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Sample records for melanoma clinically simulating

  1. 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.

  2. 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

  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. Geant4 simulation of clinical proton and carbon ion beams for the treatment of ocular melanomas with the full 3-D pencil beam scanning system

    Energy Technology Data Exchange (ETDEWEB)

    Farina, Edoardo; Riccardi, Cristina; Rimoldi, Adele; Tamborini, Aurora [University of Pavia and the INFN section of Pavia, via Bassi 6, 27100 Pavia (Italy); Piersimoni, Pierluigi [Division of Radiation Research, Loma Linda University, Loma Linda, CA 92354 (United States); Ciocca, Mario [Medical Physics Unit, CNAO Foundation, Strada Campeggi 53, 27100 Pavia (Italy)

    2015-07-01

    This work investigates the possibility to use carbon ion beams delivered with active scanning modality, for the treatment of ocular melanomas at the Centro Nazionale di Adroterapia Oncologica (CNAO) in Pavia. The radiotherapy with carbon ions offers many advantages with respect to the radiotherapy with protons or photons, such as a higher relative radio-biological effectiveness (RBE) and a dose release better localized to the tumor. The Monte Carlo (MC) Geant4 10.00 patch-03 toolkit is used to reproduce the complete CNAO extraction beam line, including all the active and passive components characterizing it. The simulation of proton and carbon ion beams and radiation scanned field is validated against CNAO experimental data. For the irradiation study of the ocular melanoma an eye-detector, representing a model of a human eye, is implemented in the simulation. Each element of the eye is reproduced with its chemical and physical properties. Inside the eye-detector a realistic tumor volume is placed and used as the irradiation target. A comparison between protons and carbon ions eye irradiations allows to study possible treatment benefits if carbon ions are used instead of protons. (authors)

  5. 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 ...

  6. 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.

  7. Melanoma

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    ... 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 ...

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

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    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.

  9. Characterization of ex vivo expanded tumor infiltrating lymphocytes from patients with malignant melanoma for clinical application

    DEFF Research Database (Denmark)

    Junker, Niels; Thor Straten, Per; Andersen, Mads Hald

    2011-01-01

    Clinical trials of adoptive transfer of autologous tumor infiltrating lymphocytes (TILs) to patients with advanced malignant melanoma have shown remarkable results with objective clinical responses in 50% of the treated patients. In order to initiate a clinical trial in melanoma, we have establis......Clinical trials of adoptive transfer of autologous tumor infiltrating lymphocytes (TILs) to patients with advanced malignant melanoma have shown remarkable results with objective clinical responses in 50% of the treated patients. In order to initiate a clinical trial in melanoma, we have...

  10. 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...

  11. Mutational and putative neoantigen load predict clinical benefit of adoptive T cell therapy in melanoma

    DEFF Research Database (Denmark)

    Lauss, Martin; Donia, Marco; Harbst, Katja

    2017-01-01

    Adoptive T-cell therapy (ACT) is a highly intensive immunotherapy regime that has yielded remarkable response rates and many durable responses in clinical trials in melanoma; however, 50-60% of the patients have no clinical benefit. Here, we searched for predictive biomarkers to ACT in melanoma. ...

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

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    Monica Marzagalli

    2016-10-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  14. Monoclonal anti-melanoma antibodies and their possible clinical use

    International Nuclear Information System (INIS)

    Hellstroem, K.E.; Hellstroem, Ingegerd; Washington Univ., Seattle; Washington Univ., Seattle

    1985-01-01

    Cell surface antigens of human melanoma, as defined by monoclonal antibodies, are discussed and in particular the three antigens p97, a GD3 ganglioside and a proteoglycan. The potential diagnostic uses of antibodies to melanoma antigens are reviewed including in vitro diagnosis by immuno-histology, in vitro diagnosis by serum assays and in vivo diagnosis by tumour imaging using radioactively labelled antibodies. The potential therapeutic uses of monoclonal antibodies to melanoma antigens are also reviewed including targets for antibody therapy, the use of antibodies alone, radiolabelled antibodies, antibody-toxin conjugates, antibody-drug conjugates, anti-idiotypic antibodies and vaccines. (UK)

  15. Clinical utility of nivolumab in the treatment of advanced melanoma

    Directory of Open Access Journals (Sweden)

    Asmar R

    2016-02-01

    Full Text Available Ramsey Asmar,1 Jessica Yang,1 Richard D Carvajal1,2 1Department of Medicine, College of Physicians and Surgeons, 2Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY, USA Abstract: Melanomas are highly immunogenic tumors that evade the immune system by exploiting innate checkpoint pathways, rendering effector T-cells anergic. The immunotherapeutic approach of checkpoint inhibition can restore and invigorate endogenous antitumor T-cell responses and has become an important treatment option for patients with advanced melanoma. The CTLA-4 inhibitor ipilimumab and the PD-1 inhibitors nivolumab and pembrolizumab have been shown to induce durable responses and improve overall survival in metastatic, refractory melanoma. Optimization and validation of pretreatment biomarkers to predict response to these agents is a crucial area of ongoing research. Combination immunotherapy has recently demonstrated superior response rates compared to monotherapy; further investigation is needed to refine combinatorial strategies. Keywords: nivolumab, immune checkpoint inhibitors, PD-1, melanoma

  16. BNCT clinical trials of skin melanoma patients in Argentina

    International Nuclear Information System (INIS)

    Roth, Berta M.; Bonomi, Marcelo R.; Gonzalez, Sara J.

    2006-01-01

    The clinical outcome of six skin melanoma BNCT irradiations is presented. Three patients (A, B and C), with multiple subcutaneous skin metastases progressed to chemotherapy were infused with ∼14 g/m 2 of boronophenylalanine ( 10 BPA)-fructose and irradiated in the hyperthermal neutron beam of the RA-6 reactor. Patient A received two one fraction irradiations in different areas of the leg, B received one fraction and C was irradiated in three consecutive fields at the calf, heel and foot sole. The maximum prescribed dose to normal skin ranged from 16.5 to 24 Gy-Eq. With a minimum follow-up of 10 months there was a G1 acute epithelitis in A and B and a G3 in C. No late toxicity was observed. Due to the in-field tumor-growth-delay and the absence of severe acute and/or late toxicity observed during the follow-up period, a dose-escalation trial is ongoing. (author)

  17. Rare clinical experiences for surgical treatment of melanoma with osseous metastases in Taiwan

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    Yang Rong-Sen

    2007-07-01

    Full Text Available Abstract Background Malignant melanoma occurs infrequently in Taiwan. Once it has progressed into osseous metastases, the prognosis is poor. There are no reported clinical experiences of surgical management in this area. Methods To improve our understanding of the rare clinical experiences, we retrospectively investigated clinical characteristics, radiological findings, treatment modalities, survival outcomes and prognoses of 11 Taiwanese patients with osseous metastasis of melanoma treated surgically at two national medical centers, National Taiwan University Hospital and National Cheng Kung University Hospital from January 1983 to December 2006. Results Six patients suffered from acral-lentiginous melanoma. Nine patients sustained multiple osseous metastases and most lesions were osteolytic. Nine patients also had sustained metastases to other organs including liver, lungs, lymph nodes, brain and spleen. Second malignancies including lung cancer, thyroid papillary carcinoma, renal cell carcinoma and cervical cancer co-existed in four patients. The interval from the initial diagnosis of melanoma to the clinical detection of osseous metastases varied from 0–37.8 months (mean 9.75 months. Metastatic melanoma was invariably fatal; the mean survival time from bone metastases to death was 5.67 months. Conclusion Due to the high morbidity and poor survival of Taiwanese patients with osseous metastases of melanoma, surgical treatment should be directed towards pain relief and the prevention of skeletal debilitation in order to maintain their quality of life.

  18. Clinical simulation practise framework.

    Science.gov (United States)

    Khalili, Hossein

    2015-02-01

    Historically, simulation has mainly been used to teach students hands-on skills in a relatively safe environment. With changes in the patient population, professional regulations and clinical environments, clinical simulation practise (CSP) must assist students to integrate and apply their theoretical knowledge and skills with their critical thinking, clinical judgement, prioritisation, problem solving, decision making, and teamwork skills to provide holistic care and treatment to their patients. CSP holds great potential to derive a positive transformation in students' transition into the workplace, by associating and consolidating learning from classrooms to clinical settings, and creating bridges between theory and practice. For CSP to be successful in filling the gap, the design and management of the simulation is crucial. In this article a new framework called 'Clinical simulation practise framework: A knowledge to action strategy in health professional education' is being introduced that aims to assist educators and curriculum developers in designing and managing their simulations. This CSP framework theorises that simulation as an experiential educational tool could improve students' competence, confidence and collaboration in performing professional practice in real settings if the CSP provides the following three dimensions: (1) a safe, positive, reflective and fun simulated learning environment; (2) challenging, but realistic, and integrated simulated scenarios; and (3) interactive, inclusive, interprofessional patient-centred simulated practise. © 2015 John Wiley & Sons Ltd.

  19. Primary melanoma of the esophagus treated with esophagectomy. Clinical Cases

    International Nuclear Information System (INIS)

    Butte, Jean M; Visscher, Alvaro; De la Fuente, Hernan; Meneses, Manuel; Carrasco, Ana Maria; Amaral, Horacio; Waugh, Enrique

    2010-01-01

    Esophageal melanomas correspond to 0.1 to 0.2% of esophageal tumors. We report two patients with the disease. The first patient is a 51 year-old woman pre-sentingwith dysphagia and weight loss. An upper gastrointestinal endoscopy showed a polypoid ulcerated lesion in the middle third of the esophagus. The pathological study of the biopsy disclosed a malignant melanoma. The patient was subjected to an esophagectomy with a satisfactory postoperative evolution. Four months later, liver metastases were detected and the patient died eleven months after the operation. The second patient is a 59 year-old mole that consulted by dysphagia. An endoscopy showed a pigmented esophageal lesion whose pathological diagnosis was a malignant melanoma. The patient was subjected to an esophagectomy and sixteen months after surgery there was no evidence of relaps

  20. Fidelity in clinical simulation

    DEFF Research Database (Denmark)

    Jensen, Sanne; Nøhr, Christian; Rasmussen, Stine Loft

    2013-01-01

    Clinical simulation may be used to identify user needs for context sensitive functionalities in e-Health. The objective with this paper is to describe how user requirements and use cases in a large EHR-platform procurement may be validated by clinical simulation using a very low-fidelity prototype...... without any existing test data. Instead of using test scenarios and use cases, the healthcare professionals who are participating in the clinical simulation are generating both scenario and patient data themselves. We found that this approach allows for an imaginative discussion, not restricted by known...... functionalities and limitations, of the ideal EHR-platform. Subsequently, we discuss benefits and challenges of using an extremely low fidelity environment and discuss the degree of fidelity necessary for conducting clinical simulation....

  1. Computerized Clinical Simulations.

    Science.gov (United States)

    Reinecker, Lynn

    1985-01-01

    Describes technique involved in designing a clinical simulation problem for the allied health field of respiratory therapy; discusses the structure, content, and scoring categories of the simulation; and provides a sample program which illustrates a programming technique in BASIC, including a program listing and a sample flowchart. (MBR)

  2. Phenotypic and functional characteristics of blood natural killer cells from melanoma patients at different clinical stages.

    Directory of Open Access Journals (Sweden)

    Giulia Fregni

    Full Text Available Melanomas are aggressive skin tumors characterized by high metastatic potential. Immunotherapy is a valuable alternative for metastatic melanoma patients resistant to chemotherapy. Natural Killer (NK cells are efficient anti-tumor cytotoxic effectors. We previously showed that blood NK cells from stage IV metastatic melanoma patients display decreased NK receptors and that chemotherapy modifies the functional status of blood NK cells. To investigate the role of NK cells along melanoma progression, we have here studied NK cells from patients at different stages of the disease. First, we showed that ex vivo NK cells from certain stage III-IV patients displayed low degranulation potential. Using a dynamic label-free assay, we found that immunoselected IL-2 activated blood NK cells from patients efficiently lysed melanoma cells through NKp46 and NKG2D receptors, independently to the clinical stage. Moreover, the ex vivo phenotype of circulating NK cells from 33 patients (stage I to IV was extensively analyzed. NK cells from patients displayed higher variability in the percentages of Natural Cytotoxicity Receptors (NCR and Natural Killer Group 2D (NKG2D receptor expression compared to donor NK cells. The main defect was the decreased expression of NCR1 (NKp46 by NK cells from metastatic patients. Interestingly, we found a positive correlation between the NK cell percentages of NKp46 and the duration of stage IV in melanoma patients. Finally, we showed that NK cells infiltrated primary melanomas and displayed a predominant peritumoral distribution. These results are new arguments for the development of NK-based therapies in melanoma patients.

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

    Science.gov (United States)

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

    2015-05-15

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

  4. Clinical impact of sentinel lymph node biopsy in patients with thick (>4 mm) melanomas.

    Science.gov (United States)

    White, Ian; Fortino, Jeanine; Curti, Brendan; Vetto, John

    2014-05-01

    The role of sentinel lymph node status (SLNS) in thick melanoma is evolving. The purpose of this study was to determine the prognostic value of SLNS in thick melanoma. A retrospective analysis of 120 prospectively collected clinically node-negative thick melanomas over 5 years was performed. Patient (age/sex) and tumor (thickness, ulceration, SLNS, mitoses, metastases, and recurrence) features were collected. Multivariate analysis was performed using Cox proportional hazard model. Factors predictive of positive SLN included male sex, ulceration, and high mitoses. Factors associated with positive SLN had higher local-regional recurrence and metastases than negative SLN. SLNS and tumor thickness impacted 5-year disease-free survival (DFS) and overall survival (OS). Positive SLN, ulceration, age, and mitoses were independent predictors of DFS/OS. Nonulcerated/lower mitoses thick melanomas had lower positive SLN rates. Positive SLN develop recurrence and metastases and have worse OS/DFS. SLNS is an important prognosticator for OS/DFS. Sentinel lymph node biopsy delineates prognostic groups in thick melanomas and can impact management. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Radiation therapy of malignant melanomas: an evaluation of clinically used fractionation schemes

    International Nuclear Information System (INIS)

    Strauss, A.; Dritschilo, A.; Nathanson, L.; Piro, A.J.

    1981-01-01

    To assess the importance of radiation dose fraction size in the treatment of malignant melanomas, the records of 48 patients (83 sites) treated at Tufts-New England Medical Center from 1971 to 1979 have been retrospectively reviewed. During this period, the dose fractionation schemes evolved from standard fraction size to large-dose techniques. Radiation fraction size was observed to be the major factor in the clinical response of melanoma. Fractions of 600-800 rad resulted in the best overall response (80%). The rapid fractionation scheme of 800-400-400 rad on successive days resulted in intermediate response (58%) and may be useful for the palliative treatment of selected patients

  6. 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.

  7. Combining radiotherapy and ipilimumab induces clinically relevant radiation-induced abscopal effects in metastatic melanoma patients: A systematic review

    Directory of Open Access Journals (Sweden)

    Rodolfo Chicas-Sett

    2018-02-01

    Conclusion: Early clinical outcomes reports suggest that the combination of ipilimumab and RT may improve survival in metastatic melanoma patients. The abscopal responses become a clinically relevant effect of such combination and should be studied in controlled randomized trials.

  8. Simulation study of melanoma detection in human skin tissues by laser-generated surface acoustic waves.

    Science.gov (United States)

    Chen, Kun; Fu, Xing; Dorantes-Gonzalez, Dante J; Lu, Zimo; Li, Tingting; Li, Yanning; Wu, Sen; Hu, Xiaotang

    2014-01-01

    Air pollution has been correlated to an increasing number of cases of human skin diseases in recent years. However, the investigation of human skin tissues has received only limited attention, to the point that there are not yet satisfactory modern detection technologies to accurately, noninvasively, and rapidly diagnose human skin at epidermis and dermis levels. In order to detect and analyze severe skin diseases such as melanoma, a finite element method (FEM) simulation study of the application of the laser-generated surface acoustic wave (LSAW) technique is developed. A three-layer human skin model is built, where LSAW’s are generated and propagated, and their effects in the skin medium with melanoma are analyzed. Frequency domain analysis is used as a main tool to investigate such issues as minimum detectable size of melanoma, filtering spectra from noise and from computational irregularities, as well as on how the FEM model meshing size and computational capabilities influence the accuracy of the results. Based on the aforementioned aspects, the analysis of the signals under the scrutiny of the phase velocity dispersion curve is verified to be a reliable, a sensitive, and a promising approach for detecting and characterizing melanoma in human skin.

  9. Simulation study of melanoma detection in human skin tissues by laser-generated surface acoustic waves

    Science.gov (United States)

    Chen, Kun; Fu, Xing; Dorantes-Gonzalez, Dante J.; Lu, Zimo; Li, Tingting; Li, Yanning; Wu, Sen; Hu, Xiaotang

    2014-07-01

    Air pollution has been correlated to an increasing number of cases of human skin diseases in recent years. However, the investigation of human skin tissues has received only limited attention, to the point that there are not yet satisfactory modern detection technologies to accurately, noninvasively, and rapidly diagnose human skin at epidermis and dermis levels. In order to detect and analyze severe skin diseases such as melanoma, a finite element method (FEM) simulation study of the application of the laser-generated surface acoustic wave (LSAW) technique is developed. A three-layer human skin model is built, where LSAW's are generated and propagated, and their effects in the skin medium with melanoma are analyzed. Frequency domain analysis is used as a main tool to investigate such issues as minimum detectable size of melanoma, filtering spectra from noise and from computational irregularities, as well as on how the FEM model meshing size and computational capabilities influence the accuracy of the results. Based on the aforementioned aspects, the analysis of the signals under the scrutiny of the phase velocity dispersion curve is verified to be a reliable, a sensitive, and a promising approach for detecting and characterizing melanoma in human skin.

  10. Combinations of Radiation Therapy and Immunotherapy for Melanoma: A Review of Clinical Outcomes

    International Nuclear Information System (INIS)

    Barker, Christopher A.; Postow, Michael A.

    2014-01-01

    Radiation therapy has long played a role in the management of melanoma. Recent advances have also demonstrated the efficacy of immunotherapy in the treatment of melanoma. Preclinical data suggest a biologic interaction between radiation therapy and immunotherapy. Several clinical studies corroborate these findings. This review will summarize the outcomes of studies reporting on patients with melanoma treated with a combination of radiation therapy and immunotherapy. Vaccine therapies often use irradiated melanoma cells, and may be enhanced by radiation therapy. The cytokines interferon-α and interleukin-2 have been combined with radiation therapy in several small studies, with some evidence suggesting increased toxicity and/or efficacy. Ipilimumab, a monoclonal antibody which blocks cytotoxic T-lymphocyte antigen-4, has been combined with radiation therapy in several notable case studies and series. Finally, pilot studies of adoptive cell transfer have suggested that radiation therapy may improve the efficacy of treatment. The review will demonstrate that the combination of radiation therapy and immunotherapy has been reported in several notable case studies, series and clinical trials. These clinical results suggest interaction and the need for further study

  11. Combinations of Radiation Therapy and Immunotherapy for Melanoma: A Review of Clinical Outcomes

    Energy Technology Data Exchange (ETDEWEB)

    Barker, Christopher A., E-mail: barkerc@mskcc.org [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Postow, Michael A. [Department of Medicine, Melanoma and Sarcoma Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, New York (United States)

    2014-04-01

    Radiation therapy has long played a role in the management of melanoma. Recent advances have also demonstrated the efficacy of immunotherapy in the treatment of melanoma. Preclinical data suggest a biologic interaction between radiation therapy and immunotherapy. Several clinical studies corroborate these findings. This review will summarize the outcomes of studies reporting on patients with melanoma treated with a combination of radiation therapy and immunotherapy. Vaccine therapies often use irradiated melanoma cells, and may be enhanced by radiation therapy. The cytokines interferon-α and interleukin-2 have been combined with radiation therapy in several small studies, with some evidence suggesting increased toxicity and/or efficacy. Ipilimumab, a monoclonal antibody which blocks cytotoxic T-lymphocyte antigen-4, has been combined with radiation therapy in several notable case studies and series. Finally, pilot studies of adoptive cell transfer have suggested that radiation therapy may improve the efficacy of treatment. The review will demonstrate that the combination of radiation therapy and immunotherapy has been reported in several notable case studies, series and clinical trials. These clinical results suggest interaction and the need for further study.

  12. Retrospective study of 338 canine oral melanomas with clinical, histologic, and immunohistochemical review of 129 cases.

    Science.gov (United States)

    Ramos-Vara, J A; Beissenherz, M E; Miller, M A; Johnson, G C; Pace, L W; Fard, A; Kottler, S J

    2000-11-01

    Diagnostic records from 338 canine oral melanomas in 338 dogs received at the Veterinary Medical Diagnostic Laboratory (1992-1999) were reviewed. Of these tumors, 122 plus an additional 7 metastatic melanomas of unknown origin were selected for clinical follow-up, histologic review, and immunohistochemistry. Chow Chow, Golden Retriever, and Pekingese/Poodle mix breeds were overrepresented, whereas Boxer and German Shepherd breeds were underrepresented. There was no gender predisposition and the average age at presentation was 11.4 years. Forty-nine dogs were euthanized due to recurrence or metastasis. The average postsurgical survival time was 173 days. The gingiva and the labial mucosa were the most common sites. Most tumors were composed of either polygonal cells (27 cases, 20.9%), spindle cells (44 cases, 34.1%), or a mixture of the two (polygonal and spindle) (54 cases, 41.9%). Clear cell (3 cases, 2.3%) and adenoid/papillary (1 case, 0.8%) patterns were uncommon. The metastases of 6/6 oral melanomas had morphologic and immunohistochemical features similar to those of the primary tumors. Immunohistochemically, Melan A was detected in 113/122 oral (92.6%) and 5/7 (71.9%) metastatic melanomas. Only 4/163 nonmelanocytic tumors were focally and weakly positive for Melan A. Antibodies against vimentin, S100 protein, and neuron-specific enolase stained 129 (100%), 98 (76%), and 115 (89.1%) of 129 melanomas, respectively. Antibodies against other melanocytic-associated antigens (tyrosinase, glycoprotein 100) did not yield adequate staining. We conclude that Melan A is a specific and sensitive marker for canine melanomas.

  13. Primary Sinonasal Malignant Melanoma: Effect of Clinical and Histopathologic Prognostic Factors on Survival

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    Sercan Göde

    2017-06-01

    Full Text Available Background: Mucosal melanoma is a rare malignancy arising from melanocytes of the mucosal surfaces. The pattern and frequency of oncogenic mutations and histopathological biomarkers have a role on distinct tumour behaviour and survival. Aims: To assess the rate of C-KIT positivity and its effect on survival of surgically treated sinonasal malignant melanoma patients with other histopathological biomarkers and clinical features. Study Design: Retrospective cross-sectional study. Methods: Seventeen sinonasal malignant melanoma patients with a mean age of 65.41 (39-86 years were included. Overall survival and disease-specific survival rates were calculated. The impact of age, gender, stage and extent of the disease, type of surgery, and adjuvant therapies were also taken into consideration. The effect of mitotic index, pigmentation, S100, HMB-45, Melan-A and C-KIT on survival were evaluated. Results: Median tumour size was 20 mm (interquartile range=27.5 mm. Pigmentation was present in 7 (41.2% cases. Median number of mitoses per millimetre squared was 11 (interquartile range=13. Melan A was positive in 7 (41.2% patients, ulceration was present in 6 cases (35.3%, and necrosis was present in (47.1% 8 cases. Six patients (35.3% were positive for S100, 14 (82.4% specimens stained positive for HMB-45 and C-KIT (CD117 was positive in 9 cases (52.9%. Three patients (16.7% developed distant metastasis. Five year overall and disease free survival rates were 61.4% and 43.8%, respectively. Conclusion: Although C-KIT positive sinonasal malignant melanoma patients (52.9% can be candidates for targeted tumour therapies, the studied clinical or histopathological features along with C-KIT seem to have no significant effect on survival in a small group of patients with sinonasal malignant melanoma

  14. Melanoma costs: a dynamic model comparing estimated overall costs of various clinical stages.

    Science.gov (United States)

    Alexandrescu, Doru Traian

    2009-11-15

    The rapidly increasing incidence of melanoma occurs at the same time as an increase in general healthcare costs, particularly the expenses associated with cancer care. Previous cost estimates in melanoma have not utilized a dynamic model considering the evolution of the disease and have not integrated the multiple costs associated with different aspects of medical interventions and patient-related factors. Futhermore, previous calculations have not been updated to reflect the modern tendencies in healthcare costs. We designed a comprehensive model of expenses in melanoma that considers the dynamic costs generated by the natural progression of the disease, which produces costs associated with treatment, surveillance, loss of income, and terminal care. The complete range of initial clinical (TNM) stages of the disease and initial tumor stages were analyzed in this model and the total healthcare costs for the five years following melanoma presentation at each particular stage were calculated. We have observed dramatic incremental total costs associated with progressively higher initial stages of the disease, ranging from a total of $4,648.48 for in situ tumors to $159,808.17 for Stage IV melanoma. By stage, early lesions associate 30-55 percent of their costs for the treatment of the primary tumor, due to a low rate of recurrence (local, regional, or distant), which limits the need for additional interventions. For in situ melanoma, T1a, and T1b, surveillance is an important contributor to the medical costs, accounting for more than 25 percent of the total cost over 5 years. In contrast, late lesions incur a much larger proportion of their associated costs (up to 80-85%) from the diagnosis and treatment of metastatic disease because of the increased propensity of those lesions to disseminate. This cost increases with increasing tumor stage (from $2,442.17 for T1a to $6,678.00 for T4b). The most expensive items in the medical care of patients with melanoma consist of

  15. Tumor-infiltrating CD8+ lymphocytes effect on clinical outcome of muco-cutaneous melanoma

    Directory of Open Access Journals (Sweden)

    Mahtab Rahbar

    2015-01-01

    Full Text Available Background: Recent data have changed our views of prognostic factors in cutaneous melanoma, while some newer methods have yielded better prognostic information. Tumor-infiltrating lymphocytes are believed to represent the immune reaction/response to melanoma cells which is often found in melanocytic cancer. Aim and Objective: We carried out an analysis, aiming to establish pooled estimates for clinical outcomes based on the presence of CD8+ T cell in melanocytic cancer. Materials and Methods: We have included 42 patients with primary cutaneous melanocytic cancer without preoperative treatments in our study. We next analyzed the proliferative activity of CD8+ T cells that infiltrated in tumor cell nests. The intratumoral and adjacent to invasive margin of tumor CD+ T-cell infiltration were analyzed which could also reflect antitumor immunity. Results: The total number of CD8+ cells especially adjacent to invasive margin of tumor was positively correlated with anatomical tumor thickness (P < .001 and not correlated with patient′s age and sex. The stage of tumor which is related to vascular-neural invasion, regional lymph nodes involvement and tumor thickness shows positive correlation with CD8+ infiltration in tumor (P < .004, P < .005, P < .001, respectively. Acral melanoma shows more CD8 lymphocytes infiltration and also recurrence rate of tumor (P < .005. Conclusion: We believe that CD8+ T-cell infiltration in primary cutaneous melanocytic cancer represents the immune reaction/response to melanoma which could be an important new therapy for melanoma although more research is needed on this treatment modality.

  16. Extramammary Paget disease: review of patients seen in a non-melanoma skin cancer clinic.

    Science.gov (United States)

    Pang, J; Assaad, D; Breen, D; Fialkov, J; Antonyshyn, O; Balogh, J; Tsao, M; Kamra, J; Czarnota, G; Barnes, E A

    2010-10-01

    Extramammary Paget disease (EMPD) is a rare skin disease commonly found in the anogenital region. In this study, we aimed to identify EMPD patients seen in the non-melanoma skin cancer clinic at Odette Cancer Centre and to describe the treatments delivered and outcomes achieved. From 2000 to 2009, 14 patients were seen. Initial treatment recommendations included imiquimod and surgical excision, although half the patients required more than one treatment modality, highlighting the difficulty of achieving complete eradication of this disease.

  17. Radiation therapy of malignant melanomas: an evaluation of clinically used fractionation schemes

    International Nuclear Information System (INIS)

    Strauss, A.; Dritschilo, A.; Nathanson, L.; Piro, A.J.

    1981-01-01

    To assess the importance of radiation dose fraction size in the treatment of malignant melanomas, the records of 48 patients (83 sites) treated at Tufts-New England Medical Center from 1971 to 1979 have been retrospectively reviewed. During this period, the dose fractionation schemes evolved from standard fraction size to large-dose techniques. Radiation fraction size was observed to be the major factor in the clinical response of melanoma. Fractions of 600 to 800 rad resulted in the best overall response (80%). The rapid fractionation scheme of 800 to 400 to 400 rad on successive days resulted in intermediate response (58%) and may be useful for the palliative treatment of selected patients

  18. Malignant melanoma arising in congenital melanocytic nevi: clinical and dermoscopic challenges

    Directory of Open Access Journals (Sweden)

    Fatma Pelin Cengiz

    2017-01-01

    Full Text Available Congenital melanocytic nevi (CMN are visible pigmented lesions in the skin that are present at birth. CMN are benign malformations resulting from defective development of melanocyte precursors in the embryo. Six MMs from six patients were analyzed by clinical and dermoscopic examination. Of the patients, 33.3% were female (N = 2 and 66.6% were male (N = 4. Of the MMs, four (66.6% were superficial spreading MM and two (33.3 % were in situ MM. A reticular pattern was present in the MMs of three patients (50%, a homogeneous pattern was present in the other patients (50% at the base of the MMs. Superficial spreading melanomas and in situ melanomas with atypical dots and globules and a blue-white veil were the most common dermoscopic features of MMs found in CMN.

  19. 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.

  20. Clinical benefit from ipilimumab therapy in melanoma patients may be associated with serum CTLA4 levels

    Directory of Open Access Journals (Sweden)

    Anna M. Leung

    2014-05-01

    Full Text Available Stage IV metastatic melanoma patients historically have a poor prognosis with 5-10% 5-year survival. Ipilimumab, a monoclonal antibody against cytotoxic T-lymphocyte antigen 4 (CTLA4, is one of the first treatments to provide beneficial durable responses in advanced melanoma. However, less than 25% of those treated benefit, treatment is expensive, and side effects can be fatal. Since soluble (s CTLA4 may mediate inhibitory effects previously ascribed to the membrane-bound isoform (mCTLA4, we hypothesized patients benefiting from ipilimumab have higher serum levels of sCTLA4. We found that higher sCTLA4 levels correlated both with response and improved survival in patients treated with ipilimumab in a small patient cohort (patients with (n=9 and without (n=5 clinical benefit. sCTLA4 levels were statistically higher in ipilimumab-treated patients with response to ipilimumab. In contrast, sCTLA4 levels did not correlate with survival in patients who did not receive ipilimumab (n=11. These preliminary observations provide a previously unrecognized link between serum sCTLA-4 levels and response to ipilimumab as well as to improved survival in ipilimumab-treated melanoma patients and a potential mechanism by which ipilimumab functions.

  1. Improved malignant melanoma prognosis at a consultant-delivered multidisciplinary pigmented lesion clinic in Cork.

    LENUS (Irish Health Repository)

    Field, S

    2012-02-01

    Early detection and excision is the only effective treatment for malignant melanoma. To assess the effect of a consultant-delivered, rapid-access pigmented lesion clinic (PLC) established at the South Infirmary-Victoria University Hospital (SIVUH), we analyzed melanoma tumour-stage prior to (1998-2002) and after (2003-2007) the advent of the PLC. Patients attending SIVUH had a greater proportion of early-stage tumours (65.3%) compared to the rest of Cork (51.2%), County Cork as a whole (56.7%) and all of Ireland (57.4%). The proportion of SIVUH males with early-stage tumours was statistically significantly higher than the rest of County Cork (chi2 = 11.23, P < 0.05). The proportion of patients > 50y with early-stage tumours was also statistically significantly higher than the rest of County Cork (chi2 = 18.88, P < 0.05), the whole of County Cork (chi2 = 7.84, P < 0.05) and all of Ireland (chi2 = 9.67, P < 0.05). We believe that the early detection and improved prognosis of Cork melanoma patients is at least partly due to the PLC.

  2. Improved malignant melanoma prognosis at a consultant-delivered multidisciplinary pigmented lesion clinic in Cork.

    Science.gov (United States)

    Field, S; Deady, S; Fitzgibbon, J; Murphy, M; Comber, H

    2010-02-01

    Early detection and excision is the only effective treatment for malignant melanoma. To assess the effect of a consultant-delivered, rapid-access pigmented lesion clinic (PLC) established at the South Infirmary-Victoria University Hospital (SIVUH), we analyzed melanoma tumour-stage prior to (1998-2002) and after (2003-2007) the advent of the PLC. Patients attending SIVUH had a greater proportion of early-stage tumours (65.3%) compared to the rest of Cork (51.2%), County Cork as a whole (56.7%) and all of Ireland (57.4%). The proportion of SIVUH males with early-stage tumours was statistically significantly higher than the rest of County Cork (chi2 = 11.23, P 50y with early-stage tumours was also statistically significantly higher than the rest of County Cork (chi2 = 18.88, P Cork (chi2 = 7.84, P Cork melanoma patients is at least partly due to the PLC.

  3. Improved malignant melanoma prognosis at a consultant-delivered multidisciplinary pigmented lesion clinic in Cork.

    LENUS (Irish Health Repository)

    Field, S

    2010-02-01

    Early detection and excision is the only effective treatment for malignant melanoma. To assess the effect of a consultant-delivered, rapid-access pigmented lesion clinic (PLC) established at the South Infirmary-Victoria University Hospital (SIVUH), we analyzed melanoma tumour-stage prior to (1998-2002) and after (2003-2007) the advent of the PLC. Patients attending SIVUH had a greater proportion of early-stage tumours (65.3%) compared to the rest of Cork (51.2%), County Cork as a whole (56.7%) and all of Ireland (57.4%). The proportion of SIVUH males with early-stage tumours was statistically significantly higher than the rest of County Cork (chi2 = 11.23, P < 0.05). The proportion of patients > 50y with early-stage tumours was also statistically significantly higher than the rest of County Cork (chi2 = 18.88, P < 0.05), the whole of County Cork (chi2 = 7.84, P < 0.05) and all of Ireland (chi2 = 9.67, P < 0.05). We believe that the early detection and improved prognosis of Cork melanoma patients is at least partly due to the PLC.

  4. Dendritic cell-based vaccine in advanced melanoma: update of clinical outcome.

    Science.gov (United States)

    Ridolfi, Laura; Petrini, Massimiliano; Fiammenghi, Laura; Granato, Anna Maria; Ancarani, Valentina; Pancisi, Elena; Brolli, Claudia; Selva, Mirna; Scarpi, Emanuela; Valmorri, Linda; Nicoletti, Stefania Vittoria Luisa; Guidoboni, Massimo; Riccobon, Angela; Ridolfi, Ruggero

    2011-12-01

    Dendritic cells (DCs) are unique specialized antigen-presenting cells capable of priming naive T cells and inducing antigen-specific cytotoxic T lymphocytes. This study presents an update of clinical results from a DC-based phase I-II clinical vaccine trial in stage IV melanoma. From 2003 to 2010, 27 patients with metastatic melanoma were treated with mature DCs pulsed with autologous tumor lysate and keyhole limpet hemocyanin and with subcutaneous low-dose interleukin-2. Delayed-type hypersensitivity (DTH) tests for in-vivo immunomonitoring were performed at baseline and every four vaccinations thereafter. Two complete, two mixed and six partial responses, and five stable diseases were observed (overall response, 37.0%; clinical benefit, 55.5%). All 15 responders showed DTH positivity. A median overall survival of 22.9 months [95% confidence interval (CI): 13.4-61.3] for DTH-positive patients (19) and 4.8 months (95% CI: 3.9-11.9) for DTH-negative patients (8; log rank=7.26; P=0.007) was observed. The overall median overall survival was 16 months (95% CI: 9-33). Our results would seem to highlight a relationship between positive-DTH test and an improved survival.

  5. Primary ovarian malignant melanoma

    Directory of Open Access Journals (Sweden)

    Kostov Miloš

    2010-01-01

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

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

    International Nuclear Information System (INIS)

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

    1998-01-01

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

  7. Nonoverlapping Clinical and Mutational Patterns in Melanomas from the Female Genital Tract and Atypical Genital Nevi.

    Science.gov (United States)

    Yélamos, Oriol; Merkel, Emily A; Sholl, Lauren Meldi; Zhang, Bin; Amin, Sapna M; Lee, Christina Y; Guitart, Gerta E; Yang, Jingyi; Wenzel, Alexander T; Bunick, Christopher G; Yazdan, Pedram; Choi, Jaehyuk; Gerami, Pedram

    2016-09-01

    Genital melanomas (GM) are the second most common cancer of the female external genitalia and may be confused with atypical genital nevi (AGN), which exhibit atypical histological features but have benign behavior. In this study, we compared the clinical, histological, and molecular features of 19 GM and 25 AGN. We described chromosomal copy number aberrations and the mutational status of 50 oncogenes and tumor suppressor genes in both groups. Our study showed that a pigmented lesion occurring in mucosal tissue, particularly in postmenopausal women, was more likely to be a melanoma than a nevus. GM had high levels of chromosomal instability, with many copy number aberrations. Furthermore, we found a completely nonoverlapping pattern of oncogenic mutations when comparing GM and AGN. In GM, we report somatic mutations in KIT and TP53. Conversely, AGN had frequent BRAF V600E mutations, which were not seen in any of the GM. Our results show that GM and AGN have distinct clinical and molecular changes and that GM have a different mutational pattern compared with AGN. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  8. [Clinical Simulation and Emotional Learning].

    Science.gov (United States)

    Afanador, Adalberto Amaya

    2012-01-01

    At present, the clinical simulation has been incorporated into medical school curriculum. It is considered that the simulation is useful to develop skills, and as such its diffusion. Within the acquisition of skills, meaningful learning is an essential emotional component for the student and this point is essential to optimize the results of the simulation experience. Narrative description on the subject of simulation and the degree of "emotionality." The taxonomy is described for the types of clinical simulation fidelity and correlates it with the degree of emotionality required to achieve significant and lasting learning by students. It is essential to take into account the student's level of emotion in the learning process through simulation strategy. Copyright © 2012 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  9. 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.

  10. Assessing the clinical utility of measuring Insulin-like Growth Factor Binding Proteins in tissues and sera of melanoma patients

    Directory of Open Access Journals (Sweden)

    Buckley Michael T

    2008-11-01

    Full Text Available Abstract Background Different Insulin-like Growth Factor Binding Proteins (IGFBPs have been investigated as potential biomarkers in several types of tumors. In this study, we examined both IGFBP-3 and -4 levels in tissues and sera of melanoma patients representing different stages of melanoma progression. Methods The study cohort consisted of 132 melanoma patients (primary, n = 72; metastatic, n = 60; 64 Male, 68 Female; Median Age = 56 prospectively enrolled in the New York University School of Medicine Interdisciplinary Melanoma Cooperative Group (NYU IMCG between August 2002 and December 2006. We assessed tumor-expression and circulating sera levels of IGFBP-3 and -4 using immunohistochemistry and ELISA assays. Correlations with clinicopathologic parameters were examined using Wilcoxon rank-sum tests and Spearman-rank correlation coefficients. Results Median IGFBP-4 tumor expression was significantly greater in primary versus metastatic patients (70% versus 10%, p = 0.01 A trend for greater median IGFBP-3 sera concentration was observed in metastatic versus primary patients (4.9 μg/ml vs. 3.4 μg/ml, respectively, p = 0.09. However, sera levels fell within a normal range for IGFBP-3. Neither IGFBP-3 nor -4 correlated with survival in this subset of patients. Conclusion Decreased IGFBP-4 tumor expression might be a step in the progression from primary to metastatic melanoma. Our data lend support to a recently-described novel tumor suppressor role of secreting IGFBPs in melanoma. However, data do not support the clinical utility of measuring levels of IGFBP-3 and -4 in sera of melanoma patients.

  11. Clinical Perspective of 3D Total Body Photography for Early Detection and Screening of Melanoma.

    Science.gov (United States)

    Rayner, Jenna E; Laino, Antonia M; Nufer, Kaitlin L; Adams, Laura; Raphael, Anthony P; Menzies, Scott W; Soyer, H Peter

    2018-01-01

    Melanoma incidence continues to increase across many populations globally and there is significant mortality associated with advanced disease. However, if detected early, patients have a very promising prognosis. The methods that have been utilized for early detection include clinician and patient skin examinations, dermoscopy (static and sequential imaging), and total body photography via 2D imaging. Total body photography has recently witnessed an evolution from 2D imaging with the ability to now create a 3D representation of the patient linked with dermoscopy images of individual lesions. 3D total body photography is a particularly beneficial screening tool for patients at high risk due to their personal or family history or those with multiple dysplastic naevi-the latter can make monitoring especially difficult without the assistance of technology. In this perspective, we discuss clinical examples utilizing 3D total body photography, associated advantages and limitations, and future directions of the technology. The optimal system for melanoma screening should improve diagnostic accuracy, be time and cost efficient, and accessible to patients across all demographic and socioeconomic groups. 3D total body photography has the potential to address these criteria and, most importantly, optimize crucial early detection.

  12. 131/123 iodine labeled benzamides for the detection of melanomas and metastases. Synthesis, labeling, animal experiences and preliminary clinical studies

    International Nuclear Information System (INIS)

    Pozzi, Oscar R.; Edreira, Martin M.; Castiglia, Silvia G.; Soroa, Victoria E.

    1999-01-01

    Radioiodine labeled benzamides are being studied as radiopharmaceuticals for the detection of melanomas and metastases. With this purpose the synthesis and labeling of N-(2-diethylaminoethyl)-3-[ 131 I]-4-methoxybenzamide (IMBA) has been carried out. Tissue distribution of the labeled compound has been studied in C 57 mice, showing a fast renal excretion. The labeled benzamide was also injected in mice with previously induced subcutaneous melanomas and lung metastases using B 16-F0 murine melanoma cells. The tumors show a good uptake of the labeled benzamide. The melanoma/other tissues uptake ratio is suitable for scintigraphic detection. Clinical studies in patients are under way. (author)

  13. Monte Carlo simulations for optimal light delivery in photodynamic therapy of non-melanoma skin cancer

    International Nuclear Information System (INIS)

    Valentine, R M; Ibbotson, S H; Moseley, H; Wood, K; Brown, C T A

    2012-01-01

    The choice of light source is important for the efficacy of photodynamic therapy (PDT) of non-melanoma skin cancer. We simulated the photodynamic dose (PDD) delivered to a tumour during PDT using theoretical radiation transfer simulations performed via our 3D Monte Carlo radiation transfer (MCRT) model for a range of light sources with light doses up to 75 J cm −2 . The PDD delivered following superficial irradiation from (A) non-laser light sources, (B) monochromatic light, (C) alternate beam diameters and (D) re-positioning of the tumour within the tissue was computed. (A) The final PDD deposited to the tumour at a depth of 2 mm by the Paterson light source was 2.75, 2.50 and 1.04 times greater than the Waldmann 1200, Photocure and Aktilite, respectively. (B) Tumour necrosis occurred at a depth of 2.23 mm and increased to 3.81 mm for wavelengths 405 and 630 nm, respectively. (C) Increasing the beam diameter from 10 to 50 mm had very little effect on depth of necrosis. (D) As expected, necrosis depths were reduced when the tumour was re-positioned deeper into the tissue. These MCRT simulations show clearly the importance of choosing the correct light source to ensure optimal light delivery to achieve tumour necrosis. (paper)

  14. Monte Carlo simulation of a protontherapy platform devoted to ocular melanoma

    International Nuclear Information System (INIS)

    Herault, J.; Iborra, N.; Serrano, B.; Chauvel, P.

    2005-01-01

    Patients with ocular melanoma have been treated since June 1991 at the medical cyclotron of the Centre Antoine Lacassagne (CAL). Positions and sizes of the ocular nozzle elements were initially defined based on experimental work, taking as a pattern functional existing facilities. Nowadays Monte Carlo (MC) calculation offers a tool to refine this geometry by adjusting size and place of beam modeling devices. Moreover, the MC tool is a useful way to calculate the dose and to evaluate the impact of secondary particles in the field of radiotherapy or radiation protection. Both LINAC and cyclotron producing x rays, electrons, protons, and neutrons are available in CAL, which suggests choosing MCNPX for its particle versatility. As a first step, the existing installation was input in MCNPX to check its aptitude to reproduce experimentally measured depth-dose profile, lateral profile, output-factor (OF), and absolute dose. The geometry was defined precisely and described from the last achromatic bending magnet of our proton beam line to the position of treated eyes. Relative comparisons of percentage depth-dose and lateral profiles, performed between measured data and simulations, show an agreement of the order of 2% in dose and 0.1 mm in range accuracy. These comparisons, carried out with and without beam-modifying device, yield results compatible to the required precision in ocular melanoma treatments, as long as adequate choices are made on MCNPX input decks for physics card. Absolute dose and OF issued from calculations and measurements were also compared. Results obtained for these two kinds of data, carried out in the simplified situation of an unmodulated beam, indicate that MC calculation could effectively complement measurements. These encouraging results are a large source of motivation to promote further studies, first in a new design of the ocular nozzle, and second in the analysis of the influence of beam-modifying devices attached to the final patient

  15. 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

  16. Correlation between vitiligo occurrence and clinical benefit in advanced melanoma patients treated with nivolumab: A multi-institutional retrospective study.

    Science.gov (United States)

    Nakamura, Yasuhiro; Tanaka, Ryota; Asami, Yuri; Teramoto, Yukiko; Imamura, Taichi; Sato, Sayuri; Maruyama, Hiroshi; Fujisawa, Yasuhiro; Matsuya, Taisuke; Fujimoto, Manabu; Yamamoto, Akifumi

    2017-02-01

    Vitiligo is occasionally seen in melanoma patients. Although several studies indicate a correlation between vitiligo occurrence and clinical response in melanoma patients receiving immunotherapy, most studies have included heterogeneous patient and treatment settings. The aim of this study is to investigate the correlation between the occurrence of vitiligo and clinical benefit of nivolumab treatment in advanced melanoma patients. We retrospectively reviewed unresectable stage III or IV melanoma patients treated with nivolumab. Of 35 melanoma patients treated with nivolumab, 25.7% (9/35) developed vitiligo during treatment. The time from the start of nivolumab treatment to occurrence of vitiligo ranged 2-9 months (mean, 5.2). Of nine patients who developed vitiligo, two (22.2%) had a complete response to nivolumab and two (22.2%) had a partial response. The objective response rate was significantly higher in patients with vitiligo than in patients without vitiligo (4/9 [44.4%] vs 2/26 [7.7%]; P = 0.027). The mean time to vitiligo occurrence in patients achieving an objective response was significantly less than that in patients who showed no response (3.1 vs 6.8 months, P = 0.004). Vitiligo occurrence was significantly associated with prolonged progression-free and overall survival (hazard ratio, 0.24 and 0.16; 95% confidence interval, 0.11-0.55 and 0.03-0.79; P = 0.005, and 0.047, respectively). At the 20-week landmark analysis, however, vitiligo was not associated with a statistically significant overall survival benefit (P = 0.28). The occurrence of vitiligo during nivolumab treatment may be correlated with favorable clinical outcome. © 2016 Japanese Dermatological Association.

  17. 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.

  18. Primary melanoma lung purposely clinico pathologic considerations of a clinical case

    International Nuclear Information System (INIS)

    Rodríguez, R.; Roldán, G.; Sosa, A.; Mañana, G.; Rodríguez, A.; Panuncio, A.

    2004-01-01

    Introduction: There are few reports of primary malignant melanomas (M M) of visceral organs, general case of metastatic cutaneous and ocular M M regression suffering go unnoticed or diagnosis. Cases of lung primary melanomas (MPP) that meet the clinico pathologic to be considered as such criteria constitute about 0.01% lung tumors and are published as individual case analysis is impossible series of patients. These criteria are under constant review, constituting a field permanent controversial.Materials and method: A case review of the clinical literature on the most relevant of MPP clinico pathological aspects is performed. Case: This is a patient (Pt), 58 years old, smoker, who consults for elements progressive intracranial hypertension installation without other symptoms to note. the Computed tomography (CT) of the skull shows an expansive process only right temporal. Radiography and CT of the chest then show a right parahiliar single nodule without liver involvement without mediastinal symphadenopathy. Flexible bronchoscopy and bronchial brushing are negative. With the proposition that it is a bearer of a lung carcinoma with second only symptomatic brain macroscopically complete resection is performed head injury. The pathology reports that metastasis is a M M. Is discarded the presence of other injuries, especially to skin and eye. Receive brain radiotherapy and a right lower lobectomy whose analysis confirms that this is a M M is performed and that no there are other lesions in the resected lobe. Analyzed the cost / benefit profile indication treatment (t to) with systemic disease in the absence of other obvious injuries continues regular clinical exams. Remained asymptomatic for 5 months relapsing to brain level no new lesions in the lungs. The p te refuses to receive palliative systemic t to reaching, to the presentation of this work, a survival of 11 months. Discussion: Within the clinical criteria that state that is an MPP, the absence of a history of

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

    Science.gov (United States)

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

    2014-10-01

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

  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. Pre-clinical assessment of A-674563 as an anti-melanoma agent

    International Nuclear Information System (INIS)

    Zou, Ying; Fan, Guobiao; Wang, Xuemin

    2016-01-01

    The present study aims to investigate the anti-melanoma activity by an Akt1 specific inhibitor A-674563. We showed that A-674563 was anti-proliferative and cytotoxic when added to human melanoma cells (A375, WM-115 and SK-Mel-2 lines). A-674563 induced caspase-dependent apoptotic death of human melanoma cells, and its cytotoxicity was inhibited with pre-treatment of caspase inhibitors. Further, A-674563 treatment blocked Akt and its downstream S6 Kinase 1 (S6K1) activation in A375 melanoma cells. Significantly, restoring Akt-S6K1 activation via introduction of constitutively-active Akt1 (ca-Akt1) only partially attenuated A-674563's cytotoxicity against A375 cells. Further, A-674563 induced pro-apoptotic ceramide production in A375 cells. Significantly, sphingosine-1-phosphate (S1P) inhibited A-674563-induced ceramide production and subsequent A375 cell apoptosis. On the other hand, co-treatment with the glucosylceramide synthase (GCS) inhibitor PDMP or the cell permeable short-chain ceramide (C6) potentiated A-674563's cytotoxicity against A375 cells. In vivo, A-674563 oral gavage inhibited A375 xenograft growth in severe combined immunodeficiency (scid) mice. Akt inactivation, caspase-3 activation and ceramide production were also observed in A-674563-treated A375 xenografts. Together, these results suggest that A-674563 exerts potent anti-melanoma activity, involving Akt-dependent and Akt-independent mechanisms. - Highlights: • A-674563 inhibits human melanoma cell survival and proliferation. • A-674563 induces melanoma cell apoptotic death, inhibited by caspase inhibitors. • A-674563 inhibits melanoma cells via Akt-dependent and -independent mechanisms. • A-674563 induces ceramide production in melanoma cells, independent of Akt inhibition. • A-674563 oral administration potently inhibits A375 xenograft growth in mice.

