immunohistochemical staining profiles were reviewed in 49 cases of acral melanoma. Twenty-one (43%) specimens contained tumor cells with clear cell changes in focal areas, whereas in 7 (14%) specimens clear cells were the major tumor constituting cells. The tumor thickness ranged from melanoma in situ to 14 mm. Immunohistochemistry demonstrated weak staining for S100 and HMB45 as well as strong positivity for Melan A and NK1C3. Recognition of clear cell features is important since differential diagnosis includes a variety of other clear cell malignancies, among them metastasis from renal cell carcinoma, clear cell sarcoma and hidradenocarcinoma.

  7. Communication Among Melanoma Family Members

    Science.gov (United States)

    Bowen, Deborah J; Albrecht, Terrance; Hay, Jennifer; Eggly, Susan; Harris-Wei, Julie; Meischke, Hendrika; Burke, Wylie

    2017-01-01

    Interventions to improve communication among family members may facilitate information flow about familial risk and preventive health behaviors. This is a secondary analysis of the effects of an interactive website intervention aimed at increasing communication frequency and agreement about health risk among melanoma families. Participants were family units, consisting of one family member with melanoma identified from a previous research study (the case) and an additional first degree relative and a parent of a child 0–17. Family triads were randomized to receive access to the website intervention or to serve as control families. Family communication frequency and agreement about melanoma prevention behaviors and beliefs were measured at baseline and again at one year post randomization. Intervention participants of all three types significantly increased the frequency of communication to their first degree relatives (Parents, siblings, children; range =14–18 percentage points; all pcommunication about cancer risk. PMID:28248624

  8. Genetic alterations and markers of melanoma

    Directory of Open Access Journals (Sweden)

    N. N. Mazurenko

    2014-01-01

    Full Text Available Melanoma remains the most deadly form of malignant skin disease with high risk of metastases. Metastatic melanoma is prognostic highly unfavorable and resistant to traditional chemotherapy and biologic treatment. There is a great progress in understanding of the molecular mechanisms underlying melanoma initiation and progression. The external (ultraviolet irradiation and internal (genetic factors are involved in melanoma genesis. 5–14 % of melanoma cases occur in familial context due to genetic predisposition risk factors. Among them rare germinal mutations in the cell cycle genes regulators CDKN2A and CDK4 and in the master gene of melanocyte homeostasis MITF, as well as single nucleotide polymorphisms of several low-penetrated genes, namely MC1R, have been identified. The main cell signaling pathways and oncogene driver mutations are involved in melanoma pathogenesis. RAS / RAF / MEK / ERK cascade is hyperactivated in 75 % of cutaneous melanoma cases. Activation of PI3K / AKT / mTOR signaling pathway is important for melanoma progression. Recent studies revealed that melanomas are genetically and phenotypically heterogeneous tumors. Spectrum of chromosomal alterations and activating mutations corresponding to tumor molecular portraits varies in melanomas of different location. Most of cutaneous melanomas contain BRAF (50 % or NRAS (20 % mutations, and NRAS mutations occur on chronically sun-exposed skin. Activating KIT mutations have been reported in approximately 20–30 % of certain subtypes of melanoma, including acral and mucosal, and melanoma that develop on photodamaged skin. Cutaneous metastatic melanoma derive from preexisting nevi in 25 % of cases, molecular mechanisms of nevi malignization are discussed. Deepsequencing approaches of melanoma samples of different melanoma types highlighted new melanoma driver genes, that are damaged due to tumorigenic effects of ultraviolet: PPP6C, RAC1, SNX31, TACC1 and STK19. The

  9. Familial skin cancer syndromes: Increased melanoma risk.

    Science.gov (United States)

    Ransohoff, Katherine J; Jaju, Prajakta D; Jaju, Prajaka D; Tang, Jean Y; Carbone, Michele; Leachman, Sancy; Sarin, Kavita Y

    2016-03-01

    Phenotypic traits, such as red hair and freckling, increase melanoma risk by 2- to 3-fold. In addition, approximately 10% of melanomas are caused by inherited germline mutations that increase melanoma risk from 4- to >1000-fold. This review highlights the key genes responsible for inherited melanoma, with an emphasis on when a patient should undergo genetic testing. Many genetic syndromes associated with increased melanoma risk are also associated with an increased risk of other cancers. Identification of these high-risk patients is essential for preventive behavior reinforcement, genetic counseling, and ensuring other required cancer screenings. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  10. Melanoma: oncogenic drivers and the immune system.

    Science.gov (United States)

    Karachaliou, Niki; Pilotto, Sara; Teixidó, Cristina; Viteri, Santiago; González-Cao, María; Riso, Aldo; Morales-Espinosa, Daniela; Molina, Miguel Angel; Chaib, Imane; Santarpia, Mariacarmela; Richardet, Eduardo; Bria, Emilio; Rosell, Rafael

    2015-10-01

    Advances and in-depth understanding of the biology of melanoma over the past 30 years have contributed to a change in the consideration of melanoma as one of the most therapy-resistant malignancies. The finding that oncogenic BRAF mutations drive tumor growth in up to 50% of melanomas led to a molecular therapy revolution for unresectable and metastatic disease. Moving beyond BRAF, inactivation of immune regulatory checkpoints that limit T cell responses to melanoma has provided targets for cancer immunotherapy. In this review, we discuss the molecular biology of melanoma and we focus on the recent advances of molecularly targeted and immunotherapeutic approaches.

  11. Choroidal melanoma in a dog.

    Science.gov (United States)

    Miwa, Yasutsugu; Matsunaga, Satoru; Kato, Kumiko; Ogawa, Hiroyuki; Nakayama, Hiroyuki; Tsujimoto, Saori; Sasaki, Nobuo

    2005-08-01

    A 7-year-old intact female golden Retriever was referred for evaluation of an intraorbital mass of the left eye. Based on ophthalmoscopy, ultrasonography and magnetic resonance imaging (MRI), the tentative diagnosis was made as an intraocular neoplasia, especially choroidal melanoma. The orbital exenteration of the affected eye was performed. The mass was histologically diagnosed as malignant choroidal melanoma. No signs of recurrence and metastasis were detected by thoracic radiographs, blood examinations and MR images, and the dog was clinically healthy for 23 months after operation.

