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Sample records for presumed uveal melanomas

  1. 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.

  2. 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.

  3. [Telomerase activity in uveal melanomas].

    Science.gov (United States)

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

    2000-05-01

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

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

    Science.gov (United States)

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

    2016-05-01

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

  5. Combined treatment of uveal melanoma liver metastases

    Directory of Open Access Journals (Sweden)

    Brasiuniene B

    2011-02-01

    Full Text Available Abstract Uveal melanoma (UM is the most prevalent intraocular malignant tumor in the Western world. The prognosis of survival in the presence of metastatic disease is 2-7 months, depending on the treatment applied. This article presents a case of metastatic UM with successful complex treatment of liver metastases. A 49-year old female, underwent removal of the right eyeball in 1996 due to a histologically confirmed uveal melanoma. After 11 years, CT revealed a mass in the left kidney and multiple metastases in the liver. After left nephrectomy, 6 chemotherapy courses with dacarbazine were performed. The increasing liver metastases were observed. Additional 4 intraarterial (i/a chemotherapy courses were administered using cisplatin, doxorubicin, fluorouracil, and interferon alfa. After few courses increase in CTC Grade 4 liver transaminases was seen. A partial response was observed, and in December 2008 the patient underwent surgery removing all liver metastases by 7 wedge or atypical resections. All margins were tumor-free. 21 months after liver resections and 14 years since diagnosis, the patient is alive without evidence of disease. Successful treatment of metastatic uveal melanoma was due to a timely application of a combination of several treatment methods and good prognostic factors of the patient.

  6. Management of uveal tract melanoma: A comprehensive review

    International Nuclear Information System (INIS)

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

    2016-01-01

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

  7. 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.

  8. GPNMB expression in uveal melanoma: a potential for targeted therapy.

    Science.gov (United States)

    Williams, Michelle D; Esmaeli, Bita; Soheili, Aydin; Simantov, Ronit; Gombos, Dan S; Bedikian, Agop Y; Hwu, Patrick

    2010-06-01

    Uveal melanoma is an aggressive disease without effective adjuvant therapy for metastases. Despite genomic differences between cutaneous and uveal melanomas, therapies based on shared biological factors could be effective against both tumor types. High expression of glycoprotein-NMB (GPNMB) in cutaneous melanomas led to the development of CDX-011 (glembatumumab vedotin), a fully human monoclonal antibody against the extracellular domain of GPNMB conjugated to the cytotoxic microtubule toxin monomethylauristatin E. Ongoing phase II trials suggest that CDX-011 has activity against advanced cutaneous melanomas. To determine the potential role of CDX-011 in uveal melanomas, we studied their GPNMB expression. Paraffin-embedded tissues from 22 uveal melanomas treated by enucleation from 2004-2007 at one institution were evaluated immunohistochemically for expression of GPNMB using biotinylated CDX-011 (unconjugated) antibody. Melanoma cells were evaluated for percentage and intensity of expression. Spectral imaging was used in one case with high melanin content. Clinical data were reviewed. Twelve women and 10 men with a median age of 58.7 years (range: 28-83 years) were included. Eighteen of 21 tumors evaluated immunohistochemically (85.7%) expressed GPNMB in 10-90% of tumor cells with variable intensity (5 tumors, 1+; 11, 2+; and 2, 3+). Eleven of 18 tumors (61.1%) expressed GPNMB in >or=50% of cells. Spectral imaging showed diffuse CDX-011 (unconjugated) reactivity in the remaining case. Uveal melanoma, like cutaneous melanoma, commonly expresses GPNMB. Ongoing clinical trials of CDX-011 should be extended to patients with metastatic uveal melanoma to determine potential efficacy in this subset of patients with melanoma.

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

    NARCIS (Netherlands)

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

    2010-01-01

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

  10. 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.

  11. 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.

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

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    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.

  13. 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.

  14. 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....

  15. Effect of Gamma Knife Surgery for Uveal Melanoma

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    Kim, Gi Hong [Det. of Neurosurgery, Yensei Medical Center,Seoul (Korea, Republic of); Cho, Jung Hee; Park, Jae Il [Dept. of Radition Oncology, Yensei Medical Center, Seoul (Korea, Republic of)

    1997-11-15

    The optimal management of uveal melanoma is still a matter of controversy. To determine the effect of Gamma Knife surgery for patients with uveal malanoma. The authors reviewed the results of 5 patients underwent Gamma Knife surgery between Sep. 1993 and Dec. 1996. The mean age was 60.7 years ranging from 42.5 to 76.5 years. Median follow-up was 13.29 months and the patient with follow up period more than 6 months was 4. The mean tumor volume was 3442 mm{sup 3} (mean diameter 15.3 mm) and all patients were irradiated with a mean maximum dose of 74 Gy (range 60-80 Gy), using the 50% isodose. After Gamma Knife surgery. One patient showed complete disappearance in tumor size with follow-up 32 months, One enucleation due to progression, and 2 no interval change. In regard to vision, one patient blind. One enucleation, and 2 patients had no interval change. According to our experiences, Gamma Knife surgery for uveal melanoma be able to achieve local tumor control, spare the eyeball, and have possibility of save vision.

  16. 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

  17. Radiation related complications after ruthenium plaque radiotherapy of uveal melanoma

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    Summanen, P.; Immonen, I.; Kivela, T.; Tommila, P.; Tarkkanen, A. [Helsinki Univ. Central Hospital (Finland). Meilahti Clinic; Heikkonen, J. [Helsinki Univ. (Finland). Dept of Radiotherapy and Oncology

    1996-08-01

    The aims were to analyse radiation related complications and secondary enucleation after irradiation of malignant uveal melanoma with ruthenium-106 plaques. A series of 100 consecutive eyes irradiated in 1981-91 was analysed using the life table method and the Cox proportional hazards model. The 3 and 5 year probabilities of being without radiation cataract were 73% and 63%, without neovascular glaucoma 91% and 81%, without vitreous haemorrhage 83% and 74%, without radiation maculopathy 85% and 70%, and without radiation optic neuropathy 90% and 88%, respectively. (Author).

  18. Radiation related complications after ruthenium plaque radiotherapy of uveal melanoma

    International Nuclear Information System (INIS)

    Summanen, P.; Immonen, I.; Kivela, T.; Tommila, P.; Tarkkanen, A.; Heikkonen, J.

    1996-01-01

    The aims were to analyse radiation related complications and secondary enucleation after irradiation of malignant uveal melanoma with ruthenium-106 plaques. A series of 100 consecutive eyes irradiated in 1981-91 was analysed using the life table method and the Cox proportional hazards model. The 3 and 5 year probabilities of being without radiation cataract were 73% and 63%, without neovascular glaucoma 91% and 81%, without vitreous haemorrhage 83% and 74%, without radiation maculopathy 85% and 70%, and without radiation optic neuropathy 90% and 88%, respectively. (Author)

  19. 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

  20. 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.

  1. Optic nerve invasion of uveal melanoma

    DEFF Research Database (Denmark)

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

    2007-01-01

    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...... juxtapapillary tumors invading the optic nerve because of simple proximity to the nerve. A neurotropic subtype invades the optic nerve and retina in a diffuse fashion unrelated to tumor size or location. Udgivelsesdato: 2007-Jan...

  2. 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

  3. 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.

  4. 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

  5. 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.)

  6. Uveal melanoma: episcleral plaque radiotherapy. First Brazilian experience

    International Nuclear Information System (INIS)

    Erwenne, Clelia Maria; Freitas, Maria Alice Fernandes da Costa; Palazzi, Maristela Amaral; Pacheco, Jose Carlos Gouvea; Salvajoli, Joao Victor; Novaes, Paulo Eduardo; Trippe, Nivaldo; Pereira, Adelino Jose

    1994-01-01

    This paper describes the evolution of ten uveal melanoma carries who have been treated by cobalt-60 episcleral plaques since December, 1998 in A.C. Camargo Hospital, Antonio Prudente Foundation, Sao Paulo. The size of the lesions ranged from four to 11 mm in height and from 11 to 16 mm is the tumor base. The radiation doses applied ranged from 8.000 to 10.000 c Gy in the tumor apex and from 24.000 to 39.000 c Gy in the tumor base. A tumor reduction was observed in nine (90%) patients; in six (60%) the height and the base diameter reduced simultaneously; in three (30%) only the height reduced and in one (10%) the tumor dimensions became the same seven months after therapy. The follow-up of these cases ranged from four to 27 months. The authors discussed the indications, methods, visual results and observed complications of this kind of therapy. (author)

  7. Proton therapy for uveal melanomas and other eye lesions

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    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.)

  8. 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)

  9. Co-expression modules construction by WGCNA and identify potential prognostic markers of uveal melanoma.

    Science.gov (United States)

    Wan, Qi; Tang, Jing; Han, Yu; Wang, Dan

    2018-01-01

    Uveal melanoma is an aggressive cancer which has a high percentage recurrence and with a worse prognosis. Identify the potential prognostic markers of uveal melanoma may provide information for early detection of recurrence and treatment. RNA sequence data of uveal melanoma and patient clinic traits were obtained from The Cancer Genome Atlas (TCGA) database. Co-expression modules were built by weighted gene co -expression network analysis (WGCNA) and applied to investigate the relationship underlying modules and clinic traits. Besides, functional enrichment analysis was performed on these co-expression genes from interested modules. First, using WGCNA, identified 21 co-expression modules were constructed by the 10975 genes from the 80 human uveal melanoma samples. The number of genes in these modules ranged from 42 to 5091. Found four co -expression modules significantly correlated with three clinic traits (status, recurrence and recurrence Time). Module red, and purple positively correlated with patient's life status and recurrence Time. Module green positively correlates with recurrence. The result of functional enrichment analysis showed that the module magenta was mainly enriched genetic material assemble processes, the purple module was mainly enriched in tissue homeostasis and melanosome membrane and the module red was mainly enriched metastasis of cell, suggesting its critical role in the recurrence and development of the disease. Additionally, identified the hug gene (top connectivity with other genes) in each module. The hub gene SLC17A7, NTRK2, ABTB1 and ADPRHL1 might play a vital role in recurrence of uveal melanoma. Our findings provided the framework of co-expression gene modules of uveal melanoma and identified some prognostic markers might be detection of recurrence and treatment for uveal melanoma. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    1990-09-15

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

  11. 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.

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

    Science.gov (United States)

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

    2018-05-01

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

  13. Long-Term Metastatic Risk after Biopsy of Posterior Uveal Melanoma

    DEFF Research Database (Denmark)

    Bagger, Mette; Smidt-Nielsen, Isabel; Andersen, Mette K

    2018-01-01

    PURPOSE: Biopsy of posterior uveal melanoma continues to be intensely debated in terms of the clinical benefits and safety profile. Although several studies have reported a low frequency of ocular complications after tumor biopsy, the potential long-term risk of iatrogenic dissemination remains...... unresolved. The purpose of this study was to assess the risk of metastatic disease after biopsy of posterior uveal melanoma. DESIGN: Retrospective nationwide cohort study linking clinical and histopathologic records to pathology, cancer, and mortality registries. PARTICIPANTS: All patients with posterior...... uveal melanoma treated in Denmark between January 1985 and December 2016. METHODS: For each patient, we recorded detailed information on age, gender, tumor characteristics, and diagnostic and therapeutic measures, including tumor biopsy, if any, and the primary treating hospital. Absolute risk...

  14. Monosomy 3 by FISH in uveal melanoma: variability in techniques and results.

    Science.gov (United States)

    Aronow, Mary; Sun, Yang; Saunthararajah, Yogen; Biscotti, Charles; Tubbs, Raymond; Triozzi, Pierre; Singh, Arun D

    2012-09-01

    Tumor monosomy 3 confers a poor prognosis in patients with uveal melanoma. We critically review the techniques used for fluorescence in situ hybridization (FISH) detection of monosomy 3 in order to assess variability in practice patterns and to explain differences in results. Significant variability that has likely affected reported results was found in tissue sampling methods, selection of FISH probes, number of cells counted, and the cut-off point used to determine monosomy 3 status. Clinical parameters and specific techniques employed to report FISH results should be specified so as to allow meta-analysis of published studies. FISH-based detection of monosomy 3 in uveal melanoma has not been performed in a standardized manner, which limits conclusions regarding its clinical utility. FISH is a widely available, versatile technology, and when performed optimally has the potential to be a valuable tool for determining the prognosis of uveal melanoma. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. Diffusion-weighted MRI for uveal melanoma liver metastasis detection

    Energy Technology Data Exchange (ETDEWEB)

    Wagner, Mathilde; Petras, Slavomir; Servois, Vincent [Institut Curie, Department of Radiology and Nuclear Medicine, Paris (France); Mariani, Pascale; Cassoux, Nathalie [Institut Curie, Department of Surgery, Paris (France); Bidard, Francois Clement; Rodrigues, Manuel Jorge; Piperno-Neumann, Sophie [Institut Curie, Department of Medical Oncology, Paris (France); Farkhondeh, Fereshteh [Institut Curie, Department of Pathology, Paris (France)

    2015-08-15

    We aimed to assess the sensitivity of diffusion-weighted (DW) magnetic resonance (MR) imaging for the detection of pathologically confirmed uveal melanoma liver metastases (UMLM). Twenty patients who underwent complete surgical resection of their UMLM (N = 83) were included. Pre-surgery liver MR imaging included T2-weighted, T1-weighted, DW and dynamic-gadolinium-enhanced MR sequences. Two radiologists independently reviewed three sets of images (DW / morphologic-dynamic / combined) for each patient using intraoperative and pathological findings as a standard of reference. The sensitivities of the morphologic-dynamic and DW images for UMLM detection were 63 % and 59 %, respectively, for reader 1 (R1) and 64 % and 53 %, for reader 2 (R2). Sensitivity of the combined set was higher than sensitivity in the two other sets (R1:69 %, R2:67 %), but was only significantly different than the sensitivity of the DW images (McNemar test). For the three sets and the two readers, the sensitivity for UMLM smaller than 5 mm (37-46 %) was significantly lower than that for UMLM larger than 5 mm (67-90 %). The sensitivity for UMLM located in the subcapsular area (41-54 %) was significantly lower than that for intraparenchymal UMLM (68-86 %) (Chi-square test). Our study shows that the addition of DW imaging to morphologic-dynamic images does not significantly increase MR sensitivities for UMLM detection. (orig.)

  16. The gamma knife in ophthalmology. Part One--Uveal melanoma.

    Science.gov (United States)

    Wygledowska-Promieńska, Dorota; Jurys, Małgorzata; Wilczyński, Tomasz; Drzyzga, Łukasz

    2014-01-01

    The Gamma Knife was designed by Lars Leksell in the early 1950's. It gave rise to a new discipline of medicine--stereotactic radiosurgery. Primarily dedicated to neurosurgery, the Gamma Knife has become an alternative, widely used surgery technique. According to Elekta's statistics, approximately 60,000 people are treated with Leksell Gamma Knife every year and it is the most extensively studied stereotactic radiosurgery system in the world. The Leksell Gamma Knife can also be used in ophthalmology. The gamma ray beam concentration enables effective treatment of uveal melanoma, choroidal hemangioma, orbital tumors or even choroidal neovascularization. The virtue of Leksell Gamma Knife is its extreme precision, non-invasiveness and the possibility of outpatient treatment, which significantly reduces costs and diminishes post-operative complications. Innovative solutions shorten a single session to a minimum, which is very comfortable and safe for both staff and patients. Advantages and possible side effects of gamma knife radiosurgery are well-documented in the professional literature. The objective of this review is to present the recognized applications of Leksell Gamma Knife in ophthalmology.

  17. 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.

  18. 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

  19. 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.

  20. Survival analysis of patients with uveal melanoma after organ preserving and liquidation treatment

    Directory of Open Access Journals (Sweden)

    E. E. Grishina

    2018-01-01

    Full Text Available Rationale: Uveal melanoma is the most common primary malignancy of the eye.Aim: To evaluate survival in patients with uveal melanoma stratified according to the type of treatment and to identify factors significantly associated with their survival.Materials and methods: The study was performed on the data extracted from medical files and follow-up forms of patients with uveal melanoma seen in the Ophthalmological Clinical Hospital of the Department of Healthcare, Moscow, from 1977 to 2012. Analysis of survival was used to assess the life longevity of patients with uveal melanoma. The analysis was censored at January 2013, when vital status (dead or alive of all patients was assessed. The factors included into the study analysis, were those taken from the follow-up forms. The incidence of uveal melanoma in Moscow (2012 was 0.9 per 100,000 of the population, whereas its prevalence was 11.1 per 100,000.Results: 698 patients with uveal melanoma were included into the study, among them 260 (37% men (aged from 19 to 87 years, median age 60 years and 438 (63% women (aged from 18 to 93 years, median age 63 years; therefore, the proportion of women under the follow-up monitoring was by 26% higher than that of men. The liquidation treatment (mostly enucleation was performed in 358 (51% of the patients, whereas the organ preserving treatment in 340 (49%. At 5, 7, and 10 years of the follow-up, the disease-specific survival of patients with uveal melanoma after the organ preserving treatment (median survival has not been reached and after the liquidation treatment (median, 88 months were 89 ± 2, 83 ± 3, and 75 ± 4% versus 63 ± 3, 52 ± 4, and 47 ± 5%, respectively (р = 0.001. Overall survival and disease-specific survival of the patients after the liquidation treatment were significantly lower than in the patients after the organ-preserving treatment. According to multiple regression analysis, this was associated not with the type of

  1. 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.

  2. 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

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

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    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.

  4. 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.

  5. 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.

  6. Late prostatic metastasis of an uveal melanoma in a miniature Schnauzer dog.

    Science.gov (United States)

    Delgado, Esmeralda; Silva, João X; Pissarra, Hugo; Peleteiro, Maria C; Dubielzig, Richard R

    2016-07-01

    This manuscript describes a previously unreported clinical case of canine uveal melanoma in a miniature Schnauzer dog with an unusual location of metastasis (prostate) and delayed occurrence (3 years after primary tumor diagnosis and enucleation). Immunohistochemical labeling of both tumors with Melan A, Ki-67, and c-kit added some valuable information.

  7. Late prostatic metastasis of an uveal melanoma in a miniature Schnauzer dog

    OpenAIRE

    Delgado, Esmeralda; Silva, Jo?o X.; Pissarra, Hugo; Peleteiro, Maria C.; Dubielzig, Richard R.

    2016-01-01

    Key Clinical Message This manuscript describes a previously unreported clinical case of canine uveal melanoma in a miniature Schnauzer dog with an unusual location of metastasis (prostate) and delayed occurrence (3 years after primary tumor diagnosis and enucleation). Immunohistochemical labeling of both tumors with Melan A, Ki?67, and c?kit added some valuable information.

  8. 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...

  9. ADVANCED UVEAL MELANOMA WITH SUBDURAL METASTASIS MIMICKING MENINGEOMA - A CASE REPORT

    Directory of Open Access Journals (Sweden)

    Predrag Kovačević

    2011-03-01

    Full Text Available Uveal melanoma is a rare malignancy. Its clinical course is highly agressive. At thetime of diagnosis, extraocular extension is present in most of the cases.We present a case of 69-year-old white man admitted for sharp orbital pain. Advanced uveal melanoma was diagnosed. We found black-colored tumor rotruding from the left eye and multiple cutaneous metastases on the scalp. CT scan revealed intracranial tumor mimicking meningeoma in the left parietal region. Lymhogenous metastases were not found and other hematogenous metastases were excluded. After biopsy of the eye tumor and excisional biopsy of one skin tumor, the uveal melanoma was diagnosed and the left orbital exenteration and extirpation of intracranial tumor were performed. The reconstruction was performed using galeacutaneous flap harvested from craniotomy flap. Postoperative course was uneventful and the patient was released from pain. He refused the additional oncological treatment. After four months, he died of liver metastatic disease.The uveal melanoma is highly aggressive malignancy and isolated subdural metastasis is quite rare. The reconstruction with transposed galeacutaneous flap is versatile and secure technique after orbital exenteration.

  10. 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...

  11. Genetic evolution of uveal melanoma guides the development of an inflammatory microenvironment

    NARCIS (Netherlands)

    G. Gezgin (Gülçin); M. Dogrusöz (Mehmet); T.H. van Essen (T. Huibertus); W.G. Kroes (W.); G. Luyten (Gre); P.A. van der Velden (Pieter); V. Walter (Vonn); R.M. Verdijk (Robert); T. van Hall (Thorbald); S.H. van der Burg (Sjoerd); M.J. Jager (Martine J.)

    2017-01-01

    textabstractUveal melanoma (UM) is characterized by a number of genetic aberrations that follow a certain chronology and are tightly linked to tumor recurrence and survival. Loss of chromosome 3, bi-allelic loss of BAP1 expression, and gain in chromosome 8q have been associated with metastasis

  12. A- and B-mode ultrasound biometry in the proton beam irradiation of uveal melanomas

    International Nuclear Information System (INIS)

    Lou, P.L.; Gragoudas, E.

    1984-01-01

    Ultrasound biometry data were used for a treatment planning computer program that allows three-dimensional viewing of the eye containing a uveal melanoma. This program enables one to select an orientation of the eye relative to the path of the proton beam which best covers the tumor while avoiding important ocular structures. (Auth.)

  13. 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.

  14. 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.

  15. 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...... of the longest surviving patients in Sweden during the same time period (26 versus 12 months). METHODS/DESIGN: This is the protocol for a multicenter phase III trial randomizing patients with isolated liver metastases of uveal melanoma to IHP or best alternative care (BAC). Inclusion criteria include liver....... The planned sample size is 78 patients throughout five years. DISCUSSION: Patients with isolated liver metastases of uveal melanoma origin have a short expected survival and no standard treatment option exists. This is the first randomized clinical trial to evaluate IHP as a treatment option with overall...

  16. The use of single fraction Leksell stereotactic radiosurgery in the treatment of uveal melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Rennie, I. [Univ. of Sheffield, Dept. of Ophthalmology and Orthoptics (United Kingdom); Forster, D.; Kemeny, A. [Royal Hallamshire Hospital, Dept. of Neurosurgery (United Kingdom); Walton, L. [Royal Hallamshire Hospital, Dept. of Medical Physics (United Kingdom); Kunkler, I. [Weston Park Hospital, Dept. of Radiotherapy, Sheffield (United Kingdom)

    1996-11-01

    Fourteen patients with posterior uveal melanomas were treated using single fraction stereotactic radiosurgery. In each case a dose of 70 Gy was administered to the periphery of the tumour. Regression of the tumour has been observed in 13 patients, whilst the lesion has remained unchanged in one patient. The visual acuity has deteriorated in all 14 patients. Significant radiation induced adverse reactions were noted in 13 patients and include; retinopathy, optic neuropathy, rubeosis iridis, and secondary glaucoma. Two patients have required enucleation because of intractable rubeotic glaucoma. One patient has died from proven metastases. Although stereotactic radiosurgery appears to be a practical and effective method of treating uveal melanomas, its usefulness is limited by a high incidence of radiation induced adverse reactions. Further works is required to refine the current treatment protocol and establish an optimal prescription dose. (au) 30 refs.

  17. The use of single fraction Leksell stereotactic radiosurgery in the treatment of uveal melanoma

    International Nuclear Information System (INIS)

    Rennie, I.; Forster, D.; Kemeny, A.; Walton, L.; Kunkler, I.

    1996-01-01

    Fourteen patients with posterior uveal melanomas were treated using single fraction stereotactic radiosurgery. In each case a dose of 70 Gy was administered to the periphery of the tumour. Regression of the tumour has been observed in 13 patients, whilst the lesion has remained unchanged in one patient. The visual acuity has deteriorated in all 14 patients. Significant radiation induced adverse reactions were noted in 13 patients and include; retinopathy, optic neuropathy, rubeosis iridis, and secondary glaucoma. Two patients have required enucleation because of intractable rubeotic glaucoma. One patient has died from proven metastases. Although stereotactic radiosurgery appears to be a practical and effective method of treating uveal melanomas, its usefulness is limited by a high incidence of radiation induced adverse reactions. Further works is required to refine the current treatment protocol and establish an optimal prescription dose. (au) 30 refs

  18. CD147 and matrix-metalloproteinase-2 expression in metastatic and non-metastatic uveal melanomas.

    Science.gov (United States)

    Lüke, Julia; Vukoja, Vlatka; Brandenbusch, Tim; Nassar, Khaled; Rohrbach, Jens Martin; Grisanti, Salvatore; Lüke, Matthias; Tura, Aysegül

    2016-06-03

    Extracellular matrix remodelling regulated by matrix-metalloproteinase (MMP) inducer (CD147) is a crucial process during tumor cell invasion and regulation of blood supply. In this study, we evaluated the correlation of CD147 and MMP-2 expression with major prognostic factors for uveal melanoma and the development of metastasis. The expression of CD147 and MMP-2 was analyzed in 49 samples of uveal melanomas. Triple immunofluorescence stainings using markers against glial cells (GFAP), endothelial cells (CD34) and macrophages (CD68) were performed to further analyse the exact localisation of CD147 and MMP-2 positivity. In 28 cases clinical metastatic disease were found. The remaining 21 cases showed no signs of metastatic disease for an average follow-up of 10 years. Correlation analysis (Pearson correlation) was performed to analyse the association of CD147 and MMP-2 expression with known prognostic factors, vasculogenic mimicry (VM), the mature vasculature (von Willebrand Factor) and tumor induced angiogenesis (by means of Endoglin expression). CD147 and MMP-2 were expressed in 47 (96.0 %) of the uveal melanomas. CD147 up-regulation was significantly correlated with a higher MMP-2 expression. The overall expression analysis revealed no significant difference in the metastatic (p = 0.777) and non-metastatic subgroup (p = 0.585). No correlation of CD147 expression and any system of blood supply was evident. In the non-metastatic sub-group a significant correlation of clustered CD147 positive cells with largest basal diameter (p = 0.039), height (p = 0.047) and TNM-stage (p = 0.013) was evident. These data may indicate that CD147 regulates MMP-2 expression in uveal melanoma cells.

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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

    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...... 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 transplanted tumour cells were epithelioid and slightly larger than the primary tumour cells and had prominent nucleoli. However, the transplanted tumour retained a morphological appearance similar to that of the primary tumour. Immunohistochemical examinations demonstrated that the cells preserved...

  8. 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.

  9. About the value of Ruthenium 106 brachytherapy in the treatment of uveal melanomas

    International Nuclear Information System (INIS)

    Langmann, G.; Mosboeck, G.; Stuecklschwaiger, G.; Muellner, K.; Lechner, H.; Faulborn, J.

    2002-01-01

    Background: to investigate the clinical course, sequelae and visual function of uveal melanomas treated with Ruthenium 106 brachytherapy. Patients and method: 47 patients who underwent Ruthenium 106 brachytherapy between 1985 and 2000 were evaluated using Kaplan Meier statistical method. Mean follow up interval was 22 month (range 8 - 152 months). Results: Local tumor control rate was 85 %, 5 years possibility to avoid enucleation was 75 %. The most important sequelae were radiation optic neuropathy (29 %), maculopathy (37 %) and radiation retinopathy (32 %). After terminating the study the 34 % of the patients achieved a visual acuity of 20/40 and more, another 34 % had a visual function of 20/200 and lower. Conclusion: Ruthenium 106 brachytherapy is our method of choice in small medium sized uveal melanomas and a maximum tumor prominence of 6 mm. Tumors have to be located in the midperiphery and outer periphery of the fundus including the ciliary body. In addition to the indications introduced by Lommatzsch we treated ciliary body melanomas with a tumor base more than 3 clock hours (by shifting the plaque) as an alternative therapy to enucleation. (author)

  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. 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.

  12. 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...

  13. 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

  14. 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

  15. 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.

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

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    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. 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.

  18. Quantitative multiparametric MRI in uveal melanoma: increased tumor permeability may predict monosomy 3

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    Kamrava, Mitchell; Wang, Pin-Chieh; Roberts, Kristofer; Demanes, D.J. [University of California Los Angeles, Department of Radiation Oncology, Los Angeles, CA (United States); Sepahdari, Ali R.; Leu, Kevin; Ellingson, Benjamin M. [University of California Los Angeles, Department of Radiological Sciences, Los Angeles, CA (United States); McCannel, Tara [University of California Los Angeles, Department of Ophthalmology, Los Angeles, CA (United States)

    2015-08-15

    Uveal melanoma is a rare intraocular tumor with heterogeneous biological behavior, and additional noninvasive markers that may predict outcome are needed. Diffusion- and perfusion-weighted imaging may prove useful but have previously been limited in their ability to evaluate ocular tumors. Our purpose was to show the feasibility and potential value of a multiparametric (mp-) MRI protocol employing state of the art diffusion- and perfusion-weighted imaging techniques. Sixteen patients with uveal melanoma were imaged with mp-MRI. Multishot readout-segmented echoplanar diffusion-weighted imaging, quantitative dynamic contrast-enhanced (DCE) MR perfusion imaging, and anatomic sequences were obtained. Regions of interest (ROIs) were drawn around tumors for calculation of apparent diffusion coefficient (ADC) and perfusion metrics (K{sup trans}, v{sub e}, k{sub ep}, and v{sub p}). A generalized linear fit model was used to compare various MRI values with the American Joint Commission on Cancer (AJCC) tumor group and monosomy 3 status with significance set at P < 0.05. mp-MRI was performed successfully in all cases. MRI tumor height (mean [standard deviation]) was 6.5 mm (3.0). ROI volume was 278 mm{sup 3} (222). ADC was 1.07 (0.27) x 10-3 mm{sup 2}/s. DCE metrics were K{sup trans} 0.085/min (0.063), v{sub e} 0.060 (0.052), k{sub ep} 1.20/min (0.32), and v{sub p} 1.48 % (0.82). Patients with >33 % monosomy 3 had higher K{sup trans} and higher v{sub e} values than those with disomy 3 or ≤33 % monosomy (P < 0.01). There were no significant differences between ADC (P = 0.07), k{sub ep} (P = 0.37), and v{sub p} with respect to monosomy 3. mp-MRI for ocular tumor imaging using multishot EPI DWI and quantitative DCE perfusion is technically feasible. mp-MRI may help predict monosomy 3 in uveal melanoma. (orig.)

  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. Ovarian metastasis from uveal melanoma with MLH1/PMS2 protein loss in a patient with germline MLH1 mutated Lynch syndrome: consequence or coincidence?

    Science.gov (United States)

    Lobo, João; Pinto, Carla; Freitas, Micaela; Pinheiro, Manuela; Vizcaino, Rámon; Oliva, Esther; Teixeira, Manuel R; Jerónimo, Carmen; Bartosch, Carla

    2017-03-01

    Currently, uveal melanoma is not considered within the Lynch syndrome tumor spectrum. However, there are studies suggesting a contribution of microsatellite instability in sporadic uveal melanoma tumorigenesis. We report a 45-year-old woman who was referred for genetic counseling due to a family history of Lynch syndrome caused by a MLH1 mutation. She originally underwent enucleation of the right eye secondary to a uveal spindle cell melanoma diagnosed at age 25. The tumor recurred 22 years later presenting as an ovarian metastasis and concurrently a microscopic endometrial endometrioid carcinoma, grade 1/3 was diagnosed. Subsequent studies highlighted that the uveal melanoma showed high microsatellite instability and loss of MLH1 and PMS2 protein expression, with no MLH1 promoter methylation or BRAF mutation. Additionally, a GNAQ mutation was found. We conclude that our patient's uveal melanoma is most likely related to MLH1 germline mutation and thus Lynch syndrome related. To the best of our knowledge, this is the first report of uveal melanoma showing MLH1/PMS2 protein loss in the context of Lynch syndrome.

  1. 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.

  2. Association between traditional clinical high-risk features and gene expression profile classification in uveal melanoma.

    Science.gov (United States)

    Nguyen, Brandon T; Kim, Ryan S; Bretana, Maria E; Kegley, Eric; Schefler, Amy C

    2018-02-01

    To evaluate the association between traditional clinical high-risk features of uveal melanoma patients and gene expression profile (GEP). This was a retrospective, single-center, case series of patients with uveal melanoma. Eighty-three patients met inclusion criteria for the study. Patients were examined for the following clinical risk factors: drusen/retinal pigment epithelium (RPE) changes, vascularity on B-scan, internal reflectivity on A-scan, subretinal fluid (SRF), orange pigment, apical tumor height/thickness, and largest basal dimensions (LBD). A novel point system was created to grade the high-risk clinical features of each tumor. Further analyses were performed to assess the degree of association between GEP and each individual risk factor, total clinical risk score, vascularity, internal reflectivity, American Joint Committee on Cancer (AJCC) tumor stage classification, apical tumor height/thickness, and LBD. Of the 83 total patients, 41 were classified as GEP class 1A, 17 as class 1B, and 25 as class 2. The presence of orange pigment, SRF, low internal reflectivity and vascularity on ultrasound, and apical tumor height/thickness ≥ 2 mm were not statistically significantly associated with GEP class. Lack of drusen/RPE changes demonstrated a trend toward statistical association with GEP class 2 compared to class 1A/1B. LBD and advancing AJCC stage was statistically associated with higher GEP class. In this cohort, AJCC stage classification and LBD were the only clinical features statistically associated with GEP class. Clinicians should use caution when inferring the growth potential of melanocytic lesions solely from traditional funduscopic and ultrasonographic risk factors without GEP data.

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

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    Caujolle, Jean-Pierre, E-mail: ncaujolle@aol.com [Department of Ophthalmology, Saint Roch Hospital, Nice Teaching Hospital, Nice (France); Paoli, Vincent [Department of Ophthalmology, Saint Roch Hospital, Nice Teaching Hospital, Nice (France); Chamorey, Emmanuel [Department of Radiation Oncology, Protontherapy Center, Centre Antoine Lacassagne, Nice (France); Department of Biostatistics and Epidemiology, Centre Antoine Lacassagne, Nice (France); Maschi, Celia; Baillif, Stéphanie [Department of Ophthalmology, Saint Roch Hospital, Nice Teaching Hospital, Nice (France); Herault, Joël [Department of Radiation Oncology, Protontherapy Center, Centre Antoine Lacassagne, Nice (France); Gastaud, Pierre [Department of Ophthalmology, Saint Roch Hospital, Nice Teaching Hospital, Nice (France); Hannoun-Levi, Jean Michel [Department of Radiation Oncology, Protontherapy Center, Centre Antoine Lacassagne, Nice (France)

    2013-04-01

    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.

  4. 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

  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 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.)

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

    Directory of Open Access Journals (Sweden)

    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. Use of cabalt 60 and ruthenium 106 in the treatment of uveal malignant melanomas

    International Nuclear Information System (INIS)

    Bacin, F.; Rozan, R.; Escudero, P.; Donnarieix, D.; Dalens, H.

    1988-01-01

    Forty-one patients with uveal malignant melanomas were treated using local radiotherapy. Mean follow-up was two years. Tumor size was small (23.5%), intermediate (36.5%) or large (34%). Tumors were located in the mid-periphery (63.4%), posterior pole (24.3%) or outermost posterior segment (12.1%). Approximately 85 Gys were delivered to the tumor apex. 60 Co was used in 40 patients, and 106 Ru 106 Rh in one patient with a ciliary melanoma. Metastases developed in four patients, and three of these died (8.3%). A good response was observed in 55% of tumors, and stabilization with no further growth in 36.1%. Three lesions (8.3%) continued to grow despite treatment; one was enucleated and the two others were retreated conservatively. Visual acuity decreased in 43.3% of cases, but remained greater than 0.1 in 77.4% of patients. 63.3% of treated eyeballs developed complications including radiation-induced retinopathy (30%), exudative retinal detachment (26.6%), and vitreous hemorrhage (23.3%). These rates increased over time and after two years complications had developed in 80% of eyeballs [fr

  9. 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......, 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......-genome or whole-exome sequencing of 28 tumors or primary cell lines. These samples have a low mutation burden, with a mean of 10.6 protein changing mutations per sample (range 0 to 53). As expected for these sun-shielded melanomas the mutation spectrum was not consistent with an ultraviolet radiation signature...

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

    Directory of Open Access Journals (Sweden)

    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. 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

  13. 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

  14. Hippo-independent activation of YAP by the GNAQ uveal melanoma oncogene through a trio-regulated rho GTPase signaling circuitry.

    Science.gov (United States)

    Feng, Xiaodong; Degese, Maria Sol; Iglesias-Bartolome, Ramiro; Vaque, Jose P; Molinolo, Alfredo A; Rodrigues, Murilo; Zaidi, M Raza; Ksander, Bruce R; Merlino, Glenn; Sodhi, Akrit; Chen, Qianming; Gutkind, J Silvio

    2014-06-16

    Mutually exclusive activating mutations in the GNAQ and GNA11 oncogenes, encoding heterotrimeric Gαq family members, have been identified in ∼ 83% and ∼ 6% of uveal and skin melanomas, respectively. However, the molecular events underlying these GNAQ-driven malignancies are not yet defined, thus limiting the ability to develop cancer-targeted therapies. Here, we focused on the transcriptional coactivator YAP, a critical component of the Hippo signaling pathway that controls organ size. We found that Gαq stimulates YAP through a Trio-Rho/Rac signaling circuitry promoting actin polymerization, independently of phospholipase Cβ and the canonical Hippo pathway. Furthermore, we show that Gαq promotes the YAP-dependent growth of uveal melanoma cells, thereby identifying YAP as a suitable therapeutic target in uveal melanoma, a GNAQ/GNA11-initiated human malignancy. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Development and external validation of a prognostic nomogram for metastatic uveal melanoma.