  2. Pre-clinical assessment of A-674563 as an anti-melanoma agent

    Energy Technology Data Exchange (ETDEWEB)

    Zou, Ying; Fan, Guobiao; Wang, Xuemin, E-mail: wangxuemeidr@yeah.net

    2016-08-12

    The present study aims to investigate the anti-melanoma activity by an Akt1 specific inhibitor A-674563. We showed that A-674563 was anti-proliferative and cytotoxic when added to human melanoma cells (A375, WM-115 and SK-Mel-2 lines). A-674563 induced caspase-dependent apoptotic death of human melanoma cells, and its cytotoxicity was inhibited with pre-treatment of caspase inhibitors. Further, A-674563 treatment blocked Akt and its downstream S6 Kinase 1 (S6K1) activation in A375 melanoma cells. Significantly, restoring Akt-S6K1 activation via introduction of constitutively-active Akt1 (ca-Akt1) only partially attenuated A-674563's cytotoxicity against A375 cells. Further, A-674563 induced pro-apoptotic ceramide production in A375 cells. Significantly, sphingosine-1-phosphate (S1P) inhibited A-674563-induced ceramide production and subsequent A375 cell apoptosis. On the other hand, co-treatment with the glucosylceramide synthase (GCS) inhibitor PDMP or the cell permeable short-chain ceramide (C6) potentiated A-674563's cytotoxicity against A375 cells. In vivo, A-674563 oral gavage inhibited A375 xenograft growth in severe combined immunodeficiency (scid) mice. Akt inactivation, caspase-3 activation and ceramide production were also observed in A-674563-treated A375 xenografts. Together, these results suggest that A-674563 exerts potent anti-melanoma activity, involving Akt-dependent and Akt-independent mechanisms. - Highlights: • A-674563 inhibits human melanoma cell survival and proliferation. • A-674563 induces melanoma cell apoptotic death, inhibited by caspase inhibitors. • A-674563 inhibits melanoma cells via Akt-dependent and -independent mechanisms. • A-674563 induces ceramide production in melanoma cells, independent of Akt inhibition. • A-674563 oral administration potently inhibits A375 xenograft growth in mice.

  3. Malignant melanoma in the penguin: characterization of the clinical, histologic, and immunohistochemical features of malignant melanoma in 10 individuals from three species of penguin.

    Science.gov (United States)

    Duncan, Ann E; Smedley, Rebecca; Anthony, Simon; Garner, Michael M

    2014-09-01

    Malignant melanomas are aggressive neoplasms that are relatively common in penguins compared to other avian species. In this study, the clinical and pathologic characteristics of melanocytic neoplasms in five macaroni (Eudyptes chrysolophus), three rock hopper (Eudyptes chrysocome), and two Humboldt (Spheniscus humboldti) penguins are described. Tumors most commonly occurred in the skin of the foot or hock, and were seen in the subcutaneous muscle, especially near the beak/oral cavity. Gross lesions were usually heavily pigmented, becoming raised and ulcerated over time. Humboldt penguins had a unique presentation, forming variably pigmented, cornified lesions in the inguinal area. Original case materials were obtained from all but two cases, and were assessed to define the characteristics of malignancy, evaluate four immunohistochemical markers for melanoma, and look for factors useful to informing prognosis and clinical decisions. Diagnosis was made histologically, based on morphologic features and pigmentation. Though not necessary for diagnosis, PNL-2 was found to be a useful immunohistochemical marker. HMB-45 showed unreliable positive labelling and S-100, Melan-A and Ki67 were not useful. Several factors were associated with prognosis, including gross surface dimension, mitotic index, depth of neoplastic cell invasion, and degree of surface ulceration. Metastatic spread occurred to the liver, lung, adrenal gland, brain, and bone; all lesions showed positive labelling to PNL-2. The average survival after diagnosis was 7 mo, though complete surgical excision of tumors less than 2.0 cm was curative in two cases and radiation therapy prolonged survival in one penguin. The underlying pathogenesis associated with the high prevalence of melanocytic neoplasms in captive penguins could not be identified. Three different molecular methods were performed to look for viral particles and results were negative. Advanced age is the most probable associated risk factor

  4. Estrogen Receptor ? in Melanoma: From Molecular Insights to Potential Clinical Utility

    OpenAIRE

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

    2016-01-01

    Cutaneous melanoma is an aggressive tumor with its incidence increasing faster than any other cancer in the past decades. Melanoma is a heterogeneous tumor, with most patients harboring mutations in the BRAF or NRAS oncogenes, leading to the overactivation of the MAPK/ERK and PI3K/Akt pathways. The current therapeutic approaches are based on therapies targeting mutated BRAF and the downstream pathway, and on monoclonal antibodies against the immune checkpoint blockade. However, treatment res...

  5. Primary malignant melanoma of the urinary bladder: clinical, morphological, and molecular analysis of five cases.

    Science.gov (United States)

    Karabulut, Yasemin Y; Erdogan, Seyda; Sayar, Hamide; Ergen, Ali; Ertoy Baydar, Dilek

    2016-12-01

    The aim of our study was to evaluate the clinical and morphological features of primary malignant melanomas of the urinary bladder. We obtained information on five such cases from three different institutions. These were three men and two women between 52 and 76 years of age. Three tumors presented with hematuria, one with dysuria, and one was discovered incidentally on imaging studies. All were invasive to muscularis propria on transuretral resections performed for diagnosis. Neoplastic cells showed variable patterns (large cell epithelioid, small cell diffuse, storiform, or mixed) in different tumors. Pigmentation was prominent in all except one case. Each case was labeled diffusely for S-100, HMB-45, and Melan-A. Pan-cytokeratin showed a perinuclear dot-like reaction in two tumors. Three cases showed the BRAF mutation in molecular studies. Two patients were already metastatic at the time of diagnosis. Two patients died, one is alive with disease after 15 months, and two patients are disease free at 1 and 5 years of surveillance.

  6. Estimation of Direct Melanoma-related Costs by Disease Stage and by Phase of Diagnosis and Treatment According to Clinical Guidelines

    Directory of Open Access Journals (Sweden)

    Alessandra Buja

    2017-11-01

    Full Text Available Cutaneous melanoma is a major concern in terms of healthcare systems and economics. The aim of this study was to estimate the direct costs of melanoma by disease stage, phase of diagnosis, and treatment according to the pre-set clinical guidelines drafted by the AIOM (Italian Medical Oncological Association. Based on the AIOM guidelines for malignant cutaneous melanoma, a highly detailed decision-making model was developed describing the patient’s pathway from diagnosis through the subsequent phases of disease staging, surgical and medical treatment, and follow-up. The model associates each phase potentially involving medical procedures with a likelihood measure and a cost, thus enabling an estimation of the expected costs by disease stage and clinical phase of melanoma diagnosis and treatment according to the clinical guidelines. The mean per-patient cost of the whole melanoma pathway (including one year of follow-up ranged from €149 for stage 0 disease to €66,950 for stage IV disease. The costs relating to each phase of the disease’s diagnosis and treatment depended on disease stage. It is essential to calculate the direct costs of managing malignant cutaneous melanoma according to clinical guidelines in order to estimate the economic burden of this disease and to enable policy-makers to allocate appropriate resources.

  7. 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. ...

  8. 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...

  9. Negative argininosuccinate synthetase expression in melanoma tumours may predict clinical benefit from arginine-depleting therapy with pegylated arginine deiminase

    Science.gov (United States)

    Feun, L G; Marini, A; Walker, G; Elgart, G; Moffat, F; Rodgers, S E; Wu, C J; You, M; Wangpaichitr, M; Kuo, M T; Sisson, W; Jungbluth, A A; Bomalaski, J; Savaraj, N

    2012-01-01

    Background: Arginine-depleting therapy with pegylated arginine deiminase (ADI-PEG20) was reported to have activity in advanced melanoma in early phase I–II trial, and clinical trials are currently underway in other cancers. However, the optimal patient population who benefit from this treatment is unknown. Methods: Advanced melanoma patients with accessible tumours had biopsy performed before the start of treatment with ADI-PEG20 and at the time of progression or relapse when amenable to determine whether argininosuccinate synthetase (ASS) expression in tumour was predictive of response to ADI-PEG20. Results: Twenty-seven of thirty-eight patients treated had melanoma tumours assessable for ASS staining before treatment. Clinical benefit rate (CBR) and longer time to progression were associated with negative expression of tumour ASS. Only 1 of 10 patients with ASS-positive tumours (ASS+) had stable disease, whereas 4 of 17 (24%) had partial response and 5 had stable disease, when ASS expression was negative (ASS−), giving CBR rates of 52.9 vs 10%, P=0.041. Two responding patients with negative ASS expression before therapy had rebiopsy after tumour progression and the ASS expression became positive. The survival of ASS− patients receiving at least four doses at 320 IU m−2 was significantly better than the ASS+ group at 26.5 vs 8.5 months, P=0.024. Conclusion: ADI-PEG20 is safe and the drug is only efficacious in melanoma patients whose tumour has negative ASS expression. Argininosuccinate synthetase tumour positivity is associated with drug resistance and tumour progression. PMID:22472884

  10. 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.

  11. A prospective phase II trial exploring the association between tumor microenvironment biomarkers and clinical activity of ipilimumab in advanced melanoma

    Directory of Open Access Journals (Sweden)

    Hamid Omid

    2011-11-01

    Full Text Available Abstract Background Ipilimumab, a fully human monoclonal antibody that blocks cytotoxic T-lymphocyte antigen-4, has demonstrated an improvement in overall survival in two phase III trials of patients with advanced melanoma. The primary objective of the current trial was to prospectively explore candidate biomarkers from the tumor microenvironment for associations with clinical response to ipilimumab. Methods In this randomized, double-blind, phase II biomarker study (ClinicalTrials.gov NCT00261365, 82 pretreated or treatment-naïve patients with unresectable stage III/IV melanoma were induced with 3 or 10 mg/kg ipilimumab every 3 weeks for 4 doses; at Week 24, patients could receive maintenance doses every 12 weeks. Efficacy was evaluated per modified World Health Organization response criteria and safety was assessed continuously. Candidate biomarkers were evaluated in tumor biopsies collected pretreatment and 24 to 72 hours after the second ipilimumab dose. Polymorphisms in immune-related genes were also evaluated. Results Objective response rate, response patterns, and safety were consistent with previous trials of ipilimumab in melanoma. No associations between genetic polymorphisms and clinical activity were observed. Immunohistochemistry and histology on tumor biopsies revealed significant associations between clinical activity and high baseline expression of FoxP3 (p = 0.014 and indoleamine 2,3-dioxygenase (p = 0.012, and between clinical activity and increase in tumor-infiltrating lymphocytes (TILs between baseline and 3 weeks after start of treatment (p = 0.005. Microarray analysis of mRNA from tumor samples taken pretreatment and post-treatment demonstrated significant increases in expression of several immune-related genes, and decreases in expression of genes implicated in cancer and melanoma. Conclusions Baseline expression of immune-related tumor biomarkers and a post-treatment increase in TILs may be positively associated with

  12. 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

  13. 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

  14. Analysis of non-melanoma skin cancer across the tofacitinib rheumatoid arthritis clinical programme.

    Science.gov (United States)

    Curtis, Jeffrey R; Lee, Eun Bong; Martin, George; Mariette, Xavier; Terry, Ketti K; Chen, Yan; Geier, Jamie; Andrews, John; Kaur, Mandeep; Fan, Haiyun; Nduaka, Chudy I

    2017-01-01

    Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We evaluated the incidence of non-melanoma skin cancer (NMSC) across the tofacitinib RA development programme. NMSC events (through August 2013) were identified in patients receiving tofacitinib in two Phase (P)1, eight P2, six P3 and two long-term extension (LTE) studies. In P123 studies, tofacitinib was administered at various doses (1-30 mg twice daily [BID], 20 mg once daily), as monotherapy or with conventional synthetic disease-modifying anti-rheumatic drugs, mainly methotrexate. In LTE studies, patients from qualifying P123 studies received tofacitinib 5 or 10 mg BID. Crude incidence rates (IRs; patients with events/100 patient-years) for first NMSC event were evaluated across doses and over time. In the overall population, comprising data from 18 studies (15,103 patient-years), 83 of 6092 tofacitinib-treated patients had NMSC events. The IR for NMSC (0.55 [95% confidence interval, 0.45-0.69] overall population) was stable up to 84 months of observation. IRs for tofacitinib 5 and 10 mg BID in combined P123 trials were 0.61 (0.34-1.10) and 0.47 (0.24-0.90), respectively. Corresponding IRs for LTE studies were 0.41 (0.26-0.66) and 0.79 (0.60-1.05). The IR for NMSC across the tofacitinib RA clinical development programme was low and remained stable over time. The IR for NMSC in LTE studies was numerically but not significantly higher with tofacitinib 10 versus 5 mg BID; an inverse dose relationship was observed in P123 trials. Longer follow-up is required to confirm these results.

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

    International Nuclear Information System (INIS)

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

    2000-01-01

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

  16. Oral malignant melanoma: A case report of an unusual clinical and histologic presentation

    Directory of Open Access Journals (Sweden)

    Uzma Iqbal Belgaumi

    2013-01-01

    Full Text Available Malignant melanoma is a potentially aggressive tumor of melanocytic origin. Primary oral malignant melanoma is a rare neoplasm, accounting for 0.5% of all oral malignancies. The present case occurred in a 60-year-old female patient, as a pedunculated growth involving the palate and alveolar ridge and histologically showing a desmoplastic differentiation. The article discusses the distinct clinico-pathologic presentation of this case and emphasizes on the need to identify and report such cases for further understanding of their biologic behavior.

  17. 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.

  18. 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...

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

    DEFF Research Database (Denmark)

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

    2008-01-01

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

  20. Analysis of Vδ1 T cells in clinical grade melanoma-infiltrating lymphocytes

    DEFF Research Database (Denmark)

    Donia, Marco; Ellebaek, Eva; Andersen, Mads Hald

    2012-01-01

    . In this study, we have detected low frequencies of Vδ1 T cells among tumor-infiltrating lymphocyte (TIL) products for adoptive cell transfer generated from melanoma metastases. An increased frequency of Vδ1 T cells was found among the cell products from patients with an advanced disease stage. Vδ1 T cells...

  1. Clinical value of FDG-PET in cutaneous malignant melanoma: First experience in Estonia

    International Nuclear Information System (INIS)

    Nazarenko, S.; Niin, M.; Paats, A.; Tonnov, A.

    2004-01-01

    Full text: In November 2002 first 18F-FDG-PET was performed in Estonia using a mobile truck-mounted scanning technology (Accel, Siemens) provided by the International Healthcare Group (IHG, Amersfoort, Netherlands). The FDG was provided by MAP Medical Technologies, Schering, (Helsinki, Finland). In 2003 this scheme was repeated for further scanning sessions. Evaluation of cutaneous malignant melanoma (CMM) using nuclear technique is of particular interest in Estonia as its incidence is on the rise. F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) in CMM has a well-documented high diagnostic accuracy, especially in staging of the disease. The aim of the current study was to assess the impact of 18F-FDG-PET on detailed staging and clinical management in CMM. 30 patients of CMM, 16 males and 14 females, all non-diabetic, in the age range of 26 to 69 years were studied. Of these 30 patients, 12 were of high risk primary CMM, 7 had regional lymph node metastases and 11 had distant metastases. Patients were asked to consume a low-carbohydrate diet 3 days prior to the FDG-PET scan. 194 to 410 MBq (average 335 MBq) 18F-FDG was administered to the patients who were asked to come fasting for a minimum of 6 hours. Whole body scan was performed 40 to 65 minutes after the administration of FDG on the mobile PET. In 13 of the 30 patients (43%) 18F-FDG-PET changed the staging. In remaining 17 patients (57%) 18F-FDG-PET increased confidence level for the chosen treatment. Lymphadenectomy was planned in 2 patients showing lymph node involvement on FDG-PET. In other 2 patients, one with small pulmonary and other with a liver lesions found on PET but negative on radiological examination 'wait-and-watch' strategy was chosen. An unexpected hypermetabolic lesion seen in 1 case turned out to be a benign focus of connective tissue. One patient shown to have multiple distant metastases was started on chemotherapy. Finally in 8 of the 30 (27%) patients an immediate positive

  2. 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...

  3. 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.

  4. Dosimetric Calculations of a Radioactive Eye Plaque used in Management of Ocular Melanoma Using Monte Carlo Simulations

    Directory of Open Access Journals (Sweden)

    P Shokrani

    2009-10-01

    Full Text Available Introduction & Objective: Brachytherapy using I-125 radioactive seeds in removable episcleral plaques (EP is often used in treatment of ocular malignant melanoma. Some radioactive seeds are fixed in a gold bowl-shaped plaque. The plaque is sutured to the sclera surface corresponding to the base of the intraocular tumor, allowing for a localized radiation dose delivery to the tumor. Minimum target doses as high as 85Gy are directed at malignant tumor. The aim of this study was to develop a Monte Carlo simulation of an ocular plaque in order to calculate the resulting isodose distributions. Materials & Methods: The MCNP-4C Monte Carlo code is used to simulate the plan of an episcleral plaque treatment. A 20-mm Collaborative Ocular Melanoma Study (COMS plaque with 3, I-125 seed of model 6711 was used. Resulting dose distributions, including central axis dose and off-axis dose profiles, were calculated in a water phantom with 12mm radius. The calculated dose distributions were compared to the corresponding dose measured by Knuten et al., 2001. Results: Central axis dose calculations represent a rapid dose fall off, which is an important factor in selection of appropriate eye plaque for management of tumors with known dimension. Calculated off-axis dose profiles show decreased dose uniformity at distances close to the plaque. Increasing of distance from the plaque resulted in increasing of the dose uniformity. Conclusion: Monte Carlo simulation of eye plaques can be used as a useful tool in process of design, development and treatment planning of ocular radioactive plaques.

  5. 131/123 iodine labeled benzamides for the detection of melanomas and metastases. Synthesis, labeling, animal experiences and preliminary clinical studies; Benzamidas marcadas con 131/123 iodo para deteccion de melanomas y metastasis. Sintesis, marcacion, estudio en animales y primeros estudios clinicos

    Energy Technology Data Exchange (ETDEWEB)

    Pozzi, Oscar R; Edreira, Martin M; Castiglia, Silvia G [Comision Nacional de Energia Atomica, Ezeiza (Argentina). Dept. de Radioquimica; Zarlenga, Ana C; Arashiro, Jorge G; Parma, P [Instituto de Oncologia Angel H. Roffo, Buenos Aires (Argentina); Soroa, Victoria E [Hospital Clinicas Jose de San Martin, Buenos Aires (Argentina)

    1999-07-01

    Radioiodine labeled benzamides are being studied as radiopharmaceuticals for the detection of melanomas and metastases. With this purpose the synthesis and labeling of N-(2-diethylaminoethyl)-3-[{sup 131}I]-4-methoxybenzamide (IMBA) has been carried out. Tissue distribution of the labeled compound has been studied in C 57 mice, showing a fast renal excretion. The labeled benzamide was also injected in mice with previously induced subcutaneous melanomas and lung metastases using B 16-F0 murine melanoma cells. The tumors show a good uptake of the labeled benzamide. The melanoma/other tissues uptake ratio is suitable for scintigraphic detection. Clinical studies in patients are under way. (author)

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

    DEFF Research Database (Denmark)

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

    2010-01-01

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

  7. Melanoma survivors at high risk of developing new primary disease: a qualitative examination of the factors that contribute to patient satisfaction with clinical care.

    Science.gov (United States)

    McLoone, J K; Watts, K J; Menzies, S W; Barlow-Stewart, K; Mann, G J; Kasparian, N A

    2013-09-01

    Providing ongoing clinical care that adequately addresses patients' medical, psychosocial and information needs is challenging, particularly for patient groups at increased risk of developing life-threatening disease such as malignant melanoma. This study examined a model of clinical care developed by the High Risk Clinic (HRC) of the Sydney Melanoma Diagnostic Centre in relation to patient satisfaction. Semi-structured telephone interviews were conducted and analyzed using the framework of Miles and Huberman, and themes were organized using the qualitative software package, QSR NVivo8. Twenty HRC patients participated in the study (nine men, 11 women; mean age 57.6 years, age range 34-74 years; response rate 91%). Satisfaction with clinical care at the HRC was high. Factors contributing to patient satisfaction included: rapid and regular access to physicians who were perceived by participants as experts, the development of confidence and trust in one's treating doctor, and a sense of being cared about and understood by one's healthcare team. Although one-third of the participants reported some inconveniences in attending the clinic, these were viewed as minor difficulties and not significant barriers to care. Formal psychological support was not sought or expected by participants, although many expressed long-standing melanoma-related fears and concerns. Accessible, expert medical attention, delivered in a patient-centered manner was integral to melanoma survivors' satisfaction with clinical management. Appropriate referrals to psychological support may further increase satisfaction with clinical care. Copyright © 2013 John Wiley & Sons, Ltd.

  8. The clinical role of immunoscintigraphy for the detection of ocular melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Schaling, D.F. [Leiden, Univ. Hospital (Netherlands). Dipt. of Ophtalmology. Dpt. of Diagnostic Radiology and Nuclear Medicine; Pauwels, E.K. [Leiden, Univ. Hospital (Netherlands). Dipt. of Diagnostic Radiology and Nuclear Medicine

    1996-12-01

    The value of immunoscintigraphy in the diagnostic of choroidal melanoma is discussed and compared with other diagnostic procedures with isotopes and diagnostic modalities like fluorescein angiography, standardized ultrasonography and magnetic resonance imaging. Consecutive studies with immunoscintigraphy in choroidal melanoma show a sensitivity of 41 to 49%, witch can be improved by use of single photon emission computerized tomography (SPECT). Another technique which has improved the results of radio-immunoscintigraphy is the use of a three-step labelling procedure with biotinylated anti-tumor antibodies and avidin. The specificity of the 225.288 antibody is discussed with regard to the expression of the chondroitin sulfate proteoglycan (CSPG) - to which the 225.288 antibody is directed - in normal tissue and in other malignant tumours.

  9. Tumor DNA in cerebral spinal fluid reflects clinical course in a patient with melanoma leptomeningeal brain metastases

    Science.gov (United States)

    Li, Yingmei; Pan, Wenying; Connolly, Ian D.; Reddy, Sunil; Nagpal, Seema

    2017-01-01

    Cerebral spinal fluid (CSF) from brain tumor patients contains tumor cellular and cell-free DNA (cfDNA), which provides a less-invasive and routinely accessible method to obtain tumor genomic information. In this report, we used droplet digital PCR to test mutant tumor DNA in CSF of a patient to monitor the treatment response of metastatic melanoma leptomeningeal disease (LMD). The primary melanoma was known to have a BRAFV600E mutation, and the patient was treated with whole brain radiotherapy and BRAF inhibitors. We collected 9 CSF samples over 6 months. The mutant cfDNA fraction gradually decreased from 53 % (time of diagnosis) to 0 (time of symptom alleviation) over the first 6 time points. Three months after clinical improvement, the patient returned with severe symptoms and the mutant cfDNA was again detected in CSF at high levels. The mutant DNA fraction corresponded well with the patient’s clinical response. We used whole exome sequencing to examine the mutation profiles of the LMD tumor DNA in CSF before therapeutic response and after disease relapse, and discovered a canonical cancer mutation PTENR130* at both time points. The cellular and cfDNA revealed similar mutation profiles, suggesting cfDNA is representative of LMD cells. This study demonstrates the potential of using cellular or cfDNA in CSF to monitor treatment response for LMD. PMID:26961773

  10. Design, development, and performance of an adapter for simulation of ocular melanoma patients in supine position for proton beam therapy

    International Nuclear Information System (INIS)

    Daftari, I.; Phillips, T.L.

    2003-01-01

    A patient assembly adapter system for ocular melanoma patient simulation was developed and its performance evaluated. The aim for the construction of the apparatus was to simulate the patients in supine position using a commercial x-ray simulator. The apparatus consists of a base plate, head immobilization holder, patient assembly system that includes fixation light and collimator system. The reproducibility of the repeated fixation was initially tested with a head phantom. Simulation and verification films were studied for seven consecutive patients treated with proton beam therapy. Patient's simulation was performed in a supine position using a dental fixation bite block and a thermoplastic head mask immobilization device with a patient adapter system. Two orthogonal x rays were used to obtain the x, y, and z coordinates of sutured tantalum rings for treatment planning with the EYEPLAN software. The verification films were obtained in treatment position with the fixation light along the central axis of the eye. The results indicate good agreement within 0.5 mm deviations. The results of this investigation showed that the same planning accuracy could be achieved by performing simulation using the adapter described above with a patient in the supine position as that obtained by performing simulation with the patient in the seated, treatment position. The adapter can also be attached to the head of the chair for simulating in the seated position using a fixed x-ray unit. This has three advantages: (1) this will save radiation therapists time; (2) it eliminates the need for arranging access to the treatment room, thus avoiding potential conflicts in treatment room usage; and (3) it allows the use of a commercial simulator

  11. Design, development, and performance of an adapter for simulation of ocular melanoma patients in supine position for proton beam therapy

    Science.gov (United States)

    Daftari, I.; Phillips, T. L.

    2003-06-01

    A patient assembly adapter system for ocular melanoma patient simulation was developed and its performance evaluated. The aim for the construction of the apparatus was to simulate the patients in supine position using a commercial x-ray simulator. The apparatus consists of a base plate, head immobilization holder, patient assembly system that includes fixation light and collimator system. The reproducibility of the repeated fixation was initially tested with a head phantom. Simulation and verification films were studied for seven consecutive patients treated with proton beam therapy. Patient's simulation was performed in a supine position using a dental fixation bite block and a thermoplastic head mask immobilization device with a patient adapter system. Two orthogonal x rays were used to obtain the x, y, and z coordinates of sutured tantalum rings for treatment planning with the EYEPLAN software. The verification films were obtained in treatment position with the fixation light along the central axis of the eye. The results indicate good agreement within 0.5 mm deviations. The results of this investigation showed that the same planning accuracy could be achieved by performing simulation using the adapter described above with a patient in the supine position as that obtained by performing simulation with the patient in the seated, treatment position. The adapter can also be attached to the head of the chair for simulating in the seated position using a fixed x-ray unit. This has three advantages: (1) this will save radiation therapists time; (2) it eliminates the need for arranging access to the treatment room, thus avoiding potential conflicts in treatment room usage; and (3) it allows the use of a commercial simulator.

  12. Safety, correlative markers, and clinical results of adjuvant nivolumab in combination with vaccine in resected high-risk metastatic melanoma.

    Science.gov (United States)

    Gibney, Geoffrey T; Kudchadkar, Ragini R; DeConti, Ronald C; Thebeau, Melissa S; Czupryn, Maria P; Tetteh, Leticia; Eysmans, Cabell; Richards, Allison; Schell, Michael J; Fisher, Kate J; Horak, Christine E; Inzunza, H David; Yu, Bin; Martinez, Alberto J; Younos, Ibrahim; Weber, Jeffrey S

    2015-02-15

    The anti-programmed death-1 (PD-1) antibody nivolumab (BMS-936558) has clinical activity in patients with metastatic melanoma. Nivolumab plus vaccine was investigated as adjuvant therapy in resected stage IIIC and IV melanoma patients. HLA-A*0201 positive patients with HMB-45, NY-ESO-1, and/or MART-1 positive resected tumors received nivolumab (1 mg/kg, 3 mg/kg, or 10 mg/kg i.v.) with a multi-peptide vaccine (gp100, MART-1, and NY-ESO-1 with Montanide ISA 51 VG) every 2 weeks for 12 doses followed by nivolumab maintenance every 12 weeks for 8 doses. Primary objective was safety and determination of a maximum tolerated dose (MTD). Secondary objectives included relapse-free survival (RFS), overall survival (OS), and immunologic correlative studies. Thirty-three patients were enrolled. Median age was 47 years; 55% were male. Two patients had stage IIIC disease; 31 patients had stage IV disease. Median follow-up was 32.1 months. MTD was not reached. Most common related adverse events (>40%) were vaccine injection site reaction, fatigue, rash, pruritus, nausea, and arthralgias. Five related grade 3 adverse events [hypokalemia (1), rash (1), enteritis (1), and colitis (2)] were observed. Ten of 33 patients relapsed. Estimated median RFS was 47.1 months; median OS was not reached. Increases in CTLA-4(+)/CD4(+), CD25(+)Treg/CD4(+), and tetramer specific CD8(+) T-cell populations were observed with treatment (P < 0.05). Trends for lower baseline myeloid-derived suppressor cell and CD25(+)Treg/CD4(+) populations were seen in nonrelapsing patients; PD-L1 tumor status was not significantly associated with RFS. Nivolumab with vaccine is well tolerated as adjuvant therapy and demonstrates immunologic activity with promising survival in high-risk resected melanoma, justifying further study. ©2014 American Association for Cancer Research.

  13. A Prospective Clinical Trial Combining Radiation Therapy With Systemic Immunotherapy in Metastatic Melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Hiniker, Susan M., E-mail: shiniker@stanford.edu [Department of Radiation Oncology, Stanford University Medical Center and Cancer Institute, Stanford, California (United States); Reddy, Sunil A. [Division of Oncology, Department of Medicine, Stanford University Medical Center and Cancer Institute, Stanford, California (United States); Maecker, Holden T.; Subrahmanyam, Priyanka B.; Rosenberg-Hasson, Yael [Human Immune Monitoring Center, Institute for Immunity, Transplantation, and Infection, Stanford University Medical Center, Stanford, California (United States); Swetter, Susan M. [Department of Dermatology, Pigmented Lesion and Melanoma Program, Stanford University Medical Center and Cancer Institute, Stanford, California (United States); Dermatology Service, Veterans Affairs Palo Alto Health Care System, Palo Alto, California (United States); Saha, Saurabh [Atlas Venture, Cambridge, Massachusetts (United States); Shura, Lei; Knox, Susan J. [Department of Radiation Oncology, Stanford University Medical Center and Cancer Institute, Stanford, California (United States)

    2016-11-01

    Purpose: Local radiation therapy (RT) combined with systemic anti-cytotoxic T-lymphocyte–associated protein-4 immunotherapy may enhance induction of systemic antimelanoma immune responses. The primary objective of the present trial was to assess the safety and efficacy of combining ipilimumab with RT in patients with stage IV melanoma. The secondary objectives included laboratory assessment of induction of antimelanoma immune responses. Methods and Materials: In our prospective clinical trial, 22 patients with stage IV melanoma were treated with palliative RT and ipilimumab for 4 cycles. RT to 1 to 2 disease sites was initiated within 5 days after starting ipilimumab. Patients had ≥1 nonirradiated metastasis measuring ≥1.5 cm available for response assessment. Tumor imaging studies were obtained at baseline, 2 to 4 weeks after cycle 4 of ipilimumab, and every 3 months until progression. Laboratory immune response parameters were measured before and during treatment. Results: Combination therapy was well-tolerated without unexpected toxicities. Eleven patients (50.0%) experienced clinical benefit from therapy, including complete and partial responses and stable disease at median follow-up of 55 weeks. Three patients (27.3%) achieved an ongoing systemic complete response at a median follow-up of 55 weeks (range 32-65), and 3 (27.3%) had an initial partial response for a median of 40 weeks. Analysis of immune response data suggested a relationship between elevated CD8-activated T-cells and response. Conclusion: This is the second prospective clinical trial of treatment of metastatic melanoma using the combination of RT and systemic immunotherapy and the first using this sequence of therapy. The results from the present trial demonstrate that a subset of patients may benefit from combination therapy, arguing for continued clinical investigation of the use of RT combined with immunotherapy, including programmed cell death 1 inhibitors, which might have the

  14. A Prospective Clinical Trial Combining Radiation Therapy With Systemic Immunotherapy in Metastatic Melanoma

    International Nuclear Information System (INIS)

    Hiniker, Susan M.; Reddy, Sunil A.; Maecker, Holden T.; Subrahmanyam, Priyanka B.; Rosenberg-Hasson, Yael; Swetter, Susan M.; Saha, Saurabh; Shura, Lei; Knox, Susan J.

    2016-01-01

    Purpose: Local radiation therapy (RT) combined with systemic anti-cytotoxic T-lymphocyte–associated protein-4 immunotherapy may enhance induction of systemic antimelanoma immune responses. The primary objective of the present trial was to assess the safety and efficacy of combining ipilimumab with RT in patients with stage IV melanoma. The secondary objectives included laboratory assessment of induction of antimelanoma immune responses. Methods and Materials: In our prospective clinical trial, 22 patients with stage IV melanoma were treated with palliative RT and ipilimumab for 4 cycles. RT to 1 to 2 disease sites was initiated within 5 days after starting ipilimumab. Patients had ≥1 nonirradiated metastasis measuring ≥1.5 cm available for response assessment. Tumor imaging studies were obtained at baseline, 2 to 4 weeks after cycle 4 of ipilimumab, and every 3 months until progression. Laboratory immune response parameters were measured before and during treatment. Results: Combination therapy was well-tolerated without unexpected toxicities. Eleven patients (50.0%) experienced clinical benefit from therapy, including complete and partial responses and stable disease at median follow-up of 55 weeks. Three patients (27.3%) achieved an ongoing systemic complete response at a median follow-up of 55 weeks (range 32-65), and 3 (27.3%) had an initial partial response for a median of 40 weeks. Analysis of immune response data suggested a relationship between elevated CD8-activated T-cells and response. Conclusion: This is the second prospective clinical trial of treatment of metastatic melanoma using the combination of RT and systemic immunotherapy and the first using this sequence of therapy. The results from the present trial demonstrate that a subset of patients may benefit from combination therapy, arguing for continued clinical investigation of the use of RT combined with immunotherapy, including programmed cell death 1 inhibitors, which might have the

  15. Specialized surveillance for individuals at high risk for melanoma: a cost analysis of a high-risk clinic.

    Science.gov (United States)

    Watts, Caroline G; Cust, Anne E; Menzies, Scott W; Coates, Elliot; Mann, Graham J; Morton, Rachael L

    2015-02-01

    Regular surveillance of individuals at high risk for cutaneous melanoma improves early detection and reduces unnecessary excisions; however, a cost analysis of this specialized service has not been undertaken. To determine the mean cost per patient of surveillance in a high-risk clinic from the health service and societal perspectives. We used a bottom-up microcosting method to measure resource use in a consecutive sample of 102 patients treated in a high-risk hospital-based clinic in Australia during a 12-month period. Surveillance and treatment of melanoma. All surveillance and treatment procedures were identified through direct observation, review of medical records, and interviews with staff and were valued using scheduled fees from the Australian government. Societal costs included transportation and loss of productivity. The mean number of clinic visits per year was 2.7 (95% CI, 2.5-2.8) for surveillance and 3.8 (95% CI, 3.4-4.1) for patients requiring surgical excisions. The mean annual cost per patient to the health system was A $882 (95% CI, A $783-$982) (US $599 [95% CI, US $532-$665]); the cost discounted across 20 years was A $11,546 (95% CI, A $10,263-$12,829) (US $7839 [95% CI, US $6969-$8710]). The mean annual societal cost per patient (excluding health system costs) was A $972 (95% CI, A $899-$1045) (US $660 [95% CI, US $611-$710]); the cost discounted across 20 years was A $12,721 (95% CI, A $12,554-$14,463) (US $8637 [95% CI, US $8523-$9820]). Diagnosis of melanoma or nonmelanoma skin cancer and frequent excisions for benign lesions in a relatively small number of patients was responsible for positively skewed health system costs. Microcosting techniques provide an accurate cost estimate for the provision of a specialized service. The high societal cost reflects the time that patients are willing to invest to attend the high-risk clinic. This alternative model of care for a high-risk population has relevance for decision making about health policy.

  16. Differential Regulation of cGMP Signaling in Human Melanoma Cells at Altered Gravity: Simulated Microgravity Down-Regulates Cancer-Related Gene Expression and Motility

    Science.gov (United States)

    Ivanova, Krassimira; Eiermann, Peter; Tsiockas, Wasiliki; Hemmersbach, Ruth; Gerzer, Rupert

    2018-03-01

    Altered gravity is known to affect cellular function by changes in gene expression and cellular signaling. The intracellular signaling molecule cyclic guanosine-3',5'-monophosphate (cGMP), a product of guanylyl cyclases (GC), e.g., the nitric oxide (NO)-sensitive soluble GC (sGC) or natriuretic peptide-activated GC (GC-A/GC-B), is involved in melanocyte response to environmental stress. NO-sGC-cGMP signaling is operational in human melanocytes and non-metastatic melanoma cells, whereas up-regulated expression of GC-A/GC-B and inducible NO synthase (iNOS) are found in metastatic melanoma cells, the deadliest skin cancer. Here, we investigated the effects of altered gravity on the mRNA expression of NOS isoforms, sGC, GC-A/GC-B and multidrug resistance-associated proteins 4/5 (MRP4/MRP5) as selective cGMP exporters in human melanoma cells with different metastatic potential and pigmentation. A specific centrifuge (DLR, Cologne Germany) was used to generate hypergravity (5 g for 24 h) and a fast-rotating 2-D clinostat (60 rpm) to simulate microgravity values ≤ 0.012 g for 24 h. The results demonstrate that hypergravity up-regulates the endothelial NOS-sGC-MRP4/MRP5 pathway in non-metastatic melanoma cells, but down-regulates it in simulated microgravity when compared to 1 g. Additionally, the suppression of sGC expression and activity has been suggested to correlate inversely to tumor aggressiveness. Finally, hypergravity is ineffective in highly metastatic melanoma cells, whereas simulated microgravity down-regulates predominantly the expression of the cancer-related genes iNOS and GC-A/GC-B (shown additionally on protein levels) as well as motility in comparison to 1 g. The results suggest that future studies in real microgravity can benefit from considering GC-cGMP signaling as possible factor for melanocyte transformation.

  17. 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.

  18. Clinical Benefit of Allogeneic Melanoma Cell Lysate-Pulsed Autologous Dendritic Cell Vaccine in MAGE-Positive Colorectal Cancer Patients

    DEFF Research Database (Denmark)

    Toh, Han Chong; Wang, Who-Whong; Chia, Whay Kuang

    2009-01-01

    PURPOSE: We evaluated the clinical benefit of an allogeneic melanoma cell lysate (MCL)-pulsed autologous dendritic cell (DC) vaccine in advanced colorectal cancer patients expressing at least one of six MAGE-A antigens overexpressed by the cell line source of the lysate. EXPERIMENTAL DESIGN: DCs...... were cultured from peripheral blood mononuclear cells (PBMC), pulsed with the allogeneic MCL, and matured using cytokines that achieved high CD83- and CCR7-expressing DCs. Each patient received up to 10 intradermal vaccinations (3-5 x 10(6) cells per dose) at biweekly intervals. RESULTS: Twenty......-free for >27 and >37 months, respectively. This result is particularly meaningful as all patients had progressive disease before treatment. Overall, DC vaccination was associated with a serial decline in regulatory T cells. Using an antibody array, we characterized plasma protein profiles in responding...

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

    International Nuclear Information System (INIS)

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

    2005-01-01

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

  20. Skin examination behavior: the role of melanoma history, skin type, psychosocial factors, and region of residence in determining clinical and self-conducted skin examination.

    Science.gov (United States)

    Kasparian, Nadine A; Bränström, Richard; Chang, Yu-mei; Affleck, Paul; Aspinwall, Lisa G; Tibben, Aad; Azizi, Esther; Baron-Epel, Orna; Battistuzzi, Linda; Bruno, William; Chan, May; Cuellar, Francisco; Debniak, Tadeusz; Pjanova, Dace; Ertmanski, Slawomir; Figl, Adina; Gonzalez, Melinda; Hayward, Nicholas K; Hocevar, Marko; Kanetsky, Peter A; Leachman, Sancy; Bergman, Wilma; Heisele, Olita; Palmer, Jane; Peric, Barbara; Puig, Susana; Schadendorf, Dirk; Gruis, Nelleke A; Newton-Bishop, Julia; Brandberg, Yvonne

    2012-10-01

    To examine the frequency and correlates of skin examination behaviors in an international sample of individuals at varying risk of developing melanoma. A cross-sectional, web-based survey. Data were collected from the general population over a 20-month period on behalf of the Melanoma Genetics Consortium (GenoMEL). A total of 8178 adults from Northern (32%), Central (33%), and Southern (14%) Europe, Australia (13%), and the United States (8%). Self-reported frequency of skin self-examination (SSE) and clinical skin examination (CSE). After adjustment for age and sex, frequency of skin examination was higher in both Australia (odds ratio [OR]SSE=1.80 [99% CI, 1.49-2.18]; ORCSE=2.68 [99% CI, 2.23-3.23]) and the United States (ORSSE=2.28 [99% CI, 1.76-2.94]; ORCSE=3.39 [99% CI, 2.60-4.18]) than in the 3 European regions combined. Within Europe, participants from Southern Europe reported higher rates of SSE than those in Northern Europe (ORSSE=1.61 [99% CI, 1.31-1.97]), and frequency of CSE was higher in both Central (ORCSE=1.47 [99% CI, 1.22-1.78]) and Southern Europe (ORCSE=3.46 [99% CI, 2.78, 4.31]) than in Northern Europe. Skin examination behavior also varied according to melanoma history: participants with no history of melanoma reported the lowest levels of skin examination, while participants with a previous melanoma diagnosis reported the highest levels. After adjustment for region, and taking into account the role of age, sex, skin type, and mole count, engagement in SSE and CSE was associated with a range of psychosocial factors, including perceived risk of developing melanoma; perceived benefits of, and barriers to, skin examination; perceived confidence in one's ability to engage in screening; and social norms. In addition, among those with no history of melanoma, higher cancer-related worry was associated with greater frequency of SSE. Given the strong association between psychosocial factors and skin examination behaviors, particularly among people with

  1. 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

  2. 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.

  3. 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.

  4. [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

  5. Proton therapy of iris melanoma with 50 CGE. Influence of target volume on clinical outcome

    Energy Technology Data Exchange (ETDEWEB)

    Riechardt, Aline I.; Joussen, Antonia M. [Charite University of Medicine, Department of Ophthalmology, Berlin (Germany); Karle, Bettina [Helios Klinikum Emil-von-Behring, Department of Radiation Oncology, Berlin (Germany); Cordini, Dino; Heufelder, Jens [Charite University of Medicine, Department of Ophthalmology, Berlin (Germany); Helmholtz-Zentrum Berlin, Lise-Meitner-Campus, Berlin-Protonen, Berlin (Germany); Budach, Volker [Charite University of Medicine, Department of Radiation Oncology, Berlin (Germany); Gollrad, Johannes [Helmholtz-Zentrum Berlin, Lise-Meitner-Campus, Berlin-Protonen, Berlin (Germany); Charite University of Medicine, Department of Radiation Oncology, Berlin (Germany)

    2017-11-15

    The aim of this study was to evaluate local tumour control, incidence of radiation-induced glaucoma and associated interventions of sector-based and whole anterior segment proton beam therapy (PBT) for the treatment of iris melanoma. We retrospectively analysed the data of 77 patients with iris melanoma who underwent PBT applied as 50 CGE in four daily fractions. Of the patients, 47 received PBT with a circular-shaped collimator and 30 with a conformal sector-shaped target volume. Local control, eye preservation and secondary glaucoma were evaluated. Median follow-up time was 54.9 months. Local tumour control was 100% in patients receiving whole anterior segment irradiation. Two patients developed pigment dispersion in the non-irradiated area after sector-based PBT and received whole anterior segment salvage PBT. The mean volume of ciliary body irradiated was 89.0% and 34.9% for whole anterior segment and lesion-based irradiation, respectively. At the end of follow-up, secondary glaucoma was found in 74.3% of the patients with whole anterior segment irradiation and in 19.2% with sector-based irradiation. Patients with sector-based PBT had a stable visual acuity of logMAR 0.1, while it declined from logMAR 0.1 to 0.4 after whole anterior segment irradiation. We found a significant reduction in radiation-induced secondary glaucoma and glaucoma-associated surgical interventions and stable visual acuity after sector-based irradiation compared with whole anterior segment irradiation. Sector-based irradiation revealed a higher risk for local recurrence, but selected patients with well-circumscribed iris melanoma benefit from applying a lesion-based target volume when treated with sector-based PBT. (orig.) [German] Ziel der Arbeit war es, nach Irismelanomtherapie durch sektorielle oder Ganzfeldbestrahlung mittels Protonentherapie mit 50 CGE (Cobalt-Gray-Aequivalent) Tumorkontrolle, Inzidenz des strahleninduzierten Glaukoms und damit assoziierte Interventionen auszuwerten

  6. 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.

  7. [Clinical and economic evaluation of the introduction of the combinazion trametinib + dabrafenib in the management of advanced melanoma in the Italian market

    Directory of Open Access Journals (Sweden)

    Lorenzo Pradelli

    2016-12-01

    Full Text Available Melanoma is the most aggressive type of all skin cancers. In Italy the incidence is increasing both in men and in women with 13,800 new cases expected in 2016. The advanced melanoma therapy has changed in recent years with the use of immunotherapy and targeted therapies. In particular, treatment with BRAF inhibitors in patients with advanced BRAF V600 mutated melanoma has shown high rates of rapid response and survival. Due to development of acquired resistance with disease progression the rapid response observed with BRAF inhibitor therapy is not long lasting. Combining a BRAF inhibitor with a MEK inhibitor may help to delay the development of resistance and to enhance the antitumor activities with a further increase in the response and survival rate. Trametinib, an inhibitor of MEK kinases, and dabrafenib, an inhibitor of BRAF kinase, have authorizations as monotherapies and in combination with each other for treating adults with unresectable or metastatic melanoma with BRAF V600 mutation. Purpose of this report is to describe the combination in terms of clinical efficacy, safety, and economic impact. In particular, a cost-effectiveness analysis and a budget impact analysis were performed in order to evaluate the combination versus monotherapy and the financial sustainability of trametinib + dabrafenib on the Italian market. [In Italian

  8. NRASQ61K mutated primary leptomeningeal melanoma in a child: case presentation and discussion on clinical and diagnostic implications

    International Nuclear Information System (INIS)

    Angelino, Giulia; De Pasquale, Maria Debora; De Sio, Luigi; Serra, Annalisa; Massimi, Luca; De Vito, Rita; Marrazzo, Antonio; Lancella, Laura; Carai, Andrea; Antonelli, Manila; Giangaspero, Felice; Gessi, Marco; Menchini, Laura; Scarciolla, Laura; Longo, Daniela; Mastronuzzi, Angela

    2016-01-01

    Primary melanocytic neoplasms are rare in the pediatric age. Among them, the pattern of neoplastic meningitis represents a peculiar diagnostic challenge since neuroradiological features may be subtle and cerebrospinal fluid analysis may not be informative. Clinical misdiagnosis of neoplastic meningitis with tuberculous meningitis has been described in few pediatric cases, leading to a significant delay in appropriate management of patients. We describe the case of a child with primary leptomeningeal melanoma (LMM) that was initially misdiagnosed with tuberculous meningitis. We review the clinical and molecular aspects of LMM and discuss on clinical and diagnostic implications. A 27-month-old girl with a 1-week history of vomiting with mild intermittent strabismus underwent Magnetic Resonance Imaging, showing diffuse brainstem and spinal leptomeningeal enhancement. Cerebrospinal fluid analysis was unremarkable. Antitubercular treatment was started without any improvement. A spinal intradural biopsy was suggestive for primary leptomeningeal melanomatosis. Chemotherapy was started, but general clinical conditions progressively worsened and patient died 11 months after diagnosis. Molecular investigations were performed post-mortem on tumor tissue and revealed absence of BRAF V600E , GNAQ Q209 and GNA11 Q209 mutations but the presence of a NRAS Q61K mutation. Our case adds some information to the limited experience of the literature, confirming the presence of the NRAS Q61K mutation in children with melanomatosis. To our knowledge, this is the first case of leptomeningeal melanocytic neoplasms (LMN) without associated skin lesions to harbor this mutation. Isolated LMN presentation might be insidious, mimicking tuberculous meningitis, and should be suspected if no definite diagnosis is possible or if antitubercular treatment does not result in dramatic clinical improvement. Leptomeningeal biopsy should be considered, not only to confirm diagnosis of LMN but also to study

  9. Some Molecular and Clinical Aspects of Genetic Predisposition to Malignant Melanoma and Tumours of Various Site of Origin

    Directory of Open Access Journals (Sweden)

    Dębniak Tadeusz

    2007-06-01

    Full Text Available Abstract Based on epidemiological data we can assume that at least some malignant melanoma (MM and breast cancer cases can be caused by the same genetic factors. CDKN2A, which encodes the p16 protein, a cyclin-dependent kinase inhibitor suppressing cell proliferation, is regarded as a major melanoma susceptibility gene and the literature has also implicated this gene in predisposition to breast cancer. Genes also known to predispose to MM include XPD and MC1R. We studied CDKN2A/ARF, XPD and MC1R for their associations with melanoma and breast cancer risk in Polish patients and controls. We found that CDKN2A and ARF do not contribute significantly to either familial melanoma or malignant melanoma within the context of a cancer familial aggregation of disease with breast cancer. However, the common variant of the CDKN2A gene A148T, previously regarded as non-pathogenic, may predispose to malignant melanoma, early-onset breast cancer and lung cancer. Compound carriers of common XPD variants may be at slightly increased risk of breast cancer or late–onset malignant melanoma. Common recurrent variants of the MC1R gene (V60L, R151C, R163Q and R160W may predispose to malignant melanoma. In general, the establishment of surveillance protocols proposed as an option for carriers of common alterations in CDKN2A, XPD or MC1R variants requires additional studies. It is possible that missense variants of genes for which truncating mutations are clearly pathogenic may also be deleterious, but with reduced penetrance. This may be overlooked unless large numbers of patients and controls are studied. A registry that includes 2000 consecutive breast cancer cases, 3500 early onset breast cancer patients, 500 unselected malignant melanoma and over 700 colorectal cancer patients has been established in the International Hereditary Cancer Centre and can contribute to these types of large association studies.

