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Sample records for melanoma clinical experience

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

    Directory of Open Access Journals (Sweden)

    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.

  2. Clinical characteristics and management of melanoma families

    NARCIS (Netherlands)

    Rhee, Jasper Immanuel van der

    2013-01-01

    Being a member of a melanoma family is a major risk factor for cutaneous malignant melanoma. In this thesis clinical characteristics and management of melanoma families are discussed. In the first part of the thesis clinical and histological characteristics of melanoma (patients) from families with

  3. 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

  4. 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

  5. Peculiarities of lymphatic drainage in cutaneous malignant melanoma: clinical experience in 75 cases.

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    Voinea, S; Sandru, A; Gherghe, M; Blidaru, A

    2014-01-01

    In the recent years, the identification and biopsy of the sentinel lymph node (SLN) has become standard in the treatment of cutaneous malignant melanoma (CMM). In order to correctly apply the technique and to decrease the risk of false negatives,it is compulsory to track the lymphatic drainage of the primary tumor and to detect all SLN, regardless of their site. At the Bucharest Oncologic Institute, over the last three years, selective lymphadenectomy was performed in 75 patients with CMM, stages I and II (AJCC). In 39 cases, the primary tumor was at the level of the upper and lower limbs and in 36 on the trunk. In all patients, lymphoscintigraphy was performed through intradermal injection of Nanocoll,with dynamic follow up of the radiotracer, with the purpose of finding the possible unusual locations of the SLN. The sentinel lymph nodes were identified in 100%of the cases. In 63 patients (84%), the primary tumor drained in only one lymphatic field and in the other 12 the drainage was towards 2 or more lymphatic basins. The CMM situated on the trunk had a particular behaviour, presenting more often (33%) with multiple nodal basin drainage. CMM of the trunk, mostly those situated close to the midline, but others as well, tend to drain into several lymphatic areas. The existence of interval lymph nodes and atypical lymphatic drainage, in a minor lymphatic basin,must be determined preoperatively in order to allow the biopsy of all SLN and establish the right therapy. Celsius.

  6. 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)

  7. Anorectal Malignant Melanomas: Experience of Uludag University

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    Berna Aytac

    2010-12-01

    Full Text Available Anorectal melanomas represent a group of mucosal melanomas with unknown etiology and poor prognosis. The lesions can be misdiagnosed as hemorrhoids during clinical examination. We reviewed the morphological and clinical features of 14 anorectal melanomas, and discuss the treatment modalities of this entity. Fourteen patients who were diagnosed with anorectal malignant melanoma between 1997 and 2004 were evaluated with regard to age, sex, size, morphology, lymph node or distant metastasis, treatment modality and survival. Eight patients were female and six were male, and their mean age was 58 years. The size of melanoma ranged from 3 cm to 8 cm. Pathological evaluation revealed epithelioid and spindle cell type tumor in seven and two patients, respectively, whereas, in the remaining seven patients, the tumor was composed of both types. Pigmentation was apparent in all tumors. There was lymph node metastasis in 11 patients and distant metastasis in all patients. Eleven patients underwent abdominoperineal resection and three were treated by local excision. Mean survival was 8.7 months. Prognosis of anorectal melanoma remains poor. Awareness of the diverse clinicopathological features of these lesions, both on the part of the clinicians and pathologists, is crucial for their early detection and proper treatment.

  8. Melanoma

    Science.gov (United States)

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

  9. 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

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

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    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.

  11. Nodular melanoma: a distinct clinical entity and the largest contributor to melanoma deaths in Victoria, Australia.

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    Mar, Victoria; Roberts, Hugh; Wolfe, Rory; English, Dallas R; Kelly, John W

    2013-04-01

    There is a growing body of evidence that nodular melanoma (NM), because of its association with increased growth rate and thickness at diagnosis, accounts for a substantial proportion of melanoma deaths. We sought to assess the contribution of NM to melanoma deaths in comparison with other tumor subtypes. Four cohorts were established comprising 5775 cases of invasive primary cutaneous melanoma reported to the Victorian Cancer Registry during 1989, 1994, 1999, and 2004. Original pathology reports were reviewed. Age-standardized melanoma incidence rates were compared from 1989 to 2004 with annual percentage change using Poisson regression. The incidence of thick tumors (>4 mm) increased by 3.8% (95% confidence interval 1.4 to 6.2) and 2.5% (95% confidence interval -0.5 to 5.5) per year for male and female patients, respectively. The median thickness of NM at diagnosis was 2.6 mm compared with 0.6 mm for superficial spreading melanoma. A third of patients who died from melanoma during the follow-up period had thick tumors (>4 mm), most of which were nodular subtype (61%). NM accounted for 14% of invasive melanomas, but was responsible for 43% of melanoma deaths in a total of 57,461 person-years of follow-up. By comparison, superficial spreading melanoma contributed 56% of invasive melanoma but only 30% of deaths. Pathology review was limited to reports only. Mortality information relied mostly on death certificate information. The incidence of thick melanomas continues to increase. Nodular melanoma is clinically distinct and the predominant contributor to melanoma-related deaths, representing a public health challenge in reducing skin cancer mortality. Copyright © 2012 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  12. Melanoma: From Melanocyte to Genetic Alterations and Clinical Options

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    Corine Bertolotto

    2013-01-01

    Full Text Available Metastatic melanoma remained for decades without any effective treatment and was thus considered as a paradigm of cancer resistance. Recent progress with understanding of the molecular mechanisms underlying melanoma initiation and progression revealed that melanomas are genetically and phenotypically heterogeneous tumors. This recent progress has allowed for the development of treatment able to improve for the first time the overall disease-free survival of metastatic melanoma patients. However, clinical responses are still either too transient or limited to restricted patient subsets. The complete cure of metastatic melanoma therefore remains a challenge in the clinic. This review aims to present the recent knowledge and discoveries of the molecular mechanisms involved in melanoma pathogenesis and their exploitation into clinic that have recently facilitated bench to bedside advances.

  13. Melanoma

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

  14. The clinical and dermoscopic features of extremity melanomas

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    Fatma Pelin Cengiz

    2015-03-01

    Full Text Available Objectives: Dermoscopy is a noninvasive tool that helps to differentiate structures which can not be seen by naked eye. Dermoscopic and clinical features of malignant melanomas on the extremities are not well described in the literature. Therefore, in this study we aim to determine dermoscopic and clinical characteristics of melanoma on the extremities. Materials and Methods: 40 patients with melanoma on the extremities were included in this study. Their dermoscopic and clinical images, histopathological and clinical data were assessed. The relations between Breslow thickness and dermoscopic characteristics were evaluated. Results: The most frequent localization for women was lower extremities, whereas it was upper extremities for men. The most common subtype of melanoma was superficial spreading melanoma on the extremities. The mean age of patients with extremity melanoma was 56,21 ± 15,20 in men, as well as the mean age of patients with extremity melanoma was 53,09 ± 13,96 in women. The most common dermoscopic feature for extremity melanoma was irregular dots (85%. There were positive correlations between Breslow thickness and diameter, 3 or more colors in lesion, blue-white veil and lineer white streaks, respectively (p< 0.005, r= +0.462 (p< 0.001, r= +0.550 (p< 0.001, r= +0.606 (p< 0.001, r= +0.662. Conclusions: To our knowledge, this is the first study investigating dermoscopic and clinical features in patients with extremity melanomas. We should suggest that melanomas on the lower extremities are more common in women than men and the patients with lower extremity melanomas were younger than the patients with upper extremity melanomas and there are associations between Breslow thickness and some dermoscopic characteristics.