  12. Oral mucosal melanoma: A case report

    Directory of Open Access Journals (Sweden)

    Ramlal Gantala

    2017-01-01

    Full Text Available Malignant melanoma is most deadly of all primary skin cancers. Over 90% of melanomas occur on the skin. Half of such melanomas occur in the oral cavity, followed by nasal cavity (44% and sinuses (8%. In the oral cavity, the most frequent sites of occurrence are hard palate and maxillary gingiva. Mucosal melanomas represent a diagnostic challenge than the more common cutaneous melanomas because oral melanomas demonstrate significant heterogeneity in morphological features, developmental process, and biological behaviour. This case report highlights an exophytic, lobulated oral malignant melanoma involving maxillary gingiva and is presented to reemphasize the fact that any pigmented lesion in the oral cavity should be examined with suspicion; proper investigation should be carried out to rule out any untoward experiences later.

  13. Systemic administration of platelets incorporating inactivated Sendai virus eradicates melanoma in mice.

    Science.gov (United States)

    Nishikawa, Tomoyuki; Tung, Li Yu; Kaneda, Yasufumi

    2014-12-01

    Tumor microenvironments include a number of fibrin clots due to the microbleeding caused by cancer cell invasion into blood vessels, which suggests the potential utility of a platelet vector for systemic cancer treatment. We previously reported that inactivated Sendai virus (hemagglutinating virus of Japan; HVJ) envelope (HVJ-E) activates anti-tumor immunity and induces cancer cell-selective apoptosis. The hemagglutination activity that blocks the systemic administration of HVJ-E was dramatically attenuated by incorporation into platelets. Platelets incorporating HVJ-E (PH complex) were then injected into the tail veins of B16F10 melanoma-bearing mice. The PH complex primarily accumulated in tumor tissues and caused the significant accumulation of various immune cells in the tumor bed. Injections of the PH complex to the melanoma-bearing mouse significantly reduced the tumor size, and the tumor growth was ultimately arrested. Secretion of the chemokine regulated upon activation normal T-expressed and presumably secreted (RANTES) was upregulated following PH stimulation. The RANTES-depletion in melanoma-bearing mice significantly attenuated the cytotoxic T lymphocyte activity and led to a dramatic abrogation of the mouse melanoma suppression induced by the PH complex. Thus, a platelet vector incorporating viral particles, a Trojan horse for cancer treatment, will provide a new approach for cancer therapy using oncolytic viruses.

  14. Ipsilateral facial and uveal arteriovenous and capillary angioma, microphthalmos, heterochromia of the iris, and hypotony: an oculocutaneous syndrome simulating Sturge-Weber syndrome.

    Science.gov (United States)

    Gass, J D

    1996-01-01

    Sturge-Weber syndrome is a disorder characterized by ipsilateral cavernous hemangioma of the face, uvea, and brain in patients who may present with an enlarged eye, exudative retinal detachment, glaucoma, and seizures. This report presents the clinicopathologic findings of an otherwise healthy infant with ipsilateral arteriovenous and capillary hemangiomas of the face and uveal tract, microphthalmos, iris heterochromia, hypotony, and absence of central nervous system involvement. The association of an arteriovenous-capillary angioma of the ocular adnexa and ipsilateral uveal tract is a syndrome that is distinct from Sturge-Weber syndrome.

  15. Presumed consent in organ donation: the devil is in the detail

    OpenAIRE

    Hutchinson, Odette

    2008-01-01

    This article follows the recent publication of the Organs for Donation Task Force report, "Organs for Transplants", and considers the debate surrounding a change in the law in favour of presumed consent in organ donation.

  16. Cutavirus in Cutaneous Malignant Melanoma

    DEFF Research Database (Denmark)

    Mollerup, Sarah; Fridholm, Helena; Vinner, Lasse

    2017-01-01

    A novel human protoparvovirus related to human bufavirus and preliminarily named cutavirus has been discovered. We detected cutavirus in a sample of cutaneous malignant melanoma by using viral enrichment and high-throughput sequencing. The role of cutaviruses in cutaneous cancers remains...

  17. Prognostic stratification of ulcerated melanoma

    DEFF Research Database (Denmark)

    Bønnelykke-Behrndtz, Marie L; Schmidt, Henrik; Christensen, Ib J

    2014-01-01

    OBJECTIVES: For patients with melanoma, ulceration is an important prognostic marker and interestingly also a predictive marker for the response of adjuvant interferon. A consensual definition and accurate assessment of ulceration are therefore crucial for proper staging and clinical management. We...

  18. Meridional lenticular astigmatism associated with bilateral concurrent uveal metastases in renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Priluck JC

    2012-11-01

    Full Text Available Joshua C Priluck, Sandeep Grover, KV ChalamDepartment of Ophthalmology, University of Florida College of Medicine, Jacksonville, FL, USAPurpose: To demonstrate a case illustrating meridional lenticular astigmatism as a result of renal cell carcinoma uveal metastases.Methods: Case report with images.Results: Clinical findings and diagnostic testing of a patient with acquired meridional lenticular astigmatism are described. The refraction revealed best-corrected visual acuity of 20/20–1 OD (−2.50 + 0.25 × 090 and 20/50 OS (−8.25 + 3.25 × 075. Bilateral concurrent renal cell carcinoma metastases to the choroid and ciliary body are demonstrated by utilizing ultrasonography, ultrawidefield fluorescein angiography, and unique spectral-domain optical coherence tomography.Conclusions: Metastatic disease should be included in the differential of acquired astigmatism. Spectral-domain optical coherence tomography, ultrawidefield fluorescein angiography, and ultrasonography have roles in delineating choroidal metastases.Keywords: astigmatism, metastasis, optical coherence tomography, renal cell carcinoma