  10. 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.

  11. 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.

  12. 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

  13. 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.)

  14. 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.

  15. AMP kinase-related kinase NUAK2 affects tumor growth, migration, and clinical outcome of human melanoma.

    Science.gov (United States)

    Namiki, Takeshi; Tanemura, Atsushi; Valencia, Julio C; Coelho, Sergio G; Passeron, Thierry; Kawaguchi, Masakazu; Vieira, Wilfred D; Ishikawa, Masashi; Nishijima, Wataru; Izumo, Toshiyuki; Kaneko, Yasuhiko; Katayama, Ichiro; Yamaguchi, Yuji; Yin, Lanlan; Polley, Eric C; Liu, Hongfang; Kawakami, Yutaka; Eishi, Yoshinobu; Takahashi, Eishi; Yokozeki, Hiroo; Hearing, Vincent J

    2011-04-19

    The identification of genes that participate in melanomagenesis should suggest strategies for developing therapeutic modalities. We used a public array comparative genomic hybridization (CGH) database and real-time quantitative PCR (qPCR) analyses to identify the AMP kinase (AMPK)-related kinase NUAK2 as a candidate gene for melanomagenesis, and we analyzed its functions in melanoma cells. Our analyses had identified a locus at 1q32 where genomic gain is strongly associated with tumor thickness, and we used real-time qPCR analyses and regression analyses to identify NUAK2 as a candidate gene at that locus. Associations of relapse-free survival and overall survival of 92 primary melanoma patients with NUAK2 expression measured using immunohistochemistry were investigated using Kaplan-Meier curves, log rank tests, and Cox regression models. Knockdown of NUAK2 induces senescence and reduces S-phase, decreases migration, and down-regulates expression of mammalian target of rapamycin (mTOR). In vivo analysis demonstrated that knockdown of NUAK2 suppresses melanoma tumor growth in mice. Survival analysis showed that the risk of relapse is greater in acral melanoma patients with high levels of NUAK2 expression than in acral melanoma patients with low levels of NUAK2 expression (hazard ratio = 3.88; 95% confidence interval = 1.44-10.50; P = 0.0075). These data demonstrate that NUAK2 expression is significantly associated with the oncogenic features of melanoma cells and with the survival of acral melanoma patients. NUAK2 may provide a drug target to suppress melanoma progression. This study further supports the importance of NUAK2 in cancer development and tumor progression, while AMPK has antioncogenic properties.

  16. 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.

  17. Whole Brain Radiotherapy and RRx-001: Two Partial Responses in Radioresistant Melanoma Brain Metastases from a Phase I/II Clinical Trial: A TITE-CRM Phase I/II Clinical Trial.

    Science.gov (United States)

    Kim, Michelle M; Parmar, Hemant; Cao, Yue; Pramanik, Priyanka; Schipper, Matthew; Hayman, James; Junck, Larry; Mammoser, Aaron; Heth, Jason; Carter, Corey A; Oronsky, Arnold; Knox, Susan J; Caroen, Scott; Oronsky, Bryan; Scicinski, Jan; Lawrence, Theodore S; Lao, Christopher D

    2016-04-01

    Kim et al. report two patients with melanoma metastases to the brain that responded to treatment with RRx-001 and whole brain radiotherapy (WBRT) without neurologic or systemic toxicity in the context of a phase I/II clinical trial. RRx-001 is an reactive oxygen and reactive nitrogen species (ROS/RNS)-dependent systemically nontoxic hypoxic cell radiosensitizer with vascular normalizing properties under investigation in patients with various solid tumors including those with brain metastases. Metastatic melanoma to the brain is historically associated with poor outcomes and a median survival of 4 to 5 months. WBRT is a mainstay of treatment for patients with multiple brain metastases, but no significant therapeutic advances for these patients have been described in the literature. To date, candidate radiosensitizing agents have failed to demonstrate a survival benefit in patients with brain metastases, and in particular, no agent has demonstrated improved outcome in patients with metastatic melanoma. Kim et al. report two patients with melanoma metastases to the brain that responded to treatment with novel radiosensitizing agent RRx-001 and WBRT without neurologic or systemic toxicity in the context of a phase I/II clinical trial. Published by Elsevier Inc.

  18. 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.

  19. Clinical Macrosystem Simulation Translates Between Organizations.

    Science.gov (United States)

    Bender, G Jesse; Maryman, James A

    2018-04-01

    Simulation has become an integral tool in healthcare facility redesign. Immersing clinical experts into their future environment has demonstrated benefits for transition planning. This study evaluates translation of a proven macrosystems testing protocol, TESTPILOT, to an organization with limited simulation experience. An experienced TESTPILOT team guided Woman's Hospital Baton Rouge's simulation preparation for their new neonatal intensive care unit. Metrics included participant evaluations, latent safety threats (LST), and clinician surveys. Latent safety threats recorded during debriefings were addressed by workflow committees. Clinicians were surveyed at four time points for readiness and preparedness on 24 key processes. The local team invested nearly 750 hours into learning and implementing seven simulations that participants rated positively. Most of the 305 LST were minor issues. Surveys at baseline (42% of staff), postsim (18%), pretransition (26%), and postmove (29%) demonstrated strong internal consistency. System readiness lagged behind staff preparedness (P structure, team coverage, and feedback were still evolving as of move day (P organizations with limited prior exposure. Woman's Hospital Baton Rouge accrued essential skills to model and orchestrate an immersive neonatal intensive care unit and then drive effective multidisciplinary debriefings. Staff immersed in the new environment began to articulate their jobs before moving in. The trajectory of system readiness improvement corroborated LST correction. Future research is needed to determine the extent of simulation required for different organizational structures.

  20. 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.

  1. Clinical training: a simulation program for phlebotomy

    Directory of Open Access Journals (Sweden)

    Araki Toshitaka

    2008-01-01

    Full Text Available Abstract Background Basic clinical skills training in the Japanese medical education system has traditionally incorporated on-the-job training with patients. Recently, the complementary use of simulation techniques as part of this training has gained popularity. It is not known, however, whether the participants view this new type of education program favorably; nor is the impact of this program known. In this study we developed a new simulation-based training program in phlebotomy for new medical residents and assessed their satisfaction with the program Methods The education program comprised two main components: simulator exercise sessions and the actual drawing of blood from other trainees. At the end of the session, we surveyed participant sentiment regarding the program. Results There were 43 participants in total. In general, they were highly satisfied with the education program, with all survey questions receiving scores of 3 or more on a scale of 1–5 (mean range: 4.3 – 4.8, with 5 indicating the highest level of satisfaction. Additionally, their participation as a 'patient' for their co-trainees was undertaken willingly and was deemed to be a valuable experience. Conclusion We developed and tested an education program using a simulator for blood collection. We demonstrated a high satisfaction level among the participants for this unique educational program and expect that it will improve medical training, patient safety, and quality of care. The development and dissemination of similar educational programs involving simulation for other basic clinical skills will be undertaken in the future.

  2. Phase I clinical trial of the vaccination for the patients with metastatic melanoma using gp100-derived epitope peptide restricted to HLA-A*2402

    Directory of Open Access Journals (Sweden)

    Baba Toshiyuki

    2010-09-01

    Full Text Available Abstract Background The tumor associated antigen (TAA gp100 was one of the first identified and has been used in clinical trials to treat melanoma patients. However, the gp100 epitope peptide restricted to HLA-A*2402 has not been extensively examined clinically due to the ethnic variations. Since it is the most common HLA Class I allele in the Japanese population, we performed a phase I clinical trial of cancer vaccination using the HLA-A*2402 gp100 peptide to treat patients with metastatic melanoma. Methods The phase I clinical protocol to test a HLA-A*2402 gp100 peptide-based cancer vaccine was designed to evaluate safety as the primary endpoint and was approved by The University of Tokyo Institutional Review Board. Information related to the immunologic and antitumor responses were also collected as secondary endpoints. Patients that were HLA-A*2402 positive with stage IV melanoma were enrolled according to the criteria set by the protocol and immunized with a vaccine consisting of epitope peptide (VYFFLPDHL, gp100-in4 emulsified with incomplete Freund's adjuvant (IFA for the total of 4 times with two week intervals. Prior to each vaccination, peripheral blood mononuclear cells (PBMCs were separated from the blood and stored at -80°C. The stored PBMCs were thawed and examined for the frequency of the peptide specific T lymphocytes by IFN-γ- ELISPOT and MHC-Dextramer assays. Results No related adverse events greater than grade I were observed in the six patients enrolled in this study. No clinical responses were observed in the enrolled patients although vitiligo was observed after the vaccination in two patients. Promotion of peptide specific immune responses was observed in four patients with ELISPOT assay. Furthermore, a significant increase of CD8+ gp100-in4+ CTLs was observed in all patients using the MHC-Dextramer assay. Cytotoxic T lymphocytes (CTLs clones specific to gp100-in4 were successfully established from the PBMC of some

  3. Unexpected High Response Rate to Traditional Therapy after Dendritic Cell-Based Vaccine in Advanced Melanoma: Update of Clinical Outcome and Subgroup Analysis

    Directory of Open Access Journals (Sweden)

    Laura Ridolfi

    2010-01-01

    Full Text Available We reviewed the clinical results of a dendritic cell-based phase II clinical vaccine trial in stage IV melanoma and analyzed a patient subgroup treated with standard therapies after stopping vaccination. From 2003 to 2009, 24 metastatic melanoma patients were treated with mature dendritic cells pulsed with autologous tumor lysate and keyhole limpet hemocyanin and low-dose interleukin-2. Overall response (OR to vaccination was 37.5% with a clinical benefit of 54.1%. All 14 responders showed delayed type hypersensitivity positivity. Median overall survival (OS was 15 months (95% CI, 8–33. Eleven patients underwent other treatments (3 surgery, 2 biotherapy, 2 radiotherapy, 2 chemotherapy, and 4 biochemotherapy after stopping vaccination. Of these, 2 patients had a complete response and 5 a partial response, with an OR of 63.6%. Median OS was 34 months (range 16–61. Our results suggest that therapeutic DC vaccination could favor clinical response in patients after more than one line of therapy.

  4. Unexpected high response rate to traditional therapy after dendritic cell-based vaccine in advanced melanoma: update of clinical outcome and subgroup analysis.

    Science.gov (United States)

    Ridolfi, Laura; Petrini, Massimiliano; Fiammenghi, Laura; Granato, Anna Maria; Ancarani, Valentina; Pancisi, Elena; Scarpi, Emanuela; Guidoboni, Massimo; Migliori, Giuseppe; Sanna, Stefano; Tauceri, Francesca; Verdecchia, Giorgio Maria; Riccobon, Angela; Valmorri, Linda; Ridolfi, Ruggero

    2010-01-01

    We reviewed the clinical results of a dendritic cell-based phase II clinical vaccine trial in stage IV melanoma and analyzed a patient subgroup treated with standard therapies after stopping vaccination. From 2003 to 2009, 24 metastatic melanoma patients were treated with mature dendritic cells pulsed with autologous tumor lysate and keyhole limpet hemocyanin and low-dose interleukin-2. Overall response (OR) to vaccination was 37.5% with a clinical benefit of 54.1%. All 14 responders showed delayed type hypersensitivity positivity. Median overall survival (OS) was 15 months (95% CI, 8-33). Eleven patients underwent other treatments (3 surgery, 2 biotherapy, 2 radiotherapy, 2 chemotherapy, and 4 biochemotherapy) after stopping vaccination. Of these, 2 patients had a complete response and 5 a partial response, with an OR of 63.6%. Median OS was 34 months (range 16-61). Our results suggest that therapeutic DC vaccination could favor clinical response in patients after more than one line of therapy.

  5. Phase III randomized clinical trial comparing tremelimumab with standard-of-care chemotherapy in patients with advanced melanoma

    NARCIS (Netherlands)

    Ribas, Antoni; Kefford, Richard; Marshall, Margaret A.; Punt, Cornelis J. A.; Haanen, John B.; Marmol, Maribel; Garbe, Claus; Gogas, Helen; Schachter, Jacob; Linette, Gerald; Lorigan, Paul; Kendra, Kari L.; Maio, Michele; Trefzer, Uwe; Smylie, Michael; McArthur, Grant A.; Dreno, Brigitte; Nathan, Paul D.; Mackiewicz, Jacek; Kirkwood, John M.; Gomez-Navarro, Jesus; Huang, Bo; Pavlov, Dmitri; Hauschild, Axel

    2013-01-01

    In phase I/II trials, the cytotoxic T lymphocyte-associated antigen-4-blocking monoclonal antibody tremelimumab induced durable responses in a subset of patients with advanced melanoma. This phase III study evaluated overall survival (OS) and other safety and efficacy end points in patients with

  6. Phase III randomized clinical trial comparing tremelimumab with standard-of-care chemotherapy in patients with advanced melanoma.

    NARCIS (Netherlands)

    Ribas, A.; Kefford, R.; Marshall, Martin; Punt, C.J.A.; Haanen, J.B.; Marmol, M.; Garbe, C.; Gogas, H.; Schachter, J.; Linette, G.; Lorigan, P.; Kendra, K.L.; Maio, M.; Trefzer, U.; Smylie, M.; McArthur, G.A.; Dreno, B.; Nathan, P.D.; Mackiewicz, J.; Kirkwood, J.M.; Gomez-Navarro, J.; Huang, B.; Pavlov, D.; Hauschild, A.

    2013-01-01

    PURPOSE: In phase I/II trials, the cytotoxic T lymphocyte-associated antigen-4-blocking monoclonal antibody tremelimumab induced durable responses in a subset of patients with advanced melanoma. This phase III study evaluated overall survival (OS) and other safety and efficacy end points in patients

  7. Vaccination of metastatic melanoma patients with autologous dendritic cell (DC derived-exosomes: results of thefirst phase I clinical trial

    Directory of Open Access Journals (Sweden)

    Piperno Sophie

    2005-03-01

    Full Text Available Abstract Background DC derived-exosomes are nanomeric vesicles harboring functional MHC/peptide complexes capable of promoting T cell immune responses and tumor rejection. Here we report the feasability and safety of the first Phase I clinical trial using autologous exosomes pulsed with MAGE 3 peptides for the immunization of stage III/IV melanoma patients. Secondary endpoints were the monitoring of T cell responses and the clinical outcome. Patients and methods Exosomes were purified from day 7 autologous monocyte derived-DC cultures. Fifteen patients fullfilling the inclusion criteria (stage IIIB and IV, HLA-A1+, or -B35+ and HLA-DPO4+ leukocyte phenotype, tumor expressing MAGE3 antigen were enrolled from 2000 to 2002 and received four exosome vaccinations. Two dose levels of either MHC class II molecules (0.13 versus 0.40 × 1014 molecules or peptides (10 versus 100 μg/ml were tested. Evaluations were performed before and 2 weeks after immunization. A continuation treatment was performed in 4 cases of non progression. Results The GMP process allowed to harvest about 5 × 1014 exosomal MHC class II molecules allowing inclusion of all 15 patients. There was no grade II toxicity and the maximal tolerated dose was not achieved. One patient exhibited a partial response according to the RECIST criteria. This HLA-B35+/A2+ patient vaccinated with A1/B35 defined CTL epitopes developed halo of depigmentation around naevi, a MART1-specific HLA-A2 restricted T cell response in the tumor bed associated with progressive loss of HLA-A2 and HLA-BC molecules on tumor cells during therapy with exosomes. In addition, one minor, two stable and one mixed responses were observed in skin and lymph node sites. MAGE3 specific CD4+ and CD8+ T cell responses could not be detected in peripheral blood. Conclusion The first exosome Phase I trial highlighted the feasibility of large scale exosome production and the safety of exosome administration.

  8. Adjuvant therapy for melanoma in dogs: results of randomized clinical trials using surgery, liposome-encapsulated muramyl tripeptide, and granulocyte macrophage colony-stimulating factor.

    Science.gov (United States)

    MacEwen, E G; Kurzman, I D; Vail, D M; Dubielzig, R R; Everlith, K; Madewell, B R; Rodriguez, C O; Phillips, B; Zwahlen, C H; Obradovich, J; Rosenthal, R C; Fox, L E; Rosenberg, M; Henry, C; Fidel, J

    1999-12-01

    Spontaneous canine oral melanoma (COM) is a highly metastatic cancer, resistant to chemotherapy, and can serve as a model for cancer immunotherapy. Liposome-encapsulated muramyl tripeptide-phosphatidylethanolamine (L-MTP-PE) can activate the tumoricidal activity of the monocyte-macrophage system following i.v. injection. The objective of these studies was to evaluate the therapeutic effectiveness of L-MTP-PE administered alone and combined with recombinant canine granulocyte macrophage colony-stimulating factor (rcGM-CSF) in dogs undergoing surgery for oral melanoma. Ninety-eight dogs with histologically confirmed, clinically staged, oral melanoma were entered into two randomized, double-blind, surgical adjuvant trials. In trial 1, 50 dogs were stratified based on clinical stage and randomized to once a week L-MTP-PE or lipid equivalent (control). When all of the clinical stages were combined, no difference in disease-free survival or in survival time (ST) were detected. However, within stage I, dogs receiving L-MTP-PE had a significant increase in ST compared with control, with 80% of the dogs treated with L-MTP-PE still alive at >2 years. Within each stage II and stage III, there was no difference detected between the treatment groups. In trial 2, 48 dogs were stratified on the basis of clinical stage and extent of surgery (simple resection or radical excision), treated with L-MTP-PE two times a week, and randomized to rcGM-CSF or saline (placebo) given s.c. daily for 9 weeks. Within each stage and when all of the stages were combined, there was no difference between the treatment groups. In both studies, stage I COM is associated with a better prognosis. No effect on survival was observed with regard to tumor location in the oral cavity, sex, type/extent of surgery, or age. In a subset of dogs tested, pulmonary alveolar macrophage cytotoxicity was enhanced with combined rcGM-CSF and L-MTP-PE but not in dogs treated with L-MTP-PE alone. The present study

  9. 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.

  10. Immunological and biological changes during ipilimumab treatment and their potential correlation with clinical response and survival in patients with advanced melanoma.

    Science.gov (United States)

    Simeone, Ester; Gentilcore, Giusy; Giannarelli, Diana; Grimaldi, Antonio M; Caracò, Corrado; Curvietto, Marcello; Esposito, Assunta; Paone, Miriam; Palla, Marco; Cavalcanti, Ernesta; Sandomenico, Fabio; Petrillo, Antonella; Botti, Gerardo; Fulciniti, Franco; Palmieri, Giuseppe; Queirolo, Paola; Marchetti, Paolo; Ferraresi, Virginia; Rinaldi, Gaetana; Pistillo, Maria Pia; Ciliberto, Gennaro; Mozzillo, Nicola; Ascierto, Paolo A

    2014-07-01

    Ipilimumab can induce durable disease control and long-term survival in patients with metastatic melanoma. Identification of a biomarker that correlates with clinical benefit and potentially provides an early marker of response is an active area of research. Ipilimumab was available upon physician request for patients aged ≥16 years with stage III (unresectable) or IV cutaneous, ocular or mucosal melanoma, who had failed or did not tolerate previous treatments and had no other therapeutic option available. Patients received ipilimumab 3 mg/kg every 3 weeks for four doses. Tumour assessments were conducted at baseline, Week 12 and Week 24 using immune-related response criteria. Patients were monitored continuously for adverse events (AEs), including immune-related AEs. Candidate immunological markers were evaluated in peripheral blood and sera samples collected at baseline and Weeks 4, 7, 10 and 12. Among 95 patients treated with ipilimumab 3 mg/kg, the immune-related disease control rate at Week 24 was 38 %. With a median follow-up of 24 months, median overall survival was 9.6 months. Both disease control and survival were significantly associated with decreasing levels of lactate dehydrogenase, C-reactive protein and FoxP3/regulatory T cells, and increasing absolute lymphocyte count, between baseline and the end of dosing (Week 12). Ipilimumab is a feasible treatment option for heavily pretreated patients with metastatic melanoma. Changes in some immunological markers between baseline and the fourth ipilimumab infusion appear to be associated with disease control and survival, but verification in prospective clinical trials is required.

  11. 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

  12. A canine chimeric monoclonal antibody targeting PD-L1 and its clinical efficacy in canine oral malignant melanoma or undifferentiated sarcoma.

    Science.gov (United States)

    Maekawa, Naoya; Konnai, Satoru; Takagi, Satoshi; Kagawa, Yumiko; Okagawa, Tomohiro; Nishimori, Asami; Ikebuchi, Ryoyo; Izumi, Yusuke; Deguchi, Tatsuya; Nakajima, Chie; Kato, Yukinari; Yamamoto, Keiichi; Uemura, Hidetoshi; Suzuki, Yasuhiko; Murata, Shiro; Ohashi, Kazuhiko

    2017-08-21

    Immunotherapy targeting immune checkpoint molecules, programmed cell death 1 (PD-1) and PD-ligand 1 (PD-L1), using therapeutic antibodies has been widely used for some human malignancies in the last 5 years. A costimulatory receptor, PD-1, is expressed on T cells and suppresses effector functions when it binds to its ligand, PD-L1. Aberrant PD-L1 expression is reported in various human cancers and is considered an immune escape mechanism. Antibodies blocking the PD-1/PD-L1 axis induce antitumour responses in patients with malignant melanoma and other cancers. In dogs, no such clinical studies have been performed to date because of the lack of therapeutic antibodies that can be used in dogs. In this study, the immunomodulatory effects of c4G12, a canine-chimerised anti-PD-L1 monoclonal antibody, were evaluated in vitro, demonstrating significantly enhanced cytokine production and proliferation of dog peripheral blood mononuclear cells. A pilot clinical study was performed on seven dogs with oral malignant melanoma (OMM) and two with undifferentiated sarcoma. Objective antitumour responses were observed in one dog with OMM (14.3%, 1/7) and one with undifferentiated sarcoma (50.0%, 1/2) when c4G12 was given at 2 or 5 mg/kg, every 2 weeks. c4G12 could be a safe and effective treatment option for canine cancers.

  13. Phase III Randomized Clinical Trial Comparing Tremelimumab With Standard-of-Care Chemotherapy in Patients With Advanced Melanoma

    Science.gov (United States)

    Ribas, Antoni; Kefford, Richard; Marshall, Margaret A.; Punt, Cornelis J.A.; Haanen, John B.; Marmol, Maribel; Garbe, Claus; Gogas, Helen; Schachter, Jacob; Linette, Gerald; Lorigan, Paul; Kendra, Kari L.; Maio, Michele; Trefzer, Uwe; Smylie, Michael; McArthur, Grant A.; Dreno, Brigitte; Nathan, Paul D.; Mackiewicz, Jacek; Kirkwood, John M.; Gomez-Navarro, Jesus; Huang, Bo; Pavlov, Dmitri; Hauschild, Axel

    2013-01-01

    Purpose In phase I/II trials, the cytotoxic T lymphocyte–associated antigen-4–blocking monoclonal antibody tremelimumab induced durable responses in a subset of patients with advanced melanoma. This phase III study evaluated overall survival (OS) and other safety and efficacy end points in patients with advanced melanoma treated with tremelimumab or standard-of-care chemotherapy. Patients and Methods Patients with treatment-naive, unresectable stage IIIc or IV melanoma were randomly assigned at a ratio of one to one to tremelimumab (15 mg/kg once every 90 days) or physician's choice of standard-of-care chemotherapy (temozolomide or dacarbazine). Results In all, 655 patients were enrolled and randomly assigned. The test statistic crossed the prespecified futility boundary at second interim analysis after 340 deaths, but survival follow-up continued. At final analysis with 534 events, median OS by intent to treat was 12.6 months (95% CI, 10.8 to 14.3) for tremelimumab and 10.7 months (95% CI, 9.36 to 11.96) for chemotherapy (hazard ratio, 0.88; P = .127). Objective response rates were similar in the two arms: 10.7% in the tremelimumab arm and 9.8% in the chemotherapy arm. However, response duration (measured from date of random assignment) was significantly longer after tremelimumab (35.8 v 13.7 months; P = .0011). Diarrhea, pruritus, and rash were the most common treatment-related adverse events in the tremelimumab arm; 7.4% had endocrine toxicities. Seven deaths in the tremelimumab arm and one in the chemotherapy arm were considered treatment related by either investigators or sponsor. Conclusion This study failed to demonstrate a statistically significant survival advantage of treatment with tremelimumab over standard-of-care chemotherapy in first-line treatment of patients with metastatic melanoma. PMID:23295794

  14. Phase III randomized clinical trial comparing tremelimumab with standard-of-care chemotherapy in patients with advanced melanoma.

    Science.gov (United States)

    Ribas, Antoni; Kefford, Richard; Marshall, Margaret A; Punt, Cornelis J A; Haanen, John B; Marmol, Maribel; Garbe, Claus; Gogas, Helen; Schachter, Jacob; Linette, Gerald; Lorigan, Paul; Kendra, Kari L; Maio, Michele; Trefzer, Uwe; Smylie, Michael; McArthur, Grant A; Dreno, Brigitte; Nathan, Paul D; Mackiewicz, Jacek; Kirkwood, John M; Gomez-Navarro, Jesus; Huang, Bo; Pavlov, Dmitri; Hauschild, Axel

    2013-02-10

    In phase I/II trials, the cytotoxic T lymphocyte-associated antigen-4-blocking monoclonal antibody tremelimumab induced durable responses in a subset of patients with advanced melanoma. This phase III study evaluated overall survival (OS) and other safety and efficacy end points in patients with advanced melanoma treated with tremelimumab or standard-of-care chemotherapy. Patients with treatment-naive, unresectable stage IIIc or IV melanoma were randomly assigned at a ratio of one to one to tremelimumab (15 mg/kg once every 90 days) or physician's choice of standard-of-care chemotherapy (temozolomide or dacarbazine). In all, 655 patients were enrolled and randomly assigned. The test statistic crossed the prespecified futility boundary at second interim analysis after 340 deaths, but survival follow-up continued. At final analysis with 534 events, median OS by intent to treat was 12.6 months (95% CI, 10.8 to 14.3) for tremelimumab and 10.7 months (95% CI, 9.36 to 11.96) for chemotherapy (hazard ratio, 0.88; P = .127). Objective response rates were similar in the two arms: 10.7% in the tremelimumab arm and 9.8% in the chemotherapy arm. However, response duration (measured from date of random assignment) was significantly longer after tremelimumab (35.8 v 13.7 months; P = .0011). Diarrhea, pruritus, and rash were the most common treatment-related adverse events in the tremelimumab arm; 7.4% had endocrine toxicities. Seven deaths in the tremelimumab arm and one in the chemotherapy arm were considered treatment related by either investigators or sponsor. This study failed to demonstrate a statistically significant survival advantage of treatment with tremelimumab over standard-of-care chemotherapy in first-line treatment of patients with metastatic melanoma.

  15. Safety, immune and clinical responses in metastatic melanoma patients vaccinated with a long peptide derived from indoleamine 2,3-dioxygenase in combination with ipilimumab

    DEFF Research Database (Denmark)

    Bjørn, Jon; Iversen, Trine Zeeberg; Nitschke, Nikolaj Juul

    2016-01-01

    antibody ipilimumab (ipi). METHODS: Ten patients with metastatic melanoma participated in a phase I first-in-human clinical study assessing safety of combining ipi with a 21-mer synthetic peptide vaccine from IDO denoted IDOlong. Secondary and tertiary end points included vaccine and clinical response......BACKGROUND AIM: Indoleamine 2,3-dioxygenase (IDO) is an emerging new target in cancer therapy that can be targeted with active immunotherapy (e.g. through peptide vaccination). Furthermore, IDO has been identified as a key mechanism underlying resistance to treatment with the checkpoint blocking....... RESULTS: Treatment was generally safe and well tolerated. Vaccine related adverse reactions included grade I and II erythema, oedema and pruritus at the vaccination site, which were manageable with mild topical corticosteroids. One patient developed presumed ipi-induced colitis. It initially responded...

  16. 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.

  17. 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.

  18. 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

  19. Central lactic acidosis, hyperventilation, and respiratory alkalosis: leading clinical features in a 3-year-old boy with malignant meningeal melanoma.

    Science.gov (United States)

    Blüher, Susann; Schulz, Manuela; Bierbach, Uta; Meixensberger, Jürgen; Tröbs, Ralf-Bodo; Hirsch, Wolfgang; Schober, Ralf; Kiess, Wieland; Siekmeyer, Werner

    2008-04-01

    Meningeal tumors are extremely rare in children and are diagnostically as well as therapeutically challenging. Among the least common types of malignancies in childhood is malignant melanoma, counting for less than 1% of pediatric tumors. Due to the rarity and the wide spectrum of appearance, initial clinical features may be misleading. A 3-year-old boy was referred to our hospital with symptoms of hyperventilation, dyspnoea, tachycardia, respiratory alkalosis, inarticulate speech, and fatigue. Measurement of pH in cerebrospinal fluid (CSF) yielded central lactic acidosis despite alkalosis in peripheral blood. Diagnostic imaging procedures as well as histology and immunohistochemistry revealed the diagnosis of a malignant meningeal melanoma. We hypothesize that central lactate production of the tumor nests might have induced central acidification, thus inducing hyperventilation by stimulation of central chemoreceptors. This case is a model example of the key role of central pH as an inducer/suppressor of ventilation in humans and illustrates the critical importance of central pH for regulating both ventilation and acid-base homeostasis. Thus, pH of CSF should be measured whenever a malignant brain tumor is suspected.

  20. 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.

  1. Clinical simulation as an evaluation method in health informatics

    DEFF Research Database (Denmark)

    Jensen, Sanne

    2016-01-01

    Safe work processes and information systems are vital in health care. Methods for design of health IT focusing on patient safety are one of many initiatives trying to prevent adverse events. Possible patient safety hazards need to be investigated before health IT is integrated with local clinical...... work practice including other technology and organizational structure. Clinical simulation is ideal for proactive evaluation of new technology for clinical work practice. Clinical simulations involve real end-users as they simulate the use of technology in realistic environments performing realistic...... tasks. Clinical simulation study assesses effects on clinical workflow and enables identification and evaluation of patient safety hazards before implementation at a hospital. Clinical simulation also offers an opportunity to create a space in which healthcare professionals working in different...

  2. Elements Explaining Learning Clinical Reasoning Using Simulation Games

    Directory of Open Access Journals (Sweden)

    Jaana-Maija Koivisto

    2016-12-01

    Full Text Available This article presents the findings on which elements in a game-based simulation affect learning clinical reasoning in nursing education. By using engaging gaming elements in virtual simulations and integrating the clinical reasoning process into game mechanics, games can enhance learning clinical reasoning and offer meaningful learning experiences. The study was designed to explore how nursing students experience gaming and learning when playing a simulation game, as well as which gaming elements explain learning clinical reasoning. The data was collected by questionnaire from nursing students (N = 166 in autumn 2014 over thirteen gaming sessions. The findings showed that usability, application of nursing knowledge, and exploration have the most impact on learning clinical reasoning when playing simulation games. Findings also revealed that authentic patient-related experiences, feedback, and reflection have an indirect effect on learning clinical reasoning. Based on these results, more efficient simulation games to improve clinical reasoning may be developed.   

  3. Iodine-125 irradiation of choroidal melanoma: clinical experience from the Prince of Wales and Sydney Eye Hospitals

    International Nuclear Information System (INIS)

    Mameghan, H.; Karolis, Ch.; Fisher, R.; Mameghan, J.; Billson, F.A.; Donaldson, E.J.; Giblin, M.E.; Hunyor, A.B.L.

    1992-01-01

    The records of 53 patients treated for choroidal melanoma between 1985 and 1989 were examined. The aim of this study was to assess the safety and short-term results of iodine-125 episcleral plaque therapy. There were 28 males and 25 females aged 20 to 77 years, treated for single tumours with a median diameter of 9 mm (range 5 to 16 mm) and with a median thickness of 4 mm (range 2 to 10 mm). The plaques containing iodine-125 seeds were chosen according to tumour size: 10 mm (16 patients); 15 mm (36 patients); 20 mm (one patient). All patients were alive at last follow-up (median 1.3 years, range 4 months to 3.3 years). Four patients underwent enucleation for melanoma progression. Thirty patients have developed some type of complication (more than one complication occurred in the same eye in 12 patients); retinitis (19), optic neuropathy (7); cataract (4), rubeosis iridis (2). Overall, visual acuity deteriorated in 32 patients, remained stable in 12 patients and improved in 9 patients. It was therefore concluded that iodine-125 plaque therapy appears to offer patients good prospects of tumour control and preservation of useful vision. 16 refs., 4 tabs

  4. Iodine-125 irradiation of choroidal melanoma: clinical experience from the Prince of Wales and Sydney Eye Hospitals.

    Science.gov (United States)

    Mameghan, H; Karolis, C; Fisher, R; Mameghan, J; Billson, F A; Donaldson, E J; Giblin, M E; Hunyor, A B

    1992-08-01

    We examined the records of 53 patients treated for choroidal melanoma between 1985 and 1989. The aim of this study was to assess the safety and short-term results of iodine-125 episcleral plaque therapy. There were 28 males and 25 females, aged 20 to 77 years (median 61 years), treated for single tumours with a median diameter of 9 mm (range 5 to 15 mm) and with a median thickness of 4 mm (range 2 to 10 mm). The plaques containing iodine-125 seeds were chosen according to tumour size: 10 mm (16 patients); 15 mm (36 patients); 20 mm (one patient). All patients are alive at last follow-up (median 1.3 years, range 4 months to 3.3 years). Four patients underwent enucleation for melanoma progression. Thirty patients have developed some type of complication (more than one complication occurred in the same eye in 12 patients): retinitis (19), optic neuropathy (7); cataract (4), rubeosis iridis (2). Overall, visual acuity deteriorated in 32 patients, remained stable in 12 patients and improved in 9 patients. Iodine-125 plaque therapy appears to offer patients good prospects of tumour control and preservation of useful vision.

  5. 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...

  6. 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.

  7. 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

  8. 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

  9. 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.

  10. Simulating Data for Clinical Research: A Tutorial

    Science.gov (United States)

    Beaujean, A. Alexander

    2018-01-01

    Simulation studies use computer-generated data to examine questions of interest that have traditionally been used to study properties of statistics and estimating algorithms. With the recent advent of powerful processing capabilities in affordable computers along with readily usable software, it is now feasible to use a simulation study to aid in…

  11. Absolute number of new lesions on 18F-FDG PET/CT is more predictive of clinical response than SUV changes in metastatic melanoma patients receiving ipilimumab.

    Science.gov (United States)

    Anwar, Hoda; Sachpekidis, Christos; Winkler, Julia; Kopp-Schneider, Annette; Haberkorn, Uwe; Hassel, Jessica C; Dimitrakopoulou-Strauss, Antonia

    2018-03-01

    Evaluation of response to immunotherapy is a matter of debate. The aim of the present study was to evaluate the response of metastatic melanoma to treatment with ipilimumab by means of 18 F-FDG PET/CT, using the patients' clinical response as reference. The final cohort included in the analyses consisted of 41 patients with metastatic melanoma who underwent 18 F-FDG PET/CT before and after administration of ipilimumab. After determination of the best clinical response, the PET/CT scans were reviewed and a separate independent analysis was performed, based on the number and functional size of newly emerged 18 F-FDG-avid lesions, as well as on the SUV changes after therapy. The median observation time of the patients after therapy was 21.4 months (range 6.3-41.9 months). Based on their clinical response, patients were dichotomized into those with clinical benefit (CB) and those without CB (No-CB). The CB group (31 patients) included those with stable disease, partial remission and complete remission, and the No-CB group (10 patients) included those with progressive disease. The application of a threshold of four newly emerged 18 F-FDG-avid lesions on the posttherapy PET/CT scan led to a sensitivity (correctly predicting CB) of 84% and a specificity (correctly predicting No-CB) of 100%. This cut-off was lower for lesions with larger functional diameters (three new lesions larger than 1.0 cm and two new lesions larger than 1.5 cm). SUV changes after therapy did not correlate with clinical response. Based on these findings, we developed criteria for predicting clinical response to immunotherapy by means of 18 F-FDG PET/CT (PET Response Evaluation Criteria for Immunotherapy, PERCIMT). Our results show that a cut-off of four newly emerged 18 F-FDG-avid lesions on posttherapy PET/CT gives a reliable indication of treatment failure in patients under ipilimumab treatment. Moreover, the functional size of the new lesions plays an important role in predicting the clinical

  12. Enhancing Higher Order Thinking Skills through Clinical Simulation

    Science.gov (United States)

    Varutharaju, Elengovan; Ratnavadivel, Nagendralingan

    2014-01-01

    Purpose: The study aimed to explore, describe and analyse the design and implementation of clinical simulation as a pedagogical tool in bridging the deficiency of higher order thinking skills among para-medical students, and to make recommendations on incorporating clinical simulation as a pedagogical tool to enhance thinking skills and align the…

  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. 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.

  15. 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

  16. 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.

  17. Using Simulated Patients to Teach Clinical Nutrition.

    Science.gov (United States)

    Carroll, J. Gregory; And Others

    1983-01-01

    "Clinical Nutrition in an Interdisciplinary Setting" is a course designed to introduce basic nutrition knowledge and concepts of nutritional assessment, counseling, and intervention in the clinical care of patients. Provides a brief course overview and descriptions of its development, use, and preliminary evaluation of the patient simulation…

  18. 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.

  19. 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.

  20. 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...

  1. 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.

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

    Directory of Open Access Journals (Sweden)

    Imam Ayesha

    2011-02-01

    . Chemotherapeutic agents including interferons, cytokines, biological agents and radiation therapy for brain metastases have been reported as adjuvant and palliative options while considering malignant melanomas in general. The average recurrence-free interval was 2.59 years. Nine of the 12 reports documented follow-up in their patients. Two of these 9 (22.2% patients died. Conclusions Primary melanoma of the colon is a rare clinical entity. Whenever a seemingly primary melanoma is detected in an atypical location such as the colon, it is prudent to conduct a thorough clinical investigation to consider the possibility of metastatic disease. Further studies are needed to document the long term follow-up, survival advantage and safety of the management approaches employed in patients with primary colonic melanoma. Based on current data, surgical resection appears to be appropriate management for primary colonic melanomas; unless the disease has metastasized to distant sites where surgery may have a limited palliative role.

  3. Piloting Augmented Reality Technology to Enhance Realism in Clinical Simulation.

    Science.gov (United States)

    Vaughn, Jacqueline; Lister, Michael; Shaw, Ryan J

    2016-09-01

    We describe a pilot study that incorporated an innovative hybrid simulation designed to increase the perception of realism in a high-fidelity simulation. Prelicensure students (N = 12) cared for a manikin in a simulation lab scenario wearing Google Glass, a wearable head device that projected video into the students' field of vision. Students reported that the simulation gave them confidence that they were developing skills and knowledge to perform necessary tasks in a clinical setting and that they met the learning objectives of the simulation. The video combined visual images and cues seen in a real patient and created a sense of realism the manikin alone could not provide.

  4. Medical simulation-based education improves medicos' clinical skills.

    Science.gov (United States)

    Wang, Zhaoming; Liu, Qiaoyu; Wang, Hai

    2013-03-01

    Clinical skill is an essential part of clinical medicine and plays quite an important role in bridging medicos and physicians. Due to the realities in China, traditional medical education is facing many challenges. There are few opportunities for students to practice their clinical skills and their dexterities are generally at a low level. Medical simulation-based education is a new teaching modality and helps to improve medicos' clinical skills to a large degree. Medical simulation-based education has many significant advantages and will be further developed and applied.

  5. Clinical simulation training improves the clinical performance of Chinese medical students

    Directory of Open Access Journals (Sweden)

    Ming-ya Zhang

    2015-10-01

    Full Text Available Background: Modern medical education promotes medical students’ clinical operating capacity rather than the mastery of theoretical knowledge. To accomplish this objective, clinical skill training using various simulations was introduced into medical education to cultivate creativity and develop the practical ability of students. However, quantitative analysis of the efficiency of clinical skill training with simulations is lacking. Methods: In the present study, we compared the mean scores of medical students (Jinan University who graduated in 2013 and 2014 on 16 stations between traditional training (control and simulative training groups. In addition, in a clinical skill competition, the objective structured clinical examination (OSCE scores of participating medical students trained using traditional and simulative training were compared. The data were statistically analyzed and qualitatively described. Results: The results revealed that simulative training could significantly enhance the graduate score of medical students compared with the control. The OSCE scores of participating medical students in the clinical skill competition, trained using simulations, were dramatically higher than those of students trained through traditional methods, and we also observed that the OSCE marks were significantly increased for the same participant after simulative training for the clinical skill competition. Conclusions: Taken together, these data indicate that clinical skill training with a variety of simulations could substantially promote the clinical performance of medical students and optimize the resources used for medical education, although a precise analysis of each specialization is needed in the future.

  6. 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.

  7. Illustrative cases for monitoring by quantitative analysis of BRAF/NRAS ctDNA mutations in liquid biopsies of metastatic melanoma patients who gained clinical benefits from anti-PD1 antibody therapy.

    Science.gov (United States)

    Seremet, Teofila; Planken, Simon; Schreuer, Max; Jansen, Yanina; Delaunoy, Mélanie; El Housni, Hakim; Lienard, Danielle; Del Marmol, Véronique; Heimann, Pierre; Neyns, Bart

    2018-02-01

    Anti-programmed death 1 (PD-1) monoclonal antibodies improve the survival of metastatic melanoma patients. Predictive or monitoring biomarkers for response to this therapy could improve the clinical management of these patients. To date, no established biomarkers are available for monitoring the response to immunotherapy. Tumor- specific mutations in circulating tumor DNA (ctDNA) such as BRAF and NRAS mutations for melanoma patients have been proposed for monitoring of immunotherapy response. We present seven illustrative cases for the use of ctDNA BRAF and NRAS mutations' monitoring in plasma. The cases described exemplify four distinct clinical benefit patterns: rapid and durable complete response (CR), early progression, followed by CR, CR followed by early progression after interrupting treatment and long-term disease stabilization. These representative cases suggest that comprehensive BRAF/NRAS ctDNA monitoring during anti-PD1 therapy is informative and can be of added value for the monitoring of melanoma patients gaining clinical benefit on anti-PD1 treatment. An important advantage of our approach is that using the cartridge system on the Idylla platform for mutation analysis, the results become available the same day 2 h after plasma collection. Therefore, in the future, the ctDNA level can be an element in the clinical management of the patients.

  8. Development of a CT simulator and its current clinical status

    International Nuclear Information System (INIS)

    Nagata, Yasushi; Hiraoka, Masahiro; Nishidai, Takehiro

    2000-01-01

    A computed tomography (CT) simulator is defined as a radiotherapy treatment planning (RTP) system which consists of an X-ray CT scanner, a treatment planning computer, and a marking projector. The developmental process from the introduction of an X-ray CT to a CT simulator is described in this article. After the development of the first CT simulator, several new developments in CT scanners, marking projector, and data transfer networks were introduced. CT simulator systems have recently become more widely available and are produced by more than 8 commercial companies. The advantages of a CT simulator are a shortening of overall RTP time, increased accuracy of RTP, and the possibility of 3-D conformal therapy. Clinical experience with CT simulators has accumulated over the past 10 years. Site-specific trials have been undertaken, and the clinical usefulness of CT simulators for breast cancer, maxillary cancer, nasopharyngeal cancer, orbital tumor, lung cancer and other tumors has been demonstrated. The use of CT simulators has resulted in a decrease in the complications of radiotherapy. It also appears to be an essential tool for dose escalation studies, which may permit increased local control of certain tumors. In Japan, CT simulators were in use at more than 134 (20%) of 682 radiotherapy institutions as of the end of 1998. In the USA, CT simulators were present in more than 12% of 1,542 radiotherapy centers in 1994. The CT simulator is now an essential RTP system for advanced radiotherapy. (author)

  9. Clinical applications of PD-1-based therapy: a focus on pembrolizumab (MK-3475 in the management of melanoma and other tumor types

    Directory of Open Access Journals (Sweden)

    Gangadhar TC

    2015-04-01

    Full Text Available Tara C Gangadhar,1 April KS Salama2 1Division of Hematology/Oncology, Department of Medicine, Abramson Cancer Center of the University of Pennsylvania, Philadelphia, PA, USA; 2Division of Medical Oncology, Department of Medicine, Duke University Medical Center, Durham, NC, USA Abstract: Preclinical work has led to an increased understanding of the immunomodulatory mechanisms involved in the regulation of the antitumor response in a variety of tumor types. PD-1 (programmed death 1 appears to be a key checkpoint involved in immune suppression in the tumor microenvironment, even in diseases not previously thought to be sensitive to immune manipulation. More recently, the subsequent clinical development of PD-1-based therapy has resulted in a major breakthrough in the field of oncology. Pembrolizumab, a humanized highly selective IgG4 anti-PD-1 monoclonal antibody, was recently approved for the treatment of advanced melanoma based on promising early-phase clinical data. Encouraging results have also been seen in other malignancies, and PD-1-targeted therapies are likely to markedly change the treatment landscape. Future work will center on rationally designed combination strategies in order to potentiate the antitumor immune response and overcome mechanisms of resistance. Keywords: PD-1, cancer, pembrolizumab, nivolumab, immunotherapy, antitumor activity 

  10. Simulation and the Development of Clinical Judgment: A Quantitative Study

    Science.gov (United States)

    Holland, Susan

    2015-01-01

    The purpose of this quantitative pretest posttest quasi-experimental research study was to explore the effect of the NESD on clinical judgment in associate degree nursing students and compare the differences between groups when the Nursing Education Simulation Design (NESD) guided simulation in order to identify educational strategies promoting…

  11. Irradiations of human melanoma cells by 14 MeV neutrons; survival curves interpretation; physical simulation of neutrons interactions in the cellular medium

    International Nuclear Information System (INIS)

    Bodez, Veronique

    2000-01-01

    14 MeV neutrons are used to irradiate human melanoma cells in order to study survival curves at low dose and low dose rate. We have simulated with the MCNP code, transport of neutrons through the experimental setup to evaluate the contamination of the primary beam by gamma and electrons, for the feasibility of our experiments. We have shown a rapid decrease of the survival curve in the first cGy followed by a plateau for doses up to 30 cGy; after we observed an exponential decrease. This results are observed for the first time, for neutrons at low dose rate (5 cGy/h). In parallel with this experimental point, we have developed a simulation code which permitted the study of neutrons interactions with the cellular medium for individual cells defined as in our experimental conditions. We show that most of the energy is deposited by protons from neutron interactions with external medium, and by heavy ions for interactions into the cell. On the other hand the code gives a good order of magnitude of the dose rate, compared to the experimental values given by silicon diodes. The first results show that we can, using a theory based on induced repair of cells, give an interpretation of the observed experimental plateau. We can give an estimation of the radial distribution of dose for the tracks of charged ions, we show the possibility of calculate interaction cross sections with cellular organelles. Such a work gives interesting perspectives for the future in radiobiology, radiotherapy or radioprotection. (author) [fr

  12. Morphea simulating paucibacillary leprosy clinically and histopathologically

    Directory of Open Access Journals (Sweden)

    José Saulo Torres Delgado

    2013-01-01

    Full Text Available Clinically and histopathologically paucibacillary leprosy shows similar features with initial morphea. In this case we report a 24 yr-old male patient who presented to our dermatology department with diagnosed paucibacillary leprosy by his local dermatologist, and confirmed by perineurovascular lymphocytic infiltrate in the histopathological exam. On physical examination we found new plaque lesions that were suggestive of morphea with alteration of sensitivity. A new biopsy was performed showing sclerotic superficial dermis with thickening of the collagen bundles in deep dermis and linear arrays lymphocytic infiltrate between the collagen bundles that confirm the diagnosis of morphea.

  13. Virtual simulation. First clinical results in patients with prostate cancer

    International Nuclear Information System (INIS)

    Buchali, A.; Dinges, S.; Koswig, S.; Rosenthal, P.; Salk, S.; Harder, C.; Schlenger, L.; Budach, V.

    1998-01-01

    Investigation of options of virtual simulation in patients with localized prostate cancer. Twenty-four patients suffering from prostate cancer were virtual simulated. The clinical target volume was contoured and the planning target volume was defined after CT scan. The isocenter of the planning target volume was determined and marked at patient's skin. The precision of patients marking was controlled with conventional simulation after physical radiation treatment planning. Mean differences of the patient's mark revealed between the 2 simulations in all room axes around 1 mm. The organs at risk were visualized in the digital reconstructed radiographs. The precise patient's mark of the isocentre by virtual simulation allows to skip the conventional simulation. The visualisation of organs at risk leeds to an unnecessarity of an application of contrast medium and to a further relieve of the patient. The personal requirement is not higher in virtual simulation than in conventional CT based radiation treatment planning. (orig./MG) [de

  14. Exploring Iconic Interpretation and Mathematics Teacher Development through Clinical Simulations

    Science.gov (United States)

    Dotger, Benjamin; Masingila, Joanna; Bearkland, Mary; Dotger, Sharon

    2015-01-01

    Field placements serve as the traditional "clinical" experience for prospective mathematics teachers to immerse themselves in the mathematical challenges of students. This article reports data from a different type of learning experience, that of a clinical simulation with a standardized individual. We begin with a brief background on…

  15. improving clinical practice through simulation: a case study of ...

    African Journals Online (AJOL)

    PROF. BARTH EKWEME

    students' perceptions of clinical simulation as a teaching/learning method to increase ... lack is reported to impact on students negatively as they ... care systems and information technology have reduced .... skilled, they become more confident and more motivated .... for achieving long-term retention of clinical competency.

  16. 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.