  15. Genomic analysis and clinical management of adolescent cutaneous melanoma.

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    Rabbie, Roy; Rashid, Mamunur; Arance, Ana M; Sánchez, Marcelo; Tell-Marti, Gemma; Potrony, Miriam; Conill, Carles; van Doorn, Remco; Dentro, Stefan; Gruis, Nelleke A; Corrie, Pippa; Iyer, Vivek; Robles-Espinoza, Carla Daniela; Puig-Butille, Joan A; Puig, Susana; Adams, David J

    2017-05-01

    Melanoma in young children is rare; however, its incidence in adolescents and young adults is rising. We describe the clinical course of a 15-year-old female diagnosed with AJCC stage IB non-ulcerated primary melanoma, who died from metastatic disease 4 years after diagnosis despite three lines of modern systemic therapy. We also present the complete genomic profile of her tumour and compare this to a further series of 13 adolescent melanomas and 275 adult cutaneous melanomas. A somatic BRAF V 600E mutation and a high mutational load equivalent to that found in adult melanoma and composed primarily of C>T mutations were observed. A germline genomic analysis alongside a series of 23 children and adolescents with melanoma revealed no mutations in known germline melanoma-predisposing genes. Adolescent melanomas appear to have genomes that are as complex as those arising in adulthood and their clinical course can, as with adults, be unpredictable. © 2017 The Authors. Pigment Cell & Melanoma Research published by John Wiley & Sons Ltd.

  16. 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 ...

  17. Primary dermal melanoma: distinct immunohistochemical findings and clinical outcome compared with nodular and metastatic melanoma.

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    Cassarino, David S; Cabral, Erik S; Kartha, Reena V; Swetter, Susan M

    2008-01-01

    To provide an updated and expanded analysis of clinical outcome and immunohistochemical (IHC) findings unique to primary dermal melanoma (PDM) that may be used to differentiate this entity from primary nodular melanoma (PNM) and cutaneous metastatic melanoma (MM). Cohort analysis and extensive IHC panel comparing PDM with PNM and cutaneous MM. Melanoma clinics and pathology departments of academic and VA medical centers. Thirteen patients with a solitary dermal or subcutaneous nodule of histologically proven melanoma, prospectively followed through April 30, 2007. Clinical, pathologic, and IHC assessment of patients diagnosed as having PDM. Long-term clinical outcome and determination of unique clinical and IHC features in the study cohort compared with other melanoma subtypes. Histologically, there was no evidence of an overlying in situ component, ulceration, or regression, and there was no associated nevus in any cases. Clinical history and findings from workup, including imaging studies, skin examination, and sentinel lymph node biopsy, were negative for evidence of melanoma elsewhere. The mean Breslow depth was 9.6 mm. Two patients developed satellite or in-transit recurrences, 1 developed pulmonary metastasis, and another died of liver metastases. Overall, the cohort showed a 92% melanoma-specific survival rate at a mean duration of follow-up of 44 months. The IHC findings showed that PDM exhibited lower levels of staining for the antigens p53 (P = .02), Ki-67 (Mib-1) (P = .002), cyclin D1 (P = .001), and podoplanin (recognized by D2-40 antibody) lymphovascular staining (P <.001) compared with MM and PNM. All other markers were comparable. Patients with PDM have remarkably prolonged survival compared with patients with MM or PNM of similar thickness. Preliminary results suggest that PDM may be characterized by lower levels of p53, Ki-67, cyclin D1, and D2-40 compared with histologically similar MM and PNM.

  18. Historical, clinical, and dermoscopic characteristics of thin nodular melanoma.

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    Kalkhoran, Sara; Milne, Olivia; Zalaudek, Iris; Puig, Susana; Malvehy, Josep; Kelly, John W; Marghoob, Ashfaq A

    2010-03-01

    Nodular melanoma (NM), representing 15% to 30% of all melanomas, constitutes nearly half of all melanomas thicker than 2 mm. Nodular melanoma frequently lacks clinical features seen in other melanoma subtypes and has a faster growth rate. We reviewed a series of cases of NM that was less than 1.3 mm thick to identify historical, clinical, and dermoscopic factors that may facilitate earlier diagnosis of NM, with the hope of reducing its associated morbidity and mortality. The thin NM lesions we analyzed had a rather subtle clinical appearance, often lacking the ABCD (asymmetry, border irregularity, color variegation, and diameter greater than 6 mm) criteria. On dermoscopy, most lesions had a homogeneous disorganized asymmetric pattern or a featureless pattern with atypical vessels. Although many dermoscopic features seen in other melanoma subtypes were frequently absent, some features such as a blue-white veil, structureless areas, and atypical vascular structures were often identified. The often unremarkable clinical presentation of NM necessitates physicians and patients to be wary of new or changing lesions. Dermoscopy may help increase suspicion in early NM because dermoscopic features are typically more suggestive of malignancy than clinical ones. We hope that secondary prevention efforts combined with prompt dermatologic consultations will allow for the timely diagnosis and management of NM.

  19. Promoting early detection of melanoma during the mammography experience

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    A.K. Rzepecki, BS

    2017-12-01

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

  20. Tissue resources for clinical use and marker studies in melanoma.

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    Curry, Jonathan L; Davies, Michael A; Calderone, Tiffany L; Nathanson, Katherine; Prieto, Victor G; Gershenwald, Jeffrey E

    2014-01-01

    The adequate procurement and preservation of high-quality tissue specimens from patients with melanoma is a critical clinical issue as patients' tumor samples are now used not only for pathological diagnosis but are also necessary to determine the molecular signature of the tumor to stratify patients who may benefit from targeted melanoma therapy. Tissue resources available for physicians and investigators include formalin-fixed paraffin-embedded (FFPE) tissue and frozen tissue, either preserved in optimal cutting temperature (OCT) media or snap frozen. Properly preserved tissue may be used to evaluate melanoma biomarkers by immunohistochemistry (IHC) with tissue microarray (TMA) technology, to perform genetic and genomic analyses, and for other types of translational research in melanoma.

  1. Ipilimumab in the treatment of advanced melanoma - a clinical update.

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    Kim, Dae Won; Trinh, Van Anh; Hwu, Wen-Jen

    2014-11-01

    Ipilimumab has become an important treatment option for patients with advanced melanoma; however, active research perseveres to resolve many clinical practice issues and to further improve the therapeutic index of this agent. This article aims to provide an update on long-term data, current challenge and recent progress relating to the clinical application of ipilimumab in the treatment of advanced melanoma. A literature search using PubMed database was conducted using search words ipilimumab, melanoma, treatment sequencing, adjuvant therapy, combination therapy, and biomarkers. Data were also obtained from meeting abstracts and clinical trial registries. Signal of clinical activity as adjuvant therapy in patients with resected high-risk melanoma begins to emerge, but longer follow-up is required for confirmation. Many issues, such as optimal dosing schedules and therapeutic sequences, remain unraveled. At present, treatment should be individualized based on patient- and disease-specific factors. Immunotherapy like ipilimumab still represents the best treatment option for durable remission; however, targeted therapies are more appropriate for patients with BRAF V600-mutated tumor who are symptomatic or have rapidly growing disease. With novel therapeutic options in the pipeline, the role of ipilimumab continues to evolve in the rapidly changing treatment landscape of advanced melanoma. Most likely, this agent will be utilized in combinatorial or sequential approach.