  19. Difference of uveal parameters between the acute primary angle closure eyes and the fellow eyes.

    Science.gov (United States)

    Li, Xingyi; Wang, Wei; Huang, Wenbin; Chen, Shida; Wang, Jiawei; Wang, Zhonghao; Liu, Yaoming; He, Mingguang; Zhang, Xiulan

    2018-03-01

    To measure the anterior and posterior ocular biometric characteristics concurrently and to explore the relationship between iris, ciliary body and choroid in acute primary angle closure eyes (APAC) and fellow eyes. It is a prospective, cross-sectional study. Thirty patients with recent APAC were finally enroled in it. Anterior and posterior uveal parameters were measured simultaneously by anterior segment optical coherence tomography (AS-OCT), swept-source optical coherence tomography (SS-OCT) and ultrasound biomicroscopy (UBM). The parameters were measured including: pupil diameter (PD); iris thickness, curvature (ICURV), area (IAREA); anterior chamber depth (ACD), width (ACW), area (ACA), volume (ACV); lens vault (LV); choroidal thickness and retinal thickness; maximum ciliary body thickness (CBTmax); ciliary body thickness at the point of the scleral spur (CBT0) and 1000 mm away (CBT1000); anterior placement of the ciliary body (APCB); and trabecular-ciliary angle (TCA). Compared with fellow eyes, APAC eyes had narrower anterior biometric parameters and presented with smaller anterior segment parameters (including ACD and ACW); (p APAC eyes had narrower anterior biometric parameters, thinner ciliary body and smaller iris area and curvature. APCB, CBT and choroidal thickness were positively correlated. However, further studies are required before these conclusions are generalised.

  20. 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

  1. Guideline on the Management of Melanoma | Board | South African ...

    African Journals Online (AJOL)

    Validation. Melanoma management involves many medical specialties. Guidelines should therefore be developed through a multidisciplinary consensus. The Melanoma Advisory Board consists of a forum of dermatologists, oncologists, plastic surgeons and pathologists. Guideline sponsor. The meetings of the Melanoma ...

  2. Mucosal malignant melanoma - a clinical, oncological, pathological and genetic survey

    DEFF Research Database (Denmark)

    Mikkelsen, Lauge H; Larsen, Ann-Cathrine; von Buchwald, Christian

    2016-01-01

    Mucosal melanomas constitute 1.3% of all melanomas and they may develop in any mucosal membrane. Conjunctival melanomas (0.5/million/year) and melanomas in the sinonasal cavity (0.5/million/year) are the most common, followed by anorectal melanomas (0.4/million/year) and melanomas in the oral...... cavity (0.2/million/year). Anorectal melanoma occurs slightly more often in females, whereas oral melanoma has a male predilection. Mucosal melanoma most commonly develops in a patient's sixth or seventh decade of life, and no differences between races have been found except for sinonasal melanoma...... is the treatment of choice. The prognosis is poor, with the 5-year survival rate ranging from 0% (gastric melanoma) to 80% (conjunctival melanoma)....

  3. Risk factors for second primary melanoma among Dutch patients with melanoma

    NARCIS (Netherlands)

    Schuurman, M.S.; Waal, A.C. de; Thijs, E.J.M.; Rossum, M.M. van; Kiemeney, L.A.L.M.; Aben, K.K.H.

    2017-01-01

    BACKGROUND: Patients with melanoma are at increased risk of developing subsequent primary melanomas. Knowledge about risk factors for these subsequent primaries is scarce. More evidence may help clinicians in tailoring surveillance schedules by selecting patients who could benefit from intensified

  4. 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.

  5. Molecular insights into melanoma brain metastases.

    Science.gov (United States)

    Westphal, Dana; Glitza Oliva, Isabella C; Niessner, Heike

    2017-06-01

    Substantial proportions of patients with metastatic melanoma develop brain metastases during the course of their disease, often resulting in significant morbidity and death. Despite recent advances with BRAF/MEK and immune-checkpoint inhibitors in the treatment of patients who have melanoma with extracerebral metastases, patients who have melanoma brain metastases still have poor overall survival, highlighting the need for further therapy options. A deeper understanding of the molecular pathways involved in the development of melanoma brain metastases is required to develop more brain-specific therapies. Here, the authors summarize the currently known preclinical data and describe steps involved in the development of melanoma brain metastases. Only by knowing the molecular background is it possible to design new therapeutic agents that can be used to improve the outcome of patients with melanoma brain metastases. Cancer 2017;123:2163-75. © 2017 American Cancer Society. © 2017 American Cancer Society.

  6. 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.

  7. Melanoma of unknown origin: a case series.

    LENUS (Irish Health Repository)

    Kelly, J

    2010-12-01

    The natural history of metastatic melanoma involving lymph nodes, in the absence of a known primary site (cutaneous, ocular or mucosal) has, to date, been poorly defined; and the optimal management of this rare subtype of disease is therefore unclear. Melanomas of unknown primary site (MUP) are estimated to comprise between 3.7 and 6% of all melanomas (Anbari et al. in Cancer 79:1861-1821, 1997).