  17. Simulation-based medical education in clinical skills laboratory.

    Science.gov (United States)

    Akaike, Masashi; Fukutomi, Miki; Nagamune, Masami; Fujimoto, Akiko; Tsuji, Akiko; Ishida, Kazuko; Iwata, Takashi

    2012-01-01

    Clinical skills laboratories have been established in medical institutions as facilities for simulation-based medical education (SBME). SBME is believed to be superior to the traditional style of medical education from the viewpoint of the active and adult learning theories. SBME can provide a learning cycle of debriefing and feedback for learners as well as evaluation of procedures and competency. SBME offers both learners and patients a safe environment for practice and error. In a full-environment simulation, learners can obtain not only technical skills but also non-technical skills, such as leadership, team work, communication, situation awareness, decision-making, and awareness of personal limitations. SBME is also effective for integration of clinical medicine and basic medicine. In addition, technology-enhanced simulation training is associated with beneficial effects for outcomes of knowledge, skills, behaviors, and patient-related outcomes. To perform SBME, effectively, not only simulators including high-fidelity mannequin-type simulators or virtual-reality simulators but also full-time faculties and instructors as professionals of SBME are essential in a clinical skills laboratory for SBME. Clinical skills laboratory is expected to become an integrated medical education center to achieve continuing professional development, integrated learning of basic and clinical medicine, and citizens' participation and cooperation in medical education.

  18. 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.

  19. 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

  20. 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.

  1. A novel flexible clinical multiphoton tomograph for early melanoma detection, skin analysis, testing of anti-age products, and in situ nanoparticle tracking

    Science.gov (United States)

    Weinigel, Martin; Breunig, Hans Georg; Gregory, Axel; Fischer, Peter; Kellner-Höfer, Marcel; Bückle, Rainer; König, Karsten

    2010-02-01

    High-resolution 3D microscopy based on multiphoton induced autofluorescence and second harmonic generation have been introduced in 1990. 13 years later, CE-marked clinical multiphoton systems for 3D imaging of human skin with subcellular resolution have first been launched by JenLab company with the tomography DermaInspect®. This year, the second generation of clinical multiphoton tomographs was introduced. The novel multiphoton tomograph MPTflex, equipped with a flexible articulated optical arm, provides an increased flexibility and accessibility especially for clinical and cosmetical examinations. Improved image quality and signal to noise ratio (SNR) are achieved by a very short source-drain spacing, by larger active areas of the detectors and by single photon counting (SPC) technology. Shorter image acquisition time due to improved image quality reduces artifacts and simplifies the operation of the system. The compact folded optical design and the light-weight structure of the optical head eases the handling. Dual channel detectors enable to distinguish between intratissue elastic fibers and collagenous structures simultaneously. Through the use of piezo-driven optics a stack of optical cross-sections (optical sectioning) can be acquired and 3D imaging can be performed. The multiphoton excitation of biomolecules like NAD(P)H, flavins, porphyrins, elastin, and melanin is done by picojoule femtosecond laser pulses from an tunable turn-key femtosescond near infrared laser system. The ability for rapid high-quality image acquisition, the user-friendly operation of the system and the compact and flexible design qualifies this system to be used for melanoma detection, diagnostics of dermatological disorders, cosmetic research and skin aging measurements as well as in situ drug monitoring and animal research.

  2. The impact of simulation sequencing on perceived clinical decision making.

    Science.gov (United States)

    Woda, Aimee; Hansen, Jamie; Paquette, Mary; Topp, Robert

    2017-09-01

    An emerging nursing education trend is to utilize simulated learning experiences as a means to optimize competency and decision making skills. The purpose of this study was to examine differences in students' perception of clinical decision making and clinical decision making-related self-confidence and anxiety based on the sequence (order) in which they participated in a block of simulated versus hospital-based learning experiences. A quasi-experimental crossover design was used. Between and within group differences were found relative to self-confidence with the decision making process. When comparing groups, at baseline the simulation followed by hospital group had significantly higher self-confidence scores, however, at 14-weeks both groups were not significantly different. Significant within group differences were found in the simulation followed by hospital group only, demonstrating a significant decrease in clinical decision making related anxiety across the semester. Finally, there were no significant difference in; perceived clinical decision making within or between the groups at the two measurement points. Preliminary findings suggest that simulated learning experiences can be offered with alternating sequences without impacting the process, anxiety or confidence with clinical decision making. This study provides beginning evidence to guide curriculum development and allow flexibility based on student needs and available resources. Copyright © 2017. Published by Elsevier Ltd.

  3. Innovative One Step Melanoma Surgical Approach (OSMS: Not a Myth-It’s a Reality! Case Related Analysis of a Patient with a Perfect Clinical Outcome Reported from the Bulgarian Society for Dermatologic Surgery (BULSDS!

    Directory of Open Access Journals (Sweden)

    Georgi Tchernev

    2018-04-01

    CONCLUSION: Thanks to this new approach, some patients could avoid one surgical intervention, which could be interpreted as a significant advantage or probably also survival benefit. This methodology and its successful application were first officialised by the representatives of the Bulgarian Society for Dermatologic Surgery- (BULSDS, and the purpose of this action, in general, is to fully improve clinical management of patients suffering from cutaneous melanoma in terms of compactness by 1 reducing the number of unnecessary surgeries or the number of surgical interventions in general; 2 reducing side effects occurring in surgeries and 3 introducing a serious optimization in terms of financial resources needed or used in the second hospitalization of patients. The question remains open whether the accepted or the current recommendations for surgical treatment of melanoma will be transformed or adapted for the matching patient groups.

  4. 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...

  5. 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.

  6. A brief simulation intervention increasing basic science and clinical knowledge

    Directory of Open Access Journals (Sweden)

    Maria L. Sheakley

    2016-04-01

    Full Text Available Background: The United States Medical Licensing Examination (USMLE is increasing clinical content on the Step 1 exam; thus, inclusion of clinical applications within the basic science curriculum is crucial. Including simulation activities during basic science years bridges the knowledge gap between basic science content and clinical application. Purpose: To evaluate the effects of a one-off, 1-hour cardiovascular simulation intervention on a summative assessment after adjusting for relevant demographic and academic predictors. Methods: This study was a non-randomized study using historical controls to evaluate curricular change. The control group received lecture (n l=515 and the intervention group received lecture plus a simulation exercise (nl+s=1,066. Assessment included summative exam questions (n=4 that were scored as pass/fail (≥75%. USMLE-style assessment questions were identical for both cohorts. Descriptive statistics for variables are presented and odds of passage calculated using logistic regression. Results: Undergraduate grade point ratio, MCAT-BS, MCAT-PS, age, attendance at an academic review program, and gender were significant predictors of summative exam passage. Students receiving the intervention were significantly more likely to pass the summative exam than students receiving lecture only (P=0.0003. Discussion: Simulation plus lecture increases short-term understanding as tested by a written exam. A longitudinal study is needed to assess the effect of a brief simulation intervention on long-term retention of clinical concepts in a basic science curriculum.

  7. 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

  8. 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...

  9. 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

  10. Numerical simulations of clinical focused ultrasound functional neurosurgery

    Science.gov (United States)

    Pulkkinen, Aki; Werner, Beat; Martin, Ernst; Hynynen, Kullervo

    2014-04-01

    A computational model utilizing grid and finite difference methods were developed to simulate focused ultrasound functional neurosurgery interventions. The model couples the propagation of ultrasound in fluids (soft tissues) and solids (skull) with acoustic and visco-elastic wave equations. The computational model was applied to simulate clinical focused ultrasound functional neurosurgery treatments performed in patients suffering from therapy resistant chronic neuropathic pain. Datasets of five patients were used to derive the treatment geometry. Eight sonications performed in the treatments were then simulated with the developed model. Computations were performed by driving the simulated phased array ultrasound transducer with the acoustic parameters used in the treatments. Resulting focal temperatures and size of the thermal foci were compared quantitatively, in addition to qualitative inspection of the simulated pressure and temperature fields. This study found that the computational model and the simulation parameters predicted an average of 24 ± 13% lower focal temperature elevations than observed in the treatments. The size of the simulated thermal focus was found to be 40 ± 13% smaller in the anterior-posterior direction and 22 ± 14% smaller in the inferior-superior direction than in the treatments. The location of the simulated thermal focus was off from the prescribed target by 0.3 ± 0.1 mm, while the peak focal temperature elevation observed in the measurements was off by 1.6 ± 0.6 mm. Although the results of the simulations suggest that there could be some inaccuracies in either the tissue parameters used, or in the simulation methods, the simulations were able to predict the focal spot locations and temperature elevations adequately for initial treatment planning performed to assess, for example, the feasibility of sonication. The accuracy of the simulations could be improved if more precise ultrasound tissue properties (especially of the

  11. Screening, early detection, education, and trends for melanoma: current status (2007-2013) and future directions: Part I. Epidemiology, high-risk groups, clinical strategies, and diagnostic technology.

    Science.gov (United States)

    Mayer, Jonathan E; Swetter, Susan M; Fu, Teresa; Geller, Alan C

    2014-10-01

    While most cancers have shown both decreased incidence and mortality over the past several decades, the incidence of melanoma has continued to grow, and mortality has only recently stabilized in the United States and in many other countries. Certain populations, such as men >60 years of age and lower socioeconomic status groups, face a greater burden from disease. For any given stage and across all ages, men have shown worse melanoma survival than women, and low socioeconomic status groups have increased levels of mortality. Novel risk factors can help identify populations at greatest risk for melanoma and can aid in targeted early detection. Risk assessment tools have been created to identify high-risk patients based on various factors, and these tools can reduce the number of patients needed to screen for melanoma detection. Diagnostic techniques, such as dermatoscopy and total body photography, and new technologies, such as multispectral imaging, may increase the accuracy and reliability of early melanoma detection. Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  12. 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.

  13. 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.

  14. 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)

  15. Successful BNCT for patients with cutaneous and mucosal melanomas. Report of 4 cases

    International Nuclear Information System (INIS)

    Morita, Norimasa; Hiratsuka, Junichi; Kuwabara, Chiaki; Aihara, Teruhito; Harada, Tamotsu; Imajo, Yoshinari; Ono, Koji; Fukuda, Hiroshi; Kumada, Hiroaki

    2006-01-01

    Since 2003 we have conducted BNCT clinical trials on melanomas at the Kyoto University Research Reactor (KUR) and Japan Research Reactor No.4 (JRR-4). We report 4 patients given BNCT for malignant melanomas: 2 with superficial spreading types on the heel, 1 with mucosal melanoma in the nasal cavity, and 1 with a melanoma on the vulva and in the vagina. The two cutaneous melanomas and the nasal cavity mucosal melanoma showed a complete response (CR) by 6 months after BNCT. The residual melanoma showed a partial response (PR) by 3 months after treatment and no regrowth since then. Although two patients experienced normal-tissue damage that exceeded the tolerance level, all the participants were cured within a few months of treatment. BNCT was shown to be a promising treatment for mucosal, as well as for cutaneous, melanomas. (author)

  16. Improving clinical practice through simulation: A case study of ...

    African Journals Online (AJOL)

    Acquisition of knowledge and skills by nursing students before real-life practice is a familiar nursing education challenge. The use of clinical simulation in nursing education provides many opportunities for students to learn and apply theoretical principles of nursing care in a safe environment. The purpose of this study was ...

  17. The effect of an interprofessional clinical simulation on medical ...

    African Journals Online (AJOL)

    Five themes emerged from the reflections: (i) difficulties with implementing knowledge and skills; (ii) importance of teamwork; (iii) skills necessary for teamwork; (iv) effect of being observed by peers; and (v) IPE in the curriculum. Conclusions. Medical students gained clinical knowledge during the simulation and became ...

  18. 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.

  19. Hybrid Simulation in Teaching Clinical Breast Examination to Medical Students.

    Science.gov (United States)

    Nassif, Joseph; Sleiman, Abdul-Karim; Nassar, Anwar H; Naamani, Sima; Sharara-Chami, Rana

    2017-10-10

    Clinical breast examination (CBE) is traditionally taught to third-year medical students using a lecture and a tabletop breast model. The opportunity to clinically practice CBE depends on patient availability and willingness to be examined by students, especially in culturally sensitive environments. We propose the use of a hybrid simulation model consisting of a standardized patient (SP) wearing a silicone breast simulator jacket and hypothesize that this, compared to traditional teaching methods, would result in improved learning. Consenting third-year medical students (N = 82) at a university-affiliated tertiary care center were cluster-randomized into two groups: hybrid simulation (breast jacket + SP) and control (tabletop breast model). Students received the standard lecture by instructors blinded to the randomization, followed by randomization group-based learning and practice sessions. Two weeks later, participants were assessed in an Objective Structured Clinical Examination (OSCE), which included three stations with SPs blinded to the intervention. The SPs graded the students on CBE completeness, and students completed a self-assessment of their performance and confidence during the examination. CBE completeness scores did not differ between the two groups (p = 0.889). Hybrid simulation improved lesion identification grades (p simulation relieved the fear of missing a lesion on CBE (p = 0.043) and increased satisfaction with the teaching method among students (p = 0.002). As a novel educational tool, hybrid simulation improves the sensitivity of CBE performed by medical students without affecting its specificity. Hybrid simulation may play a role in increasing the confidence of medical students during CBE.

  20. 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.

  1. Frequency and characteristics of familial melanoma in Spain: the FAM-GEM-1 Study.

    Directory of Open Access Journals (Sweden)

    Iván Márquez-Rodas

    Full Text Available Familial history of melanoma is a well-known risk factor for the disease, and 7% melanoma patients were reported to have a family history of melanoma. Data relating to the frequency and clinical and pathological characteristics of both familial and non-familial melanoma in Spain have been published, but these only include patients from specific areas of Spain and do not represent the data for the whole of Spain.An observational study conducted by the Spanish Group of Melanoma (GEM analyzed the family history of patients diagnosed with melanoma between 2011 and 2013 in the dermatology and oncology departments.In all, 1047 patients were analyzed, and 69 (6.6% fulfilled criteria for classical familial melanoma (two or more first-degree relatives diagnosed with melanoma. Taking into account other risk factors for familial melanoma, such as multiple melanoma, pancreatic cancer in the family or second-degree relatives with melanoma, the number of patients fulfilling the criteria increased to 165 (15.8%. Using a univariate analysis, we determined that a Breslow index of less than 1 mm, negative mitosis, multiple melanoma, and a history of sunburns in childhood were more frequent in familial melanoma patients, but a multivariate analysis revealed no differences in any pathological or clinical factor between the two groups.Similar to that observed in other countries, familial melanoma accounts for 6.6% of melanoma diagnoses in Spain. Although no differences in the multivariate analysis were found, some better prognosis factors, such as Breslow index, seem more frequent in familial melanoma, which reflect a better early detection marker and/or a different biological behavior.

  2. [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.

  3. Clinical trial optimization: Monte Carlo simulation Markov model for planning clinical trials recruitment.

    Science.gov (United States)

    Abbas, Ismail; Rovira, Joan; Casanovas, Josep

    2007-05-01

    The patient recruitment process of clinical trials is an essential element which needs to be designed properly. In this paper we describe different simulation models under continuous and discrete time assumptions for the design of recruitment in clinical trials. The results of hypothetical examples of clinical trial recruitments are presented. The recruitment time is calculated and the number of recruited patients is quantified for a given time and probability of recruitment. The expected delay and the effective recruitment durations are estimated using both continuous and discrete time modeling. The proposed type of Monte Carlo simulation Markov models will enable optimization of the recruitment process and the estimation and the calibration of its parameters to aid the proposed clinical trials. A continuous time simulation may minimize the duration of the recruitment and, consequently, the total duration of the trial.

  4. Development of a combined OCT-Raman probe for the prospective in vivo clinical melanoma skin cancer screening

    Science.gov (United States)

    Mazurenka, M.; Behrendt, L.; Meinhardt-Wollweber, M.; Morgner, U.; Roth, B.

    2017-10-01

    A combined optical coherence tomography (OCT)-Raman probe was designed and built into a spectral domain OCT head, and its performance was evaluated and compared to the most common Raman probe setups, based on a fiber bundle and confocal free space optics. Due to the use of the full field of view of an OCT scanning lens, the combined probe has a superior performance within maximum permissible exposure limits, compared to the other two probes. Skin Raman spectra, recorded in vivo, further prove the feasibility of the OCT-Raman probe for the future in vivo clinical applications in skin cancer screening.

  5. 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 .

  6. A new animal model for the imaging of melanoma: correlation of FDG PET with clinical outcome, macroscopic aspectand histological classification in Melanoblastoma-bearing Libechov Minipigs

    Czech Academy of Sciences Publication Activity Database

    Boisgard, R.; Naulleau, S. V.; Leplat, J. J.; Bouet, S.; Chalony, C.; Tricaud, Y.; Horák, Vratislav; Geffrotin, C.; Frelat, G.; Tavitian, B.

    2003-01-01

    Roč. 30, č. 6 (2003), s. 826-834 ISSN 1619-7070 R&D Projects: GA ČR GA524/01/0162 Institutional research plan: CEZ:AV0Z5045916 Keywords : melanoma * MeLiM swinw model Subject RIV: ED - Physiology Impact factor: 3.324, year: 2003

  7. Epidemiological profile of elderly patients with non-melanoma skin cancer seen at the dermatology outpatient clinic of a public hospital.

    Science.gov (United States)

    Lenzi, Thiara Cristina Rocha; Reis, Carmelia Matos Santiago; Novaes, Maria Rita Carvalho Garbi

    2017-01-01

    Basal cell carcinoma and Squamous cell carcinoma, referred to as non-melanoma skin cancer, are the most common malignancies in humans. Their incidence is increasing worldwide every year. In Brazil, even with the advent of educational campaigns on photoprotection and laws that banned tanning beds, they are the most frequent neoplasias, representing a public health problem recognized by the Ministry of health.

  8. The Crucible simulation: Behavioral simulation improves clinical leadership skills and understanding of complex health policy change.

    Science.gov (United States)

    Cohen, Daniel; Vlaev, Ivo; McMahon, Laurie; Harvey, Sarah; Mitchell, Andy; Borovoi, Leah; Darzi, Ara

    2017-05-11

    The Health and Social Care Act 2012 represents the most complex National Health Service reforms in history. High-quality clinical leadership is important for successful implementation of health service reform. However, little is known about the effectiveness of current leadership training. This study describes the use of a behavioral simulation to improve the knowledge and leadership of a cohort of medical doctors expected to take leadership roles in the National Health Service. A day-long behavioral simulation (The Crucible) was developed and run based on a fictitious but realistic health economy. Participants completed pre- and postsimulation questionnaires generating qualitative and quantitative data. Leadership skills, knowledge, and behavior change processes described by the "theory of planned behavior" were self-assessed pre- and postsimulation. Sixty-nine medical doctors attended. Participants deemed the simulation immersive and relevant. Significant improvements were shown in perceived knowledge, capability, attitudes, subjective norms, intentions, and leadership competency following the program. Nearly one third of participants reported that they had implemented knowledge and skills from the simulation into practice within 4 weeks. This study systematically demonstrates the effectiveness of behavioral simulation for clinical management training and understanding of health policy reform. Potential future uses and strategies for analysis are discussed. High-quality care requires understanding of health systems and strong leadership. Policymakers should consider the use of behavioral simulation to improve understanding of health service reform and development of leadership skills in clinicians, who readily adopt skills from simulation into everyday practice.

  9. Animated-simulation modeling facilitates clinical-process costing.

    Science.gov (United States)

    Zelman, W N; Glick, N D; Blackmore, C C

    2001-09-01

    Traditionally, the finance department has assumed responsibility for assessing process costs in healthcare organizations. To enhance process-improvement efforts, however, many healthcare providers need to include clinical staff in process cost analysis. Although clinical staff often use electronic spreadsheets to model the cost of specific processes, PC-based animated-simulation tools offer two major advantages over spreadsheets: they allow clinicians to interact more easily with the costing model so that it more closely represents the process being modeled, and they represent cost output as a cost range rather than as a single cost estimate, thereby providing more useful information for decision making.

  10. Clinical Simulation: A Protocol for Evaluation of Mobile Technology.

    Science.gov (United States)

    Mather, Carey; Jensen, Sanne; Cummings, Elizabeth

    2017-01-01

    For mobile technology to be accepted at point of care in healthcare environments there is a need to demonstrate benefits whilst ameliorating the risks and challenges. To provide a standardised approach to evaluation of mobile technology a simulation protocol was developed to provide guidance for its use in healthcare environments. Simulated conditions provide the opportunity to assess intended and unintended consequences and identify potential workarounds when using technology. The protocol can also be used to demonstrate the importance of the development of digital professionalism by end-users prior to students entering the clinical practice setting. The mobile technology protocol was adapted from a health information systems protocol developed and used at the ITX Lab, Denmark for use in other simulation laboratories. Use case scenarios were developed to enable evaluation of mobile technology for mobile learning of nurses, nurse supervisors, students and patients. The scenarios can be used in a range of simulated environments including hospital bedside, outpatient clinic or community settings. A case study exemplar of a nurse and patient is included to demonstrate how the mobile technology protocol can be applied.

  11. 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.

  12. New Therapies Offer Valuable Options for Patients with Melanoma

    Science.gov (United States)

    Two phase III clinical trials of new therapies for patients with metastatic melanoma presented in June at the 2011 ASCO conference confirmed that vemurafenib and ipilimumab (Yervoy™) offer valuable new options for the disease.

  13. Common Moles, Atypical Moles (Dysplastic Nevi), and Risk of Melanoma

    Science.gov (United States)

    ... Data Conducting Clinical Trials Statistical Tools and Data Terminology Resources NCI Data Catalog Cryo-EM NCI's Role ... freckles have an increased chance of melanoma. Certain medical conditions or medicines : Medical conditions or medicines (such ...

  14. [X-ray computed tomographic aspects of benign primary cerebral melanomas. Apropos of 4 cases].

    Science.gov (United States)

    Adam, P; Alberge, Y; Espagno, C; Bouzigues, J Y

    1986-02-01

    Benign primitive melanomas are rare tumours usually involving the leptomeninges. Four cranial localizations are reported: 2 tumours of the foramen magnum, 1 of the cerebellopontine angle and 1 supratentorial. The clinical symptomatology is variable according to the level. Slow medullary compression is frequent. One can emphasize the special and difficult problem of foramen magnum tumours that present with a very variable clinical status frequently simulating a non surgical disease of the central nervous system. The benign and primitive appearance of these tumours is evocated by the slow and favourable evolution and by the absence of extraneurologic melanotic tumour. Our purpose is essentially to emphasize the radiological and particularly the computed tomographic (CT) findings poorly described in the literature. Benign melanomas have resemblance with meningiomas: osseous or meningeal relationship, homogeneity and high density. On the other hand the angiography shows poor vascularization. One can think that a tumor simulating a meningioma by CT but not by angiography is perhaps a benign melanoma. The special problem of the radiological diagnosis of foramen magnum tumours is evocated: Computed myelography, tridimensional imaging by NMR.

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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

  20. 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

  1. Multifocal amelanotic conjunctival melanoma and acquired melanosis sine pigmento.

    Science.gov (United States)

    Paridaens, A D; McCartney, A C; Hungerford, J L

    1992-03-01

    Clinical and histopathological features of four cases of multifocal amelanotic malignant melanoma of the conjunctiva in association with 'acquired melanosis sine pigmento' are reported. The absence of conjunctival pigmentation in this extremely rare combination of lesions prevented early diagnosis and clinical monitoring. As a result orbital exenteration was required in three cases. This multicentric non-pigmented variety of conjunctival malignant melanoma tends to present later than pigmented forms and may require exenteration of the orbit as a primary procedure.

  2. Melanoma survival is superior in females across all tumour stages but is influenced by age.

    Science.gov (United States)

    Khosrotehrani, Kiarash; Dasgupta, Paramita; Byrom, Lisa; Youlden, Danny R; Baade, Peter D; Green, Adele C

    2015-10-01

    Among patients with invasive melanoma, females are known to have higher survival than males globally. However, this survival advantage has not been explored in thin melanomas, the most common form of the disease. In addition, it is unclear if this advantage is true across all age groups. We aimed to compare melanoma survival between males and females by clinical stage and within age groups. Melanomas from 1995 to 2008 were extracted from the Queensland Cancer Registry and the Surveillance, Epidemiology, and End Results (SEER) Program, and melanoma-specific deaths were ascertained up to 2011. Flexible parametric survival models compared survival between groups. The Queensland cohort of 28,979 patients experienced 1712 melanoma deaths and the SEER cohort of 57,402 patients included 6929 melanoma deaths. Survival rates were in favour of females across nearly all tumour stages, including thin invasive tumours in both cohorts after adjusting for demographic and clinical factors [odds ratio (OR) death female:male for stage I melanoma = 0.64 in Queensland; and OR = 0.79 in the US, both P age categories. In particular, the survival advantage was inconsistent in females with stage I melanoma aged under 60. Females with melanoma have a survival advantage over males including in stage I melanomas. However, this advantage is dependent on age at diagnosis, suggesting an underlying biological mechanism influenced by age that exists from the very early stages of the disease.

  3. [Innovation in healthcare processes and patient safety using clinical simulation].

    Science.gov (United States)

    Rojo, E; Maestre, J M; Díaz-Mendi, A R; Ansorena, L; Del Moral, I

    2016-01-01

    Many excellent ideas are never implemented or generalised by healthcare organisations. There are two related paradigms: thinking that individuals primarily change through accumulating knowledge, and believing that the dissemination of that knowledge within the organisation is the key element to facilitate change. As an alternative, a description and evaluation of a simulation-based inter-professional team training program conducted in a Regional Health Service to promote and facilitate change is presented. The Department of Continuing Education completed the needs assessment using the proposals presented by clinical units and management. Skills and behaviors that could be learned using simulation were selected, and all personnel from the units participating were included. Experiential learning principles based on clinical simulation and debriefing, were used for the instructional design. The Kirkpatrick model was used to evaluate the program. Objectives included: a) decision-making and teamwork skills training in high prevalence diseases with a high rate of preventable complications; b) care processes reorganisation to improve efficiency, while maintaining patient safety; and, c) implementation of new complex techniques with a long learning curve, and high preventable complications rate. Thirty clinical units organised 39 training programs in the 3 public hospitals, and primary care of the Regional Health Service during 2013-2014. Over 1,559 healthcare professionals participated, including nursing assistants, nurses and physicians. Simulation in healthcare to train inter-professional teams can promote and facilitate change in patient care, and organisational re-engineering. Copyright © 2016 SECA. Publicado por Elsevier España, S.L.U. All rights reserved.

  4. 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.

  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. An Endogenous Electron Spin Resonance (ESR signal discriminates nevi from melanomas in human specimens: a step forward in its diagnostic application.

    Directory of Open Access Journals (Sweden)

    Eleonora Cesareo

    Full Text Available Given the specific melanin-associated paramagnetic features, the Electron Spin Resonance (ESR, called also Electron Paramagnetic Resonance, EPR analysis has been proposed as a potential tool for non-invasive melanoma diagnosis. However, studies comparing human melanoma tissues to the most appropriate physiological counterpart (nevi have not been performed, and ESR direct correlation with melanoma clinical features has never been investigated. ESR spectrum was obtained from melanoma and non-melanoma cell-cultures as well as mouse melanoma and non-melanoma tissues and an endogenous ESR signal (g = 2.005 was found in human melanoma cells and in primary melanoma tissues explanted from mice, while it was always absent in non-melanoma samples. These characteristics of the measured ESR signal strongly suggested its connection with melanin. Quantitative analyses were then performed on paraffin-embedded human melanoma and nevus sections, and validated on an independent larger validation set, for a total of 112 sections (52 melanomas, 60 nevi. The ESR signal was significantly higher in melanomas (p = 0.0002 and was significantly different between "Low Breslow's and "High Breslow's" depth melanomas (p<0.0001. A direct correlation between ESR signal and Breslow's depth, expressed in millimetres, was found (R = 0.57; p<0.0001. The eu/pheomelanin ratio was found to be significantly different in melanomas "Low Breslow's" vs melanomas "High Breslow's" depth and in nevi vs melanomas "High Breslow's depth". Finally, ROC analysis using ESR data discriminated melanomas sections from nevi sections with up to 90% accuracy and p<0.0002. In the present study we report for the first time that ESR signal in human paraffin-embedded nevi is significantly lower than signal in human melanomas suggesting that spectrum variations may be related to qualitative melanin differences specifically occurring in melanoma cells. We therefore conclude that this ESR signal

  7. Tumor infiltrating BRAFV600E-specific CD4 T cells correlated with complete clinical response in melanoma. | Office of Cancer Genomics

    Science.gov (United States)

    T cells specific for neoantigens encoded by mutated genes in cancers are increasingly recognized as mediators of tumor destruction after immune checkpoint inhibitor therapy or adoptive cell transfer. Unfortunately, most neoantigens result from random mutations and are patient specific, and some cancers contain few mutations to serve as potential antigens. We describe a patient with stage IV acral melanoma who obtained a complete response following adoptive transfer of tumor infiltrating lymphocytes (TIL).

  8. HTB140 melanoma cells under proton irradiation and/or alkylating agents

    Science.gov (United States)

    Korićanac, L.; Petrović, I.; Privitera, G.; Cuttone, G.; Ristić-Fira, A.

    2007-09-01

    Chemoresistance is a major problem in the treatment of malignant melanoma. The mainstay of treatment for melanoma is the DNA-alkylating agent dacarbazine (DTIC). Fotemustine (FM), a member of the chloroethylnitrosourea group of alkylating agents, has also demonstrated significant antitumor effects in malignant melanoma. However, the intrinsic and acquired resistance of melanoma limits the clinical application of these drugs. Melanomas are also extremely radioresistant. With the objective of enhancing growth inhibition of melanoma cells, combined treatments of FM or DTIC with proton irradiation have been investigated. These effects were studied on HTB140 melanoma cell viability and proliferation. Cells exposed to treatment with FM and protons have shown inhibition of cell growth and significant reduction of proliferation capacity compared to single irradiation or drug treatment. Treatment with DTIC and protons has shown improved growth inhibition compared to appropriate single drug treatment, while the effects of single proton irradiation have been the most pronounced.

  9. 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.

  10. 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.

  11. Cell proliferation and expression of connexins differ in melanotic and amelanotic canine oral melanomas.

    Science.gov (United States)

    Teixeira, Tarso Felipe; Gentile, Luciana Boffoni; da Silva, Tereza Cristina; Mennecier, Gregory; Chaible, Lucas Martins; Cogliati, Bruno; Roman, Marco Antonio Leon; Gioso, Marco Antonio; Dagli, Maria Lucia Zaidan

    2014-03-01

    Melanoma is a malignant neoplasm occurring in several animal species, and is the most frequently found tumor in the oral cavity in dogs. Melanomas are classified into two types: melanotic and amelanotic. Prior research suggests that human amelanotic melanomas are more aggressive than their melanotic counterparts. This study evaluates the behavior of canine melanotic and amelanotic oral cavity melanomas and quantifies cell proliferation and the expression of connexins. Twenty-five melanomas (16 melanotic and 9 amelanotic) were collected from dogs during clinical procedures at the Veterinary Hospital of the School of Veterinary Medicine and Animal Science of the University of São Paulo, Brazil. After diagnosis, dogs were followed until death or euthanasia. Histopathology confirmed the gross melanotic or amelanotic characteristics and tumors were classified according to the WHO. HMB45 or Melan A immunostainings were performed to confirm the diagnosis of amelanotic melanomas. Cell proliferation was quantified both by counting mitotic figures and PCNA positive nuclei. Expressions of connexins 26 and 43 were evaluated by immunohistochemistry, qRT-PCR and Western blot. Dogs bearing amelanotic melanomas presented a shorter lifespan in comparison to those with melanotic melanomas. Cell proliferation was significantly higher in amelanotic melanomas. Expressions of Connexins 26 and 43 were significantly reduced in amelanotic melanomas. The results presented here suggest that oral cavity melanotic and amelanotic melanomas differ regarding their behavior, cell proliferation and connexin expression in dogs, indicating a higher aggressiveness of amelanotic variants.

  12. Monte Carlo simulation of a clinical linear accelerator

    International Nuclear Information System (INIS)

    Lin, S.-Y.; Chu, T.-C.; Lin, J.-P.

    2001-01-01

    The effects of the physical parameters of an electron beam from a Siemens PRIMUS clinical linear accelerator (linac) on the dose distribution in water were investigated by Monte Carlo simulation. The EGS4 user code, OMEGA/BEAM, was used in this study. Various incident electron beams, for example, with different energies, spot sizes and distances from the point source, were simulated using the detailed linac head structure in the 6 MV photon mode. Approximately 10 million particles were collected in the scored plane, which was set under the reticle to form the so-called phase space file. The phase space file served as a source for simulating the dose distribution in water using DOSXYZ. Dose profiles at D max (1.5 cm) and PDD curves were calculated following simulating about 1 billion histories for dose profiles and 500 million histories for percent depth dose (PDD) curves in a 30x30x30 cm 3 water phantom. The simulation results were compared with the data measured by a CEA film and an ion chamber. The results show that the dose profiles are influenced by the energy and the spot size, while PDD curves are primarily influenced by the energy of the incident beam. The effect of the distance from the point source on the dose profile is not significant and is recommended to be set at infinity. We also recommend adjusting the beam energy by using PDD curves and, then, adjusting the spot size by using the dose profile to maintain the consistency of the Monte Carlo results and measured data

  13. 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.

  14. A CLINICAL CASE OF ACUTE ALLERGIC MYOCARDITIS SIMULATING MYOCARDIAL INFARCTION

    Directory of Open Access Journals (Sweden)

    N. A. Shostak

    2015-01-01

    Full Text Available Objective: to describe a clinical case of evolving acute eosinophilic myocarditis simulating coronary heart disease. Subjects and methods. Patient B. aged 62 years was admitted to Intensive Care Unit Fifteen, N.I. Pirogov First Moscow City Clinical Hospital, by being transferred from Thailand with a referral diagnosis of acute myocardial infarction made on November 1, 2012, with complaints of pressing and aching heart pains. At a Phuket hospital, his electrocardiogram recorded atrial fibrillation; indirect cardiac massage, electric pulse therapy, and mechanical ventilation were performed. After being admitted to the N.I. Pirogov First Moscow City Clinical Hospital, the patient underwent examination: estimation of laboratory indicators over time, electrocardiography (ECG, echocardiography, Holter ECG monitoring, and myocardial scintigraphy. Results. The patient had a history of an allergic reaction as urticaria to the ingestion of fish products. His examination showed practically all diagnostic criteria for allergic myocarditis: hypereosinophilia (the admission level of eosinophils was 9% with their further normalization; the characteristic clinical presentation of myocarditis (pressing retrosternal pain; elevated levels of cardiac specific enzymes (creatinine phosphokinase-MB, lactate dehydrogenase, troponin T; ECG changes – myocardial hypokinesis in the acute period, followed by its pattern normalization. of the pattern. Myocardial scintigraphy (by taking into account the fact that the patient had had a new allergic reaction episode, the investigators decided not to perform coronary angiography revealed decreased radiopharmaceutical accumulation in the lower left ventricular wall in the right coronary arterial bed; perfusion remained in the other myocardial walls. Conclusion. This clinical case reflects the specific features of the course of and difficulties in the diagnosis of acute allergic myocarditis that, in most cases, has no specific

  15. 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.

  16. Technology for enhancing chest auscultation in clinical simulation.

    Science.gov (United States)

    Ward, Jeffrey J; Wattier, Bryan A

    2011-06-01

    The ability to use an acoustic stethoscope to detect lung and/or heart sounds, and then to then communicate one's interpretation of those sounds is an essential skill for many medical professionals. Interpretation of lung and heart sounds, in the context of history and other examination findings, often aids the differential diagnosis. Bedside assessment of changing auscultation findings may also guide treatment. Learning lung and heart auscultation skills typically involves listening to pre-recorded normal and adventitious sounds, often followed by laboratory instruction to guide stethoscope placement, and finally correlating the sounds with the associated pathophysiology and pathology. Recently, medical simulation has become an important tool for teaching prior to clinical practice, and for evaluating bedside auscultation skills. When simulating cardiovascular or pulmonary problems, high-quality lung and heart sounds should be able to accurately corroborate other findings such as vital signs, arterial blood gas values, or imaging. Digital audio technology, the Internet, and high-fidelity simulators have increased opportunities for educators and learners. We review the application of these technologies and describe options for reproducing lung and heart sounds, as well as their advantages and potential limitations.

  17. FREQUENT SUBCLINICAL MACULAR CHANGES IN COMBINED BRAF/MEK INHIBITION WITH HIGH-DOSE HYDROXYCHLOROQUINE AS TREATMENT FOR ADVANCED METASTATIC BRAF MUTANT MELANOMA: Preliminary Results From a Phase I/II Clinical Treatment Trial.

    Science.gov (United States)

    Nti, Akosua A; Serrano, Leona W; Sandhu, Harpal S; Uyhazi, Katherine E; Edelstein, Ilaina D; Zhou, Elaine J; Bowman, Scott; Song, Delu; Gangadhar, Tara C; Schuchter, Lynn M; Mitnick, Sheryl; Huang, Alexander; Nichols, Charles W; Amaravadi, Ravi K; Kim, Benjamin J; Aleman, Tomas S

    2018-01-10

    To assess the potential ocular toxicity of a combined BRAF inhibition (BRAFi) + MEK inhibition (MEKi) + hydroxychloroquine (HCQ) regime used to treat metastatic BRAF mutant melanoma. Patients with stage IV metastatic melanoma and BRAF V600E mutations (n = 11, 31-68 years of age) were included. Treatment was with oral dabrafenib, 150 mg bid, trametinib, 2 mg/day, and HCQ, 400 mg to 600 mg bid. An ophthalmic examination, spectral domain optical coherence tomography, near-infrared and short-wavelength fundus autofluorescence, and static perimetry were performed at baseline, 1 month, and q/6 months after treatment. There were no clinically significant ocular events; there was no ocular inflammation. The only medication-related change was a separation of the photoreceptor outer segment tip from the apical retinal pigment epithelium that could be traced from the fovea to the perifoveal retina noted in 9/11 (82%) of the patients. There were no changes in retinal pigment epithelium melanization or lipofuscin content by near-infrared fundus autofluorescence and short-wavelength fundus autofluorescence, respectively. There were no inner retinal or outer nuclear layer changes. Visual acuities and sensitivities were unchanged. BRAFi (trametinib) + MEKi (dabrafenib) + HCQ causes very frequent, subclinical separation of the photoreceptor outer segment from the apical retinal pigment epithelium without inner retinal changes or signs of inflammation. The changes suggest interference with the maintenance of the outer retinal barrier and/or phagocytic/pump functions of the retinal pigment epithelium by effective MEK inhibition.

  18. Malignant melanoma misdiagnosed as diabetic foot ulcer: A case report.

    Science.gov (United States)

    Gao, Wei; Chen, Dawei; Ran, Xingwu

    2017-07-01

    Acral lentiginous melanoma (AML) does not exhibit the classic signs of malignant melanoma. ALM is frequently misdiagnosed because of its unusual sites and atypical clinical morphologies, which lead to poor prognosis. A female patient aged 78 years was presented to our center with two ulcers on her right foot. Diabetic foot ulcer was considered as the primary diagnosis. The ulcers failed to improve after 2 weeks' therapy. An incisional biopsy of the lesion revealed malignant melanoma. The patient received wide excision, skin grafting as well as biotherapy. The lesion was healed and no other metastasis has been founded until now. Clinicians must maintain a high level of suspicion in distinguishing malignant melanoma from other more benign skin lesions of the foot. The need for early biopsy of ulcer, even when clinical suspicion is low, can not be overemphasized. Only in this way can we reduce misdiagnosis rate and improve survival rate in patients with foot ulcer.

  19. 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.

  20. 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.

  1. Geant4 simulation for a study of a possible use of carbon ions pencil beam for the treatment of ocular melanomas with the active scanning system at CNAO Centre

    International Nuclear Information System (INIS)

    Farina, E.; Piersimoni, P.; Riccardi, C.; Rimoldi, A.; Tamborini, A.; Ciocca, M.

    2015-01-01

    The aim of this work is to validate the Geant4 application reproducing the CNAO (National Centre for Oncological Hadrontherapy) beamline and to study of a possible use of carbon ion pencil beams for the treatment of ocular melanomas at the CNAO Centre. The promising aspect of carbon ions radiotherapy for the treatment of this disease lies in its superior relative radiobiological effectiveness (RBE). The Monte Carlo Geant4 toolkit is used to simulate the complete CNAO extraction beamline, with the active and passive components along it. A human eye modeled detector, including a realistic target tumor volume, is used as target. Cross check with previous studies at CNAO using protons allows comparisons on possible benefits on using such a technique with respect to proton beams. Before the eye-detector irradiation a validation of the Geant4 simulation with CNAO experimental data is carried out with both carbon ions and protons. Important beam parameters such as the transverse FWHM and scanned radiation field 's uniformity are tested within the simulation and compared with experimental measurements at CNAO Centre. The physical processes involved in secondary particles generation by carbon ions and protons in the eye-detector are reproduced to take into account the additional dose to the primary beam given to irradiated eye's tissues. A study of beam shaping is carried out to produce a uniform 3D dose distribution (shaped on the tumor) by the use of a spread out Bragg peak. The eye-detector is then irradiated through a two dimensional transverse beam scan at different depths. In the use case the eye-detector is rotated of an angle of 40 deg. in the vertical direction, in order to mis-align the tumor from healthy tissues in front of it. The treatment uniformity on the tumor in the eye-detector is tested. For a more quantitative description of the deposited dose in the eye-detector and for the evaluation of the ratio between the dose deposited in the tumor and

  2. Geant4 simulation for a study of a possible use of carbon ions pencil beam for the treatment of ocular melanomas with the active scanning system at CNAO Centre

    Energy Technology Data Exchange (ETDEWEB)

    Farina, E. [University of Pavia-Department of Physics, via Bassi 6, 27100 Pavia (Italy); Piersimoni, P. [Division of Radiation Research, Loma Linda University, Loma Linda, CA 92354 (United States); Riccardi, C.; Rimoldi, A.; Tamborini, A. [University of Pavia-Department of Physics, via Bassi 6, 27100 Pavia (Italy); INFN Section of Pavia, via Bassi 6, 27100 Pavia (Italy); Ciocca, M. [Medical Physics Unit, Centro Nazionale di Adroterapia Oncologica - CNAO Foundation, Strada Campeggi 53, 27100 Pavia (Italy)

    2015-07-01

    The aim of this work is to validate the Geant4 application reproducing the CNAO (National Centre for Oncological Hadrontherapy) beamline and to study of a possible use of carbon ion pencil beams for the treatment of ocular melanomas at the CNAO Centre. The promising aspect of carbon ions radiotherapy for the treatment of this disease lies in its superior relative radiobiological effectiveness (RBE). The Monte Carlo Geant4 toolkit is used to simulate the complete CNAO extraction beamline, with the active and passive components along it. A human eye modeled detector, including a realistic target tumor volume, is used as target. Cross check with previous studies at CNAO using protons allows comparisons on possible benefits on using such a technique with respect to proton beams. Before the eye-detector irradiation a validation of the Geant4 simulation with CNAO experimental data is carried out with both carbon ions and protons. Important beam parameters such as the transverse FWHM and scanned radiation field 's uniformity are tested within the simulation and compared with experimental measurements at CNAO Centre. The physical processes involved in secondary particles generation by carbon ions and protons in the eye-detector are reproduced to take into account the additional dose to the primary beam given to irradiated eye's tissues. A study of beam shaping is carried out to produce a uniform 3D dose distribution (shaped on the tumor) by the use of a spread out Bragg peak. The eye-detector is then irradiated through a two dimensional transverse beam scan at different depths. In the use case the eye-detector is rotated of an angle of 40 deg. in the vertical direction, in order to mis-align the tumor from healthy tissues in front of it. The treatment uniformity on the tumor in the eye-detector is tested. For a more quantitative description of the deposited dose in the eye-detector and for the evaluation of the ratio between the dose deposited in the tumor and

  3. 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

  4. 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

  5. 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.

  6. Profile of ipilimumab and its role in the treatment of metastatic melanoma

    Directory of Open Access Journals (Sweden)

    Patel SP

    2011-12-01

    Full Text Available Sapna P Patel, Scott E WoodmanMelanoma Medical Oncology Department, University of Texas, MD Anderson Cancer Center, Houston, TX, USAAbstract: Melanoma is an immunogenic cancer. However, the ability of the immune system to eradicate melanoma tumors is affected by intrinsic negative regulatory mechanisms. Multiple immune-modulatory therapies are currently being developed to optimize the immune response to melanoma tumors. Two recent Phase III studies using the monoclonal antibody ipilimumab, which targets the cytotoxic T-lymphocyte antigen (CTLA-4, a negative regulator of T-cell activation, have demonstrated improvement in overall survival of metastatic melanoma patients. This review highlights the clinical trial data that supports the efficacy of ipilimumab, the immune-related response criteria used to evaluate clinical response, and side-effect profile associated with ipilimumab treatment.Keywords: ipilimumab, melanoma, T-cells, CTLA-4

  7. Phase 1 clinical trial of the novel proteasome inhibitor marizomib with the histone deacetylase inhibitor vorinostat in patients with melanoma, pancreatic and lung cancer based on in vitro assessments of the combination.

    Science.gov (United States)

    Millward, Michael; Price, Timothy; Townsend, Amanda; Sweeney, Christopher; Spencer, Andrew; Sukumaran, Shawgi; Longenecker, Angie; Lee, Lonnie; Lay, Ana; Sharma, Girish; Gemmill, Robert M; Drabkin, Harry A; Lloyd, G Kenneth; Neuteboom, Saskia T C; McConkey, David J; Palladino, Michael A; Spear, Matthew A

    2012-12-01

    Combining proteasome and histone deacetylase (HDAC) inhibition has been seen to provide synergistic anti-tumor activity, with complementary effects on a number of signaling pathways. The novel bi-cyclic structure of marizomib with its unique proteasome inhibition, toxicology and efficacy profiles, suggested utility in combining it with an HDAC inhibitor such as vorinostat. Thus, in this study in vitro studies assessed the potential utility of combining marizomib and vorinostat, followed by a clinical trial with the objectives of assessing the recommended phase 2 dose (RP2D), pharmacokinetics (PK), pharmacodynamics (PD), safety and preliminary anti-tumor activity of the combination in patients. Combinations of marizomib and vorinostat were assessed in vitro. Subsequently, in a Phase 1 clinical trial patients with melanoma, pancreatic carcinoma or Non-small Cell Lung Cancer (NSCLC) were given escalating doses of weekly marizomib in combination with vorinostat 300 mg daily for 16 days in 28 day cycles. In addition to standard safety studies, proteasome inhibition and pharmacokinetics were assayed. Marked synergy of marizomib and vorinostat was seen in tumor cell lines derived from patients with NSCLC, melanoma and pancreatic carcinoma. In the clinical trial, 22 patients were enrolled. Increased toxicity was not seen with the combination. Co-administration did not appear to affect the PK or PD of either drug in comparison to historical data. Although no responses were demonstrated using RECIST criteria, 61% of evaluable patients demonstrated stable disease with 39% having decreases in tumor measurements. Treatment of multiple tumor cell lines with marizomib and vorinostat resulted in a highly synergistic antitumor activity. The combination of full dose marizomib with vorinostat is tolerable in patients with safety findings consistent with either drug alone.

  8. 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.

  9. 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

  10. CCR 20th Anniversary Commentary: MAPK/ERK Pathway Inhibition in Melanoma-Kinase Inhibition Redux.

    Science.gov (United States)

    Davar, Diwakar; Kirkwood, John M

    2015-12-15

    In the January 15, 2012, issue of Clinical Cancer Research, Kirkwood and colleagues published a study comparing the MEK inhibitor selumetinib with temozolomide in unselected metastatic melanoma. Although selumetinib did not improve survival or response, most responders had BRAF-activating mutations, and selumetinib has since demonstrated efficacy in BRAF-mutant melanoma. This study laid the groundwork for the evaluation of BRAF/MEK inhibitors in BRAF-mutant melanoma. ©2015 American Association for Cancer Research.

  11. Amplitude variation in calibrated audiometer systems in Clinical Simulations

    Directory of Open Access Journals (Sweden)

    Christopher Barlow

    2014-01-01

    Full Text Available Manual pure tone audiometry is considered to be the gold standard for the assessment of hearing thresholds and has been in consistent use for a long period of time. An increased legislative requirement to monitor and screen workers, and an increasing amount of legislation relating to hearing loss is putting greater reliance on this as a tool. There are a number of questions regarding the degree of accuracy of pure tone audiometry when undertaken in field conditions, particularly relating to the difference in conditions between laboratory calibration and clinical or industrial screening use. This study analyzed the output sound pressure level of four different commercial audiometers, all using TDH39 headphones and each of which had recently undergone calibration at an appropriate laboratory. Levels were measured using a Bruël and Kjaer Head and Torso simulator, which accurately replicates the size and shape of a human head, including the ears. A clinical environment was simulated by a trained audiometrist replacing the headphones for each test. Tests were undertaken at three presentation levels, and at the frequencies of 250 Hz, 500 Hz, 1 kHz, 2 kHz, 4 kHz and 6 kHz. The results showed a high level of test-retest variability, both between different audiometers and within the same audiometer. Maximum variation of sound pressure level at the ear for the same tone presentation was 21 decibels, with a particularly high level of variation at 6 kHz for all meters. An audiometer with attenuating cups exhibited significantly higher variation than ones using supral-aural headphones. Overall the variation exhibited suggests that there is a higher degree of potential error with screening pure tone audiometry than is commonly assumed and that results particularly at the 6 kHz frequency need to be assessed carefully alongside other methods such as speech audiometry.

  12. Clinical simulation as a boundary object in design of health IT-systems

    DEFF Research Database (Denmark)

    Rasmussen, Stine Loft; Jensen, Sanne; Lyng, Karen Marie

    2013-01-01

    simulation provides the opportunity to evaluate the design and the usage of clinical IT-systems without endangering the patients and interrupting clinical work. In this paper we present how clinical simulation additionally holds the potential to function as a boundary object in the design process. The case...... points out that clinical simulation provides an opportunity for discussions and mutual learning among the various stakeholders involved in design of standardized electronic clinical documentation templates. The paper presents and discusses the use of clinical simulation in the translation, transfer...... and transformation of knowledge between various stakeholders in a large healthcare organization...