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

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    Martyna Śniegocka

    2018-04-01

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

  3. Critical Assessment of Clinical Prognostic Tools in Melanoma.

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    Mahar, Alyson L; Compton, Carolyn; Halabi, Susan; Hess, Kenneth R; Gershenwald, Jeffrey E; Scolyer, Richard A; Groome, Patti A

    2016-09-01

    The 7th edition American Joint Committee on Cancer (AJCC) melanoma staging system classifies patients according to prognosis. Significant within-stage heterogeneity remains and the inclusion of additional clinicopathologic and other host- and tumor-based prognostic factors have been proposed. Clinical prognostic tools have been developed for use in clinical practice to refine survival estimates. Little is known about the comparative features of tools in melanoma. We performed a systematic search of the scientific published literature for clinical prognostic tools in melanoma and web-based resources. A priori criteria were used to evaluate their quality and clinical relevance, and included intended clinical use, model development approaches, validation strategies, and performance metrics. We identified 17 clinical prognostic tools for primary cutaneous melanoma. Patients with stages I-III and T1 or thin melanoma were the most frequently considered populations. Seventy-five percent of tools were developed using data collected from patients diagnosed in 2006 or earlier, and the well-established factors of tumor thickness, ulceration, and age were included in 70 % of tools. Internal validity using cross-validation or bootstrapping techniques was performed for two tools only. Fewer than half were evaluated for external validity; however, when done, the appropriate statistical methodology was applied and results indicated good generalizability. Several clinical prognostic tools have the potential to refine survival estimates for individual melanoma patients; however, there is a great opportunity to improve these tools and to foster the development of new, validated tools by the inclusion of contemporary clinicopathological covariates and by using improved statistical and methodological approaches.

  4. Targeting BRAF in melanoma: biological and clinical challenges.

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    Mandalà, Mario; Voit, Christiane

    2013-09-01

    Melanoma is an aggressive form of skin cancer that causes the greatest number of skin cancer-related deaths worldwide. In its early stages malignant melanoma can be cured by surgical resection, but once it has progressed to the metastatic stage it is extremely difficult to treat and does not respond to current therapies. A majority of cutaneous melanomas show activating mutations in the NRAS or BRAF proto-oncogenes, components of the Ras-Raf-Mek-Erk (MAPK) signal transduction pathway. The discovery of activating BRAF mutations in ∼50% of all melanomas has proved to be a turning point in the therapeutic management of the disseminated disease. This review summarizes the critical role of BRAF in melanoma pathophysiology, the clinical and pathological determinants of BRAF mutation status and finally addresses the current state of the art of BRAF inhibitors. We further outline the most recent findings on the mechanisms that underlie intrinsic and acquired BRAF inhibitor resistance and describe ongoing preclinical and clinical studies designed to delay or abrogate the onset of therapeutic escape. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  5. Melanoma in situ: Part II. Histopathology, treatment, and clinical management.

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    Higgins, H William; Lee, Kachiu C; Galan, Anjela; Leffell, David J

    2015-08-01

    Melanoma in situ (MIS) poses special challenges with regard to histopathology, treatment, and clinical management. The negligible mortality and normal life expectancy associated with patients with MIS should guide treatment for this tumor. Similarly, the approach to treatment should take into account the potential for MIS to transform into invasive melanoma, which has a significant impact on morbidity and mortality. Part II of this continuing medical education article reviews the histologic features, treatment, and management of MIS. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

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

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

    2014-01-01

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

  7. DNA Methylation Levels of Melanoma Risk Genes Are Associated with Clinical Characteristics of Melanoma Patients

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    Érica S. S. de Araújo

    2015-01-01

    Full Text Available In melanoma development, oncogenic process is mediated by genetic and epigenetic mutations, and few studies have so far explored the role of DNA methylation either as predisposition factor or biomarker. We tested patient samples for germline CDKN2A methylation status and found no evidence of inactivation by promoter hypermethylation. We have also investigated the association of clinical characteristics of samples with the DNA methylation pattern of twelve genes relevant for melanomagenesis. Five genes (BAP1, MGMT, MITF, PALB2, and POT1 presented statistical association between blood DNA methylation levels and either CDKN2A-mutation status, number of lesions, or Breslow thickness. In tumors, five genes (KIT, MGMT, MITF, TERT, and TNF exhibited methylation levels significantly different between tumor groups including acral compared to nonacral melanomas and matched primary lesions and metastases. Our data pinpoint that the methylation level of eight melanoma-associated genes could potentially represent markers for this disease both in peripheral blood and in tumor samples.

  8. Clinical experience of treatment of metastatic melanoma and solid tumours adopting a derivative of diphtheria toxin: cross-reacting material 197.

    Science.gov (United States)

    Fiorentini, Giammaria; Banfi, Roberto; Dentico, Patrizia; Moriconi, Sabina; Turrisi, Gina; Pelagotti, Filippo; Rossi, Susanna; Montagnani, Francesco

    2013-01-01

    Diphtheria toxin (DT) has shown anticancer activity in both experimental models and humans but its adverse effects stopped further developments. Cross-reacting Material 197 (CRM197) is the product of a single missense mutation (Gly52 to Glu) within fragment A of DT. It has been shown to induce weak toxicity in some cell strains, but it shares immunological properties with native DT. CRM197 commonly acts as an immunological adjuvant, or as an inhibitor of heparin-binding epidermal growth factor. Recently, CRM197 was shown to have promising antitumor activity. To better-define this property, we planned a phase I-II study. Twenty-nine patients bearing advanced melanoma (18 cases), and other solid tumors (two ovarian cancer, two sarcoma, two gastrointestinal cancers, one urinary bladder carcinoma, one glioblastoma, one neuroblastoma, one ocular melanoma and one primitive neuroectodermal embriogenic tumor (PNET) were evaluated and 19 of them, sub-divided in cohorts, received the following levels of CRM197: Level 1, 0.3 mg; level 2, 1.0 mg; level 3, 2.5 mg; level 4, 3.5 mg; level 5, 5.0 mg; level 6, 7.5 mg. The drug was given once every two days for 4 times and then, after a 2-week rest period, once every 2 days for 4 times. CRM197 was administered subcutaneously in the abdominal wall. grade 1-2 common toxicities included fever, chills, fatigue, dizziness, nausea, vomiting and headache, neutrophilia and skin painful reactions appeared regularly at levels 3 and 4 (2.5 mg and 3.5 mg). Vomiting and abdominal pain, skin reaction tachycardia and hypotension appeared in two patients at level 5. At 7.5 mg, we observed a severe grade 3 reaction with hypotension, dyspnea and grade 4 myalgia. This was considered the dose-limiting toxicity. Eleven patients (seven with melanoma and four with other tumors) were treated to evaluate anticancer effects at the maximum tolerated dose (5 mg). Only one patient reported a minor response, lasting eight weeks. Ten patients reported progressive

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

    Science.gov (United States)

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

    2001-06-01

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

  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

    Mucosal melanomas constitute 1.3% of all melanomas and they may develop in any mucosal membrane. Conjunctival melanomas (0.5/million/year) and melanomas in the sinonasal cavity (0.5/million/year) are the most common, followed by anorectal melanomas (0.4/million/year) and melanomas in the oral...... cavity (0.2/million/year). Anorectal melanoma occurs slightly more often in females, whereas oral melanoma has a male predilection. Mucosal melanoma most commonly develops in a patient's sixth or seventh decade of life, and no differences between races have been found except for sinonasal melanoma...... is the treatment of choice. The prognosis is poor, with the 5-year survival rate ranging from 0% (gastric melanoma) to 80% (conjunctival melanoma)....