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    Sara Valpione

    Full Text Available Approximately 50% of patients with uveal melanoma (UM will develop metastatic disease, usually involving the liver. The outcome of metastatic UM (mUM is generally poor and no standard therapy has been established. Additionally, clinicians lack a validated prognostic tool to evaluate these patients. The aim of this work was to develop a reliable prognostic nomogram for clinicians.Two cohorts of mUM patients, from Veneto Oncology Institute (IOV (N=152 and Mayo Clinic (MC (N=102, were analyzed to develop and externally validate, a prognostic nomogram.The median survival of mUM was 17.2 months in the IOV cohort and 19.7 in the MC cohort. Percentage of liver involvement (HR 1.6, elevated levels of serum LDH (HR 1.6, and a WHO performance status=1 (HR 1.5 or 2-3 (HR 4.6 were associated with worse prognosis. Longer disease-free interval from diagnosis of UM to that of mUM conferred a survival advantage (HR 0.9. The nomogram had a concordance probability of 0.75 (SE .006 in the development dataset (IOV, and 0.80 (SE .009 in the external validation (MC. Nomogram predictions were well calibrated.The nomogram, which includes percentage of liver involvement, LDH levels, WHO performance status and disease free-interval accurately predicts the prognosis of mUM and could be useful for decision-making and risk stratification for clinical trials.

  16. 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.

  17. BRD4-targeted therapy induces Myc-independent cytotoxicity in Gnaq/11-mutatant uveal melanoma cells.

    Science.gov (United States)

    Ambrosini, Grazia; Sawle, Ashley D; Musi, Elgilda; Schwartz, Gary K

    2015-10-20

    Uveal melanoma (UM) is an aggressive intraocular malignancy with limited therapeutic options. Both primary and metastatic UM are characterized by oncogenic mutations in the G-protein alpha subunit q and 11. Furthermore, nearly 40% of UM has amplification of the chromosomal arm 8q and monosomy of chromosome 3, with consequent anomalies of MYC copy number. Chromatin regulators have become attractive targets for cancer therapy. In particular, the bromodomain and extra-terminal (BET) inhibitor JQ1 has shown selective inhibition of c-Myc expression with antiproliferative activity in hematopoietic and solid tumors. Here we provide evidence that JQ1 had cytotoxic activity in UM cell lines carrying Gnaq/11 mutations, while in cells without the mutations had little effects. Using microarray analysis, we identified a large subset of genes modulated by JQ1 involved in the regulation of cell cycle, apoptosis and DNA repair. Further analysis of selected genes determined that the concomitant silencing of Bcl-xL and Rad51 represented the minimal requirement to mimic the apoptotic effects of JQ1 in the mutant cells, independently of c-Myc. In addition, administration of JQ1 to mouse xenograft models of Gnaq-mutant UM resulted in significant inhibition of tumor growth.Collectively, our results define BRD4 targeting as a novel therapeutic intervention against UM with Gnaq/Gna11 mutations.

  18. 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.

  19. 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.

  20. An ensemble method to predict target genes and pathways in uveal melanoma

    Directory of Open Access Journals (Sweden)

    Wei Chao

    2018-04-01

    Full Text Available This work proposes to predict target genes and pathways for uveal melanoma (UM based on an ensemble method and pathway analyses. Methods: The ensemble method integrated a correlation method (Pearson correlation coefficient, PCC, a causal inference method (IDA and a regression method (Lasso utilizing the Borda count election method. Subsequently, to validate the performance of PIL method, comparisons between confirmed database and predicted miRNA targets were performed. Ultimately, pathway enrichment analysis was conducted on target genes in top 1000 miRNA-mRNA interactions to identify target pathways for UM patients. Results: Thirty eight of the predicted interactions were matched with the confirmed interactions, indicating that the ensemble method was a suitable and feasible approach to predict miRNA targets. We obtained 50 seed miRNA-mRNA interactions of UM patients and extracted target genes from these interactions, such as ASPG, BSDC1 and C4BP. The 601 target genes in top 1,000 miRNA-mRNA interactions were enriched in 12 target pathways, of which Phototransduction was the most significant one. Conclusion: The target genes and pathways might provide a new way to reveal the molecular mechanism of UM and give hand for target treatments and preventions of this malignant tumor.

  1. Activation of the MAPK pathway is a common event in uveal melanomas although it rarely occurs through mutation of BRAF or RAS.

    Science.gov (United States)

    Zuidervaart, W; van Nieuwpoort, F; Stark, M; Dijkman, R; Packer, L; Borgstein, A-M; Pavey, S; van der Velden, P; Out, C; Jager, M J; Hayward, N K; Gruis, N A

    2005-06-06

    In contrast to cutaneous melanoma, there is no evidence that BRAF mutations are involved in the activation of the mitogen-activated protein kinase (MAPK) pathway in uveal melanoma, although there is increasing evidence that this pathway is activated frequently in the latter tumours. In this study, we performed mutation analysis of the RAS and BRAF genes in a panel of 11 uveal melanoma cell lines and 19 primary uveal melanoma tumours. In addition, Western blot and immunohistochemical analyses were performed on downstream members of the MAPK pathway in order to assess the contribution of each of these components. No mutations were found in any of the three RAS gene family members and only one cell line carried a BRAF mutation (V599E). Despite this, mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK), ERK and ELK were constitutively activated in all samples. These data suggest that activation of the MAPK pathway is commonly involved in the development of uveal melanoma, but occurs through a mechanism different to that of cutaneous melanoma.

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

    Directory of Open Access Journals (Sweden)

    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.

  3. Regression of uveal malignant melanomas following cobalt-60 plaque. Correlates between acoustic spectrum analysis and tumor regression

    International Nuclear Information System (INIS)

    Coleman, D.J.; Lizzi, F.L.; Silverman, R.H.; Ellsworth, R.M.; Haik, B.G.; Abramson, D.H.; Smith, M.E.; Rondeau, M.J.

    1985-01-01

    Parameters derived from computer analysis of digital radio-frequency (rf) ultrasound scan data of untreated uveal malignant melanomas were examined for correlations with tumor regression following cobalt-60 plaque. Parameters included tumor height, normalized power spectrum and acoustic tissue type (ATT). Acoustic tissue type was based upon discriminant analysis of tumor power spectra, with spectra of tumors of known pathology serving as a model. Results showed ATT to be correlated with tumor regression during the first 18 months following treatment. Tumors with ATT associated with spindle cell malignant melanoma showed over twice the percentage reduction in height as those with ATT associated with mixed/epithelioid melanomas. Pre-treatment height was only weakly correlated with regression. Additionally, significant spectral changes were observed following treatment. Ultrasonic spectrum analysis thus provides a noninvasive tool for classification, prediction and monitoring of tumor response to cobalt-60 plaque

  4. Current clinical practice: differential management of uveal melanoma in the era of molecular tumor analyses

    Directory of Open Access Journals (Sweden)

    Aaberg Jr TM

    2014-12-01

    Full Text Available Thomas M Aaberg Jr,1 Robert W Cook,2 Kristen Oelschlager,2 Derek Maetzold,2 P Kumar Rao,3 John O Mason III41Michigan State University Medical School and Retina Specialists of Michigan, Grand Rapids, MI, 2Castle Biosciences, Friendswood, TX, 3Washington University School of Medicine in St Louis, St Louis, MO, 4Retina Consultants of Alabama and University of Alabama Birmingham, Birmingham, AL, USA Objective: Assess current clinical practices for uveal melanoma (UM and the impact of molecular prognostic testing on treatment decisions.Design: Cross-sectional survey and sequential medical records review.Participants: Ophthalmologists who treat UM.Methods: (A Medical records review of all Medicare beneficiaries tested by UM gene expression profile in 2012, conducted under an institutional review board-approved protocol. (B 109 ophthalmologists specializing in the treatment of UM were invited to participate in 24-question survey in 2012; 72 were invited to participate in a 23-question survey in 2014.Main outcome measures: Responses analyzed by descriptive statistics, frequency analyses (percentages, Tukey, histograms, and Fisher’s exact test. Descriptive presentation of essay answers.Results: The review of Medicare medical records included 191 evaluable patients, 88 (46% with documented medical treatment actions or institutional policies related to surveillance plans. Of these 88, all gene expression profiling (GEP Class 1 UM patients were treated with low-intensity surveillance. All GEP Class 2 UM patients were treated with high-intensity surveillance (P<0.0001 versus Class 1. There were 36 (19% with information concerning referrals after initial diagnosis. Of these 36, all 23 Class 2 patients were referred to medical oncology; however, none of the 13 Class 1 patients were referred (P<0.0001 versus Class 1. Only Class 2 patients were recommended for adjunctive treatment regimens. 2012 survey: 50 respondents with an annual median of 35 new UM

  5. Development and External Validation of a Prognostic Nomogram for Metastatic Uveal Melanoma

    Science.gov (United States)

    Valpione, Sara; Moser, Justin C.; Parrozzani, Raffaele; Bazzi, Marco; Mansfield, Aaron S.; Mocellin, Simone; Pigozzo, Jacopo; Midena, Edoardo; Markovic, Svetomir N.; Aliberti, Camillo; Campana, Luca G.; Chiarion-Sileni, Vanna

    2015-01-01

    Background Approximately 50% of patients with uveal melanoma (UM) will develop metastatic disease, usually involving the liver. The outcome of metastatic UM (mUM) is generally poor and no standard therapy has been established. Additionally, clinicians lack a validated prognostic tool to evaluate these patients. The aim of this work was to develop a reliable prognostic nomogram for clinicians. Patients and Methods Two cohorts of mUM patients, from Veneto Oncology Institute (IOV) (N=152) and Mayo Clinic (MC) (N=102), were analyzed to develop and externally validate, a prognostic nomogram. Results The median survival of mUM was 17.2 months in the IOV cohort and 19.7 in the MC cohort. Percentage of liver involvement (HR 1.6), elevated levels of serum LDH (HR 1.6), and a WHO performance status=1 (HR 1.5) or 2–3 (HR 4.6) were associated with worse prognosis. Longer disease-free interval from diagnosis of UM to that of mUM conferred a survival advantage (HR 0.9). The nomogram had a concordance probability of 0.75 (SE .006) in the development dataset (IOV), and 0.80 (SE .009) in the external validation (MC). Nomogram predictions were well calibrated. Conclusions The nomogram, which includes percentage of liver involvement, LDH levels, WHO performance status and disease free-interval accurately predicts the prognosis of mUM and could be useful for decision-making and risk stratification for clinical trials. PMID:25780931

  6. 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.

  7. Multi-dimensional dosimetric verification of stereotactic radiotherapy for uveal melanoma using radiochromic EBT film

    International Nuclear Information System (INIS)

    Sturtewagen, E.; Fuss, M.; Georg, D.; Paelinck, L.; Wagter, C. de

    2008-01-01

    Since 1997, linac based stereotactic radiotherapy (SRT) of uveal melanoma has been continuously developed at the Department of Radiotherapy, Medical University Vienna. The aim of the present study was (i) to test a new type of radiochromic film (Gafchromic EBT) for dosimetric verification of class solutions for these treatments and (ii) to verify treatment plan acceptance criteria, which are based on gamma values statisitcs. An EPSON Expression 1680 Pro flat bed scanner was utilized for film reading. To establish a calibration curve, films were cut in squares of 2 x 2 cm 2 , positioned at 5 cm depth in a solid water phantom and were irradiated with different dose levels (0.5 and 5 Gy) in a 5 x 5 cm 2 field at 6 MV. A previously developed solid phantom (polystyrene) was used with overall dimensions corresponding to an average human head. EBT films were placed at four different depths (10, 20, 25 and 30 mm) and all films were irradiated simultaneously. Four different treatment plans were verified that resemble typical clinical situations. These plans differed in irradiation technique (conformal mMLC or circular arc SRT) and in tumour size (PTV of 1 or 2.5 cm 3 ). In-house developed software was applied to calculate gamma (γ) index values and to perform several statistical operations (e.g. γ-area histograms). At depths of 10 mm γ 1% (γ-value where 1% of the points have an equal or higher value in the region of interest) were between 1-3 and maximum γ > 1 (% of γ-values > 1 in the region of interest) areas were almost 30%. At larger depths, i.e. more close to the isocenter, γ 1% was > 1 areas were mostly < 5%. Average γ values were about 0.5. Besides the compromised accuracy in the buildup region, previously defined IMRT acceptance criteria [Stock et al., Phys. Med. Biol. 50 (2005) 399-411] could be applied as well to SRT. Radiochromic EBT films, in combination with a flat-bed scanner, were found to be an ideal multidimensional dosimetric tool for treatment

  8. Proton beam radiotherapy versus fractionated stereotactic radiotherapy for uveal melanomas: A comparative study.

    Science.gov (United States)

    Weber, Damien C; Bogner, Joachim; Verwey, Jorn; Georg, Dietmar; Dieckmann, Karin; Escudé, Lluis; Caro, Monica; Pötter, Richard; Goitein, Gudrun; Lomax, Antony J; Miralbell, Raymond

    2005-10-01

    A comparative treatment planning study was undertaken between proton and photon therapy in uveal melanoma to assess the potential benefits and limitations of these treatment modalities. A fixed proton horizontal beam (OPTIS) and intensity-modulated spot-scanning proton therapy (IMPT), with multiple noncoplanar beam arrangements, was compared with linear accelerator-based stereotactic radiotherapy (SRT), using a static and a dynamic micromultileaf collimator and intensity-modulated RT (IMRS). A planning CT scan was performed on a brain metastasis patient, with a 3-mm acquisition slice spacing and the patient looking at a luminous spot with the eyes in three different positions (neutral and 25 degrees right and left). Four different gross tumor volumes were defined for each treatment technique. These target scenarios represented different locations (involving vs. not involving the macula and temporal vs. nasal) and volumes (10 x 6 mm vs. 16 x 10 mm) to challenge the proton and photon treatment techniques. The planning target volume was defined as the gross tumor volume plus 2 mm laterally and 3 mm craniocaudally for both modalities. A dose homogeneity of 95-99% of the planning target volume was used as the "goal" for all techniques. The dose constraint (maximum) for the organs at risk (OARs) for both the proton and the SRT photon plans was 27.5, 22.5, 20, and 9 CGE-Gy for the optic apparatus, retina, lacrimal gland, and lens, respectively. The dose to the planning target volume was 50 CGE-Gy in 10 CGE-Gy daily fractions. The plans for proton and photon therapy were computed using the Paul Scherrer Institute and BrainSCAN, version 5.2 (BrainLAB, Heimstetten, Germany) treatment planning systems, respectively. Tumor and OARs dose-volume histograms were calculated. The results were analyzed using the dose-volume histogram parameters, conformity index (CI(95%)), and inhomogeneity coefficient. Target coverage of all simulated uveal melanomas was equally conformal with the

  9. Proton beam radiotherapy versus fractionated stereotactic radiotherapy for uveal melanomas: A comparative study

    International Nuclear Information System (INIS)

    Weber, Damien C.; Bogner, Joachim; Verwey, Jorn; Georg, Dietmar; Dieckmann, Karin; Escude, Lluis; Caro, Monica; Poetter, Richard; Goitein, Gudrun; Lomax, Antony J.; Miralbell, Raymond

    2005-01-01

    Purpose: A comparative treatment planning study was undertaken between proton and photon therapy in uveal melanoma to assess the potential benefits and limitations of these treatment modalities. A fixed proton horizontal beam (OPTIS) and intensity-modulated spot-scanning proton therapy (IMPT), with multiple noncoplanar beam arrangements, was compared with linear accelerator-based stereotactic radiotherapy (SRT), using a static and a dynamic micromultileaf collimator and intensity-modulated RT (IMRS). Method and Materials: A planning CT scan was performed on a brain metastasis patient, with a 3-mm acquisition slice spacing and the patient looking at a luminous spot with the eyes in three different positions (neutral and 25 deg right and left). Four different gross tumor volumes were defined for each treatment technique. These target scenarios represented different locations (involving vs. not involving the macula and temporal vs. nasal) and volumes (10 x 6 mm vs. 16 x 10 mm) to challenge the proton and photon treatment techniques. The planning target volume was defined as the gross tumor volume plus 2 mm laterally and 3 mm craniocaudally for both modalities. A dose homogeneity of 95-99% of the planning target volume was used as the 'goal' for all techniques. The dose constraint (maximum) for the organs at risk (OARs) for both the proton and the SRT photon plans was 27.5, 22.5, 20, and 9 CGE-Gy for the optic apparatus, retina, lacrimal gland, and lens, respectively. The dose to the planning target volume was 50 CGE-Gy in 10 CGE-Gy daily fractions. The plans for proton and photon therapy were computed using the Paul Scherrer Institute and BrainSCAN, version 5.2 (BrainLAB, Heimstetten, Germany) treatment planning systems, respectively. Tumor and OARs dose-volume histograms were calculated. The results were analyzed using the dose-volume histogram parameters, conformity index (CI 95% ), and inhomogeneity coefficient. Results: Target coverage of all simulated uveal

  10. PRIMARY ENDOPROSTHETIC REPLACEMENT OF THE ANOPHTHALMIC ORBIT IN PATIENTS WITH UVEAL MELANOMA: SIX-YEAR FOLLOW-UP RESULTS

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    A. A. Yarovoy

    2012-01-01

    Full Text Available A locomotor stump was formed in 36 patients (28 women and 8 men, by implanting an endoprosthesis for enucleation of the eyeball with uveal melanoma (UM. The indication for endoprosthesis implantation was no signs of extrabulbar growth. A modified 17–19 mm silicone implant covered with strips from a dura mater graft and medical mesh fabric was used as an orbital implant. The follow-up was 3 to 72 months (mean 32.5 months. All the patients achieved a satisfactory cosmetic effect. None patient was found to have a recurrent orbital tumor. Out of the complications, anterior implant surface denudation was noted in 4 patients. Two patients developed metastases. The absence of recurrent orbital UM at a 6-year follow-up enables primary endoprosthetic replacement of the orbit for UM to be regarded as a safe and reasonable method for patient cosmetic rehabilitation. 

  11. Peptidome profiling of human serum of uveal melanoma patients based on magnetic bead fractionation and mass spectrometry

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    Xiang-Yu Shi

    2017-06-01

    Full Text Available AIM: To find new biomarkers for uveal melanoma (UM by analyzing the serum peptidome profile. METHODS: Proteomic spectra in patients with UM before and after operation were analyzed and compared with those of healthy controls. Magnetic affinity beads were used to capture serum peptides and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF mass spectrometer were used to compile serum peptide profiles. RESULTS: A panel of 49 peptides were differentially expressed between UM patients and controls, of which 33 peptides were of higher intensities in patient group and 16 peptides were of higher intensities in control group. Based on combined use of these potential markers, peptides with mean molecular masses of 1467 and 9289.0 Da provide high sensitivity (83.3%, specificity (100% and accuracy rate (93.0% together to differentiate melanoma patients from healthy controls. At the time point of 6mo postoperatively, the levels of many peptides differentially expressed before surgery showed no more statistical difference between the patients and the control group. Fibrinogen α-chain precursors were identified as potential UM markers. CONCLUSION: We have shown that a convenient and fast proteomic technique, affinity bead separation and MALDI-TOF analysis combined with bioinformatic software, facilitates the identification of novel biomarkers for UM.

  12. 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

  13. The first description of the complete natural history of uveal melanoma by two Scottish surgeons, Allan Burns and James Wardrop.

    Science.gov (United States)

    Kivelä, Tero T

    2018-03-01

    James Wardrop (1782-1869), a young Scottish surgeon and an early ophthalmologist in Edinburgh, is credited for describing in 1809 retinoblastoma as an entity in his treatise 'Observations on Fungus Haematodes or Soft Cancer'. His treatise also reveals that Allan Burns (1781-1813), another young Scottish surgeon and anatomist, had invited Wardrop to assist in enucleating an eye from a 41-year-old Glasgow woman who, in retrospect, had a uveal melanoma. Her eye had become blind 4 months after symptoms of exudative retinal detachment had appeared, and it had become painful after a further 2-4 months. The tumour eventually perforated the sclera, and she died within a year thereafter of hepatic metastases. Burns and Wardrop went on to publish detailed parallel accounts of the symptoms, signs, ophthalmic pathology and post-mortem findings regarding the primary, recurrent and metastatic tumour. Burns may have performed the post-mortem after exhuming the body, a common occurrence in early 19th Century Scotland, a thriving hub for teaching morbid anatomy to young surgeons at the time. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  14. 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.

  15. 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.

  16. 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)

  17. 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

  18. 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.

  19. 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.

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

    Science.gov (United States)

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

    2014-01-01

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

  1. 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.)

  2. 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.

  3. 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

  4. 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.

  5. 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

  6. Uruguayan experience melanomauveal: results of 63 patients at 20 years follow-up; Experiencia uruguaya en melanoma uveal: resultados de 63 pacientes en 20 años de seguimiento

    Energy Technology Data Exchange (ETDEWEB)

    Krygier, G; Castillo, C; Della Valle, A; Ugartemendia, E; Sabini, G; Viola, A; Musé, I. [Hospital de Clínicas, Facultad de Medicina, Montevideo (Uruguay)

    2010-12-15

    Fulltext: Uveal melanoma is the most common malignant intraocular tumor in primitive adults (70%). It happens so often sporadic and uveal melanoma family comprises only 0.6% of patients. 63 patients assisted information was collected at six different institutions Montevideo, Uruguay, for a period of 20 years. The diagnosis was confirmed by pathology in 55/63 (87%) cases. Radical surgery (predominantly enucleation) was performed on 54/63 (86%) patients. other options treatment were orbital exenteration, radiotherapy and brachytherapy protons. 25/63 (40%) developed distant metastases, mainly in liver. The median age at diagnosis was 59 years old. The most common symptom was decreased visual acuity in 50/63 (77%). Three patients had extension extrascleral tumor and pigmented lesions presented. There was a correlation between mixed and epithelioid tumors with survival statistically significant (p <0.01) but there was no relationship between tumor diameter and survival (p = 0.06). Three clinical cases of familial uveal melanoma demonstrated that They involved the first generation of the same family (brothers), one of the which also had breast cancer 2 years before ocular tumor. a mutation in the BRCA2 gene was identified. The three brothers were enucleated and died with a median survival of 19 months due to distant metastases. Secundarismo liver was confirmed radiologically in 23/63 (36.5%) cases. The disease-free interval from diagnosis of ocular tumor metastasis was 40.5 months and the median survival for the disease metastasis was 4 months. Overall survival was 88 months (95% CI 75-100). This study illustrates the natural history of this entity by taking into account the behavior heterogeneous of it in our country, especially with outstanding fatal and family with uveal melanoma (three brothers), and commitment extrascleral as the first clinical fact present in three other cases.

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

    Science.gov (United States)

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

    2014-05-01

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

  8. A prospective analysis of {sup 18}F-FDG PET/CT in patients with uveal melanoma: comparison between metabolic rate of glucose (MRglu) and standardized uptake value (SUV) and correlations with histopathological features

    Energy Technology Data Exchange (ETDEWEB)

    Calcagni, Maria Lucia; Mattoli, Maria Vittoria; Rufini, Vittoria; Giordano, Alessandro [Universita Cattolica del Sacro Cuore, Institute of Nuclear Medicine, Roma (Italy); Blasi, Maria Antonietta; Sammarco, Maria Grazia [Universita Cattolica del Sacro Cuore, Institute of Ophthalmology, Roma (Italy); Petrone, Gianluigi; Mule, Antonino [Universita Cattolica del Sacro Cuore, Department of Pathology, Roma (Italy); Indovina, Luca [Universita Cattolica del Sacro Cuore, Physics Unit, Roma (Italy)

    2013-10-15

    To evaluate whether standardized uptake value (SUV) and/or metabolic rate of glucose (MRglu) are different among epithelioid, mixed, and spindle cell uveal melanomas, as well as between low and high risk melanomas; to correlate ultrasonographic data and metabolic parameters with histopathological features; and to assess the role of {sup 18}F-FDG PET/CT for evaluating prognosis. Of 34 eligible patients prospectively enrolled with clinical suspicion of medium/large uveal melanoma, 26 (15 men, mean age 62.8 {+-} 11.8 years) were evaluated. All patients underwent metastatic work-up, 3-D dynamic brain and whole-body {sup 18}F-FDG PET/CT, and surgery. Of the 26 ocular lesions, 23 showed {sup 18}F-FDG uptake, with a sensitivity of 88 %. MRglu was significantly higher in the epithelioid cell melanomas than in the spindle cell melanomas, as well as in high-risk lesions than in low-risk lesions (p = 0.01, p = 0.02, respectively). SUV and MRglu were correlated with histopathological features while ultrasonographic data were not. MRglu is useful for distinguishing the different cell types in uveal melanoma, as well as high-risk from low-risk lesions, while SUV is not. MRglu provides a more accurate evaluation of glucose consumption, whereas SUV provides only an estimation. In addition, the metabolic parameters correlate with histopathological features, well also reflecting cellular behaviour in ocular malignancy. A longer follow-up is needed to assess the role of {sup 18}F-FDG in evaluating prognosis. (orig.)

  9. 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.

  10. 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

  11. 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

  12. 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

  13. 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

  14. Limited value of 18F-FDG PET/CT and S-100B tumour marker in the detection of liver metastases from uveal melanoma compared to liver metastases from cutaneous melanoma

    International Nuclear Information System (INIS)

    Strobel, K.; Veit-Haibach, P.; Fischer, D.R.; Steinert, Hans C.; Schulthess, G.K. von; Bode, B.; Dummer, R.; Imhof, L.; Goldinger, S.

    2009-01-01

    The objective of this study was to evaluate the value of 18 F-FDG PET/CT and S-100B tumour marker for the detection of liver metastases from uveal melanoma in comparison to liver metastases from cutaneous melanoma. A retrospective evaluation was conducted of 27 liver metastases in 13 patients with uveal melanoma (UM) (mean age: 56.8, range: 30-77) and 43 liver metastases in 14 patients (mean age: 57.9, range: 40-82) with cutaneous melanoma (CM) regarding size and FDG uptake by measuring the maximum standardized uptake value (SUV max ). S-100B serum tumour markers were available in 20 patients. Cytology, histology, additional morphological imaging and follow-up served as reference standard. In nine patients liver metastases were further evaluated histologically regarding GLUT-1 and S-100 receptor expression and regarding epithelial or spindle cell growth pattern. Of 27 liver metastases in 6 of 13 patients (46%) with UM, 16 (59%) were FDG negative, whereas all liver metastases from CM were positive. Liver metastases from UM showed significantly (p max (mean: 3.5, range: 1.5-13.4) compared with liver metastases from CM (mean: 6.6, range: 2.3-15.3). In four of six (66.7%) patients with UM and liver metastases S-100B was normal and in two (33.3%) increased. All PET-negative liver metastases were detectable by morphological imaging (CT or MRI). S-100B was abnormal in 13 of 14 patients with liver metastases from CM. S-100B values were significantly higher (p = 0.007) in the CM patient group (mean S-100B: 10.9 μg/l, range: 0.1-115 μg/l) compared with the UM patients (mean: 0.2 μg/l, range: 0.0-0.5 μg/l). Histological work-up of the liver metastases showed no obvious difference in GLUT-1 or S-100 expression between UM and CM liver metastases. The minority (36%) of patients with UM had extrahepatic metastases and the majority (86%) of patients with CM had extrahepatic metastases, respectively. There was a close to significant trend to better survival of UM patients

  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. 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.

  17. Stages of Intraocular (Uveal) Melanoma

    Science.gov (United States)

    ... A to Z List of Cancer Drugs Complementary & Alternative Medicine (CAM) Questions to Ask about Your Treatment Research ... Treatment Side Effects Clinical Trials Cancer Drugs Complementary & Alternative Medicine Coping Feelings & Cancer Adjusting to Cancer Self Image & ...

  18. 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

  19. Melanoma

    Science.gov (United States)

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

  20. Lacrimal Gland Radiosensitivity in Uveal Melanoma Patients

    International Nuclear Information System (INIS)

    Muller, Karin; Nowak, Peter J.C.M.; Naus, Nicole; Pan, Connie de; Santen, Cornelis A. van; Levendag, Peter; Luyten, Gre P.M.

    2009-01-01

    Purpose: To find a dose-volume effect for inhomogeneous irradiated lacrimal glands. Methods and Materials: Between 1999 and 2006, 72 patients (42 men and 30 women) were treated with fractionated stereotactic radiotherapy in a prospective, nonrandomized clinical trial (median follow-up, 32 months). A total dose of 50 Gy was given on 5 consecutive days. The mean of all Schirmer test results obtained ≥6 months after treatment was correlated with the radiation dose delivered to the lacrimal gland. Also, the appearance of dry eye syndrome (DES) was related to the lacrimal gland dose distribution. Results: Of the 72 patients, 17 developed a late Schirmer value <10 mm; 9 patients developed DES. A statistically significant relationship was found between the received median dose in the lacrimal gland vs. reduced tear production (p = 0.000) and vs. the appearance of DES (p = 0.003), respectively. A median dose of 7 Gy/fraction to the lacrimal gland caused a 50% risk of low Schirmer results. A median dose of 10 Gy resulted in a 50% probability of DES. Conclusion: We found a clear dose-volume relationship for irradiated lacrimal glands with regard to reduced tear production and the appearance of DES.

  1. Treatment Options for Intraocular (Uveal) Melanoma

    Science.gov (United States)

    ... A to Z List of Cancer Drugs Complementary & Alternative Medicine (CAM) Questions to Ask about Your Treatment Research ... Treatment Side Effects Clinical Trials Cancer Drugs Complementary & Alternative Medicine Coping Feelings & Cancer Adjusting to Cancer Self Image & ...

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

    Science.gov (United States)

    ... A to Z List of Cancer Drugs Complementary & Alternative Medicine (CAM) Questions to Ask about Your Treatment Research ... Treatment Side Effects Clinical Trials Cancer Drugs Complementary & Alternative Medicine Coping Feelings & Cancer Adjusting to Cancer Self Image & ...

  3. General Information about Intraocular (Uveal) Melanoma

    Science.gov (United States)

    ... A to Z List of Cancer Drugs Complementary & Alternative Medicine (CAM) Questions to Ask about Your Treatment Research ... Treatment Side Effects Clinical Trials Cancer Drugs Complementary & Alternative Medicine Coping Feelings & Cancer Adjusting to Cancer Self Image & ...

  4. 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

  5. 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.

  6. Bilateral diffuse uveal melanocytic proliferation

    DEFF Research Database (Denmark)

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

    2017-01-01

    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...

  7. What is presumed when we presume consent?

    Directory of Open Access Journals (Sweden)

    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

  8. MRI findings of uveal metastases

    International Nuclear Information System (INIS)

    Chen Qinghua; Wang Zhenchang; Xian Junfang; Yan Fei; He Liyan; Tian Qichang; Yang Bentao; Liu Zhonglin

    2007-01-01

    Objective: To evaluate MR imaging findings of uveal metastases. Methods: MR imaging findings of 20 cases with uveal metastases comfirmed by pathology or follow-up were retrospectively analyzed. MR imaging was performed in 20 patients, of which postcontrast T 1 -weighted imaging was performed in 19 patients including dynamic contrast enhancement scanning in four cases. Results: Metastatic tumor was found in the iris and ciliary body in two cases, and in choroid in 18 cases. The tumor demonstrated slightly hypointense signal on T 1 -weighted imaging and isointense signal on T 2 -weighted imaging in two cases, isointense signal on T 1 -weighted imaging and isointense signal on T 2 -weighted imaging in nine cases, isointense signal on T 1 -weighted imaging and slightly hyperintense signal on T 2 -weighted imaging in three cases, isointense signal on T 1 -weighted imaging and slightly hypointense signal on T 2 - weighted imaging in three cases, slightly hyperintense signal on T 1 -weighted imaging and slightly hypointense signal on T 2 -weighted imaging in two cases, and slightly hyperintense signal on T 1 -weighted imaging and slightly hyperintense signal on T 2 -weighted imaging in one case. The tumor appeared as mild thickness of the wall of the globe in eight cases, a crescent mass in three cases, a fusiform mass in seven cases, and a nodule in two cases. Nineteen patients showed moderate or marked enhancement on postcontrast T 1 -weighted imaging. The time-intensity curve of dynamic contrast enhancement in four patients suggested a rapid enhancement and slow washout pattern. Retinal detachment was observed in 11 patients and abnormal signal intensity within the vitreous body was seen in two cases. Conclusion: MRI can display the location, shape, signal characteristics, and enhancement pattern of uveal metastases, contributing to diagnosis and differential diagnosis. (authors)

  9. 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.

  10. 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 patien...

  11. A challenging case of ocular melanoma.

    Science.gov (United States)

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

    2015-01-01

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

  12. 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. T...

  13. 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.

  14. MuSIC report III: tumour microcirculation patterns and development of metastasis in long-term follow-up of melanocytic uveal tumours.

    Science.gov (United States)

    Klingenstein, Annemarie; Schaumberger, Markus M; Freeman, William R; Folberg, Robert; Mueller, Arthur J; Schaller, Ulrich C

    2016-03-01

    To statistically determine differences in microcirculation patterns between nevi and uveal melanomas and the influence of these patterns on metastatic potential in the long-term follow-up of 112 patients with melanocytic uveal tumours. In vivo markers indicating malignancy and metastatic potential have implications for treatment decision. Primary diagnosis and work-up included clinical examination, fundus photography, standardized A and B scan echography as well as evaluation of tumour microcirculation patterns via confocal fluorescein and indocyanine green angiography (ICGA). Patient data were collected from the patient files, the tumour registry or personal contact. Statistical analysis was performed with spss 22.0 using chi-square, Fisher's exact test and Kaplan-Meier survival analysis. Forty-three uveal melanocytic lesions remained untreated and were retrospectively classified as benign nevi, whereas 69 lesions were malignant melanomas (T1: 32, T2: 28, T3: 6 and T4: 3). 'Silent' and 'arcs without branching' were found significantly more often in nevi (p = 0.001 and p = 0.010), whereas 'parallel with cross-linking' and 'networks' were significantly more frequent in melanomas (p = 0.022 and p = 0.029). The microcirculation pattern 'parallel with cross-linking' proved significantly more frequent in patients who developed metastases (p = 0.001). Certain microcirculation patterns may guide us in differentiating uveal nevi from malignant melanomas. A non-invasive prognostic marker can be of great value for borderline lesions in which cytology is less likely taken. 'Parallel with cross-linking' did not only indicate malignancy, but it was also associated with later tumour metastasis. © 2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  15. 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

  16. 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...

  17. 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.

  18. Ocular Melanoma

    Science.gov (United States)

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

  19. Organ procurement: let's presume consent

    OpenAIRE

    Moustarah, F

    1998-01-01

    IN WINNING FIRST PRIZE in the Logie Medical Ethics Essay Contest in 1997, Dr. Fady Moustarah made a strong and compelling argument in favour of presumed consent in the procurement of donor organs. He stressed that a major education campaign will be needed when such a policy is adopted lest some people begin to regard physicians as "organ vultures."

  20. 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...

  1. 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

  2. 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.

  3. 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...

  4. Is it sufficient to repeat LINEAR accelerator stereotactic radiosurgery in choroidal melanoma?

    Science.gov (United States)

    Furdova, A; Horkovicova, K; Justusova, P; Sramka, M

    One day session LINAC based stereotactic radiosurgery (SRS) at LINAC accelerator is a method of "conservative" attitude to treat the intraocular malignant uveal melanoma. We used model Clinac 600 C/D Varian (system Aria, planning system Corvus version 6.2 verification IMRT OmniPro) with 6 MeV X by rigid immobilization of the eye to the Leibinger frame. The stereotactic treatment planning after fusion of CT and MRI was optimized according to the critical structures (lens, optic nerve, also lens and optic nerve at the contralateral side, chiasm). The first plan was compared and the best plan was applied for therapy at C LINAC accelerator. The planned therapeutic dose was 35.0 Gy by 99 % of DVH (dose volume histogram). In our clinical study in the group of 125 patients with posterior uveal melanoma treated with SRS, in 2 patients (1.6 %) was repeated SRS indicated. Patient age of the whole group ranged from 25 to 81 years with a median of 54 TD was 35.0 Gy. In 2 patients after 5 year interval after stereotactic radiosurgery for uveal melanoma stage T1, the tumor volume increased to 50 % of the primary tumor volume and repeated SRS was necessary. To find out the changes in melanoma characteristics after SRS in long term interval after irradiation is necessary to follow up the patient by an ophthalmologist regularly. One step LINAC based stereotactic radiosurgery with a single dose 35.0 Gy is one of treatment options to treat T1 to T3 stage posterior uveal melanoma and to preserve the eye globe. In some cases it is possible to repeat the SRS after more than 5 year interval (Fig. 8, Ref. 23).

  5. 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.