  13. Imaging malignant melanoma with {sup 18}F-5-FPN

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Hongyan; Xia, Xiaotian; Li, Chongjiao; Song, Yiling; Qin, Chunxia; Liu, Qingyao; Zhang, Yongxue; Lan, Xiaoli [Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology (China); Hubei Key Laboratory of Molecular Imaging (China)

    2016-01-15

    Radiolabelled benzamides are attractive candidates for targeting melanoma because they bind to melanin and exhibit high tumour uptake and retention. {sup 18}F-5-Fluoro-N-(2-[diethylamino]ethyl)picolinamide ({sup 18}F-5-FPN), a benzamide analogue, was prepared and its pharmacokinetics and binding affinity evaluated both in vitro and in vivo to assess its clinical potential in the diagnosis and staging of melanoma. {sup 18}F-5-FPN was prepared and purified. Its binding specificity was measured in vitro in two different melanoma cell lines, one pigmented (B16F10 cells) and one nonpigmented (A375m cells), and in vivo in mice xenografted with the same cell lines. Dynamic and static PET images using {sup 18}F-5-FPN were obtained in the tumour-bearing mice, and the static images were also compared with those acquired with {sup 18}F-FDG. PET imaging with {sup 18}F-5-FPN was also performed in B16F10 tumour-bearing mice with lung metastases. {sup 18}F-5-FPN was successfully prepared with radiochemical yields of 5 - 10 %. Binding of {sup 18}F-5-FPN to B16F10 cells was much higher than to A375m cells. On dynamic PET imaging B16F10 tumours were visible about 1 min after injection of the tracer, and the uptake gradually increased over time. {sup 18}F-5-FPN was rapidly excreted via the kidneys. B16F10 tumours were clearly visible on static images acquired 1 and 2 h after injection, with high uptake values of 24.34 ± 6.32 %ID/g and 16.63 ± 5.41 %ID/g, respectively, in the biodistribution study (five mice). However, there was no visible uptake by A375m tumours. {sup 18}F-5-FPN and {sup 18}F-FDG PET imaging were compared in B16F10 tumour xenografts, and the tumour-to-background ratio of {sup 18}F-5-FPN was ten times higher than that of {sup 18}F-FDG (35.22 ± 7.02 vs. 3.29 ± 0.53, five mice). {sup 18}F-5-FPN PET imaging also detected simulated lung metastases measuring 1 - 2 mm. {sup 18}F-5-FPN specifically targeted melanin in vitro and in vivo with high retention and affinity

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

    International Nuclear Information System (INIS)

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

    2007-01-01

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

  15. 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…

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. Proteomic Analysis of Laser Microdissected Melanoma Cells from Skin Organ Cultures

    Science.gov (United States)

    Hood, Brian L.; Grahovac, Jelena; Flint, Melanie S.; Sun, Mai; Charro, Nuno; Becker, Dorothea; Wells, Alan; Conrads, Thomas P

    2010-01-01

    Gaining insights into the molecular events that govern the progression from melanoma in situ to advanced melanoma, and understanding how the local microenvironment at the melanoma site influences this progression, are two clinically pivotal aspects that to date are largely unexplored. In an effort to identify key regulators of the crosstalk between melanoma cells and the melanoma-skin microenvironment, primary and metastatic human melanoma cells were seeded into skin organ cultures (SOCs), and grown for two weeks. Melanoma cells were recovered from SOCs by laser microdissection and whole-cell tryptic digests analyzed by nanoflow liquid chromatography-tandem mass spectrometry with an LTQ-Orbitrap. The differential protein abundances were calculated by spectral counting, the results of which provides evidence that cell-matrix and cell-adhesion molecules that are upregulated in the presence of these melanoma cells recapitulate proteomic data obtained from comparative analysis of human biopsies of invasive melanoma and a tissue sample of adjacent, non-involved skin. This concordance demonstrates the value of SOCs for conducting proteomic investigations of the melanoma microenvironment. PMID:20459140

  1. High frequency of PTEN mutations in nevi and melanomas from xeroderma pigmentosum patients.

    Science.gov (United States)

    Masaki, Taro; Wang, Yun; DiGiovanna, John J; Khan, Sikandar G; Raffeld, Mark; Beltaifa, Senda; Hornyak, Thomas J; Darling, Thomas N; Lee, Chyi-Chia R; Kraemer, Kenneth H

    2014-05-01

    We examined nevi and melanomas in 10 xeroderma pigmentosum (XP) patients with defective DNA repair. The lesions had a lentiginous appearance with markedly increased numbers of melanocytes. Using laser capture microdissection, we performed DNA sequencing of 18 benign and atypical nevi and 75 melanomas (melanoma in situ and invasive melanomas). The nevi had a similar high frequency of PTEN mutations as melanomas [61% (11/18) versus 53% (39/73)]. Both had a very high proportion of UV-type mutations (occurring at adjacent pyrimidines) [91% (10/11) versus 92% (36/39)]. In contrast to melanomas in the general population, the frequency of BRAF mutations (11%, 7/61), NRAS mutations (21%, 13/62), and KIT mutations (21%, 6/28) in XP melanomas was lower than for PTEN. Phospho-S6 immunostaining indicated activation of the mTOR pathway in the atypical nevi and melanomas. Thus, the clinical and histological appearances and the molecular pathology of these UV-related XP nevi and melanomas were different from nevi and melanomas in the general population. © 2014 Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

  2. CHOROIDAL MELANOMA IN A PATIENT WITH WAARDENBURG SYNDROME.

    Science.gov (United States)

    Itty, Sujit; Richter, Elizabeth R; McCannel, Tara A

    2015-01-01

    To report a case of choroidal malignant melanoma in a patient with Waardenburg syndrome and bilateral choroidal pigmentary abnormalities. Clinical examination and multimodal imaging of the case. A 45-year-old woman presented with asymptomatic flat choroidal pigmentation abnormalities in both eyes. A choroidal lesion was identified in the inferotemporal periphery of the left eye arising from an area of hyperpigmentation; ultrasonography findings were consistent with a choroidal melanoma. The patient endorsed a personal and family history of premature graying of hair and was identified to have dystopia canthorum consistent with the diagnosis of Waardenburg syndrome. The authors present the first reported case of concurrent Waardenburg syndrome and choroidal malignant melanoma. This cooccurrence may suggest that the relative hyperpigmented regions in affected fundi may be abnormal and should be monitored closely for the development of choroidal melanoma.

  3. Kinase fusions are frequent in Spitz tumors and spitzoid melanomas

    Science.gov (United States)

    Esteve-Puig, Rosaura; Botton, Thomas; Yeh, Iwei; Lipson, Doron; Otto, Geoff; Brennan, Kristina; Murali, Rajmohan; Garrido, Maria; Miller, Vincent A.; Ross, Jeffrey S; Berger, Michael F.; Sparatta, Alyssa; Palmedo, Gabriele; Cerroni, Lorenzo; Busam, Klaus J.; Kutzner, Heinz; Cronin, Maureen T; Stephens, Philip J; Bastian, Boris C.

    2014-01-01

    Spitzoid neoplasms are a group of melanocytic tumors with distinctive histopathologic features. They include benign tumors (Spitz nevi), malignant tumors (spitzoid melanomas), and tumors with borderline histopathologic features and uncertain clinical outcome (atypical Spitz tumors). Their genetic underpinnings are poorly understood, and alterations in common melanoma-associated oncogenes are typically absent. Here we show that spitzoid neoplasms harbor kinase fusions of ROS1 (17%), NTRK1 (16%), ALK (10%), BRAF (5%), and RET (3%) in a mutually exclusive pattern. The chimeric proteins are constitutively active, stimulate oncogenic signaling pathways, are tumorigenic, and are found in the entire biologic spectrum of spitzoid neoplasms, including 55% of Spitz nevi, 56% of atypical Spitz tumors, and 39% of spitzoid melanomas. Kinase inhibitors suppress the oncogenic signaling of the fusion proteins in vitro. In summary, kinase fusions account for the majority of oncogenic aberrations in spitzoid neoplasms, and may serve as therapeutic targets for metastatic spitzoid melanomas. PMID:24445538

  4. An oracle: antituberculosis pharmacokinetics-pharmacodynamics, clinical correlation, and clinical trial simulations to predict the future.

    Science.gov (United States)

    Pasipanodya, Jotam; Gumbo, Tawanda

    2011-01-01

    Antimicrobial pharmacokinetic-pharmacodynamic (PK/PD) science and clinical trial simulations have not been adequately applied to the design of doses and dose schedules of antituberculosis regimens because many researchers are skeptical about their clinical applicability. We compared findings of preclinical PK/PD studies of current first-line antituberculosis drugs to findings from several clinical publications that included microbiologic outcome and pharmacokinetic data or had a dose-scheduling design. Without exception, the antimicrobial PK/PD parameters linked to optimal effect were similar in preclinical models and in tuberculosis patients. Thus, exposure-effect relationships derived in the preclinical models can be used in the design of optimal antituberculosis doses, by incorporating population pharmacokinetics of the drugs and MIC distributions in Monte Carlo simulations. When this has been performed, doses and dose schedules of rifampin, isoniazid, pyrazinamide, and moxifloxacin with the potential to shorten antituberculosis therapy have been identified. In addition, different susceptibility breakpoints than those in current use have been identified. These steps outline a more rational approach than that of current methods for designing regimens and predicting outcome so that both new and older antituberculosis agents can shorten therapy duration.

  5. Absolute number of new lesions on {sup 18}F-FDG PET/CT is more predictive of clinical response than SUV changes in metastatic melanoma patients receiving ipilimumab

    Energy Technology Data Exchange (ETDEWEB)

    Anwar, Hoda; Sachpekidis, Christos; Dimitrakopoulou-Strauss, Antonia [German Cancer Research Center, Medical PET Group-Biological Imaging, Clinical Cooperation Unit Nuclear Medicine, Heidelberg (Germany); Winkler, Julia; Hassel, Jessica C. [University Hospital Heidelberg, Department of Dermatology and National Center for Tumor Diseases, Heidelberg (Germany); Kopp-Schneider, Annette [German Cancer Research Center, Department of Biostatistics, Heidelberg (Germany); Haberkorn, Uwe [German Cancer Research Center, Medical PET Group-Biological Imaging, Clinical Cooperation Unit Nuclear Medicine, Heidelberg (Germany); University of Heidelberg, Division of Nuclear Medicine, Heidelberg (Germany)

    2018-03-15

    Evaluation of response to immunotherapy is a matter of debate. The aim of the present study was to evaluate the response of metastatic melanoma to treatment with ipilimumab by means of {sup 18}F-FDG PET/CT, using the patients' clinical response as reference. The final cohort included in the analyses consisted of 41 patients with metastatic melanoma who underwent {sup 18}F-FDG PET/CT before and after administration of ipilimumab. After determination of the best clinical response, the PET/CT scans were reviewed and a separate independent analysis was performed, based on the number and functional size of newly emerged {sup 18}F-FDG-avid lesions, as well as on the SUV changes after therapy. The median observation time of the patients after therapy was 21.4 months (range 6.3-41.9 months). Based on their clinical response, patients were dichotomized into those with clinical benefit (CB) and those without CB (No-CB). The CB group (31 patients) included those with stable disease, partial remission and complete remission, and the No-CB group (10 patients) included those with progressive disease. The application of a threshold of four newly emerged {sup 18}F-FDG-avid lesions on the posttherapy PET/CT scan led to a sensitivity (correctly predicting CB) of 84% and a specificity (correctly predicting No-CB) of 100%. This cut-off was lower for lesions with larger functional diameters (three new lesions larger than 1.0 cm and two new lesions larger than 1.5 cm). SUV changes after therapy did not correlate with clinical response. Based on these findings, we developed criteria for predicting clinical response to immunotherapy by means of {sup 18}F-FDG PET/CT (PET Response Evaluation Criteria for Immunotherapy, PERCIMT). Our results show that a cut-off of four newly emerged {sup 18}F-FDG-avid lesions on posttherapy PET/CT gives a reliable indication of treatment failure in patients under ipilimumab treatment. Moreover, the functional size of the new lesions plays an important

  6. Treatment of cutaneous melanoma: current approaches and future prospects

    International Nuclear Information System (INIS)

    Algazi, Alain P; Soon, Christopher W; Daud, Adil I

    2010-01-01

    Melanoma is the most aggressive and deadly type of skin cancer. Surgical resection with or without lymph node sampling is the standard of care for primary cutaneous melanoma. Adjuvant therapy decisions may be informed by careful consideration of prognostic factors. High-dose adjuvant interferon alpha-2b increases disease-free survival and may modestly improve overall survival. Less toxic alternatives for adjuvant therapy are currently under study. External beam radiation therapy is an option for nodal beds where the risk of local recurrence is very high. In-transit melanoma metastases may be treated locally with surgery, immunotherapy, radiation, or heated limb perfusion. For metastatic melanoma, the options include chemotherapy or immunotherapy; targeted anti-BRAF and anti-KIT therapy is under active investigation. Standard chemotherapy yields objective tumor responses in approximately 10%–20% of patients, and sustained remissions are uncommon. Immunotherapy with high-dose interleukin-2 yields objective tumor responses in a minority of patients; however, some of these responses may be durable. Identification of activating mutations of BRAF, NRAS, c-KIT, and GNAQ in distinct clinical subtypes of melanoma suggest that these are molecularly distinct. Emerging data from clinical trials suggest that substantial improvements in the standard of care for melanoma may be possible

  7. Clinical Simulation and Workflow by use of two Clinical Information Systems, the Electronic Health Record and Digital Dictation

    DEFF Research Database (Denmark)

    Schou Jensen, Iben; Koldby, Sven

    2013-01-01

    digital dictation and the EHR (electronic health record) were simulated in realistic and controlled clinical environments. Useful information dealing with workflow and patient safety were obtained. The clinical simulation demonstrated that the EHR locks during use of the integration of digital dictation......Clinical information systems do not always support clinician workflows. An increasing number of unintended clinical inci-dents might be related to implementation of clinical infor-mation systems and to a new registration praxis of unin-tended clinical incidents. Evidence of performing clinical...... simulations before implementation of new clinical information systems provides the basis for use of this method. The intention has been to evaluate patient safety issues, functionality, workflow, and usefulness of a new solution before implementation in the hospitals. Use of a solution which integrates...

  8. Hypofractionated stereotactic photon radiotherapy of posteriorly located choroidal melanoma with five fractions at ten Gy – Clinical results after six years of experience

    International Nuclear Information System (INIS)

    Dunavoelgyi, Roman; Zehetmayer, Martin; Gleiss, Andreas; Geitzenauer, Wolfgang; Kircher, Karl; Georg, Dietmar; Schmidt-Erfurth, Ursula; Poetter, Richard; Dieckmann, Karin

    2013-01-01

    Purpose: To evaluate long-term safety and efficacy of hypofractionated stereotactic photon radiotherapy with 5 five fractions at 10 Gy each in patients with centrally located choroidal melanoma. Materials and Methods: Ninety-one patients with centrally located choroidal melanoma were treated stereotactically at a linear accelerator with 6 MV photon beams with 5 fractions at 10 Gy each. Examinations were performed at baseline and every 3 months in the first 2 years, then every 6 months until 5 years and yearly thereafter. Median follow-up was 37.8 months (IQR 19.2–49.9). They included visual acuity assessment, routine ophthalmological examinations with fundoscopy, echography for measurement of tumor dimensions, medical examinations and, if necessary, fluorescein angiography. Results: Initial tumor base diameters, height and volume were 11.20 mm (IQR 9.10–13.70), 9.80 mm (IQR 7.80–11.70), 4.53 mm (IQR 3.33–6.43) and 253.8 mm 3 (IQR 127.5–477.0). Local tumor control and eye retention rates were 97.7% and 86.4% after 5 years, respectively. Eight patients developed metastatic disease and 3 of them died due to metastatic disease during the follow-up period. Median visual acuity decreased from 0.67 initially to 0.05 at the last individual follow-up (p < 0.001). The most common toxicities (any grade) were radiation retinopathy (n = 39), optic neuropathy (n = 32), radiogenic cataract (n = 21), neovascular glaucoma (n = 15) and dry eye syndrome (n = 10). The 5 year probabilities to remain free of these side effects (any grade) were 26.0%, 45.4%, 55.4%, 72.6% and 80.5%, respectively. The most important prognostic factors for toxicities were the largest tumor base diameter, tumor height and tumor distance to the optic disk. Conclusion: Hypofractionated stereotactic photon radiotherapy with a total dose of 50 Gy delivered in 5 fractions is a highly effective treatment option in patients with centrally located choroidal melanoma and has a moderate toxicity profile

  9. 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.

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

    Science.gov (United States)

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

    2014-01-01

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

  11. 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.

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

    Science.gov (United States)

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

    2015-01-01

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

  13. Local melanoma recurrences in the scar after limited surgery for primary tumor

    DEFF Research Database (Denmark)

    Drzewiecki, K T; Andersson, A P

    1995-01-01

    The clinical and histologic records of 46 consecutive patients were reviewed who during the period 1980-1993 had recurrence from melanoma in the scar after limited surgery for a skin tumor. They constituted about 50% of all patients admitted with local recurrence from melanoma during this period....... At reexamination of the primary tumors, 16 were found to be malignant melanomas and 9 were nevi (four atypical and five benign). Twenty-one were missing, 11 of which had never been set for histologic examination. The median thickness of nine measurable melanomas was 0.66 mm. The recurrences in scar consisted of 34...... recurrences in the form of a new primary in a scar following limited surgery supports the theory of limited field change around a primary melanoma. Furthermore, limited procedures for primary melanoma, if followed by a recurrence in the scar, worsen the prognosis....

  14. Residents’ perceptions of simulation as a clinical learning approach

    Directory of Open Access Journals (Sweden)

    Catharine M Walsh

    2017-02-01

    Results: Residents’ perceptions of simulation included: 1 simulation serves pragmatic purposes; 2 simulation provides a safe space; 3 simulation presents perils and pitfalls; and 4 optimal design for simulation: integration and tension. Key findings included residents’ markedly narrow perception of simulation’s capacity to support non-technical skills development or its use beyond introductory learning. Conclusion: Trainees’ learning expectations of simulation were restricted. Educators should critically attend to the way they present simulation to learners as, based on theories of problem-framing, trainees’ a priori perceptions may delimit the focus of their learning experiences. If they view simulation as merely a replica of real cases for the purpose of practicing basic skills, they may fail to benefit from the full scope of learning opportunities afforded by simulation.

  15. Characteristic features of cutaneous melanoma in a dermatology referral centre in Tehran, Iran.

    Science.gov (United States)

    Kamyab, Kambiz; Kazemi, Sheyda; Azimi, Pourya; Azizpour, Arghavan; Ghandi, Narges; Pirooz, Elham; Noormohammadpour, Pedram; Mirshams-Shahshahani, Mostafa; Daneshpazhooh, Maryam

    2017-11-01

    The characteristics of cutaneous melanoma in the Middle-Eastern countries is poorly described. Therefore we conducted this study to determine the characteristics of melanoma in Iran. A retrospective, cross sectional study of melanoma patients seen at a tertiary referral centre, Iran, from May 2004 to October 2014. Clinical data included age and gender of the patients at the time of diagnosis, tumour location and tumour size. Histological characteristics included Breslow thickness, Clark level and subtype of tumour. A total of 450 cases of melanoma with a male/female ratio of 1.1:1 were reviewed. The mean age of patients was 57.5 years. The most frequent histological subtypes were acral lentiginous melanoma (30%) and lentigo maligna melanoma (29%). In 215 cases (49%) the tumour was located on the extremities. The second most common site was the face. Tumour invasion was mainly at Clark level III and IV. The mean Breslow thickness was 2.8 mm; 143 (38%) melanomas had a Breslow thickness less than 1 mm (T1) and 86 (23%) were more than 4 mm (T4). This study indicates that clinical and histological features of melanoma in Iranians (who are mainly of skin phototypes 3-4) are different from those observed in Western countries. Further cohort studies are required to evaluate the role of ethnic and environmental risk factors for melanoma in different populations. © 2017 The Australasian College of Dermatologists.

  16. Residents' perceptions of simulation as a clinical learning approach.

    Science.gov (United States)

    Walsh, Catharine M; Garg, Ankit; Ng, Stella L; Goyal, Fenny; Grover, Samir C

    2017-02-01

    Simulation is increasingly being integrated into medical education; however, there is little research into trainees' perceptions of this learning modality. We elicited trainees' perceptions of simulation-based learning, to inform how simulation is developed and applied to support training. We conducted an instrumental qualitative case study entailing 36 semi-structured one-hour interviews with 12 residents enrolled in an introductory simulation-based course. Trainees were interviewed at three time points: pre-course, post-course, and 4-6 weeks later. Interview transcripts were analyzed using a qualitative descriptive analytic approach. Residents' perceptions of simulation included: 1) simulation serves pragmatic purposes; 2) simulation provides a safe space; 3) simulation presents perils and pitfalls; and 4) optimal design for simulation: integration and tension. Key findings included residents' markedly narrow perception of simulation's capacity to support non-technical skills development or its use beyond introductory learning. Trainees' learning expectations of simulation were restricted. Educators should critically attend to the way they present simulation to learners as, based on theories of problem-framing, trainees' a priori perceptions may delimit the focus of their learning experiences. If they view simulation as merely a replica of real cases for the purpose of practicing basic skills, they may fail to benefit from the full scope of learning opportunities afforded by simulation.

  17. Residents’ perceptions of simulation as a clinical learning approach

    Science.gov (United States)

    Walsh, Catharine M.; Garg, Ankit; Ng, Stella L.; Goyal, Fenny; Grover, Samir C.

    2017-01-01

    Background Simulation is increasingly being integrated into medical education; however, there is little research into trainees’ perceptions of this learning modality. We elicited trainees’ perceptions of simulation-based learning, to inform how simulation is developed and applied to support training. Methods We conducted an instrumental qualitative case study entailing 36 semi-structured one-hour interviews with 12 residents enrolled in an introductory simulation-based course. Trainees were interviewed at three time points: pre-course, post-course, and 4–6 weeks later. Interview transcripts were analyzed using a qualitative descriptive analytic approach. Results Residents’ perceptions of simulation included: 1) simulation serves pragmatic purposes; 2) simulation provides a safe space; 3) simulation presents perils and pitfalls; and 4) optimal design for simulation: integration and tension. Key findings included residents’ markedly narrow perception of simulation’s capacity to support non-technical skills development or its use beyond introductory learning. Conclusion Trainees’ learning expectations of simulation were restricted. Educators should critically attend to the way they present simulation to learners as, based on theories of problem-framing, trainees’ a priori perceptions may delimit the focus of their learning experiences. If they view simulation as merely a replica of real cases for the purpose of practicing basic skills, they may fail to benefit from the full scope of learning opportunities afforded by simulation. PMID:28344719

  18. Recommendations for the establishment of a clinical simulation unit ...

    African Journals Online (AJOL)

    Simulation-enhanced medical education involves training ... Simulation techniques include the .... What lessons did you learn regarding the planning and implementation of a ..... radiological technology students in patient interactions. J Allied ...

  19. Efficacy and Safety of Nivolumab Alone or in Combination With Ipilimumab in Patients With Mucosal Melanoma: A Pooled Analysis

    DEFF Research Database (Denmark)

    D'Angelo, Sandra P; Larkin, James; Sosman, Jeffrey A

    2017-01-01

    Purpose Mucosal melanoma is an aggressive malignancy with a poor response to conventional therapies. The efficacy and safety of nivolumab (a programmed death-1 checkpoint inhibitor), alone or combined with ipilimumab (a cytotoxic T-lymphocyte antigen-4 checkpoint inhibitor), have not been reported...... in this rare melanoma subtype. Patients and Methods Data were pooled from 889 patients who received nivolumab monotherapy in clinical studies, including phase III trials; 86 (10%) had mucosal melanoma and 665 (75%) had cutaneous melanoma. Data were also pooled for patients who received nivolumab combined...... with ipilimumab (n = 35, mucosal melanoma; n = 326, cutaneous melanoma). Results Among patients who received nivolumab monotherapy, median progression-free survival was 3.0 months (95% CI, 2.2 to 5.4 months) and 6.2 months (95% CI, 5.1 to 7.5 months) for mucosal and cutaneous melanoma, with objective response...

  20. Evaluation of skin melanoma in spectral range 450-950 nm using principal component analysis

    Science.gov (United States)

    Jakovels, D.; Lihacova, I.; Kuzmina, I.; Spigulis, J.

    2013-06-01

    Diagnostic potential of principal component analysis (PCA) of multi-spectral imaging data in the wavelength range 450- 950 nm for distant skin melanoma recognition is discussed. Processing of the measured clinical data by means of PCA resulted in clear separation between malignant melanomas and pigmented nevi.

  1. Does the sun play a role in the aetiology of malignant melanoma ...

    African Journals Online (AJOL)

    The role of the sun in the aetiology of malignant melanoma is controversial. In 1992 Schuster1 wrote provocatively, 'Despite the lack of evidence of a causal link between sun exposure and melanoma, fear has been used shamelessly to frighten people out of the sun and into pigmented lesion clinics.' He claimed that the ...

  2. Future perspectives in melanoma research. Meeting report from the "Melanoma Research: a bridge Naples-USA. Naples, December 6th-7 th2010"

    Directory of Open Access Journals (Sweden)

    Maio Michele

    2011-03-01

    Full Text Available Abstract Progress in understanding the molecular basis of melanoma has made possible the identification of molecular targets with important implications in clinical practice. In fact, new therapeutic approaches are emerging from basic science and it will be important to implement their rapid translation into clinical practice by active clinical investigation. The first meeting of Melanoma Research: a bridge Naples-USA, organized by Paolo A. Ascierto (INT, Naples, Italy and Francesco Marincola (NIH, Bethesda, USA took place in Naples, on 6-7 December 2010. This international congress gathered more than 30 international and Italian faculty members and was focused on recent advances in melanoma molecular biology, immunology and therapy, and created an interactive discussion across Institutions belonging to Government, Academy and Pharmaceutical Industry, in order to stimulate new approaches in basic, translational and clinical research. Four topics of discussion were identified: New pathways in Melanoma, Biomarkers, Clinical Trials and New Molecules and Strategies.

  3. 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.

  4. Patient safety and quality of care: How may clinical simulation contribute?

    Directory of Open Access Journals (Sweden)

    Sanne Jensen

    2015-09-01

    Full Text Available The usability of health information technology (IT is increasingly recognized as critically important to the development of systems that ensure patient safety and quality of care. The substantial complexity of organizations, work practice and physical environments within the healthcare sector influences the development and application of health IT. When health IT is introduced in local clinical work practices, potential patient safety hazards and insufficient support of work practices need to be examined. Qualitative methods, such as clinical simulation, may be used to evaluate new technology in correlation with the clinical context and to study the interaction between users, technology and work practice. Compared with the “classic” methods, such as heuristic inspection and usability testing, clinical simulation takes the clinical context into account. Clinical simulation can be useful in many processes in the human-centred design cycle. In the requirement specification, clinical simulation can be useful to analyze user requirements and work practice as well to evaluate requirements. In the design of health IT, clinical simulation can be used to evaluate clinical information systems and serve as common ground to help to achieve a shared understanding between various communities of practice. In a public procurement process, a clinical simulation-based assessment can help give insight into different solutions and how they support work practice. Before organizational implementation, clinical simulation is a very suitable means, by which to assess an application in connection with work practice.

  5. 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.

  6. 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.

  7. Cutaneous melanoma – guidelines for diagnostics and therapy in 2016

    Directory of Open Access Journals (Sweden)

    Piotr Rutkowski

    2016-02-01

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

  8. Primary Malignant Melanoma of the Lung: A Case Report

    Directory of Open Access Journals (Sweden)

    Karagianni Evangelia

    2003-11-01

    Full Text Available Abstract Background Primary melanoma of the lung is an extremely rare pathological entity and sparsely reported in the literature. Case presentation A case of primary malignant melanoma of the lung in a 41-year-old female is reported. The clinical, radiological and histopathological features are discussed. The initial symptom was cough, whereas the chest radiography showed a round opacity of the right lung. The computed tomography of the chest revealed a well-demarcated mass lesion in the right upper lobe. Endobronchial mass causing obstruction of the upper lobar bronchus was the bronchoscopic finding. Patient underwent pneumonectomy. A diagnosis of melanoma was confirmed postoperatively after the immunohistochemistry. Primary nature of the tumour in the lung results from the demonstration of characteristic junctional pattern of melanoma cells beneath the bronchial epithelium on histopathology, and from exclusion of other potential primary sites in the clinical, paraclinical and laboratory examination. Conclusions Primary melanoma of the lung represents a rare pathological entity. Careful interpretation of histopathological information in correlation with all other findings from clinical and paraclinical studies can establish a diagnosis. Follow-up is necessary in order to diagnose potential dissemination or secondary sites of the disease. Due to the small number of cases reported in the literature, there is no experience on the management and the prognosis of the disease, but surgical resection remains the cornerstone of the treatment.

  9. Interferon-β gene transfer induces a strong cytotoxic bystander effect on melanoma cells.

    Science.gov (United States)

    Rossi, Úrsula A; Gil-Cardeza, María L; Villaverde, Marcela S; Finocchiaro, Liliana M E; Glikin, Gerardo C

    2015-05-01

    A local gene therapy scheme for the delivery of type I interferons could be an alternative for the treatment of melanoma. We evaluated the cytotoxic effects of interferon-β (IFNβ) gene lipofection on tumor cell lines derived from three human cutaneous and four canine mucosal melanomas. The cytotoxicity of human IFNβ gene lipofection resulted higher or equivalent to that of the corresponding addition of the recombinant protein (rhIFNβ) to human cells. IFNβ gene lipofection was not cytotoxic for only one canine melanoma cell line. When cultured as monolayers, three human and three canine IFNβ-lipofected melanoma cell lines displayed a remarkable bystander effect. As spheroids, the same six cell lines were sensitive to IFNβ gene transfer, two displaying a significant multicell resistance phenotype. The effects of conditioned IFNβ-lipofected canine melanoma cell culture media suggested the release of at least one soluble thermolabile cytotoxic factor that could not be detected in human melanoma cells. By using a secretion signal-free truncated human IFNβ, we showed that its intracellular expression was enough to induce cytotoxicity in two human melanoma cell lines. The lower cytoplasmatic levels of reactive oxygen species detected after intracellular IFNβ expression could be related to the resistance displayed by one human melanoma cell line. As IFNβ gene transfer was effective against most of the assayed melanomas in a way not limited by relatively low lipofection efficiencies, the clinical potential of this approach is strongly supported. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  10. A case of desmoplastic melanoma that was difficult to distinguish from malignant peripheral nerve sheath tumor

    Directory of Open Access Journals (Sweden)

    Kenji Yorita

    2018-03-01

    Full Text Available The clinical and pathological diagnosis of desmoplastic melanoma is difficult, because almost 50% of desmoplastic melanoma cases involve non-pigmented lesions and the tumor cells can resemble fibroblasts or Schwannian cells based on their frequent amelanotic features. Moreover, desmoplastic melanoma typically has low positive rates for melanoma markers, with the exception of the S-100 protein. We report the case of an 81-year-old Japanese man with an 8-mm desmoplastic melanoma. He initially noticed a painless and non-pigmented skin lesion that did not grow noticeably for 6 months. It was unlikely that he had von Recklinghausen disease, and the mass was initially considered a dermatofibroma. Excisional biopsy revealed an intradermal mass, with the superficial portion mimicking neurofibroma and the deeper portion exhibiting nodular growth of sarcomatoid spindle cells. The tumor region lacked intradermal proliferation of atypical melanocytic cells, intracytoplasmic melanin, and expression of melanoma markers (except S-100 protein and Sox10. Although a malignant peripheral nerve sheath tumor derived from neurofibroma was possible, the slow growth with diffuse and strong immunoreactivity to the S-100 protein and Sox10 favored a diagnosis of desmoplastic melanoma. Pathologists should recognize that desmoplastic melanoma may not involve in situ lesions or the immunohistochemical expression of standard melanoma markers.

  11. Oncogenic mutations in melanomas and benign melanocytic nevi of the female genital tract.

    Science.gov (United States)

    Tseng, Diane; Kim, Julie; Warrick, Andrea; Nelson, Dylan; Pukay, Marina; Beadling, Carol; Heinrich, Michael; Selim, Maria Angelica; Corless, Christopher L; Nelson, Kelly

    2014-08-01

    The genetic heterogeneity of melanomas and melanocytic nevi of the female genital tract is poorly understood. We aim to characterize the frequency of mutations of the following genes: BRAF, NRAS, KIT, GNA11, and GNAQ in female genital tract melanomas. We also characterize the frequency of BRAF mutations in female genital tract melanomas compared with melanocytic nevi. Mutational screening was performed on the following female genital tract melanocytic neoplasms: 25 melanomas, 7 benign melanocytic nevi, and 4 atypical melanocytic nevi. Of the 25 female genital tract melanoma specimens queried, KIT mutations were detected in 4 (16.0%), NRAS mutations in 4 (16.0%), and BRAF mutations in 2 (8.0%) samples. Two of the tumors with KIT mutations harbored double mutations in the same exon. No GNAQ or GNA11 mutations were identified among 11 melanomas screened. BRAF V600E mutations were detected in 7 of 7 benign melanocytic genital nevi (100%) and 3 of 4 atypical genital nevi (75%). Our study is limited by the small sample size of this rare subset of melanomas. KIT, NRAS, and BRAF mutations are found in a subset of female genital tract melanomas. Screening for oncogenic mutations is important for developing and applying clinical therapies for melanomas of the female genital tract. Copyright © 2014 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  12. Impact of MAPK Pathway Activation in BRAFV600 Melanoma on T Cell and Dendritic Cell Function

    Directory of Open Access Journals (Sweden)

    Patrick A. Ott

    2013-10-01

    Full Text Available Constitutive upregulation of the MAPK pathway by a BRAFV600 mutation occurs in about half of melanomas. This leads to increased oncogenic properties such as tumor cell invasion, metastatic potential, and resistance to apoptosis. Blockade of the MAPK pathway with highly specific kinase inhibitors induces unprecedented tumor response rates in patients with advanced BRAFV600 mutant melanoma. Immune checkpoint blockade with monoclonal antibodies targeting cytotoxic T-lymphocyte antigen 4 and programed death-1/PD-L1 has also demonstrated striking anti-tumor activity in patients with advanced melanoma. Tumor responses are likely limited by multiple additional layers of immune suppression in the tumor microenvironment. There is emerging preclinical and clinical evidence suggesting that MAPK inhibition has a beneficial effect on the immunosuppressive tumor microenvironment, providing a strong rationale for combined immunotherapy and MAPK pathway inhibition in melanoma. The T cell response has been the main focus in the studies reported to date. Since dendritic cells (DCs are important in the induction of tumor-specific T cell responses, the impact of MAPK pathway activation in melanoma on DC function is critical for the melanoma directed immune response. BRAFV600E melanoma cells modulate DCs through the MAPK pathway because its blockade in melanoma cells can reverse suppression of DC function. As both MEK/BRAF inhibition and immune checkpoint blockade have recently taken center stage in the treatment of melanoma, a deeper understanding of how MAPK pathway inhibition affects the tumor immune response is needed.

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

    Science.gov (United States)

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

    2018-07-01

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

  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. 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.

  16. 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

  17. PET and SPECT imaging of melanoma: the state of the art

    Energy Technology Data Exchange (ETDEWEB)

    Wei, Weijun [Shanghai Jiao Tong University Affiliated Sixth People' s Hospital, Department of Nuclear Medicine, Shanghai (China); University of Wisconsin-Madison, Department of Radiology, Madison, WI (United States); Ehlerding, Emily B. [University of Wisconsin-Madison, Department of Medical Physics, Madison, WI (United States); Lan, Xiaoli [Huazhong University of Science and Technology (China); Hubei Key Laboratory of Molecular Imaging, Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Wuhan (China); Luo, Quanyong [Shanghai Jiao Tong University Affiliated Sixth People' s Hospital, Department of Nuclear Medicine, Shanghai (China); Cai, Weibo [University of Wisconsin-Madison, Department of Radiology, Madison, WI (United States); University of Wisconsin-Madison, Department of Medical Physics, Madison, WI (United States); University of Wisconsin Carbone Cancer Center, Madison, WI (United States)

    2018-01-15

    Melanoma represents the most aggressive form of skin cancer, and its incidence continues to rise worldwide. {sup 18}F-FDG PET imaging has transformed diagnostic nuclear medicine and has become an essential component in the management of melanoma, but still has its drawbacks. With the rapid growth in the field of nuclear medicine and molecular imaging, a variety of promising probes that enable early diagnosis and detection of melanoma have been developed. The substantial preclinical success of melanin- and peptide-based probes has recently resulted in the translation of several radiotracers to clinical settings for noninvasive imaging and treatment of melanoma in humans. In this review, we focus on the latest developments in radiolabeled molecular imaging probes for melanoma in preclinical and clinical settings, and discuss the challenges and opportunities for future development. (orig.)

  18. PET and SPECT imaging of melanoma: the state of the art

    International Nuclear Information System (INIS)

    Wei, Weijun; Ehlerding, Emily B.; Lan, Xiaoli; Luo, Quanyong; Cai, Weibo

    2018-01-01

    Melanoma represents the most aggressive form of skin cancer, and its incidence continues to rise worldwide. 18 F-FDG PET imaging has transformed diagnostic nuclear medicine and has become an essential component in the management of melanoma, but still has its drawbacks. With the rapid growth in the field of nuclear medicine and molecular imaging, a variety of promising probes that enable early diagnosis and detection of melanoma have been developed. The substantial preclinical success of melanin- and peptide-based probes has recently resulted in the translation of several radiotracers to clinical settings for noninvasive imaging and treatment of melanoma in humans. In this review, we focus on the latest developments in radiolabeled molecular imaging probes for melanoma in preclinical and clinical settings, and discuss the challenges and opportunities for future development. (orig.)

  19. Shared care in the follow-up of early-stage melanoma: a qualitative study of Australian melanoma clinicians’ perspectives and models of care

    Directory of Open Access Journals (Sweden)

    Rychetnik Lucie

    2012-12-01

    Full Text Available Abstract Background Patients with early stage melanoma have high survival rates but require long-term follow-up to detect recurrences and/or new primary tumours. Shared care between melanoma specialists and general practitioners is an increasingly important approach to meeting the needs of a growing population of melanoma survivors. Methods In-depth qualitative study based on semi-structured interviews with 16 clinicians (surgical oncologists, dermatologists and melanoma unit GPs who conduct post-treatment follow-up at two of Australia’s largest specialist referral melanoma treatment and diagnosis units. Interviews were recorded, transcribed and analysed to identify approaches to shared care in follow-up, variations in practice, and explanations of these. Results Melanoma unit clinicians utilised shared care in the follow-up of patients with early stage melanoma. Schedules were determined by patients’ clinical risk profiles. Final arrangements for delivery of those schedules (by whom and where were influenced by additional psychosocial, professional and organizational considerations. Four models of shared care were described: (a surgical oncologist alternating with dermatologist (in-house or local to patient; (b melanoma unit dermatologist and other local doctor (e.g. family physician; (c surgical oncologist and local doctor; or (d melanoma physician and local doctor. Conclusions These models of shared care offer alternative solutions to managing the requirements for long-term follow-up of a growing number of patients with stage I/II melanoma, and warrant further comparative evaluation of outcomes in clinical trials, with detailed cost/benefit analyses.

  20. Developing Clinical Competency in Crisis Event Management: An Integrated Simulation Problem-Based Learning Activity

    Science.gov (United States)

    Liaw, S. Y.; Chen, F. G.; Klainin, P.; Brammer, J.; O'Brien, A.; Samarasekera, D. D.

    2010-01-01

    This study aimed to evaluate the integration of a simulation based learning activity on nursing students' clinical crisis management performance in a problem-based learning (PBL) curriculum. It was hypothesized that the clinical performance of first year nursing students who participated in a simulated learning activity during the PBL session…

  1. [A case of pulmonary malignant melanoma mimicking lung abscess].

    Science.gov (United States)

    Mochizuki, Hideaki; Chikui, Emiko; Tokumaru, Aya; Kato, Takayuki; Arai, Tomio; Takahashi, Hideki

    2011-06-01

    An 84-year-old man was admitted with paresis of the right lower limb. Hemorrhagic lesions were demonstrated in the left frontoparietal lobe and cerebellum by cranial computed tomography (CT) and magnetic resonance imaging (MRI). Chest CT revealed an ill-defined mass measuring 4 x 6 cm in the left lower lobe of the lung, although bronchoscopic examination failed to obtain pathological diagnosis. Clinical diagnosis of primary lung cancer with multiple brain metastases was made, and he underwent whole brain radiotherapy. The pulmonary and cerebral lesions mimicked abscesses during his clinical course, and he died of respiratory failure due to bilateral pneumonia three months after admission. Autopsy revealed that both the pulmonary and brain lesions were malignant melanomas, but no other melanoma lesions could be identified despite meticulous investigation. Although malignant melanoma with an unknown primary site is rare in Japan, careful evaluation of the CT and MRI findings might be the key to correct diagnosis in this case.

  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. Use of simulation to solve outpatient clinic problems: A review of the literature

    Directory of Open Access Journals (Sweden)

    Tang Sai Hong

    2013-11-01

    Full Text Available The increasing demand for outpatient services has led to overcrowded clinics, long waiting times for patients, and extended staff working hours in outpatient clinics. Simulation tools have been used to ameliorate deficiencies in the appointment system, resource allocation, and patient flow management that are the root causes of these problems. Integrated studies that considered these three factors together produced better results than attempts to resolve individual causes. While simulation has proved to be an effective problem-solving tool for outpatient clinic management, there is still room for improvement. This paper reviews studies over the past 50 years that have applied management simulation to resolve outpatient clinic problems.

  5. 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.

  6. Self-Reflection of Video-Recorded High-Fidelity Simulations and Development of Clinical Judgment.

    Science.gov (United States)

    Bussard, Michelle E

    2016-09-01

    Nurse educators are increasingly using high-fidelity simulators to improve prelicensure nursing students' ability to develop clinical judgment. Traditionally, oral debriefing sessions have immediately followed the simulation scenarios as a method for students to connect theory to practice and therefore develop clinical judgment. Recently, video recording of the simulation scenarios is being incorporated. This qualitative, interpretive description study was conducted to identify whether self-reflection on video-recorded high-fidelity simulation (HFS) scenarios helped prelicensure nursing students to develop clinical judgment. Tanner's clinical judgment model was the framework for this study. Four themes emerged from this study: Confidence, Communication, Decision Making, and Change in Clinical Practice. This study indicated that self-reflection of video-recorded HFS scenarios is beneficial for prelicensure nursing students to develop clinical judgment. [J Nurs Educ. 2016;55(9):522-527.]. Copyright 2016, SLACK Incorporated.

  7. Optical ensemble analysis of intraocular lens performance through a simulated clinical trial with ZEMAX.

    Science.gov (United States)

    Zhao, Huawei

    2009-01-01

    A ZEMAX model was constructed to simulate a clinical trial of intraocular lenses (IOLs) based on a clinically oriented Monte Carlo ensemble analysis using postoperative ocular parameters. The purpose of this model is to test the feasibility of streamlining and optimizing both the design process and the clinical testing of IOLs. This optical ensemble analysis (OEA) is also validated. Simulated pseudophakic eyes were generated by using the tolerancing and programming features of ZEMAX optical design software. OEA methodology was verified by demonstrating that the results of clinical performance simulations were consistent with previously published clinical performance data using the same types of IOLs. From these results we conclude that the OEA method can objectively simulate the potential clinical trial performance of IOLs.

  8. Targeted alpha therapy for melanoma : from bench to bedside

    International Nuclear Information System (INIS)

    Allen, B.J.; Rizvi, S.M.A.; Li, Y.; Tsui, W.; Douglas, S.; Raja, C.; Graham, P.; Smart, R.; Butler, P.; Kearsley, J.; Thompson, J.

    2001-01-01

    Full text: The control of metastatic melanoma remains an elusive objective. Targeted alpha therapy (TAT) offers a new approach to the control of micrometastases and regression of tumours. The alpha emitting immunoconjugate (AIC) against malignant melanoma has been prepared by chelating Bi-213 to the anti-melanoma antibody 9.2.27, and injected locally at 2 d post-inoculation of 1.5 million melanoma cells, or intralesionally into skin tumours. Human subjects receive 50μCi intralesional dose, escalating to 1 mCi. The clearances from the tumour, kidneys and bladder are monitored by a NaI detector that detects the 440 keV gamma ray. Blood samples and tumour photographs are taken at O. 2 and 4 weeks; tumours are excised at 4 weeks. Isolated cancer cells and preangiogenic cell clusters in mice can be eliminated with 25 μCi local AIC injection, and intra-lesional injections of 100 μCi are sufficient to completely regress melanomas with volumes up to 300 mm 3 without side-effects. Systemic TAT with a single administration is less effective with 100% growth delay of tumours observed, and ∼20% complete inhibition. The clinical TAT trial for recurrent subcutaneous melanoma has been approved by the NSW Radiation Advisory Committee and the SES Human Ethics Committee. In a world first phase 1 study, the first 5 subjects have been treated by intralesional injection, 3 at 50 μCi, and 2 at 150 μCi. All subjects having unchanged blood profiles at 2 and 4 weeks post-therapy. Tumour volumes appear little changed. However, histology of a 3 cm melanoma shows that almost complete cell kill occurred at 150 μCi, with only a few small cell clusters surviving. Local TAT inhibits tumourogenesis and intralesional TAT completely regresses melanoma in mice. Intralesional TAT for melanoma in human subjects is non-toxic so far and appears to be a promising modality. The ultimate objective is to apply systemic TAT for the control of melanoma micrometastases. Copyright (2001) Australasian

  9. Feasibility of Augmented Reality in Clinical Simulations: Using Google Glass With Manikins.

    Science.gov (United States)

    Chaballout, Basil; Molloy, Margory; Vaughn, Jacqueline; Brisson Iii, Raymond; Shaw, Ryan

    2016-03-07

    Studies show that students who use fidelity-based simulation technology perform better and have higher retention rates than peers who learn in traditional paper-based training. Augmented reality is increasingly being used as a teaching and learning tool in a continual effort to make simulations more realistic for students. The aim of this project was to assess the feasibility and acceptability of using augmented reality via Google Glass during clinical simulation scenarios for training health science students. Students performed a clinical simulation while watching a video through Google Glass of a patient actor simulating respiratory distress. Following participation in the scenarios students completed two surveys and were questioned if they would recommend continued use of this technology in clinical simulation experiences. We were able to have students watch a video in their field of vision of a patient who mimicked the simulated manikin. Students were overall positive about the implications for being able to view a patient during the simulations, and most students recommended using the technology in the future. Overall, students reported perceived realism with augmented reality using Google Glass. However, there were technical and usability challenges with the device. As newer portable and consumer-focused technologies become available, augmented reality is increasingly being used as a teaching and learning tool to make clinical simulations more realistic for health science students. We found Google Glass feasible and acceptable as a tool for augmented reality in clinical simulations.

  10. 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...

  11. 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.

  12. 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.

  13. Comparative study of angio genesis radiopharmaceuticals for melanoma detection

    International Nuclear Information System (INIS)

    Oliveira, Erica Aparecida de

    2011-01-01

    Early diagnosis and treatment of melanoma, a cutaneous tumor with a serious prognosis, is extremely important for optimal clinical outcome. Phage display peptide libraries are a useful screening resource for identifying bioactive peptides that interact with cancer targets. The aim of this study was the evaluation of two technetium-99m tracers for angio genesis detection in melanoma model, using cyclic peguilated pentapeptide with RGD and NGR motifs conjugated with bifunctional chelator MAG3. The conjugated peptides (10 μL of a μg/μL solution) were labeled with technetium-99m using a sodium tartrate buffer. Radiochemical evaluation was done by ITLC and confirmed by HPLC. Partition coefficient was determined and internalization assays were performed in two melanoma cells (B16F10 and SKMEL28). Biodistribution evaluation of the tracers was done in healthy animals at different times and also in mice bearing the tumor cells at 120 min post injection. Blocking studies were also conducted by co-injection of cold peptides. The conjugated showed the same profile in many evaluations. They were radiolabeled with high radiochemical purity (>97%). Both were hydrophilic, with preferential renal excretion. Tumor uptake was higher for human melanoma cells than for murinic melanoma cells, specially for 99m Tc-MAG3-PEG 8 -c(RGDyK) (7.85±±2.34 %ID/g) at 120 min post injection. The performance of 99m Tc-MAG 3 -PEG 8 -c(RGDyk) was much better than NGR tracer concerning human melanoma uptake and might be considered in future investigations focusing radiotracers for melanoma diagnosis. (author)

  14. Development and Validation of Simulated Virtual Patients to Impart Early Clinical Exposure in Endocrine Physiology

    Science.gov (United States)

    Gupta, Akriti; Singh, Satendra; Khaliq, Farah; Dhaliwal, Upreet; Madhu, S. V.

    2018-01-01

    In the country presently, preclinical medical students are not routinely exposed to real patients. Thus, when they start clinical postings, they are found to have poor clinical reasoning skills. Simulated virtual patients (SVPs) can improve clinical skills without endangering real patients. This pilot study describes the development of two SVPs in…

  15. Applications of nanotechnology for melanoma treatment, diagnosis, and theranostics

    Directory of Open Access Journals (Sweden)

    Chen J

    2013-07-01

    Full Text Available Jiezhong Chen,1,2 Renfu Shao,3 Xu Dong Zhang,4 Chen Chen1 1School of Biomedical Sciences, University of Queensland, Brisbane, QLD, Australia; 2Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, NSW, Australia; 3GeneCology Research Centre, School of Science, Education and Engineering, University of the Sunshine Coast, Maroochydore, QLD, Australia; 4School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia Abstract: Melanoma is the most aggressive type of skin cancer and has very high rates of mortality. An early stage melanoma can be surgically removed, with a survival rate of 99%. However, metastasized melanoma is difficult to cure. The 5-year survival rates for patients with metastasized melanoma are still below 20%. Metastasized melanoma is currently treated by chemotherapy, targeted therapy, immunotherapy and radiotherapy. The outcome of most of the current therapies is far from optimistic. Although melanoma patients with a mutation in the oncogene v-Raf murine sarcoma viral oncogene homolog B1 (BRAF have an initially higher positive response rate to targeted therapy, the majority develop acquired drug resistance after 6 months of the therapy. To increase treatment efficacy, early diagnosis, more potent pharmacological agents, and more effective delivery systems are urgently needed. Nanotechnology has been extensively studied for melanoma treatment and diagnosis, to decrease drug resistance, increase therapeutic efficacy, and reduce side effects. In this review, we summarize the recent progress on the development of various nanoparticles for melanoma treatment and diagnosis. Several common nanoparticles, including liposome, polymersomes, dendrimers, carbon-based nanoparticles, and human albumin, have been used to deliver chemotherapeutic agents, and small interfering ribonucleic acids (siRNAs against signaling molecules have also been tested for the treatment of melanoma. Indeed

  16. A cost-effectiveness analysis of trametinib plus dabrafenib as first-line therapy for metastatic BRAF V600-mutated melanoma in the Swiss setting.