  8. Melanoma epidemiology, prognosis and trends in Latvia.

    Science.gov (United States)

    Azarjana, K; Ozola, A; Ruklisa, D; Cema, I; Rivosh, A; Azaryan, A; Pjanova, D

    2013-11-01

    Melanoma incidence and mortality rates are increasing worldwide within the white population. Clinical and histological factors have been usually used for the prognosis and assessment of the risk for melanoma. The aim of the study was to describe the clinical and histopathological features of the cutaneous melanoma (CM) in the Latvian population, to test the association between melanoma features and patient survival, and to assess the time trends for melanoma incidence. We undertook a descriptive, retrospective analysis of archive data of 984 melanoma patients treated at the largest oncological hospital of Latvia, Riga East University Hospital Latvian Oncology Centre (LOC), between 1998 and 2008. Cox proportional hazards model was used to analyse patient survival and autoregressive models were applied to detect trends in melanoma incidence over time for various categories of melanoma. The study showed a significant ascending trend in melanoma incidence in Latvia during the time period from 1998 to 2008 (ß = 1.83, 95% CI = 1.15-2.91, P = 0.011). Nodular melanoma was the most common tumour subtype with a frequency of 39.2%. Ulceration was present in 45.2% of melanomas. The mean Breslow thickness was 6.0 mm (6.8 mm) and no significant decline in median Breslow thickness was observed during the study period (P = 0.609). A better overall prognosis was detected for females in comparison with males (HR = 1.49; 95% CI = 1.22-1.81; P Latvia with the majority of melanomas diagnosed at late stages with poor prognosis for survival. © 2012 The Authors Journal of the European Academy of Dermatology and Venereology © 2012 European Academy of Dermatology and Venereology.

  9. Giant hanging melanoma of the eyelid skin

    Directory of Open Access Journals (Sweden)

    Pai Radha

    2008-01-01

    Full Text Available Cutaneous melanoma of the eyelid is a rare entity. We present a 53-year-old male who had a nevus on the left upper eyelid skin since childhood, which transformed into a huge ulcerated hanging mass in the same region. Excision of the mass was done and histopathology confirmed the diagnosis of nodular malignant melanoma. A small preauricular lymph node showed metastatic melanoma on fine needle aspiration cytology.

  10. Timely Healthcare Checkup Catches Melanoma Early

    Science.gov (United States)

    ... Skin Cancer" Articles Skin Cancer Can Strike Anyone / Skin Cancer: Biology, Risk Factors & Treatment / Timely Healthcare Checkup Catches Melanoma Early / NIH Research to Results / Skin and Sun – ...

  11. Genomic characterisation of acral melanoma cell lines.

    Science.gov (United States)

    Furney, Simon J; Turajlic, Samra; Fenwick, Kerry; Lambros, Maryou B; MacKay, Alan; Ricken, Gerda; Mitsopoulos, Costas; Kozarewa, Iwanka; Hakas, Jarle; Zvelebil, Marketa; Lord, Christopher J; Ashworth, Alan; Reis-Filho, Jorge S; Herlyn, Meenhard; Murata, Hiroshi; Marais, Richard

    2012-07-01

    Acral melanoma is a rare melanoma subtype with distinct epidemiological, clinical and genetic features. To determine if acral melanoma cell lines are representative of this melanoma subtype, six lines were analysed by whole-exome sequencing and array comparative genomic hybridisation. We demonstrate that the cell lines display a mutation rate that is comparable to that of published primary and metastatic acral melanomas and observe a mutational signature suggestive of UV-induced mutagenesis in two of the cell lines. Mutations were identified in oncogenes and tumour suppressors previously linked to melanoma including BRAF, NRAS, KIT, PTEN and TP53, in cancer genes not previously linked to melanoma and in genes linked to DNA repair such as BRCA1 and BRCA2. Our findings provide strong circumstantial evidence to suggest that acral melanoma cell lines and acral tumours share genetic features in common and that these cells are therefore valuable tools to investigate the biology of this aggressive melanoma subtype. Data are available at: http://rock.icr.ac.uk/collaborations/Furney_et_al_2012/. © 2012 John Wiley & Sons A/S.

  12. 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

    2018-01-15

    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%-100% in the Cancer Registry and 93%-100% in the Melanoma Database. The PPVs for anatomical localization were 83%-95.0% in the Cancer Registry and 93%-100% in the Melanoma Database. The data quality in both the Cancer Registry and the Melanoma Database are high, supporting their use in epidemiologic studies.

  13. UVB: suscetibilidade no melanoma maligno

    OpenAIRE

    Nasser,Nilton

    2010-01-01

    FUNDAMENTOS: Está bem definido que a radiação ultravioleta provoca depleção imunológica na pele, permitindo o desenvolvimento de tumores cutâneos malignos. A maioria dos pacientes de cânceres da pele não melanomas são considerados UVB-suscetíveis. OBJETIVOS: Estudar a UVB-suscetibilidade nos pacientes com melanoma maligno e se este é um fator de risco para o desenvolvimento desse câncer. MÉTODOS: Foram selecionados 88 voluntários divididos em dois grupos: grupo-controle saudável (n=61) e grup...

  14. [Acute dyspnea in malignant melanoma].

    Science.gov (United States)

    Franzen, A M; Günzel, T

    2011-09-01

    Metastases to the larynx are rare. The current article presents the case of a 75-year-old patient with a history of shortness of breath due to a supraglottic exophytic lesion that was identified as a metastasis of a cutaneous melanoma treated 2.5 years previously. As a result of our medline analysis we found approximately 30 cases of metastatic melanoma to the larynx published to date. Primary tumors are always cutaneous in origin and spread over the whole integument of trunk and extremities. The time interval between diagnosis of the primary and the laryngeal metastasis is often several years. In most reports a supraglottic exophytic, red coloured lesion is described. Diagnosis can only be proven by histological examination. Laryngeal metastasis is usually an indication of tumor dissemination and always has a fatal prognosis.

  15. 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

  16. BRAF mutations in conjunctival melanoma

    DEFF Research Database (Denmark)

    Larsen, Ann-Cathrine; Dahl, Christina; Dahmcke, Christina M.