  11. Patient and Oncology Nurse Preferences for the Treatment Options in Advanced Melanoma: A Discrete Choice Experiment.

    Science.gov (United States)

    Liu, Frank Xiaoqing; Witt, Edward A; Ebbinghaus, Scot; DiBonaventura Beyer, Grace; Basurto, Enrique; Joseph, Richard W

    2017-10-25

    Understanding the perceptions of patients and oncology nurses about the relative importance of benefits and risks associated with newer treatments of advanced melanoma can help to inform clinical decision-making. The aims of this study were to quantify and compare the views of patients and oncology nurses regarding the importance of attributes of treatments of advanced melanoma. A discrete choice experiment (DCE) was conducted in US-based oncology nurses and patients diagnosed with advanced melanoma. Patients and nurses were enlisted through online panels. In a series of scenarios, respondents had to choose between 2 hypothetical treatments, each with 7 attributes: mode of administration (MoA), dosing schedule (DS), median duration of therapy (DoT), objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and grade 3 or 4 adverse events (AEs). Hierarchical Bayesian logistic regression models were used to estimate preference weights. A total of 200 patients with advanced melanoma and 150 oncology nurses participated. The relative importance estimates of attributes by patients and nurses, respectively, were as follows: OS, 33% and 28%; AEs, 29% and 26%; ORR, 25% and 27%; PFS, 12% and 15%; DS, 2% and 3%; DoT, 0% and 0%; and MoA, 0% and 0%. Both patients and oncology nurses valued OS, ORR, and AEs as the most important treatment attributes for advanced melanoma, followed by PFS, whereas DS, DoT, and MoA were given less value in their treatment decisions. Oncology nurses and patients have similar views on important treatment considerations for advanced melanoma, which can help build trust in shared decision-making.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

  12. Melanoma

    Science.gov (United States)

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

  13. [Clinical observation of extraocular extension of choroidal melanoma].

    Science.gov (United States)

    Wang, Yi; Li, Yue-yue; Su, Fan; Xiao, Li-hua

    2011-03-01

    To evaluate the clinical features, diagnostic methods and treatment of extraocular extension of choroidal melanoma. It was a retrospective case series study. The records of 12 consecutive cases with extraocular extension of choroidal melanoma confirmed by pathologic examination were analyzed with special attention to the case histories, clinical manifestations, imaging findings, treatment and follow up results. Four patients were misdiagnosed as glaucoma. Another 4 patients were confirmed the diagnosis of melanoma and 3 of them received the operations of transscleral local resection. The common clinical manifestations included: impaired vision, exophthalmos, blepharoptosis, limited ocular motility, conjunctival hyperemia, and increased ocular or orbital pressure, etc. Characteristic sign was raised mass on the surface of sclera. All cases underwent orbital MRI preoperatively, 6 underwent ocular B-scan echography, and 6 underwent orbital CT scanning to evaluate for extraocular extension of tumor. Typical ultrasonography revealed the discontinued ocular wall and an intraocular mass with a continuous hypoechoic extraocular mass. In some cases the extraocular mass showed hypoechoic with medium echo area. CT scan showed a well-defined homogeneous intraconal mass connecting with intraocular lesion in 6 cases, which could infiltrate eye or optic nerve. The MR signal features of intraocular tumors with extraocular extension showed 4 patterns in all patients. The typical pattern was the tumor showed hyperintensity on T(1) and hypointensity on T(2)-weighted image. The maximum diameter of extraocular tumor was measured over 4 mm in 9 cases. MRI was useful for demonstrating multiple extraocular lesions, remote metastatic lesion or micro extraocular tumor, of which minimal diameter was 3 mm in our cases. Orbital exenteration was performed in 11 cases and ocular enucleation with excision of extraocular tumor was in 1 cases. Microscopic examination showed the epithelioid

  14. 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...

  15. Diagnosis and clinical management of melanoma patients at higher risk of a new primary melanoma: A population-based study in New South Wales, Australia.

    Science.gov (United States)

    Watts, Caroline G; Madronio, Christine M; Morton, Rachael L; Goumas, Chris; Armstrong, Bruce K; Curtin, Austin; Menzies, Scott W; Mann, Graham J; Thompson, John F; Cust, Anne E

    2017-11-01

    To describe the method of diagnosis, clinical management and adherence to clinical practice guidelines for melanoma patients at high risk of a subsequent primary melanoma, and compare this with melanoma patients at lower risk. The Melanoma Patterns of Care study was a population-based, observational study based on doctors' reported clinical management of melanoma patients in New South Wales, Australia, diagnosed with in situ or invasive melanoma over a 12-month period from October 2006. Of 2605 patients with localised melanoma, 1019 (39%) were defined as at higher risk due to the presence of one or more of the following factors: a family history of melanoma (11%), multiple primary melanomas (17%), or many naevi (24%). Compared to patients at lower risk, high risk patients were more likely to receive their initial care from a primary care physician (56% vs 50%, P = 0.002), have their melanoma detected during a routine skin check (40% vs 33%, P < 0.001), have their lesion assessed with dermoscopy (63% vs 56%, P = 0.002), and be encouraged to have skin surveillance (84% vs 77%, P < 0.001) and skin self-examination (87% vs 83%, P = 0.03). Higher socioeconomic status and urban residence were associated with patients at higher risk receiving initial treatment from a specialist doctor. Clinical management of higher risk patients was more likely to conform to clinical practice guidelines for diagnosis and skin surveillance than to melanoma patients at lower risk. © 2016 The Australasian College of Dermatologists.

  16. Single institution experience of paediatric melanoma in Victoria, Australia.

    Science.gov (United States)

    Le, Quynh; Norris, Diana; McClean, Catriona A; Mcguiness, Myra; Meani, Rowena; Kelly, John W; Pan, Yan

    2017-05-01

    Paediatric melanoma is an uncommon presentation of melanoma that accounts for 3% of all paediatric cancers. The objective was to describe a series of paediatric melanoma cases presenting to a state-wide tertiary referral service over the past 19 years. A search of the Victorian Melanoma Service database was performed to identify all patients under the age of 20 years diagnosed with melanoma from 1994 to 2013. Histological, demographic and phenotypical information for each patient was collected. Patients were matched against the Victorian Death Registry to identify those who had died. Fisher's exact test was used to examine associations. Melanoma-specific survival was estimated using the Kaplan-Meier method. A total of 65 paediatric melanoma patients were included for analysis, in whom 72.3% of melanomas were diagnosed when they were 16-19 years of age with a mean age at diagnosis of 16 years. The mean Breslow thickness was 1.4 mm. It was greatest (3.4 mm) in the youngest age group (melanoma-specific survival rate was 96.8%. This is the first descriptive epidemiological study of paediatric melanoma in Victoria. Further large, population-based, multi-institutional studies of paediatric melanoma are warranted to provide a clearer understanding of this group of melanoma patients. © 2016 The Australasian College of Dermatologists.

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

    Science.gov (United States)

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

    2015-08-01

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

  18. Malignant melanoma clinically masquerading vascular tumor: A diagnostic dilemma

    Directory of Open Access Journals (Sweden)

    Samiksha Pradhan

    2015-01-01

    Full Text Available Malignant melanoma is an invasive neoplasm of the skin, whose incidence is reported to be rising among Indians. We hereby present a unique case of unilateral, multiple, asymptomatic, pigmented, nodular lesions over the lower limb; resembling vascular tumor, revealing itself as malignant melanoma only on histopathology. To the best of our knowledge, such a unique presentation of malignant melanoma has not yet been reported from the Indian subcontinent.