    Science.gov (United States)

    Matter-Walstra, K; Braun, R; Kolb, C; Ademi, Z; Dummer, R; Pestalozzi, B C; Schwenkglenks, M

    2015-12-01

    The treatment of patients with metastatic melanomas that harbour BRAF V600E or V600K mutations with trametinib plus dabrafenib appears to be superior to treatment with vemurafenib alone. This treatment regimen is likely to become available in Switzerland in the near future. To determine the cost-effectiveness of trametinib plus dabrafenib. A Markov cohort simulation was conducted to model the clinical course of typical patients with metastatic melanoma. Information on response rates, clinical condition and follow-up treatments were derived and transition probabilities estimated based on the results of a clinical trial that compared treatment with trametinib plus dabrafenib vs. vemurafenib alone. Treatment with trametinib plus dabrafenib was estimated to cost an additional CHF199 647 (Swiss francs) on average and yield a gain of 0·52 quality-adjusted life years (QALYs), resulting in an incremental cost-effectiveness ratio of CHF385 603 per QALY. Probabilistic sensitivity analyses showed that a willingness-to-pay threshold of CHF100 000 per QALY would not be reached at the current US price of trametinib. The introduction of trametinib in Switzerland at US market prices for the treatment of metastatic BRAF V600-mutated melanoma with trametinib plus dabrafenib is unlikely to be cost-effective compared with vemurafenib monotherapy. A reduction in the total price of the combination therapy is required to achieve an acceptable cost-effectiveness ratio for this clinically promising treatment. © 2015 British Association of Dermatologists.

  17. 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.

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

    Directory of Open Access Journals (Sweden)

    Amy E Gilbert

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

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

    Science.gov (United States)

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

    2011-01-01

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

  20. Comparative study of angio genesis radiopharmaceuticals for melanoma detection; Estudo comparativo de radiofarmacos para angiogenese na deteccao de melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, Erica Aparecida de

    2011-07-01

    Early diagnosis and treatment of melanoma, a cutaneous tumor with a serious prognosis, is extremely important for optimal clinical outcome. Phage display peptide libraries are a useful screening resource for identifying bioactive peptides that interact with cancer targets. The aim of this study was the evaluation of two technetium-99m tracers for angio genesis detection in melanoma model, using cyclic peguilated pentapeptide with RGD and NGR motifs conjugated with bifunctional chelator MAG3. The conjugated peptides (10 {mu}L of a {mu}g/{mu}L solution) were labeled with technetium-99m using a sodium tartrate buffer. Radiochemical evaluation was done by ITLC and confirmed by HPLC. Partition coefficient was determined and internalization assays were performed in two melanoma cells (B16F10 and SKMEL28). Biodistribution evaluation of the tracers was done in healthy animals at different times and also in mice bearing the tumor cells at 120 min post injection. Blocking studies were also conducted by co-injection of cold peptides. The conjugated showed the same profile in many evaluations. They were radiolabeled with high radiochemical purity (>97%). Both were hydrophilic, with preferential renal excretion. Tumor uptake was higher for human melanoma cells than for murinic melanoma cells, specially for {sup 99m}Tc-MAG3-PEG{sub 8}-c(RGDyK) (7.85{+-}{+-}2.34 %ID/g) at 120 min post injection. The performance of {sup 99m}Tc-MAG{sub 3}-PEG{sub 8}-c(RGDyk) was much better than NGR tracer concerning human melanoma uptake and might be considered in future investigations focusing radiotracers for melanoma diagnosis. (author)

  1. Rectal malignant melanoma mistaken for thrombotic hemorrhoids - rare tumor with poor prognosis

    International Nuclear Information System (INIS)

    Kovacova, E.; Hvizdakova, A.; Vyskocil, M.; Kinova, S.; Sesovsky, V.; Kobzova, D.; Palkovic, M.

    2011-01-01

    Rectal malignant melanoma originates in the melanocytes of the anorectal area. Represent less than 1 % of all melanomas, and 4 % of all malignant tumors of the rectum and anus. The most common clinical manifestation is bleeding, the clinical examination may be mistaken for benign lesions or hemorrhoids. Given the rarity of the diagnosis are not well-defined therapeutic procedures. Prognosis for patient is poor. The authors present a case of 70-year old patient with rectal melanoma diagnosed at an advanced stage of disease, initially with diagnosis a thrombotic hemorrhoid. (author)

  2. Primary mediastinal melanoma presenting as superior vena cava syndrome: A case study

    Directory of Open Access Journals (Sweden)

    Ann C Gaffey

    2016-03-01

    Full Text Available The rates of melanoma have increased over the past 30 years. Malignant melanoma most commonly occurs in the skin with secondary involvement of other organs. Here, we present an extremely rare case of malignant melanoma of the mediastinum with presentation of superior vena cava syndrome without clinical evidence of extrathoracic disease. The incidence of this clinical presentation is uncommon, resulting in only a handful of case reports in the literature. [Arch Clin Exp Surg 2016; 5(1.000: 56-58

  3. The role of thioredoxin reductase 1 in melanoma metabolism and metastasis.

    Science.gov (United States)

    Cassidy, Pamela B; Honeggar, Matthew; Poerschke, Robyn L; White, Karen; Florell, Scott R; Andtbacka, Robert H I; Tross, Joycelyn; Anderson, Madeleine; Leachman, Sancy A; Moos, Philip J

    2015-11-01

    Although significant progress has been made in targeted and immunologic therapeutics for melanoma, many tumors fail to respond, and most eventually progress when treated with the most efficacious targeted combination therapies thus far identified. Therefore, alternative approaches that exploit distinct melanoma phenotypes are necessary to develop new approaches for therapeutic intervention. Tissue microarrays containing human nevi and melanomas were used to evaluate levels of the antioxidant protein thioredoxin reductase 1 (TR1), which was found to increase as a function of disease progression. Melanoma cell lines revealed metabolic differences that correlated with TR1 levels. We used this new insight to design a model treatment strategy that creates a synthetic lethal interaction wherein targeting TR1 sensitizes melanoma to inhibition of glycolytic metabolism, resulting in a decrease in metastases in vivo. This approach holds the promise of a new clinical therapeutic strategy, distinct from oncoprotein inhibition. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. The human simulation lab-dissecting sex in the simulator lab: the clinical lacuna of transsexed embodiment.

    Science.gov (United States)

    Singer, Ben

    2013-06-01

    This article begins with an ethnographically documented incident whereby nursing students dissected a medical human simulator model and rearranged it so that the "male" head and torso was attached to the "female" lower half. They then joked about the embodiment of the model, thus staging a scene of anti-trans ridicule. The students' lack of ability, or purposeful refusal, to recognize morphological biodiversity in medical settings indicates a lacuna in clinical imaginaries. Even as trans-identified and gender nonconforming people increasingly access care in the clinic, the lacuna of transsex-as a proxy term for non-binary embodiment-persists at the heart of clinical practice. This article concludes that we might engage in more ethical clinical practice if we recognize and affirm the trace of multiple forms of human being in the non-human simulator.

  5. First-line treatment of metastatic melanoma: role of nivolumab

    Directory of Open Access Journals (Sweden)

    Force J

    2017-02-01

    Full Text Available Jeremy Force,1 April KS Salama,1,2 1Division of Hematology/Oncology, Duke University Medical Center, Durham, NC, USA; 2Division of Medical Oncology, Duke University Medical Center, Durham, NC, USA Abstract: Historically, the median overall survival of metastatic melanoma patients was less than 1 year and long-term survivors were rare. Recent advances in therapies have dramatically shifted this landscape with increased survival rates and the real possibility that long-term disease control is achievable. Advances in immune modulators, including cytotoxic T-lymphocyte antigen-4 and programmed death-1 based treatments, have been an integral part of this success. In this article, we review previous and recent therapeutic developments for metastatic melanoma patients. We discuss advances in immunotherapy while focusing on the use of nivolumab alone and in combination with other agents, including ipilimumab in advanced melanoma. One major goal in melanoma research is to optimize combination strategies allowing for more patients to experience benefit while minimizing toxicity. A better understanding of the optimal sequencing, combinations, and mechanisms underlying the development of resistance may provide evidence for rational clinical trial designs of novel immunotherapy strategies in melanoma and other cancer subtypes. Keywords: PD-1, immunotherapy, pembrolizumab, PD-L1, resistance, checkpoint, BRAF

  6. Clinical use of a simulation-multileaf collimator

    Energy Technology Data Exchange (ETDEWEB)

    Marx, M; Vacha, P; Riis, B; Feyerabend, T; Richter, E [Medizinische Univ., Luebeck (Germany). Klinik fuer Strahlentherapie und Nuklearmedizin

    1998-07-01

    Background: At the University of Luebeck, radiotherapy is delivered by a 6/18-MV linear accelerator. Using the integrated multileaf collimator, irradiation of individually shaped treatment fields is possible in place of alloy blocks. Due to unsatisfactory pretherapeutic review of the radiation-field-specific multileaf collimator (MLC) configuration, we developed a simulation-multileaf collimator (SMLC) and assessed its feasibility at different tumor sites. Material and Methods: The SMLC is made of a perspex carrier with 52 horizontal sliding leaves. The position of each leaf is calculated by a 3D treatment-planning computer. The technician manually adjusts the leaves according to the beams-eye-view plot of the planning computer. Consequently, the SMLC is mounted on the therapy simulator at a distance of 64.8 cm from the focus. The treatment fields and the position of the leaves are documented by X-ray films. Results: Using the SMLC, radiation oncologists are able to review exactly the leaf configuration of each MLC-shaped radiation field and to correlate the MLC-shaped radiation field with the treated volume, the organs at risk and the port films acquired by the Portal Vision {sup trademark} system. Conclusion: The SMLC is a new tool to review radiation planning that uses an MLC in daily routine. The use of the SMLC improves the documentation and the quality assurance. It accelerates the treatment field review at the linear accelerator by comparing the SMLC simulator films with the portal images. (orig.) [Deutsch] Hintergrund: Seit 1994 werden Patienten an der Luebecker Universitaetsklinik fuer Strahlentherapie und Nuklearmedizin an einem Linearbeschleuniger bestrahlt, der mit einem Multileaf-Kollimator ausgeruestet ist. Dieser ermoeglicht die Bestrahlung individuell geformter Zielvolumina ohne gegossene Individualsatelliten. Wegen der unzureichenden praetherapeutischen Kontrolle der Lamellenkonfiguration des Multileaf-Kollimators wurde ein Simulations

  7. 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.

  8. 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 ...

  9. Sentinel nodes outside lymph node basins in patients with melanoma

    NARCIS (Netherlands)

    Roozendaal, GK; de Vries, JDH; van Poll, D; Jansen, L; Nieweg, OE; Kroon, BBR; Schraffordt Koops, H.

    Background: Lymphoscintigraphy occasionally reveals hot spots outside lymph node basins in patients with melanoma. The aim of this study was to evaluate such abnormally located hot spots. Methods: Sentinel node biopsy was studied prospectively in 379 patients with clinically localized cutaneous

  10. Melanomas: radiobiology and role of radiation therapy

    International Nuclear Information System (INIS)

    Peschel, Richard E.

    1995-01-01

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

  11. Methods to Improve Adoptive T-Cell Therapy for Melanoma

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  12. Thioredoxin induces Tregs to generate an immunotolerant tumor microenvironment in metastatic melanoma

    Science.gov (United States)

    Wang, Xiaogang; Dong, Haisheng; Li, Qi; Li, Yingxian; Hong, An

    2015-01-01

    Metastatic melanoma is a highly aggressive cancer that is very difficult to treat. Additionally, the antitumor immune reaction of melanoma is still unclear. Here we demonstrate an association between the expression and secretion of the antioxidant protein thioredoxin (TRX) and increasing tumor stage and metastasis in melanoma. To elucidate the role of TRX in melanoma, we assessed the correlation of TRX expression with different disease parameters in melanoma. We also examined the in vitro and in vivo effects of modulating TRX levels in melanoma cells using various methods of TRX depletion and augmentation. We further explored the effects of TRX on the cytokine milieu and the ability of TRX to regulate the proportion and specific activities of T-cell populations. We demonstrate that TRX expression correlates with Treg representation in clinical samples and, that modulation of TRX influences the induction of Tregs and the generation of an immunotolerant cytokine profile in mouse serum. Using a murine metastatic melanoma model, we identified a tumor immunoevasion mechanism whereby melanoma cell-secreted TRX enhances Treg infiltration. TRX displays chemotactic effects in recruiting Tregs, stimulates the conversion of conventional T cells to Tregs, and confers survival advantage to Tregs in the tumor microenvironment. In turn, this increase of Tregs generates immunotolerance in tissues and therefore decreases antitumor immune reactions. These results elucidate a mechanism by which TRX promotes metastatic melanoma in part through Treg recruitment to inhibit T-cell antitumor effects and suggest that TRX antibody may be useful in the clinic as a therapy against melanoma. PMID:26405597

  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. 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.

  15. Use of clinical simulation for assessment in EHR-procurement

    DEFF Research Database (Denmark)

    Jensen, Sanne; Rasmussen, Stine L.; Lyng, Karen M.

    2013-01-01

    In Denmark, two large regions cooperate in a public intervention process of acquiring a new eHealth-platform to support the daily clinical work of approximately 40,000 users in 14 hospitals. It is essential that the new platform, besides fulfilling comprehensive detailed specifications, supports...... the daily work practice consisting of numerous mixed tasks executed by many different clinical actors in various settings. Within health informatics it has proven beneficial to use human factors approaches in the design process to secure systems that are responsive to the actual field of application. While...

  16. Clinical use of a simulation-multileaf collimator

    International Nuclear Information System (INIS)

    Marx, M.; Vacha, P.; Riis, B.; Feyerabend, T.; Richter, E.

    1998-01-01

    Background: At the University of Luebeck, radiotherapy is delivered by a 6/18-MV linear accelerator. Using the integrated multileaf collimator, irradiation of individually shaped treatment fields is possible in place of alloy blocks. Due to unsatisfactory pretherapeutic review of the radiation-field-specific multileaf collimator (MLC) configuration, we developed a simulation-multileaf collimator (SMLC) and assessed its feasibility at different tumor sites. Material and Methods: The SMLC is made of a perspex carrier with 52 horizontal sliding leaves. The position of each leaf is calculated by a 3D treatment-planning computer. The technician manually adjusts the leaves according to the beams-eye-view plot of the planning computer. Consequently, the SMLC is mounted on the therapy simulator at a distance of 64.8 cm from the focus. The treatment fields and the position of the leaves are documented by X-ray films. Results: Using the SMLC, radiation oncologists are able to review exactly the leaf configuration of each MLC-shaped radiation field and to correlate the MLC-shaped radiation field with the treated volume, the organs at risk and the port films acquired by the Portal Vision trademark system. Conclusion: The SMLC is a new tool to review radiation planning that uses an MLC in daily routine. The use of the SMLC improves the documentation and the quality assurance. It accelerates the treatment field review at the linear accelerator by comparing the SMLC simulator films with the portal images. (orig.) [de

  17. Highlights of the 2012 Congress of the Society for Melanoma Research, 8-11 November 2012, Hollywood, CA.

    Science.gov (United States)

    Vultur, Adina; Webster, Marie; Villanueva, Jessie; Herlyn, Dorothee

    2013-06-01

    The 2012 Congress of the Society for Melanoma Research was attended by researchers with widespread expertise in basic, translational, and clinical research. Exciting research has led to the discovery of therapies to target mutations found in melanoma; however, it is clear that much still needs to be learned about how to use these therapies and the role of the microenvironment in therapy resistance and melanoma progression. This summary highlights recent discoveries in genetics and epigenetics, biology, immunotherapy, and targeted therapies for melanoma discussed at this year's meeting.

  18. 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

  19. 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.

  20. The effect of an interprofessional clinical simulation on medical ...

    African Journals Online (AJOL)

    2014-05-04

    May 4, 2014 ... with a safe, structured and supportive environment that links the lecture room and clinical practice. .... Leadership. They reflected on the need to clearly delegate work and direct team members.[9]. 'In the beginning there was no leader … no one took the initiative to start the whole thing.' 'I have learned how ...

  1. Utilization of the Nursing Process to Foster Clinical Reasoning During a Simulation Experience

    Directory of Open Access Journals (Sweden)

    Amanda Lambie

    2015-11-01

    Full Text Available Nursing practice includes complex reasoning and multifaceted decision making with minimal standardized guidance in how to evaluate this phenomenon among nursing students. Learning outcomes related to the clinical reasoning process among novice baccalaureate nursing students during a simulation experience were evaluated. Nursing process records were utilized to evaluate and foster the development of clinical reasoning in a high-fidelity medical-surgical simulation experience. Students were unable to describe and process pertinent patient information appropriately prior to the simulation experience. Students’ ability to identify pertinent patient cues and plan appropriate patient care improved following the simulation. The learning activity afforded a structured opportunity to identify cues, prioritize the proper course of nursing interventions, and engage in collaboration among peers. The simulation experience provides faculty insight into the students’ clinical reasoning processes, while providing students with a clear framework for successfully accomplishing learning outcomes.

  2. Comparison of the Serum Tumor Markers S100 and Melanoma-inhibitory Activity (MIA) in the Monitoring of Patients with Metastatic Melanoma Receiving Vaccination Immunotherapy with Dendritic Cells.

    Science.gov (United States)

    Uslu, Ugur; Schliep, Stefan; Schliep, Klaus; Erdmann, Michael; Koch, Hans-Uwe; Parsch, Hans; Rosenheinrich, Stina; Anzengruber, Doris; Bosserhoff, Anja Katrin; Schuler, Gerold; Schuler-Thurner, Beatrice

    2017-09-01

    In patients with melanoma, early dissemination via lymphatic and hematogenous routes is frequently seen. Thus, besides clinical follow-up examination and imaging, reliable melanoma-specific serological tumor markers are needed. We retrospectively compared two serum markers for melanoma, S100 and melanoma-inhibitory activity (MIA), for monitoring of patients with metastatic melanoma under either adjuvant or therapeutic vaccination immunotherapy with dendritic cells (DC). Serum was obtained from a total of 100 patients (28 patients in stage III and 72 patients in stage IV, according to the American Joint Committee on Cancer 2002) at regular intervals during therapy, accompanied by follow-up imaging. When relapse was detected, both markers often remained within normal range. In contrast, in patients with metastatic measurable disease receiving therapeutic and not adjuvant DC vaccination, an increase of both markers was a strong indicator for disease progression. When comparing both markers in the whole study population, MIA showed a superior sensitivity to detect disease progression. S100 and MIA are highly sensitive tumor markers for monitoring of patients with melanoma with current metastases, but less sensitive for monitoring of tumor-free patients. In the current study, MIA had a slightly superior sensitivity to detect progressive disease compared to S100 and seems to be more useful in monitoring of patients with metastatic melanoma receiving immunotherapy. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  3. Teaching medical students a clinical approach to altered mental status: simulation enhances traditional curriculum

    Directory of Open Access Journals (Sweden)

    Jeremy D. Sperling

    2013-04-01

    Full Text Available Introduction: Simulation-based medical education (SBME is increasingly being utilized for teaching clinical skills in undergraduate medical education. Studies have evaluated the impact of adding SBME to third- and fourth-year curriculum; however, very little research has assessed its efficacy for teaching clinical skills in pre-clerkship coursework. To measure the impact of a simulation exercise during a pre-clinical curriculum, a simulation session was added to a pre-clerkship course at our medical school where the clinical approach to altered mental status (AMS is traditionally taught using a lecture and an interactive case-based session in a small group format. The objective was to measure simulation's impact on students’ knowledge acquisition, comfort, and perceived competence with regards to the AMS patient. Methods: AMS simulation exercises were added to the lecture and small group case sessions in June 2010 and 2011. Simulation sessions consisted of two clinical cases using a high-fidelity full-body simulator followed by a faculty debriefing after each case. Student participation in a simulation session was voluntary. Students who did and did not participate in a simulation session completed a post-test to assess knowledge and a survey to understand comfort and perceived competence in their approach to AMS. Results: A total of 154 students completed the post-test and survey and 65 (42% attended a simulation session. Post-test scores were higher in students who attended a simulation session compared to those who did not (p<0.001. Students who participated in a simulation session were more comfortable in their overall approach to treating AMS patients (p=0.05. They were also more likely to state that they could articulate a differential diagnosis (p=0.03, know what initial diagnostic tests are needed (p=0.01, and understand what interventions are useful in the first few minutes (p=0.003. Students who participated in a simulation session

  4. Human eye modelling for ophthalmic simulators project for clinic applications

    International Nuclear Information System (INIS)

    Sanchez, Andrea; Santos, Adimir dos; Yoriyaz, Helio

    2002-01-01

    Most of eye tumors are treated by surgical means, which involves the enucleation of affected eyes. In terms of treatment and control of diseases, there is brachytherapy, which often utilizes small applicator of Co-60, I-125, Ru-106, Ir-192, etc. These methods are shown to be very efficient but highly cost. The objective of this work is propose a detailed simulator modelling for eye characterization. Additionally, this study can contribute to design and build a new applicator in order to reduce the cost and to allow more patients to be treated

  5. Use of clinical simulations for patient education: targeting an untapped audience.

    Science.gov (United States)

    Siwe, Karin; Berterö, Carina; Pugh, Carla; Wijma, Barbro

    2009-01-01

    In most cases, the health professional has been the target for simulation based learning curricula. We have developed a simulation based curriculum for patient education. In our curriculum lay-women learn how to perform the clinical female pelvic examination using a manikin-based trainer. Learner assessments show that prior negative expectations turned into positive expectations regarding future pelvic examinations.

  6. Exploring the use of high-fidelity simulation training to enhance clinical skills.

    Science.gov (United States)

    Ann Kirkham, Lucy

    2018-02-07

    The use of interprofessional simulation training to enhance nursing students' performance of technical and non-technical clinical skills is becoming increasingly common. Simulation training can involve the use of role play, virtual reality or patient simulator manikins to replicate clinical scenarios and assess the nursing student's ability to, for example, undertake clinical observations or work as part of a team. Simulation training enables nursing students to practise clinical skills in a safe environment. Effective simulation training requires extensive preparation, and debriefing is necessary following a simulated training session to review any positive or negative aspects of the learning experience. This article discusses a high-fidelity simulated training session that was used to assess a group of third-year nursing students and foundation level 1 medical students. This involved the use of a patient simulator manikin in a scenario that required the collaborative management of a deteriorating patient. ©2018 RCN Publishing Company Ltd. All rights reserved. Not to be copied, transmitted or recorded in any way, in whole or part, without prior permission of the publishers.

  7. Design and construction of ophthalmic simulators for clinical applications

    International Nuclear Information System (INIS)

    Sanchez, Andrea

    2006-01-01

    This work presents a calculational methodology for dose determination in human eye structures, such as: sclera, choroid, retina, lens, vitreous body, optic nerve and disc, and cornea, as well as tumor due to treatment to the eye plaques. A human eye model was constructed taking into consideration its main structural and dimension characteristics. Beyond that a mathematical model for the Co-60 and 1-125 plaques with all geometric details were built employing the MCNP-4C code. This model is able to calculate the axial and radial doses in any point of the eye and for each of its structures. An acrylic eye simulator was also built with the aim to obtain experimental results for the both model validations. This simulator is made of an acrylic sphere split into foils of 1 mm thickness which allow the introduction of a radiographic film to measure the axial and radial doses. The experimental data were used to validate the MCNP-4C results. The data from the mathematical model will serve as the basis to build a data bank for all the eye structures allowing different position and sizes of tumor as well as the replacement of all ophthalmic plaques used in the treatment. This data bank will be the principal part for the construction of a national software for the dose calculation and can be of great help for a reliable treatment system planning in radiotherapy/brachytherapy. (author)

  8. Ipilimumab in advanced melanoma: reports of long-lasting responses.

    Science.gov (United States)

    Farolfi, Alberto; Ridolfi, Laura; Guidoboni, Massimo; Nicoletti, Stefania Vittoria Luisa; Piciucchi, Sara; Valmorri, Linda; Costantini, Matteo; Scarpi, Emanuela; Amadori, Dino; Ridolfi, Ruggero

    2012-06-01

    Patients with metastatic melanoma have a poor prognosis; the results of chemotherapy remain unsatisfactory. Ipilimumab, an anticytotoxic T lymphocyte-associated antigen-4 antibody, has shown promising results in several clinical trials. In this report, advanced melanoma patients receiving ipilimumab were scored according to novel immune-related response criteria (irRC) in an attempt to capture additional response patterns and to avoid premature treatment cessation. Thirty-six heavily pretreated metastatic melanoma patients recieved ipilimumab within five international clinical trials at our Institution from May 2006 to August 2008. Disease progression was defined as an increase in tumor burden by at least 25% compared with the nadir, irrespective of any initial increase in baseline lesions or the appearance of new lesions. We report unusually long-lasting responses in patients treated with ipilimumab 10 mg/kg. An overall response was observed in six out of 30 patients (20%), a complete response in three (10%), and disease control in 11 (37%), which seemed to be of a long duration (median of 16 months; complete response 36+, 34+, and 41+ months). All irRC patterns seemed to be strongly associated with an improvement in overall survival. Interestingly, we found a correlation between the presence of a grade 3/4 immune-related adverse event and responses, time to progression, and overall survival. Ipilimumab therapy resulted in clinically meaningful responses in advanced melanoma patients, supporting the need for further irRC validation.

  9. The occurrence of non-melanoma malignant skin lesions and non-cutaneous squamous-cell carcinoma among metastatic melanoma patients: an observational cohort study in Denmark.

    Science.gov (United States)

    Li, Haojie; Pedersen, Lars; Nørgaard, Mette; Ulrichsen, Sinna P; Thygesen, Sandra K; Nelson, Jeanenne J

    2016-05-03

    Inhibitors of mutant BRAF are emerging as standard of care in patients with metastatic melanoma who carry relevant oncogenic mutations. However, BRAF inhibitors are found to induce cutaneous squamous cell carcinoma (cuSCC). Population-based background rates of cuSCC and non-cutaneous squamous cell carcinoma (non-cuSCC) in the metastatic melanoma population may contextualize safety signals from randomized clinical trials or the clinics. However, these background rates are lacking. We conducted a historical cohort study to evaluate the background rates of new-onset non-melanoma skin lesions and non-cuSCC among 2,814 metastatic malignant melanoma patients diagnosed in 1997-2010, identified through the Danish Cancer Registry and the National Pathology Registry. Patients were excluded if they had a history of cancer before the metastatic melanoma diagnosis, other than skin cancers. We determined the incidence of non-melanoma malignant skin lesions and non-cuSCC that occurred post metastatic melanoma diagnosis, censoring patients at death, emigration, or December 31, 2011 (end of study period), whichever came first. The median age at metastatic melanoma diagnosis was 64 years. Over 40% of patients died within one year of metastatic diagnosis and ~70% died within 5 years. The percentages of patients with prior history or prevalent disease at metastatic melanoma diagnosis included: 8.6% with cuSCC or basal cell carcinoma (BCC), 3.9% with actinic keratosis (AK), and 0.7% with Bowen's disease. No patients had past or current non-cuSCC per study exclusion criterion. The incidence of non-melanoma skin lesions during the 6 months post-metastatic melanoma diagnosis was as follows: BCC, 1.8% (42.5 per 1000 person-years [PY]); AK, 0.8% (18.6 per 1000 PY); cuSCC, 0.1% (1.7 per 1000 PY); Bowen's disease, 0.04% (0.8 per 1000 PY); and keratoacanthoma (KA), 0%. Non-cuSCC was observed in 3 patients (0.1%; 2.5 per 1000 PY) at 3 sites: bronchi, heart and lung. CuSCC and non-cuSCC were

  10. The occurrence of non-melanoma malignant skin lesions and non-cutaneous squamous-cell carcinoma among metastatic melanoma patients: an observational cohort study in Denmark

    International Nuclear Information System (INIS)

    Li, Haojie; Pedersen, Lars; Nørgaard, Mette; Ulrichsen, Sinna P.; Thygesen, Sandra K.; Nelson, Jeanenne J.

    2016-01-01

    Inhibitors of mutant BRAF are emerging as standard of care in patients with metastatic melanoma who carry relevant oncogenic mutations. However, BRAF inhibitors are found to induce cutaneous squamous cell carcinoma (cuSCC). Population-based background rates of cuSCC and non-cutaneous squamous cell carcinoma (non-cuSCC) in the metastatic melanoma population may contextualize safety signals from randomized clinical trials or the clinics. However, these background rates are lacking. We conducted a historical cohort study to evaluate the background rates of new-onset non-melanoma skin lesions and non-cuSCC among 2,814 metastatic malignant melanoma patients diagnosed in 1997–2010, identified through the Danish Cancer Registry and the National Pathology Registry. Patients were excluded if they had a history of cancer before the metastatic melanoma diagnosis, other than skin cancers. We determined the incidence of non-melanoma malignant skin lesions and non-cuSCC that occurred post metastatic melanoma diagnosis, censoring patients at death, emigration, or December 31, 2011 (end of study period), whichever came first. The median age at metastatic melanoma diagnosis was 64 years. Over 40 % of patients died within one year of metastatic diagnosis and ~70 % died within 5 years. The percentages of patients with prior history or prevalent disease at metastatic melanoma diagnosis included: 8.6 % with cuSCC or basal cell carcinoma (BCC), 3.9 % with actinic keratosis (AK), and 0.7 % with Bowen’s disease. No patients had past or current non-cuSCC per study exclusion criterion. The incidence of non-melanoma skin lesions during the 6 months post-metastatic melanoma diagnosis was as follows: BCC, 1.8 % (42.5 per 1000 person-years [PY]); AK, 0.8 % (18.6 per 1000 PY); cuSCC, 0.1 % (1.7 per 1000 PY); Bowen’s disease, 0.04 % (0.8 per 1000 PY); and keratoacanthoma (KA), 0 %. Non-cuSCC was observed in 3 patients (0.1 %; 2.5 per 1000 PY) at 3 sites: bronchi, heart and lung. CuSCC and

  11. lncRNA H19 predicts poor prognosis in patients with melanoma and regulates cell growth, invasion, migration and epithelial–mesenchymal transition in melanoma cells

    Directory of Open Access Journals (Sweden)

    Shi G

    2018-06-01

    Full Text Available Gaofeng Shi,1,2 Hu Li,2 Fengshan Gao,2 Qian Tan1 1Drum Tower Clinical Medical College of Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Plastic Surgery, the Affiliated Wuxi No 4 People’s Hospital of Jiangnan University, Wuxi, People’s Republic of China Introduction: Melanoma is a deadly malignancy and the poor prognosis of patients with advanced disease is relatively poor. Recent studies indicate that long non-coding RNAs are involved in the pathogenesis of malignant melanoma. This study aims to investigate the role of the long non-coding RNA H19 in melanoma and to explore the underlying molecular mechanisms. Materials and methods: The expression levels of H19 in clinical samples and melanoma cells were determined by quantitative real-time PCR. The cell growth and cell metastasis were assessed by Cell Counting Kit 8, cell invasion and wound healing assays. Cell apoptosis and cell cycle were determined by flow cytometry. Protein levels were determined by Western blotting assay. Results: H19 was highly expressed in melanoma tissues compared to normal adjacent skin tissues, and the tissue expression level of H19 from melanoma patients with metastasis was significantly higher than that from patients without distant metastasis. In addition, the high expression of H19 in melanoma tissues was associated with advanced tumor invasion and TNM stage, distal metastasis, lymph node metastasis and shorter overall survival in patients with melanoma. The in vitro functional assays showed that knockdown of H19 inhibited cell growth, invasion and migration and also induced cell apoptosis as well as G0/G1 arrest in melanoma cells. Further quantitative real-time PCR and Western blot experiments showed that knockdown of H19 differentially regulated the epithelial–mesenchymal transition (EMT-related gene expressions and reversed EMT in melanoma cell lines. Knockdown of H19 suppressed in vivo tumor growth and modulated the

  12. Accelerated prompt gamma estimation for clinical proton therapy simulations

    Science.gov (United States)

    Huisman, Brent F. B.; Létang, J. M.; Testa, É.; Sarrut, D.

    2016-11-01

    There is interest in the particle therapy community in using prompt gammas (PGs), a natural byproduct of particle treatment, for range verification and eventually dose control. However, PG production is a rare process and therefore estimation of PGs exiting a patient during a proton treatment plan executed by a Monte Carlo (MC) simulation converges slowly. Recently, different approaches to accelerating the estimation of PG yield have been presented. Sterpin et al (2015 Phys. Med. Biol. 60 4915-46) described a fast analytic method, which is still sensitive to heterogeneities. El Kanawati et al (2015 Phys. Med. Biol. 60 8067-86) described a variance reduction method (pgTLE) that accelerates the PG estimation by precomputing PG production probabilities as a function of energy and target materials, but has as a drawback that the proposed method is limited to analytical phantoms. We present a two-stage variance reduction method, named voxelized pgTLE (vpgTLE), that extends pgTLE to voxelized volumes. As a preliminary step, PG production probabilities are precomputed once and stored in a database. In stage 1, we simulate the interactions between the treatment plan and the patient CT with low statistic MC to obtain the spatial and spectral distribution of the PGs. As primary particles are propagated throughout the patient CT, the PG yields are computed in each voxel from the initial database, as a function of the current energy of the primary, the material in the voxel and the step length. The result is a voxelized image of PG yield, normalized to a single primary. The second stage uses this intermediate PG image as a source to generate and propagate the number of PGs throughout the rest of the scene geometry, e.g. into a detection device, corresponding to the number of primaries desired. We achieved a gain of around 103 for both a geometrical heterogeneous phantom and a complete patient CT treatment plan with respect to analog MC, at a convergence level of 2% relative

  13. Isolated malignant melanoma metastasis to the pancreas

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  14. T-Cell Mediated Immune Responses Induced in ret Transgenic Mouse Model of Malignant Melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Abschuetz, Oliver [Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg and Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim , Heidelberg 69120 (Germany); Osen, Wolfram [Division of Translational Immunology, German Cancer Center, Heidelberg 69120 (Germany); Frank, Kathrin [Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg and Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim , Heidelberg 69120 (Germany); Kato, Masashi [Unit of Environmental Health Sciences, Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, Aichi 487-8501 (Japan); Schadendorf, Dirk [Department of Dermatology, University Hospital Essen, Essen 45122 (Germany); Umansky, Viktor, E-mail: v.umansky@dkfz.de [Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg and Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim , Heidelberg 69120 (Germany)

    2012-04-26

    Poor response of human malignant melanoma to currently available treatments requires a development of innovative therapeutic strategies. Their evaluation should be based on animal models that resemble human melanoma with respect to genetics, histopathology and clinical features. Here we used a transgenic mouse model of spontaneous skin melanoma, in which the ret transgene is expressed in melanocytes under the control of metallothionein-I promoter. After a short latency, around 25% mice develop macroscopic skin melanoma metastasizing to lymph nodes, bone marrow, lungs and brain, whereas other transgenic mice showed only metastatic lesions without visible skin tumors. We found that tumor lesions expressed melanoma associated antigens (MAA) tyrosinase, tyrosinase related protein (TRP)-1, TRP-2 and gp100, which could be applied as targets for the immunotherapy. Upon peptide vaccination, ret transgenic mice without macroscopic melanomas were able to generate T cell responses not only against a strong model antigen ovalbumin but also against typical MAA TRP-2. Although mice bearing macroscopic primary tumors could also display an antigen-specific T cell reactivity, it was significantly down-regulated as compared to tumor-free transgenic mice or non-transgenic littermates. We suggest that ret transgenic mice could be used as a pre-clinical model for the evaluation of novel strategies of melanoma immunotherapy.

  15. Data Set for Pathology Reporting of Cutaneous Invasive Melanoma

    Science.gov (United States)

    Judge, Meagan J.; Evans, Alan; Frishberg, David P.; Prieto, Victor G.; Thompson, John F.; Trotter, Martin J.; Walsh, Maureen Y.; Walsh, Noreen M.G.; Ellis, David W.

    2013-01-01

    An accurate and complete pathology report is critical for the optimal management of cutaneous melanoma patients. Protocols for the pathologic reporting of melanoma have been independently developed by the Royal College of Pathologists of Australasia (RCPA), Royal College of Pathologists (United Kingdom) (RCPath), and College of American Pathologists (CAP). In this study, data sets, checklists, and structured reporting protocols for pathologic examination and reporting of cutaneous melanoma were analyzed by an international panel of melanoma pathologists and clinicians with the aim of developing a common, internationally agreed upon, evidence-based data set. The International Collaboration on Cancer Reporting cutaneous melanoma expert review panel analyzed the existing RCPA, RCPath, and CAP data sets to develop a protocol containing “required” (mandatory/core) and “recommended” (nonmandatory/noncore) elements. Required elements were defined as those that had agreed evidentiary support at National Health and Medical Research Council level III-2 level of evidence or above and that were unanimously agreed upon by the review panel to be essential for the clinical management, staging, or assessment of the prognosis of melanoma or fundamental for pathologic diagnosis. Recommended elements were those considered to be clinically important and recommended for good practice but with lesser degrees of supportive evidence. Sixteen core/required data elements for cutaneous melanoma pathology reports were defined (with an additional 4 core/required elements for specimens received with lymph nodes). Eighteen additional data elements with a lesser level of evidentiary support were included in the recommended data set. Consensus response values (permitted responses) were formulated for each data item. Development and agreement of this evidence-based protocol at an international level was accomplished in a timely and efficient manner, and the processes described herein may

  16. Incorporating Standardized Colleague Simulations in a Clinical Assessment Course and Evaluating the Impact on Interprofessional Communication.

    Science.gov (United States)

    Shrader, Sarah; Dunn, Brianne; Blake, Elizabeth; Phillips, Cynthia

    2015-05-25

    To determine the impact of incorporating standardized colleague simulations on pharmacy students' confidence and interprofessional communication skills. Four simulations using standardized colleagues portraying attending physicians in inpatient and outpatient settings were integrated into a required course. Pharmacy students interacted with the standardized colleagues using the Situation, Background, Assessment, Request/Recommendation (SBAR) communication technique and were evaluated on providing recommendations while on simulated inpatient rounds and in an outpatient clinic. Additionally, changes in student attitudes and confidence toward interprofessional communication were assessed with a survey before and after the standardized colleague simulations. One hundred seventy-one pharmacy students participated in the simulations. Student interprofessional communication skills improved after each simulation. Student confidence with interprofessional communication in both inpatient and outpatient settings significantly improved. Incorporation of simulations using standardized colleagues improves interprofessional communication skills and self-confidence of pharmacy students.

  17. 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

  18. Integrating Simulation Scenarios and Clinical Practices Guided by Concepts of Translational Medicine

    Science.gov (United States)

    Yang, Jing; Huang, Si-min; Li, Ze-jian; Feng, Lie; Lu, Chun-ting

    2018-01-01

    Purpose: To develop a novel method for closely and effectively integrating simulation scenarios and clinical practices to improve clinical skills training in the concepts of translational medicine. Methods: Forty-two and 38 third-year medical students in the classes of 2010 and 2009 at Jinan University were selected as an observation group and a…

  19. Sustained effect of simulation-based ultrasound training on clinical performance

    DEFF Research Database (Denmark)

    Tolsgaard, M G; Ringsted, C; Dreisler, E

    2015-01-01

    on a virtual-reality transvaginal ultrasound simulator until an expert performance level was attained followed by training on a pelvic mannequin. After two months of clinical training, one transvaginal ultrasound scan was recorded for assessment of participants' clinical performance. Two blinded ultrasound...

  20. Clinical validation of robot simulation of toothbrushing - comparative plaque removal efficacy

    Science.gov (United States)

    2014-01-01

    Background Clinical validation of laboratory toothbrushing tests has important advantages. It was, therefore, the aim to demonstrate correlation of tooth cleaning efficiency of a new robot brushing simulation technique with clinical plaque removal. Methods Clinical programme: 27 subjects received dental cleaning prior to 3-day-plaque-regrowth-interval. Plaque was stained, photographically documented and scored using planimetrical index. Subjects brushed teeth 33–47 with three techniques (horizontal, rotating, vertical), each for 20s buccally and for 20s orally in 3 consecutive intervals. The force was calibrated, the brushing technique was video supported. Two different brushes were randomly assigned to the subject. Robot programme: Clinical brushing programmes were transfered to a 6-axis-robot. Artificial teeth 33–47 were covered with plaque-simulating substrate. All brushing techniques were repeated 7 times, results were scored according to clinical planimetry. All data underwent statistical analysis by t-test, U-test and multivariate analysis. Results The individual clinical cleaning patterns are well reproduced by the robot programmes. Differences in plaque removal are statistically significant for the two brushes, reproduced in clinical and robot data. Multivariate analysis confirms the higher cleaning efficiency for anterior teeth and for the buccal sites. Conclusions The robot tooth brushing simulation programme showed good correlation with clinically standardized tooth brushing. This new robot brushing simulation programme can be used for rapid, reproducible laboratory testing of tooth cleaning. PMID:24996973

  1. Assessment of a learning intervention in palliative care based on clinical simulations for nursing students.

    Science.gov (United States)

    Sarabia-Cobo, Carmen María; Alconero-Camarero, Ana Rosa; Lavín-Alconero, Lucía; Ibáñez-Rementería, Isabel

    2016-10-01

    Major deficiencies exist in undergraduate nursing education for Palliative Care. Opportunities to care for dying patients are often unavailable to students in traditional clinical settings. Palliative care simulation is an innovative strategy that may help to prepare undergraduate nursing students to provide quality palliative/end of life care. It is valuable to explore the student nurses' beliefs, feelings and satisfaction regarding the impact that simulation clinic applied to palliative care has and how it influenced their overall experience of caring for a dying patient and the patient's family. This study aimed to evaluate a learning intervention in palliative care using a low-fidelity clinical simulation for undergraduate nursing students from a Spanish university, based on the analytics of their expectations and learning objectives. Sixty-eight students participated in this mixed descriptive design study, they participated in a palliative care simulation scenario and completed three questionnaires which assess the knowledge and expectations before the simulation and the subsequent satisfaction with the performance and learning received. The intervention in question met students' learning expectations, singling out social abilities as important tools in palliative care training, and the students were satisfied with the presented case studies. Our results suggest that low-fidelity clinical simulation intervention training in palliative care is an appropriate and low-cost tool for acquiring competitive skills. Learning in the simulation scenarios provides a mechanism for students to improve student communication skills. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. The Predictive Value of Ultrasound Learning Curves Across Simulated and Clinical Settings

    DEFF Research Database (Denmark)

    Madsen, Mette E; Nørgaard, Lone N; Tabor, Ann

    2017-01-01

    OBJECTIVES: The aim of the study was to explore whether learning curves on a virtual-reality (VR) sonographic simulator can be used to predict subsequent learning curves on a physical mannequin and learning curves during clinical training. METHODS: Twenty midwives completed a simulation-based tra......OBJECTIVES: The aim of the study was to explore whether learning curves on a virtual-reality (VR) sonographic simulator can be used to predict subsequent learning curves on a physical mannequin and learning curves during clinical training. METHODS: Twenty midwives completed a simulation......-based training program in transvaginal sonography. The training was conducted on a VR simulator as well as on a physical mannequin. A subgroup of 6 participants underwent subsequent clinical training. During each of the 3 steps, the participants' performance was assessed using instruments with established...... settings. RESULTS: A good correlation was found between time needed to achieve predefined performance levels on the VR simulator and the physical mannequin (Pearson correlation coefficient .78; P VR simulator correlated well to the clinical performance scores (Pearson...

  3. A study of melanoma in Eastern European migrants in Italy.

    Science.gov (United States)

    Astrua, Chiara; Fava, Paolo; Brizio, Matteo; Savoia, Paola

    2017-04-01

    Cancer survival rates are lower in Eastern Europe. To describe, based on a single-centre database in northern Italy, clinical, histopathological, and prognostic features of melanoma in a migrant population from Eastern Europe. We retrospectively analysed data from 18,190 consecutive foreign patients who visited our institution, with 49 cases of melanoma from Eastern Europe. The control group was represented by 1,003 Italian melanoma patients diagnosed and followed at our centre during the same time period. Patients from Eastern Europe were mainly females with lower median age, without significant differences regarding primary melanoma site, relative to the control group. Diagnosis was made at the place of birth in 30.6% and in our centre for the remainder. Median Breslow thickness was greater (p = 0.0178), and aggressive histotypes (p = 0.0017) and ulcerated melanomas (p = 0.002) were significantly over-represented, particularly when diagnosed in the patients' native country. Disease was more advanced at diagnosis (p = 0.0001), regardless of the place of initial diagnosis (51% had a progressive disease within one year which rose to 80% if diagnosed before admission to our centre), and the percentage of patients who died within one year was significantly higher (p = 0.022), relative to the control group. Our study shows a poor prognosis for melanoma patients diagnosed in Eastern Europe. Moreover, for migrant populations moving from Eastern to Western European countries, financial difficulties, poor social integration, and language barriers, with consequent late access to healthcare facilities, may account for a worse prognosis.

  4. 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.

  5. Simulation-based education for building clinical teams

    Directory of Open Access Journals (Sweden)

    Marshall Stuart

    2010-01-01

    Full Text Available Failure to work as an effective team is commonly cited as a cause of adverse events and errors in emergency medicine. Until recently, individual knowledge and skills in managing emergencies were taught, without reference to the additional skills required to work as part of a team. Team training courses are now becoming commonplace, however their strategies and modes of delivery are varied. Just as different delivery methods of traditional education can result in different levels of retention and transfer to the real world, the same is true in team training of the material in different ways in traditional forms of education may lead to different levels of retention and transfer to the real world, the same is true in team training. As team training becomes more widespread, the effectiveness of different modes of delivery including the role of simulation-based education needs to be clearly understood. This review examines the basis of team working in emergency medicine, and the components of an effective emergency medical team. Lessons from other domains with more experience in team training are discussed, as well as the variations from these settings that can be observed in medical contexts. Methods and strategies for team training are listed, and experiences in other health care settings as well as emergency medicine are assessed. Finally, best practice guidelines for the development of team training programs in emergency medicine are presented.

  6. Integrating usability testing and think-aloud protocol analysis with "near-live" clinical simulations in evaluating clinical decision support.

    Science.gov (United States)

    Li, Alice C; Kannry, Joseph L; Kushniruk, Andre; Chrimes, Dillon; McGinn, Thomas G; Edonyabo, Daniel; Mann, Devin M

    2012-11-01

    Usability evaluations can improve the usability and workflow integration of clinical decision support (CDS). Traditional usability testing using scripted scenarios with think-aloud protocol analysis provide a useful but incomplete assessment of how new CDS tools interact with users and clinical workflow. "Near-live" clinical simulations are a newer usability evaluation tool that more closely mimics clinical workflow and that allows for a complementary evaluation of CDS usability as well as impact on workflow. This study employed two phases of testing a new CDS tool that embedded clinical prediction rules (an evidence-based medicine tool) into primary care workflow within a commercial electronic health record. Phase I applied usability testing involving "think-aloud" protocol analysis of 8 primary care providers encountering several scripted clinical scenarios. Phase II used "near-live" clinical simulations of 8 providers interacting with video clips of standardized trained patient actors enacting the clinical scenario. In both phases, all sessions were audiotaped and had screen-capture software activated for onscreen recordings. Transcripts were coded using qualitative analysis methods. In Phase I, the impact of the CDS on navigation and workflow were associated with the largest volume of negative comments (accounting for over 90% of user raised issues) while the overall usability and the content of the CDS were associated with the most positive comments. However, usability had a positive-to-negative comment ratio of only 0.93 reflecting mixed perceptions about the usability of the CDS. In Phase II, the duration of encounters with simulated patients was approximately 12 min with 71% of the clinical prediction rules being activated after half of the visit had already elapsed. Upon activation, providers accepted the CDS tool pathway 82% of times offered and completed all of its elements in 53% of all simulation cases. Only 12.2% of encounter time was spent using the

  7. 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 ...

  8. PERCEPTION OF SATISFACTION OF STUDENTS IN THE USE OF CLINICAL SIMULATION

    Directory of Open Access Journals (Sweden)

    Lubia del Carmen Castillo-Arcos

    2017-07-01

    Full Text Available This study determinesthe perception of student satisfaction in the use of clinical simulation as a technique of teaching and learning to the development of "nursing care" competition. An assumption was raised; a greater perception of student satisfaction in the use of clinical simulation, the greater the development of competition. The methodology consisted of a qualitative design was used, the sample was not random, through a focus group composed of eight students of the fourth semester of the Bachelor of Nursing at the Autonomous University of Carmen. Semi-structured interview according to Miller model for the evaluation of skills was developed. In the results, the students reported that clinical simulation is an excellent learning strategy that allows them to integrate theory and practice without harming others, stated that previous contact with clinical simulation improves critical thinking, strengthen the knowledge, skills, decision making and professional ethics. The integration of this methodology improves develops clinical competence "nursing care". In conclusion, the Clinical Simulation is a method of teaching innovation of great interest, to be applied in the curricula of Health Sciences, due to its effectiveness as a learning strategy in the training of nursing students.

  9. Open Source AV solution supporting In Situ Simulation and Clinical education

    DEFF Research Database (Denmark)

    Simonsen, Eivind Ortind; Pociunas, Gintas; Dahl, Mads Ronald

    2015-01-01

    In situ simulation is simulation done in the actual clinical environment exceeding the simulation immersion compared to that of the embedded simulation centers and facilitating an increased realistic learning experience. Doing this without compromising (all) the educational principals used....... • Rapid or instant playback capability. • Lightweight and compact design. • Non-cabled AV recording. • Simple, reliable set up and operation. Summary of work Commercial products did not meet our requirements why a programmer was hired to design and program the software to meet our expectations...

  10. Exploring a New Simulation Approach to Improve Clinical Reasoning Teaching and Assessment: Randomized Trial Protocol.