  6. Genetic Background of Iris Melanomas and Iris Melanocytic Tumors of Uncertain Malignant Potential.

    Science.gov (United States)

    van Poppelen, Natasha M; Vaarwater, Jolanda; Mudhar, Hardeep S; Sisley, Karen; Rennie, Ian G; Rundle, Paul; Brands, Tom; van den Bosch, Quincy C C; Mensink, Hanneke W; de Klein, Annelies; Kiliç, Emine; Verdijk, Robert M

    2018-01-19

    Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. Iris melanoma comprises 4% to 10% of all UMs and has a lower mortality rate. The genetic changes in iris melanoma are not as well characterized as ciliary body or choroidal melanoma. The aim of this study was to gain more insight into the genetic background of iris melanoma and iris nevi. Multicenter, retrospective case series. Patients diagnosed with iris melanoma or iris nevi who underwent surgical intervention as primary or secondary treatment. Next-generation sequencing of GNAQ, GNA11, EIF1AX, SF3B1, BAP1, NRAS, BRAF, PTEN, c-Kit, TP53, and TERT was performed on 30 iris melanomas and 7 iris nevi. Copy number status was detected using single nucleotide polymorphisms (SNPs) included in the next-generation sequencing (NGS) panel, SNP array, or fluorescent in situ hybridization. BAP1 immunohistochemistry was performed on all samples. Mutation and copy number status were analyzed. Results of BAP1 immunohistochemistry were used for survival analysis. In 26 of the 30 iris melanoma and all iris nevi, at least 1 mutation was identified. Multiple mutations were detected in 23 iris melanoma and 5 nevi, as well as mutations in GNAQ and GNA11. Furthermore, 13 of 30 BAP1, 5 of 30 EIF1AX, and 2 of 30 SF3B1 mutations were identified in iris melanoma. No correlation between BAP1 status and disease-free survival was found. The iris nevi showed 1 EIF1AX and 3 BAP1 mutations. Two of the nevi, with a BAP1 mutation, were histologically borderline malignant. Mutations in NRAS, BRAF, PTEN, c-KIT, and TP53 were detected in 6 iris melanomas and 4 iris nevi. Mutations that are often found in uveal and cutaneous melanoma were identified in this cohort of iris melanomas and iris nevi. Therefore, iris melanomas harbor a molecular profile comparable to both choroidal melanoma and cutaneous melanoma. These findings may offer adjuvant targeted therapies for iris melanoma. There was no prognostic significance of

  7. 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.

  8. 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....

  9. 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.

  10. Clinical experience of stereotactic radiosurgery at a linear accelerator for intraocular melanoma.

    Science.gov (United States)

    Furdova, Alena; Sramka, Miron; Chorvath, Martin; Kralik, Gabriel; Furda, Robert; Gregus, Michal

    2017-10-01

    Long-term results with linear accelerator LINAC-based stereotactic radiosurgery for intraocular uveal malignant melanoma were assessed. A retrospective study was carried out of patients with uveal melanoma after a 1-day session stereotactic radiosurgery at LINAC in Slovakia. In the period 2001-2015, a group of 150 patients with uveal melanoma (139 choroidal melanoma, 11 ciliary body melanoma) was treated. The median tumor volume at baseline was 0.5 cm (with range from 0.2 to 1.6 cm). Tumors ranged in size from 2.4 to 20.8 mm in basal diameter and from 2.0 to 18.3 mm in thickness. The therapeutic dose was 35.0 Gy by 99% of dose volume histogram. Older age at treatment was correlated with the largest basal tumor diameter, tumor thickness, and TNM stage. The survival after stereotactic irradiation was 96% in 1 year, 93% in 2 years, 84% in 5 years, 80% in 7 years, and 53% in 11 years. In 20 (13.3%) patients, secondary enucleation was necessary because of complications (secondary glaucoma). Enucleation-free interval ranged from 1 to 6 years. The median age at death was lower (65.7 years) for patients who died from metastatic disease than for those who died from any other cause (75.0 years). Survival rates at 5-year intervals and the need for secondary enucleation because of complications after linear accelerator irradiation are comparable to other techniques.

  11. Management of advanced melanoma

    International Nuclear Information System (INIS)

    Nathanson, L.

    1986-01-01

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

  12. Cervical carcinoma metastasizing to uveal tissue manifesting as pseudohypopyon

    Directory of Open Access Journals (Sweden)

    Vinay Gupta

    2017-01-01

    Full Text Available The metastasis to the eye in a patient of carcinoma of the cervix is rare. A case of carcinoma cervix in a 56-year-old female is described who presented with full chamber pseudohypopyon and deep vascularization in inferior quadrant of the cornea in the left eye. Magnetic resonance imaging revealed features suggestive of ocular metastasis in the anterior part of the uveal tract. Diagnosis was confirmed on cytology which showed features of squamous cell carcinoma. A high level of clinical suspicion in advanced cases of malignancies will help in early detection of ocular metastasis with unusual presentations.

  13. Multicavitary ciliary body melanoma presenting as a cyst

    Directory of Open Access Journals (Sweden)

    Jennifer Jang

    2013-01-01

    Full Text Available Cyst-like cavities in uveal melanoma occur rarely and can simulate a benign intraocular cystic lesion resulting in delayed diagnosis and inappropriate management. Herein, we describe a 66-year-old Caucasian female who presented with a "cystic" ciliary body mass in the right eye oculus dexter (OD. Slit lamp examination OD showed anterior bulging of the iris temporally from an underlying pigmented ciliary body mass and transillumination disclosed slight shadow from the tumor. Ultrasound biomicroscopy (UBM revealed multiple cyst-like cavities within a tumor, lined by "thick walls" of at least 200 μm and occupying 80% of the tumor volume. A clinical diagnosis of multi-cavitary ciliary body melanoma was suspected and partial lamellar sclero iridocyclectomy was performed. Histopathology confirmed the diagnosis of low-grade spindle melanoma of the ciliary body with multiple empty and fluid filled cyst-like cavities without epithelial lining. UBM is an important diagnostic tool in the differentiation of "thick walled" cavitary melanoma from "thin walled" benign pigment epithelial cyst.

  14. 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, ...

  15. Palladium-103 plaque radiotherapy for choroidal melanoma: an 11-year study

    International Nuclear Information System (INIS)

    Finger, Paul T.; Berson, Anthony; Ng, Tracy; Szechter, Andrzej

    2002-01-01

    Purpose: To describe 11 years of experience with 103 Pd ophthalmic plaque brachytherapy for intraocular melanoma. Methods and Materials: Since 1990, 152 patients have been diagnosed with uveal melanoma, found to be negative for metastatic disease, and treated with 103 Pd radioactive plaque radiotherapy. This study presents the first 100 patients treated with 103 Pd and followed for ≥2 years. Plaques were sewn to the episclera to cover the base of the intraocular tumor. Treatment involved delivery of a mean apical radiation dose of 80.5 Gy during 5-7 days' continuous treatment. Patients were evaluated for local tumor control, visual acuity, radiation damage (retinopathy, optic neuropathy, cataract), and metastatic disease. Results: Patients in this series were followed for a mean of 4.6 years (55.4 months). 103 Pd seeds were found to be equivalent to 125 I with respect to plaque manufacture and ease of dosimetric calculations. We noted a local control rate of 96% and six secondary enucleations. Including the enucleated patients, the visual acuity evaluations revealed that 35% lost six or more lines of vision and 73% had vision of 20/200 or better. Conclusion: Long-term results now exist describing the use of 103 Pd plaque radiotherapy for uveal (iris, ciliary body, and choroidal) melanoma. Compared with the results from centers using 125 I, patients in this series experienced equivalent local control rates and better visual function

  16. 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

  17. 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...

  18. 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

  19. 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.

  20. Validation of an NGS mutation detection panel for melanoma.

    Science.gov (United States)

    Reiman, Anne; Kikuchi, Hugh; Scocchia, Daniela; Smith, Peter; Tsang, Yee Wah; Snead, David; Cree, Ian A

    2017-02-22

    Knowledge of the genotype of melanoma is important to guide patient management. Identification of mutations in BRAF and c-KIT lead directly to targeted treatment, but it is also helpful to know if there are driver oncogene mutations in NRAS, GNAQ or GNA11 as these patients may benefit from alternative strategies such as immunotherapy. While polymerase chain reaction (PCR) methods are often used to detect BRAF mutations, next generation sequencing (NGS) is able to determine all of the necessary information on several genes at once, with potential advantages in turnaround time. We describe here an Ampliseq hotspot panel for melanoma for use with the IonTorrent Personal Genome Machine (PGM) which covers the mutations currently of most clinical interest. We have validated this in 151 cases of skin and uveal melanoma from our files, and correlated the data with PCR based assessment of BRAF status. There was excellent agreement, with few discrepancies, though NGS does have greater coverage and picks up some mutations that would be missed by PCR. However, these are often rare and of unknown significance for treatment. PCR methods are rapid, less time-consuming and less expensive than NGS, and could be used as triage for patients requiring more extensive diagnostic workup. The NGS panel described here is suitable for clinical use with formalin-fixed paraffin-embedded (FFPE) samples.

  1. Pregnancy and melanoma.

    Science.gov (United States)

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

    2016-10-01

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

  2. 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.

  3. 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.

  4. 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.

  5. 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...

  6. 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.

  7. Presumed choroidal metastasis of Merkel cell carcinoma

    International Nuclear Information System (INIS)

    Small, K.W.; Rosenwasser, G.O.; Alexander, E. III; Rossitch, G.; Dutton, J.J.

    1990-01-01

    Merkel cell carcinoma is a rare skin tumor of neural crest origin and is part of the amine precursor uptake and decarboxylase system. It typically occurs on the face of elderly people. Distant metastasis is almost uniformly fatal. Choroidal metastasis, to our knowledge, has not been described. We report a patient with Merkel cell carcinoma who had a synchronous solid choroidal tumor and a biopsy-proven brain metastasis. Our 56-year-old patient presented with a rapidly growing, violaceous preauricular skin tumor. Computed tomography of the head disclosed incidental brain and choroidal tumors. Light and electron microscopy of biopsy specimens of both the skin and the brain lesions showed Merkel cell carcinoma. Ophthalmoscopy, fluorescein angiography, and A and B echography revealed a solid choroidal mass. The brain and skin tumors responded well to irradiation. A radioactive episcleral plaque was applied subsequently to the choroidal tumor. All tumors regressed, and the patient was doing well 28 months later. To our knowledge this is the first case of presumed choroidal metastasis of Merkel cell carcinoma

  8. 20 CFR 219.24 - Evidence of presumed death.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Evidence of presumed death. 219.24 Section... EVIDENCE REQUIRED FOR PAYMENT Evidence of Age and Death § 219.24 Evidence of presumed death. When a person cannot be proven dead but evidence of death is needed, the Board may presume he or she died at a certain...

  9. Laparoscopic power morcellation of presumed fibroids.

    Science.gov (United States)

    Brolmann, Hans A; Sizzi, Ornella; Hehenkamp, Wouter J; Rossetti, Alfonso

    2016-06-01

    Uterine leiomyoma is a highly prevalent benign gynecologic neoplasm that affects women of reproductive age. Surgical procedures commonly employed to treat symptomatic uterine fibroids include myomectomy or total or sub-total hysterectomy. These procedures, when performed using minimally invasive techniques, reduce the risks of intraoperative and postoperative morbidity and mortality; however, in order to remove bulky lesions from the abdominal cavity through laparoscopic ports, a laparoscopic power morcellator must be used, a device with rapidly spinning blades to cut the uterine tissue into fragments so that it can be removed through a small incision. Although the minimal invasive approach in gynecological surgery has been firmly established now in terms of recovery and quality of life, morcellation is associated with rare but sometimes serious adverse events. Parts of the morcellated specimen may be spread into the abdominal cavity and enable implantation of cells on the peritoneum. In case of unexpected sarcoma the dissemination may upstage disease and affect survival. Myoma cells may give rise to 'parasitic' fibroids, but also implantation of adenomyotic cells and endometriosis has been reported. Finally the morcellation device may cause inadvertent injury to internal structures, such as bowel and vessels, with its rotating circular knife. In this article it is described how to estimate the risk of sarcoma in a presumed fibroid based on epidemiologic, imaging and laboratory data. Furthermore the first literature results of the in-bag morcellation are reviewed. With this procedure the specimen is contained in an insufflated sterile bag while being morcellated, potentially preventing spillage of tissue but also making direct morcellation injuries unlikely to happen.

  10. 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

  11. 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.

  12. Melanomas: radiobiology and role of radiation therapy

    International Nuclear Information System (INIS)

    Peschel, Richard E.

    1995-01-01

    diverse range of time-dose prescriptions are consistent with the wide diversity and complexity of the radiobiological data for MM. RT for Metastatic Melanoma: RT is the single most effective therapy for local palliation of metastatic disease. Complete response (CR) rates range from 24-75% and overall response (OR) rates are 59-98% with RT compared with CR rates of 3-10% and OR rates of only 15-36% with either chemotherapy or immunotherapy. Achieving a CR is important even for patients with metastatic disease. Five-year survival for patients with metastatic disease who achieve a CR is 49% compared to a 5-year survival of only 3% for patients who do not achieve a CR. RT for Primary Tumors: RT is effective therapy for selected primary sites including uveal melanoma and non-cutaneous, non-ocular mucosal MM. The RT results for ocular melanoma and non-cutaneous, non-ocular mucosal MM are superior to surgery. In addition, post-operative RT for residual microscopic/macroscopic disease following primary surgery produces long term local control rates of 75-88%. It is likely that radiation therapy is being under-utilized in current oncology practice

  13. Malignant melanoma - a warning

    International Nuclear Information System (INIS)

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

    1990-01-01

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

  14. 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.

  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. Retributivist Arguments against Presuming Innocence : Answering to Duff

    NARCIS (Netherlands)

    van Dijk, A.A.

    2013-01-01

    Factors justifying not presuming innocence are generally incorporated into the Presumption of Innocence (PoI). A confusing discourse has resulted: numerous guilt-presuming acts are deemed consistent with the PoI. I argue for an unusually broad PoI: any act that might convey to a reasonable actor

  17. 10 CFR 436.13 - Presuming cost-effectiveness results.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 3 2010-01-01 2010-01-01 false Presuming cost-effectiveness results. 436.13 Section 436... Methodology and Procedures for Life Cycle Cost Analyses § 436.13 Presuming cost-effectiveness results. (a) If the investment and other costs for an energy or water conservation measure considered for retrofit to...

  18. 27 CFR 70.52 - Signature presumed authentic.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Signature presumed authentic. 70.52 Section 70.52 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE... Collection of Excise and Special (Occupational) Tax Collection-General Provisions § 70.52 Signature presumed...

  19. 26 CFR 301.6064-1 - Signature presumed authentic.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 18 2010-04-01 2010-04-01 false Signature presumed authentic. 301.6064-1 Section 301.6064-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED....6064-1 Signature presumed authentic. An individual's name signed to a return, statement, or other...

  20. 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.

  1. Metastatic melanoma of mesentery

    International Nuclear Information System (INIS)

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

    2004-01-01

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

  2. 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...

  3. Bilateral acute retinal necrosis associated with bilateral uveal effusion in an immunocompetent patient: A challenging association

    Directory of Open Access Journals (Sweden)

    S Bala Murugan

    2018-01-01

    Full Text Available Bilateral uveal effusion syndrome associated with bilateral acute retinal necrosis is a diagnostic and therapeutic challenge. A 52 year old man presented with bilateral angle closure with choroidal detachment. With restricted fundus view, parenteral steroid was started. During close follow up bilateral discrete areas of peripheral retinitis were noted. Parenteral steroids were promptly stopped and parenteral antivirals with oral steroids were continued. It showed healing response with nil recurrences till last follow up. Aggressive treatment of bilateral uveal effusion with parenteral steroids can cause progression of bilateral acute retinal necrosis leading to phthisis bulbi. However early diagnosis, prompt intervention and close follow up are the key elements to therapeutic success even during diagnostic surprises and avoid costly mistakes.

  4. Thick melanoma in Tuscany.

    Science.gov (United States)

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

    2017-03-14

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

  5. Peptides in melanoma therapy.

    Science.gov (United States)

    Mocellin, Simone

    2012-01-01

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

  6. 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

  7. Melanoma survivorship: research opportunities.

    Science.gov (United States)

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

    2007-03-01

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

  8. The Danish Melanoma Database

    DEFF Research Database (Denmark)

    Hölmich, Lisbet Rosenkrantz; Klausen, Siri; Spaun, Eva

    2016-01-01

    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...... studies are based on DMD data. CONCLUSION: DMD holds unique detailed information about tumor characteristics, the surgical treatment, and follow-up of Danish melanoma patients. Registration and monitoring is currently expanding to encompass even more clinical parameters to benefit both patient treatment...

  9. 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.

  10. 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.

  11. 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

  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 "2"1"2"P"b"/"2"0"3Pb radiolabeled melanoma targeting peptide DOTA-ReCCMSH. The radiolabeled alpha-melanocyte stimulating hormone (α-MSH) peptide analog DOTA-Re(Arg"1"1)CCMSH, which binds the melanocortin-1 receptor over-expressed on melanoma tumor cells, has shown promise as a PRRT agent in pre-clinical studies. High tumor uptake of "2"1"2Pb labeled DOTA-Re(Arg"1"1)CCMSH resulted in tumor reduction or eradication in melanoma therapy studies. Of particular note was the 20-50% cure rate observed when melanoma mice were treated with alpha particle emitter "2"1"2Pb. However, as with most PRRT agents, high radiation doses to the kidneys where observed. To optimize tumor treatment efficacy and reduce nephrotoxicity, the tumor to kidney uptake ratio must be improved. Strategies to reduce kidney retention of the radiolabeled peptide, while not effecting tumor uptake and retention, can be broken into several categories including modification of the targeting peptide sequence and reducing proximal tubule reabsorption.

  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. Presumed Optic Disc Melanocytoma in a Young Nigerian: A ...

    African Journals Online (AJOL)

    homogenous soft tissue mass with broad base arising from the choroid in the optic nerve area and projecting into the vitreous cavity. No retinal detachment or sub-retinal fluid was seen. An assessment of right presumed ODM was made. She was refracted with visual acuity improvement to 6/5 in either eye and spectacles ...

  15. Compensatory cerebral motor control following presumed perinatal ischemic stroke

    NARCIS (Netherlands)

    van der Hoorn, Anouk; Potgieser, Adriaan R E; Brouwer, Oebele F; de Jong, Bauke M

    Case: A fifteen year-old left-handed girl presented with right-sided focal motor seizures. Neuroimaging showed a large left hemisphere lesion compatible with a middle cerebral artery stroke of presumed perinatal origin. She was not previously diagnosed with a motor deficit, although neurological

  16. Seven Non-melanoma Features to Rule Out Facial Melanoma

    Directory of Open Access Journals (Sweden)

    Philipp Tschandl

    2017-08-01

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

  17. Immunoscintigraphy in ocular melanoma

    International Nuclear Information System (INIS)

    Scheidhauer, K.; Scober, O.; Scheidler, J.; Leinsinger, G.; Scheiffarth, O.; Riedel, K.; Schumacher, U.

    1990-01-01

    Immunoscintigraphy (IS) of malignant tumors has become an encouraging tool in nuclear medicine. Early diagnosis of small lesions is mandatory for successful cancer therapy generally. The scintigraphic detectability of small lesions ( 2 fragments of the anti-melanoma monoclonal antibody 225.28S; this antibody recognizes the high-molecular-weight melanoma-associated antigen. No adverse effects were observed. In terms of true positive results, Single Photon Emission CT proved to be superior compared to planar scans (81 versus 46 percent true positive results). (author). 30 refs

  18. Histoanatomical study on the uveal coat of eye in mature ostrich

    Directory of Open Access Journals (Sweden)

    mohammadali Ebrahimi saadatlou

    2015-05-01

    Full Text Available In the present study, the uveal coats of 20 healthy adult ostriches were studied anatomically and histologically. At first, the appearance, dimension, structure and vicinity of choroid, ciliary body and iris were evaluated macroscopically. Then they were studied microscopically after preparing histological slides and staining by H&E, Verhoeff, Van Gieson, and P.A.S. Tapetum lucidum was not seen in the choroid. The average thickness of ciliary body was measured as 1.48±0.01 centimeters. Moreover, the number of macroscopic ciliary body process in the ostrich eye was about 120. Iris thickness in the normal state is 0.7 centimeters and the diameter of pupil was measured as 1.2 centimeters. Pupil is round shaped in ostrich. There is a hyaline cartilage membrane between the sclera and choroid. There is bruch's membrane in the choroid and the total thickness of the choroid was measured as 350 µm. The ciliary body was supported by a hyaline cartilage. Skeletal muscle fibers in the ciliary body were seen as separated masses. Epithelium is lacking on the anterior surface of the iris. Iridial muscle fibers were smooth. The posterior epithelium of the iris had two pigmented layers with the inner layer acting as myoepithelial cells. In conclusion, the uveal coat of ostrich was similar to other birds although there were little differences in anatomical dimensions and histological characteristics

  19. 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.

  20. Spice Blocks Melanoma Growth

    Science.gov (United States)

    Science Teacher, 2005

    2005-01-01

    Curcumin, the pungent yellow spice found in both turmeric and curry powders, blocks a key biological pathway needed for development of melanoma and other cancers, according to a study that appears in the journal Cancer. Researchers from The University of Texas M. D. Anderson Cancer Center demonstrate how curcumin stops laboratory strains of…

  1. 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.

  2. Preventing Melanoma PSA (:60)

    Centers for Disease Control (CDC) Podcasts

    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.

  3. Radiopharmaceuticals targeting melanoma

    Energy Technology Data Exchange (ETDEWEB)

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

    2008-02-15

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

  4. 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.

  5. 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.

  6. Sucessfull management of bilateral presumed Candida endogenous endophtalmitis following pancreatitis

    Directory of Open Access Journals (Sweden)

    Ricardo Evangelista Marrocos de Aragão

    2016-06-01

    Full Text Available ABSTRACT Endogenous endophthalmitis is a rare, and frequently devastating, ophthalmic disease. It occurs mostly in immunocompromised patients, or those with diabetes mellitus, cancer or intravenous drugs users. Candida infection is the most common cause of endogenous endophthalmitis. Ocular candidiasis develops within days to weeks of fungemia. The association of treatment for pancreatitis with endophthalmitis is unusual. Treatment with broad-spectrum antibiotics and total parenteral nutrition may explain endogenous endophthalmitis. We report the case of a patient with pancreatitis treated with broad-spectrum antibiotics and total parenteral nutrition who developed bilateral presumed Candida endogenous endophthalmitis that was successfully treated with vitrectomy and intravitreal amphotericin B.

  7. [Melanoma in organ transplant patients].

    Science.gov (United States)

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

    2000-02-01

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

  8. Detection of periprosthetic joint infections in presumed aseptic patients

    DEFF Research Database (Denmark)

    Xu, Yijuan; Lorenzen, Jan; Thomsen, Trine Rolighed

    2016-01-01

    Title: Detection of periprosthetic joint infections in presumed aseptic patients Yijuan Xu1, Jan Lorenzen1, Trine Rolighed Thomsen1,2, Kathrin Kluba3, Kathrin Chamaon3, Christoph Lohmann3 1. Danish Technological Institute, Aarhus, Denmark 2. Center for Microbial Communities, Department of Biotech......Title: Detection of periprosthetic joint infections in presumed aseptic patients Yijuan Xu1, Jan Lorenzen1, Trine Rolighed Thomsen1,2, Kathrin Kluba3, Kathrin Chamaon3, Christoph Lohmann3 1. Danish Technological Institute, Aarhus, Denmark 2. Center for Microbial Communities, Department...... of Biotechnology, Chemistry and Environmental Engineering, Aalborg University, Denmark 3. Department of Orthopaedics, Otto-von-Guericke University of Magdeburg, Germany Aim: ”The HypOrth project (New approaches in the development of Hypoallergenic implant material in Orthopaedics: Steps to personalised medicine......) aims to investigate adverse immune reactions to implant materials. For this project, it is of utmost importance to exclude patients with periprosthetic joint infections (PJIs). The aim of this study was to rule out PJIs in included patients using prolonged culture and next generation sequencing (NGS...

  9. Surgery of Primary Melanomas

    Directory of Open Access Journals (Sweden)

    Piotr Rutkowski

    2010-05-01

    Full Text Available Surgery remains the mainstay of melanoma therapy, regardless of the tumor site. Only the early diagnosis combined with proper surgical therapy currently gives patients affected by this malignancy the chance for a full cure. The main goal of surgical therapy is to provide the local control of the disease and to secure long-term survival of the patient without reasonable functional and esthetic impairment. The recommended method of biopsy—excisional biopsy, as an initial diagnostic and, to some extent, therapeutic procedure—is performed under local anesthesia as an elliptical incision with visual clear margins of 1–3 mm and with some mm of subcutaneous tissue. The extent of radical excision of the primary tumor (or scar after excisional biopsy is based on the histopathologic characteristics of the primary tumor and usually consists of 1–2 cm margins with primary closure. The philosophy behind conducted randomized clinical trials has been to find the most conservative surgical approach that is able to guarantee the same results as more demolitive treatment. This has been the background of the trials designed to define the correct margins of excision around a primary cutaneous melanoma. Much less definition can be dedicated to the surgical management of patients with non-cutaneous melanomas.

  10. Surgery of Primary Melanomas

    Energy Technology Data Exchange (ETDEWEB)

    Rutkowski, Piotr, E-mail: rutkowskip@coi.waw.pl; Zdzienicki, Marcin; Nowecki, Zbigniew I. [Soft Tissue/Bone Sarcoma and Melanoma Department, M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw (Poland); Akkooi, Alexander C. J. van [Erasmus University Medical Center-Daniel den Hoed Cancer Center, Rotterdam (Netherlands)

    2010-05-11

    Surgery remains the mainstay of melanoma therapy, regardless of the tumor site. Only the early diagnosis combined with proper surgical therapy currently gives patients affected by this malignancy the chance for a full cure. The main goal of surgical therapy is to provide the local control of the disease and to secure long-term survival of the patient without reasonable functional and esthetic impairment. The recommended method of biopsy—excisional biopsy, as an initial diagnostic and, to some extent, therapeutic procedure—is performed under local anesthesia as an elliptical incision with visual clear margins of 1–3 mm and with some mm of subcutaneous tissue. The extent of radical excision of the primary tumor (or scar after excisional biopsy) is based on the histopathologic characteristics of the primary tumor and usually consists of 1–2 cm margins with primary closure. The philosophy behind conducted randomized clinical trials has been to find the most conservative surgical approach that is able to guarantee the same results as more demolitive treatment. This has been the background of the trials designed to define the correct margins of excision around a primary cutaneous melanoma. Much less definition can be dedicated to the surgical management of patients with non-cutaneous melanomas.

  11. Surgery of Primary Melanomas

    International Nuclear Information System (INIS)

    Rutkowski, Piotr; Zdzienicki, Marcin; Nowecki, Zbigniew I.; Akkooi, Alexander C. J. van

    2010-01-01

    Surgery remains the mainstay of melanoma therapy, regardless of the tumor site. Only the early diagnosis combined with proper surgical therapy currently gives patients affected by this malignancy the chance for a full cure. The main goal of surgical therapy is to provide the local control of the disease and to secure long-term survival of the patient without reasonable functional and esthetic impairment. The recommended method of biopsy—excisional biopsy, as an initial diagnostic and, to some extent, therapeutic procedure—is performed under local anesthesia as an elliptical incision with visual clear margins of 1–3 mm and with some mm of subcutaneous tissue. The extent of radical excision of the primary tumor (or scar after excisional biopsy) is based on the histopathologic characteristics of the primary tumor and usually consists of 1–2 cm margins with primary closure. The philosophy behind conducted randomized clinical trials has been to find the most conservative surgical approach that is able to guarantee the same results as more demolitive treatment. This has been the background of the trials designed to define the correct margins of excision around a primary cutaneous melanoma. Much less definition can be dedicated to the surgical management of patients with non-cutaneous melanomas

  12. 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.

  13. Melanoma Surveillance in the US: The Economic Burden of Melanoma

    Centers for Disease Control (CDC) Podcasts

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

  14. MMP-9 immunohistochemical expression is correlated with histologic grade in feline diffuse iris melanoma

    Directory of Open Access Journals (Sweden)

    Laura Nordio

    2018-06-01

    Full Text Available Feline diffuse iris melanoma (FDIM is the most common primary intraocular neoplasm in cats. It is usually a malignant tumor, even if slowly progressive, thus representing an unique spontaneous model of the aggressive, although rare, human iris melanoma. In cats, the extent of the tumor within the eye, expressed as histological grade, is considered a good predictor of survival. In the context of the neoplastic cells-tumor microenvironment interaction, Matrix Metalloproteinase-9 (MMP-9 is an endopeptidase able to digest the extracellular matrix with involvement in tumor invasion . MMP-9 expression has been positively correlated with metastasizing behavior in human posterior uveal melanoma. The present study investigates the expression of MMP-9 in a caseload of formalin-fixed paraffin-embedded FDIMs in relation to the histological grade  and mitotic index (MI (threshold=7/10 hpf. Sixty-one samples of FDIM evaluated on light microscopy (Fig. 1 were selected (grade I n=22, grade II n=20, grade III n=19. Immunohistochemical staining with standard ABC method was performed using a mouse anti-MMP-9 antibody. Results were semi-quantitatively scored and compared by Mann-Whitney U test. MMP-9 was expressed in 59,1% grade I FDIM, 90,0% grade II and 80,0% grade III. Tumors with MMP-9 expression in more than 50% of neoplastic cells were 13,6% in grade I cases, 40,0% in grade II and 36,8% in grade III. MMP-9 was expressed in 71,4% of FDIM with MI≤7 and 92,3% of FDIM with MI>7. MMP-9 expression differed significantly between grade I and the other two grades, and between groups with low and high MI. In conclusion, intense expression of MMP-9 seems to correlate with the histological aggressiveness of FDIM.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. Presumed symbolic use of diurnal raptors by Neanderthals.

    Science.gov (United States)

    Morin, Eugène; Laroulandie, Véronique

    2012-01-01

    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.

  1. Radiation biology of malignant melanoma

    International Nuclear Information System (INIS)

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

    1986-01-01

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

  2. 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.

  3. 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

  4. 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...

  5. Simulants of malignant melanoma

    Directory of Open Access Journals (Sweden)

    Gérald E. Piérard

    2015-08-01

    Full Text Available During the recent period, dermoscopy has yielded improvement in the early disclosure of various atypical melanocytic neoplasms (AMN of the skin. Beyond this clinical procedure, AMN histopathology remains mandatory for establishing their precise diagnosis. Of note, panels of experts in AMN merely report moderate agreement in various puzzling cases. Divergences in opinion and misdiagnosis are likely increased when histopathological criteria are not fine-tuned and when facing a diversity of AMN types. Furthermore, some AMN have been differently named in the literature including atypical Spitz tumor, metastasizing Spitz tumor, borderline and intermediate melanocytic tumor, malignant Spitz nevus, pigmented epithelioid melanocytoma or animal-type melanoma. Some acronyms have been further suggested such as MELTUMP (after melanocytic tumor of uncertain malignant potential and STUMP (after Spitzoid melanocytic tumor of uncertain malignant potential. In this review, such AMN at the exclusion of cutaneous malignant melanoma (MM variants, are grouped under the tentative broad heading skin melanocytoma. Such set of AMN frequently follows an indolent course, although they exhibit atypical and sometimes worrisome patterns or cytological atypia. Rare cases of skin melanocytomas progress to loco regional clusters of lesions (agminate melanocytomas, and even to regional lymph nodes. At times, the distinction between a skin melanocytoma and MM remains puzzling. However, multipronged immunohistochemistry and emerging molecular biology help profiling any malignancy risk if present.

  6. Vaccines against advanced melanoma.

    Science.gov (United States)

    Blanchard, Tatiana; Srivastava, Pramod K; Duan, Fei

    2013-01-01

    Research shows that cancers are recognized by the immune system but that the immune recognition of tumors does not uniformly result in tumor rejection or regression. Quantitating the success or failure of the immune system in tumor elimination is difficult because we do not really know the total numbers of encounters of the immune system with the tumors. Regardless of that important issue, recognition of the tumor by the immune system implicitly contains the idea of the tumor antigen, which is what is actually recognized. We review the molecular identity of all forms of tumor antigens (antigens with specific mutations, cancer-testis antigens, differentiation antigens, over-expressed antigens) and discuss the use of these multiple forms of antigens in experimental immunotherapy of mouse and human melanoma. These efforts have been uniformly unsuccessful; however, the approaches that have not worked or have somewhat worked have been the source of many new insights into melanoma immunology. From a critical review of the various approaches to vaccine therapy we conclude that individual cancer-specific mutations are truly the only sources of cancer-specific antigens, and therefore, the most attractive targets for immunotherapy. Published by Elsevier Inc.

  7. Melanoma Lentiginoso Acral

    Directory of Open Access Journals (Sweden)

    Gloria Andrea Vargas Suaza

    2008-12-01

    Full Text Available El melanoma lentiginoso acral (MLA es una variante rápidamente progresiva del melanoma maligno (MM. Constituye el 5-10% de todos los tipos de MM y se presenta con mayor frecuencia en pacientes de raza negra, asiáticos y latinoamericanos. En Colombia el MM se encuentra en aumento, con una incidencia de 3.5/100.000, siendo el MLA una de las variantes más comunes. La edad promedio de presentación es de 58 años, con una tasa de sobrevida menor para las personas de raza negra, asociado a un diagnóstico tardío. EL MLA se localiza en plantas, palmas y región subungueal y en su etiopatología se ha descrito la presencia de mutaciones en genes: 9p21 (p16: 67%, 11q13 (CCND1 (47%, 22q11-q13 (40% y 5p15 (20%. El diagnóstico de MLA, se ha fundamentado clásicamente en la histopatología. Herramientas de diagnóstico como la dermatoscopia, la evaluación del ganglio centinela y la determinación de alteraciones en las proteínas del ciclo celular contribuyen a la detección precoz del MLA y el MM en general.

  8. 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.

  9. 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)

  10. The role of methotrexate in resolving ocular inflammation after specific therapy for presumed latent syphilitic uveitis and presumed tuberculosis-related uveitis.

    Science.gov (United States)

    Sahin, Ozlem; Ziaei, Alireza

    2014-07-01

    This study was designed to investigate whether the antiinflammatory and antiproliferative activity of oral and intravitreal methotrexate (MTX) suppresses intraocular inflammation in patients with presumed latent syphilitic uveitis and presumed tuberculosis-related uveitis. Interventional prospective study including three cases with presumed latent syphilitic uveitis treated with intravenous penicillin and oral MTX, and two cases with presumed tuberculosis-related uveitis treated with standard antituberculosis therapy and intravitreal MTX injections. Treatment efficacy of all cases was assessed by best-corrected visual acuity, fundus fluorescein angiography, and optical coherence tomography. Four eyes of 3 patients with presumed latent syphilitic uveitis had improved best-corrected visual acuity, suppression of intraocular inflammation, and resolution of cystoid macular edema in 6 months with oral MTX therapy. No recurrence of intraocular inflammation was observed in 6 months to 18 months of follow-up period after cessation of MTX. Two eyes of two patients with presumed tuberculosis-related uveitis showed improved best-corrected visual acuity, suppression of intraocular inflammation, and resolution of cystoid macular edema after intravitreal injections of MTX. No recurrence of intraocular inflammation was observed in 6 months to 8 months of follow-up period after cessation of antituberculous therapy. For the first time in the treatment of presumed latent syphilitic uveitis and presumed tuberculosis-related uveitis, we believe that MTX might have an adjunctive role to suppress intraocular inflammation, reduce uveitic macular edema, and prevent the recurrences of the diseases.

  11. 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.

  12. What Does Melanoma Look Like?

    Science.gov (United States)

    ... begins in melanocytes ( cells that make the pigment melanin ). Below are photos of melanoma that formed on ... Services Website Linking U.S. Department of Health and Human Services National Institutes of Health National Cancer Institute ...

  13. 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...

  14. Immunoscintigraphy of malignant melanomas

    International Nuclear Information System (INIS)

    Nicol, L.; Sandron, A.; Herry, J.Y.; Chevrant-Breton, J.

    1990-01-01

    This work is part of a multicentric European evaluation of the monoclonal antibody 225.28s targeted against malignant melanoma and its metastases. Twenty-eight patients (12 males, 16 females, mean age: 53 yrs), who had initially been treated by resection of the primary tumour, were included in the study. Twenty-three of the 26 metastases more than 1 cm in diameter were visualized by immunoscintigraphy. The sensitivity of the procedure (88%) is limited however by the small size of the lesions and their depth, as well as by background noise caused by circulating antibodies. Immunoscintigraphy enables non-invasive investigation of the whole body and can detect lesions that other conventional complementary explorations fail to identify [fr

  15. Primary Anorectal Melanoma

    Directory of Open Access Journals (Sweden)

    Maliha Khan

    2014-03-01

    Full Text Available Primary malignant melanoma of the anus and rectum is a rare and aggressive neoplasm that tends to invade locally and metastasize early in the course of the disease. It is often misdiagnosed as hemorrhoids or as one of the other benign anorectal conditions and is thus linked to an overall poor prognosis and a 5-year survival rate of less than 20%. Optimal treatment is still controversial, and current evidence does not show any preferential survival benefit from abdominoperineal resection over wide local excision. Chemotherapy or radiotherapy may be used for advanced disease. We report a 71-year-old female presenting with painful bowel movements and blood in stools. She was eventually found to have a mass arising from the anorectal junction with regional lymph node involvement. The patient underwent an abdominoperineal resection and is currently scheduled for chemotherapy.

  16. Isolated malignant melanoma metastasis to the pancreas

    DEFF Research Database (Denmark)

    Larsen, Anne K; Krag, Christen; Geertsen, Poul

    2013-01-01

    SUMMARY: Malignant melanomas rarely develop isolated pancreatic metastases. We describe a unique patient who is still alive 22 years following an isolated pancreatic melanoma metastasis, and we review the sparse literature in the field....

  17. Immunohistochemical detection of XIAP in melanoma.

    Science.gov (United States)

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

    2008-03-01

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

  18. PRIMARY MALIGNANT MELANOMA OF ARYEPIGLOTTIC FOLD

    African Journals Online (AJOL)

    2015-12-01

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

  19. 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

  20. 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.

  1. 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

  2. Intraocular (Eye) Melanoma—Health Professional Version

    Science.gov (United States)

    Intraocular (uveal) melanoma of the uveal tract (iris, ciliary body, and choroid), though rare, is the most common primary intraocular malignancy in adults. Find evidence-based information on intraocular melanoma treatment.

  3. 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

  4. 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...

  5. 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 to be in...