    2016-01-01

    with atypia. BRAF mutations were identified in 39 of 111 (35%) cases. The rate ratio of BRAF-mutated versus BRAF-wild-type melanoma did not change over time. BRAF mutations were associated with T1 stage (p = 0.007), young age (p = 0.001), male gender (p = 0.02), sun-exposed location (p = 0.01), mixed....../non-pigmented tumour colour (p = 0.02) and nevus origin (p = 0.005), but did not associate with prognosis. BRAF status in conjunctival melanoma and paired premalignant lesions corresponded in 19 of 20 cases. Immunohistochemistry detected BRAF V600E mutations with a sensitivity of 0.94 and a specificity of 1...

  17. 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.

  18. Thigmotropism of Malignant Melanoma Cells

    OpenAIRE

    Quatresooz, Pascale; Pi?rard-Franchimont, Claudine; No?l, Fanchon; Pi?rard, G?rald E.

    2011-01-01

    During malignant melanoma (MM) progression including incipient metastasis, neoplastic cells follow some specific migration paths inside the skin. In particular, they progress along the dermoepidermal basement membrane, the hair follicles, the sweat gland apparatus, nerves, and the near perivascular space. These features evoke the thigmotropism phenomenon defined as a contact-sensing growth of cells. This process is likely connected to modulation in cell tensegrity (control of the cell shape)....

  19. Dermoscopic evaluation of nodular melanoma.

    Science.gov (United States)

    Menzies, Scott W; Moloney, Fergal J; Byth, Karen; Avramidis, Michelle; Argenziano, Giuseppe; Zalaudek, Iris; Braun, Ralph P; Malvehy, Josep; Puig, Susana; Rabinovitz, Harold S; Oliviero, Margaret; Cabo, Horacio; Bono, Riccardo; Pizzichetta, Maria A; Claeson, Magdalena; Gaffney, Daniel C; Soyer, H Peter; Stanganelli, Ignazio; Scolyer, Richard A; Guitera, Pascale; Kelly, John; McCurdy, Olivia; Llambrich, Alex; Marghoob, Ashfaq A; Zaballos, Pedro; Kirchesch, Herbert M; Piccolo, Domenico; Bowling, Jonathan; Thomas, Luc; Terstappen, Karin; Tanaka, Masaru; Pellacani, Giovanni; Pagnanelli, Gianluca; Ghigliotti, Giovanni; Ortega, Blanca Carlos; Crafter, Greg; Ortiz, Ana María Perusquía; Tromme, Isabelle; Karaarslan, Isil Kilinc; Ozdemir, Fezal; Tam, Anthony; Landi, Christian; Norton, Peter; Kaçar, Nida; Rudnicka, Lidia; Slowinska, Monika; Simionescu, Olga; Di Stefani, Alessandro; Coates, Elliot; Kreusch, Juergen

    2013-06-01

    Nodular melanoma (NM) is a rapidly progressing potentially lethal skin tumor for which early diagnosis is critical. To determine the dermoscopy features of NM. Eighty-three cases of NM, 134 of invasive non-NM, 115 of nodular benign melanocytic tumors, and 135 of nodular nonmelanocytic tumors were scored for dermoscopy features using modified and previously described methods. Lesions were separated into amelanotic/hypomelanotic or pigmented to assess outcomes. Predominantly hospital-based clinics from 5 continents. Sensitivity, specificity, and odds ratios for features/models for the diagnosis of melanoma. Nodular melanoma occurred more frequently as amelanotic/hypomelanotic (37.3%) than did invasive non-NM (7.5%). Pigmented NM had a more frequent (compared with invasive non-NM; in descending order of odds ratio) symmetrical pigmentation pattern (5.8% vs 0.8%), large-diameter vessels, areas of homogeneous blue pigmentation, symmetrical shape, predominant peripheral vessels, blue-white veil, pink color, black color, and milky red/pink areas. Pigmented NM less frequently displayed an atypical broadened network, pigment network or pseudonetwork, multiple blue-gray dots, scarlike depigmentation, irregularly distributed and sized brown dots and globules, tan color, irregularly shaped depigmentation, and irregularly distributed and sized dots and globules of any color. The most important positive correlating features of pigmented NM vs nodular nonmelanoma were peripheral black dots/globules, multiple brown dots, irregular black dots/globules, blue-white veil, homogeneous blue pigmentation, 5 to 6 colors, and black color. A model to classify a lesion as melanocytic gave a high sensitivity (>98.0%) for both nodular pigmented and nonnodular pigmented melanoma but a lower sensitivity for amelanotic/hypomelanotic NM (84%). A method for diagnosing amelanotic/hypomelanotic malignant lesions (including basal cell carcinoma) gave a 93% sensitivity and 70% specificity for NM. When

  20. 41 CFR 301-72.1 - Why is common carrier presumed to be the most advantageous method of transportation?

    Science.gov (United States)

    2010-07-01

    ... presumed to be the most advantageous method of transportation? 301-72.1 Section 301-72.1 Public Contracts... Transportation § 301-72.1 Why is common carrier presumed to be the most advantageous method of transportation? Travel by common carrier is presumed to be the most advantageous method of transportation because it...

  1. UVB: suscetibilidade no melanoma maligno UVB: susceptibility in malignant melanoma

    Directory of Open Access Journals (Sweden)