  19. Radiotherapy of primary human melanomas - experiences and suggestions

    International Nuclear Information System (INIS)

    Elsmann, H.J.; Ernst, K.; Suter, L.

    1991-01-01

    We treated 60 invasive primary human melanomas by soft X-rays. In 23 additional cases radiotherapy was applied after total excision of a primary melanoma. Only in two cases was a tumor observed in the field of irradiation during the follow-up period: A recurrence of a primary melanoma and a skin metastasis. Radioresistance cannot be unequivocally assumed in either case. Since deeply situated in-transit metastases cannot be destroyed by soft X-rays in spite of our good results we regard radiotherapy of invasive primary melanomas as a second choice treatment to be administered if impaired general health, excessive tumor growth in certain localisations or refusal of the patient to not allow a major operation. Nodular parts of primary melanomas should be excised before radiotherapy to obtain material for histopathological confirmation of the diagnosis and to determine the thickness of the tumor. X-rays of lower hardness can subsequently be applied. (orig.) [de

  20. Radiotherapy of primary human melanomas - experiences and suggestions

    Energy Technology Data Exchange (ETDEWEB)

    Elsmann, H.J.; Ernst, K.; Suter, L. (Muenster Univ. (Germany). Fachklinik Hornheide fuer Tumoren, Tuberkulose und Wiederherstellung an Gesicht und Haut)

    1991-07-01

    We treated 60 invasive primary human melanomas by soft X-rays. In 23 additional cases radiotherapy was applied after total excision of a primary melanoma. Only in two cases was a tumor observed in the field of irradiation during the follow-up period: A recurrence of a primary melanoma and a skin metastasis. Radioresistance cannot be unequivocally assumed in either case. Since deeply situated in-transit metastases cannot be destroyed by soft X-rays in spite of our good results we regard radiotherapy of invasive primary melanomas as a second choice treatment to be administered if impaired general health, excessive tumor growth in certain localisations or refusal of the patient to not allow a major operation. Nodular parts of primary melanomas should be excised before radiotherapy to obtain material for histopathological confirmation of the diagnosis and to determine the thickness of the tumor. X-rays of lower hardness can subsequently be applied. (orig.).

  1. Malignant melanoma – etiopathogenesis, clinical picture, diagnosis and patient management

    International Nuclear Information System (INIS)

    Murarova, Z.; Borecka, D.

    2016-01-01

    Malignant melanoma belongs to the most malignant and aggressive tumors due to its fast growing metastasis. Despite the fact that the incidence of melanoma has been on the increase for the past years and mortality to low and medium risk melanoma has decreased, the mortality of aggressive fast growing high risk melanomas has been stable. Diagnosis of “typical” melanomas, fulfilling ABCDEF criteria, usually does not cause any problems. Particular attention should be paid to the problems of fast growing melanomas, which are very similar to benign lesions at the beginning so they are often detected too late. Melanomas have two extreme properties: on one edge of the spectrum there are patients with small and thin skin lesions, who are usually completely cured by wide surgical excision. On the other edge of the spectrum there are patients with generalized metastatic disease. In these patients the treatment options are very limited and the probability to survive is about 6-9 months. The most significant factor for survival is the early melanoma detection. (author)

  2. A clinical trial of fast neutron therapy for malignant melanoma

    International Nuclear Information System (INIS)

    Tsunemoto, Hiroshi; Morita, Shinroku; Ishikawa, Tatsuo

    1985-01-01

    Fifty-four patients with malignant melanoma of the skin or the head and neck underwent fast neutron therapy between November 1975 and March 1983. Of these patients, 21 patients with melanoma of the skin and 12 patients with melanoma of the head and neck were chosen as subjects for this study. Of the 21 patients with skin lesions, complete regression was seen in 2 patients undergoing fast neutron therapy alone and in 17 patients undergoing fast neutron therapy combined with salvage surgery. A cumulative five-year survival rate was 47 %. Preoperative fast neutron therapy is a promising method used in the treatment of malignant melanoma. Two of 12 patients with advanced melanoma of the head and neck were long-term survivors. Fast neutron-induced skin damage was seen in one of the 33 patients. (Namekawa, K.)

  3. The dermoscopic (7FFM) versus the clinical (ABCDE) diagnosis of small diameter melanoma.

    Science.gov (United States)

    Benellii, C; Roscetti, E; Dal Pozzo, V

    2000-06-01

    The diagnosis of small diameter melanoma, that is early melanoma, is particularly difficult. For this reason we decided to evaluate the improvement given from our diagnostic dermoscopic method 7FFM to the clinical diagnosis, ABCDE rule, of small diameter melanoma. A retrospective study evaluating the clinical and the dermoscopic slides of 76 small diameter melanomas observed from January 1 1993 to December 31 1998, and of 524 small melanocytic nevi consecutively observed from September 1 1997 to September 30 1999, has been undertaken. The sensitivity and the specificity of the ABCDE rule and of our diagnostic dermoscopic method 7FFM in the diagnosis of small diameter melanoma have been calculated. The difference of diagnostic power between the two methods has been calculated with chi square test. The sensitivity and the specificity of the ABCDE rule in the diagnosis of small melanomas were 47.3% and 56%, while the sensitivity and the specificity of our method 7FFM were 68.8% and 86%. The difference of diagnostic power between the two methods was statistically significant: P<0.01 for both sensitivity and specificity. The sensitivity of the two methods together was 81.5% while the specificity of the two methods together was 50.6%. Our results show that our diagnostic dermoscopic method 7FFM improves both sensitivity and specificity in the clinical diagnosis of small diameter melanomas. Anyway the clinical and the dermoscopic diagnosis are not mutually exclusive as the best sensitivity is obtained with the two methods together.

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

    Directory of Open Access Journals (Sweden)

    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

  5. 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

  6. Individual risk of cutaneous melanoma in New Zealand: developing a clinical prediction aid.

    Science.gov (United States)

    Sneyd, Mary Jane; Cameron, Claire; Cox, Brian

    2014-05-22

    New Zealand and Australia have the highest melanoma incidence rates worldwide. In New Zealand, both the incidence and thickness have been increasing. Clinical decisions require accurate risk prediction but a simple list of genetic, phenotypic and behavioural risk factors is inadequate to estimate individual risk as the risk factors for melanoma have complex interactions. In order to offer tailored clinical management strategies, we developed a New Zealand prediction model to estimate individual 5-year absolute risk of melanoma. A population-based case-control study (368 cases and 270 controls) of melanoma risk factors provided estimates of relative risks for fair-skinned New Zealanders aged 20-79 years. Model selection techniques and multivariate logistic regression were used to determine the important predictors. The relative risks for predictors were combined with baseline melanoma incidence rates and non-melanoma mortality rates to calculate individual probabilities of developing melanoma within 5 years. For women, the best model included skin colour, number of moles > =5 mm on the right arm, having a 1st degree relative with large moles, and a personal history of non-melanoma skin cancer (NMSC). The model correctly classified 68% of participants; the C-statistic was 0.74. For men, the best model included age, place of occupation up to age 18 years, number of moles > =5 mm on the right arm, birthplace, and a history of NMSC. The model correctly classified 67% of cases; the C-statistic was 0.71. We have developed the first New Zealand risk prediction model that calculates individual absolute 5-year risk of melanoma. This model will aid physicians to identify individuals at high risk, allowing them to individually target surveillance and other management strategies, and thereby reduce the high melanoma burden in New Zealand.