  6. Uveal effusion syndrome in 104 eyes: Response to corticosteroids – The 2017 Axel C. Hansen lecture

    Directory of Open Access Journals (Sweden)

    Carol L Shields

    2017-01-01

    Full Text Available Purpose: The purpose of the study was to investigate the corticosteroids for uveal effusion syndrome (UES. Methods: Retrospective series of 104 eyes with UES treated with oral corticosteroids (OCS, periocular corticosteroids (PCS, topical corticosteroids (TCS, or observation (OBS. Main outcome measure was UES resolution. Results: Of 104 eyes, treatment included OCS (n = 27, PCS (n = 12, TCS (n = 11, and OBS (n = 54. A comparison of the four groups (OCS vs. PCS vs. TCS vs. OBS revealed differences in those managed with OCS versus OBS as younger (66 vs. 72 years, P = 0.049, PCS versus OBS as male (100% vs. 54%, P = 0.002, PCS versus OBS with decreased visual acuity (VA/visual field (91% vs. 51%, P = 0.018, and OBS versus OCS as asymptomatic (28% vs. 0%, P = 0.001. Of the 59 with follow-up information, management included OCS (n = 21, PCS (n = 12, TCS (n = 6, and OBS (n = 20. There were differences in initial VA <20/400 in PCS versus OBS (42% vs. 5%, P = 0.018, effusion thickness in TCS versus OCS (7 vs. 3 mm, P = 0.004, and serous retinal detachment in PCS versus OBS (100% vs. 30%, P < 0.001 and PCS versus OCS (100% vs. 57%, P = 0.012. Regarding outcomes, VA showed less worsening in OCS versus OBS (0% vs. 30%, P = 0.008 and OCS versus PCS (0% vs. 33%, P = 0.012. There was no difference in rate of effusion resolution or effusion recurrence. Overall, using combination of corticosteroid therapies, effusion resolution was achieved in 56/59 (95% cases and the need for surgical management with scleral windows was necessary in only 3/59 (5% cases. Complications included cataract (n = 9 and no instance of steroid-induced glaucoma. Conclusion: Management of UES is complex and depends on disease severity. Using various corticosteroid delivery routes, UES control was achieved in 95%, and scleral window surgery was required in only 5%. A trial of corticosteroids can benefit patients with UES.

  7. 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

  8. NEAR-INFRARED AUTOFLUORESCENCE IN BILATERAL DIFFUSE UVEAL MELANOCYTIC PROLIFERATION ASSOCIATED WITH ESOPHAGEAL CARCINOMA AND CHOROIDAL METASTASIS.

    Science.gov (United States)

    Golshahi, Azadeh; Bornfeld, Norbert; Weinitz, Silke; Kellner, Ulrich

    2016-01-01

    To investigate the advantage of near-infrared autofluorescence (787 nm) for the detection of melanocytic lesions in a patient with bilateral diffuse uveal melanocytic proliferation in association with esophageal carcinoma complicated by most likely unilateral choroidal metastasis. In this retrospective case report, a 55-year-old woman referred for the evaluation of sudden visual loss underwent normal ophthalmological evaluation and, in addition, was examined with near-infrared reflectance, near-infrared autofluorescence, fundus autofluorescence (Heidelberg Retina Angiograph II [HRA2; Heidelberg Engineering]), spectral domain optical coherence tomography (Spectralis OCT; Heidelberg Engineering), and multifocal electroretinography (RetiScan; Roland Consult). The patient had been diagnosed with esophageal carcinoma 3 months before the onset of visual symptoms. The visual acuity was 20/40 in the right eye and 20/20 in the left eye. Bilateral patchy melanocytic proliferation was detected on ophthalmoscopy. The extent of lesions was best detected with near-infrared reflectance and near-infrared autofluorescence, whereas fundus autofluorescence and spectral domain optical coherence tomography did not reveal alterations of the outer retina or retinal pigment epithelium in this early stage of bilateral diffuse uveal melanocytic proliferation. The right eye showed in addition to the findings on the left eye choroidal folds in the fovea and an elevated lesion inferotemporal of the fovea suspicious of a choroidal metastasis. In the B-scan ultrasonography, a homogenous lesion was seen. Spectral domain optical coherence tomography demonstrated a mild accumulation of subretinal fluid adjacent to and over the choroidal metastasis. Transretinal biopsy of this elevated lesion revealed a low differentiated carcinoma of squamous epithelium, compatible with choroidal metastasis of the esophageal carcinoma. The choroidal metastasis increased within 3 months after the first visit. The

  9. 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.

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

    Directory of Open Access Journals (Sweden)

    Jinah Kim

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

  11. 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.

  12. Melanoma Surveillance in the US: Collecting Melanoma Data

    Centers for Disease Control (CDC) Podcasts

    This podcast accompanies the publication of a series of articles on melanoma surveillance in the United States, available in the November supplement edition of the Journal of the American Academy of Dermatology. Dr. Suephy Chen, a dermatologist from Emory University, discusses why the articles are important, as well as the need to increase dermatologists’ awareness of cancer registries and reporting requirements.

  13. 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).

  14. Sunnier European countries have lower melanoma mortality.

    Science.gov (United States)

    Shipman, A R; Clark, A B; Levell, N J

    2011-07-01

    Doubt has been cast on sunlight as the major causative factor for malignant melanoma. We performed statistical analysis of the average annual sunlight hours in 36 European capital cities compared with the country's melanoma mortality rate. A significant inverse proportionality was identified in both men and women, indicating that sun exposure is unlikely to be the strongest factor affecting mortality from malignant melanoma. © The Author(s). CED © 2011 British Association of Dermatologists.

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

    Science.gov (United States)

    Haddad, R

    1979-04-01

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

  16. Laser radiation therapy of skin melanoma

    Energy Technology Data Exchange (ETDEWEB)

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

    1981-10-01

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

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

    Science.gov (United States)

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

    2018-05-01

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

  18. 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.

  19. 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

  20. [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.

  1. 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...

  2. 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.

  3. Perineural extension of facial melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Kalina, Peter [Mayo Clinic, Department of Radiology, Rochester, Minnesota (United States); Bevilacqua, Paula

    2005-05-01

    A 64-year-old man presented with a pigmented cutaneous lesion on the right side of his face along with right facial numbness. Histological examination revealed malignant melanoma. Magnetic resonance imaging (MRI) revealed perineural extension along the entire course of the maxillary division of the right trigeminal nerve. This is a rare but important manifestation of the spread of head and neck malignancy. (orig.)

  4. Evaluation of autopsy imaging (postmortem CT) to presume causes of death

    International Nuclear Information System (INIS)

    Nishihara, Keisuke; Sugihara, Shuji; Morioka, Nobuo; Sato, Shinya; Tsukamoto, Kazumichi; Ogawa, Toshihide

    2010-01-01

    A total of 123 patients arrived at the emergency room in a state of cardiopulmonary arrest were examined by CT after death. Forty one patients (33.3%) were presumed the causes of death by autopsy imaging (Ai). Only 30 patients (24.4%) could be presumed causes of death with postmortem inspection and clinical information. However, presumption rate of cause of death was improved up to 46.3% (22.0 points increase) by adding information provided in Ai. (author)

  5. 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.

  6. Gamma Knife Perfexion® radiosurgery and endo diode laser thermotherapy for choroidal melanoma with technical analysis: A case report.

    Science.gov (United States)

    Tsai, Yi-Chieh; Kuo, Chun-Yuan; Lin, Jia-Wei; Yang, Shun-Tai; Lai, Shih-Chung; Tsai, Jo-Ting

    2018-01-01

    Radiosurgery serves an important function in the treatment of patients with intraocular tumors and preserves visual function via organ conservation. Therefore, it is important to ensure the safety and precision of GK-SRS as a primary treatment for intraocular tumors. The present case study described a 57-year-old female with uveal melanoma treated with GK-SRS. Retrobulbar anesthesia following fixation of the treated eye, via the suture of two of the extraocular muscles to the stereotactic frame, was performed to immobilize the eye during treatment. Computed tomography (CT) scans were performed following eye fixation, immediately prior to and following GK-SRS, to validate the accuracy of the tumor localization. The eye movement analysis revealed that the gravity center point deviations of the tumor and lens during treatment were <0.110 mm. At least 95% of the tumor volume was covered by the prescription dose according to three sets of CT images. The patient underwent a trans pars plana vitrectomy owing to a right eye vitreous hemorrhage. A 37-month follow-up assessment revealed tumor shrinkage, and the disappearance of the serous retinal detachments was noted on the basis of ophthalmoscopy and orbital magnetic resonance imaging. No major complications developed during the follow-up period. Using our treatment protocol, GK-SRS is a non-invasive procedure which is used as a brief single fraction treatment for intraocular tumor. The eye fixation method used in the present study has high accuracy.

  7. A 62-MeV Proton Beam for the Treatment of Ocular Melanoma at Laboratori Nazionali del Sud-INFN

    Science.gov (United States)

    Cirrone, G. A. P.; Cuttone, G.; Lojacono, P. A.; Lo Nigro, S.; Mongelli, V.; Patti, I. V.; Privitera, G.; Raffaele, L.; Rifuggiato, D.; Sabini, M. G.; Salamone, V.; Spatola, C.; Valastro, L. M.

    2004-06-01

    At the Istituto Nazionale di Fisica Nucleare-Laboratori Nazionali del Sud (INFN-LNS) in Catania, Italy, the first Italian protontherapy facility, named Centro di AdroTerapia e Applicazioni Nucleari Avanzate (CATANA) has been built in collaboration with the University of Catania. It is based on the use of the 62-MeV proton beam delivered by the K=800 Superconducting Cyclotron installed and working at INFN-LNS since 1995. The facility is mainly devoted to the treatment of ocular diseases like uveal melanoma. A beam treatment line in air has been assembled together with a dedicated positioning patient system. The facility has been in operation since the beginning of 2002 and 66 patients have been successfully treated up to now. The main features of CATANA together with the clinical and dosimetric features will be extensively described; particularly, the proton beam line, that has been entirely built at LNS, with all its elements, the experimental transversal and depth dose distributions of the 62-MeV proton beam obtained for a final collimator of 25-mm diameter and the experimental depth dose distributions of a modulated proton beam obtained for the same final collimator. Finally, the clinical results over 1 yr of treatments, describing the features of the treated diseases will be reported.

  8. Prognosis of patients with transected melanomas.

    Science.gov (United States)

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

    2013-04-01

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

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

    Science.gov (United States)

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

    1985-01-01

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

  10. Expression and prognostic value of putative cancer stem cell markers CD117 and CD15 in choroidal and ciliary body melanoma.

    Science.gov (United States)

    Lukenda, Adrian; Dotlic, Snjezana; Vukojevic, Nenad; Saric, Borna; Vranic, Semir; Zarkovic, Kamelija

    2016-03-01

    The aim of the present study was to immunohistochemically investigate the expression and prognostic significance of putative cancer stem cell markers CD117 (c-kit), CD34, CD20 and CD15 in a cohort of patients with primary choroidal and ciliary body melanoma. The immunohistochemical expression of these markers was evaluated using 3,3'-diaminobenzidine tetrahydrochloride (DAB) and 3-amino-9-ethylcarbazole (AEC) chromogens on paraffin-embedded tissue samples from 40 patients who underwent enucleation in the period from 1985 through 2000. Thirty-one patients had adequate tissue specimens for the analysis. CD117 overexpression was observed in 12 of the 31 samples (39%) when AEC chromogen was used and in 14 of 26 (54%) samples when DAB was used. CD15 positivity was seen in three out of 30 (10%) samples with AEC and in six out of 26 (23%) samples with DAB. CD20 and CD34 exhibited no positivity in the tested samples. During the average follow-up time of 8.7 years (range 0.5-22 years), 17 patients (55%) died due to metastatic disease. The Kaplan-Meier plots showed a significantly shorter overall and disease-free survival in CD117-positive patients when the AEC chromogen was used. CD15 expression was not associated with patients' survival. In multivariate analysis, patients expressing the CD117 AEC had 4.13 times higher risk of lethal outcome in comparison with CD117 AEC negative patients. Our retrospective cohort study has for the first time demonstrated a small proportion of CD15-positive uveal melanomas. CD117 AEC overexpression was associated with a worse outcome in patients with choroidal and ciliary body melanoma. Further studies should confirm the validity of these observations and their potential for targeted treatment modalities. 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/

  11. Metastatic breast disease from cutaneous malignant melanoma.

    Science.gov (United States)

    Moschetta, Marco; Telegrafo, Michele; Lucarelli, Nicola Maria; Martino, Gianluigi; Rella, Leonarda; Stabile Ianora, Amato Antonio; Angelelli, Giuseppe

    2014-01-01

    Malignant melanoma is one of the most rapidly increasing cancer in the world. Breast metastases from melanoma are uncommon but could reflect a widespread disease. We report a case of malignant widespread melanoma presenting with bilateral breast nodules in a 39 year-old pre-menopausal Caucasian woman with an history of cutaneous melanoma of the trunk. Breast clinical examination revealed the presence of a hard and mobile lump located on the left breast. Ultrasound detected two bilateral nodules corresponding to oval opacities with well-defined edges and without calcifications or architectural distortion on mammography. Fine needle aspiration cytology performed on both breast nodules confirmed that the breast lesions were metastases from primary cutaneous malignant melanoma. A total-body CT examination detected brain, lung and abdominal lymph nodes metastases. The breast represents an uncommon site of metastatic disease from extra-mammary tumors. Imaging features of breast metastases from melanoma usually do not allow a differential diagnosis with breast primary tumors. Breast metastases may be asymptomatic or palpable as dense and well-circumscribed nodules. Breast metastases indicate a widespread disease and should lead to avoid aggressive surgical procedures because of the poor prognosis of patients affected by metastatic melanoma. The detection of bilateral breast metastases from melanoma is highly suggestive of metastatic multi-organ disease and could be useful to address the therapeutic approach. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. 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.

  13. Malignant melanoma at a scientific laboratory

    International Nuclear Information System (INIS)

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

    1985-01-01

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

  14. 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 ...

  15. 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

  16. Xeroderma pigmentosum genes and melanoma risk.

    Science.gov (United States)

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

    2013-09-01

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

  17. Alpha particles for treatment of disseminated melanoma

    International Nuclear Information System (INIS)

    Link, E.M.

    2010-01-01

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

  18. 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

    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...

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

    African Journals Online (AJOL)

    Malignant melanomas of the mucosal regions of the head and neck are extremely rare neoplasms accounting for less than 1% of all melanomas. Approximately half of all head and neck melanomas occur in the oral cavity. Less than 2% of all melanomas lack pigmentation, in the oral mucosa however, up to 75% of cases ...

  20. primary malignant amelanotic melanoma arising from a vitiligo patch

    African Journals Online (AJOL)

    2014-05-05

    May 5, 2014 ... Malignant melanoma is a rare tumour in people of. African descent including those affected by albinism. (1). The incidence of malignant melanoma in Africans is estimated to ranging from 0.5 to 1.5 per 100,000 people (2). Acrolentiginous melanoma is the most common type of melanoma in this population.

  1. Animal type melanoma: a report of two cases

    Directory of Open Access Journals (Sweden)

    Mariângela Esther Alencar Marques

    2010-08-01

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

  2. Melanoma Surveillance in the US: Collecting Melanoma Data

    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. Suephy Chen, a dermatologist from Emory University, discusses why the articles are important, as well as the need to increase dermatologists’ awareness of cancer registries and reporting requirements.  Created: 10/19/2011 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 10/19/2011.

  3. Comparative magnetic resonance imaging findings between gliomas and presumed cerebrovascular accidents in dogs.

    Science.gov (United States)

    Cervera, Vicente; Mai, Wilfried; Vite, Charles H; Johnson, Victoria; Dayrell-Hart, Betsy; Seiler, Gabriela S

    2011-01-01

    Cerebrovascular accidents, or strokes, and gliomas are common intraaxial brain lesions in dogs. An accurate differentiation of these two lesions is necessary for prognosis and treatment decisions. The magnetic resonance (MR) imaging characteristics of 21 dogs with a presumed cerebrovascular accident and 17 with a glioma were compared. MR imaging findings were reviewed retrospectively by three observers unaware of the final diagnosis. Statistically significant differences between the appearance of gliomas and cerebrovascular accidents were identified based on lesion location, size, mass effect, perilesional edema, and appearance of the apparent diffusion coefficient map. Gliomas were predominantly located in the cerebrum (76%) compared with presumed cerebrovascular accidents that were located mainly in the cerebellum, thalamus, caudate nucleus, midbrain, and brainstem (76%). Gliomas were significantly larger compared with presumed cerebrovascular accidents and more commonly associated with mass effect and perilesional edema. Wedge-shaped lesions were seen only in 19% of presumed cerebrovascular accidents. Between the three observers, 10-47% of the presumed cerebrovascular accidents were misdiagnosed as gliomas, and 0-12% of the gliomas were misdiagnosed as cerebrovascular accidents. Diffusion weighted imaging increased the accuracy of the diagnosis for both lesions. Agreement between observers was moderate (kappa = 0.48, P < 0.01).

  4. Current management and novel agents for malignant melanoma

    Directory of Open Access Journals (Sweden)

    Lee Byung

    2012-02-01

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

  5. Future perspectives in melanoma research

    Directory of Open Access Journals (Sweden)

    Paolo A. Ascierto

    2016-11-01

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

  6. Avaliação clínica da ablação uveal intravítrea com gentamicina em cães portadores de glaucoma crônico Clinical evaluation of intravitreal uveal ablation with gentamicin in chronic glaucomatous dogs

    Directory of Open Access Journals (Sweden)

    J.L.V. Chiurciu

    2007-04-01

    Full Text Available Investigou-se, clinicamente o resultado da ablação uveal intravítrea em 13 olhos cegos de cães com glaucoma crônico unilateral. Os olhos acometidos foram submetidos à ablação uveal intravítrea, por meio de injeção na câmara vítrea de 0,5ml de sulfato de gentamicina (40mg/ml associado a 0,3ml de fosfato de dexametasona (4mg/ml. As variáveis clinicas oftálmicas foram quali-quantificadas em escores, por até 48 semanas do pós-operatório; além de aspectos relacionados à dor, como variações do apetite e peso corporal. Nos sinais clínicos, de secreção ocular, blefaroespasmo, quemose, hifema e pigmentação, neovascularização, pannus e variações de apetite e peso corporal, não se notaram diferenças significativas entre os momentos. A ablação uveal intravítrea diminuiu a hiperemia conjuntival, porém acarretou aumento de opacidade corneana. A associação da ablação com antiinflamatórios tópico e sistêmico indicou não se tratar de procedimento doloroso.The purpose of the study was to investigate the clinical alterations of intravitreal uveal ablation. Thirteen irreversible blind canine eyes, presenting unilateral chronic glaucoma. All the glaucomatous eyes were submitted to intravitreal uveal ablation but the injection of 0.5ml of gentamicin sulfate solution (40mg/ml associated with 0.3ml of dexametasone phosphate (4mg/ml through the vitreous chamber. The oftalmic clinical variables were evaluated and classified in scores until 48 weeks after surgery. Clinical signs of pain, like apetite variations and body weight were also evaluated. Clinical signs of ocular discharge, blepharoespasm, quemosis, hifema and pigmentation, neovascularization, pannus and appetite variations and body weight did not show significant differences. The intravitreal uveal ablation reduced the conjunctival hyperemia, however caused increase in corneal opacity. The association of ablation with topic and sistemic antiflamatories was not a

  7. 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...

  8. Differentiating regressed melanoma from regressed lichenoid keratosis.

    Science.gov (United States)

    Chan, Aegean H; Shulman, Kenneth J; Lee, Bonnie A

    2017-04-01

    Distinguishing regressed lichen planus-like keratosis (LPLK) from regressed melanoma can be difficult on histopathologic examination, potentially resulting in mismanagement of patients. We aimed to identify histopathologic features by which regressed melanoma can be differentiated from regressed LPLK. Twenty actively inflamed LPLK, 12 LPLK with regression and 15 melanomas with regression were compared and evaluated by hematoxylin and eosin staining as well as Melan-A, microphthalmia transcription factor (MiTF) and cytokeratin (AE1/AE3) immunostaining. (1) A total of 40% of regressed melanomas showed complete or near complete loss of melanocytes within the epidermis with Melan-A and MiTF immunostaining, while 8% of regressed LPLK exhibited this finding. (2) Necrotic keratinocytes were seen in the epidermis in 33% regressed melanomas as opposed to all of the regressed LPLK. (3) A dense infiltrate of melanophages in the papillary dermis was seen in 40% of regressed melanomas, a feature not seen in regressed LPLK. In summary, our findings suggest that a complete or near complete loss of melanocytes within the epidermis strongly favors a regressed melanoma over a regressed LPLK. In addition, necrotic epidermal keratinocytes and the presence of a dense band-like distribution of dermal melanophages can be helpful in differentiating these lesions. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. A modified COMS plaque for iris melanoma

    Directory of Open Access Journals (Sweden)

    Daniel J. Scanderbeg

    2011-09-01

    Full Text Available Melanoma of the iris is a rare condition compared to posterior ocular tumors and in this case report we presenta 51-year-old female patient with diffuse iris melanoma. Traditional COMS (Collaborative Ocular Melanoma Studyplaques are used at our institution for radiation therapy, so a novel modification of the traditional plaque was requiredto allow better conformance with placement on the cornea. The usual silastic insert was machined to dimensions incompliance with the cornea, placed without incident, and treatment delivered with excellent patient tolerance of themodified plaque.

  10. Immunotherapy for advanced melanoma: future directions.

    Science.gov (United States)

    Valpione, Sara; Campana, Luca G

    2016-02-01

    As calculated by the meta-analysis of Korn et al., the prognosis of metastatic melanoma in the pretarget and immunological therapy era was poor, with a median survival of 6.2 and a 1-year life expectancy of 25.5%. Nowadays, significant advances in melanoma treatment have been gained, and immunotherapy is one of the promising approaches to get to durable responses and survival improvement. The aim of the present review is to highlight the recent innovations in melanoma immunotherapy and to propose a critical perspective of the future directions of this enthralling oncology subspecialty.

  11. Gingival osteogenic melanoma in two dogs.

    Science.gov (United States)

    Ellis, Angela E; Harmon, Barry G; Miller, Debra L; Northrup, Nicole C; Latimer, Kenneth S; Uhl, Elizabeth W

    2010-01-01

    Osteogenic melanoma is a rare variant of metaplastic malignant melanoma in human medicine and appears to be a similarly rare variant in dogs. Two dogs with oral malignant melanoma with neoplastic bone formation are reported in this study. Both tumors were characterized by malignant melanocytes that transitioned into neoplastic bone at the deep margins of the neoplasm. Immunohistochemical analysis revealed S100- and Melan-A-positive neoplastic cells adjacent to, and occasionally embedded within, an osteoid and chondroblastic matrix. Scattered clusters of neoplastic cells were also positive for osteocalcin. The findings indicate that in dogs, as in humans, neoplastic melanocytes have metaplastic potential and can be osteogenic.

  12. Dermatoscopic Findings of Seborrheic Keratosis in Melanoma.

    Science.gov (United States)

    Brandão, Maria Luiza; Oliveira Lima, Cíntia Maria; Moura, Heloísa Helena; Ishida, Cleide; Campos-do-Carmo, Gabriella; Cuzzi, Tullia; Ramos-E-Silva, Marcia

    2016-06-01

    Cutaneous melanoma may in some instances be confused with seborrheic keratosis, which is a very common neoplasia, more often mistaken for actinic keratosis and verruca vulgaris. Melanoma may clinically resemble seborrheic keratosis and should be considered as its possible clinical simulator. We report a case of melanoma with dermatoscopic characteristics of seborrheic keratosis and emphasize the importance of the dermatoscopy algorithm in differentiating between a melanocytic and a non-melanocytic lesion, of the excisional biopsy for the establishment of the diagnosis of cutaneous tumors, and of the histopathologic examination in all surgically removed samples.

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2010-06-01

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

  15. Presumed cultural similarity paradox : Expatriate adjustment and performance across the border or over the globe

    NARCIS (Netherlands)

    Vromans, P.; van Engen, M.L.; Mol, S.

    2013-01-01

    Purpose To introduce the presumed cultural similarity paradox as a possible explanation for the findings that adjusting to a culturally similar country is just as difficult as adjusting to a culturally dissimilar country. We provide a conceptual framework, enabling further understanding and research

  16. Presumed cultural similarity paradox: expatriate adjustment and performance across the border or over the globe

    NARCIS (Netherlands)

    Vromans, P.; van Engen, M.; Mol, S.

    2013-01-01

    Purpose - To introduce the presumed cultural similarity paradox as a possible explanation for the findings that adjusting to a culturally similar country is just as difficult as adjusting to a culturally dissimilar country. We provide a conceptual framework, enabling further understanding and

  17. Presumed atypical HDR syndrome associated with Band Keratopathy and pigmentary retinopathy.

    Science.gov (United States)

    Kim, Cinoo; Cheong, Hae Il; Kim, Jeong Hun; Yu, Young Suk; Kwon, Ji Won

    2011-01-01

    This report describes presumed atypical hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome associated with unexpected ocular findings. The patient had exotropia, bilateral band keratopathy, and pigmentary retinopathy, including attenuated retinal vessels and atrophy of the retinal pigment epithelium. Even though the calcific plaques were successfully removed, visual acuity in both eyes gradually decreased and electroretinography was extinguished. Copyright 2009, SLACK Incorporated.

  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. Presumed PDF modeling of microjet assisted CH4–H2/air turbulent flames

    International Nuclear Information System (INIS)

    Chouaieb, Sirine; Kriaa, Wassim; Mhiri, Hatem; Bournot, Philippe

    2016-01-01

    Highlights: • Microjet assisted CH 4 –H 2 /air turbulent flames are numerically investigated. • Temperature, species and soot are well predicted by the Presumed PDF model. • An inner flame is identified due to the microjet presence. • The addition of hydrogen to the microjet assisted flames enhances mixing. • Soot emission is reduced by 36% for a 10% enriched microjet assisted flame. - Abstract: The characteristics of microjet assisted CH 4 –H 2 /air flames in a turbulent mode are numerically investigated. Simulations are performed using the Computational Fluid Dynamics code Fluent. The Presumed PDF and the Discrete Ordinates models are considered respectively for combustion and radiation modeling. The k–ε Realizable model is adopted as a turbulence closure model. The Tesner model is used to calculate soot particle quantities. In the first part of this paper, the Presumed PDF model is compared to the Eddy Dissipation model and to slow chemistry combustion models from literature. Results show that the Presumed PDF model predicts correctly thermal and species fields, as well as soot formation. The effect of hydrogen enrichment on CH 4 /air confined flames under the addition of an air microjet is investigated in the second part of this work. The found results show that an inner flame was identified due to the air microjet for the CH 4 –H 2 /air flames. Moreover, the increase of hydrogen percentage in the fuel mixture leads to mixing enhancement and consequently to considerable soot emission reduction.

  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…

  1. 28 CFR 104.44 - Determination of presumed noneconomic losses for decedents.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Determination of presumed noneconomic losses for decedents. 104.44 Section 104.44 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) SEPTEMBER 11TH VICTIM COMPENSATION FUND OF 2001 Amount of Compensation for Eligible Claimants. § 104.44...

  2. 28 CFR 104.46 - Determination of presumed noneconomic losses for claimants who suffered physical harm.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Determination of presumed noneconomic losses for claimants who suffered physical harm. 104.46 Section 104.46 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) SEPTEMBER 11TH VICTIM COMPENSATION FUND OF 2001 Amount of Compensation for...

  3. Clinical radiobiology of malignant melanoma

    International Nuclear Information System (INIS)

    Bentzen, S.M.; Overgaard, J.; Overgaard, M.; Thames, H.D.; Vejby Hansen, P.; Von der Maase, H.; Meder, J.

    1989-01-01

    Tumor-control probability (TCP) was analyzed in a series of 121 patients having 239 histologically proven recurrent or metastatic malignant melanomas. These were treated with fractionated radiotherapy with various doses per fraction, total doses, and overall times. Cutaneous lesions (127,53%) were treated with electron beams, and more deeply seated tumors (112,47%) with 60 Co or 4-8 MV X-rays. The fraction size was highly variable, and this permitted determination of the α/β ration in the multifraction linearquadratic model, which was estimated at 0.57 Gy with 95% confidence limits [-1.07,2.5]Gy Threatment time had no demonstrable influenc on TCP. Thus this tumor exhibits the fractionation sensitivity characteristic of a late-responding normal tissue, suggesting that an adequate fractionation schedule for malignant melanomas would be characterized by larger-than-conventional doses per fraction, possibly about 6 Gy per fraction. This is consistent with the conclusions of other authors. Tumor size, evaluated as mean tumor diameter, S, had a major impact on TCP: the number of target cells increased as a power function of S with exponent 0.72 (95% confidence limits) [1.49, 0.94]. In fact, a considerable amount of the heterogeneity in the dose-responce data could be removed by accounting for size. Thus, the weak, or absent dose response became highly significant. When a patient had multiple lesions, the responses of these to radiotherapy tended to be similar, thus implying that results were significantly influenced by a 'hidden parameter' (such as inherent radiosensitivity or immunological status). A test of the predictive value of the TCP-model was performed in a different series of 183 cutaneous and lymph node malignant melanomas. The observed dose-response relationship in this data set was in good agreement with the model prediction. A chi-square test for goodness-of-fit showed that the variation between predicted and observed results could be explained by the

  4. Anti-SEMA4D Monoclonal Antibody VX15/2503 With Nivolumab or Ipilimumab in Treating Patients With Stage III or IV Melanoma

    Science.gov (United States)

    2018-04-26

    Metastatic Melanoma; Stage III Cutaneous Melanoma AJCC v7; Stage IIIA Cutaneous Melanoma AJCC v7; Stage IIIB Cutaneous Melanoma AJCC v7; Stage IIIC Cutaneous Melanoma AJCC v7; Stage IV Cutaneous Melanoma AJCC v6 and v7

  5. Isolated Pancreatic Metastasis from Malignant Melanoma: Is ...

    African Journals Online (AJOL)

    [1] Renal-cell cancer, colorectal cancer, melanoma and ... types of cancer, such as colorectal and renal cancers,[5] is the gold standard ... Department of Surgical Oncology, Institute Paoli Calmettes .... [20] Whether or not these innovative.

  6. Poliosis circumscripta unmasking a scalp melanoma.

    Science.gov (United States)

    Yeo, L; Husain, E; Rajpara, S

    2015-12-01

    A 28-year-old man presented with a 1-year history of a localized patch of grey hair and an underlying darkly pigmented lesion on his right occipital area. Clinical appearance revealed poliosis overlying an asymmetrical plaque with variable degrees of brown pigmentation and white discolouration. Owing to the suspicious nature of the lesion, excision with a 2 mm margin was performed. Histology revealed an invasive melanoma with extensive regression and prominent involvement of multiple hair follicles. Scalp melanoma with associated poliosis is extremely rare, and has only been reported once in the literature to date. There have been two reports in the opthalmology literature regarding eyelash poliosis associated with orbital melanoma. The pathogenesis of poliosis still remains unclear. This is the second reported case of poliosis circmscripta unmasking a scalp melanoma, and highlights the importance of being vigilant when examining patients with poliosis of the scalp. © 2014 British Association of Dermatologists.

  7. Metastatic malignant subungal melanoma: Importance of FNAC

    Directory of Open Access Journals (Sweden)

    Radhika Punshi Nandwani

    2014-01-01

    Full Text Available Subungual melanoma is a rare type of skin cancer. It is an uncommon form of acral lentiginous melanoma. Approximately 85% of cases are misdiagnosed initially, and it is generally associated with a poor prognosis. Herein, we describe a case of metastatic subungal melanoma to the axillary lymph node in a 45-year-old male. Diagnosis of metastasis was made based on cytology, where the clinicians were guided to search for primary. This case report highlights the role of fine-needle aspiration cytology (FNAC in the diagnosis of this entity to draw the attention of the reader to the possible underreporting of melanoma because of a variant that evades diagnosis and our reluctance to think about its existence.

  8. Nivolumab-Based Treatments for Advanced Melanoma

    Science.gov (United States)

    A summary of results from an international, double-blind, randomized phase III trial testing the combination of nivolumab (Opdivo®) and ipilimumab (Yervoy®) against nivolumab alone and ipilimumab alone in patients with advanced melanoma.

  9. CT findings of diffuse malignant leptomeningeal melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Fujii, Katsuro; Sahashi, Ko; Takahashi, Akira; Nakagawa, Hiroshi [Aichi Medical Univ., Aichi (Japan); Sumi, Yasuhiko

    1982-04-01

    This was a case of malignant melanoma which spreaded diffusely in the meninges. The diagnosis was established by cytology of the cerebrospinal fluid. The CT images, cerebral angiographic findings and pathological findings by autopsy were presented.

  10. Timely Healthcare Checkup Catches Melanoma Early

    Science.gov (United States)

    ... please turn Javascript on. Feature: Skin Cancer Timely Healthcare Checkup Catches Melanoma Early Past Issues / Summer 2013 ... left the Congress and starting working as a healthcare consultant, when I finally decided to have a ...

  11. Treatment and outcomes of anorectal melanoma.

    LENUS (Irish Health Repository)

    Heeney, Anna

    2012-02-01

    INTRODUCTION: anorectal melanoma is an uncommon disease constituting less than 3% of all melanomas. Due to its rarity, there are a lack of randomized control trials regarding appropriate management and current evidence is based mainly on retrospective studies. METHODS: in view of the controversial surgical treatment of anorectal melanoma, we review the most published literature in an attempt to elucidate its typical clinical features along with current thinking with respect to management approaches to this aggressive disease. Using the keywords "anorectal" and "malignant melanoma", a medline search of all articles in English was performed and the relevant articles procured. Additional references were retrieved by cross reference from key articles. RESULTS: anorectal melanoma affects the elderly with a slight preponderance for females. It commonly presents disguised as benign disease with local bleeding or suspicion for haemorrhoidal disease. There is no convincing evidence to indicate that radical resection of primary anorectal melanoma is associated with improvement in local control or survival, and local excision is an acceptable treatment option. CONCLUSION: optimum management depends on several factors and the therapeutic goals should be to lengthen survival and preserve quality-of-life. Given that wide local excision is a more limited intervention with comparable survival it should be considered as the initial treatment choice. Unfortunately prognosis for patients with this disease remains poor despite choice of treatment strategy with overall five year disease-free survival less than twenty percent in most studies.

  12. Melanoma or Pseudo melanoma Change in a pigmented lesion after application of topical 5-Fluorouracil

    Science.gov (United States)

    2017-10-26

    2. REPORT TYPE 3. DATES COVERED (From - To) 10/26/2017 Poster 10/26/2017-10/29/2017 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Melanoma or Pseudo...melanoma? Change in a pigmented lesion after application of topical 5-Fluorouracil. 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d

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

    Science.gov (United States)

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

    2017-11-01

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

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

    DEFF Research Database (Denmark)

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

    2018-01-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Centers for Disease Control (CDC) Podcasts

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

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

    Science.gov (United States)

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

    2016-07-01

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

  18. Melanoma

    Science.gov (United States)

    ... surfaces that reflect light more, such as water, sand, concrete, and white-painted areas. Be extra careful ... A.D.A.M. follows rigorous standards of quality and accountability. A.D.A.M. is among ...

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

    Directory of Open Access Journals (Sweden)

    Quentin Godechal

    2013-06-01

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

  20. Presuming consent in the ethics of posthumous sperm procurement and conception.

    Science.gov (United States)

    Kroon, Frederick

    2015-12-01

    This paper compares standard conceptions of consent with the conception of consent defended by Kelton Tremellen and Julian Savulescu in their attempt to re-orient the ethical debate around posthumous sperm procurement and conception, as published in Reproductive BioMedicine Online in 2015. According to their radical proposal, the surviving partner's wishes are, in effect, the only condition that needs to be considered for there to be a legitimate moral case for these procedures: the default should be presumed consent to the procedures, whether or not the agent did consent or would have consented. The present paper argues that Tremellen and Savulescu's case for this position is flawed, but offers a reconstruction that articulates what may well be a hidden, and perhaps reasonable, assumption behind the argument. But while the new argument appears more promising, the reconstruction also suggests that the position of presumed consent is currently unlikely to be acceptable as policy.

  1. Presuming consent in the ethics of posthumous sperm procurement and conception

    Directory of Open Access Journals (Sweden)

    Frederick Kroon

    2015-12-01

    Full Text Available This paper compares standard conceptions of consent with the conception of consent defended by Kelton Tremellen and Julian Savulescu in their attempt to re-orient the ethical debate around posthumous sperm procurement and conception, as published in Reproductive BioMedicine Online in 2015. According to their radical proposal, the surviving partner’s wishes are, in effect, the only condition that needs to be considered for there to be a legitimate moral case for these procedures: the default should be presumed consent to the procedures, whether or not the agent did consent or would have consented. The present paper argues that Tremellen and Savulescu’s case for this position is flawed, but offers a reconstruction that articulates what may well be a hidden, and perhaps reasonable, assumption behind the argument. But while the new argument appears more promising, the reconstruction also suggests that the position of presumed consent is currently unlikely to be acceptable as policy.