    Science.gov (United States)

    Pennaforte, Thomas; Moussa, Ahmed; Loye, Nathalie; Charlin, Bernard; Audétat, Marie-Claude

    2016-02-17

    Helping trainees develop appropriate clinical reasoning abilities is a challenging goal in an environment where clinical situations are marked by high levels of complexity and unpredictability. The benefit of simulation-based education to assess clinical reasoning skills has rarely been reported. More specifically, it is unclear if clinical reasoning is better acquired if the instructor's input occurs entirely after or is integrated during the scenario. Based on educational principles of the dual-process theory of clinical reasoning, a new simulation approach called simulation with iterative discussions (SID) is introduced. The instructor interrupts the flow of the scenario at three key moments of the reasoning process (data gathering, integration, and confirmation). After each stop, the scenario is continued where it was interrupted. Finally, a brief general debriefing ends the session. System-1 process of clinical reasoning is assessed by verbalization during management of the case, and System-2 during the iterative discussions without providing feedback. The aim of this study is to evaluate the effectiveness of Simulation with Iterative Discussions versus the classical approach of simulation in developing reasoning skills of General Pediatrics and Neonatal-Perinatal Medicine residents. This will be a prospective exploratory, randomized study conducted at Sainte-Justine hospital in Montreal, Qc, between January and March 2016. All post-graduate year (PGY) 1 to 6 residents will be invited to complete one SID or classical simulation 30 minutes audio video-recorded complex high-fidelity simulations covering a similar neonatology topic. Pre- and post-simulation questionnaires will be completed and a semistructured interview will be conducted after each simulation. Data analyses will use SPSS and NVivo softwares. This study is in its preliminary stages and the results are expected to be made available by April, 2016. This will be the first study to explore a new

  11. [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.

  12. Individualized 3D scanning and printing for non-melanoma skin cancer brachytherapy: a financial study for its integration into clinical workflow.

    Science.gov (United States)

    Arenas, Meritxell; Sabater, Sebastià; Sintas, Andreu; Arguís, Monica; Hernández, Víctor; Árquez, Miguel; López, Iolanda; Rovirosa, Àngeles; Puig, Doménec

    2017-06-01

    Skin cancer is the most common tumor in the population. There are different therapeutic modalities. Brachytherapy is one of the techniques used, in which it is necessary to build customized moulds for some patients. Currently, these moulds are made by hand using rudimentary techniques. We present a new procedure based on 3D printing and the analysis of the clinical workflow. Moulds can be made either by hand or by automated 3D printing. For making moulds by hand, a patient's alginate negative is created and, from that, the gypsum cast and customized moulds are made by hand from the patient's negative template. The new process is based on 3D printing. The first step is to take a 3D scan of the surface of the patient and then, 3D modelling software is used to obtain an accurate anatomical reconstruction of the treatment area. We present the clinical workflow using 3D scanning and printing technology, comparing its costs with the usual custom handmade mould protocol. The time spent for the new process is 6.25 hours, in contrast to the time spent for the conventional process, which is 9.5 hours. We found a 34% reduction in time required to create a mould for brachytherapy treatment. The labor cost of the conventional process is 211.5 vs. 152.5 hours, so the reduction is 59 hours. There is also a 49.5% reduction in the financial costs, mostly due to lack of need of a computed tomography (CT) scan of the gypsum and the mould. 3D scanning and printing offers financial benefits and reduces the clinical workload. As the present project demonstrates, through the application of 3D printing technologies, the costs and time spent during the process in the clinical workload in brachytherapy treatment are reduced. Overall, 3D printing is a promising technique for brachytherapy that might be well received in the community.

  13. Germline BAP1 inactivation is preferentially associated with metastatic ocular melanoma and cutaneous-ocular melanoma families.

    Directory of Open Access Journals (Sweden)

    Ching-Ni Jenny Njauw

    Full Text Available BAP1 has been shown to be a target of both somatic alteration in high-risk ocular melanomas (OM and germline inactivation in a few individuals from cancer-prone families. These findings suggest that constitutional BAP1 changes may predispose individuals to metastatic OM and that familial permeation of deleterious alleles could delineate a new cancer syndrome.To characterize BAP1's contribution to melanoma risk, we sequenced BAP1 in a set of 100 patients with OM, including 50 metastatic OM cases and 50 matched non-metastatic OM controls, and 200 individuals with cutaneous melanoma (CM including 7 CM patients from CM-OM families and 193 CM patients from CM-non-OM kindreds.Germline BAP1 mutations were detected in 4/50 patients with metastatic OM and 0/50 cases of non-metastatic OM (8% vs. 0%, p = 0.059. Since 2/4 of the BAP1 carriers reported a family history of CM, we analyzed 200 additional hereditary CM patients and found mutations in 2/7 CM probands from CM-OM families and 1/193 probands from CM-non-OM kindreds (29% vs. 0.52%, p = .003. Germline mutations co-segregated with both CM and OM phenotypes and were associated with the presence of unique nevoid melanomas and highly atypical nevoid melanoma-like melanocytic proliferations (NEMMPs. Interestingly, 7/14 germline variants identified to date reside in C-terminus suggesting that the BRCA1 binding domain is important in cancer predisposition.Germline BAP1 mutations are associated with a more aggressive OM phenotype and a recurrent phenotypic complex of cutaneous/ocular melanoma, atypical melanocytic proliferations and other internal neoplasms (ie. COMMON syndrome, which could be a useful clinical marker for constitutive BAP1 inactivation.

  14. Characterization of individuals at high risk of developing melanoma in Latin America: bases for genetic counseling in melanoma.

    Science.gov (United States)

    Puig, Susana; Potrony, Miriam; Cuellar, Francisco; Puig-Butille, Joan Anton; Carrera, Cristina; Aguilera, Paula; Nagore, Eduardo; Garcia-Casado, Zaida; Requena, Celia; Kumar, Rajiv; Landman, Gilles; Costa Soares de Sá, Bianca; Gargantini Rezze, Gisele; Facure, Luciana; de Avila, Alexandre Leon Ribeiro; Achatz, Maria Isabel; Carraro, Dirce Maria; Duprat Neto, João Pedreira; Grazziotin, Thais C; Bonamigo, Renan R; Rey, Maria Carolina W; Balestrini, Claudia; Morales, Enrique; Molgo, Montserrat; Bakos, Renato Marchiori; Ashton-Prolla, Patricia; Giugliani, Roberto; Larre Borges, Alejandra; Barquet, Virginia; Pérez, Javiera; Martínez, Miguel; Cabo, Horacio; Cohen Sabban, Emilia; Latorre, Clara; Carlos-Ortega, Blanca; Salas-Alanis, Julio C; Gonzalez, Roger; Olazaran, Zulema; Malvehy, Josep; Badenas, Celia

    2016-07-01

    CDKN2A is the main high-risk melanoma-susceptibility gene, but it has been poorly assessed in Latin America. We sought to analyze CDKN2A and MC1R in patients from Latin America with familial and sporadic multiple primary melanoma (SMP) and compare the data with those for patients from Spain to establish bases for melanoma genetic counseling in Latin America. CDKN2A and MC1R were sequenced in 186 Latin American patients from Argentina, Brazil, Chile, Mexico, and Uruguay, and in 904 Spanish patients. Clinical and phenotypic data were obtained. Overall, 24 and 14% of melanoma-prone families in Latin America and Spain, respectively, had mutations in CDKN2A. Latin American families had CDKN2A mutations more frequently (P = 0.014) than Spanish ones. Of patients with SMP, 10% of those from Latin America and 8.5% of those from Spain had mutations in CDKN2A (P = 0.623). The most recurrent CDKN2A mutations were c.-34G>T and p.G101W. Latin American patients had fairer hair (P = 0.016) and skin (P < 0.001) and a higher prevalence of MC1R variants (P = 0.003) compared with Spanish patients. The inclusion criteria for genetic counseling of melanoma in Latin America may be the same criteria used in Spain, as suggested in areas with low to medium incidence, SMP with at least two melanomas, or families with at least two cases among first- or second-degree relatives.Genet Med 18 7, 727-736.

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

    Science.gov (United States)

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

    2017-01-01

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

  16. Early detection of melanoma with the combined use of acoustic microscopy, infrared reflectance and Raman spectroscopy

    Science.gov (United States)

    Karagiannis, Georgios T.; Grivas, Ioannis; Tsingotjidou, Anastasia; Apostolidis, Georgios K.; Grigoriadou, Ifigeneia; Dori, I.; Poulatsidou, Kyriaki-Nefeli; Doumas, Argyrios; Wesarg, Stefan; Georgoulias, Panagiotis

    2015-03-01

    Malignant melanoma is a form of skin cancer, with increasing incidence worldwide. Early diagnosis is crucial for the prognosis and treatment of the disease. The objective of this study is to develop a novel animal model of melanoma and apply a combination of the non-invasive imaging techniques acoustic microscopy, infrared (IR) and Raman spectroscopies, for the detection of developing tumors. Acoustic microscopy provides information about the 3D structure of the tumor, whereas, both spectroscopic modalities give qualitative insight of biochemical changes during melanoma development. In order to efficiently set up the final devices, propagation of ultrasonic and electromagnetic waves in normal skin and melanoma simulated structures was performed. Synthetic and grape-extracted melanin (simulated tumors), endermally injected, were scanned and compared to normal skin. For both cases acoustic microscopy with central operating frequencies of 110MHz and 175MHz were used, resulting to the tomographic imaging of the simulated tumor, while with the spectroscopic modalities IR and Raman differences among spectra of normal and melanin- injected sites were identified in skin depth. Subsequently, growth of actual tumors in an animal melanoma model, with the use of human malignant melanoma cells was achieved. Acoustic microscopy and IR and Raman spectroscopies were also applied. The development of tumors at different time points was displayed using acoustic microscopy. Moreover, the changes of the IR and Raman spectra were studied between the melanoma tumors and adjacent healthy skin. The most significant changes between healthy skin and the melanoma area were observed in the range of 900-1800cm-1 and 350-2000cm-1, respectively.

  17. 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

  18. Design and analysis of a health care clinic for homeless people using simulations.

    Science.gov (United States)

    Reynolds, Jared; Zeng, Zhen; Li, Jingshan; Chiang, Shu-Yin

    2010-01-01

    Improving quality of care is important in health care management. For health care clinics, reducing patient waiting time and improving throughput with efficient utilization of the workforce are important issues to achieve better quality of care. This paper seeks to introduce a simulation study on design and analysis of a health clinic for homeless patients in Lexington, Kentucky, USA. Using the simulation model, the patient flow of the clinic and analyze quality of care for different staffing levels is simulated. In addition, the dependence of distributions on service times is investigated. Moreover, the impact of service time variability on quality of care (e.g. patient waiting time) is analyzed. The necessary staffing level and utilizations to reduce patient waiting times and improve throughput to achieve better quality of care are obtained. In addition, it is shown that the system performance is primarily dependent on the mean and coefficients of variation, rather than a complete distribution, of service times. In addition, a piece-wise linear approximation formula is proposed so that patient waiting time in the clinic can be estimated for any variability with only two simulations. The simulation method may need long model development time and long simulation executing time for complex systems. The quality of care delivery in a health care clinic can be evaluated using simulations. The results presented in the paper provide an easier approach for medical practitioners to evaluate different scenarios, examine needed resources, and carry out what-if analysis to predictthe impact of any changes in the system, to determine an optimal system configuration. The paper shows that such models provide a quantitative tool for clinic operations and management to achieve better care quality. Moreover, it can be easily adapted to model other health care facilities, such as hospitals, emergency rooms, operating rooms, supply chain in health care industry.

  19. Clinical Simulation in Psychiatric-Mental Health Nursing: Post-Graduation Follow Up.

    Science.gov (United States)

    Lilly, Mary LuAnne; Hermanns, Melinda; Crawley, Bill

    2016-10-01

    In psychiatric-mental health, creating an innovative strategy to help students learn content that may not be frequently seen in a clinical setting is challenging. Thus, simulation helps narrow this gap. Using Kirkpatrick and Kirkpatrick's model of evaluation to guide the current study, faculty contacted baccalaureate nursing program graduates who completed a psychiatric-mental health clinical simulation scenario featuring a hanging suicide and wrist cutting suicide attempt scenario in the "Behind the Door" series as part of the clinical component of their undergraduate psychiatric-mental health course. Eleven nurses responded to a survey regarding their post-graduate encounters with these types of clinical situations, and their perception of recall and application of knowledge and skills acquired during the simulation experience to the clinical situation. Nursing graduates' responses are expressed through three major themes: emotional, contextual/behavioral, and assessment outcomes. Data from the survey indicate that nursing graduates perceived the "Behind the Door" simulations as beneficial to nursing practice. This perception is important in evaluating knowledge transfer from a simulation experience as a student into application in nursing practice. [Journal of Psychosocial Nursing and Mental Health Services, 54(10), 40-45.]. Copyright 2016, SLACK Incorporated.

  20. On the role of classical and novel forms of vitamin D in melanoma progression and management.

    Science.gov (United States)

    Slominski, Andrzej T; Brożyna, Anna A; Skobowiat, Cezary; Zmijewski, Michal A; Kim, Tae-Kang; Janjetovic, Zorica; Oak, Allen S; Jozwicki, Wojciech; Jetten, Anton M; Mason, Rebecca S; Elmets, Craig; Li, We; Hoffman, Robert M; Tuckey, Robert C

    2018-03-01

    Melanoma represents a significant clinical problem affecting a large segment of the population with a relatively high incidence and mortality rate. Ultraviolet radiation (UVR) is an important etiological factor in malignant transformation of melanocytes and melanoma development. UVB, while being a full carcinogen in melanomagenesis, is also necessary for the cutaneous production of vitamin D3 (D3). Calcitriol (1,25(OH) 2 D3) and novel CYP11A1-derived hydroxyderivatives of D3 show anti-melanoma activities and protective properties against damage induced by UVB. The former activities include inhibitory effects on proliferation, plating efficiency and anchorage-independent growth of cultured human and rodent melanomas in vitro, as well as the in vivo inhibition of tumor growth by 20(OH)D3 after injection of human melanoma cells into immunodeficient mice. The literature indicates that low levels of 25(OH)D3 are associated with more advanced melanomas and reduced patient survivals, while single nucleotide polymorphisms of the vitamin D receptor or the D3 binding protein gene affect development or progression of melanoma, or disease outcome. An inverse correlation of VDR and CYP27B1 expression with melanoma progression has been found, with low or undetectable levels of these proteins being associated with poor disease outcomes. Unexpectedly, increased expression of CYP24A1 was associated with better melanoma prognosis. In addition, decreased expression of retinoic acid orphan receptors α and γ, which can also bind vitamin D3 hydroxyderivatives, showed positive association with melanoma progression and shorter disease-free and overall survival. Thus, inadequate levels of biologically active forms of D3 and disturbances in expression of the target receptors, or D3 activating or inactivating enzymes, can affect melanomagenesis and disease progression. We therefore propose that inclusion of vitamin D into melanoma management should be beneficial for patients, at least as

  1. Melanoma in Buckinghamshire: Data from the Inception of the Skin Cancer Multidisciplinary Team

    International Nuclear Information System (INIS)

    Cubitt, J. J.; Khan, A. A.; Royston, E.; Rughani, M.; Budny, B. G.; Cubitt, J. J.; Middleton, M. R.

    2013-01-01

    Background. Melanoma incidence is increasing faster than any other cancer in the UK. The introduction of specialist skin cancer multidisciplinary teams intends to improve the provision of care to patients suffering from melanoma. This study aims to investigate the management and survival of patients diagnosed with melanoma around the time of inception of the regional skin cancer multidisciplinary team both to benchmark the service against published data and to enable future analysis of the impact of the specialisation of skin cancer care. Methods. All patients diagnosed with primary cutaneous melanoma between January 1, 2003 and December 3, 2005 were identified. Data on clinical and histopathological features, surgical procedures, complications, disease recurrence and 5-year survival were collected and analysed. Results. Two hundred and fourteen patients were included, 134 female and 80 males. Median Breslow thickness was 0.74 mm (0.7 mm female and 0.8 mm male). Overall 5-year survival was 88% (90% female and 85% male). Discussion. Melanoma incidence in Buckinghamshire is in keeping with published data. Basic demographics details concur with classic melanoma distribution and more recent trends, with increased percentage of superficial spreading and thin melanomas, leading to improved survival are reflected

  2. Transformation of a Silent Adrencorticotrophic Pituitary Tumor Into Central Nervous System Melanoma

    Directory of Open Access Journals (Sweden)

    Brandon A. Miller MD, PhD

    2013-06-01

    Full Text Available Silent adrenocorticotrophic pituitary adenomas are nonfunctioning pituitary adenomas that express adrenocorticotrophic hormone (ACTH but do not cause the clinical or laboratory features of hypercortisolemia. Primary central nervous system (CNS melanoma is well documented, but rarely originates in the sellar region or pituitary gland. Here we report transformation of an aggressive silent adrenocorticotrophic pituitary adenoma that transformed into CNS melanoma and review other presentations of pituitary melanoma. A 37-year-old woman initially presented with apoplexy and an invasive nonfunctioning pituitary macroadenoma for which she underwent transphenoidal surgery. The patient underwent 3 subsequent surgeries as the tumor continued to progress. Pathology from the first 3 operations showed pituitary adenoma or carcinoma. Pathology from the final surgery showed melanoma and the magnetic resonance imaging characteristics of the tumor had changed to become consistent with CNS melanoma. Dermatologic and ophthalmologic examinations did not identify cutaneous or ocular melanoma. The patient’s disease progressed despite aggressive surgical, medical and radiologic treatment. To our knowledge, this is the first report demonstrating transformation of a primary pituitary tumor into melanoma. The mechanism of tumor transformation is unclear, but it is possible that a mutation in the original ACTH-producing tumor lead to increased cleavage of pro-opiomelanocortin or ACTH into α-melanocyte-stimulating hormone, which in turn stimulated the expression of microopthalmia transcription factor, leading to melanocytic phenotype transformation.

  3. Genetic and Genomic Characterization of 462 Melanoma Patient-Derived Xenografts, Tumor Biopsies, and Cell Lines

    Directory of Open Access Journals (Sweden)

    Bradley Garman

    2017-11-01

    Full Text Available Summary: Tumor-sequencing studies have revealed the widespread genetic diversity of melanoma. Sequencing of 108 genes previously implicated in melanomagenesis was performed on 462 patient-derived xenografts (PDXs, cell lines, and tumors to identify mutational and copy number aberrations. Samples came from 371 unique individuals: 263 were naive to treatment, and 108 were previously treated with targeted therapy (34, immunotherapy (54, or both (20. Models of all previously reported major melanoma subtypes (BRAF, NRAS, NF1, KIT, and WT/WT/WT were identified. Multiple minor melanoma subtypes were also recapitulated, including melanomas with multiple activating mutations in the MAPK-signaling pathway and chromatin-remodeling gene mutations. These well-characterized melanoma PDXs and cell lines can be used not only as reagents for a large array of biological studies but also as pre-clinical models to facilitate drug development. : Garman et al. have characterized melanoma PDXs and cell lines described in Krepler et al. (see the related paper in this issue of Cell Reports, identifying major and minor subtypes, some of which were previously not well defined, targeted and immunotherapy resistance, and tumor heterogeneity, creating a set of reagents for future drug discovery and biological studies. Keywords: melanoma, patient-derived xenografts, massively parallel sequencing, cell lines

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

    International Nuclear Information System (INIS)

    Mishima, Yutaka

    1991-11-01

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

  5. Investigation for the extended application of melanoma Boron Neutron Capture Therapy

    International Nuclear Information System (INIS)

    Mishima, Yutaka

    1991-11-01

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

  6. Sustained effect of simulation-based ultrasound training on clinical performance: a randomized trial

    Science.gov (United States)

    Tolsgaard, M G; Ringsted, C; Dreisler, E; Nørgaard, L N; Petersen, J H; Madsen, M E; Freiesleben, N L C; Sørensen, J L; Tabor, A

    2015-01-01

    Objective To study the effect of initial simulation-based transvaginal sonography (TVS) training compared with clinical training only, on the clinical performance of residents in obstetrics and gynecology (Ob-Gyn), assessed 2 months into their residency. Methods In a randomized study, new Ob-Gyn residents (n = 33) with no prior ultrasound experience were recruited from three teaching hospitals. Participants were allocated to either simulation-based training followed by clinical training (intervention group; n = 18) or clinical training only (control group; n = 15). The simulation-based training was performed using a virtual-reality TVS simulator until an expert performance level was attained, and was followed by training on a pelvic mannequin. After 2 months of clinical training, one TVS examination was recorded for assessment of each resident's clinical performance (n = 26). Two ultrasound experts blinded to group allocation rated the scans using the Objective Structured Assessment of Ultrasound Skills (OSAUS) scale. Results During the 2 months of clinical training, participants in the intervention and control groups completed an average ± SD of 58 ± 41 and 63 ± 47 scans, respectively (P = 0.67). In the subsequent clinical performance test, the intervention group achieved higher OSAUS scores than did the control group (mean score, 59.1% vs 37.6%, respectively; P training leads to substantial improvement in clinical performance that is sustained after 2 months of clinical training. © 2015 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology. PMID:25580809

  7. Evaluating clinical simulations for learning procedural skills: a theory-based approach.

    Science.gov (United States)

    Kneebone, Roger

    2005-06-01

    Simulation-based learning is becoming widely established within medical education. It offers obvious benefits to novices learning invasive procedural skills, especially in a climate of decreasing clinical exposure. However, simulations are often accepted uncritically, with undue emphasis being placed on technological sophistication at the expense of theory-based design. The author proposes four key areas that underpin simulation-based learning, and summarizes the theoretical grounding for each. These are (1) gaining technical proficiency (psychomotor skills and learning theory, the importance of repeated practice and regular reinforcement), (2) the place of expert assistance (a Vygotskian interpretation of tutor support, where assistance is tailored to each learner's needs), (3) learning within a professional context (situated learning and contemporary apprenticeship theory), and (4) the affective component of learning (the effect of emotion on learning). The author then offers four criteria for critically evaluating new or existing simulations, based on the theoretical framework outlined above. These are: (1) Simulations should allow for sustained, deliberate practice within a safe environment, ensuring that recently-acquired skills are consolidated within a defined curriculum which assures regular reinforcement; (2) simulations should provide access to expert tutors when appropriate, ensuring that such support fades when no longer needed; (3) simulations should map onto real-life clinical experience, ensuring that learning supports the experience gained within communities of actual practice; and (4) simulation-based learning environments should provide a supportive, motivational, and learner-centered milieu which is conducive to learning.

  8. The Melanoma care study: protocol of a randomised controlled trial of a psycho-educational intervention for melanoma survivors at high risk of developing new primary disease.

    Science.gov (United States)

    Dieng, Mbathio; Kasparian, Nadine A; Morton, Rachael L; Mann, Graham J; Butow, Phyllis; Menzies, Scott; Costa, Daniel S J; Cust, Anne E

    2015-01-01

    Despite a good prognosis for most melanoma survivors, many experience substantial fear of new or recurrent melanoma, worry and anxiety about the future, and unmet healthcare needs. In this protocol, we outline the design and methods of the Melanoma Care Study for melanoma survivors at high risk of developing new primary disease. The objective of this study is to evaluate the efficacy and cost-effectiveness of a psycho-educational intervention for improving psychological and behavioural adjustment to melanoma risk. The study design is a two-arm randomised controlled trial comparing a psycho-educational intervention to usual care. The intervention is comprised of a newly-developed psycho-educational booklet and three telephone sessions delivered by a trained psychologist. A total of 154 melanoma survivors at high risk of developing new primary disease who are attending one of three melanoma high risk clinics in New South Wales, Australia, will be recruited. Participants will be assessed at baseline (6 weeks before their high risk clinic dermatological appointment), and then 4 weeks and 6 months after their appointment. If effectiveness of the intervention is demonstrated at 6 months, an additional assessment at 12 months is planned. The primary outcome is fear of new or recurrent melanoma, as assessed by the Fear of Cancer Recurrence Inventory (FCRI). Secondary outcomes include anxiety, depression, unmet supportive care needs, satisfaction with clinical care, knowledge, behavioural adjustment to melanoma risk, quality of life, and cost-effectiveness of the intervention from a health system perspective. Following the intention-to-treat principle, linear mixed models will be used to analyse the data to account for repeated measures. A process evaluation will also be carried out to inform and facilitate potential translation and implementation into clinical practice. This study will provide high quality evidence on the efficacy and cost-effectiveness of a psycho

  9. 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)

  10. Conjunctival amelanotic malignant melanoma arising in primary acquired melanosis sine pigmento.

    Science.gov (United States)

    Jay, V; Font, R L

    1998-01-01

    The authors describe an amelanotic malignant melanoma of the conjunctiva in association with primary acquired melanosis (PAM) sine pigmento, and highlight the clinical and pathologic features of this rare entity. Histopathologic and immunohistochemical studies were performed on a conjunctival tumor in a 54-year-old white woman. Case report. Histopathologic examination revealed an invasive amelanotic melanoma of the conjunctiva, with anterior orbital extension arising from intraepithelial dysplastic melanocytes that lacked melanin pigment (PAM sine pigmento). Both the malignant melanoma cells and the intraepithelial dysplastic melanocytes in the areas of PAM exhibited S-100 and HMB-45 positivity. The patient underwent an orbital exenteration that disclosed tumor within the anterior orbit inferiorly. Amelanotic invasive malignant melanoma can arise in association with PAM sine pigmento, as seen in our patient who had orbital invasion necessitating exenteration. This aggressive form of conjunctival melanoma is often associated with a poor prognosis and risk of metastatic disease. Absence of conjunctival pigmentation in PAM sine pigmento prevents early clinical detection of this variant of PAM. This lack of pigmentation also makes clinical diagnosis virtually impossible, and diagnosis can only be established histopathologically. Awareness of this nonpigmented variety of PAM is crucial for early recognition and appropriate management of the associated melanoma.

  11. Credibility, Replicability, and Reproducibility in Simulation for Biomedicine and Clinical Applications in Neuroscience

    Science.gov (United States)

    Mulugeta, Lealem; Drach, Andrew; Erdemir, Ahmet; Hunt, C. A.; Horner, Marc; Ku, Joy P.; Myers Jr., Jerry G.; Vadigepalli, Rajanikanth; Lytton, William W.

    2018-01-01

    Modeling and simulation in computational neuroscience is currently a research enterprise to better understand neural systems. It is not yet directly applicable to the problems of patients with brain disease. To be used for clinical applications, there must not only be considerable progress in the field but also a concerted effort to use best practices in order to demonstrate model credibility to regulatory bodies, to clinics and hospitals, to doctors, and to patients. In doing this for neuroscience, we can learn lessons from long-standing practices in other areas of simulation (aircraft, computer chips), from software engineering, and from other biomedical disciplines. In this manuscript, we introduce some basic concepts that will be important in the development of credible clinical neuroscience models: reproducibility and replicability; verification and validation; model configuration; and procedures and processes for credible mechanistic multiscale modeling. We also discuss how garnering strong community involvement can promote model credibility. Finally, in addition to direct usage with patients, we note the potential for simulation usage in the area of Simulation-Based Medical Education, an area which to date has been primarily reliant on physical models (mannequins) and scenario-based simulations rather than on numerical simulations. PMID:29713272

  12. A simulation framework for mapping risks in clinical processes: the case of in-patient transfers.

    Science.gov (United States)

    Dunn, Adam G; Ong, Mei-Sing; Westbrook, Johanna I; Magrabi, Farah; Coiera, Enrico; Wobcke, Wayne

    2011-05-01

    To model how individual violations in routine clinical processes cumulatively contribute to the risk of adverse events in hospital using an agent-based simulation framework. An agent-based simulation was designed to model the cascade of common violations that contribute to the risk of adverse events in routine clinical processes. Clinicians and the information systems that support them were represented as a group of interacting agents using data from direct observations. The model was calibrated using data from 101 patient transfers observed in a hospital and results were validated for one of two scenarios (a misidentification scenario and an infection control scenario). Repeated simulations using the calibrated model were undertaken to create a distribution of possible process outcomes. The likelihood of end-of-chain risk is the main outcome measure, reported for each of the two scenarios. The simulations demonstrate end-of-chain risks of 8% and 24% for the misidentification and infection control scenarios, respectively. Over 95% of the simulations in both scenarios are unique, indicating that the in-patient transfer process diverges from prescribed work practices in a variety of ways. The simulation allowed us to model the risk of adverse events in a clinical process, by generating the variety of possible work subject to violations, a novel prospective risk analysis method. The in-patient transfer process has a high proportion of unique trajectories, implying that risk mitigation may benefit from focusing on reducing complexity rather than augmenting the process with further rule-based protocols.

  13. Credibility, Replicability, and Reproducibility in Simulation for Biomedicine and Clinical Applications in Neuroscience

    Directory of Open Access Journals (Sweden)

    Lealem Mulugeta

    2018-04-01

    Full Text Available Modeling and simulation in computational neuroscience is currently a research enterprise to better understand neural systems. It is not yet directly applicable to the problems of patients with brain disease. To be used for clinical applications, there must not only be considerable progress in the field but also a concerted effort to use best practices in order to demonstrate model credibility to regulatory bodies, to clinics and hospitals, to doctors, and to patients. In doing this for neuroscience, we can learn lessons from long-standing practices in other areas of simulation (aircraft, computer chips, from software engineering, and from other biomedical disciplines. In this manuscript, we introduce some basic concepts that will be important in the development of credible clinical neuroscience models: reproducibility and replicability; verification and validation; model configuration; and procedures and processes for credible mechanistic multiscale modeling. We also discuss how garnering strong community involvement can promote model credibility. Finally, in addition to direct usage with patients, we note the potential for simulation usage in the area of Simulation-Based Medical Education, an area which to date has been primarily reliant on physical models (mannequins and scenario-based simulations rather than on numerical simulations.

  14. Primary pulmonary malignant melanoma: a clinicopathologic study of two cases.

    Science.gov (United States)

    Gong, Li; Liu, Xiao-Yan; Zhang, Wen-Dong; Zhu, Shao-Jun; Yao, Li; Han, Xiu-Juan; Lan, Miao; Li, Yan-Hong; Zhang, Wei

    2012-09-19

    Malignant melanoma involving the respiratory tract is nearly always metastatic in origin, and primary tumors are very rare. To our knowledge, about 30 cases have been reported in the English literature, one of which involved multiple brain metastases. Here, we report two cases of primary pulmonary malignant melanoma. The first case, which occurred in a 52-year-old Chinese female patient who died 4 months after the initial diagnosis, involved rapid intrapulmonary and intracranial metastases. The second patient, a 65-year-old female, underwent surgical excision, and clinical examination, histopathological characteristics, and immunohistochemical features supported the diagnosis of pulmonary malignant melanoma. No evidence for recurrence and/or metastasis has been found more than one year after the initial surgery. To establish the diagnosis of primary pulmonary malignant melanoma, any extrapulmonary origin must be excluded by detailed examination. Moreover, the tumor should be removed surgically whether it occurs as a single lesion or multiple lesions. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1480477335765055.

  15. Primary pulmonary malignant melanoma: a clinicopathologic study of two cases

    Directory of Open Access Journals (Sweden)

    Gong Li

    2012-09-01

    Full Text Available Abstract Malignant melanoma involving the respiratory tract is nearly always metastatic in origin, and primary tumors are very rare. To our knowledge, about 30 cases have been reported in the English literature, one of which involved multiple brain metastases. Here, we report two cases of primary pulmonary malignant melanoma. The first case, which occurred in a 52-year-old Chinese female patient who died 4 months after the initial diagnosis, involved rapid intrapulmonary and intracranial metastases. The second patient, a 65-year-old female, underwent surgical excision, and clinical examination, histopathological characteristics, and immunohistochemical features supported the diagnosis of pulmonary malignant melanoma. No evidence for recurrence and/or metastasis has been found more than one year after the initial surgery. To establish the diagnosis of primary pulmonary malignant melanoma, any extrapulmonary origin must be excluded by detailed examination. Moreover, the tumor should be removed surgically whether it occurs as a single lesion or multiple lesions. Virtual slide The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1480477335765055.

  16. Melanoma and melanocytic nevi in decorative tattoos: three case reports.

    Science.gov (United States)

    Varga, Erika; Korom, Irma; Varga, János; Kohán, József; Kemény, Lajos; Oláh, Judit

    2011-12-01

    In response to the demands of style and fashion, the number of decorative tattoos has been increasing worldwide. This has been paralleled by a rising incidence of melanocytic proliferations, including melanoma. The coincidence of various dermatological diseases and skin tumors with tattoos has been documented with some frequency, but reports of melanoma associated with tattoos are exceedingly rare. To date, only 13 cases have been documented in the English language literature. The possibility of an association between melanocytic proliferations and tattoos remains an area for further study. This report presents two cases of melanocytic nevi and one of melanoma occurring in association with a decorative tattoos. At present, the pathogenesis of melanoma developing in a tattoo is unknown. Mere coincidence cannot be ruled out. However, trauma, ultraviolet light exposure, a photoallergic effect, or an inflammatory reaction may promote malignant transformation. Clinicians and histopathologists should be aware of the clinical and pathological features if they are to make a correct diagnosis. Copyright © 2011 John Wiley & Sons A/S.

  17. The burden of malignant melanoma--lessons to be learned from Austria.

    Science.gov (United States)

    Monshi, Babak; Vujic, Marin; Kivaranovic, Danijel; Sesti, Alma; Oberaigner, Willi; Vujic, Igor; Ortiz-Urda, Susana; Posch, Christian; Feichtinger, Hans; Hackl, Monika; Rappersberger, Klemens

    2016-03-01

    Incidence rates of melanoma, generated by cancer registries (CRs), are susceptible to reporting inconsistencies due to increasing decentralisation of diagnosis. We therefore independently assessed the burden of melanoma in Austria. We collected histopathological reports on melanoma of all patients diagnosed in Austria in 2011. Demographic and clinical characteristics, histopathological tumour stages were assessed. Their regional distributions and incidence rates were analysed and compared with data of national and international CRs. A total of 5246 patients were diagnosed with 1951 in-situ and 3295 invasive melanomas in Austria in 2011 (population 8.4 million). Age, sex and anatomic distribution corresponded to findings in other European countries, however, the incidence of 25/100,000 (world age-standardised rate) for invasive melanomas was two-fold higher than published by the Austrian CR (12/100,000). Varying frequencies in diagnosing thin melanomas (≤1 mm; n = 4415) accounted exclusively for significant regional disparities, while advanced tumours (>1 mm; n = 761) were evenly distributed. Western Austria showed the highest rates (36/100,000). Patients from eastern Austria whose melanomas were diagnosed in laboratories in western Austria (n = 76) showed significantly higher proportions of in-situ lesions (n = 43; 57%) compared to those whose tumours were diagnosed in eastern Austria (n = 4014; in-situ = 1369; 34%) (p Austria, the melanoma burden and its potential socio-economic implications are significantly underestimated. Similarities of incidences indicate this could affect other European countries with well-established CRs and compromise international comparability of data. Austrian regional disparities suggest overdiagnosis of thin melanomas due to the variability of pathologists' thresholds for the diagnosis of early stage tumours. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  18. Simulation can contribute a part of cardiorespiratory physiotherapy clinical education: two randomized trials.

    Science.gov (United States)

    Blackstock, Felicity C; Watson, Kathryn M; Morris, Norman R; Jones, Anne; Wright, Anthony; McMeeken, Joan M; Rivett, Darren A; O'Connor, Vivienne; Peterson, Raymond F; Haines, Terry P; Watson, Geoffrey; Jull, Gwendolen Anne

    2013-02-01

    Simulated learning environments (SLEs) are used worldwide in health professional education, including physiotherapy, to train certain attributes and skills. To date, no randomized controlled trial (RCT) has evaluated whether education in SLEs can partly replace time in the clinical environment for physiotherapy cardiorespiratory practice. Two independent single-blind multi-institutional RCTs were conducted in parallel using a noninferiority design. Participants were volunteer physiotherapy students (RCT 1, n = 176; RCT 2, n = 173) entering acute care cardiorespiratory physiotherapy clinical placements. Two SLE models were investigated as follows: RCT 1, 1 week in SLE before 3 weeks of clinical immersion; RCT 2, 2 weeks of interspersed SLE/clinical immersion (equivalent to 1 SLE week) within the 4-week clinical placement. Students in each RCT were stratified on academic grade and randomly allocated to an SLE plus clinical immersion or clinical immersion control group. The primary outcome was competency to practice measured in 2 clinical examinations using the Assessment of Physiotherapy Practice. Secondary outcomes were student perception of experience and clinical educator and patient rating of student performance. There were no significant differences in student competency between the SLE and control groups in either RCT, although students in the interspersed group (RCT 2) achieved a higher score in 5 of 7 Assessment of Physiotherapy Practice standards (all P Students rated the SLE experience positively. Clinical educators and patients reported comparability between groups. An SLE can replace clinical time in cardiorespiratory physiotherapy practice. Part education in the SLE satisfied clinical competency requirements, and all stakeholders were satisfied.

  19. Developing authentic clinical simulations for effective listening and communication in pediatric rehabilitation service delivery.

    Science.gov (United States)

    King, Gillian; Shepherd, Tracy A; Servais, Michelle; Willoughby, Colleen; Bolack, Linda; Strachan, Deborah; Moodie, Sheila; Baldwin, Patricia; Knickle, Kerry; Parker, Kathryn; Savage, Diane; McNaughton, Nancy

    2016-10-01

    To describe the creation and validation of six simulations concerned with effective listening and interpersonal communication in pediatric rehabilitation. The simulations involved clinicians from various disciplines, were based on clinical scenarios related to client issues, and reflected core aspects of listening/communication. Each simulation had a key learning objective, thus focusing clinicians on specific listening skills. The article outlines the process used to turn written scenarios into digital video simulations, including steps taken to establish content validity and authenticity, and to establish a series of videos based on the complexity of their learning objectives, given contextual factors and associated macrocognitive processes that influence the ability to listen. A complexity rating scale was developed and used to establish a gradient of easy/simple, intermediate, and hard/complex simulations. The development process exemplifies an evidence-based, integrated knowledge translation approach to the teaching and learning of listening and communication skills.

  20. 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...

  1. Anti-cytotoxic T lymphocyte antigen-4 antibodies in melanoma

    Directory of Open Access Journals (Sweden)

    Tosti G

    2013-10-01

    Full Text Available Giulio Tosti, Emilia Cocorocchio, Elisabetta PennacchioliDivisione Melanomi e Sarcomi, Istituto Europeo di Oncologia, Milano, ItalyAbstract: Approaches aimed at enhancement of the tumor specific response have provided proof for the rationale of immunotherapy in cancer, both in animal models and in humans. Ipilimumab, an anti-cytotoxic T lymphocyte antigen-4 (CTLA-4 antibody, is a new generation immunotherapeutic agent that has shown activity in terms of disease free and overall survival in metastatic melanoma patients. Its use was approved by the US Food and Drug Administration in March 2011 to treat patients with late stage melanoma that has spread or that cannot be removed by surgery. The mechanism of action of CTLA-4 antibodies in the activation of an antitumor immune response and selected clinical studies of ipilimumab in advanced melanoma patients are discussed. Ipilimumab treatment has been associated with immune related adverse events due to T-cell activation and proliferation. Most of these serious adverse effects are associated with the gastrointestinal tract and include severe diarrhea and colitis. The relationship between immune related adverse events and antitumor activity associated with ipilimumab was explored in clinical studies. Potential biomarkers predictive for clinical response and survival in patients treated with anti-CTLA-4 therapy are presently under investigation. Besides the conventional patterns of response and stable disease as defined by standard Response Evaluation Criteria in Solid Tumors criteria, in subsets of patients, ipilimumab has shown patterns of delayed clinical activity which were associated with an improved overall survival. For this reason a new set of response criteria for tumor immunotherapy has been proposed, which was termed immune related response criteria. These new criteria are presently used to better analyze clinical activity of immunotherapeutic regimens. Ipilimumab is currently under

  2. Effectiveness of Standardized Patient Simulations in Teaching Clinical Communication Skills to Dental Students.

    Science.gov (United States)

    McKenzie, Carly T; Tilashalski, Ken R; Peterson, Dawn Taylor; White, Marjorie Lee

    2017-10-01

    The aim of this study was to investigate dental students' long-term retention of clinical communication skills learned in a second-year standardized patient simulation at one U.S. dental school. Retention was measured by students' performance with an actual patient during their fourth year. The high-fidelity simulation exercise focused on clinical communication skills took place during the spring term of the students' second year. The effect of the simulation was measured by comparing the fourth-year clinical performance of two groups: those who had participated in the simulation (intervention group; Class of 2016) and those who had not (no intervention/control group; Class of 2015). In the no intervention group, all 47 students participated; in the intervention group, 58 of 59 students participated. Both instructor assessments and students' self-assessments were used to evaluate the effectiveness of key patient interaction principles as well as comprehensive presentation of multiple treatment options. The results showed that students in the intervention group more frequently included cost during their treatment option presentation than did students in the no intervention group. The instructor ratings showed that the intervention group included all key treatment option components except duration more frequently than did the no intervention group. However, the simulation experience did not result in significantly more effective student-patient clinical communication on any of the items measured. This study presents limited evidence of the effectiveness of a standardized patient simulation to improve dental students' long-term clinical communication skills with respect to thorough presentation of treatment options to a patient.

  3. Melanoma brain metastases presenting as delirium: a case report

    Directory of Open Access Journals (Sweden)

    Sofia Morais

    Full Text Available Abstract Background Metastatic tumours sometimes present with neuropsychiatric symptoms, however psychiatric symptoms as rarely the first clinical manifestation. Cutaneous melanoma is the third most common cause of brain metastasis, with known risk factors increasing the chance of such central nervous system metastization. Objectives We present a clinical report of delirium as the first clinical manifestation of melanoma brain metastases, illustrating the relevance of an adequate and early differential diagnosis. Methods In addition to describing the clinical case, searches were undertaken in PubMed and other databases using keywords such as “brain metastasis”, “melanoma”, “agitation”, “psychiatric” and “delirium”. Results We here report the case of a 52-year-old female patient evaluated by Liaison Psychiatry after sudden onset of delirium while admitted at the Gastroenterology Department to study a hypothesis of pancreatitis. A head CT scan identified brain metastases, and after further examination, including brain biopsy, melanoma brain metastization was confirmed. Discussion Some of the diagnostic challenges of psychiatric symptoms associated with secondary brain tumours are discussed, underlining the importance of an adequate differential diagnosis when working in Psychiatry Liaison.

  4. 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

  5. Progressive learning in endoscopy simulation training improves clinical performance: a blinded randomized trial.

    Science.gov (United States)

    Grover, Samir C; Scaffidi, Michael A; Khan, Rishad; Garg, Ankit; Al-Mazroui, Ahmed; Alomani, Tareq; Yu, Jeffrey J; Plener, Ian S; Al-Awamy, Mohamed; Yong, Elaine L; Cino, Maria; Ravindran, Nikila C; Zasowski, Mark; Grantcharov, Teodor P; Walsh, Catharine M

    2017-11-01

    A structured comprehensive curriculum (SCC) that uses simulation-based training (SBT) can improve clinical colonoscopy performance. This curriculum may be enhanced through the application of progressive learning, a training strategy centered on incrementally challenging learners. We aimed to determine whether a progressive learning-based curriculum (PLC) would lead to superior clinical performance compared with an SCC. This was a single-blinded randomized controlled trial conducted at a single academic center. Thirty-seven novice endoscopists were recruited and randomized to either a PLC (n = 18) or to an SCC (n = 19). The PLC comprised 6 hours of SBT, which progressed in complexity and difficulty. The SCC included 6 hours of SBT, with cases of random order of difficulty. Both groups received expert feedback and 4 hours of didactic teaching. Participants were assessed at baseline, immediately after training, and 4 to 6 weeks after training. The primary outcome was participants' performance during their first 2 clinical colonoscopies, as assessed by using the Joint Advisory Group Direct Observation of Procedural Skills assessment tool (JAG DOPS). Secondary outcomes were differences in endoscopic knowledge, technical and communication skills, and global performance in the simulated setting. The PLC group outperformed the SCC group during first and second clinical colonoscopies, measured by JAG DOPS (P PLC group had superior technical and communication skills and global performance in the simulated setting (P  .05). Our findings demonstrate the superiority of a PLC for endoscopic simulation, compared with an SCC. Challenging trainees progressively is a simple, theory-based approach to simulation whereby the performance of clinical colonoscopies can be improved. (Clinical trial registration number: NCT02000180.). Copyright © 2017 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

  6. Malignant melanoma risk after exposure to fertility drugs: results from a large Danish cohort study

    DEFF Research Database (Denmark)

    Hannibal, C.G.; Jensen, A.; Sharif, H.

    2008-01-01

    . A detailed data collection including information about type and amount of treatment was conducted. Using case-cohort techniques, we calculated rate ratios (RRs) of malignant melanoma associated with different fertility drugs after adjustment for parity status. RESULTS: 112 malignant melanomas were identified......OBJECTIVE: The aim was to examine the effects of fertility drugs on malignant melanoma risk using data from the largest cohort of infertile women to date. METHODS: A cohort of 54,362 women with infertility problems referred to Danish fertility clinics in the period 1963-1998 was established...... with a significant increased risk. For all groups of fertility drugs, we found no association with number of cycles of use or years since first use (latency). CONCLUSIONS: Our findings showed no strong association between malignant melanoma risk and use of fertility drugs, although the results indicated that use...

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

    Science.gov (United States)

    Nissan, Moriah H; Solit, David B

    2011-12-01

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

  8. Exploiting cannabinoid-induced cytotoxic autophagy to drive melanoma cell death.

    Science.gov (United States)

    Armstrong, Jane L; Hill, David S; McKee, Christopher S; Hernandez-Tiedra, Sonia; Lorente, Mar; Lopez-Valero, Israel; Eleni Anagnostou, Maria; Babatunde, Fiyinfoluwa; Corazzari, Marco; Redfern, Christopher P F; Velasco, Guillermo; Lovat, Penny E

    2015-06-01

    Although the global incidence of cutaneous melanoma is increasing, survival rates for patients with metastatic disease remain viability, and activation of apoptosis, whereas cotreatment with chloroquine or knockdown of Atg7, but not Beclin-1 or Ambra1, prevented THC-induced autophagy and cell death in vitro. Administration of Sativex-like (a laboratory preparation comprising equal amounts of THC and cannabidiol (CBD)) to mice bearing BRAF wild-type melanoma xenografts substantially inhibited melanoma viability, proliferation, and tumor growth paralleled by an increase in autophagy and apoptosis compared with standard single-agent temozolomide. Collectively, our findings suggest that THC activates noncanonical autophagy-mediated apoptosis of melanoma cells, suggesting that cytotoxic autophagy induction with Sativex warrants clinical evaluation for metastatic disease.

  9. Shaggy Photoreceptors with Subfoveal Fluid Associated with a Distant Choroidal Melanoma

    Directory of Open Access Journals (Sweden)

    Ann Q. Tran

    2015-01-01

    Full Text Available Purpose. To describe the enhanced depth imaging optical coherence tomography (EDI-OCT findings in a patient with an extra macula choroidal melanoma before and after treatment. Methods. Observational case report. Results. A 45 year-old Caucasian male patient was referred to retina clinic for management of choroidal melanoma. Examination revealed a nasal choroidal melanoma while EDI-OCT illustrated subfoveal fluid pocket with elongated shaggy photoreceptors distant and separate from the tumor. The patient was treated with plaque brachytherapy and intravitreal bevacizumab. One week after plaque removal, there was a dramatic reduction in the shaggy photoreceptors. Conclusion. Choroidal melanomas have effects that are not localized to the area of the tumor. This loculated pocket of subretinal fluid and coinciding changes to photoreceptor morphology may be related to global changes in choroidal function or release of tumor related cytokines.

  10. Comparing Melanoma Invasiveness in Dermatologist- versus Patient-Detected Lesions: A Retrospective Chart Review

    Directory of Open Access Journals (Sweden)

    Cindy L. Lamerson

    2012-01-01

    Full Text Available This study examined whether patient-identified melanomas were more advanced than dermatologist-identified tumors at routine clinic visits, and whether a personal or family history of skin cancer was associated with patterns of detection. A retrospective chart review was performed on melanoma patients (N=201 in a private dermatology clinic. Variables included age, gender, pattern of detection (i.e., patient or a board certified dermatologist, personal or family history of skin cancer, skin type, and previous sun exposure, as well as tumor location and severity. Dermatologist-diagnosed melanomas were less invasive (P<0.0005, and more likely present on the chest, back, and legs (P<0.01. Conversely, patient-identified lesions were more likely to occur on the face, neck and scalp, be associated with younger patients, and a family history of melanoma, but not other types of skin cancer (P<0.01. In a post-hoc analysis examining these factors as predictors of tumor invasiveness, only diagnostic source was significant. Specifically, dermatologist-identified tumors were significantly less invasive than patient-identified tumors. Although age, family history, and tumor location played roles in the early detection of melanomas, the most important factor was diagnostic source. Thus, board-certified dermatologists play a key role in the early detection of malignant melanoma.

  11. In-depth characterization of microRNA transcriptome in melanoma.

    Directory of Open Access Journals (Sweden)

    James Kozubek

    Full Text Available The full repertoire of human microRNAs (miRNAs that could distinguish common (benign nevi from cutaneous (malignant melanomas remains to be established. In an effort to gain further insight into the role of miRNAs in melanoma, we applied Illumina next-generation sequencing (NGS platform to carry out an in-depth analysis of miRNA transcriptome in biopsies of nevi, thick primary (>4.0 mm and metastatic melanomas with matched normal skin in parallel to melanocytes and melanoma cell lines (both primary and metastatic (n=28. From this data representing 698 known miRNAs, we defined a set of top-40 list, which properly classified normal from cancer; also confirming 23 (58% previously discovered miRNAs while introducing an additional 17 (42% known and top-15 putative novel candidate miRNAs deregulated during melanoma progression. Surprisingly, the miRNA signature distinguishing specimens of melanoma from nevus was significantly different than that of melanoma cell lines from melanocytes. Among the top list, miR-203, miR-204-5p, miR-205-5p, miR-211-5p, miR-23b-3p, miR-26a-5p and miR-26b-5p were decreased in melanomas vs. nevi. In a validation cohort (n=101, we verified the NGS results by qRT-PCR and showed that receiver-operating characteristic curves for miR-211-5p expression accurately discriminated invasive melanoma (AUC=0.933, melanoma in situ (AUC=0.933 and dysplastic (atypical nevi (AUC=0.951 from common nevi. Target prediction analysis of co-transcribed miRNAs showed a cooperative regulation of key elements in the MAPK signaling pathway. Furthermore, we found extensive sequence variations (isomiRs and other non-coding small RNAs revealing a complex melanoma transcriptome. Deep-sequencing small RNAs directly from clinically defined specimens provides a robust strategy to improve melanoma diagnostics.