    Nilton Nasser

    2010-12-01

    Full Text Available FUNDAMENTOS: Está bem definido que a radiação ultravioleta provoca depleção imunológica na pele, permitindo o desenvolvimento de tumores cutâneos malignos. A maioria dos pacientes de cânceres da pele não melanomas são considerados UVB-suscetíveis. OBJETIVOS: Estudar a UVB-suscetibilidade nos pacientes com melanoma maligno e se este é um fator de risco para o desenvolvimento desse câncer. MÉTODOS: Foram selecionados 88 voluntários divididos em dois grupos: grupo-controle saudável (n=61 e grupo de portadores de melanoma (n=27, todos identificados de acordo com os critérios: tipo histológico, nível de invasão, fotótipos de pele, sexo e idade. A suscetibilidade à radiação ultravioleta B (UVB foi medida pela reação de hipersensibilidade ao contato com o difenciprone nos voluntários sensibilizados em áreas previamente irradiadas. RESULTADOS: A suscetibilidade à radiação UVB foi de 81,5% nos pacientes com melanoma maligno e de 31,2% no grupo-controle. O risco de um indivíduo desenvolver o melanoma maligno foi 9,7 vezes maior do que nos indivíduos UVB-resistentes. CONCLUSÕES: A UVB-suscetibilidade pode ser considerada um fator de risco importante para o desenvolvimento do melanoma maligno.BACKGROUND: It is well established that UV radiation provokes an immunological depletion in the skin, enabling the development of malignant cutaneous tumors. Most nonmelanoma skin cancer patients are considered to be UVB-susceptible. OBJECTIVE: To study the behavior of UVB- susceptibility in malignant melanoma (MM patients and whether this is a risk factor to the development of MM. METHODS: Eighty-eight volunteers were selected and divided into two groups: healthy control group (n = 61 and MM group (n = 27, which were identified according to the following clinical criteria: histopathological type, level of invasion, skin phototype, sex and age. Susceptibility to ultraviolet B (UVB radiation was measured by the onset of a contact

  2. Spontaneous Splenic Rupture in Melanoma

    Directory of Open Access Journals (Sweden)

    Hadi Mirfazaelian

    2014-01-01

    Full Text Available Spontaneous rupture of spleen due to malignant melanoma is a rare situation, with only a few case reports in the literature. This study reports a previously healthy, 30-year-old man who came with chief complaint of acute abdominal pain to emergency room. On physical examination, abdominal tenderness and guarding were detected to be coincident with hypotension. Ultrasonography revealed mild splenomegaly with moderate free fluid in abdominopelvic cavity. Considering acute abdominal pain and hemodynamic instability, he underwent splenectomy with splenic rupture as the source of bleeding. Histologic examination showed diffuse infiltration by tumor. Immunohistochemical study (positive for S100, HMB45, and vimentin and negative for CK, CD10, CK20, CK7, CD30, LCA, EMA, and chromogranin confirmed metastatic malignant melanoma. On further questioning, there was a past history of a nasal dark skin lesion which was removed two years ago with no pathologic examination. Spontaneous (nontraumatic rupture of spleen is an uncommon situation and it happens very rarely due to neoplastic metastasis. Metastasis of malignant melanoma is one of the rare causes of the spontaneous rupture of spleen.

  3. Uveal effusion following acute primary angle-closure: a retrospective case series

    Directory of Open Access Journals (Sweden)

    Jian-Gang Yang

    2017-03-01

    Full Text Available AIM: To evaluate the morphological changes in anterior segment in Chinese patients with uveal effusion (UE after the attack of acute primary angle-closure (APAC using ultrasound biomicroscopy (UBM, and to assess the clinical course and prognosis of the disease. METHODS: In a retrospective case series, 26 eyes in 26 consecutive patients diagnosed with UE after the treatment of intraocular pressure (IOP-lowering medication for the attack of APAC were enrolled. The unaffected fellow eyes served as controls. The morphological changes were observed by ultrasonography, slit lamp microscopy and gonioscopy. UBM was used to assess the degree and extent of effusion based on the analysis of parameters associated with UE. RESULTS: The mean IOP was 9.2 (SD 2.1 mm Hg at the diagnosis of UE after IOP-lowering medication, while 14.1 (SD, 2.6 mm Hg in the fellow eyes (P=0.000. The anterior chamber depth (ACD (P=0.000, angle opening distance at 500 μm (AOD500 (P<0.01 and anterior chamber angle (ACA (P<0.05 were decreased significantly, while ciliary body thickness (CBT (P<0.05 increased significantly in UE eyes. UE grade analysis showed 7 eyes in grade 1, 9 eyes in grade 2, and 10 eyes in grade 3. Quadrant scores were performed of 4 eyes in 1 quadrant, 3 eyes in 3 quadrants, and 19 eyes in 4 quadrants. There was the positive correlation between grade and quadrant score (r=0.644, P=0.000. The effusion on all eyes were recovered after medication, which mean IOP was 13.9 (SD, 2.8 mm Hg. CONCLUSION: UE is a frequent complication in Chinese patients after the attack of APAC, partially associated with hypotony. The severity of UE is correlation with height of effusion, extent of detachment, and shallower ACD.

  4. Do melanoma patients with melanoma of unknown primary have better survival than patients with melanoma of known primary?

    DEFF Research Database (Denmark)

    Rødgaard, Jes Christian; Kjerkegaard, Ulrik; Sørensen, Jens Ahm

    2018-01-01

    Background: Several studies have compared the survival rate of melanoma of unknown primary (MUP) patients with patients with a known primary melanoma (MKP). Some studies found improved survival in MUP patients, whereas others found similar or poorer outcomes. The aim of this study was to evaluate...

  5. Is the prognosis and course of acral melanoma related to site-specific clinicopathological features?

    NARCIS (Netherlands)

    Paolino, G.; Bekkenk, M. W.; Didona, D.; Eibenschutz, L.; Richetta, A. G.; Cantisani, C.; Viti, G.; Carbone, A.; Buccini, P.; de Simone, P.; Ferrari, A.; Scali, E.; Calvieri, S.; Silipo, V.; Cigna, E.; Viti, G. P.; Bottoni, U.