  2. Safety of a Brief Emergency Department Observation Protocol for Patients With Presumed Fentanyl Overdose.

    Science.gov (United States)

    Scheuermeyer, Frank X; DeWitt, Christopher; Christenson, Jim; Grunau, Brian; Kestler, Andrew; Grafstein, Eric; Buxton, Jane; Barbic, David; Milanovic, Stefan; Torkjari, Reza; Sahota, Indy; Innes, Grant

    2018-03-09

    Fentanyl overdoses are increasing and few data guide emergency department (ED) management. We evaluate the safety of an ED protocol for patients with presumed fentanyl overdose. At an urban ED, we used administrative data and explicit chart review to identify and describe consecutive patients with uncomplicated presumed fentanyl overdose (no concurrent acute medical issues) from September to December 2016. We linked regional ED and provincial vital statistics databases to ascertain admissions, revisits, and mortality. Primary outcome was a composite of admission and death within 24 hours. Other outcomes included treatment with additional ED naloxone, development of a new medical issue while in the ED, and length of stay. A prespecified subgroup analysis assessed low-risk patients with normal triage vital signs. There were 1,009 uncomplicated presumed fentanyl overdose, mainly by injection. Median age was 34 years, 85% were men, and 82% received out-of-hospital naloxone. One patient was hospitalized and one discharged patient died within 24 hours (combined outcome 0.2%; 95% confidence interval [CI] 0.04% to 0.8%). Sixteen patients received additional ED naloxone (1.6%; 95% CI 1.0% to 2.6%), none developed a new medical issue (0%; 95% CI 0% to 0.5%), and median length of stay was 173 minutes (interquartile range 101 to 267). For 752 low-risk patients, no patients were admitted or developed a new issue, and one died postdischarge; 3 (0.4%; 95% CI 0.01% to 1.3%) received ED naloxone. In our cohort of ED patients with uncomplicated presumed fentanyl overdose-typically after injection-deterioration, admission, mortality, and postdischarge complications appear low; the majority can be discharged after brief observation. Patients with normal triage vital signs are unlikely to require ED naloxone. Copyright © 2018 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

  3. The presumed central nervous system effects of rocuronium in a neonate and its reversal with sugammadex.

    Science.gov (United States)

    Langley, Ross J; McFadzean, Jillian; McCormack, Jon

    2016-01-01

    We describe a 2-day-old male infant who received rocuronium as part of general anesthesia for a tracheal esophageal fistula repair. Postoperatively, he had prolonged central and peripheral neuromuscular blockade despite cessation of the rocuronium infusion several hours previously. This case discusses the presumed central nervous system effects of rocuronium in a neonate and its effective reversal with sugammadex. © 2015 John Wiley & Sons Ltd.

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

    Directory of Open Access Journals (Sweden)

    Goldenberg A

    2015-08-01

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

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

    Directory of Open Access Journals (Sweden)

    Ana Maria Carreño

    2013-04-01

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

  6. Presumed Cases of Mumps in Pregnancy: Clinical and Infection Control Implications

    Directory of Open Access Journals (Sweden)

    Svjetlana Lozo

    2012-01-01

    Full Text Available Recently, a mumps outbreak in New York and New Jersey was reported by the Centers for Disease Control and Prevention (CDC. Subsequently, the dissemination of the disease was rapid, and, from June 28th 2009 through January 29th 2010, a total of 1,521 cases of mumps were reported in New York and New Jersey. Seven presumed cases occurred in pregnant women cared for at our institution. Mumps diagnosis as per the NYC Department of Health and Mental Hygiene was based on clinical manifestations, particularly parotitis. Prior immunizations with mumps vaccine and negative IgM were not adequate to rule out mumps infections. All of our seven patients had exposure to mumps in either their household or their community, and some of the them had symptoms of mumps. Due to the difficulties in interpreting serologies of these patients, their cases led to a presumed diagnosis of mumps. The diagnosis of mumps lead to the isolation of patients and health care personnel that were in contact with them. In this paper, we detail the presenting findings, diagnostic dilemmas and infection control challenges associated with presumed cases of mumps in pregnancy.

  7. Optical coherence tomography and fundus autofluorescence findings in presumed congenital simple retinal pigment epithelium hamartoma

    Directory of Open Access Journals (Sweden)

    Baskaran, Prabu

    2017-10-01

    Full Text Available Aim: Presumed congenital simple retinal pigment epithelium hamartoma is a rare benign lesion of the macula that mimics congenital hypertrophy of the retinal pigment epithelium (RPE and combined hamartoma of the retina and the RPE; newer imaging modalities can help in diagnosis. We report three patients with presumed congenital simple RPE hamartoma, and describe the enhanced-depth imaging optical coherence tomography (EDI-OCT and fundus autofluorescence (FAF findings. Methods: Two patients were asymptomatic; one had an intraocular foreign body in addition to the hamartoma. All had a similar jet black, elevated lesion in the macula, sparing the fovea. EDI-OCT showed a characteristic hyperreflective layer with complete optical shadowing of the deeper layers; FAF showed pronounced hypoautofluorescence of the lesion. Conclusion: Multimodal imaging with FAF and EDI-OCT can help to differentiate simple RPE hamartoma from similar RPE lesions, and may serve as a useful adjunct to clinical diagnosis of this rare tumor. We present the second largest series of presumed congenital simple RPE hamartoma, and – to the best of our knowledge – the first report of FAF findings of this tumor.

  8. Pancreatic metastases from ocular malignant melanoma: the use of endoscopic ultrasound-guided fine-needle aspiration to establish a definitive cytologic diagnosis: a case report

    Directory of Open Access Journals (Sweden)

    Diogo Turiani Hourneaux De Moura

    2016-12-01

    Full Text Available Abstract Background When encountering solid pancreatic lesions, nonpancreatic primary metastases are rare and differentiating a metastasis from a primary neoplastic lesion is challenging. The clinical presentation and radiologic features can be similar and the possibility of a pancreatic metastasis should be considered when the patient refers to a history of a different primary cancer. Endoscopic ultrasound offers a key anatomical advantage in accessing the pancreas and endoscopic ultrasound-guided fine-needle aspiration has become the gold standard method for diagnosing pancreatic lesions. Case presentation A 58-year-old white Hispanic woman with a history of uveal malignant melanoma, presented with abdominal pain and jaundice. On admission, laboratory tests were performed (her total bilirubin was 6.37 mg/dL with a direct fraction of 5.30 mg/dL. Cross-sectional, abdominal computed tomography with contrast, showed a low-attenuating lesion localized in the pancreatic head (measuring 4 × 3 cm and a thinner section of the distal bile duct suspicious for compression. Our patient was scheduled for an endoscopic ultrasound-guided fine-needle aspiration to establish a diagnosis. Endoscopic ultrasound showed a solid, hypoechoic, well-defined lesion with regular contours (measuring 3.17 × 2.61 cm, localized between the head and neck of the pancreas. Endoscopic ultrasound-guided fine-needle aspiration was performed with a 22G needle and cytology confirmed the diagnosis of metastatic melanoma. Our patient subsequently underwent right orbital exenteration, followed by duodenopancreatectomy without complications. At the moment our patient is receiving adjuvant chemotherapy at an outside oncology clinic. Conclusions To the best of our knowledge, this is a very rare presentation of an ocular malignant melanoma with an isolated pancreatic metastasis causing symptomatic biliary obstruction. Endoscopic ultrasound-guided fine-needle aspiration has

  9. Do We Know What Causes Melanoma Skin Cancer?

    Science.gov (United States)

    ... Skin Cancer Causes, Risk Factors, and Prevention What Causes Melanoma Skin Cancer? Many risk factors for melanoma have been found, ... it’s not always clear exactly how they might cause cancer. For example, while most moles never turn into ...

  10. Addison's disease as a presentation of metastatic malignant melanoma.

    Science.gov (United States)

    Srinivasan, B; Patel, M; Ethunandan, M; Ilankovan, V

    2016-01-01

    Melanoma accounts for 5% of all skin cancers. The risk of metastasis is related to the thickness of the tumour, and can affect local, regional and distant sites. Adrenal metastasis from melanoma of the head and neck is uncommon and often asymptomatic. Addison's disease as a presentation of metastatic melanoma is extremely rare and we are unaware of previous reports in the world literature. We report a case of a patient with metastatic melanoma presenting with signs and symptoms of Addison's disease.

  11. Subretinal lipid exudation associated with untreated choroidal melanoma

    Directory of Open Access Journals (Sweden)

    C K Minija

    2011-01-01

    Full Text Available Subretinal lipid exudation in an untreated choroidal melanoma is very rare. It is seen following plaque radiotherapy in choroidal melanoma. There is only one case report of untreated choroidal melanoma with massive lipid exudation in a patient with metastatic hypernephroma. We report here a rare case of untreated choroidal melanoma with lipid exudation. Subretinal exudation that is rarely seen following plaque brachytherapy was noted at the borders of this untreated tumor. Lipid exudation partially resolved following brachytherapy.

  12. Immunotherapy of metastatic melanoma by reversal of immune suppression

    Energy Technology Data Exchange (ETDEWEB)

    Biggs, M.W.; Eiselein, J.E.

    1997-01-01

    Beginning with the observation that the human enteorvirus, Poliovirus Sabin 1, will lyse human melanoma cells in culture, clinical trials involving two patients with advance melanoma were performed. Parenteral injection of the viable Poliovirus into cutaneous melanoma metastases followed in 24 hours by oral administration of cyclophosphamide. The results of these two trials are described.

  13. Ocular melanoma: Detection using iodine-123-iodoamphetamine and SPECT imaging

    International Nuclear Information System (INIS)

    Dewey, S.H.; Leonard, J.C.

    1990-01-01

    Uptake of iodine-123-iodoamphetamine has been demonstrated in malignant melanoma using planar imaging techniques and has been used to detect an ocular melanoma at 12 hr postinjection. Using SPECT technique, an ocular melanoma is identified in a 64-yr-old male at 1 hr postinjection

  14. Oral Malignant Melanoma in a Ferret ( Mustela putorius furo).

    Science.gov (United States)

    d'Ovidio, Dario; Rossi, Giacomo; Meomartino, Leonardo

    2016-06-01

    Oral malignant melanomas are one of the most common oral malignant neoplasms in dogs but are rare in other domesticated species. This case report describes the clinical manifestations and histological appearance of oral melanoma in a ferret ( Mustela putorius furo). To the authors' knowledge, this is the first published description of a clinical case and histopathological findings of oral melanoma in this species.

  15. Vemurafenib for the treatment of melanoma.

    LENUS (Irish Health Repository)

    Jordan, Emmet John

    2012-12-01

    Metastatic melanoma is an aggressive disease resistant to chemotherapy. Recent clinical trials have reported improved survival for two novel agents; ipilimumab, a humanized, IgG1 monoclonal antibody that blocks cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and vemurafenib , a BRAF (v-raf murine sarcoma viral oncogene homolog B1) inhibitor targeting an activating mutation in the serine-threonine-protein kinase BRAF gene. AREAS COVERED: The authors reviewed preclinical and clinical data examining the safety of vemurafenib in melanoma. MEDLINE and EMBASE were searched using the medical subject heading \\'vemurafenib\\' and the following text terms: melanoma, BRAF inhibition, vemurafenib. This review provides the reader with an overview of current data examining the efficacy and safety of vemurafenib in metastatic melanoma. EXPERT OPINION: Vemurafenib is an oral agent licensed for patients with BRAF V600E mutation-positive inoperable and metastatic melanoma. The most common adverse effects observed in Phase III clinical trials were dermatological events, arthralgia and fatigue. Specific dermatological toxicities included development of cutaneous squamous cell cancers and keratoacanthomas. Prolongation of the QT interval was also reported. Regular dermatological assessments and electrocardiograms are recommended. Ongoing trials are examining vemurafenib in both the adjuvant setting and metastatic setting in combination with ipilimumab and MEK inhibitors (mitogen-activated protein kinase\\/extracellular signal-regulated kinase). Understanding and overcoming mechanisms of resistance to BRAF inhibitors is the focus of ongoing research.

  16. [Molecular and immunohistochemical diagnostics in melanoma].

    Science.gov (United States)

    Schilling, B; Griewank, K G

    2016-07-01

    To provide appropriate therapy and follow-up to patients with malignant melanoma, proper diagnostics are of critical importance. Targeted therapy of advanced melanoma is based on the molecular genetic analyses of tumor tissue. In addition, sequencing of genes and other genetic approaches can provide insight into the origin of melanocytic tumors and can aid in distinguishing benign from malignant lesions. In this regard, spizoid neoplasms remain a challenging entity. Aside from genetic analyses of tumor tissue, immunohistochemistry remains an essential tool in melanoma diagnostics and TNM classification. With new immunotherapies being approved for advanced melanoma, immunohistochemistry to determine PD-L1 expression has gained clinical interest. While PD-L1 expression is associated with response to PD-1 blockade, a substantial number of patients without PD-L1 expression can still experience tumor remission upon treatment. In this review, current and future developments in melanoma diagnostics with regard to molecular genetics and immunohistochemistry are summarized. The utilization of such analyses in clinical decision making is also discussed.

  17. Selenium for the Prevention of Cutaneous Melanoma

    Directory of Open Access Journals (Sweden)

    Douglas Grossman

    2013-03-01

    Full Text Available The role of selenium (Se supplementation in cancer prevention is controversial; effects often depend on the nutritional status of the subject and on the chemical form in which Se is provided. We used a combination of in vitro and in vivo models to study two unique therapeutic windows for intervention in the process of cutaneous melanomagenisis, and to examine the utility of two different chemical forms of Se for prevention and treatment of melanoma. We studied the effects of Se in vitro on UV-induced oxidative stress in melanocytes, and on apoptosis and cell cycle progression in melanoma cells. In vivo, we used the HGF transgenic mouse model of UV-induced melanoma to demonstrate that topical treatment with l-selenomethionine results in a significant delay in the time required for UV-induced melanoma development, but also increases the rate of growth of those tumors once they appear. In a second mouse model, we found that oral administration of high dose methylseleninic acid significantly decreases the size of human melanoma xenografts. Our findings suggest that modestly elevation of selenium levels in the skin might risk acceleration of growth of incipient tumors. Additionally, certain Se compounds administered at very high doses could have utility for the treatment of fully-malignant tumors or prevention of recurrence.

  18. Selenium for the Prevention of Cutaneous Melanoma

    Science.gov (United States)

    Cassidy, Pamela B.; Fain, Heidi D.; Cassidy, James P.; Tran, Sally M.; Moos, Philip J.; Boucher, Kenneth M.; Gerads, Russell; Florell, Scott R.; Grossman, Douglas; Leachman, Sancy A.

    2013-01-01

    The role of selenium (Se) supplementation in cancer prevention is controversial; effects often depend on the nutritional status of the subject and on the chemical form in which Se is provided. We used a combination of in vitro and in vivo models to study two unique therapeutic windows for intervention in the process of cutaneous melanomagenisis, and to examine the utility of two different chemical forms of Se for prevention and treatment of melanoma. We studied the effects of Se in vitro on UV-induced oxidative stress in melanocytes, and on apoptosis and cell cycle progression in melanoma cells. In vivo, we used the HGF transgenic mouse model of UV-induced melanoma to demonstrate that topical treatment with l-selenomethionine results in a significant delay in the time required for UV-induced melanoma development, but also increases the rate of growth of those tumors once they appear. In a second mouse model, we found that oral administration of high dose methylseleninic acid significantly decreases the size of human melanoma xenografts. Our findings suggest that modestly elevation of selenium levels in the skin might risk acceleration of growth of incipient tumors. Additionally, certain Se compounds administered at very high doses could have utility for the treatment of fully-malignant tumors or prevention of recurrence. PMID:23470450

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

    International Nuclear Information System (INIS)

    Mishima, Yutaka; Ichihashi, Masamitsu; Nakanishi, Takafumi

    1985-01-01

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

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  1. The Antibiotic Prescribing Pathway for Presumed Urinary Tract Infections in Nursing Home Residents.

    Science.gov (United States)

    Kistler, Christine E; Zimmerman, Sheryl; Scales, Kezia; Ward, Kimberly; Weber, David; Reed, David; McClester, Mallory; Sloane, Philip D

    2017-08-01

    Due to the high rates of inappropriate antibiotic prescribing for presumed urinary tract infections (UTIs) in nursing home (NH) residents, we sought to examine the antibiotic prescribing pathway and the extent to which it agrees with the Loeb criteria; findings can suggest strategies for antibiotic stewardship. Chart review of 260 randomly-selected cases from 247 NH residents treated with an antibiotic for a presumed UTI in 31 NHs in North Carolina. We examined the prescribing pathway from presenting illness, to the prescribing event, illness work-up and subsequent clinical events including emergency department use, hospitalization, and death. Analyses described the decision-making processes and outcomes and compared decisions made with Loeb criteria for initiation of antibiotics. Of 260 cases, 60% had documented signs/symptoms of the presenting illness and 15% met the Loeb criteria. Acute mental status change was the most commonly documented sign/symptom (24%). NH providers (81%) were the most common prescribers and ciprofloxacin (32%) was the most commonly prescribed antibiotic. Fourteen percent of presumed UTI cases included a white blood cell count, 71% included a urinalysis, and 72% had a urine culture. Seventy-five percent of cultures grew at least one organism with ≥100,000 colony-forming units/milliliter and 12% grew multi-drug resistant organisms; 28% of antibiotics were prescribed for more than 7 days, and 7% of cases had a subsequent death, emergency department visit, or hospitalization within 7 days. Non-specific signs/symptoms appeared to influence prescribing more often than urinary tract-specific signs/symptoms. Prescribers rarely stopped antibiotics, and a minority prescribed for overly long periods. Providers may need additional support to guide the decision-making process to reduce antibiotic overuse and antibiotic resistance. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.

  2. Epidemiology of ocular disorders presumed to be inherited in three large Italian dog breeds in Italy.

    Science.gov (United States)

    Guandalini, Adolfo; Di Girolamo, Nicola; Santillo, Daniele; Andreani, Valentina; Corvi, Roberta; Bandini, Marina; Peruccio, Claudio

    2017-09-01

    To describe the epidemiology and the types of eye disorders that are presumed to be inherited (PIED) in three large Italian dog breeds. Three large Italian dog breeds: Neapolitan Mastiff (FCI code: 197), Maremma Sheepdog (FCI code: 201), and Italian Corso dog (FCI code: 343). All dogs that underwent a complete ophthalmic examination between 1992 and 2012 were included in this prospective observational study. The prevalence of eye disorders with 95% confidence intervals was reported for presumed healthy dogs and for dogs referred to a veterinary center for an ophthalmic consultation. Univariate and multivariate logistic regression techniques were used to generate odds ratios. Of 605 dogs examined during the study period, 351 dogs were affected by at least one PIED (58%; 95% CI: 54-62%). The prevalence of PIED was significantly lower in dogs presented for ophthalmic examination (53.8%) as compared to presumed healthy dogs (62.2%)(OR: 1.4; 95% CI: 1.02-1.9; P = 0.037). Also after multivariate adjustment for the period of observation, the odds of Neapolitan Mastiff (92.1%; OR: 21.4; 95% CI: 11.1-41.4) and of Cane Corso (57.7%; OR: 2.5; 95% CI: 1.7-3.6) suffering a PIED were greater than the Maremma Sheepdog (35.4%). The most common PIED in each breed were entropion (24.3% of all the PIED) in the Neapolitan Mastiff, ectropion (36.6%) in the Corso dog, and cataract (27.9%) in the Maremma Sheepdog. Clinicians should be aware that three large Italian dog breeds frequently suffer PIED. Breed standards should be reconsidered, and breeding programs should be directed at limiting such disorders. © 2016 American College of Veterinary Ophthalmologists.

  3. Bioelectric Applications for Treatment of Melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Beebe, Stephen J., E-mail: sbeebe@odu.edu; Schoenbach, Karl H.; Heller, Richard [Frank Reidy Research Center for Bioelectrics/Old Dominion University 4211 Monarch Way, Suite 300, Norfolk, Virginia 23508 (United States)

    2010-09-27

    Two new cancer therapies apply bioelectric principles. These methods target tumor structures locally and function by applying millisecond electric fields to deliver plasmid DNA encoding cytokines using electrogene transfer (EGT) or by applying rapid rise-time nanosecond pulsed electric fields (nsPEFs). EGT has been used to locally deliver cytokines such as IL-12 to activate an immune response, resulting in bystander effects. NsPEFs locally induce apoptosis-like effects and affect vascular networks, both promoting tumor demise and restoration of normal vascular homeostasis. EGT with IL-12 is in melanoma clinical trials and nsPEFs are used in models with B16F10 melanoma in vitro and in mice. Applications of bioelectrics, using conventional electroporation and extensions of it, provide effective alternative therapies for melanoma.

  4. Bioelectric Applications for Treatment of Melanoma

    Directory of Open Access Journals (Sweden)

    Richard Heller

    2010-09-01

    Full Text Available Two new cancer therapies apply bioelectric principles. These methods target tumor structures locally and function by applying millisecond electric fields to deliver plasmid DNA encoding cytokines using electrogene transfer (EGT or by applying rapid rise-time nanosecond pulsed electric fields (nsPEFs. EGT has been used to locally deliver cytokines such as IL-12 to activate an immune response, resulting in bystander effects. NsPEFs locally induce apoptosis-like effects and affect vascular networks, both promoting tumor demise and restoration of normal vascular homeostasis. EGT with IL-12 is in melanoma clinical trials and nsPEFs are used in models with B16F10 melanoma in vitro and in mice. Applications of bioelectrics, using conventional electroporation and extensions of it, provide effective alternative therapies for melanoma.

  5. Sequential Acral Lentiginous Melanomas of the Foot

    Directory of Open Access Journals (Sweden)

    Jiro Uehara

    2010-12-01

    Full Text Available A 64-year-old Japanese woman had a lightly brown-blackish pigmented macule (1.2 cm in diameter on the left sole of her foot. She received surgical excision following a diagnosis of acral lentiginous melanoma (ALM, which was confirmed histopathologically. One month after the operation, a second melanoma lesion was noticed adjacent to the grafted site. Histopathologically, the two lesions had no continuity, but HMB-45 and cyclin D1 double-positive cells were detected not only on aggregates of atypical melanocytes but also on single cells near the cutting edge of the first lesion. The unique occurrence of a sequential lesion of a primary melanoma might be caused by stimulated subclinical field cells during the wound healing process following the initial operation. This case warrants further investigation to establish the appropriate surgical margin of ALM lesions.

  6. Bioelectric Applications for Treatment of Melanoma

    International Nuclear Information System (INIS)

    Beebe, Stephen J.; Schoenbach, Karl H.; Heller, Richard

    2010-01-01

    Two new cancer therapies apply bioelectric principles. These methods target tumor structures locally and function by applying millisecond electric fields to deliver plasmid DNA encoding cytokines using electrogene transfer (EGT) or by applying rapid rise-time nanosecond pulsed electric fields (nsPEFs). EGT has been used to locally deliver cytokines such as IL-12 to activate an immune response, resulting in bystander effects. NsPEFs locally induce apoptosis-like effects and affect vascular networks, both promoting tumor demise and restoration of normal vascular homeostasis. EGT with IL-12 is in melanoma clinical trials and nsPEFs are used in models with B16F10 melanoma in vitro and in mice. Applications of bioelectrics, using conventional electroporation and extensions of it, provide effective alternative therapies for melanoma

  7. Control of differentiation of melanoma cells

    International Nuclear Information System (INIS)

    Eguchi, Goro

    1980-01-01

    To develop the method to induce the appearance of differentiation in amelanotic melanoma, experimental control of differentiation in B-16 melanoma cells of mice was discussed. Human melanoma cells and yellow melanin pigment cells useful for a fundamental study of radiotherapy for cancer were cultured and were differentiated into some lines. Melanotic B-16 cells and amelanotic B-16 cells were irradiated with thermal neutron (neutron: 2.7 x 10 12 , γ-dose: 32.3 rad) after they were cultured in culture solution containing 10 γ/ml of 10 B-dopa for 13 hours. A fine structure 5 hours after the irradiation in one of 5 experimental cases showed aggregated disintegration of melanin pigment particles, markedly deformed and fragmentized nucleus, and structural changes in cell membrane. (Tsunoda, M.)

  8. Malignant melanoma in children: imaging spectrum

    International Nuclear Information System (INIS)

    Kaste, S.C.; Pappo, Alberto S.; Jenkins, J.J. III; Pratt, C.B.

    1996-01-01

    Objective. The objective of this study was to investigate the role of diagnostic imaging in detecting unsuspected metastatic disease in children with malignant melanoma. This has not been well studied previously. Materials and methods. We correlated imaging findings of 33 children diagnosed with melanoma with the level of invasion and clinical stage of disease. Results. Clinically undetectable metastases were identified in eight patients (25 %), four of whom had multiple metastases. All eight patients had deep lesions (Clark's level IV or V) or unknown primary sites of disease. Conclusion. Children with thick melanomas and those with unknown site of primary tumors are at increased risk of having clinically unsuspected metastases and should undergo CT of the chest, abdomen, and local-regional nodal basins at diagnosis to determine disease extent. (orig.). With 8 figs

  9. Current Research and Development of Chemotherapeutic Agents for Melanoma

    Directory of Open Access Journals (Sweden)

    Kyaw Minn Hsan

    2010-04-01

    Full Text Available Cutaneous malignant melanoma is the most lethal form of skin cancer and an increasingly common disease worldwide. It remains one of the most treatment-refractory malignancies. The current treatment options for patients with metastatic melanoma are limited and in most cases non-curative. This review focuses on conventional chemotherapeutic drugs for melanoma treatment, by a single or combinational agent approach, but also summarizes some potential novel phytoagents discovered from dietary vegetables or traditional herbal medicines as alternative options or future medicine for melanoma prevention. We explore the mode of actions of these natural phytoagents against metastatic melanoma.

  10. Circulating tumor cells in melanoma patients.

    Directory of Open Access Journals (Sweden)

    Gary A Clawson

    Full Text Available Circulating tumor cells (CTCs are of recognized importance for diagnosis and prognosis of cancer patients. With melanoma, most studies do not show any clear relationship between CTC levels and stage of disease. Here, CTCs were enriched (∼400X from blood of melanoma patients using a simple centrifugation device (OncoQuick, and 4 melanocyte target RNAs (TYR, MLANA, MITF, and MIF were quantified using QPCR. Approximately one-third of melanoma patients had elevated MIF and MLANA transcripts (p<0.0001 and p<0.001, respectively compared with healthy controls. In contrast, healthy controls had uniformly higher levels of TYR and MITF than melanoma patients (p<0.0001. There was a marked shift of leukocytes into the CTC-enriched fractions (a 430% increase in RNA recovery, p<0.001, and no relationship between CTC levels and stage of disease was found. CTCs were captured on microfabricated filters and cultured. Captured melanoma CTCs were large cells, and consisted of 2 subpopulations, based on immunoreactivity. One subpopulation (∼50% stained for both pan-cytokeratin (KRT markers and the common leukocyte marker CD-45, whereas the second subpopulation stained for only KRT. Since similar cells are described in many cancers, we also examined blood from colorectal and pancreatic cancer patients. We observed analogous results, with most captured CTCs staining for both CD-45/KRT markers (and for the monocyte differentiation marker CD-14. Our results suggest that immature melanocyte-related cells (expressing TYR and MITF RNA may circulate in healthy controls, although they are not readily detectable without considerable enrichment. Further, as early-stage melanomas develop, immature melanocyte migration into the blood is somehow curtailed, whereas a significant proportion of patients develop elevated CTC levels (based on MIF and MLANA RNAs. The nature of the captured CTCs is consistent with literature describing leukocyte/macrophage-tumor cell fusion hybrids

  11. WITHDRAWN: Systemic treatments for metastatic cutaneous melanoma.

    Science.gov (United States)

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

    2018-02-07

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

  12. Intercellular crosstalk in human malignant melanoma

    Czech Academy of Sciences Publication Activity Database

    Dvořánková, Barbora; Szabo, Pavol; Kodet, O.; Strnad, Hynek; Kolář, Michal; Lacina, L.; Krejčí, E.; Nanka, O.; Sedo, A.; Smetana, K.

    2017-01-01

    Roč. 254, č. 3 (2017), s. 1143-1150 ISSN 0033-183X R&D Projects: GA ČR GA16-05534S; GA MŠk(CZ) LQ1604; GA MŠk(CZ) ED1.1.00/02.0109 Grant - others:GA MŠk(CZ) LM2015042 Institutional support: RVO:68378050 Keywords : Melanocyte * Melanoma cells * Melanoma ecosystem * cancer -associated fibroblast * Keratinocyte * Cytokine Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Cell biology Impact factor: 2.870, year: 2016

  13. Sarcoidosis in Melanoma Patients: Case Report and Literature Review

    Energy Technology Data Exchange (ETDEWEB)

    Beutler, Bryce D., E-mail: brycebeutler@hotmail.com [School of Allied Health Sciences, University of Nevada, Las Vegas, 1060 Wiegand Road, Encinitas, CA 92024 (United States); Cohen, Philip R., E-mail: brycebeutler@hotmail.com [Department of Dermatology, University of California San Diego, 10991 Twinleaf Court, San Diego, CA 92131 (United States)

    2015-06-15

    Sarcoidosis is a systemic inflammatory disease characterized by the development of noncaseating granulomas in multiple organ systems. Many hematologic malignancies and solid tumors, including melanoma, have been associated with sarcoidosis. We describe the clinical and pathologic findings of a 54-year-old man with melanoma-associated sarcoidosis. In addition, we not only review the literature describing characteristics of other melanoma patients with sarcoidosis, but also the features of melanoma patients with antineoplastic therapy-associated sarcoidosis. Sarcoidosis has been described in 80 melanoma patients; sufficient information for analysis was provided in 39 of these individuals. In 43.6% of individuals (17 out of 39), sarcoidosis was directly associated with melanoma; in 56.4% of oncologic patients (22 out of 39), sarcoidosis was induced by antineoplastic therapy that had been administered for the treatment of their metastatic melanoma. The discovery of melanoma preceded the development of sarcoidosis in 12 of the 17 (70.5%) individuals who did not receive systemic treatment. Pulmonary and/or cutaneous manifestations of sarcoidosis were common among both groups of patients. Most patients did not require treatment for sarcoidosis. Melanoma patients—either following antineoplastic therapy or without systemic treatment—may be at an increased risk to develop sarcoidosis. In antineoplastic therapy naive melanoma patients, a common etiologic factor—such as exposure to ultraviolet light—may play a role in their developing melanoma and sarcoidosis.

  14. BAP1 PLAYS A SURVIVAL ROLE IN CUTANEOUS MELANOMA

    Science.gov (United States)

    Kumar, Raj; Taylor, Michael; Miao, Benchun; Ji, Zhenyu; Njauw, Jenny Ching-Ni; Jönsson, Göran; Frederick, Dennie Tompers; Tsao, Hensin

    2014-01-01

    Although the pattern of BAP1 inactivation in ocular melanoma specimens and in the BAP1 cutaneous/ocular melanoma (CM/OM) predisposition syndrome suggests a tumor suppressor function, the specific role of this gene in the pathogenesis of cutaneous melanoma is not fully understood. We thus set out to characterize BAP1 in cutaneous melanoma and discovered an unexpected pro-survival effect of this protein. Tissue and cell lines analysis showed that BAP1 expression was maintained, rather than lost, in primary melanomas compared to nevi and normal skin. Genetic depletion of BAP1 in melanoma cells reduced proliferation and colony forming capability, induced apoptosis and inhibited melanoma tumor growth in vivo. On the molecular level, suppression of BAP1 led to a concomitant drop in the protein levels of survivin a member of anti-apoptotic proteins and a known mediator of melanoma survival. Restoration of survivin in melanoma cells partially rescued the growth-retarding effects of BAP1 loss. In contrast to melanoma cells, stable overexpression of BAP1 into immortalized but non-transformed melanocytes did suppress proliferation and reduce survivin. Taken together, these studies demonstrate that BAP1 may play a growth-sustaining role in melanoma cells, but that its impact on ubiquitination underpins a complex physiology which is context and cell dependent. PMID:25521456

  15. Epidermotropic metastatic melanoma with perilesional depigmentation in an Indian male

    Directory of Open Access Journals (Sweden)

    Bhavana Doshi

    2013-01-01

    Full Text Available Melanoma is a rare form of cutaneous malignancy encountered in the dark skin population. Epidermotropic metastatic melanoma is a rare form of cutaneous metastatic melanoma which can mimic primary melanoma on histopathology. Hence its differentiation is of immense prognostic importance. The occurrence of rim of depigmentation around the primary cutaneous melanoma has previously been reported to portend a bad prognosis. The occurrence of vitiligo like lesions in patients with metastatic melanoma in comparison has a better prognosis. However the occurrence of depigmentation around the secondaries is rare and its importance is not well known. Hence we wish to report a case of epidermotropic metastatic melanoma with perilesional depigmentation in a 78 year old Indian male.

  16. Echocardiographic findings in infants with presumed congenital Zika syndrome: Retrospective case series study

    Science.gov (United States)

    Santos, Cleusa C.; Feitosa, Fabiana G.; Ribeiro, Maria C.; Menge, Paulo; Lira, Izabelle M.

    2017-01-01

    Objective To report the echocardiographic evaluation of 103 infants with presumed congenital Zika syndrome. Methods An observational retrospective study was performed at Instituto de Medicina Integral Prof. Fernando Figueira (IMIP), Recife, Brazil. 103 infants with presumed congenital Zika syndrome. All infants had microcephaly and head computed tomography findings compatible with congenital Zika syndrome. Zika IgM antibody was detected in cerebrospinal fluid samples of 23 infants. In 80 infants, the test was not performed because it was not available at that time. All infants had negative serology for HIV, syphilis, rubella, cytomegalovirus and toxoplasmosis. A complete transthoracic two-dimensional, M-mode, continuous wave and pulsed wave Doppler and color Doppler echocardiographic (PHILIPS HD11XE or HD15) examination was performed on all infants. Results 14/103 (13.5%) echocardiograms were compatible with congenital heart disease: 5 with an ostium secundum atrial septal defect, 8 had a hemodynamically insignificant small apical muscular ventricular septal defect and one infant with dyspnea had a large membranous ventricular septal defect. The echocardiograms considered normal included 45 infants with a persistent foramen ovale and 16 with a minimum patent ductus arteriosus. Conclusions Preliminarily this study suggests that congenital Zika syndrome may be associated with an increase prevalence of congenital heart disease. However the types of defects noted were septal defects, a proportion of which would not be hemodynamically significant. PMID:28426680

  17. Echocardiographic findings in infants with presumed congenital Zika syndrome: Retrospective case series study.

    Directory of Open Access Journals (Sweden)

    Danielle Di Cavalcanti

    Full Text Available To report the echocardiographic evaluation of 103 infants with presumed congenital Zika syndrome.An observational retrospective study was performed at Instituto de Medicina Integral Prof. Fernando Figueira (IMIP, Recife, Brazil. 103 infants with presumed congenital Zika syndrome. All infants had microcephaly and head computed tomography findings compatible with congenital Zika syndrome. Zika IgM antibody was detected in cerebrospinal fluid samples of 23 infants. In 80 infants, the test was not performed because it was not available at that time. All infants had negative serology for HIV, syphilis, rubella, cytomegalovirus and toxoplasmosis. A complete transthoracic two-dimensional, M-mode, continuous wave and pulsed wave Doppler and color Doppler echocardiographic (PHILIPS HD11XE or HD15 examination was performed on all infants.14/103 (13.5% echocardiograms were compatible with congenital heart disease: 5 with an ostium secundum atrial septal defect, 8 had a hemodynamically insignificant small apical muscular ventricular septal defect and one infant with dyspnea had a large membranous ventricular septal defect. The echocardiograms considered normal included 45 infants with a persistent foramen ovale and 16 with a minimum patent ductus arteriosus.Preliminarily this study suggests that congenital Zika syndrome may be associated with an increase prevalence of congenital heart disease. However the types of defects noted were septal defects, a proportion of which would not be hemodynamically significant.

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

    DEFF Research Database (Denmark)

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

    2002-01-01

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

  19. Pathogenesis, diagnosis and management of primary melanoma of the colon

    Directory of Open Access Journals (Sweden)

    Imam Ayesha

    2011-02-01

    Full Text Available Abstract Background Melanomas within the alimentary tract are usually metastatic in origin. On the other hand, primary melanomas of the gastrointestinal tract are relatively uncommon. There are several published reports of melanomas occurring in the esophagus, stomach, small bowel, and anorectum. The occurrence of primary melanoma of the colon has, however, only been rarely reported. The optimum modus operandi for the management of primary colonic melanoma remains nebulous due to the limited number of reports in literature. Methods A comprehensive search of Medline, Cochrane and Highwire was performed using the following keywords: 'melanoma', 'malignant melanoma', 'primary melanoma', 'colon', 'gastrointestinal tract', 'alimentary tract', 'digestive tract', and 'large bowel'. All patients with primary melanoma localized to the colon were included in the review. Patients with metastatic melanomas to the gastrointestinal (GI tract and primary melanomas localized to the GI tract in anatomic locations other than colon were excluded. Results There have been only 12 reported cases of primary melanoma of the colon to date. The average age of patients on presentation was 60.4 years without any significant gender predilection. Right colon (33% and cecum (33% were the most common sites for the occurrence of primary colonic melanoma while abdominal pain (58% and weight loss (50% were the most common presenting complaints. Colonoscopy is the most reliable diagnostic investigation and offers the additional advantage of obtaining tissue for diagnosis. S-100 and HMB-45 are highly sensitive and specific for the diagnosis of this malignancy. For primary colonic melanomas that have not metastasized to any distant parts of the body, surgical resection with wide margins appears to be the treatment of choice. Although the management was individualized in every case, most of the authors preferred traditional hemicolectomy as the favored surgical approach

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

    International Nuclear Information System (INIS)

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

    2012-01-01

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

  1. Immunizing Patients With Metastatic Melanoma Using Recombinant Adenoviruses Encoding MART-1 or gp100 Melanoma Antigens

    Science.gov (United States)

    Rosenberg, Steven A.; Zhai, Yifan; Yang, James C.; Schwartzentruber, Douglas J.; Hwu, Patrick; Marincola, Francesco M.; Topalian, Suzanne L.; Restifo, Nicholas P.; Seipp, Claudia A.; Einhorn, Jan H.; Roberts, Bruce; White, Donald E.