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

    International Nuclear Information System (INIS)

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

    1997-01-01

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

  8. Human melanoma metastasis in NSG mice correlates with clinical outcome in patients.

    Science.gov (United States)

    Quintana, Elsa; Piskounova, Elena; Shackleton, Mark; Weinberg, Daniel; Eskiocak, Ugur; Fullen, Douglas R; Johnson, Timothy M; Morrison, Sean J

    2012-11-07

    Studies of human cancer metastasis have been limited by a lack of experimental assays in which cancer cells from patients metastasize in vivo in a way that correlates with clinical outcome. This makes it impossible to study intrinsic differences in the metastatic properties of cancers from different patients. We recently developed an assay in which human melanomas readily engraft in nonobese diabetic/severe combined immunodeficient interleukin-2 receptor-γ chain null (NSG) mice. We show that melanomas from 25 patients exhibited reproducible differences in the rate of spontaneous metastasis after transplantation into NSG mice and that these differences correlated with clinical outcome in the patients. Stage IIIB/C melanomas that formed distant metastases within 22 months in patients also formed tumors that metastasized widely in NSG mice, whereas stage IIIB/C melanomas that did not form distant metastases within 22 to 50 months in patients metastasized more slowly in NSG mice. These differences in the efficiency of metastasis correlated with the presence of circulating melanoma cells in the blood of NSG mice, suggesting that the rate of entry into the blood is one factor that limits the rate of metastasis. The study of NSG mice can therefore yield information about the metastasis of human melanomas in vivo, in this case revealing intrinsic differences among stage III melanomas in their ability to circulate/survive in the blood and to metastasize.

  9. Conjunctival Melanoma: A New Clinical and Therapeutical Approach

    Directory of Open Access Journals (Sweden)

    M. Rodríguez-Martín

    2010-08-01

    Full Text Available Melanoma involving the conjunctiva is extremely rare. Graver prognosis has been reported with primary conjunctival melanoma than with their cutaneous counterparts [Collin et al.: Aust N Z J Ophthalmol 1986;14:29–34]. Among conjunctival melanomas, two significant risk factors for tumour-related death have been identified: (i age older than 55 years and (ii unfavourable tumour location (caruncle, cornea, fornix, palpebral conjunctiva [Werschnik and Lommatzsch: Am J Clin Oncol 2002;25:248–255]. Here we present a rare case of lentigo maligna involving the palpebral, bulbar conjunctiva and the caruncle. We describe dermoscopic patterns observed and the use of a novel ocular melanoma therapy with topical imiquimod.

  10. Radiosensitivity of malignant melanomas. Part II. Clinical studies

    International Nuclear Information System (INIS)

    Trott, K.R.; von Lieven, H.; Kummermehr, J.; Skopal, D.; Lukacs, S.; Braun-Falco, O.; Kellerer, A.M.

    1981-01-01

    Forty-four lymph node or skin metastases of malignant melanomas received definite radiotherapy. Twenty were locally controlled for 2 or more years. Local control rate increased with dose. TCD-50 was about 1800 ret. The effectiveness of radiotherapy was more dependent on overall treatment time than on fraction size or number of fractions. Radiotherapy is suggested to decrease the high rate of locoregional failure of surgery of nodular melanomas in the foot and face

  11. Malign Melanoma: Risk Factors and Major Clinical Findings

    Directory of Open Access Journals (Sweden)

    Can Baykal

    2015-03-01

    Full Text Available Malignant melanoma (MM shows rapid increase in the incidence and it is the most common cause of death due to skin cancer. On the other hand, MM can completely be removed in patients noticing the lesions early and applying to physicians on time. Thus the life expectancy of these patients is not altered. Although MM can occur in every individual, it is more common in patients with some of the established risk factors such as fair skin, increased sun exposure, genetic basis (CDKN2A mutation, and existence of increased number of melanocytic nevi and/or dysplastic nevi. A specialized care of patients with risk factors and their regular follow-up is critical to lower the mortality and morbidity in MM. Early diagnosis of MM prevents metastasis and decreases mortality rate. Nowadays, there are many newly developed imaging methods to help the clinicians before biopsy. However, the suspicion of MM should initially be based upon major clinical findings of the lesion subject to changes during the evolution of the tumor. In this review, risk factors of MM will be summarized and clues for early diagnosis of this dangerous tumor will be discussed.

  12. 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)

  13. Hsps are up-regulated in melanoma tissue and correlate with patient clinical parameters.

    Science.gov (United States)

    Shipp, Christopher; Weide, Benjamin; Derhovanessian, Evelyna; Pawelec, Graham

    2013-03-01

    Heat shock proteins (hsps) have been studied in numerous cancer types, but a clear view of their clinical relevance in melanoma remains elusive. Therefore, the aim of this study was to investigate the expression of hsps in melanoma with respect to patient clinical parameters. Using Western immunoblotting, hsps 90, 70, 60, 40 and 32 were observed to be widely expressed in metastatic melanomas (n = 31), while immunofluorescence demonstrated that in the majority of samples these hsps, apart from hsp32, were increased in expression in melanoma cells compared with surrounding non-melanoma cells in situ (n = 8). Correlating hsp expression with patient clinical parameters indicated that greater hsp90 (P < 0.02) and hsp40 (P < 0.03) expression correlated with advanced stage (stage III Vs stage IV), while in the case of hsp40, this was additionally associated with reduced patient survival (P < 0.05). In contrast, higher hsp32 expression was associated with improved patient survival (P < 0.007). On the other hand, the expression of the other hsps did not correlate with any obtainable patient clinical parameters. This study provides further evidence for the importance of hsps in melanoma and for their use as therapeutic targets and biomarkers, but larger-scale follow-up studies are required to confirm these results.

  14. Human melanoma metastasis in NSG mice correlates with clinical outcome in patients

    OpenAIRE

    Quintana, Elsa; Piskounova, Elena; Shackleton, Mark; Weinberg, Daniel; Eskiocak, Ugur; Fullen, Douglas R.; Johnson, Timothy M.; Morrison, Sean J.

    2012-01-01

    Studies of human cancer metastasis have been limited by a lack of experimental assays in which cancer cells from patients metastasize in vivo in a way that correlates with clinical outcome. This makes it impossible to study intrinsic differences in the metastatic properties of cancers from different patients. We recently developed an assay in which human melanomas readily engraft in NOD/SCID IL2Rγnull (NSG) mice (1, 2). Here we show that melanomas from 25 patients exhibited reproducible diffe...