    2016-01-01

    Acral melanoma is an uncommon type of melanoma in Caucasian patients. However, acral melanoma is the most common type of melanoma in African and Asian patients. Comparison analyses between hand-acral melanoma and foot-acral melanoma have been rarely reported in the literature. Acral melanoma is an

  6. Nodular melanoma: a distinct clinical entity and the largest contributor to melanoma deaths in Victoria, Australia.

    Science.gov (United States)

    Mar, Victoria; Roberts, Hugh; Wolfe, Rory; English, Dallas R; Kelly, John W

    2013-04-01

    There is a growing body of evidence that nodular melanoma (NM), because of its association with increased growth rate and thickness at diagnosis, accounts for a substantial proportion of melanoma deaths. We sought to assess the contribution of NM to melanoma deaths in comparison with other tumor subtypes. Four cohorts were established comprising 5775 cases of invasive primary cutaneous melanoma reported to the Victorian Cancer Registry during 1989, 1994, 1999, and 2004. Original pathology reports were reviewed. Age-standardized melanoma incidence rates were compared from 1989 to 2004 with annual percentage change using Poisson regression. The incidence of thick tumors (>4 mm) increased by 3.8% (95% confidence interval 1.4 to 6.2) and 2.5% (95% confidence interval -0.5 to 5.5) per year for male and female patients, respectively. The median thickness of NM at diagnosis was 2.6 mm compared with 0.6 mm for superficial spreading melanoma. A third of patients who died from melanoma during the follow-up period had thick tumors (>4 mm), most of which were nodular subtype (61%). NM accounted for 14% of invasive melanomas, but was responsible for 43% of melanoma deaths in a total of 57,461 person-years of follow-up. By comparison, superficial spreading melanoma contributed 56% of invasive melanoma but only 30% of deaths. Pathology review was limited to reports only. Mortality information relied mostly on death certificate information. The incidence of thick melanomas continues to increase. Nodular melanoma is clinically distinct and the predominant contributor to melanoma-related deaths, representing a public health challenge in reducing skin cancer mortality. Copyright © 2012 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  7. Nodular melanoma is less likely than superficial spreading melanoma to be histologically associated with a naevus.

    Science.gov (United States)

    Pan, Yan; Adler, Nikki R; Wolfe, Rory; McLean, Catriona A; Kelly, John W

    2017-10-16

    To determine the frequency of naevus-associated melanoma among superficial spreading and nodular subtypes; and to investigate associations between naevus-associated melanoma and other clinico-pathological characteristics. Cross-sectional study of all patients with nodular and superficial spreading melanomas diagnosed between 1994 and 2015 at the Victorian Melanoma Service, Melbourne. Clinical and pathological characteristics of naevus-associated and de novo melanomas were assessed in univariable and multivariable logistic regression analyses. Of 3678 primary melanomas, 1360 (37.0%) were histologically associated with a naevus and 2318 (63.0%) were de novo melanomas; 71 of 621 nodular (11.4%) and 1289 of 3057 superficial spreading melanomas (42.2%) were histologically associated with a naevus. In multivariable analyses, the odds of being associated with a naevus were higher for melanomas located on the trunk (v head and neck: adjusted odds ratio [OR], 2.27; 95% CI, 1.73-2.96; P melanomas (adjusted OR, 0.68; 95% CI, 0.48-0.97; P = 0.035), and older age (patients 70 years or older v patients under 30 at diagnosis: adjusted OR, 0.28; 95% CI, 0.20-0.40; P melanomas as for nodular melanomas (adjusted OR, 3.05; 95% CI, 2.24-4.17; P Melanomas are most likely to arise in the absence of a pre-existing naevus, particularly nodular melanomas. Public health campaigns should therefore emphasise the detection of suspicious de novo lesions, as well as of changing lesions.

  8. Isolated Pancreatic Metastasis from Malignant Melanoma: Is ...

    African Journals Online (AJOL)

    Isolated pancreatic metastasis from malignant melanoma (IPMMM) is rare because most melanoma patients already have a widespread disease at diagnosis. No adjuvant systemic treatment is known to be effi cient in this setting. Experience with pancreatic resection for IPMMM is limited and controversial. We report here ...

  9. Primary malignant melanoma of the nasal cavity.

    Science.gov (United States)

    Uysal, Ismail Önder; Misir, Mustafa; Polat, Kerem; Altuntaş, Emine Elif; Atalar, Mehmet Haydar; Tuncer, Ersin; Müderris, Suphi

    2012-01-01

    Primary malignant melanoma of the nose and paranasal sinus mucosa is a rare disease and seen in less than 1% among all melanomas. Malignant melanomas have 2 origins: cutaneous and mucosal. The mucosal form has a worse prognosis because of its aggressiveness compared with that of the cutaneous form. Mucosal melanomas often occur at a rate of 2% to 3% among all melanomas and are typically found in the nasal cavity and paranasal sinuses. Generally, it is more common in males and in those older than 50 years. In this study, 4 patients were observed at the Cumhuriyet University Faculty of Medicine; 2 of them were a 64-year-old man and an 82-year-old woman who had a malignant melanoma originating from the nasal septal mucosa, 1 patient was a 72-year-old woman whose malignant melanoma originated from the inferior turbinate, and 1 patient was a 77-year-old woman with a sinonasally located melanoma. The conditions of these patients were discussed under the light of literature instructions.

  10. PRIMARY MALIGNANT MELANOMA OF ARYEPIGLOTTIC FOLD

    African Journals Online (AJOL)

    2015-12-01

    Dec 1, 2015 ... ing including positron emission tomography (PET) scan failed to reveal a primary source of malignant melanoma. So, the patient was diagnosed as primary malignant melanoma of aryepiglottic mucosa. Figure 1 Photomicrograph showing origin of melano- ma (H&E, 100x). Figure 2 Photomicrograph ...

  11. Malignant melanoma at a scientific laboratory

    Energy Technology Data Exchange (ETDEWEB)

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

    1985-11-15

    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.

  12. Histopathological study of malignant melanoma in highlanders ...

    African Journals Online (AJOL)

    Histopathological study of malignant melanoma in highlanders. AZ Mohammed, AN Manasseh, BM Mandong, ST Edino. Abstract. Background:Malignant melanoma is a fatal skin cancer that is curable when detected and treated early. Recent reports indicate a rising incidence globally. This study aims at identifying the ...