    2008-01-01

    Background: The characterization of the genes encoding melanoma-associated antigens MART-1 or gp100, recognized by T cells, has opened new possibilities for the development of immunization strategies for patients with metastatic melanoma. With the use of recombinant adenoviruses expressing either MART-1 or gp100 to immunize patients with metastatic melanoma, we evaluated the safety, immunologic, and potential therapeutic aspects of these immunizations. Methods: In phase I studies, 54 patients received escalating doses (between 107 and 1011 plaque-forming units) of recombinant adenovirus encoding either MART-1 or gp100 melanoma antigen administered either alone or followed by the administration of interleukin 2 (IL-2). The immunologic impact of these immunizations on the development of cellular and antibody reactivity was assayed. Results: Recombinant adenoviruses expressing MART-1 or gp100 were safely administered. One of 16 patients with metastatic melanoma receiving the recombinant adenovirus MART-1 alone experienced a complete response. Other patients achieved objective responses, but they had received IL-2 along with an adenovirus, and their responses could be attributed to the cytokine. Immunologic assays showed no consistent immunization to the MART-1 or gp100 transgenes expressed by the recombinant adenoviruses. High levels of neutralizing antibody were found in the pretreatment sera of the patients. Conclusions: High doses of recombinant adenoviruses could be safely administered to cancer patients. High levels of neutralizing antibody present in patients' sera prior to treatment may have impaired the ability of these viruses to immunize patients against melanoma antigens. PMID:9862627

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Science.gov (United States)

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

    2017-10-16

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

  4. Radiation therapy of malignant melanoma: Experience with high individual treatment doses

    International Nuclear Information System (INIS)

    Habermalz, H.J.; Fischer, J.J.

    1984-01-01

    Melanoma is a complex tumor, metastasizes early both by lymphatic and blood vessels, and which may invoke a significant host ''immune,'' response. One can imagine a number of potentially useful roles for an effective radiation therapy regimen: 1. Treatment of the primary lesion. For small lesions located on the extremities, surgery may be simpler and obviate the risk of radiation failure. In other areas, e.g., head and neck, which may require more cosmetically or functionally debilitating surgery, a trial of radiation therapy may be worthwhile. 2. Preoperative radiation to the primary lesion before surgical resection in the hope of preventing tumor dissemination. 3. Prophylactic, local and regional lymph node radiation therapy. It has been popular in the past to remove malignant melanoma with wide local excision and dissection of adjacent node areas. It is still an open question whether some or any additional patients will be cured by the more vigorous local and extended treatment. Generally, those procedures have fallen into disfavor because of the associated morbidity. Presumably subclinical amounts of malignant melanoma could be sterilized with doses of radiation smaller than those necessary for bulk tumor. Wide field irradiation to the areas surrounding the primary lesion and the adjacent lymph nodes, to doses causing little morbidity, may well be worth clinical trial. 4. In combination with other forms of therapy, e.g., chemotherapy, immunotherapy, hyperthermia, to reduce the number of malignant cells in localized areas known to contain diseases. This may be particularly important prior to initiation of immunotherapy which may be much more effective in the absence of gross disease

  5. Ciliary body melanoma with optic nerve invasion.

    Science.gov (United States)

    al-Haddab, S; Hidayat, A; Tabbara, K F

    1990-01-01

    A case of melanoma of the ciliary body is presented. Initially the patient was diagnosed and treated for uveitis, but following CT scanning and ultrasound a tumour was detected and the eye enucleated. Histopathologically it was found that the tumour had invaded the optic nerve head, apparently via Cloquet's canal. Images PMID:2310725

  6. Intratumor and Intertumor Heterogeneity in Melanoma.

    Science.gov (United States)

    Grzywa, Tomasz M; Paskal, Wiktor; Włodarski, Paweł K

    2017-12-01

    Melanoma is a cancer that exhibits one of the most aggressive and heterogeneous features. The incidence rate escalates. A high number of clones harboring various mutations contribute to an exceptional level of intratumor heterogeneity of melanoma. It also refers to metastases which may originate from different subclones of primary lesion. Such component of the neoplasm biology is termed intertumor and intratumor heterogeneity. These levels of tumor heterogeneity hinder accurate diagnosis and effective treatment. The increasing number of research on the topic reflects the need for understanding limitation or failure of contemporary therapies. Majority of analyses concentrate on mutations in cancer-related genes. Novel high-throughput techniques reveal even higher degree of variations within a lesion. Consolidation of theories and researches indicates new routes for treatment options such as targets for immunotherapy. The demand for personalized approach in melanoma treatment requires extensive knowledge on intratumor and intertumor heterogeneity on the level of genome, transcriptome/proteome, and epigenome. Thus, achievements in exploration of melanoma variety are described in details. Particularly, the issue of tumor heterogeneity or homogeneity given BRAF mutations is discussed. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  7. Intratumor and Intertumor Heterogeneity in Melanoma

    Directory of Open Access Journals (Sweden)

    Tomasz M. Grzywa

    2017-12-01

    Full Text Available Melanoma is a cancer that exhibits one of the most aggressive and heterogeneous features. The incidence rate escalates. A high number of clones harboring various mutations contribute to an exceptional level of intratumor heterogeneity of melanoma. It also refers to metastases which may originate from different subclones of primary lesion. Such component of the neoplasm biology is termed intertumor and intratumor heterogeneity. These levels of tumor heterogeneity hinder accurate diagnosis and effective treatment. The increasing number of research on the topic reflects the need for understanding limitation or failure of contemporary therapies. Majority of analyses concentrate on mutations in cancer-related genes. Novel high-throughput techniques reveal even higher degree of variations within a lesion. Consolidation of theories and researches indicates new routes for treatment options such as targets for immunotherapy. The demand for personalized approach in melanoma treatment requires extensive knowledge on intratumor and intertumor heterogeneity on the level of genome, transcriptome/proteome, and epigenome. Thus, achievements in exploration of melanoma variety are described in details. Particularly, the issue of tumor heterogeneity or homogeneity given BRAF mutations is discussed.

  8. 7-Piperazinethylchrysin inhibits melanoma cell proliferation by ...

    African Journals Online (AJOL)

    In B16F10 and A375 cells, treatment with PEC caused the inhibition ... Conclusion: PEC inhibited melanoma cell proliferation, apparently by blocking the cell cycle at G0/G1 .... all statistical analyses. .... Financial support from the Department of.

  9. Melanoma continues to rise throughout the world

    African Journals Online (AJOL)

    depletion of the earth's ozone layer, thought to be induced by artificial chlorofluorocarbons, and the subsequent increase in the amount of ultraviolet light reaching the earth, may exacerbate the increase in melanoma in ... development of raised areas on a previously flat lesion, or scaling, ulceration, crusting or bleeding.

  10. SVM classifier on chip for melanoma detection.

    Science.gov (United States)

    Afifi, Shereen; GholamHosseini, Hamid; Sinha, Roopak

    2017-07-01

    Support Vector Machine (SVM) is a common classifier used for efficient classification with high accuracy. SVM shows high accuracy for classifying melanoma (skin cancer) clinical images within computer-aided diagnosis systems used by skin cancer specialists to detect melanoma early and save lives. We aim to develop a medical low-cost handheld device that runs a real-time embedded SVM-based diagnosis system for use in primary care for early detection of melanoma. In this paper, an optimized SVM classifier is implemented onto a recent FPGA platform using the latest design methodology to be embedded into the proposed device for realizing online efficient melanoma detection on a single system on chip/device. The hardware implementation results demonstrate a high classification accuracy of 97.9% and a significant acceleration factor of 26 from equivalent software implementation on an embedded processor, with 34% of resources utilization and 2 watts for power consumption. Consequently, the implemented system meets crucial embedded systems constraints of high performance and low cost, resources utilization and power consumption, while achieving high classification accuracy.

  11. Dermoscopic appearance of an amelanotic mucosal melanoma

    Science.gov (United States)

    Blum, Andreas; Beck-Zoul, Ulrike; Held, Laura; Haase, Sylvie

    2016-01-01

    Background Hypomelanotic or amelanotic melanomas are challenging to identify, especially at mucosal sites. The dermoscopic clues to the diagnosis of mucosal melanomas have been reported to be structureless zones with the presence of blue, gray, or white colors. Case A female in her seventies noted a new lesion on the inside of her right labia that first appeared two months prior. Her past medical history was significant for rheumatoid arthritis requiring ongoing treatment with methotrexate for 20 years and adalimumab for 10 years. After no response to two weeks of local treatment for suspected herpes simplex infection, her gynecologist performed a skin biopsy. Based on the histopathological diagnosis of an amelanotic melanoma (Breslow thickness of 1.3 mm) the patient was referred to dermatology for further assessment. Polarized dermoscopy revealed a distinct asymmetric, sharply demarcated homogenous white papule (4 × 5 mm) as well as polymorphous vessels. Conclusion Dermoscopy may aid in the diagnosis of amelanotic mucosal melanomas. Our case revealed a structureless white area and polymorphous vessels. Additional clues to the diagnosis were the advanced age of the patient and the clinical presentation of a new lesion. PMID:27867742

  12. CDC Vital Signs-Preventing Melanoma

    Centers for Disease Control (CDC) Podcasts

    This podcast 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.

  13. 7-Piperazinethylchrysin inhibits melanoma cell proliferation by ...

    African Journals Online (AJOL)

    PEC) on melanoma cell lines. Methods: Cell viability was analyzed by trypan blue exclusion assays and the cell cycle by flow cytometry using ModFit LT software. Specifically, cells were stained with propidium iodide (0.5 mg/mL) supplemented ...

  14. Human malignant melanomas in nude mice

    International Nuclear Information System (INIS)

    Atlas, S.W.; Braffman, B.H.; Lo Brutto, R.; Elder, D.E.; Herlyn, D.

    1988-01-01

    The purpose of this study was to correlate signal intensities and relaxation times on MR images in malignant melanomas with histopathologic features and electron paramagnetic resonance (EPR) spectra. Cell lines from human malignant melanomas in tissue culture were implanted subcutaneously into nude mice. MR imaging was performed in vivo at 1.9 T to assess 12 separate lesions in ten mice using spin-echo and inversion-recovery techniques. T1,T2, and N(H) were calculated in all cases. Histopathologic examination was performed on specimens resected immediately after imaging, using hematoxylin and eosin, Prussian blue, and Fontan stains to assess for tumor necrosis, iron, and melanin content. EPR spectra were also obtained on four resected specimens. The authors' results indicate that the relaxation behavior of nonhemorrhagic malignant melanomas cannot be explained solely by the presence of necrosis, water content, or iron content. The degree of melanin within these tumors did correlate with T1 relaxation enhancement. T2 relaxation times did not correlate with the sole presence of either iron, melanin, or necrosis. Although the unique relaxation behavior of nonhemorrhagic malignant melanoma seems to have many causes, their data suggest that, contrary to previous investigations, it is influenced by the presence of melanin rather than iron

  15. UK National Data Centre archive of seismic recordings of (presumed) underground nuclear tests 1964-1996

    Science.gov (United States)

    Young, John; Peacock, Sheila

    2016-04-01

    The year 1996 has particular significance for forensic seismologists. This was the year when the Comprehensive Test Ban Treaty (CTBT) was signed in September at the United Nations, setting an international norm against nuclear testing. Blacknest, as a long time seismic centre for research into detecting and identifying underground explosions using seismology, provided significant technical advice during the CTBT negotiations. Since 1962 seismic recordings of both presumed nuclear explosions and earthquakes from the four seismometer arrays Eskdalemuir, Scotland (EKA), Yellowknife, Canada (YKA), Gauribidanur, India (GBA), and Warramunga, Australia (WRA) have been copied, digitised, and saved. There was a possibility this archive would be lost. It was decided to process the records and catalogue them for distribution to other groups and institutions. This work continues at Blacknest but the archive is no longer under threat. In addition much of the archive of analogue tape recordings has been re-digitised with modern equipment, allowing sampling rates of 100 rather than 20 Hz.

  16. Therapeutic High-Density Barium Enema in a Case of Presumed Diverticular Hemorrhage

    Directory of Open Access Journals (Sweden)

    Nonthalee Pausawasdi

    2011-02-01

    Full Text Available Many patients with lower gastrointestinal bleeding do not have an identifiable source of bleeding at colonoscopy. A significant percentage of these patients will have recurrent bleeding. In many patients, the presence of multiple diverticula leads to a diagnosis of presumed diverticular bleeding. Current treatment options include therapeutic endoscopy, angiography, or surgical resection, all of which depend on the identification of the diverticular source of bleeding. This report describes a case of recurrent bleeding in an elderly patient with diverticula but no identifiable source treated successfully with barium impaction therapy. This therapeutic modality does not depend on the identification of the bleeding diverticular lesion and was well tolerated by our 86-year-old patient.

  17. Predictors for the need for endoscopic therapy in patients with presumed acute upper gastrointestinal bleeding.

    Science.gov (United States)

    Kim, Su Sun; Kim, Kyung Up; Kim, Sung Jun; Seo, Seung In; Kim, Hyoung Su; Jang, Myoung Kuk; Kim, Hak Yang; Shin, Woon Geon

    2017-12-15

    Selecting patients with an urgent need for endoscopic hemostasis is difficult based only on simple parameters of presumed acute upper gastrointestinal bleeding. This study assessed easily applicable factors to predict cases in need of urgent endoscopic hemostasis due to acute upper gastrointestinal bleeding. The consecutively included patients were divided into the endoscopic hemostasis and nonendoscopic hemostasis groups. We reviewed the enrolled patients' medical records and analyzed various variables and parameters for acute upper gastrointestinal bleeding outcomes such as demographic factors, comorbidities, symptoms, signs, laboratory findings, rebleeding rate, and mortality to evaluate simple predictive factors for endoscopic treatment. A total of 613 patients were analyzed, including 329 patients in the endoscopic hemostasis and 284 patients in the non-endoscopic hemostasis groups. In the multivariate analysis, a bloody nasogastric lavage (adjusted odds ratio [AOR], 6.786; 95% confidence interval [CI], 3.990 to 11.543; p upper gastrointestinal bleeding.

  18. Presumed appendiceal abscess discovered to be ruptured Meckel diverticulum following percutaneous drainage

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Jeannie C.; Ostlie, Daniel J. [Children' s Mercy Hospital, Department of Surgery, Kansas City, MO (United States); Rivard, Douglas C.; Morello, Frank P. [Children' s Mercy Hospital, Department of Radiology, Kansas City, MO (United States)

    2008-08-15

    A Meckel diverticulum is an embryonic remnant of the omphalomesenteric duct that occurs in approximately 2% of the population. Most are asymptomatic; however, they are vulnerable to inflammation with subsequent consequences including diverticulitis and perforation. We report an 11-year-old boy who underwent laparoscopic appendectomy for perforated appendicitis at an outside institution. During his convalescence he underwent percutaneous drainage of a presumed postoperative abscess. A follow-up drain study demonstrated an enteric fistula. The drain was slowly removed from the abdomen over a period of 1 week. Three weeks following drain removal the patient reported recurrent nausea and abdominal pain. A CT scan demonstrated a 3.7-cm rim-enhancing air-fluid level with dependent contrast consistent with persistent enteric fistula and abscess. Exploratory laparoscopy was performed, at which time a Meckel diverticulum was identified and resected. This case highlights the diagnostic challenge and limitations of conventional radiology in complicated Meckel diverticulum. (orig.)

  19. BAP1 has a survival role in cutaneous melanoma.

    Science.gov (United States)

    Kumar, Raj; Taylor, Michael; Miao, Benchun; Ji, Zhenyu; Njauw, Jenny C-N; Jönsson, Göran; Frederick, Dennie T; Tsao, Hensin

    2015-04-01

    Although the pattern of BAP1 inactivation in ocular melanoma specimens and in the BAP1 cutaneous melanoma (CM)/ocular melanoma predisposition syndrome suggests a tumor suppressor function, the specific role of this gene in the pathogenesis of CM is not fully understood. We thus set out to characterize BAP1 in CM and discovered an unexpected pro-survival effect of this protein. Tissue and cell lines analysis showed that BAP1 expression was maintained, rather than lost, in primary melanomas compared with nevi and normal skin. Genetic depletion of BAP1 in melanoma cells reduced proliferation and colony-forming capability, induced apoptosis, and inhibited melanoma tumor growth in vivo. On the molecular level, suppression of BAP1 led to a concomitant drop in the protein levels of survivin, a member of anti-apoptotic proteins and a known mediator of melanoma survival. Restoration of survivin in melanoma cells partially rescued the growth-retarding effects of BAP1 loss. In contrast to melanoma cells, stable overexpression of BAP1 into immortalized but non-transformed melanocytes did suppress proliferation and reduce survivin. Taken together, these studies demonstrate that BAP1 may have a growth-sustaining role in melanoma cells, but that its impact on ubiquitination underpins a complex physiology, which is context and cell dependent.

  20. Importance of glycolysis and oxidative phosphorylation in advanced melanoma

    Directory of Open Access Journals (Sweden)

    Ho Jonhan

    2012-10-01

    Full Text Available Abstract Serum lactate dehydrogenase (LDH is a prognostic factor for patients with stage IV melanoma. To gain insights into the biology underlying this prognostic factor, we analyzed total serum LDH, serum LDH isoenzymes, and serum lactate in up to 49 patients with metastatic melanoma. Our data demonstrate that high serum LDH is associated with a significant increase in LDH isoenzymes 3 and 4, and a decrease in LDH isoenzymes 1 and 2. Since LDH isoenzymes play a role in both glycolysis and oxidative phosphorylation (OXPHOS, we subsequently determined using tissue microarray (TMA analysis that the levels of proteins associated with mitochondrial function, lactate metabolism, and regulators of glycolysis were all elevated in advanced melanomas compared with nevic melanocytes. To investigate whether in advanced melanoma, the glycolysis and OXPHOS pathways might be linked, we determined expression of the monocarboxylate transporters (MCT 1 and 4. Analysis of a nevus-to-melanoma progression TMA revealed that MCT4, and to a lesser extend MCT1, were elevated with progression to advanced melanoma. Further analysis of human melanoma specimens using the Seahorse XF24 extracellular flux analyzer indicated that metastatic melanoma tumors derived a large fraction of energy from OXPHOS. Taken together, these findings suggest that in stage IV melanomas with normal serum LDH, glycolysis and OXPHOS may provide metabolic symbiosis within the same tumor, whereas in stage IV melanomas with high serum LDH glycolysis is the principle source of energy.

  1. Undiagnosed and comorbid disorders in patients with presumed chronic fatigue syndrome.

    Science.gov (United States)

    Mariman, An; Delesie, Liesbeth; Tobback, Els; Hanoulle, Ignace; Sermijn, Erica; Vermeir, Peter; Pevernagie, Dirk; Vogelaers, Dirk

    2013-11-01

    To assess undiagnosed and comorbid disorders in patients referred to a tertiary care center with a presumed diagnosis of chronic fatigue syndrome (CFS). Patients referred for chronic unexplained fatigue entered an integrated diagnostic pathway, including internal medicine assessment, psychodiagnostic screening, physiotherapeutic assessment and polysomnography+multiple sleep latency testing. Final diagnosis resulted from a multidisciplinary team discussion. Fukuda criteria were used for the diagnosis of CFS, DSM-IV-TR criteria for psychiatric disorders, ICSD-2 criteria for sleep disorders. Out of 377 patients referred, 279 (74.0%) were included in the study [84.9% female; mean age 38.8years (SD 10.3)]. A diagnosis of unequivocal CFS was made in 23.3%. In 21.1%, CFS was associated with a sleep disorder and/or psychiatric disorder, not invalidating the diagnosis of CFS. A predominant sleep disorder was found in 9.7%, 19.0% had a psychiatric disorder and 20.8% a combination of both. Only 2.2% was diagnosed with a classical internal disease. In the total sample, a sleep disorder was found in 49.8%, especially obstructive sleep apnea syndrome, followed by psychophysiologic insomnia and periodic limb movement disorder. A psychiatric disorder was diagnosed in 45.2%; mostly mood and anxiety disorder. A multidisciplinary approach to presumed CFS yields unequivocal CFS in only a minority of patients, and reveals a broad spectrum of exclusionary or comorbid conditions within the domains of sleep medicine and psychiatry. These findings favor a systematic diagnostic approach to CFS, suitable to identify a wide range of diagnostic categories that may be subject to dedicated care. © 2013. Published by Elsevier Inc. All rights reserved.

  2. Consenting options for posthumous organ donation: presumed consent and incentives are not favored

    Directory of Open Access Journals (Sweden)

    Hammami Muhammad M

    2012-11-01

    Full Text Available Abstract Background Posthumous organ procurement is hindered by the consenting process. Several consenting systems have been proposed. There is limited information on public relative attitudes towards various consenting systems, especially in Middle Eastern/Islamic countries. Methods We surveyed 698 Saudi Adults attending outpatient clinics at a tertiary care hospital. Preference and perception of norm regarding consenting options for posthumous organ donation were explored. Participants ranked (1, most agreeable the following, randomly-presented, options from 1 to 11: no-organ-donation, presumed consent, informed consent by donor-only, informed consent by donor-or-surrogate, and mandatory choice; the last three options ± medical or financial incentive. Results Mean(SD age was 32(9 year, 27% were males, 50% were patients’ companions, 60% had ≥ college education, and 20% and 32%, respectively, knew an organ donor or recipient. Mandated choice was among the top three choices for preference of 54% of respondents, with an overall median[25%,75%] ranking score of 3[2,6], and was preferred over donor-or-surrogate informed consent (4[2,7], p vs. 11[6,11], respectively, p = 0.002. Compared to females, males more perceived donor-or-surrogate informed consent as the norm (3[1,6] vs. 5[3,7], p vs. 8[4,9], p vs. 5[2,7], p  Conclusions We conclude that: 1 most respondents were in favor of posthumous organ donation, 2 mandated choice system was the most preferred and presumed consent system was the least preferred, 3 there was no difference between preference and perception of norm in consenting systems ranking, and 4 financial (especially in females and medical (especially in males incentives reduced preference.

  3. Use of iodine-125 brachytherapy in treatment of choroidal melanomas, technic and preliminary analysis of 78 patients; Traitement conservateur des melanomes choroidiens par curietherapie par l'iode 125, technique et analyse preliminaire d'une serie de 78 patients

    Energy Technology Data Exchange (ETDEWEB)

    Quetin, P.; Schumacher, C.; Schraub, S. [Centre Paul-Strauss, Dept. de Radiotherapie, 67 - Strasbourg (France); Meyer, L.; Polto, F.; Sahel, J. [Hopitaux Universitaires de Strasbourg, Clinique Ophtalmologique, 67 (France); Magnenet, P. [Centre Paul-Strauss, Dept. de Radiophysique, 67 - Strasbourg (France); Andres, E. [Hopital de Hautepierre, Medecine Interne, 67 - Strasbourg (France)

    2001-12-01

    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)

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

    International Nuclear Information System (INIS)

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

    2015-01-01

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

  5. Long-term Survival after Metastatic Childhood Melanoma

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  6. Growth of melanoma brain tumors monitored by photoacoustic microscopy

    Science.gov (United States)

    Staley, Jacob; Grogan, Patrick; Samadi, Abbas K.; Cui, Huizhong; Cohen, Mark S.; Yang, Xinmai

    2010-07-01

    Melanoma is a primary malignancy that is known to metastasize to the brain and often causes death. The ability to image the growth of brain melanoma in vivo can provide new insights into its evolution and response to therapies. In our study, we use a reflection mode photoacoustic microscopy (PAM) system to detect the growth of melanoma brain tumor in a small animal model. The melanoma tumor cells are implanted in the brain of a mouse at the beginning of the test. Then, PAM is used to scan the region of implantation in the mouse brain, and the growth of the melanoma is monitored until the death of the animal. It is demonstrated that PAM is capable of detecting and monitoring the brain melanoma growth noninvasively in vivo.

  7. Approach to Malign Melanoma in Anorectal Area

    Directory of Open Access Journals (Sweden)

    Huseyin Pulat

    2014-12-01

    Full Text Available Aim: Anorectal malign melanoma comprise 0.2-1 % of all malign melanoma. They are extremely aggressive. Most patients are lost beacuse of incurable systemic illness. In our study, we aim to evaluate the results of surgical and oncological follow-up of our patients that we operated because of anorectal malign melanoma. Material and Method: Our 4 patients operated because of anorectal malign melanoma between October 2008 and April 2013 were analysed. The patients were analysed in terms of demographic datas, complaint and its time, physical examination and imaging findings, treatment procedure, local recurrence or presence of metastasis and follow-up results.Results: Our study group comprised 4 people (2 men and 2 women with the mean age of 64,2 years. The main complaint was rectal bleeding. The avarage complaint duration was 7.5 months. In all patients, anorectal mass was detected after physical examination and imaging studies. Biopsies of the mass were reported to be consistent with malign melanoma. With the further studies, one patient was detected to have metastasis in liver. Abdominoperineal resection was applied to one patient after wide local excision and to three patients during the first aplication. The avarage follow-up time was 19,25 months. The avarage diameter of tumor was 3,9 cm. One patient was applied lymph node dissection because of recurrence in iliac region. The avarage stay time at hospital of the patients who had no postoperative problems was 9,7 days. During follow-up time, three of the patients died because of common metastasis. A patient followed regularly is still continuing his life without illness in his postoperative 22nd month. Discussion: Anorectal malign melanoma is a rare, with a bad prognosis and a late diagnosed entity as it has a similarity with benign illnesses which are mostly seen in anorectal area in terms of clinical symptoma. To correct the prognosis of the illness, the suitable surgery and adjuvant treatment

  8. Consenting options for posthumous organ donation: presumed consent and incentives are not favored

    Science.gov (United States)

    2012-01-01

    Background Posthumous organ procurement is hindered by the consenting process. Several consenting systems have been proposed. There is limited information on public relative attitudes towards various consenting systems, especially in Middle Eastern/Islamic countries. Methods We surveyed 698 Saudi Adults attending outpatient clinics at a tertiary care hospital. Preference and perception of norm regarding consenting options for posthumous organ donation were explored. Participants ranked (1, most agreeable) the following, randomly-presented, options from 1 to 11: no-organ-donation, presumed consent, informed consent by donor-only, informed consent by donor-or-surrogate, and mandatory choice; the last three options ± medical or financial incentive. Results Mean(SD) age was 32(9) year, 27% were males, 50% were patients’ companions, 60% had ≥ college education, and 20% and 32%, respectively, knew an organ donor or recipient. Mandated choice was among the top three choices for preference of 54% of respondents, with an overall median[25%,75%] ranking score of 3[2,6], and was preferred over donor-or-surrogate informed consent (4[2,7], p < 0.001), donor-only informed consent (5[3,7], p < 0.001), and presumed consent (7[3,10], p < 0.001). The addition of a financial or medical incentive, respectively, reduced ranking of mandated choice to 7[4,9], p < 0.001, and 5[3,8], p < 0.001; for donor-or-surrogate informed consent to 7[5,9], p < 0.001, and 5[3,7], p = 0.004; and for donor-only informed consent to 8[6,10], p < 0.001, and 5[3,7], p = 0.56. Distribution of ranking score of perception of norm and preference were similar except for no-organ donation (11[7,11] vs. 11[6,11], respectively, p = 0.002). Compared to females, males more perceived donor-or-surrogate informed consent as the norm (3[1,6] vs. 5[3,7], p < 0.001), more preferred mandated choice with financial incentive option (6[3,8] vs. 8[4,9], p < 0.001), and

  9. The patterns of melanoma presentation in Rijeka region.

    Science.gov (United States)

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

    2013-01-01

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

  10. Melanoma genetics and the development of rational therapeutics.

    Science.gov (United States)

    Chudnovsky, Yakov; Khavari, Paul A; Adams, Amy E

    2005-04-01

    Melanoma is a cancer of the neural crest-derived cells that provide pigmentation to skin and other tissues. Over the past 4 decades, the incidence of melanoma has increased more rapidly than that of any other malignancy in the United States. No current treatments substantially enhance patient survival once metastasis has occurred. This review focuses on recent insights into melanoma genetics and new therapeutic approaches being developed based on these advances.

  11. Unilateral lichen planus pigmentosus mimicking acral lentiginous melanoma.

    Science.gov (United States)

    Bickle, Kelly; Smithberger, Erica; Lien, Mary H; Fenske, Neil Alan

    2010-07-01

    The authors report a case of a Latin American woman who developed progressive pigmentation primarily involving two digits of her right hand. She was scheduled for amputation based on a presumptive histologic diagnosis of melanoma with regression. Dermatology consultation with repeat biopsies disclosed a lichenoid tissue reaction with marked pigment incontinence and no evidence of melanoma. This report should prompt physicians to include lichen planus pigmentosus in the differential diagnosis of acral lentiginous melanoma.

  12. Reflectance confocal microscopy features of thin versus thick melanomas.

    Science.gov (United States)

    Kardynal, Agnieszka; Olszewska, Małgorzata; de Carvalho, Nathalie; Walecka, Irena; Pellacani, Giovanni; Rudnicka, Lidia

    2018-01-24

    In vivo reflectance confocal microscopy (RCM) plays an increasingly important role in differential diagnosis of melanoma. The aim of the study was to assess typical confocal features of thin (≤1mm according to Breslow index) versus thick (>1mm) melanomas. 30 patients with histopathologically confirmed cutaneous melanoma were included in the study. Reflectance confocal microscopy was performed with Vivascope equipment prior to excision. Fifteen melanomas were thin (Breslow thickness ≤ 1mm) and 15 were thick melanomas (Breslow thickness >1mm). In the RCM examination, the following features were more frequently observed in thin compared to thick melanomas: edged papillae (26.7% vs 0%, p=0.032) and areas with honeycomb or cobblestone pattern (33.3% vs 6.7%, p=0.068). Both features are present in benign melanocytic lesions, so in melanoma are good prognostic factors. The group of thick melanomas compared to the group of thin melanomas in the RCM images presented with greater frequency of roundish cells (100% vs 40%, p=0.001), non-edged papillae (100% vs 60%, p=0.006), numerous pagetoid cells (73.3% vs 33.3%, p=0.028), numerous atypical cells at dermal-epidermal junction (53.3% vs 20%, p=0.058) and epidermal disarray (93.3% vs 66.7%, p=0.068). Non-invasive imaging methods helps in deepening of knowledge about the evolution and biology of melanoma. The most characteristic features for thin melanomas in confocal examination are: fragments of cobblestone or honeycomb pattern and edged papillae (as good prognostic factors). The features of thick melanomas in RCM examination are: roundish cells, non-edged papillae, numerous pagetoid cells at dermal-epidermal junction and epidermal disarray.

  13. Dissection of T-cell antigen specificity in human melanoma

    DEFF Research Database (Denmark)

    Andersen, Rikke Sick; Albæk Thrue, Charlotte; Junker, Niels

    2012-01-01

    Tumor-infiltrating lymphocytes (TIL) isolated from melanoma patients and expanded in vitro by interleukin (IL)-2 treatment can elicit therapeutic response after adoptive transfer, but the antigen specificities of the T cells transferred have not been determined. By compiling all known melanoma-as...... from different fragments of resected melanoma lesions. In summary, our findings provide an initial definition of T-cell populations contributing to tumor recognition in TILs although the specificity of many tumor-reactive TILs remains undefined....

  14. Cost-Effectiveness of Laparoscopic Hysterectomy With Morcellation Compared With Abdominal Hysterectomy for Presumed Myomas.

    Science.gov (United States)

    Rutstein, Sarah E; Siedhoff, Matthew T; Geller, Elizabeth J; Doll, Kemi M; Wu, Jennifer M; Clarke-Pearson, Daniel L; Wheeler, Stephanie B

    2016-02-01

    Hysterectomy for presumed leiomyomata is 1 of the most common surgical procedures performed in nonpregnant women in the United States. Laparoscopic hysterectomy (LH) with morcellation is an appealing alternative to abdominal hysterectomy (AH) but may result in dissemination of malignant cells and worse outcomes in the setting of an occult leiomyosarcoma (LMS). We sought to evaluate the cost-effectiveness of LH versus AH. Decision-analytic model of 100 000 women in the United States assessing the incremental cost-effectiveness ratio (ICER) in dollars per quality-adjusted life-year (QALY) gained (Canadian Task Force classification III). U.S. hospitals. Adult premenopausal women undergoing LH or AH for presumed benign leiomyomata. We developed a decision-analytic model from a provider perspective across 5 years, comparing the cost-effectiveness of LH to AH in terms of dollar (2014 US dollars) per QALY gained. The model included average total direct medical costs and utilities associated with the procedures, complications, and clinical outcomes. Baseline estimates and ranges for cost and probability data were drawn from the existing literature. Estimated overall deaths were lower in LH versus AH (98 vs 103). Death due to LMS was more common in LH versus AH (86 vs 71). Base-case assumptions estimated that average per person costs were lower in LH versus AH, with a savings of $2193 ($24 181 vs $26 374). Over 5 years, women in the LH group experienced 4.99 QALY versus women in the AH group with 4.91 QALY (incremental gain of .085 QALYs). LH dominated AH in base-case estimates: LH was both less expensive and yielded greater QALY gains. The ICER was sensitive to operative costs for LH and AH. Varying operative costs of AH yielded an ICER of $87 651/QALY gained (minimum) to AH being dominated (maximum). Probabilistic sensitivity analyses, in which all input parameters and costs were varied simultaneously, demonstrated a relatively robust model. The AH approach was dominated

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

    Science.gov (United States)

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

    1991-08-01

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

  16. Assessment of PALB2 as a candidate melanoma susceptibility gene.

    Directory of Open Access Journals (Sweden)

    Lauren G Aoude

    Full Text Available Partner and localizer of BRCA2 (PALB2 interacts with BRCA2 to enable double strand break repair through homologous recombination. Similar to BRCA2, germline mutations in PALB2 have been shown to predispose to Fanconi anaemia as well as pancreatic and breast cancer. The PALB2/BRCA2 protein interaction, as well as the increased melanoma risk observed in families harbouring BRCA2 mutations, makes PALB2 a candidate for melanoma susceptibility. In order to assess PALB2 as a melanoma predisposition gene, we sequenced the entire protein-coding sequence of PALB2 in probands from 182 melanoma families lacking pathogenic mutations in known high penetrance melanoma susceptibility genes: CDKN2A, CDK4, and BAP1. In addition, we interrogated whole-genome and exome data from another 19 kindreds with a strong family history of melanoma for deleterious mutations in PALB2. Here we report a rare known deleterious PALB2 mutation (rs118203998 causing a premature truncation of the protein (p.Y1183X in an individual who had developed four different cancer types, including melanoma. Three other family members affected with melanoma did not carry the variant. Overall our data do not support a case for PALB2 being associated with melanoma predisposition.

  17. Integrative Genome Comparison of Primary and Metastatic Melanomas

    Science.gov (United States)

    Feng, Bin; Nazarian, Rosalynn M.; Bosenberg, Marcus; Wu, Min; Scott, Kenneth L.; Kwong, Lawrence N.; Xiao, Yonghong; Cordon-Cardo, Carlos; Granter, Scott R.; Ramaswamy, Sridhar; Golub, Todd; Duncan, Lyn M.; Wagner, Stephan N.; Brennan, Cameron; Chin, Lynda

    2010-01-01

    A cardinal feature of malignant melanoma is its metastatic propensity. An incomplete view of the genetic events driving metastatic progression has been a major barrier to rational development of effective therapeutics and prognostic diagnostics for melanoma patients. In this study, we conducted global genomic characterization of primary and metastatic melanomas to examine the genomic landscape associated with metastatic progression. In addition to uncovering three genomic subclasses of metastastic melanomas, we delineated 39 focal and recurrent regions of amplification and deletions, many of which encompassed resident genes that have not been implicated in cancer or metastasis. To identify progression-associated metastasis gene candidates, we applied a statistical approach, Integrative Genome Comparison (IGC), to define 32 genomic regions of interest that were significantly altered in metastatic relative to primary melanomas, encompassing 30 resident genes with statistically significant expression deregulation. Functional assays on a subset of these candidates, including MET, ASPM, AKAP9, IMP3, PRKCA, RPA3, and SCAP2, validated their pro-invasion activities in human melanoma cells. Validity of the IGC approach was further reinforced by tissue microarray analysis of Survivin showing significant increased protein expression in thick versus thin primary cutaneous melanomas, and a progression correlation with lymph node metastases. Together, these functional validation results and correlative analysis of human tissues support the thesis that integrated genomic and pathological analyses of staged melanomas provide a productive entry point for discovery of melanoma metastases genes. PMID:20520718

  18. Precision Medicine and PET/Computed Tomography in Melanoma.

    Science.gov (United States)

    Mena, Esther; Sanli, Yasemin; Marcus, Charles; Subramaniam, Rathan M

    2017-10-01

    Recent advances in genomic profiling and sequencing of melanoma have provided new insights into the development of the basis for molecular biology to more accurately subgroup patients with melanoma. The development of novel mutation-targeted and immunomodulation therapy as a major component of precision oncology has revolutionized the management and outcome of patients with metastatic melanoma. PET imaging plays an important role in noninvasively assessing the tumor biological behavior, to guide individualized treatment and assess response to therapy. This review summarizes the recent genomic discoveries in melanoma in the era of targeted therapy and their implications for functional PET imaging. Published by Elsevier Inc.

  19. Preoperative nuclear scans in patients with melanoma

    International Nuclear Information System (INIS)

    Au, F.C.; Maier, W.P.; Malmud, L.S.; Goldman, L.I.; Clark, W.H. Jr.