  15. Preliminary experiences of intralesional immunotherapy in cutaneous metastatic melanoma.

    Science.gov (United States)

    Ridolfi, Laura; Ridolfi, Ruggero

    2002-01-01

    Antigen presenting cells are inactive within tumor tissue because of local immunosuppression. Tumor infiltrating lymphocyte signal activation transducing mechanisms are also seriously impaired. Administration of granulocyte macrophage-colony stimulating factor may lead to antigen-presenting cell recovery and interleukin-2 may restore local tumor infiltrating lymphocyte activation. Moreover, interleukin-2 increases the systemic lymphocyte population, an event which seems to correlate with a better prognosis. The present phase I-II study was carried out to examine whether intralesional injection of granulocyte macrophage-colony stimulating factor followed by subcutaneous interleukin-2 would induce a clinical response in advanced, pretreated and elderly melanoma patients. Fourteen patients over 60 years of age received intralesional granulocyte macrophage-colony stimulating factor (150 micrograms per lesion on day 1), generally divided between the two largest cutaneous lesions, followed by perilesional subcutaneous interleukin-2 (3.000.000/IU) for 5 days (3 to 7) every 3 weeks. All patients received 6 courses of treatment unless progression occurred. Clinical evaluation of the treated cutaneous lesions was assessed at the baseline and before every cycle. Distant lesions were checked every two cycles. Four clinical responses (2 partial responses and 2 minimal responses) (28.5%), which also involved lesions that had not been directly treated, and seven cases of stable disease were observed. The response duration for partial response and minimal response was 9, 4, 4 and 2.5+ months, respectively. Stable disease (50%) recorded in the 7 patients was short term, 3-6 months. Three patients rapidly progressed after 2, 2, and 1 therapy cycles, respectively. The patient who reached the best partial response had a fairly high absolute lymphocyte count (1600 to 2400/mm3). The second one, who reached a complete remission after subsequent locoregional chemotherapy and hyperthermia

  16. Pembrolizumab for advanced melanoma: experience from the Spanish Expanded Access Program.

    Science.gov (United States)

    González-Cao, M; Arance, A; Piulats, J M; Marquez-Rodas, I; Manzano, J L; Berrocal, A; Crespo, G; Rodriguez, D; Perez-Ruiz, E; Berciano, M; Soria, A; Castano, A G; Espinosa, E; Montagut, C; Alonso, L; Puertolas, T; Aguado, C; Royo, M A; Blanco, R; Rodríguez, J F; Muñoz, E; Mut, P; Barron, F; Martin-Algarra, S

    2017-06-01

    The programmed death (PD-1) inhibitor pembrolizumab has been recently approved for the treatment of advanced melanoma. We evaluated the clinical activity of pembrolizumab in melanoma patients treated under the Spanish Expanded Access Program. Advanced melanoma patients who failed to previous treatment lines were treated with pembrolizumab 2 mg/kg every three weeks. Patients with brain metastases were not excluded if they were asymptomatic. Data were retrospectively collected from 21 centers in the Spanish Melanoma Group. Sixty-seven advanced melanoma patients were analyzed. Most patients were stage M1c (73.1%), had high LDH levels (55.2%) and had ECOG PS 1 or higher (59.7%). For cutaneous melanoma patients, median overall survival was 14.0 months; the 18-month overall survival rate was 47.1%. Overall response rate was 27%, including three patients with complete responses (6.5%). Median response duration was not reached, with 83.3% of responses ongoing (3.5 m+ to 20.4 m+). From ten patients included with brain metastases, four (40%) had an objective response, two (20%) of them achieved a complete response. Significant prognostic factors for overall survival were LDH level, ECOG PS and objective response. There were no serious adverse events. Although this was a heavily pretreated cohort, pembrolizumab activity at the approved dose and schedule was confirmed in the clinical setting with long-term responders, also including patients with brain metastases.

  17. 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

  18. 15 years experience with helium ion radiotherapy for uveal melanoma

    International Nuclear Information System (INIS)

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

    1996-01-01

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

  19. Integrating first-line treatment options into clinical practice: what's new in advanced melanoma?

    Science.gov (United States)

    Dummer, Reinhard; Schadendorf, Dirk; Ascierto, Paolo A; Larkin, James; Lebbé, Celeste; Hauschild, Axel

    2015-12-01

    Melanoma remains a serious form of skin cancer in Europe and worldwide. Localized, early-stage melanomas can usually be treated with surgical excision. However, the prognosis is poorer for patients with advanced disease. Before 2011, treatment for advanced melanoma included palliative surgery and/or radiotherapy, and chemotherapy with or without immunotherapy, such as interleukin-2. As none of these treatments had shown survival benefits in patients with advanced melanoma, European guidelines had recommended that patients be entered into clinical trials. The lack of approved first-line options and varying access to clinical trials meant that European clinicians relied on experimental regimens and chemotherapy-based treatments when no other options were available. Since 2011, ipilimumab, an immuno-oncology therapy, and vemurafenib and dabrafenib, targeted agents that inhibit mutant BRAF, have been approved by the European Medicines Agency for the treatment of advanced melanoma. More recently, the MEK inhibitor, trametinib, received European marketing authorization for use in patients with BRAF mutation-positive advanced melanoma. In 2014, the anti-PD-1 antibody nivolumab was approved as a first-line therapy in Japan. Whereas nivolumab and another anti-PD-1 antibody, pembrolizumab, were approved as second-line therapies in the USA, their recent approval in Europe are for first-line use based on new clinical trial data in this setting. Together these agents are changing clinical practice and making therapeutic decisions more complex. Here, we discuss current and emerging therapeutic options for the first-line treatment of advanced melanoma, and how these therapies can be optimized to provide the best possible outcomes for patients.

  20. [Clinical and histopathological characteristics of malignant melanoma cases seen at "Dr. Manuel Gea González" General Hospital].

    Science.gov (United States)

    Káram-Orantes, Marcia; Toussaint-Caire, Sonia; Domínguez-Cherit, Judith; Veja-Memije, Elisa

    2008-01-01

    Melanoma is a type of tumor that arises from melanocytes generally located in the dermoepidermal junction. Although melanoma is found in less than 10% of cases, mortality is high representing 75% of deaths attributed to cutaneous cancer. There are four major subtypes: Superficial spreading melanoma, lentigo malignant melanoma, acral lentiginous melanoma and nodular melanoma. Superficial spreading melanoma is the most common type among Caucasians. In a Mexican case series, the nodular type is the most common type reported. The aim of this study was to determine the most common type seen at our medical facility. We analyzed patient's medical records from March 1981 to December 2006. Demographic data included sex, age, place of residence, occupation, tumor progression, location and clinical description. Histologically we evaluated tumor thickness using the Breslow scale; invasion was measured using the Clark scale. This is a descriptive, cross-sectional and retrospective study. 165 patients were studied, 112 were females and 53 males. The most common location was the lower limb. Acral lentiginous melanoma was the most common subtype. Our findings differ from the other series where they report nodular and superficial spreading melanoma as the most common types. The most common subtypes in our study were acral lentiginous melanoma and lentigo malignant melanoma among females, with a ratio of female-male of 2.1:1.

  1. Targeted next generation sequencing identifies clinically actionable mutations in patients with melanoma.

    Science.gov (United States)

    Jeck, William R; Parker, Joel; Carson, Craig C; Shields, Janiel M; Sambade, Maria J; Peters, Eldon C; Burd, Christin E; Thomas, Nancy E; Chiang, Derek Y; Liu, Wenjin; Eberhard, David A; Ollila, David; Grilley-Olson, Juneko; Moschos, Stergios; Neil Hayes, D; Sharpless, Norman E

    2014-07-01

    Somatic sequencing of cancers has produced new insight into tumorigenesis, tumor heterogeneity, and disease progression, but the vast majority of genetic events identified are of indeterminate clinical significance. Here, we describe a NextGen sequencing approach to fully analyzing 248 genes, including all those of known clinical significance in melanoma. This strategy features solution capture of DNA followed by multiplexed, high-throughput sequencing and was evaluated in 31 melanoma cell lines and 18 tumor tissues from patients with metastatic melanoma. Mutations in melanoma cell lines correlated with their sensitivity to corresponding small molecule inhibitors, confirming, for example, lapatinib sensitivity in ERBB4 mutant lines and identifying a novel activating mutation of BRAF. The latter event would not have been identified by clinical sequencing and was associated with responsiveness to a BRAF kinase inhibitor. This approach identified focal copy number changes of PTEN not found by standard methods, such as comparative genomic hybridization (CGH). Actionable mutations were found in 89% of the tumor tissues analyzed, 56% of which would not be identified by standard-of-care approaches. This work shows that targeted sequencing is an attractive approach for clinical use in melanoma. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. Clinical characteristics, management and survival in young adults diagnosed with malignant melanoma: A population-based cohort study.