  13. Intraoral malignant melanoma | Babburi | Nigerian Medical Journal

    African Journals Online (AJOL)

    Primary oral mucosal melanoma is a rare aggressive neoplasm and accounts for only 0.2‑8% of all reported melanomas. It is a malignant neoplasm of melanocytes that may arise from a benign melanocytic lesion or de novo from melanocytes within normal skin or mucosa. It is considered to be the most deadly and ...

  14. 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.

  15. Checkpoint Inhibitors Hold Promise for Rare Melanoma

    Science.gov (United States)

    Patients with a rare form of melanoma, called desmoplastic melanoma, may be particularly likely to benefit from immune checkpoint inhibitors, a new study shows. As this Cancer Currents post explains, an NCI-sponsored clinical trial is already testing one such drug, pembrolizumab (Keytruda) in patients with this cancer.

  16. 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

  17. Primary malignant melanoma of aryepiglottic fold | Chhabra | Ghana ...

    African Journals Online (AJOL)

    Background: Primary malignant melanoma rarely arises from noncutaneous tissues that contain melanocytes. Head and neck mucosal melanomas account for 0.7% to 3.8% of all melanomas. Here we report a case of primary malignant melanoma of aryepiglottic fold. Result: Here we reported a case of primary malignant ...

  18. Secondary prevention after cerebral ischaemia of presumed arterial origin: is aspirin still the touchstone?

    NARCIS (Netherlands)

    A. Algra (Ale); P.J. Koudstaal (Peter Jan); J. van Gijn (Jan)

    1999-01-01

    textabstractPatients who have had a transient ischaemic attack or nondisabling ischaemic stroke of presumed arterial origin have an annual risk of death from all vascular causes, non-fatal stroke, or non-fatal myocardial infarction that ranges between 4% and 11% without treatment. In the

  19. A randomized trial of anticoagulants versus aspirin after cerebral ischemia of presumed arterial origin

    NARCIS (Netherlands)

    Franke, CL; Koehler, PJJ; Gorter, JW; Kappelle, LJ; Rinkel, GJE; Tjeerdsma, HC; van Gijn, J; Dammers, JWHH; Straatman, HJS; ten Houten, R; Veering, MM; Bakker, SLM; Dippel, D; Koudstaal, PJ; van Gemert, HMA; van Swieten, JC; Horn, J; Kwa, IH; Limburg, M; Stam, J; Boon, AM; Lieuwens, WHG; Visscher, F; Bouwsma, C; Rutgers, AWF; Snoek, JW; Brouwers, PJAM; Nihom, J; Solleveld, H; Carbaat, PAT; Hertzberger, LI; Kleijweg, RP; Nanninga-van den Neste, VMH; van Diepen, AJH; Linssen, WHJP; Vanneste, JAL; Vos, J; Weinstein, HC; Schipper, JP; Berntsen, PJIM; de Vries-Leenders, EM; Geervliet, JP; Tans, RJJ; Feikema, WJ; Lohmann, HJHM; van Kasteel, [No Value; Jongebloed, FA; Leyten, QH; van Wensen, PJM; Jansen, C; Driesen, JJM; van Oudenaarden, WF; Verhey, JCB; Bottger, HRF; Driessen-Kletter, MF; Zwols, F; van der Gaast, JB; Wittebol, MC; van Oostenbrugge, RJ; Beintema, KD; Hilbers, J; van der Weil, HL; van Lieshout, HBM; Weststrate, W; Bernsen, PLJA; Frenken, CWGM; Poels, EFJ; Lindeboom, SF; van der Steen, A; Glimmerveen, WF; Martens, EIF; Bulens, C; de Vries-Bos, LHP; Venables, GS; Koster, JG; Sinnige, LGF; Klaver, MM; Koetsveld-Baart, JC; Mauser, HW; van Geusau, RBA; Dijkman, MH; Hoppenbrouwers, WJJF; Banford, WJJF; Briet, PE; Eekhof, JLA; Witjes, R; Hamburger, HL; van der Sande, JJ; Bath, P; Hankey, GJ; Koning, E; Ricci, S; Berendes, JN; Hooff, LJMA; van Spreeken, ACGA; Kuhler, AR; Mallo, GN; van Walbeek, HK; Gauw, JC; Vermeij, AJ; Verheij, JCB; Swen, JWA; Canhao, P; Keyser, A; Holscher, RS; de Jong, GJ; Kraaier, [No Value; Algra, A; Briet, E; deVries-Goldschemdingi, J; Eikelboom, BC; Greebe, P; Hauer, RNW; Hermsen, MG; Loeliger, EA; Pop, GAM; Rosendaal, FR; Schobben, AFAM; Sixma, FF; Slabbers, DCV; Tijssen, JCP; van Creval, H; van Es, GA; Verheugt, FWA; Vermeulin, M; Wulfsen, EKM; van der Meer, W.K.; Wever, Eric F. D.; Don, J

    1997-01-01

    Aspirin is only modestly effective in the secondary prevention after cerebral ischemia Studies in other vascular disorders suggest that anticoagulant drugs in patients with cerebral ischemia of presumed arterial (noncardiac) origin might be more effective. The aim of the Stroke Prevention in

  20. Presumed Perinatal Stroke in a Child with Down Syndrome and Moyamoya Disease

    Science.gov (United States)

    Pysden, Karen; Fallon, Penny; Moorthy, Bhagavatheswaran; Ganesan, Vijeya

    2010-01-01

    Moyamoya disease describes a cerebral arteriopathy characterized by stenosis or occlusion of the terminal internal carotid and/or the proximal middle cerebral arteries. We report a female child with trisomy 21 and bilateral moyamoya disease who presented, unusually, with a presumed perinatal cerebral infarct. The clinical, radiological, and…