    1984-01-01

    One hundred forty-one liver scans, 137 brain scans, and 112 bone scans were performed in 192 patients with clinical Stage 1 melanoma. One liver scan was interpreted as abnormal; liver biopsy of that patient showed no metastasis. There were 11 suggestive liver scans; three of the patients with suggestive liver scans had negative liver biopsies. The remaining eight patients were followed from 4 to 6 years and none of those patients developed clinical evidence of hepatic metastases. All of the brain scans were normal. Five patients had suggestive bone scans and none of those patients had manifested symptoms of osseous metastases with a follow-up of 2 to 4.5 years. This study demonstrates that the use of preoperative liver, brain and bone scan in the evaluation of patients with clinical Stage 1 melanoma is virtually unproductive

  20. Psychosocial care to patients with Malignant Melanoma

    DEFF Research Database (Denmark)

    Thorup, Charlotte Brun

    Psychosocial care to patients with Malignant Melanoma Intensions: The intension of this project is to link new knowledge with the nurses experience based knowledge within the psychosocial care to patients, who have been diagnosed with Malignant Melanoma (MM), thereby improving the care...... to elaborate the care to these patients. Method: In 2007 the nurses from our ward gained experience from the psychosocial care to these patients. These experiences are a starting point to the study of literature the group has made. A group of five nurses have from this literature study, substantiated...... the psychosocial perspective. Results: After the literature review, the psychosocial aspects have been divided into five main areas: 1. Diagnosis, hospitalisation, and treatment 2. The body with cancer 3. Psychological 4. Social 5. Existential/spiritual Primary results show that patients with MM in general respond...

  1. Sun behaviour after cutaneous malignant melanoma

    DEFF Research Database (Denmark)

    Idorn, L W; Datta, P; Heydenreich, J

    2013-01-01

    Background  It has been reported that patients with cutaneous malignant melanoma (CMM) can lower their risk of a second primary melanoma by limiting recreational sun exposure. Previous studies based on questionnaires and objective surrogate measurements indicate that before their diagnosis......, patients with CMM are exposed to higher ultraviolet radiation (UVR) doses than controls, followed by a reduction after diagnosis. Objectives  In a prospective, observational case-control study, we aimed to assess sun exposure after diagnosis of CMM by objective measurements to substantiate advice about sun...... months and 6 years before the start of the study. During a summer season participants filled in sun exposure diaries daily and wore personal electronic UVR dosimeters in a wristwatch that continuously measured time-stamped UVR doses in standard erythema dose. Results  The UVR dose of recently diagnosed...

  2. Emerging biomarkers for cancer immunotherapy in melanoma.

    Science.gov (United States)

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

    2017-09-14

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

  3. The presumed reader in car advertisements published in Teresina's printed newspapers, from 1950 to 2002

    Directory of Open Access Journals (Sweden)

    Francisco Alves Filho

    2015-08-01

    Full Text Available This article aims to present how the image of the presumed reader has been built in the printed newspapers of the city of Teresina (Piaui State, Brazil, with them being the following: O Piauí, Folha da Manhã, O Dia, and Diário do Povo. In order to do so, we have researched the bibliography referent to the studies of authors such as Charles Bazerman (2011, Carolyn Miller (2009 [1984], and Amy Devitt (2004, representatives of Gender Rhetorical Studies. Besides these, we have consulted Bakhtin's assumptions for studying genre, mainly extracted from Marxism and the Philosophy of Language, and Aesthetics of Verbal Creation, as well as Brazilian authors related to the study of discursive genres, such as Fiorin (2008, Marcuschi (2008, and Faraco (2009. With the research, we could confirm that the advertisements actually build social-historic blocks capable of mirroring the values of a society, but also capable of contributing directly for determined values to be restored or forgotten.

  4. ISC origin times for announced and presumed underground nuclear explosions at several test sites

    International Nuclear Information System (INIS)

    Rodean, H.C.

    1979-01-01

    Announced data for US and French underground nuclear explosions indicate that nearly all detonations have occurred within one or two tenths of a second after the minute. This report contains ISC origin-time data for announced explosions at two US test sites and one French test site, and includes similar data for presumed underground nuclear explosions at five Soviet sites. Origin-time distributions for these sites are analyzed for those events that appeared to be detonated very close to the minute. Particular attention is given to the origin times for the principal US and Soviet test sites in Nevada and Eastern Kazakhstan. The mean origin times for events at the several test sites range from 0.4 s to 2.8 s before the minute, with the earlier mean times associated with the Soviet sites and the later times with the US and French sites. These times indicate lower seismic velocities beneath the US and French sites, and higher velocities beneath the sites in the USSR 9 figures, 8 tables

  5. A discussion supporting presumed consent for posthumous sperm procurement and conception.

    Science.gov (United States)

    Tremellen, Kelton; Savulescu, Julian

    2015-01-01

    Conception of a child using cryopreserved sperm from a deceased man is generally considered ethically sound provided explicit consent for its use has been made, thereby protecting the man's autonomy. When death is sudden (trauma, unexpected illness), explicit consent is not possible, thereby preventing posthumous sperm procurement (PSP) and conception according to current European Society of Human Reproduction and Embryology and the American Society for Reproductive Medicine guidelines. Here, we argue that autonomy of a deceased person should not be considered the paramount ethical concern, but rather consideration of the welfare of the living (widow and prospective child) should be the primary focus. Posthumous conception can bring significant advantages to the widow and her resulting child, with most men supporting such practice. We suggest that a deceased man can benefit from posthumous conception (continuation of his 'bloodline', allowing his widow's wishes for a child to be satisfied), and has a moral duty to allow his widow access to his sperm, if she so wishes, unless he clearly indicated that he did not want children when alive. We outline the arguments favouring presumed consent over implied or proxy consent, plus practical considerations for recording men's wishes to opt-out of posthumous conception. Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  6. Evidence for presumable feline origin of sporadic G6P[9] rotaviruses in humans.

    Science.gov (United States)

    Pietsch, Corinna; Liebert, Uwe G

    2018-05-31

    Species A rotaviruses are highly diverse and impose a substantial burden to human and animal health. Interspecies transmission between livestock, domestic animals and humans is commonly observed, but spread of animal-like rotaviruses within the human population is limited. During the continued monitoring of rotavirus strains in Germany, an unusual G6P[9] rotavirus strain was detected in feces of a child. The complete rotavirus coding sequences revealed a unique G6-P[9]-I2-R2-C2-M2-A3-N2-T3-E2-H3 genotype constellation. The virus was phylogenetically related to feline G3P[9] strains and other human G6P[9] rotaviruses of presumable zoonotic origin. Analysis of primer binding sites of G6 specific genotyping revealed further evidence of a G6P[9] feline reservoir. Moreover, substantial deficits of conventional semi-nested PCR genotyping approaches in detecting contemporary G6P[9] were revealed. Rotavirus strain GER29-14 most likely resulted from a direct or recent interspecies transmission from a cat to human. Further studies could assess nucleic acid sequences and genotype constellations of feline rotavirus to confirm the likely feline origin of sporadic human G6P[9] strains. Copyright © 2018 Elsevier B.V. All rights reserved.

  7. Feline dry eye syndrome of presumed neurogenic origin: a case report.

    Science.gov (United States)

    Sebbag, Lionel; Pesavento, Patricia A; Carrasco, Sebastian E; Reilly, Christopher M; Maggs, David J

    2018-01-01

    A 14-year-old female spayed Abyssinian cat, which about 1 year previously underwent thoracic limb amputation, radiotherapy and chemotherapy for an incompletely excised vaccine-related fibrosarcoma, was presented for evaluation of corneal opacity in the left eye (OS). The ocular surface of both eyes (OU) had a lackluster appearance and there was a stromal corneal ulcer OS. Results of corneal aesthesiometry, Schirmer tear test-1 (STT-1) and tear film breakup time revealed corneal hypoesthesia, and quantitative and qualitative tear film deficiency OU. Noxious olfactory stimulation caused increased lacrimation relative to standard STT-1 values suggesting an intact nasolacrimal reflex. Various lacrimostimulants were administered in succession; namely, 1% pilocarpine administered topically (15 days) or orally (19 days), and topically applied 0.03% tacrolimus (47 days). Pilocarpine, especially when given orally, was associated with notable increases in STT-1 values, but corneal ulceration remained/recurred regardless of administration route, and oral pilocarpine resulted in gastrointestinal upset. Tacrolimus was not effective. After 93 days, the cat became weak and lame and a low thyroxine concentration was detected in serum. The cat was euthanized and a necropsy performed. Both lacrimal glands were histologically normal, but chronic neutrophilic keratitis and reduced conjunctival goblet cell density were noted OU. The final diagnosis was dry eye syndrome (DES) of presumed neurogenic origin, associated with corneal hypoesthesia. This report reinforces the importance of conducting tearfilm testing in cats with ocular surface disease, as clinical signs of DES were different from those described in dogs.

  8. Presumed congenital infection by Zika virus: findings on psychomotor development - a case report

    Directory of Open Access Journals (Sweden)

    Ana Carla Gomes Botelho

    Full Text Available Abstract Introduction: the identification of Zika virus (ZikV in the amniotic fluid, in the placenta and in newborns' brains suggests a neurotropism of this agent in the brain development, resulting in neuro-psycho-motor alterations. Thus, this present study reports the assessment of children diagnosed by a congenital infection, presumably by ZikV, followed-up at the Rehabilitation Center Prof. Ruy Neves Baptist at the Instituto de Medicina Integral Prof. Fernando Figueira (IMIP. Description: as proposed by the Ministry of Health, the following instruments were used to evaluate the neuro-motor functions of four children with microcephaly aged between three and four months: The Test of Infant Motor Performance (TIMP; the functional vision assessment; the manual function scale development; and the clinical evaluation protocol on pediatric dysphagia (PAD-PED. Discussion: the children evaluated presented atypical motor performance, muscle tone and spontaneous motricity which encompass the symmetry and the motion range of the upper and lower limbs proven to be altered. The functional vision showed alterations which can cause limitations in the performance of functional activities and the learning process. Regarding to the speech articulator's functions observed that the maturation and coordination of sucking, swallowing and breathing did not yet encounter the appropriate age maturity level.

  9. Excimer Laser Phototherapeutic Keratectomy for the Treatment of Clinically Presumed Fungal Keratitis

    Directory of Open Access Journals (Sweden)

    Liang-Mao Li

    2014-01-01

    Full Text Available This retrospective study was to evaluate treatment outcomes of excimer laser phototherapeutic keratectomy (PTK for clinically presumed fungal keratitis. Forty-seven eyes of 47 consecutive patients underwent manual superficial debridement and PTK. All corneal lesions were located in the anterior stroma and were resistant to medication therapy for at least one week. Data were collected by a retrospective chart review with at least six months of follow-up data available. After PTK, infected corneal lesions were completely removed and the clinical symptoms resolved in 41 cases (87.2%. The mean ablation depth was 114.39±45.51 μm and diameter of ablation was 4.06±1.07 mm. The mean time for healing of the epithelial defect was 8.8±5.6 days. Thirty-four eyes (82.9% showed an improvement in best spectacle-corrected visual acuity of two or more lines. PTK complications included mild to moderate corneal haze, hyperopic shift, irregular astigmatism, and thinning cornea. Six eyes (12.8% still showed progressed infection, and conjunctival flap covering, amniotic membrane transplantation, or penetrating keratoplasty were given. PTK is a valuable therapeutic alternative for superficial infectious keratitis. It can effectively eradicate lesions, hasten reepithelialization, and restore and preserve useful visual function. However, the selection of surgery candidates should be conducted carefully.

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

    Science.gov (United States)

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

    2009-12-01

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

  11. Metastatic melanoma after 23 years of primary ocular melanoma.

    LENUS (Irish Health Repository)

    Karde, Supriya Ramesh

    2016-11-23

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

  12. I-125 ellipticines as melanoma imaging radiopharmaceuticals

    International Nuclear Information System (INIS)

    Heindel, N.D.; Wilson, A.; Varkey, T.; Garnes, K.; Burns, H.D.

    1990-01-01

    Polycyclic nitrogen heterocyclics such as ellipticine are high affinity binders to melanin and DNA. In search of a melanoma imaging agent the authors developed syntheses for I-125 analogs within two new classes of this anti-tumor agent. One of these substances displayed marked anti-tumor activity, strong DNA binding, a 10/1 tumor/blood and a 25/1 eye/blood ratio at 48 hrs post-dosing

  13. Intramuscular metastasis from malignant melanoma: MR findings

    Energy Technology Data Exchange (ETDEWEB)

    Yoshioka, Hirohi; Itai, Yuji; Niitsu, Mamoru [Dept. of Radiology, Institute of Clinical Medicine, University of Tsukuba, Ibaraki (Japan); Fujiwara, Masachika; Watanabe, Teruo [Department of Pathology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba (Japan); Satomi, Hisae; Otsuka, Fujio [Department of Dermatology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba (Japan)

    1999-12-01

    We present a rare case of intramuscular metastasis from malignant melanoma. The lesion showed intermediate to high signal intensity on T1-weighted magnetic resonance (MR) images and mixed signal intensities containing high and low signals on T2-weighted images. The signal intensity on T1-weighted images, which is due to the paramagnetic effect of melanin, is a characteristic MR finding of this entity. (orig.)

  14. CDC Vital Signs-Preventing Melanoma

    Centers for Disease Control (CDC) Podcasts

    2015-06-02

    This podcast 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.

  15. Prognosis of mucous naso-sinus melanomas

    International Nuclear Information System (INIS)

    Thariat, J.; Poissonnet, G.; Dassonville, O.; Santini, J.; Castillo, L.; Iattes, L.; Bensadoun, R.J.; Castillo, L.

    2009-01-01

    Purpose: The mucous melanoma of superior aero-digestive tracts represents 1-2% of malignant melanomas, 5-10% of head and neck melanomas, and concerns particularly, the nasal cavities and naso-sinus cavities. The recurrences are frequent, often local ones, sometimes multifocal ones, the survival rate at five years is ≤ 30%. The Ballantyne classification distinguishes three stages: 1 localised tumors, 2 ganglions attack, 3 metastases. Are pejorative: a stage number 3 ( deep invasion, muscles, bones, cartilages) according to the Prasad classification (1: in situ or micro invasive, 2: invasion of the lamina propria), the achromia sub-type, a pseudo papillary or sarcoma, vascular emboli, necrosis. The recommendations rest on evidence level at 4. The complete excision is the rule and must be counterbalanced with the morbidity in case of orbital, dura-mater, frontal lobe, and infra temporal fossa. The adjuvant irradiation is debated.We evaluated the prognosis of mucous naso-sinus melanomas. Conclusion: The principal cause of death was the local failure. The Ballantyne classification does not take into account the extensions and overestimates the prognosis impact of ganglions invasion that is yet ≤10% ( and does not justify a radiotherapy in lack of adenopathy). It underestimates probably the impact of adjuvant radiotherapy. One should be able to distinguish the unfavourable stage 1 tumors (receiving eventually a radiotherapy) and these ones of very localised stage 1 for which it could be omitted. The fractionation and the optimal dose remain to be defined. The volume ≥100 ml and the irradiation by carbon ions seem promising in term of local control but the metastases stay a problem in the recent series. (N.C.)

  16. Hypoxia independent drivers of melanoma angiogenesis

    Directory of Open Access Journals (Sweden)

    Svenja eMeierjohann

    2015-05-01

    Full Text Available Tumor angiogenesis is a process which is traditionally regarded as the tumor`s response to low nutrient supply occurring under hypoxic conditions. However, hypoxia is not a prerequisite for angiogenesis. The fact that even single tumor cells or small tumor cell aggregates are capable of attracting blood vessels reveals the early metastatic capability of tumor cells. This review sheds light on the hypoxia independent mechanisms of tumor angiogenesis in melanoma.

  17. Targeting Increased Polyamine Transport of Resistant Melanomas

    Science.gov (United States)

    2017-08-01

    NanoCulture Plates (NCP, from SCIVAX Life Sciences ) which is a scaffold-based 3D culture system in which cells can easily form spheroids. The...on society beyond science and technology? The impact of this project will be a new therapy for melanoma patients that will prevent tumor...new drug design predicated upon non- polyamine based platforms. 2. Title: I-Corps: Orlando Pharmaceuticals PI: Phanstiel, Otto Supporting Agency

  18. Study of melanoma invasion by FTIR spectroscopy

    Science.gov (United States)

    Yang, Y.; Sulé-Suso, J.; Sockalingum, G. D.

    2008-02-01

    Compared to other forms of skin cancer, a malignant melanoma has a high risk of spreading to other parts of the body. Melanoma invasion is a complex process involving changes in cell-extracellular matrix (ECM) interaction and cell-cell interactions. To fully understand the factors which control the invasion process, a human skin model system was reconstructed. HBL (a commercially available cell line) melanoma cells were seeded on a skin model with and without the presence of keratinocytes and/or fibroblasts. After 14 days culture, the skin specimens were fixed, parafin embedded and cut into 7 µm sections. The de-parafinised sections were investigated by synchrotron Fourier transformed infrared (FTIR) microspectroscopy to study skin cell invasion behaviour. The advantage of using FTIR is its ability to obtain the fingerprint information of the invading cells in terms of protein secondary structure in comparison to non-invading cells and the concentration of the enzyme (matrix-metalloproteinase) which digests protein matrix, near the invading cells. With aid of the spectral mapping images, it is possible to pinpoint the cells in non-invasion and invasion area and analyse the respective spectra. It has been observed that the protein bands in cells and matrix shifted between non-invasive and invasive cells in the reconstructed skin model. We hypothesise that by careful analysis of the FTIR data and validation by other models, FTIR studies can reveal information on which type of cells and proteins are involved in melanoma invasion. Thus, it is possible to trace the cell invasion path by mapping the spectra along the interface of cell layer and matrix body by FTIR spectroscopy.

  19. Primary Malignant Melanoma of the Esophagus

    OpenAIRE

    Oya Yonal; Duygu Ibrisim; Yıldıran Songur; Yılmaz Cakaloglu; Koray Tuncer; Hale Kırımlıoglu; Sadakat Ozdil

    2013-01-01

    Primary malignant melanoma of the esophagus (PMME) comprises only 0.1?0.2% of all malignant esophageal tumors. PMME tumors are highly aggressive and metastasize early via hematogenic and lymphatic pathways. Treatment outcome is poor because the cancer has often advanced at the time of diagnosis. Inoperability, unsuccessful treatment with radiotherapy and chemotherapy in advanced tumors and metastases have contributed to its poor prognosis. Here, we present the endoscopic features, endoscopic ...

  20. Melanoma Vaccines: Mixed Past, Promising Future

    Science.gov (United States)

    Ozao-Choy, Junko; Lee, Delphine J.; Faries, Mark B.

    2014-01-01

    Synopsis Cancer vaccines were one of the earliest forms of immunotherapy to be investigated. Past attempts to vaccinate against cancer, including melanoma, have mixed results, revealing the complexity of what was thought to be a simple concept. However, several recent successes and the combination of improved knowledge of tumor immunology and the advent of new immunomodulators make vaccination a promising strategy for the future. PMID:25245965

  1. Proton beam radiotherapy of iris melanoma

    International Nuclear Information System (INIS)

    Damato, Bertil; Kacperek, Andrzej; Chopra, Mona; Sheen, Martin A.; Campbell, Ian R.; Errington, R. Douglas

    2005-01-01

    Purpose: To report on outcomes after proton beam radiotherapy of iris melanoma. Methods and Materials: Between 1993 and 2004, 88 patients with iris melanoma received proton beam radiotherapy, with 53.1 Gy in 4 fractions. Results: The patients had a mean age of 52 years and a median follow-up of 2.7 years. The tumors had a median diameter of 4.3 mm, involving more than 2 clock hours of iris in 32% of patients and more than 2 hours of angle in 27%. The ciliary body was involved in 20%. Cataract was present in 13 patients before treatment and subsequently developed in another 18. Cataract had a 4-year rate of 63% and by Cox analysis was related to age (p = 0.05), initial visual loss (p < 0.0001), iris involvement (p < 0.0001), and tumor thickness (p < 0.0001). Glaucoma was present before treatment in 13 patients and developed after treatment in another 3. Three eyes were enucleated, all because of recurrence, which had an actuarial 4-year rate of 3.3% (95% CI 0-8.0%). Conclusions: Proton beam radiotherapy of iris melanoma is well tolerated, the main problems being radiation-cataract, which was treatable, and preexisting glaucoma, which in several patients was difficult to control

  2. Ultrasonic characterisation of malignant melanoma of choroid

    Directory of Open Access Journals (Sweden)

    John Sheila

    1998-01-01

    Full Text Available An in-vitro study of wave spectral analysis in 8 enucleated eyes was conducted in order to differentiate histological subtypes of malignant melanoma. To obtain the backscattering coefficient for the tissues, we used a broadband focussed transducer with a frequency range of 7-12 MHz and a centre frequency of 10 MHz. Experimental measurement of backscattering coefficient and attenuation coefficient at various frequencies was done by substitution techniques. The backscattering coefficient, scatterer size, and root mean square velocity fluctuation were derived by the numerical method, while the attenuation coefficient at 1 MHz was derived from attenuation coefficient at different frequencies. This study revealed that backscattering coefficient and attenuation coefficient, over a frequency range of 7-12 MHz, show an increase in the spindle cell type compared to the mixed cell type of malignant melanoma. Particularly, the scatterer size was significantly higher in the spindle cell group (p = 0.013 in contrast to the mixed cell type. Spindle cells have uniform and compact histological pattern which contributes to an increase in scatterer size and root mean square velocity fluctuation. The ultrasonically obtained parameters have been shown to have a good correlation with the histology of malignant melanoma.

  3. Melanoma detection using a mobile phone app

    Science.gov (United States)

    Diniz, Luciano E.; Ennser, K.

    2016-03-01

    Mobile phones have had their processing power greatly increased since their invention a few decades ago. As a direct result of Moore's Law, this improvement has made available several applications that were impossible before. The aim of this project is to develop a mobile phone app, integrated with its camera coupled to an amplifying lens, to help distinguish melanoma. The proposed device has the capability of processing skin mole images and suggesting, using a score system, if it is a case of melanoma or not. This score system is based on the ABCDE signs of melanoma, and takes into account the area, the perimeter and the colors present in the nevus. It was calibrated and tested using images from the PH2 Dermoscopic Image Database from Pedro Hispano Hospital. The results show that the system created can be useful, with an accuracy of up to 100% for malign cases and 80% for benign cases (including common and atypical moles), when used in the test group.

  4. Skin protection behaviour and sex differences in melanoma location in patients with multiple primary melanomas.

    Science.gov (United States)

    Warren, Matthew; McMeniman, Erin; Adams, Agnieszka; De'Ambrosis, Brian

    2017-02-01

    Previous studies have shown that sunscreen usage, sun-protection measures and self-examination rates in patients with single primary melanomas (SPM) are similar to that in the general population. This study hypothesises that these rates would be different in a population with multiple primary melanomas (MPM). We further hypothesise that there would be a sex difference in melanoma location in patients with MPM. The objectives of this study were to determine skin protection measures, self-examinations and melanoma location in a cohort of patients with MPM. A survey was conducted on 137 patients with MPM examining their sun-protection measures, skin self-examination rates and medical and phenotypic characteristics. These data were combined with a review of their medical records to examine the patients' skin cancer history. Patients with MPM had higher rates of skin self-evaluation (74% vs 22%), sunscreen usage (70% vs 45%) and other sun-protection measures (95% vs 46%) than has been published for patients with a history of a SPM. We have also shown that women have a higher risk of developing melanomas on their arms (p skin self-examination, sunscreen usage and other sun-protection methods in patients with MPM is higher than in studies of patients with SPM. It also highlighted sex differences in terms of melanoma location for patients with MPM. Further studies to examine the cause of the differences in these forms of protective behaviour could help improve the utilisation of these important preventative measures in all patients. © 2015 The Australasian College of Dermatologists.

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

    Centers for Disease Control (CDC) Podcasts

    2011-10-19

    This podcast accompanies the publication of a series of articles on melanoma surveillance in the United States, available in the November supplement edition of the Journal of the American Academy of Dermatology. Chris Johnson, from the Cancer Data Registry of Idaho, discusses analyses examining the relationship between melanoma and two variables at the county level, ultraviolet radiation and socioeconomic status.  Created: 10/19/2011 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 10/19/2011.

  6. Facts about Uveal Coloboma

    Science.gov (United States)

    ... NEI Intranet (Employees Only) *PDF files require the free Adobe® Reader® software for viewing. This website is maintained by the NEI Office of Science Communications, Public Liaison, and Education. Technical questions about this website can be addressed ...

  7. Chorioretinal Lesions Presumed Secondary to Zika Virus Infection in an Immunocompromised Adult.

    Science.gov (United States)

    Henry, Christopher R; Al-Attar, Luma; Cruz-Chacón, Alexis M; Davis, Janet L

    2017-04-01

    Zika virus has spread rapidly throughout the Americas since 2015. The public health implications of Zika virus infection lend special importance to identifying the virus in unsuspected hosts. To describe relevant imaging studies and clinical features of chorioretinal lesions that are presumably associated with Zika virus and that share analogous features with chorioretinal lesions reported in cases of Dengue fever and West Nile virus. This is a case report from an academic referral center in Miami, Florida, of a woman in her 60s from Guaynabo, Puerto Rico, who presented with reduced visual acuity and bilateral diffuse, subretinal, confluent, placoid, and multifocal chorioretinal lesions. The patient was observed over a 5-month period. Visual acuity, clinical course, and multimodal imaging study results. Fluorescein angiography revealed early hypofluorescence and late staining of the chorioretinal lesions. Optical coherence tomography demonstrated outer retinal disruption in the placoid macular lesions. Zika RNA was detected in a plasma sample by real-time reverse transcription polymerase chain reaction testing and was suspected to be the cause of chorioretinal lesions after other viral and infectious causes were ruled out. Three weeks after the onset of symptoms, the patient's visual acuity had improved to 20/60 OD and 20/25 OS, with intraocular pressures of 18 mm Hg OD and 19 mm Hg OS. In 6 weeks, the chorioretinal lesions had healed and visual acuity had improved to 20/25 OD and 20/20 OS. Follow-up optical coherence tomography demonstrated interval recovery of the outer retina and photoreceptors. Acute-onset, self-resolving, placoid, or multifocal nonnecrotizing chorioretinal lesions may be a feature of active Zika virus chorioretinitis, as reported in other Flavivirus infections in adults. Similar findings in potentially exposed adults suggest that clinicians should consider IgM antibody or polymerase chain reaction testing for Zika virus as well as diagnostic

  8. Feline dry eye syndrome of presumed neurogenic origin: a case report

    Directory of Open Access Journals (Sweden)

    Lionel Sebbag

    2017-12-01

    Full Text Available Case summary A 14-year-old female spayed Abyssinian cat, which about 1 year previously underwent thoracic limb amputation, radiotherapy and chemotherapy for an incompletely excised vaccine-related fibrosarcoma, was presented for evaluation of corneal opacity in the left eye (OS. The ocular surface of both eyes (OU had a lackluster appearance and there was a stromal corneal ulcer OS. Results of corneal aesthesiometry, Schirmer tear test-1 (STT-1 and tear film breakup time revealed corneal hypoesthesia, and quantitative and qualitative tear film deficiency OU. Noxious olfactory stimulation caused increased lacrimation relative to standard STT-1 values suggesting an intact nasolacrimal reflex. Various lacrimostimulants were administered in succession; namely, 1% pilocarpine administered topically (15 days or orally (19 days, and topically applied 0.03% tacrolimus (47 days. Pilocarpine, especially when given orally, was associated with notable increases in STT-1 values, but corneal ulceration remained/recurred regardless of administration route, and oral pilocarpine resulted in gastrointestinal upset. Tacrolimus was not effective. After 93 days, the cat became weak and lame and a low thyroxine concentration was detected in serum. The cat was euthanized and a necropsy performed. Both lacrimal glands were histologically normal, but chronic neutrophilic keratitis and reduced conjunctival goblet cell density were noted OU. Relevance and novel information The final diagnosis was dry eye syndrome (DES of presumed neurogenic origin, associated with corneal hypoesthesia. This report reinforces the importance of conducting tearfilm testing in cats with ocular surface disease, as clinical signs of DES were different from those described in dogs.

  9. Joint maximum-likelihood magnitudes of presumed underground nuclear test explosions

    Science.gov (United States)

    Peacock, Sheila; Douglas, Alan; Bowers, David

    2017-08-01

    Body-wave magnitudes (mb) of 606 seismic disturbances caused by presumed underground nuclear test explosions at specific test sites between 1964 and 1996 have been derived from station amplitudes collected by the International Seismological Centre (ISC), by a joint inversion for mb and station-specific magnitude corrections. A maximum-likelihood method was used to reduce the upward bias of network mean magnitudes caused by data censoring, where arrivals at stations that do not report arrivals are assumed to be hidden by the ambient noise at the time. Threshold noise levels at each station were derived from the ISC amplitudes using the method of Kelly and Lacoss, which fits to the observed magnitude-frequency distribution a Gutenberg-Richter exponential decay truncated at low magnitudes by an error function representing the low-magnitude threshold of the station. The joint maximum-likelihood inversion is applied to arrivals from the sites: Semipalatinsk (Kazakhstan) and Novaya Zemlya, former Soviet Union; Singer (Lop Nor), China; Mururoa and Fangataufa, French Polynesia; and Nevada, USA. At sites where eight or more arrivals could be used to derive magnitudes and station terms for 25 or more explosions (Nevada, Semipalatinsk and Mururoa), the resulting magnitudes and station terms were fixed and a second inversion carried out to derive magnitudes for additional explosions with three or more arrivals. 93 more magnitudes were thus derived. During processing for station thresholds, many stations were rejected for sparsity of data, obvious errors in reported amplitude, or great departure of the reported amplitude-frequency distribution from the expected left-truncated exponential decay. Abrupt changes in monthly mean amplitude at a station apparently coincide with changes in recording equipment and/or analysis method at the station.

  10. Neuropathological and biochemical criteria to identify acquired Creutzfeldt-Jakob disease among presumed sporadic cases.

    Science.gov (United States)

    Kobayashi, Atsushi; Parchi, Piero; Yamada, Masahito; Mohri, Shirou; Kitamoto, Tetsuyuki

    2016-06-01

    As an experimental model of acquired Creutzfeldt-Jakob disease (CJD), we performed transmission studies of sporadic CJD using knock-in mice expressing human prion protein (PrP). In this model, the inoculation of the sporadic CJD strain V2 into animals homozygous for methionine at polymorphic codon 129 (129 M/M) of the PRNP gene produced quite distinctive neuropathological and biochemical features, that is, widespread kuru plaques and intermediate type abnormal PrP (PrP(Sc) ). Interestingly, this distinctive combination of molecular and pathological features has been, to date, observed in acquired CJD but not in sporadic CJD. Assuming that these distinctive phenotypic traits are specific for acquired CJD, we revisited the literature and found two cases showing widespread kuru plaques despite the 129 M/M genotype, in a neurosurgeon and in a patient with a medical history of neurosurgery without dura mater grafting. By Western blot analysis of brain homogenates, we revealed the intermediate type of PrP(Sc) in both cases. Furthermore, transmission properties of brain extracts from these two cases were indistinguishable from those of a subgroup of dura mater graft-associated iatrogenic CJD caused by infection with the sporadic CJD strain V2. These data strongly suggest that the two atypical CJD cases, previously thought to represent sporadic CJD, very likely acquired the disease through exposure to prion-contaminated brain tissues. Thus, we propose that the distinctive combination of 129 M/M genotype, kuru plaques, and intermediate type PrP(Sc) , represents a reliable criterion for the identification of acquired CJD cases among presumed sporadic cases. © 2015 Japanese Society of Neuropathology.

  11. Differences in mycorrhizal communities between Epipactis palustris, E. helleborine and its presumed sister species E. neerlandica.

    Science.gov (United States)

    Jacquemyn, Hans; Waud, Michael; Lievens, Bart; Brys, Rein

    2016-07-01

    In orchid species that have populations occurring in strongly contrasting habitats, mycorrhizal divergence and other habitat-specific adaptations may lead to the formation of reproductively isolated taxa and ultimately to species formation. However, little is known about the mycorrhizal communities associated with recently diverged sister taxa that occupy different habitats. In this study, 454 amplicon pyrosequencing was used to investigate mycorrhizal communities associating with Epipactis helleborine in its typical forest habitat and with its presumed sister species E. neerlandica that almost exclusively occurs in coastal dune habitats. Samples of the phylogenetically more distant E. palustris, which co-occurred with E. neerlandica, were also included to investigate the role of habitat-specific conditions on mycorrhizal communities. A total of 105 operational taxonomic units (OTUs) of putative orchid mycorrhizal fungi were observed in the three studied species. The majority of these fungi were endophytic fungi of Helotiales and ectomycorrhizal fungi belonging to Thelephoraceae, Sebacinaceae and Inocybaceae. In addition, a large number of other ectomycorrhizal taxa were detected, including Cortinarius, Cenococcum, Tuber, Geopora, Wilcoxina, Meliniomyces, Hebeloma, Tricholoma, Russula and Peziza Mycorrhizal communities differed significantly between the three species, but differences were most pronounced between the forest species (E. helleborine) and the two dune slack species (E. neerlandica and E. palustris). The results clearly showed that recently diverged orchid species that occupy different habitats were characterized by significantly different mycorrhizal communities and call for more detailed experiments that aim at elucidating the contribution of habitat-specific adaptations in general and mycorrhizal divergence in particular to the process of speciation in orchids. © The Author 2016. Published by Oxford University Press on behalf of the Annals of Botany

  12. Performance of thirteen clinical rules to distinguish bacterial and presumed viral meningitis in Vietnamese children.

    Directory of Open Access Journals (Sweden)

    Nguyen Tien Huy

    Full Text Available BACKGROUND AND PURPOSE: Successful outcomes from bacterial meningitis require rapid antibiotic treatment; however, unnecessary treatment of viral meningitis may lead to increased toxicities and expense. Thus, improved diagnostics are required to maximize treatment and minimize side effects and cost. Thirteen clinical decision rules have been reported to identify bacterial from viral meningitis. However, few rules have been tested and compared in a single study, while several rules are yet to be tested by independent researchers or in pediatric populations. Thus, simultaneous test and comparison of these rules are required to enable clinicians to select an optimal diagnostic rule for bacterial meningitis in settings and populations similar to ours. METHODS: A retrospective cross-sectional study was conducted at the Infectious Department of Pediatric Hospital Number 1, Ho Chi Minh City, Vietnam. The performance of the clinical rules was evaluated by area under a receiver operating characteristic curve (ROC-AUC using the method of DeLong and McNemar test for specificity comparison. RESULTS: Our study included 129 patients, of whom 80 had bacterial meningitis and 49 had presumed viral meningitis. Spanos's rule had the highest AUC at 0.938 but was not significantly greater than other rules. No rule provided 100% sensitivity with a specificity higher than 50%. Based on our calculation of theoretical sensitivity and specificity, we suggest that a perfect rule requires at least four independent variables that posses both sensitivity and specificity higher than 85-90%. CONCLUSIONS: No clinical decision rules provided an acceptable specificity (>50% with 100% sensitivity when applying our data set in children. More studies in Vietnam and developing countries are required to develop and/or validate clinical rules and more very good biomarkers are required to develop such a perfect rule.

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

    Directory of Open Access Journals (Sweden)

    Alexander Joseph Trevarton

    2013-07-01

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

  14. Ambulatory Melanoma Care Patterns in the United States

    International Nuclear Information System (INIS)

    Ji, A. L.; Davis, S. A.; Feldman, S. R.; Fleischer, A. B.; Baze, M. R.; Feldman, S. R.; Feldman, S. R.; Fleischer, A. B.

    2013-01-01

    To examine trends in melanoma visits in the ambulatory care setting. Methods. Data from the National Ambulatory Medical Care Survey (NAMCS) from 1979 to 2010 were used to analyze melanoma visit characteristics including number of visits, age and gender of patients, and physician specialty. These data were compared to US Census population estimates during the same time period. Results. The overall rate of melanoma visits increased (ρ< 0.0001) at an apparently higher rate than the increase in population over this time. The age of patients with melanoma visits increased at approximately double the rate (0.47 year per interval year, ρ< 0.0001) of the population increase in age (0.23 year per interval year). There was a nonsignificant(ρ=0.19) decline in the proportion of female patients seen over the study interval. Lastly, ambulatory care has shifted towards dermatologists and other specialties managing melanoma patients and away from family/internal medicine physicians and general/plastic surgeons. Conclusions. The number and age of melanoma visits has increased over time with respect to the overall population, mirroring the increase in melanoma incidence over the past three decades. These trends highlight the need for further studies regarding melanoma management efficiency

  15. Oral malignant melanoma: a rare case with unusual clinical ...

    African Journals Online (AJOL)

    Primary Oral malignant melanoma is a rare tumor with an indigent prognosis. This is a case report of 47-year-old Sudanese female diagnosed as Oral malignant melanoma of the mandible with an unusual pattern of growth and clinical presentation. Furthermore, a possibility of intraosseous origin is suggested. Pan African ...

  16. Skin Cancer (Including Melanoma)—Patient Version

    Science.gov (United States)

    Skin cancer is the most common type of cancer. The main types of skin cancer are squamous cell carcinoma, basal cell carcinoma, and melanoma. Most deaths from skin cancer are caused by melanoma. Start here to find information on skin cancer treatment, causes and prevention, screening, research, and statistics.