  12. 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

  13. Simulating clinical studies of the glucoregulatory system: in vivo meets in silico

    DEFF Research Database (Denmark)

    Wendt, Sabrina Lyngbye; Ranjan, Ajenthen; Møller, Jan Kloppenborg

    metabolism at varying ambient insulin levels. The report compares in vivo and in silico results head-to-head, and discusses similarities and differences. We design and simulate simple studies to emphasize the implications of some glucoregulatory dynamics which are ignored in most previous clinical studies...

  14. Applying Kane's Validity Framework to a Simulation Based Assessment of Clinical Competence

    Science.gov (United States)

    Tavares, Walter; Brydges, Ryan; Myre, Paul; Prpic, Jason; Turner, Linda; Yelle, Richard; Huiskamp, Maud

    2018-01-01

    Assessment of clinical competence is complex and inference based. Trustworthy and defensible assessment processes must have favourable evidence of validity, particularly where decisions are considered high stakes. We aimed to organize, collect and interpret validity evidence for a high stakes simulation based assessment strategy for certifying…

  15. eLearning techniques supporting problem based learning in clinical simulation.

    Science.gov (United States)

    Docherty, Charles; Hoy, Derek; Topp, Helena; Trinder, Kathryn

    2005-08-01

    This paper details the results of the first phase of a project using eLearning to support students' learning within a simulated environment. The locus was a purpose built clinical simulation laboratory (CSL) where the School's philosophy of problem based learning (PBL) was challenged through lecturers using traditional teaching methods. a student-centred, problem based approach to the acquisition of clinical skills that used high quality learning objects embedded within web pages, substituting for lecturers providing instruction and demonstration. This encouraged student nurses to explore, analyse and make decisions within the safety of a clinical simulation. Learning was facilitated through network communications and reflection on video performances of self and others. Evaluations were positive, students demonstrating increased satisfaction with PBL, improved performance in exams, and increased self-efficacy in the performance of nursing activities. These results indicate that eLearning techniques can help students acquire clinical skills in the safety of a simulated environment within the context of a problem based learning curriculum.

  16. Sun protection and skin self-examination in melanoma survivors.

    Science.gov (United States)

    Mujumdar, Urvi J; Hay, Jennifer L; Monroe-Hinds, Yvette C; Hummer, Amanda J; Begg, Colin B; Wilcox, Homer B; Oliveria, Susan A; Berwick, Marianne

    2009-10-01

    Patients diagnosed with melanoma are at risk for developing recurrent and second primary disease. Skin self-examination (SSE) and sun protection are standard clinical recommendations to minimize risk. In this study we examined performance of these behaviors in individuals with melanoma drawn from the general population. Potential participants (N=148) with a first primary melanoma diagnosed in 2000 were identified through a population-based cancer registry in New Jersey, USA. One hundred and fifteen individuals participated in a 30 min telephone interview concerning behavioral adherence with SSE and sun protection, self-efficacy for performing these behaviors, and perceived risk of developing another skin cancer. We utilized logistic regression to estimate potential associations of demographic, medical, and psychosocial factors with SSE and sun protection, respectively. Seventeen percent of subjects reported performing comprehensive SSE at least once every two months and 23% engaged in regular sun protection. Utilization of SSE was related to the presence of moles (OR=4.2, 95% CI: 1.1-15) and higher SSE self-efficacy (OR=14.4, 95% CI: 1.9-112). Regular sun protection was related to older age (>60 years; OR=3.3, 95% CI: 1.3-8.7), being female (OR=2.8, 95% CI: 1.1-7.3), and higher sun protection self-efficacy (OR=5.0, 95% CI: 1.4-18). These factors remained significant in multivariate models. In this group of primary melanoma survivors, the rates of SSE and sun protection are comparable to, but do not exceed, general population estimates. This study provides justification for further research to address barriers to prevention and control behaviors in melanoma survivors.

  17. The validity of a professional competence tool for physiotherapy students in simulation-based clinical education: a Rasch analysis.

    Science.gov (United States)

    Judd, Belinda K; Scanlan, Justin N; Alison, Jennifer A; Waters, Donna; Gordon, Christopher J

    2016-08-05

    Despite the recent widespread adoption of simulation in clinical education in physiotherapy, there is a lack of validated tools for assessment in this setting. The Assessment of Physiotherapy Practice (APP) is a comprehensive tool used in clinical placement settings in Australia to measure professional competence of physiotherapy students. The aim of the study was to evaluate the validity of the APP for student assessment in simulation settings. A total of 1260 APPs were collected, 971 from students in simulation and 289 from students in clinical placements. Rasch analysis was used to examine the construct validity of the APP tool in three different simulation assessment formats: longitudinal assessment over 1 week of simulation; longitudinal assessment over 2 weeks; and a short-form (25 min) assessment of a single simulation scenario. Comparison with APPs from 5 week clinical placements in hospital and clinic-based settings were also conducted. The APP demonstrated acceptable fit to the expectations of the Rasch model for the 1 and 2 week clinical simulations, exhibiting unidimensional properties that were able to distinguish different levels of student performance. For the short-form simulation, nine of the 20 items recorded greater than 25 % of scores as 'not-assessed' by clinical educators which impacted on the suitability of the APP tool in this simulation format. The APP was a valid assessment tool when used in longitudinal simulation formats. A revised APP may be required for assessment in short-form simulation scenarios.

  18. A comparative study of proliferative nodules and lethal melanomas in congenital nevi from children.

    Science.gov (United States)

    Yélamos, Oriol; Arva, Nicoleta C; Obregon, Roxana; Yazdan, Pedram; Wagner, Annette; Guitart, Joan; Gerami, Pedram

    2015-03-01

    Differentiating proliferative nodules (PNs) from melanomas arising in congenital nevi (CN) is a considerable challenge for dermatopathologists. Most of the specimens dermatopathologists assess that deal with this differential diagnosis involve proliferations of melanocytes arising in the dermis. In this study, we compare the clinical, histologic, and molecular findings of these 2 conditions. In our database, we found 22 examples of PNs arising in the dermis of CN and 2 cases of lethal melanomas arising from the dermis/epidermis of CN of children. Importantly, we found that among dermal melanocytic proliferations arising from CN in children, PNs are far more common than lethal melanomas. Clinically, multiplicity of lesions favored a diagnosis of PNs, whereas ulceration was infrequent in PNs compared with lethal melanomas. Histologically, PNs showed several distinct patterns including expansile nodules of epithelioid melanocytes with mitotic counts lower than that seen in the melanomas (1.67 vs. 12.5 mitoses/mm), a small round blue cell pattern often highly mitotically active, neurocristic-like, blue nevus-like, a nevoid melanoma-like pattern, or an undifferentiated spindle cell pattern. The lethal melanomas both featured expansile nodules of epithelioid melanocytes with high mitotic counts (range, 5 to 20 mitoses/mm) and an ulcerated overlying epidermis. At the molecular level, the PNs showed mostly whole chromosomal copy number aberrations, which in some cases were accompanied by rare partial chromosomal aberrations, whereas both lethal melanomas showed highly elevated copy number aberrations involving 6p25 without gains of the long arm of chromosome 6.

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

    Directory of Open Access Journals (Sweden)

    Michael Ngo

    2016-08-01

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

  20. Dark sputum: An atypical presentation of primary pulmonary malignant melanoma

    Directory of Open Access Journals (Sweden)

    Alida Filippini

    2015-01-01

    Primary lung melanoma is an uncommon neoplasm that may be confused with more conventional types of lung cancer. Careful interpretation of histopathological information in correlation with all other clinical, laboratory and imaging studies may be needed to establish a diagnosis. Evaluation for metastases should include looking at the eyes, brain, skin. Due to the small number of cases reported in literature, there is no experience on the management and the prognosis of the disease.

  1. 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.

  2. 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.

  3. 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.

  4. A gene expression signature associated with survival in metastatic melanoma

    Science.gov (United States)

    Mandruzzato, Susanna; Callegaro, Andrea; Turcatel, Gianluca; Francescato, Samuela; Montesco, Maria C; Chiarion-Sileni, Vanna; Mocellin, Simone; Rossi, Carlo R; Bicciato, Silvio; Wang, Ena; Marincola, Francesco M; Zanovello, Paola

    2006-01-01

    Background Current clinical and histopathological criteria used to define the prognosis of melanoma patients are inadequate for accurate prediction of clinical outcome. We investigated whether genome screening by means of high-throughput gene microarray might provide clinically useful information on patient survival. Methods Forty-three tumor tissues from 38 patients with stage III and stage IV melanoma were profiled with a 17,500 element cDNA microarray. Expression data were analyzed using significance analysis of microarrays (SAM) to identify genes associated with patient survival, and supervised principal components (SPC) to determine survival prediction. Results SAM analysis revealed a set of 80 probes, corresponding to 70 genes, associated with survival, i.e. 45 probes characterizing longer and 35 shorter survival times, respectively. These transcripts were included in a survival prediction model designed using SPC and cross-validation which allowed identifying 30 predicting probes out of the 80 associated with survival. Conclusion The longer-survival group of genes included those expressed in immune cells, both innate and acquired, confirming the interplay between immunological mechanisms and the natural history of melanoma. Genes linked to immune cells were totally lacking in the poor-survival group, which was instead associated with a number of genes related to highly proliferative and invasive tumor cells. PMID:17129373

  5. A gene expression signature associated with survival in metastatic melanoma

    Directory of Open Access Journals (Sweden)

    Rossi Carlo R

    2006-11-01

    Full Text Available Abstract Background Current clinical and histopathological criteria used to define the prognosis of melanoma patients are inadequate for accurate prediction of clinical outcome. We investigated whether genome screening by means of high-throughput gene microarray might provide clinically useful information on patient survival. Methods Forty-three tumor tissues from 38 patients with stage III and stage IV melanoma were profiled with a 17,500 element cDNA microarray. Expression data were analyzed using significance analysis of microarrays (SAM to identify genes associated with patient survival, and supervised principal components (SPC to determine survival prediction. Results SAM analysis revealed a set of 80 probes, corresponding to 70 genes, associated with survival, i.e. 45 probes characterizing longer and 35 shorter survival times, respectively. These transcripts were included in a survival prediction model designed using SPC and cross-validation which allowed identifying 30 predicting probes out of the 80 associated with survival. Conclusion The longer-survival group of genes included those expressed in immune cells, both innate and acquired, confirming the interplay between immunological mechanisms and the natural history of melanoma. Genes linked to immune cells were totally lacking in the poor-survival group, which was instead associated with a number of genes related to highly proliferative and invasive tumor cells.

  6. 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.

  7. Melanoma of unknown origin: a case series.

    LENUS (Irish Health Repository)

    Kelly, J

    2010-12-01

    The natural history of metastatic melanoma involving lymph nodes, in the absence of a known primary site (cutaneous, ocular or mucosal) has, to date, been poorly defined; and the optimal management of this rare subtype of disease is therefore unclear. Melanomas of unknown primary site (MUP) are estimated to comprise between 3.7 and 6% of all melanomas (Anbari et al. in Cancer 79:1861-1821, 1997).

  8. 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.

  9. [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.

  10. Interprofessional teamwork skills as predictors of clinical outcomes in a simulated healthcare setting.

    Science.gov (United States)

    Shrader, Sarah; Kern, Donna; Zoller, James; Blue, Amy

    2013-01-01

    Teaching interprofessional (IP) teamwork skills is a goal of interprofessional education. The purpose of this study was to examine the relationship between IP teamwork skills, attitudes and clinical outcomes in a simulated clinical setting. One hundred-twenty health professions students (medicine, pharmacy, physician assistant) worked in interprofessional teams to manage a "patient" in a health care simulation setting. Students completed the Interdisciplinary Education Perception Scale (IEPS) attitudinal survey instrument. Students' responses were averaged by team to create an IEPS attitudes score. Teamwork skills for each team were rated by trained observers using a checklist to calculate a teamwork score (TWS). Clinical outcome scores (COS) were determined by summation of completed clinical tasks performed by the team based on an expert developed checklist. Regression analyses were conducted to determine the relationship of IEPS and TWS with COS. IEPS score was not a significant predictor of COS (p=0.054), but TWS was a significant predictor (pstudents' interprofessional teamwork skills are significant predictors of positive clinical outcomes. Interprofessional curricular models that produce effective teamwork skills can improve student performance in clinical environments and likely improve teamwork practice to positively affect patient care outcomes.

  11. 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.

  12. Prosthetic rehabilitation of a patient after partial maxillectomy: A clinical report

    Directory of Open Access Journals (Sweden)

    Shobha J Rodrigues

    2011-01-01

    Full Text Available Malignant melanoma of the oral cavity is very rare. This clinical report describes a method for prosthetic rehabilitation of a patient with malignant melanoma of the palate following partial maxillectomy with a closed hollow interim obturator.

  13. Prosthetic rehabilitation of a patient after partial maxillectomy: A clinical report

    OpenAIRE

    Rodrigues, Shobha J.; Saldanha, Sharon

    2011-01-01

    Malignant melanoma of the oral cavity is very rare. This clinical report describes a method for prosthetic rehabilitation of a patient with malignant melanoma of the palate following partial maxillectomy with a closed hollow interim obturator.

  14. Design principles for simulation games for learning clinical reasoning: A design-based research approach.

    Science.gov (United States)

    Koivisto, J-M; Haavisto, E; Niemi, H; Haho, P; Nylund, S; Multisilta, J

    2018-01-01

    Nurses sometimes lack the competence needed for recognising deterioration in patient conditions and this is often due to poor clinical reasoning. There is a need to develop new possibilities for learning this crucial competence area. In addition, educators need to be future oriented; they need to be able to design and adopt new pedagogical innovations. The purpose of the study is to describe the development process and to generate principles for the design of nursing simulation games. A design-based research methodology is applied in this study. Iterative cycles of analysis, design, development, testing and refinement were conducted via collaboration among researchers, educators, students, and game designers. The study facilitated the generation of reusable design principles for simulation games to guide future designers when designing and developing simulation games for learning clinical reasoning. This study makes a major contribution to research on simulation game development in the field of nursing education. The results of this study provide important insights into the significance of involving nurse educators in the design and development process of educational simulation games for the purpose of nursing education. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Development and implementation of a clinical pathway approach to simulation-based training for foregut surgery.

    Science.gov (United States)

    Miyasaka, Kiyoyuki W; Buchholz, Joseph; LaMarra, Denise; Karakousis, Giorgos C; Aggarwal, Rajesh

    2015-01-01

    Contemporary demands on resident education call for integration of simulation. We designed and implemented a simulation-based curriculum for Post Graduate Year 1 surgery residents to teach technical and nontechnical skills within a clinical pathway approach for a foregut surgery patient, from outpatient visit through surgery and postoperative follow-up. The 3-day curriculum for groups of 6 residents comprises a combination of standardized patient encounters, didactic sessions, and hands-on training. The curriculum is underpinned by a summative simulation "pathway" repeated on days 1 and 3. The "pathway" is a series of simulated preoperative, intraoperative, and postoperative encounters in following up a single patient through a disease process. The resident sees a standardized patient in the clinic presenting with distal gastric cancer and then enters an operating room to perform a gastrojejunostomy on a porcine tissue model. Finally, the resident engages in a simulated postoperative visit. All encounters are rated by faculty members and the residents themselves, using standardized assessment forms endorsed by the American Board of Surgery. A total of 18 first-year residents underwent this curriculum. Faculty ratings of overall operative performance significantly improved following the 3-day module. Ratings of preoperative and postoperative performance were not significantly changed in 3 days. Resident self-ratings significantly improved for all encounters assessed, as did reported confidence in meeting the defined learning objectives. Conventional surgical simulation training focuses on technical skills in isolation. Our novel "pathway" curriculum targets an important gap in training methodologies by placing both technical and nontechnical skills in their clinical context as part of managing a surgical patient. Results indicate consistent improvements in assessments of performance as well as confidence and support its continued usage to educate surgery residents

  16. A simulation framework for mapping risks in clinical processes: the case of in-patient transfers

    Science.gov (United States)

    Ong, Mei-Sing; Westbrook, Johanna I; Magrabi, Farah; Coiera, Enrico; Wobcke, Wayne

    2011-01-01

    Objective To model how individual violations in routine clinical processes cumulatively contribute to the risk of adverse events in hospital using an agent-based simulation framework. Design An agent-based simulation was designed to model the cascade of common violations that contribute to the risk of adverse events in routine clinical processes. Clinicians and the information systems that support them were represented as a group of interacting agents using data from direct observations. The model was calibrated using data from 101 patient transfers observed in a hospital and results were validated for one of two scenarios (a misidentification scenario and an infection control scenario). Repeated simulations using the calibrated model were undertaken to create a distribution of possible process outcomes. The likelihood of end-of-chain risk is the main outcome measure, reported for each of the two scenarios. Results The simulations demonstrate end-of-chain risks of 8% and 24% for the misidentification and infection control scenarios, respectively. Over 95% of the simulations in both scenarios are unique, indicating that the in-patient transfer process diverges from prescribed work practices in a variety of ways. Conclusions The simulation allowed us to model the risk of adverse events in a clinical process, by generating the variety of possible work subject to violations, a novel prospective risk analysis method. The in-patient transfer process has a high proportion of unique trajectories, implying that risk mitigation may benefit from focusing on reducing complexity rather than augmenting the process with further rule-based protocols. PMID:21486883

  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. Termoterapia transpupilar em melanoma maligno da coróide Transpupillary thermotherapy for malignant choroidal melanoma

    Directory of Open Access Journals (Sweden)

    Martha M. Motomo Chojniak

    2001-04-01

    ,63%, vitreite associada a tênues membranas vítreas em 1 paciente (9,09% e quemose associada a edema palpebral em 1 paciente (9,09%. Controle tumoral local com conservação do globo ocular foi observado durante este pequeno tempo de seguimento em 100% dos pacientes tratados. Por ocasião da "última revisão", 100% dos pacientes estavam vivos e sem doença metastática. Conclusão: Este estudo preliminar sugere que a termoterapia transpupilar apresenta-se como um método efetivo e seguro para o tratamento de selecionados melanomas pequenos da coróide. Para melhor avaliação é necessário tempo de seguimento prolongado.Purpose: Several methods have been used for treatment of choroidal melanoma. The purpose of this preliminary paper is to evaluate the effectiveness of transpupillary thermo- therapy (TTT as a primary treatment of small choroidal melanomas. Methods: This is a prospective nonrandomized study evaluating clinical aspects, tumor response, complications and visual outcome in patients presenting small choroidal melanomas (up to 4.0 mm thick and 12 mm base diameter treated with TTT over 810 nm laser diode applications. Results: There were 11 patients treated with trans-pupillary thermotherapy, all of them presenting pig-mented small choroidal melanomas. Growth previous to treatment was documented in 5 patients and risk factors for growth or metastatic disease was present in all the patients. After treatment the patients were followed for 3 to 8 months (mean 5.7 months. Three laser sessions were used in 5 pa-tients and 4 sessions in 6 patients. The lesions presented at the beginning of the treatment a mean thickness of 2.7 mm, with a mean larger base diameter of 7.8 mm. All the lesions responded to treatment and presented decrease of thickness and base diameters. After transpupillary thermotherapy, the lesions' mean thickness was 1.8 mm and the mean larger base diameter was 6.7 mm. The mean reduction in thickness was 0.9 mm and the mean decrease in larger base

  19. 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.

  20. 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

  1. [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.

  2. 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...

  3. Clinical relevance of positron emission tomography for initial staging and follow-up of malignant melanoma; Klinischer Stellenwert der Positronenemissionstomographie im Primaerstaging und in der Nachsorge des malignen Melanoms

    Energy Technology Data Exchange (ETDEWEB)

    Baum, R.P. [Zentralklinik Bad Berka GmbH (Germany). Klinik fuer Nuklearmedizin/PET-Zentrum; Rinne, D.; Kaufmann, R. [Frankfurt Univ. (Germany). Klinik fuer Dermatologie und Venerologie

    2000-12-01

    The incidence of melanoma is rapidly increasing (at a rate of 5 percent per year) throughout the world. In Europe, the incidence is approximately 10-12 new cases of invasive melanoma per 100,000 inhabitants. The most important prognostic factor is the stage of disease (Clark Level and vertical tumor depth (TD) according to BRESLOW) at the time of presentation. Ten year survival is 90 percent with a TD of <1.5 mm, and 65 percent with a TD of >1.5 mm; 5-year survival is 15-50 percent when there is regional lymph node involvement, and 5 percent when there is disseminated disease. Conventional diagnostic tests for staging include a chest X-ray, lymph node sonography and laboratory tests. Sentinel node biopsy is becoming an increasingly common procedure since melanoma usually metastasizes to regional lymph nodes before dissemination. CT scan of the thorax or abdomen, MRI of the brain and other tests are used only when signs or symptoms warrant. The results of a prospective study which we performed in 100 patients for staging of high risk melanoma (n=48) or for re-staging patients with suspected recurrence demonstrated that FDG whole-body PET is superior to conventional imaging techniques (X-ray, sonography, CT scan) except for the detection of brain metastases. The diagnostic accuracy of PET for the detection of metastases was 92.1% versus 55.7% for conventional imaging (p<0.001). In accordance with other publications, the recommendations of the 1997 German PET Consensus Conference and the ICP recommendations we suggest that the role of PET with FDG in melanoma is: 1) detection of occult regional nodal or distant metastatic disease at the time of initial presentation of patients with higher risk (depth >1.5 mm); and 2) detection of occult metastases in patients with recurrent disease who are being considered for surgery. PET often changes the diagnostic evaluation and therapeutic management of patients with melanoma. PET has also shown to be cost effective in diagnosis

  4. Dermoscopic clues in the diagnosis of amelanotic and hypomelanotic malignant melanoma Pistas dermatoscópicas no diagnóstico de melanoma maligno amelanótico e hipomelanótico

    Directory of Open Access Journals (Sweden)

    Raquel Bissacotti Steglich

    2012-12-01

    Full Text Available The clinical identification of amelanotic malignant melanoma (AMM and hypomelanotic malignant melanoma (HMM becomes difficult due to the lack of pigmentation and to the diverse clinical presentations. Dermoscopy is very useful in these cases, increasing the level of suspicion of malignancy. We report 4 cases of amelanotic malignant melanoma and hypomelanotic malignant melanoma with characteristic dermoscopic findings. Dermoscopy under polarized light demonstrates vascular polymorphism, globules and milky-red areas, in addition to chrysalis and multiple blue-gray dots.A identificação clínica de melanoma maligno amelanótico e hipomelanótico torna-se difícil devido à falta de pigmentação e às diversas apresentações desse tipo de tumor. A dermatoscopia é muito útil nestes casos, aumentando o grau de suspeição de malignidade. Relatamos 4 casos de melanoma maligno amelanótico e melanoma maligno hipomelanótico com achados dermatoscópicos característicos. A dermatoscopia com luz polarizada demonstra polimorfismo vascular, glóbulos e áreas vermelholeitosas, assim como crisálides e múltiplos pontos azul-acinzentados.

  5. 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.)

  6. Humanistic burden of disease for patients with advanced melanoma in Canada.

    Science.gov (United States)

    Cheung, Winson Y; Bayliss, Martha S; White, Michelle K; Stroupe, Angela; Lovley, Andrew; King-Kallimanis, Bellinda L; Lasch, Kathryn

    2018-06-01

    Metastatic melanoma is a highly aggressive cancer, often striking in the prime of life. This study provides new information directly from advanced melanoma (stage III and IV) patients on how their disease impacts their health-related quality of life (HRQL). Twenty-nine in-depth, qualitative interviews were conducted with adult patients with advanced melanoma in Canada. A semi-structured interview guide was used. Interviews were transcribed verbatim and key concepts were identified using a grounded theory analytic approach. Many patients' journeys began with the startling diagnosis of an invasive disease and a vastly shortened life expectancy. By the time they reached an advanced stage of melanoma, these patients' overall functioning and quality of life had been greatly diminished by this quickly progressing cancer. The impact was described in terms of physical pain and disability, emotional distress, diminished interactions with friends and family, and burden on caregivers. Our findings provide evidence of signs, symptoms, and functional impacts of advanced melanoma. Signs and symptoms reported (physical, mental, and social) confirm and expand on those reported in the existing clinical literature. Primary care physicians should be better trained to identify melanomas early. Oncology care teams can improve on their current approaches for helping patients navigate treatment options, with information about ancillary services to mitigate disease impacts on HRQL, such as mental health and social supports, as well as employment or financial support services.

  7. Rare nodular malignant melanoma of the heel in the Caribbean: A case report.

    Science.gov (United States)

    Warner, Wayne A; Sookdeo, Vandana Devika; Umakanthan, Srikanth; Sarran, Kevin; Pran, Lemuel; Fortuné, Maurice; Greaves, Wesley; Narinesingh, Sharda; Harnanan, Dave; Maharaj, Ravi

    2017-01-01

    Malignant melanoma of the heel is a rare melanoma subtype with incidence rates that reflect the complex relationship between sun exposure at certain geographic locations, individual melanin levels and overall melanoma risk. It is oftentimes characterized by poor prognosis because of delays in presentation resulting in longitudinal tumor invasion, lymph node involvement and metastasis. A 59-year-old woman was admitted to the Eric Williams Medical Sciences Complex, Trinidad and Tobago with a 5mm pruritic lesion on her left heel. At presentation, the lesion was asymmetric with border irregularities, color heterogeneity, with dynamics in elevation and overall size. She was subsequently diagnosed with malignant melanoma with left inguinal lymphadenopathy. A single stage wide local excision (WLE) of the left heel lesion with a split-thickness skin graft (STSG) and a left inguinal lymphadenectomy were performed. Dacarbazine (Bayer) was administered post operatively. Globally, the incidence of malignant melanoma is rapidly increasing, particularly, in countries like Trinidad and Tobago with a significant population of non-fair skinned individuals. There is need for strategic initiatives to increase patient adherence in these populations. The rarity of malignant heel melanomas heightens the need for increased patient awareness and greater clinical surveillance to ensure early diagnosis and treatment. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  8. In vivo and ex vivo proton MR spectroscopy of primary and secondary melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Bourne, Roger M.; Stanwell, Peter; Stretch, Jonathan R.; Scolyer, Richard A.; Thompson, John F.; Mountford, Carolyn E.; Lean, Cynthia L

    2005-03-01

    In vivo magnetic resonance (MR) spectroscopy at 1.5T was performed on a large polypoid cutaneous melanoma, and two enlarged lymph nodes containing metastatic melanoma, from three patients. Spectra were acquired in vivo from voxels wholly within the primary tumour or secondary lymph node and were thus uncontaminated by signals from adjacent tissue. Tissue biopsies taken after resection of primary tumours and secondary lymph nodes were examined by 8.5T magnetic resonance spectroscopy (MRS) and the results compared with the in vivo spectra, and with spectra from normal skin and a benign skin lesion. There was good agreement between the dominant features of 1.5T spectra acquired in vivo and 8.5T spectra acquired from resected tissue. However, less intense resonances observed at 8.5T in malignant biopsy tissue were not consistently observed at 1.5T in vivo. In vivo spectra from primary and metastatic melanoma showed high levels of choline metabolites. An intense lactate resonance was also present in the in vivo spectrum of primary melanoma. All 8.5T spectra of biopsies from primary and secondary melanoma showed high levels of choline metabolites and lactate, and additional resonances consistent with elevated levels of taurine, alanine, lysine, and glutamate/glutamine relative to normal and benign tissue. Elevated levels of choline, lactate, taurine, and amino acids appear to be clinically useful markers for identifying the pathology of primary and metastatic melanoma.

  9. Enhanced expression of melanoma progression markers in mouse model of sleep apnea

    Directory of Open Access Journals (Sweden)

    S. Perini

    2016-07-01

    Full Text Available Introduction: Obstructive sleep apnea has been associated with higher cancer incidence and mortality. Increased melanoma aggressivity was reported in obstructive sleep apnea patients. Mice exposed to intermittent hypoxia (IH mimicking sleep apnea show enhanced melanoma growth. Markers of melanoma progression have not been investigated in this model. Objective: The present study examined whether IH affects markers of melanoma tumor progression. Methods: Mice were exposed to isocapnic IH to a nadir of 8% oxygen fraction for 14 days. One million B16F10 melanoma cells were injected subcutaneously. Immunohistochemistry staining for Ki-67, PCNA, S100-beta, HMB-45, Melan-A, TGF-beta, Caspase-1, and HIF-1alpha were quantified using Photoshop. Results: Percentage of positive area stained was higher in IH than sham IH group for Caspase-1, Ki-67, PCNA, and Melan-A. The greater expression of several markers of tumor aggressiveness, including markers of ribosomal RNA transcription (Ki-67 and of DNA synthesis (PCNA, in mice exposed to isocapnic IH than in controls provide molecular evidence for a apnea–cancer relationship. Conclusions: These findings have potential repercussions in the understanding of differences in clinical course of tumors in obstructive sleep apnea patients. Further investigation is necessary to confirm mechanisms of these descriptive results. Keywords: Apnea, Melanoma, Biological markers

  10. Linear Malignant Melanoma In Situ: Reports and Review of Cutaneous Malignancies Presenting as Linear Skin Cancer.

    Science.gov (United States)

    Cohen, Philip R

    2017-09-18

    Melanomas usually present as oval lesions in which the borders may be irregular. Other morphological features of melanoma include clinical asymmetry, variable color, diameter greater than 6 mm and evolving lesions. Two males whose melanoma in situ presented as linear skin lesions are described and cutaneous malignancies that may appear linear in morphology are summarized in this report. A medical literature search engine, PubMed, was used to search the following terms: cancer, cutaneous, in situ, linear, malignant, malignant melanoma, melanoma in situ, neoplasm, and skin. The 25 papers that were generated by the search and their references, were reviewed; 10 papers were selected for inclusion. The cancer of the skin typically presents as round lesions. However, basal cell carcinoma and squamous cell carcinoma may arise from primary skin conditions or benign skin neoplasms such as linear epidermal nevus and linear porokeratosis. In addition, linear tumors such as basal cell carcinoma can occur. The development of linear cutaneous neoplasms may occur secondary to skin tension line or embryonal growth patterns (as reflected by the lines of Langer and lines of Blaschko) or exogenous factors such as prior radiation therapy. Cutaneous neoplasms and specifically melanoma in situ can be added to the list of linear skin lesions.

  11. Effect of dabrafenib on melanoma cell lines harbouring the BRAFV600D/R mutations

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    Gentilcore Giusy

    2013-01-01

    Full Text Available Abstract Background Conventional therapeutic agents are largely unsatisfactory into the treatment of malignant melanoma. Recently, an innovative approach based on inhibitors of the mutated BRAF gene (which represents the most prevalent alteration in melanoma patients appears very promising from the clinical point of view. On this regard, a new compound, dabrafenib (GSK2118436, has been demonstrated to be effective in patients carrying the BRAFV600E/K mutations. We here tested dabrafenib for its capability to inhibit cell growth on primary melanoma cell lines, established from patients' tumour tissues and carrying the BRAFV600D/R mutations. Methods Three melanoma cell lines were tested: M257 wild-type BRAF, LCP BRAFV600R and WM266 BRAFV600D. The MTT assays were performed using standardized approaches. To evaluate the inhibition of MAPK pathway and the consequent inhibition of cellular proliferation, the phosphorylation of ERK was examined by Western Blot analysis performed on total protein extracts from cell lines after treatment with dabrafenib. Results Our experiments demonstrated an effective action of Dabrafenib (GSK2118436 and the inhibition of MAPK pathway in melanoma cell lines carrying BRAFV600D/R mutations. Conclusion These results could be helpful to enlarge the number of melanoma patients who may benefit of a more effective targeted treatment.

  12. Spontaneous Splenic Rupture in Melanoma

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    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.

  13. Simulating clinical trial visits yields patient insights into study design and recruitment

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    Lim SS

    2017-07-01

    Full Text Available S Sam Lim,1 Alan J Kivitz,2 Doug McKinnell,3 M Edward Pierson,4 Faye S O’Brien4 1Division of Rheumatology, Department of Medicine, Emory University, Atlanta, GA, USA; 2Altoona Center for Clinical Research, Altoona, PA, USA; 3Deloitte Life Sciences Advisory, Basel, Switzerland; 4Clinical Operations, Global Medicines Development, AstraZeneca, Gaithersburg, MD, USA Purpose: We elicited patient experiences from clinical trial simulations to aid in future trial development and to improve patient recruitment and retention.Patients and methods: Two simulations of draft Phase II and Phase III anifrolumab studies for systemic lupus erythematosus (SLE/lupus nephritis (LN were performed involving African-American patients from Grady Hospital, an indigent care hospital in Atlanta, GA, USA, and white patients from Altoona Arthritis and Osteoporosis Center in Altoona, PA, USA. The clinical trial simulation included an informed consent procedure, a mock screening visit, a mock dosing visit, and a debriefing period for patients and staff. Patients and staff were interviewed to obtain sentiments and perceptions related to the simulated visits.Results: The Atlanta study involved 6 African-American patients (5 female aged 27–60 years with moderate to severe SLE/LN. The Altoona study involved 12 white females aged 32–75 years with mild to moderate SLE/LN. Patient experiences had an impact on four patient-centric care domains: 1 information, communication, and education; 2 responsiveness to needs; 3 access to care; and 4 coordination of care; and continuity and transition. Patients in both studies desired background material, knowledgeable staff, family and friend support, personal results, comfortable settings, shorter wait times, and greater scheduling flexibility. Compared with the Altoona study patients, Atlanta study patients reported greater preferences for information from the Internet, need for strong community and online support, difficulties in

  14. Accuracy of routine cytology and immunocytochemistry in preoperative diagnosis of oral amelanotic melanomas in dogs.

    Science.gov (United States)

    Przeździecki, Rafał; Czopowicz, Michał; Sapierzyński, Rafał

    2015-12-01

    Amelanotic melanomas are one of the most common oral malignancies. The cytologic and histopathologic differentiation between amelanotic melanoma, sarcoma, and poorly differentiated carcinoma is often difficult or even impossible. The aim of this study was to assess the reliability of routine cytology and immunocytochemistry in preoperative diagnosis of canine oral amelanotic melanoma. Cytologic preparations from undifferentiated canine oral tumors were stained with Giemsa and by immunocytochemistry (ICC) using anti-cytokeratin, anti-vimentin, and anti-Melan A antibodies. The final cytologic diagnosis (including ICC) was compared to the final diagnosis based on histopathology and immunohistochemistry (IHC) results, and sensitivity and specificity of cytologic examination were determined. Final cytologic diagnoses of 38 cases agreed well with the histopathologic/immunohistochemical diagnoses, thus both specificity and sensitivity of combined routine cytology and ICC were 100% (95% confidence interval 90.8-100%). Of 32 oral tumors, diagnosis of amelanotic melanoma, sarcoma, and carcinoma was made using routine cytology and ICC. In 4 of 6 aspirates taken from lymph nodes, a preliminary diagnosis of metastatic amelanotic melanoma corresponded with the final diagnosis. Both sensitivity and specificity of routine cytology in diagnosis of amelanotic melanomas were considered moderate (66.7% and 85.7%, respectively). In conclusion, routine cytology is a reliable diagnostic method for canine oral amelanotic melanoma and metastatic amelanotic melanoma, and ICC, using anti-cytokeratin, anti-vimentin, and anti-Melan A antibodies, is an excellent supporting method for presurgical diagnosis of poorly differentiated oral malignancies in dogs. © 2015 American Society for Veterinary Clinical Pathology.

  15. Epidemiology of Malignant Melanoma over a Thirty-two Year Period (1981-2013 in Southern Iran

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    Farhad Handjani

    2016-10-01

    Full Text Available Background:Malignant melanoma, one of the most deadly skin cancers, is a skin tumor that arises from the epidermal melanocytes. The aim of this study is to evaluate the demographic and clinical data of malignant melanoma patients in a referral dermatology center in the south of Iran. Methods: In this retrospective study, we have reviewed files of 116 patients diagnosed with malignant melanoma at hospitals affiliated with Shiraz University of Medical Sciences, Shiraz, Iran from March 1981 to March 2013. Results: There was a total 116 malignant melanoma patients (79 male and 37 female with the mean age of 54.7 (SD=13.9 years old for men and 51.7 (SD=12.4 years old for women. The male to female ratio of malignant melanoma was approximately two, as was the male to female mortality ratio. The most common clinical form was acral lentiginous melanoma. We have identified the most common site to be the sole of the foot. Malignant melanoma mostly presented as a mass and it was most common in farmers. Conclusion: The national health system should improve the quality and quantity of cancer registry offices so that better and more complete data can be collected for further research and possible implementation of preventive measures with respect to this cancer.

  16. 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.

  17. 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.

  18. Immunohistochemical characterization and evaluation of prognostic factors in canine oral melanomas with osteocartilaginous differentiation.

    Science.gov (United States)

    Sánchez, J; Ramirez, G A; Buendia, A J; Vilafranca, M; Martinez, C M; Altimira, J; Navarro, J A

    2007-09-01

    Melanomas are the most common malignant oral neoplasm in dogs. Osteocartilaginous differentiation in oral melanomas is a rare feature described both in veterinary and human medicine. Here, 10 cases of this type of neoplasm were used to study their immunohistochemical, biological, and clinical characteristics. Reactivity for S100 and melan A antigen was evaluated, and 4 prognosis factors (mitotic index, invasiveness of epithelium, nuclear atypia, and proliferation index) were analyzed and correlated with the clinical course of the neoplasms after diagnosis. Immunohistochemical analysis of the studied neoplasms, including the osteocartilaginous areas, showed positive immunoreaction for S100 and melan A, except in one dog, which was negative for melan A. Analysis of the results showed that oral melamonas with osteocartilaginous differentiation have a clinical course similar to that of other melanomas in the oral cavity. Analysis of the mitotic index and the expression of proliferation marker Ki-67 could be useful tools for predicting the biological behavior of these neoplasms.

  19. The role of spectrophotometry in the diagnosis of melanoma

    Science.gov (United States)

    2010-01-01

    Background Spectrophotometry (SPT) could represent a promising technique for the diagnosis of cutaneous melanoma (CM) at earlier stages of the disease. Starting from our experience, we further assessed the role of SPT in CM early detection. Methods During a health campaign for malignant melanoma at National Cancer Institute of Naples, we identified a subset of 54 lesions to be addressed to surgical excision and histological examination. Before surgery, all patients were investigated by clinical and epiluminescence microscopy (ELM) screenings; selected lesions underwent spectrophotometer analysis. For SPT, we used a video spectrophotometer imaging system (Spectroshade® MHT S.p.A., Verona, Italy). Results Among the 54 patients harbouring cutaneous pigmented lesions, we performed comparison between results from the SPT screening and the histological diagnoses as well as evaluation of both sensitivity and specificity in detecting CM using either SPT or conventional approaches. For all pigmented lesions, agreement between histology and SPT classification was 57.4%. The sensitivity and specificity of SPT in detecting melanoma were 66.6% and 76.2%, respectively. Conclusions Although SPT is still considered as a valuable diagnostic tool for CM, its low accuracy, sensitivity, and specificity represent the main hamper for the introduction of such a methodology in clinical practice. Dermoscopy remains the best diagnostic tool for the preoperative diagnosis of pigmented skin lesions. PMID:20707921

  20. Cancer immunology and canine malignant melanoma: A comparative review.

    Science.gov (United States)

    Atherton, Matthew J; Morris, Joanna S; McDermott, Mark R; Lichty, Brian D

    2016-01-01

    Oral canine malignant melanoma (CMM) is a spontaneously occurring aggressive tumour with relatively few medical treatment options, which provides a suitable model for the disease in humans. Historically, multiple immunotherapeutic strategies aimed at provoking both innate and adaptive anti-tumour immune responses have been published with varying levels of activity against CMM. Recently, a plasmid DNA vaccine expressing human tyrosinase has been licensed for the adjunct treatment of oral CMM. This article reviews the immunological similarities between CMM and the human counterpart; mechanisms by which tumours evade the immune system; reasons why melanoma is an attractive target for immunotherapy; the premise of whole cell, dendritic cell (DC), viral and DNA vaccination strategies alongside preliminary clinical results in dogs. Current "gold standard" treatments for advanced human malignant melanoma are evolving quickly with remarkable results being achieved following the introduction of immune checkpoint blockade and adoptively transferred cell therapies. The rapidly expanding field of cancer immunology and immunotherapeutics means that rational targeting of this disease in both species should enhance treatment outcomes in veterinary and human clinics. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. 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.

  2. Perceived Benefits of Pre-Clinical Simulation-based Training on Clinical Learning Outcomes among Omani Undergraduate Nursing Students

    Directory of Open Access Journals (Sweden)

    Girija Madhavanprabhakaran

    2015-01-01

    Full Text Available Objectives: This study aimed to explore the benefits perceived by Omani undergraduate maternity nursing students regarding the effect of pre-clinical simulation-based training (PSBT on clinical learning outcomes. Methods: This non-experimental quantitative survey was conducted between August and December 2012 among third-year baccalaureate nursing students at Sultan Qaboos University in Muscat, Oman. Voluntary participants were exposed to faculty-guided PSBT sessions using low- and medium-fidelity manikins, standardised scenarios and skill checklists on antenatal, intranatal, postnatal and newborn care and assessment. Participants answered a purposely designed self-administered questionnaire on the benefits of PSBT in enhancing learning outcomes. Items were categorised into six subscales: knowledge, skills, patient safety, academic safety, confidence and satisfaction. Scores were rated on a four-point Likert scale. Results: Of the 57 participants, the majority (95.2% agreed that PSBT enhanced their knowledge. Most students (94.3% felt that their patient safety practices improved and 86.5% rated PSBT as beneficial for enhancing skill competencies. All male students and 97% of the female students agreed that PSBT enhanced their confidence in the safe holding of newborns. Moreover, 93% of participants were satisfied with PSBT. Conclusion: Omani undergraduate nursing students perceived that PSBT enhanced their knowledge, skills, patient safety practices and confidence levels in providing maternity care. These findings support the use of simulation training as a strategy to facilitate clinical learning outcomes in future nursing courses in Oman, although further research is needed to explore the objective impact of PSBT on learning outcomes.

  3. Patient safety and quality of care: how may clinical simulation contribute?

    DEFF Research Database (Denmark)

    Jensen, Sanne

    2015-01-01

    The usability of health information technology (IT) is increasingly recognized as critically important to the development of systems that ensure patient safety and quality of care. The substantial complexity of organizations, work practice and physical environments within the healthcare sector...... influences the development and application of health IT. When health IT is introduced in local clinical work practices, potential patient safety hazards and insufficient support of work practices need to be examined. Qualitative methods, such as clinical simulation, may be used to evaluate new technology...

  4. Amelanotic Melanoma Masquerading as a Granular Cell Lesion

    Directory of Open Access Journals (Sweden)

    Deepak Pandiar

    2013-01-01

    Full Text Available Amelanotic melanoma (AM presents a diagnostic challenge due to its wide clinical presentations, lack of pigmentation, and varied histological appearances. Immunohistochemistry plays a crucial role in the diagnosis of these lesions. Amelanotic melanoma of oral mucosa is an uncommon lesion. We report a case of a 50-year-old male patient with a growth on the anterior mandibular gingiva of seven-month duration. In the present case, histologically, the tumour resembled a granular cell lesion, which has not been reported previously in AM. Diagnosis was possible by a sequential panel of immunohistochemical markers, of which finally vimentin, S100, HMB45, and Melan-A were positive. The tumor was surgically excised, and postsurgical radiotherapy was given.

  5. 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

  6. A Generic Discrete-Event Simulation Model for Outpatient Clinics in a Large Public Hospital

    Directory of Open Access Journals (Sweden)

    Waressara Weerawat

    2013-01-01

    Full Text Available The orthopedic outpatient department (OPD ward in a large Thai public hospital is modeled using Discrete-Event Stochastic (DES simulation. Key Performance Indicators (KPIs are used to measure effects across various clinical operations during different shifts throughout the day. By considering various KPIs such as wait times to see doctors, percentage of patients who can see a doctor within a target time frame, and the time that the last patient completes their doctor consultation, bottlenecks are identified and resource-critical clinics can be prioritized. The simulation model quantifies the chronic, high patient congestion that is prevalent amongst Thai public hospitals with very high patient-to-doctor ratios. Our model can be applied across five different OPD wards by modifying the model parameters. Throughout this work, we show how DES models can be used as decision-support tools for hospital management.

  7. Determination of electron clinical spectra from percentage depth dose (PDD) curves by classical simulated annealing method

    International Nuclear Information System (INIS)

    Visbal, Jorge H. Wilches; Costa, Alessandro M.

    2016-01-01

    Percentage depth dose of electron beams represents an important item of data in radiation therapy treatment since it describes the dosimetric properties of these. Using an accurate transport theory, or the Monte Carlo method, has been shown obvious differences between the dose distribution of electron beams of a clinical accelerator in a water simulator object and the dose distribution of monoenergetic electrons of nominal energy of the clinical accelerator in water. In radiotherapy, the electron spectra should be considered to improve the accuracy of dose calculation since the shape of PDP curve depends of way how radiation particles deposit their energy in patient/phantom, that is, the spectrum. Exist three principal approaches to obtain electron energy spectra from central PDP: Monte Carlo Method, Direct Measurement and Inverse Reconstruction. In this work it will be presented the Simulated Annealing method as a practical, reliable and simple approach of inverse reconstruction as being an optimal alternative to other options. (author)

  8. Using clinical simulation centers to test design interventions: a pilot study of lighting and color modifications.

    Science.gov (United States)

    Gray, Whitney Austin; Kesten, Karen S; Hurst, Stephen; Day, Tama Duffy; Anderko, Laura

    2012-01-01

    The aim of this pilot study was to test design interventions such as lighting, color, and spatial color patterning on nurses' stress, alertness, and satisfaction, and to provide an example of how clinical simulation centers can be used to conduct research. The application of evidence-based design research in healthcare settings requires a transdisciplinary approach. Integrating approaches from multiple fields in real-life settings often proves time consuming and experimentally difficult. However, forums for collaboration such as clinical simulation centers may offer a solution. In these settings, identical operating and patient rooms are used to deliver simulated patient care scenarios using automated mannequins. Two identical rooms were modified in the clinical simulation center. Nurses spent 30 minutes in each room performing simulated cardiac resuscitation. Subjective measures of nurses' stress, alertness, and satisfaction were collected and compared between settings and across time using matched-pair t-test analysis. Nurses reported feeling less stressed after exposure to the experimental room than nurses who were exposed to the control room (2.22, p = .03). Scores post-session indicated a significant reduction in stress and an increase in alertness after exposure to the experimental room as compared to the control room, with significance levels below .10. (Change in stress scores: 3.44, p = .069); (change in alertness scores: 3.6, p = .071). This study reinforces the use of validated survey tools to measure stress, alertness, and satisfaction. Results support human-centered design approaches by evaluating the effect on nurses in an experimental setting.

  9. 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.

  10. New developments in the management of advanced melanoma - role of pembrolizumab

    DEFF Research Database (Denmark)

    Improta, Giuseppina; Leone, Isabella; Donia, Marco

    2015-01-01

    Cancer immunotherapy is now recognized to be fundamental in modern oncology, because immune system recruitment may represent a powerful and innovative strategy in cancer therapy. Pembrolizumab, a highly selective humanized monoclonal antibody directly blocking the interaction between programmed...... inhibitor. This review will focus on the clinical development and use of pembrolizumab in the clinical practice and in the management of advanced melanoma....

  11. Unusual ventilation perfusion scintigram in a case of immunologic pulmonary edema clinically simulating pulmonary embolism

    International Nuclear Information System (INIS)

    Campeau, R.J.; Faust, J.M.; Ahmad, S.

    1987-01-01

    A case of immunologic pulmonary edema secondary to hydrochlorothiazide allergy developed in a 55-year-old woman that clinically simulated pulmonary embolism. The patient had abnormal washin images with normal washout images on an Xe-133 ventilation study. On the perfusion study, large bilateral central and posterior perfusion defects were present that showed an unusual mirror image pattern on the lateral and posterior oblique views. Resolution of radiographic and scintigraphic abnormalities occurred over a 3-day period in conjunction with corticosteroid therapy

  12. SIMulation of Medication Error induced by Clinical Trial drug labeling: the SIMME-CT study.

    Science.gov (United States)

    Dollinger, Cecile; Schwiertz, Vérane; Sarfati, Laura; Gourc-Berthod, Chloé; Guédat, Marie-Gabrielle; Alloux, Céline; Vantard, Nicolas; Gauthier, Noémie; He, Sophie; Kiouris, Elena; Caffin, Anne-Gaelle; Bernard, Delphine; Ranchon, Florence; Rioufol, Catherine

    2016-06-01

    To assess the impact of investigational drug labels on the risk of medication error in drug dispensing. A simulation-based learning program focusing on investigational drug dispensing was conducted. The study was undertaken in an Investigational Drugs Dispensing Unit of a University Hospital of Lyon, France. Sixty-three pharmacy workers (pharmacists, residents, technicians or students) were enrolled. Ten risk factors were selected concerning label information or the risk of confusion with another clinical trial. Each risk factor was scored independently out of 5: the higher the score, the greater the risk of error. From 400 labels analyzed, two groups were selected for the dispensing simulation: 27 labels with high risk (score ≥3) and 27 with low risk (score ≤2). Each question in the learning program was displayed as a simulated clinical trial prescription. Medication error was defined as at least one erroneous answer (i.e. error in drug dispensing). For each question, response times were collected. High-risk investigational drug labels correlated with medication error and slower response time. Error rates were significantly 5.5-fold higher for high-risk series. Error frequency was not significantly affected by occupational category or experience in clinical trials. SIMME-CT is the first simulation-based learning tool to focus on investigational drug labels as a risk factor for medication error. SIMME-CT was also used as a training tool for staff involved in clinical research, to develop medication error risk awareness and to validate competence in continuing medical education. © The Author 2016. Published by Oxford University Press in association with the International Society for Quality in Health Care; all rights reserved.

  13. Unusual presentation of a lymphoma that simulated an Ewing sarcoma: clinical, radiological and pathological differential diagnostic

    International Nuclear Information Sy