  17. Prolonged Survival in Stage III Melanoma with Ipilimumab Adjuvant Therapy

    DEFF Research Database (Denmark)

    Eggermont, Alexander M M; Chiarion-Sileni, Vanna; Grob, Jean-Jacques

    2016-01-01

    undergone complete resection of stage III melanoma. Methods After patients had undergone complete resection of stage III cutaneous melanoma, we randomly assigned them to receive ipilimumab at a dose of 10 mg per kilogram (475 patients) or placebo (476) every 3 weeks for four doses, then every 3 months...

  18. Sentinel node biopsy for melanoma: a study of 241 patients

    DEFF Research Database (Denmark)

    Chakera, Annette Hougaard; Drzewiecki, Krzysztof Tadeusz; Jakobsen, Annika Loft

    2004-01-01

    The aim of this study was to evaluate the sentinel node biopsy (SNB) technique for melanoma using both radiocolloid and blue dye in 241 clinically N0 patients with melanomas >1.0 mm, or thinner lesions exhibiting regression/ulceration. We showed that an increase in injected radioactivity increased...

  19. Balloon Cell Urethral Melanoma: Differential Diagnosis and Management

    Directory of Open Access Journals (Sweden)

    M. McComiskey

    2015-01-01

    Full Text Available Introduction. Primary malignant melanoma of the urethra is a rare tumour (0.2% of all melanomas that most commonly affects the meatus and distal urethra and is three times more common in women than men. Case. A 76-year-old lady presented with vaginal pain and discharge. On examination, a 4 cm mass was noted in the vagina and biopsy confirmed melanoma of a balloon type. Preoperative CT showed no distant metastases and an MRI scan of the pelvis demonstrated no associated lymphadenopathy. She underwent anterior exenterative surgery and vaginectomy also. Histology confirmed a urethral nodular malignant melanoma. Discussion. First-line treatment of melanoma is often surgical. Adjuvant treatment including chemotherapy, radiotherapy, or immunotherapy has also been reported. Even with aggressive management, malignant melanoma of the urogenital tract generally has a poor prognosis. Recurrence rates are high and the mean period between diagnosis and recurrence is 12.5 months. A 5-year survival rate of less than 20% has been reported in balloon cell melanomas along with nearly 20% developing local recurrence. Conclusion. To the best of our knowledge, this case is the first report of balloon cell melanoma arising in the urethra. The presentation and surgical management has been described and a literature review provided.

  20. Prevalence of left-sided melanomas in an Irish population.

    LENUS (Irish Health Repository)

    de Blacam, C

    2012-02-01

    BACKGROUND: A predominance of melanomas on the left side of the body has recently been described. No associations between tumour laterality and gender, age or anatomical site have been identified. AIM: The aim of this study was to investigate the prevalence of left-sided melanomas in an Irish population and to examine potential associations with various patient and tumour characteristics. METHODS: A retrospective chart review of patients with cutaneous melanoma who were treated over a 10-year period was carried out. Lateral distribution of melanoma on either side of the body was compared using chi(2) analysis and evaluated by gender, age group, anatomic location, histologic subtype and Breslow depth. RESULTS: More melanomas occurred on the left side (57%, P = 0.015), and this finding was particularly significant in females. For both genders combined, there were no statistically significant differences in laterality by age group, anatomic location, type of melanoma and Breslow depth. There were significantly more superficial spreading melanomas on the left side in both men and women. CONCLUSIONS: This study demonstrates a predominance of left-sided melanomas in Irish patients. While a number of demographic and molecular associations have been proposed, further research is required to fully explain this phenomenon.

  1. Prevalence of left-sided melanomas in an Irish population.

    LENUS (Irish Health Repository)

    de Blacam, C

    2011-04-17

    BACKGROUND: A predominance of melanomas on the left side of the body has recently been described. No associations between tumour laterality and gender, age or anatomical site have been identified. AIM: The aim of this study was to investigate the prevalence of left-sided melanomas in an Irish population and to examine potential associations with various patient and tumour characteristics. METHODS: A retrospective chart review of patients with cutaneous melanoma who were treated over a 10-year period was carried out. Lateral distribution of melanoma on either side of the body was compared using χ(2) analysis and evaluated by gender, age group, anatomic location, histologic subtype and Breslow depth. RESULTS: More melanomas occurred on the left side (57%, P = 0.015), and this finding was particularly significant in females. For both genders combined, there were no statistically significant differences in laterality by age group, anatomic location, type of melanoma and Breslow depth. There were significantly more superficial spreading melanomas on the left side in both men and women. CONCLUSIONS: This study demonstrates a predominance of left-sided melanomas in Irish patients. While a number of demographic and molecular associations have been proposed, further research is required to fully explain this phenomenon.

  2. The Nodal Location of Metastases in Melanoma Sentinel Lymph Nodes

    DEFF Research Database (Denmark)

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

    2009-01-01

    BACKGROUND: The design of melanoma sentinel lymph node (SLN) histologic protocols is based on the premise that most metastases are found in the central parts of the nodes, but the evidence for this belief has never been thoroughly tested. METHODS: The nodal location of melanoma metastases in 149...

  3. Melanoma in Organ Transplant Recipients: Incidence, Outcomes and Management Considerations

    Directory of Open Access Journals (Sweden)

    Faisal R. Ali

    2012-01-01

    Full Text Available The incidence of melanoma continues to increase year on year. With better surgical techniques and medical management, greater numbers of organ transplants are being performed annually with much longer graft survival. The authors review our current understanding of the incidence of melanoma amongst organ transplant recipients, outcomes compared to the immunocompetent population, and management strategies in this burgeoning group.

  4. Stereological estimates of nuclear volume in thin malignant melanomas

    DEFF Research Database (Denmark)

    Björnhagen, V; Månsson-Brahme, E; Lindholm, J

    1998-01-01

    melanomas were individually compared with 33 thin non-metastasizing melanomas after individual matching of cases with one or two randomly chosen controls for site of primary tumour, tumour thickness, level of invasion, tumour regression and follow-up. Conditional logistic regression analysis showed...

  5. Immunohistochemical Expression of MCAM/CD146 in Canine Melanoma.

    Science.gov (United States)

    Abou Asa, S

    2017-07-01

    MCAM/CD146 (melanoma cell adhesion molecule/CD146) is a transmembrane immunoglobulin superfamily cell adhesion molecule involved in transendothelial migration and signal transduction. It is expressed in melanoma, squamous cell carcinoma, prostatic, ovarian, cervical and endometrial cancers and promotes tumour growth, angiogenesis and metastasis. Melanoma is the most common malignant oral tumour of dogs and also arises in the skin, nail bed and footpad. The aim of this study was to investigate the immunohistochemical expression of MCAM/CD146 in 51 canine melanomas, including oral, cutaneous and ocular tumours. Seventeen of the 51 (33.3%) cases were negative, eight (15.7%) were weakly positive, seven (13.7%) were moderately positive and 19 (37.3%) were strongly positive. MCAM/CD146 was expressed by both oral and cutaneous melanomas; however, the intensity and the extent of the immunoreactivity was higher in oral (P = 0.009) than in cutaneous tumours (P = 0.058). Most ocular melanomas did not express MCAM/CD146 (P = 0.256). Expression of MCAM/CD146 by canine melanomas may suggest the molecule as a target for treatment, especially in oral melanomas. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Thick melanoma: prognostic value of positive sentinel nodes

    NARCIS (Netherlands)

    Vermeeren, Lenka; van der Ent, Fred W. C.; Sastrowijoto, Prapto S. H.; Hulsewé, Karel W. E.

    2009-01-01

    BACKGROUND: Sentinel lymph node biopsy (SNB) is a widely accepted procedure used to accurately stage patients with melanoma. Its value in patients with thick melanoma (Breslow thickness >4 mm) is reason for discussion because of the generally poor prognosis of these patients. The purpose of this

  7. Oral melanoma with pulmonary metastasis in a Nigerian local dog ...

    African Journals Online (AJOL)

    Melanomas are the most commonly diagnosed neoplasm of the canine oral cavity accounting for about 7% of all malignant tumours in the dog. Less frequently, metastasis via regional lymph nodes and to the lungs and other organs may occur. A case report of oral melanoma with pulmonary metastasis in a Nigerian local ...

  8. DMBT1 expression distinguishes anorectal from cutaneous melanoma

    DEFF Research Database (Denmark)

    Helmke, Burkhard Maria; Renner, Marcus; Poustka, Annemarie

    2009-01-01

    tumours 1 (DMBT1) in cases of primary anorectal malignant melanoma and CM. METHODS AND RESULTS: Expression analyses of classical immunohistochemical markers (S100, HMB45, Melan A and MiTF) and of the protein DMBT1 were carried out in 27 cases of primary anorectal malignant melanoma and 26 cases of CM. All...

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

    Science.gov (United States)

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

    2017-05-01

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

  10. Malignant melanoma of the tongue following low-dose radiation

    Energy Technology Data Exchange (ETDEWEB)

    Kalemeris, G.C.; Rosenfeld, L.; Gray, G.F. Jr.; Glick, A.D.

    1985-03-01

    A 47-year-old man had a spindly malignant melanoma of the tongue many years after low-dose radiation therapy for lichen planus. To our knowledge, only 12 melanomas of the tongue have been reported previously, and in none of these was radiation documented.

  11. Malignant melanoma of the tongue following low-dose radiation

    International Nuclear Information System (INIS)

    Kalemeris, G.C.; Rosenfeld, L.; Gray, G.F. Jr.; Glick, A.D.

    1985-01-01

    A 47-year-old man had a spindly malignant melanoma of the tongue many years after low-dose radiation therapy for lichen planus. To our knowledge, only 12 melanomas of the tongue have been reported previously, and in none of these was radiation documented

  12. Potential Role of Meiosis Proteins in Melanoma Chromosomal Instability

    International Nuclear Information System (INIS)

    Lindsey, S. F.; Byrnes, D. M.; Eller, M. S.; Rosa, A. M.; Dabas, N.; Escandon, J.; Grichnik, J. M.; Grichnik, J. M.; Grichnik, J. M.; Grichnik, J. M.

    2013-01-01

    Melanomas demonstrate chromosomal instability (CIN). In fact, CIN can be used to differentiate melanoma from benign nevi. The exact molecular mechanisms that drive CIN in melanoma have yet to be fully elucidated. Cancer/testis antigens are a unique group of germ cell proteins that are found to be primarily expressed in melanoma as compared to benign nevi. The abnormal expression of these germ cell proteins, normally expected only in the testis and ovaries, in somatic cells may lead to interference with normal cellular pathways. Germ cell proteins that may be particularly critical in CIN are meiosis proteins. Here, we review pathways unique to meiosis with a focus on how the aberrant expression of meiosis proteins in normal mitotic cells "meiomitosis"could impact chromosomal instability in melanoma and other cancers.

  13. Malignant melanoma of the oral cavity: Report of two cases

    Directory of Open Access Journals (Sweden)

    Anita Munde

    2014-01-01

    Full Text Available Primary malignant melanoma is a rare and aggressive neoplasm that originates from the proliferation of melanocytes. Although, it comprises 1.3% of all cancers, malignant melanoma of the oral cavity accounts for only 0.2-8% of all reported melanomas and occurs approximately 4 times more frequently in the oral mucosa of the upper jaw, usually on the palate or alveolar gingivae. Most of the mucosal melanomas are usually asymptomatic in early stages, and presents as pigmented patch or a mass delaying the diagnosis until symptoms of swelling, ulceration, bleeding, or loosening of teeth are noted. The prognosis is extremely poor, especially in advanced stages. Therefore, any pigmented lesion of undetermined origin should always be biopsied. We herewith report of two cases of oral malignant melanoma in a 60 and 75-year-old female.

  14. Prognostic Parameters for the Primary Care of Melanoma Patients: What Is Really Risky in Melanoma

    International Nuclear Information System (INIS)

    Goppner, D.; Leverkus, M.

    2011-01-01

    Due to intensified research in recent years, the understanding of the molecular mechanisms involved in the development of melanoma has dramatically improved. The discovery of specific, causal mutations such as BRAF or KIT oncogenes not only renders a targeted and thus more effective therapeutic approach possible, but also gives rise to a new genetic-based classification. Targeting just a few out of several potential mutations, BRAF-Inhibitors such as PLX 4032 achieved already tremendous results in the therapy of metastatic melanoma. Up to now, the correlation of clinical, histomorphologic, and genetic features is, however, not understood. Even more, is it not well known precisely what kind of molecular changes predispose the primary melanoma for metastasis. The identification of morphological surrogates and prognostic parameters in tumors with such genetic alteration seems therefore crucial when differentiating and classifying this heterogeneous tumor entity in more detail and thus facilitates the stratification of prognosis as well as therapy. This review summarizes the current understanding of carcinogenesis and gives a detailed overview of known morphologic and potentially future genetic prognostic parameters in malignant melanoma.

  15. Meningeal Melanomas Associated With Transforming Ota Nevus to Malignant Melanoma: A Case Report

    Directory of Open Access Journals (Sweden)

    Seyed-Mohammad Fereshtehnejad

    2010-11-01

    Full Text Available Intracranial invasion of cellular blue nevus (CBN from the skin is extremely rare and such a condition with malignant transformation is even rarer.A case of meningeal melanoma with malignant transformation which was derived from an Ota   nevus is presented in this report.   A21-year-old man with a neurocutaneous syndrome since childhood was referred with headache and mild left hemiparesia. CT scan and MRI demonstrated intracranial lesions and conjunctival biopsy leads to the pathologic diagnosis of blue nevus.Thereafter his parietal lesion was operated by craniotomy with total gross excision.On histopathological examination, diagnosis of malignant melanoma was confirmed.Approximately 2 months after radiotherapy and chemotherapy, he afflicted to diplopia and blurred vision on the leftside due to enlargement of orbital and cavernous sinus lesion. Following one year follow-up,he was survived and thrived with diffuse leptomeningeal nodular enhancement in favor of melanoma dissemination.Primary intracranial melanomas are though rare, but it should be suspected especially in the presence of periorbital blue nevus or nevus of Ota. Moreover, although CBN is considered benign, scalp or periorbital CBN has the potential for intracranial invasion and malignant ransformation.

  16. MMP19 is upregulated during melanoma progression and increases invasion of melanoma cells

    Czech Academy of Sciences Publication Activity Database

    Muller, M.; Beck, Inken; Gadesmann, J.; Karschuk, N.; Paschen, A.; Proksch, E.; Djonov, V.; Reiss, K.; Sedláček, Radislav

    2010-01-01

    Roč. 23, č. 4 (2010), s. 511-521 ISSN 0893-3952 Institutional research plan: CEZ:AV0Z50520514 Keywords : melanoma * invasion * matrix metalloproteinase Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.176, year: 2010

  17. Relato de um caso de melanoma de conjuntiva Conjuntival melanoma: a case report

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    Carlos Gustavo Leite Vieira

    2000-10-01

    Full Text Available Objetivo: Relatar um caso raro de melanoma de conjuntiva de longa evolução em paciente melanodérmica. Método: Análise de caso. Resultado: Até a presente data a paciente encontra-se bem sem evidências de recorrência da patologia em questão após excisão local. Conclusão: Observamos que mesmo sem a realização de crioterapia adjuvante ou medidas mais agressivas, existem alguns casos como esse que acabamos de relatar para o qual a excisão simples pode garantir a cura. Um aspecto importante deste relato é a importância do exame histopatológico de peças e fragmentos cirúrgicos removidos.Purpose: The authors describe a rare case of malignant conjunctival melanoma with a long evolution. Methods: A case report. Results: Until this time the patient does not show any sign of relapse of this melanoma, after local excision. Conclusion: Without cryotherapy or more agressive methods we observe that there are some cases of conjunctival melanoma that might be cured with only a local excision. An important aspect of this case is the relevance of the histopathologic analysis of the removed surgical fragments.

  18. Dermatologia comparativa: dermatoscopia em melanoma cutâneo Comparative dermatology: dermatoscopy of cutaneous melanoma

    Directory of Open Access Journals (Sweden)

    Otávio Sérgio Lopes

    2008-10-01

    Full Text Available Os autores apresentam imagens de dermatoscopia em uma fruta (manga-rosa, contaminada pela antracnose, mostrando sua semelhança com o melanoma extensivo superficial.The authors present images from a dermatoscopy performed in a fruit (mango that was contaminated by anthracnosis, showing its similarity to superficial spreading melanona.

  19. Suppression of immune surveillance in melanoma [Immunotherapy of metastatic melanoma by reversal of immune suppression

    Energy Technology Data Exchange (ETDEWEB)

    Biggs, M. W. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Eiselein, J. E. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2001-06-01

    In this paper we develop the hypothesis that a significant fraction of patients with advanced melanoma can be successfully treated with immunotherapy. Reversal of antigen-specific immune suppression to melanoma polypeptide antigens is an essential, first step. We postulate the key regulation of CTL responses resides within the CD4+ T-lymphocytes and macrophage/dendritic cells. There is a pluri-potential cell within this regulatory arm that functions either as a Th1 cell or as a suppressor T-cell, Ths, depending on how antigen is presented. We have shown that poliovirus 1 Sabin will lyse human melanoma cells in tissue culture, and a special "vaccine" prepared from this lysis actively stimulates Ths cell function. The Ths arm of the regulatory system can be down-regulated with cyclophosphamide given 24 hours after the vaccine. The capacity to generate a CTL response is retained. The summary conclusion is that a phase 1 clinical trial in advanced melanoma using the special viral-tumor-lysate followed by cyclophosphamide, plus expanded autologous dendritic cells sensitized with the polypeptide epitopes captained in the viral-lysate will produce beneficial results.

  20. "Presumed fair: Ironic effects of organizational diversity structures": Correction to Kaiser et al. (2013).

    Science.gov (United States)

    2016-06-01

    Reports an error in "Presumed fair: Ironic effects of organizational diversity structures" by Cheryl R. Kaiser, Brenda Major, Ines Jurcevic, Tessa L. Dover, Laura M. Brady and Jenessa R. Shapiro (Journal of Personality and Social Psychology, 2013[Mar], Vol 104[3], 504-519). In the article, a raw data merging error in one racial discrimination claim condition from Experiment 6 inadvertently resulted in data analyses on an inaccurate data set. When the error was discovered by the authors and corrected, all analyses reported in Experiment 6 for claim validity, seriousness of the claim, and support for the claimant were inaccurate and none were statistically significant. The conclusions should be altered to indicate that participants with management experience who reflected on their own workplace diversity policies did not show the predicted effects. The literature review, remaining five studies, and remaining conclusions in the article are unaffected by this error. Experiment 6 should also report that 26.4% (not 26.4.7%) of participants had a graduate degree and eight participants (not 8%) did not provide educational data. Experiment 5 should have referred to the claim validity measure as a six-item measure ( .92) rather than a five-item measure; analyses on claim validity are accurate in text. Table 2's note should have said standard errors, not standard deviations. (The following abstract of the original article appeared in record 2012-31077-001.) This research tests the hypothesis that the presence (vs. absence) of organizational diversity structures causes high-status group members (Whites, men) to perceive organizations with diversity structures as procedurally fairer environments for underrepresented groups (racial minorities, women), even when it is clear that underrepresented groups have been unfairly disadvantaged within these organizations. Furthermore, this illusory sense of fairness derived from the mere presence of diversity structures causes high

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

    Science.gov (United States)

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

    2001-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Elton Rexhepaj

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

  3. GAB2 amplifications refine molecular classification of melanoma.

    Science.gov (United States)

    Chernoff, Karen A; Bordone, Lindsey; Horst, Basil; Simon, Katherine; Twadell, William; Lee, Keagan; Cohen, Jason A; Wang, Shuang; Silvers, David N; Brunner, Georg; Celebi, Julide Tok

    2009-07-01

    Gain-of-function mutations in BRAF, NRAS, or KIT are associated with distinct melanoma subtypes with KIT mutations and/or copy number changes frequently observed among melanomas arising from sun-protected sites, such as acral skin (palms, soles, and nail bed) and mucous membranes. GAB2 has recently been implicated in melanoma pathogenesis, and increased copy numbers are found in a subset of melanomas. We sought to determine the association of increased copy numbers of GAB2 among melanoma subtypes in the context of genetic alterations in BRAF, NRAS, and KIT. A total of 85 melanomas arising from sun-protected (n = 23) and sun-exposed sites (n = 62) were analyzed for copy number changes using array-based comparative genomic hybridization and for gain-of-function mutations in BRAF, NRAS, and KIT. GAB2 amplifications were found in 9% of the cases and were associated with melanomas arising from acral and mucosal sites (P = 0.005). Increased copy numbers of the KIT locus were observed in 6% of the cases. The overall mutation frequencies for BRAF and NRAS were 43.5% and 14%, respectively, and were mutually exclusive. Among the acral and mucosal melanomas studied, the genetic alteration frequency was 26% for GAB2, 13% for KIT, 30% for BRAF, and 4% for NRAS. Importantly, the majority of GAB2 amplifications occurred independent from genetic events in BRAF, NRAS, and KIT. GAB2 amplification is critical for melanomas arising from sun-protected sites. Genetic alterations in GAB2 will help refine the molecular classification of melanomas.

  4. IQGAP1 is an oncogenic target in canine melanoma.

    Directory of Open Access Journals (Sweden)

    Becky H Lee

    Full Text Available Canine oral mucosal melanoma is an aggressive malignant neoplasm and is characterized by local infiltration and a high metastatic potential. The disease progression is similar to that of human oral melanomas. Whereas human cutaneous melanoma is primarily driven by activating mutations in Braf (60% or Nras (20%, human mucosal melanoma harbors these mutations much less frequently. This makes therapeutic targeting and research modeling of the oral form potentially different from that of the cutaneous form in humans. Similarly, research has found only rare Nras mutations and no activating Braf mutations in canine oral melanomas, but they are still reliant on MAPK signaling. IQGAP1 is a signaling scaffold that regulates oncogenic ERK1/2 MAPK signaling in human Ras- and Raf- driven cancers, including melanomas. To investigate whether IQGAP1 is a potential target in canine melanoma, we examined the expression and localization of IQGAP1 in primary canine melanomas and canine oral melanoma cell lines obtained from the University of California-Davis. Using CRISPR/Cas9 knockout of IQGAP1, we examined effects on downstream ERK1/2 pathway activity and assayed proliferation of cell lines when treated with a peptide that blocks the interaction between IQGAP1 and ERK1/2. We observed that canine IQGAP1 is expressed and localizes to a similar extent in both human and canine melanoma by qPCR, Western blot, and immunofluorescence. Deletion of IQGAP1 reduces MAPK pathway activation in cell lines, similar to effects seen in human BrafV600E cell lines. Additionally, we demonstrated reduced proliferation when these cells are treated with a blocking peptide in vitro.

  5. The risk of melanoma associated with ambient summer ultraviolet radiation.

    Science.gov (United States)

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

    2017-05-17

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

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

    Science.gov (United States)

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

    2017-11-01

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

  7. Radiation sensitivity of B-16 melanoma

    International Nuclear Information System (INIS)

    Griem, M.L.; Malkinson, F.D.; Kalis, J.B.; Shefner, A.

    1984-01-01

    A model has been developed for radiation studies of melanoma. Β-16 melanoma (NCI), carried by subcutaneous implant in C57BL/6NCr mice was implanted instramuscularly into the right rear leg of female B6C3F1 mice. Test mice were inoculated with 1 x 10/sup 5/, 5 x 10/sup 5/, and 1 x 10/sup 6/ tumor cells to determine an appropriate tumor challenge for a reproducible and suitable median survival time. A challenge inoculum of 5 x 10/sup 5/ tumor cells was subsequently chosen as the standard tumor dose for test animals used in subsequent radiation dose response studies. Tumor-bearing test animals were treated with 500, 1000, 1500, or 2000 rads of 250 kV x-rays either 4 days or 14 days after tumor implantation. Only the tumorbearing leg of the test mouse was exposed during irradiation; the animal was otherwise protected by lead shielding. The median survival time of tumorbearing unirradiated mice was 24.4 days. Radiation on day 4 postinoculation was more effective than radiation administered on day 14. Median survival time for the 4 radiation dose groups given x-rays on day 4 were 31.0, 38.2, 59.0, and 60.0 days with progressive increases in radiation dose. Median survival times for mice irradiated on day 14 were 26.8, 31.8, 34.8, and 49.2 days as the radiation doses increased. This mouse melanoma model can be used in combined modality studies

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

    Science.gov (United States)

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

    2017-02-01

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

  9. Computer-assisted diagnosis of melanoma.

    Science.gov (United States)

    Fuller, Collin; Cellura, A Paul; Hibler, Brian P; Burris, Katy

    2016-03-01

    The computer-assisted diagnosis of melanoma is an exciting area of research where imaging techniques are combined with diagnostic algorithms in an attempt to improve detection and outcomes for patients with skin lesions suspicious for malignancy. Once an image has been acquired, it undergoes a processing pathway which includes preprocessing, enhancement, segmentation, feature extraction, feature selection, change detection, and ultimately classification. Practicality for everyday clinical use remains a vital question. A successful model must obtain results that are on par or outperform experienced dermatologists, keep costs at a minimum, be user-friendly, and be time efficient with high sensitivity and specificity. ©2015 Frontline Medical Communications.

  10. Bydgoszcz universities students' awareness about melanoma

    OpenAIRE

    Mirończuk, Katarzyna; Kałużna, Lucyna; Łakomski, Mateusz; Zukow, Walery

    2017-01-01

    Mirończuk Katarzyna, Kałużna Lucyna, Łakomski Mateusz, Zukow Walery. Bydgoszcz universities students' awareness about melanoma. Journal of Education, Health and Sport. 2017;7(8):566-575. eISSN 2391-8306. DOI http://dx.doi.org/10.5281/zenodo.887380 http://ojs.ukw.edu.pl/index.php/johs/article/view/4784 The journal has had 7 points in Ministry of Science and Higher Education parametric evaluation. Part B item 1223 (26.01.2017). 1223 Journal of Edu...

  11. Akt Inhibitor MK2206 and Hydroxychloroquine in Treating Patients With Advanced Solid Tumors, Melanoma, Prostate or Kidney Cancer

    Science.gov (United States)

    2018-05-15

    Adult Solid Neoplasm; Hormone-Resistant Prostate Carcinoma; Recurrent Melanoma; Recurrent Prostate Carcinoma; Recurrent Renal Cell Carcinoma; Stage IIIA Cutaneous Melanoma AJCC v7; Stage IIIB Cutaneous Melanoma AJCC v7; Stage IIIC Cutaneous Melanoma AJCC v7; Stage IV Cutaneous Melanoma AJCC v6 and v7; Stage IV Prostate Cancer AJCC v7; Stage IV Renal Cell Cancer AJCC v7

  12. Intussusception of the small intestine caused by a primary melanoma?

    Science.gov (United States)

    Schoneveld, M; De Vogelaere, K; Van De Winkel, N; Hoorens, A; Delvaux, G

    2012-01-01

    Although the gastrointestinal tract is a fairly frequent site of melanoma metastases, reports of small bowel intussusception caused by melanoma are very rare. We report the case of a 77-year-old man who was admitted to our hospital with epigastric pain, melena and anaemia. After clinical examination, laboratory evaluation and radiological work-up the diagnosis of a jejunal intussusception was made. Exploratory laparoscopy revealed a large tumour arising from the jejunum, approximately 20 cm distal to the angle of Treitz. Small bowel resection with an end-to-end anastomosis was performed. Histological examination showed an intestinal melanoma. There are different theories concerning the origin of malignant melanoma in the small bowel. Although the small and large intestines normally contain no melanocytes, these cells have occasionally been found in the alimentary and respiratory tracts and even in lymph nodes, which supports the theory of a primary origin of melanoma at these sites. Since this was a solitary intestinal lesion and there was no history of cutaneous melanoma, we conclude that this could be an example of a very rare primary melanoma of the small intestine.

  13. Intussusception of the Small Intestine Caused by a Primary Melanoma

    Directory of Open Access Journals (Sweden)

    M. Schoneveld

    2012-01-01

    Full Text Available Although the gastrointestinal tract is a fairly frequent site of melanoma metastases, reports of small bowel intussusception caused by melanoma are very rare. We report the case of a 77-year-old man who was admitted to our hospital with epigastric pain, melena and anaemia. After clinical examination, laboratory evaluation and radiological work-up the diagnosis of a jejunal intussusception was made. Exploratory laparoscopy revealed a large tumour arising from the jejunum, approximately 20 cm distal to the angle of Treitz. Small bowel resection with an end-to-end anastomosis was performed. Histological examination showed an intestinal melanoma. There are different theories concerning the origin of malignant melanoma in the small bowel. Although the small and large intestines normally contain no melanocytes, these cells have occasionally been found in the alimentary and respiratory tracts and even in lymph nodes, which supports the theory of a primary origin of melanoma at these sites. Since this was a solitary intestinal lesion and there was no history of cutaneous melanoma, we conclude that this could be an example of a very rare primary melanoma of the small intestine.

  14. LOSS OF 5-HYDROXYMETHYLCYTOSINE IS AN EPIGENETIC HALLMARK OF MELANOMA

    Science.gov (United States)

    Lian, Christine Guo; Xu, Yufei; Ceol, Craig; Wu, Feizhen; Larson, Allison; Dresser, Karen; Xu, Wenji; Tan, Li; Hu, Yeguang; Zhan, Qian; Lee, Chung-wei; Hu, Di; Lian, Bill Q.; Kleffel, Sonja; Yang, Yijun; Neiswender, James; Khorasani, Abraham J.; Fang, Rui; Lezcano, Cecilia; Duncan, Lyn M.; Scolyer, Richard A.; Thompson, John F.; Kakavand, Hojabr; Houvras, Yariv; Zon, Leonard; Mihm, Martin C.; Kaiser, Ursula B.; Schatton, Tobias; Woda, Bruce A.; Murphy, George F.; Shi, Yujiang G.

    2013-01-01

    SUMMARY DNA methylation at the 5-position of cytosine (5-mC) is a key epigenetic mark critical for various biological and pathological processes. 5-mC can be converted to 5-hydroxymethylcytosine (5-hmC) by the Ten-Eleven Translocation (TET) family of DNA hydroxylases. Here we report that “loss of 5-hmC” is an epigenetic hallmark of melanoma with diagnostic and prognostic implications. Genome-wide mapping of 5-hmC reveals loss of 5-hmC landscape in the melanoma epigenome. We show that down-regulation of Isocitrate Dehydrogenase 2 (IDH2) and TET family enzymes is likely one of the mechanisms underlying 5-hmC loss in melanoma. Rebuilding the 5-hmC landscape in melanoma cells by reintroducing active TET2 or IDH2 suppresses melanoma growth and increases tumor-free survival in animal models. Thus, our study reveals a critical function of 5-hmC in melanoma development and directly links the IDH and TET activity-dependent epigenetic pathway to 5-hmC-mediated suppression of melanoma progression, suggesting a new strategy for epigenetic cancer therapy. PMID:22980977

  15. Promoting early detection of melanoma during the mammography experience

    Directory of Open Access Journals (Sweden)

    A.K. Rzepecki, BS

    2017-12-01

    Full Text Available Background: Invasive melanoma, a lethal form of skin cancer, is the seventh most common cancer in women. Factors such as a history of indoor tanning or sunburn and a personal or family history of skin cancer increase a woman’s risk of developing a melanoma. Objective: Because the majority of melanomas occur in patients age 40 years or older, which is the age that is recommended for women to begin screening mammograms, the mammogram experience could be used to promote early detection of melanoma by introducing skin self-examinations (SSE to a population of women who are already invested in preventive health. Methods: This was a pilot and feasibility study that was designed to promote the early detection of melanoma among women who undergo a mammogram at the Lynn Sage Breast Center at the Northwestern Medicine/Prentice Women’s Hospital in Chicago, Illinois. The study was conducted in three phases: development of the materials, delivery of the program, and assessment of the program effectiveness. Results: Eighty six percent of women with scheduled mammogram appointments participated in the study (n = 560. Among these women, 68% noticed the SSE information in the changing rooms, 78% thought the information applied to them, and 68% identified with at least one of the risk factors for melanoma. Twenty percent of the patients checked their skin in the changing room, 13% noticed a concerning mole, and 60% of those women who noted a concerning lesion stated their intent to see a dermatologist for further evaluation. Conclusion: A large proportion of the women in our study had risk factors for developing a melanoma and noticed the SSE information in the screening center. Placing an intervention to encourage methods for the early detection of melanoma in an outpatient mammography environment is an effective strategy to increase awareness in a large proportion of at-risk women. Keywords: melanoma, skin self-examination, skin cancer screening

  16. Classical and molecular genetics of malignant melanoma and dysplastic naevi

    International Nuclear Information System (INIS)

    Traupe, H.; Macher, E.

    1988-01-01

    The authors conclude that the prevailing concept of monogenic autosomaldominant inheritance of dysplastic naevi and familial melanoma is not compatible with the principles of formal (Mendelian) genetics. The concept of polygenic inheritance offers instead a sound basis to explain familial aggregation of dysplastic naevi and melanoma. The various genes involved have not yet been identified at the molecular level. The recent advances made possible by modern DNA technology have given us a new view of carcinogenesis. In human malignant melanoma, chromosomes 1, 6, 7 are of particular interest and oncogenes located on these chromosomes may be involved with the initiation, promotion and progression of melanoma. Carcinogenesis is viewed as a multistep process and even tumour initiation requires the input of at least two independent oncogenes. Molecular genetics thus adds an important argument for the existence of a polygenic predisposition to melanoma. The concept of polygenic inheritance is not restricted to familial melanoma, but implies that all melanomas basically share the same predisposition and are due to similar genetic mechanisms. In some patients an inherited genetic predisposition is of great importance, whereas in others (the majority) environmental factors (e.g. UV-light-induced mutations) will be the cause of initial steps in the malignant transformation. The concept of polygenic inheritance has consequences for the management of our patients. In contrast to simple Mendelian inheritance, the risk for dysplastic naevi and melanoma is not constantly 50%, but increases with the number of family members already affected. Persons belonging to families with more that 2 affected close relatives should be considered at high risk regardless of the dysplastic naevus status. Strict surveillance of this patient group is warranted for melanoma prevention

  17. Histologic differentiation of desmoplastic melanoma from cicatrices.

    Science.gov (United States)

    Kaneishi, N K; Cockerell, C J

    1998-04-01

    Desmoplastic malignant melanoma (DMM) is a rare variant of melanoma that can be very difficult to diagnose correctly both clinically and histologically. The problem is compounded by the fact that many lesions persist at previous biopsy or excision sites so that scar tissue is often present admixed with or adjacent to the spindle cell neoplasm which may exhibit fibroblastic differentiation itself. In order to assess this problem, we compared and contrasted the histologic features of six DMM with 15 examples of cicatrices from various sources. Mature scars were readily differentiated from DMM by light microscopy. In contrast, immature scar and DMM had many features in common including hypercellularity, nodular lymphoid infiltrates, myxoid stroma, and atypical nuclei. The presence of a melanocytic proliferation within the epidermis above the dermal component, neurotropism, and S-100 and/or HMB-45 positivity of neoplastic cells were the only features that permitted reliable differentiation between the two. Clinical correlation and review of previous biopsy specimens are crucial in preventing a delayed diagnosis of DMM. Re-excision is advised in all questionable cases.

  18. Early melanoma diagnosis with mobile imaging.

    Science.gov (United States)

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

    2014-01-01

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

  19. GdNCT of spontaneous canine melanoma

    International Nuclear Information System (INIS)

    Mitin, V.N.; Kulakov, V.N.; Khokhlov, V.F.

    2006-01-01

    The effectiveness of GdNCT has been studied in dogs with spontaneous melanoma of the mucousmembrane of the oral cavity patients on the NCT base at the IRT MEPhI reactor. The control group with melanomas was treated with neutrons. Fourteen canine patients were selected in the Clinic of Experimental Therapy affiliated with the RCRC RAMS. The calculation of doses has shown that the total dose of energy release depending on Gd concentration in the target can be several times higher than the dose produced by the reactor neutron beam. The calculations were carried out using the diffusion pharmacokinetic model. The gadolinium drug dipentast was administered intratumorally immediately prior to irradiation. The tumor size was estimated by measuring it in three projections. The tumor was irradiated for 60-90 minutes with a thermal neutron flux of 0.7x10 9 n/cm 2 s. The dose on tumor was 80-120 Gy, on surrounding tissues - 12-15 Gy. The treatment plan included immunotherapy with Roncoleikin in a dose of (15-10)x10 3 IE/kg. The results of GdNCT are still under observation. The results conform to those obtained by us earlier in cell cultures and inoculated experimental tumors. GdNCT is also effective in combination with immunotherapy. (author)

  20. Radioimmunoscintigraphy of human malignant melanoma. I

    International Nuclear Information System (INIS)

    Svec, J.; Makaiova, I.; Veselovska, Z.; Keszeghova, V.; Reinerova, M.

    1989-01-01

    The novel RG-12 monoclonal antibody (MoAb) recognizing a high-molecular-weight antigen of human melanoma cells was radioiodinated and its biodistribution and tumor imaging was determined in immunosuppressed mice bearing xenografted human malignant melanoma HMB-2. Control and tumor-bearing mice were injected with 6 μg of 125 I-labeled RG-12 IgG (8.9 MBq 125 I-IgG/animal). Clearance of the MoAb from plasma had a mean half life of 20.6 hours. At day 2 after injection, radiolabeled RG-12 IgG localized in the tumor was 1.43% of the injected dose bound per gram tissue (ID/g), whereas the localization in the healthy kidney was below 0.5%. Tumor to tissue ratio of MoAb accumulation was low for hepatic tissue (1.25) but high for spleen (3.30) and kidney (3.25). Scanning with a gamma camera localized tumor mass in the right kidney and implanted peritoneal metastases. (author). 3 figs., 1 tab., 9 refs