    Science.gov (United States)

    Plym, Anna; Ullenhag, Gustav J; Breivald, Mats; Lambe, Mats; Berglund, Anders

    2014-05-01

    Few studies to date have described the clinical features of malignant melanoma in young adulthood. Also, little is known about patterns of care in young patients. We examined and compared clinical characteristics, management and survival between young adult (15-39 years) and older adult melanoma patients in Central Sweden. Patients diagnosed with invasive malignant melanoma between 1997 and 2011 were identified in the Regional Quality Register of Cutaneous Malignant Melanoma in Central Sweden, a population-based register covering a source population of about two million. Data on clinical characteristics, management and survival were retrieved and compared according to age at diagnosis. Of 5915 patients included in the study, 584 (9.9%) were between 15 and 39 years of age at diagnosis. Compared with older patients, young adult patients were more likely to be female, with higher proportions of thin, non-ulcerated melanomas, superficial spreading melanoma and melanomas located on the lower extremity. Young adults had shorter waiting times for surgical procedures and a higher proportion received surgical treatment according to guidelines. Overall, young patients had better relative survival than older patients. Age-related survival differences varied by stage of disease at diagnosis, and were most prominent in stage II disease. The observed differences in clinical characteristics, management and survival between young adult and older melanoma patients call for an improved understanding of not only disease etiology but also factors driving management decisions. A better understanding of these differences may help improve care and prognosis for melanoma patients of all ages.

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

    DEFF Research Database (Denmark)

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

    2006-01-01

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

  4. Melanoma detection by analysis of clinical images using convolutional neural network.

    Science.gov (United States)

    Nasr-Esfahani, E; Samavi, S; Karimi, N; Soroushmehr, S M R; Jafari, M H; Ward, K; Najarian, K

    2016-08-01

    Melanoma, most threatening type of skin cancer, is on the rise. In this paper an implementation of a deep-learning system on a computer server, equipped with graphic processing unit (GPU), is proposed for detection of melanoma lesions. Clinical (non-dermoscopic) images are used in the proposed system, which could assist a dermatologist in early diagnosis of this type of skin cancer. In the proposed system, input clinical images, which could contain illumination and noise effects, are preprocessed in order to reduce such artifacts. Afterward, the enhanced images are fed to a pre-trained convolutional neural network (CNN) which is a member of deep learning models. The CNN classifier, which is trained by large number of training samples, distinguishes between melanoma and benign cases. Experimental results show that the proposed method is superior in terms of diagnostic accuracy in comparison with the state-of-the-art methods.

  5. Epidemiological and clinical characteristics of malignant melanoma in Southeast Anatolia in Turkey.

    Science.gov (United States)

    Sula, Bilal; Uçmak, Feyzullah; Kaplan, Mehmet Ali; Urakçi, Zuhat; Arica, Mustafa; Isikdogan, Abdurrahman

    2016-01-01

    The present study aimed to establish the epidemiological and clinical characteristics of patients who were histopathologically diagnosed with malignant melanoma (MM). The present study retrospectively analyzed the data of 78 patients who were histopathologically diagnosed with MM in Dicle University Medical Faculty, Dermatology and Medical Oncology departments between 2005 and 2014. The study included 78 patients in total with 44 (56.4%) male and 34 (43.6%) female. Median age of the patients was 62.50 years (range: 27 - 84 years). Of the patients, 78.2% (n = 61) had cutaneous melanoma, 8.9% had solid organ melanoma, and 2.5% had ocular and mucosal melanoma. The most common tumor localization among the patients was the lower extremities with 29.4% (n = 23). The most common histopathological type was nodular malignant melanoma with 35.8% (n = 28). Based on TNM, Clark and Breslow classifications, 26.9% (n = 21) of the patients were stage 4, 26.9% (n = 21) were Clark stage 4, and 37.1% (n = 29) were Breslow stage 4. Median overall survival in all patients was 14.9 months (95% CI 10.9 - 18.8 months). In the multivariate Cox analysis, only stage statistically significantly affecting survival [odds ratio (OR): 0.54; (95% CI 0.16-1.82, p = 0.02)]. Malignant melanoma data are also important for the optimal utilization of effective methods and healthcare resources to prevent the disease. In order to minimize MM mortality and morbidity, not only the society but also physicians from primary and secondary care hospitals should become familiar with melanoma.

  6. The impact of melanoma genetics on treatment response and resistance in clinical and experimental studies.

    Science.gov (United States)

    Kunz, M; Hölzel, M

    2017-03-01

    Recent attempts to characterize the melanoma mutational landscape using high-throughput sequencing technologies have identified new genes and pathways involved in the molecular pathogenesis of melanoma. Apart from mutated BRAF, NRAS, and KIT, a series of new recurrently mutated candidate genes with impact on signaling pathways have been identified such as NF1, PTEN, IDH1, RAC1, ARID2, and TP53. Under targeted treatment using BRAF and MEK1/2 inhibitors either alone or in combination, a majority of patients experience recurrences, which are due to different genetic mechanisms such as gene amplifications of BRAF or NRAS, MEK1/2 and PI3K mutations. In principle, resistance mechanisms converge on two signaling pathways, MAPK and PI3K-AKT-mTOR pathways. Resistance may be due to small subsets of resistant cells within a heterogeneous tumor mass not identified by sequencing of the bulk tumor. Future sequencing studies addressing tumor heterogeneity, e.g., by using single-cell sequencing technology, will most likely improve this situation. Gene expression patterns of metastatic lesions were also shown to predict treatment response, e.g., a MITF-low/NF-κB-high melanoma phenotype is resistant against classical targeted therapies. Finally, more recent treatment approaches using checkpoint inhibitors directed against PD-1 and CTLA-4 are very effective in melanoma and other tumor entities. Here, the mutational and neoantigen load of melanoma lesions may help to predict treatment response. Taken together, the new sequencing, molecular, and bioinformatic technologies exploiting the melanoma genome for treatment decisions have significantly improved our understanding of melanoma pathogenesis, treatment response, and resistance for either targeted treatment or immune checkpoint blockade.

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

    International Nuclear Information System (INIS)

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

    1999-01-01

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

  8. Anorectal melanoma: experience from a tertiary cancer care centre in South India.

    Science.gov (United States)

    Ranjith, S; Muralee, M; Sajeed, A; Arun, P M; Cherian, K; Nair, C K; Augustine, P; Ahamed, I

    2018-03-01

    Introduction Mucosal malignant melanoma of the anorectum is a rare and aggressive disease, in which early diagnosis is difficult. The prognosis remains extremely poor, irrespective of the treatment. We share our experience in treating this malignancy at our centre in South India. Methods This study describes a retrospective analysis of 31 cases of anorectal melanoma presented to our centre between January 2001 and December 2013. Results Twenty-two patients (71%) presented with metastasis and had a median overall survival of nine months. None of the 22 patients survived for two years. Nine patients (29%) had curative surgery, in the form of abdominoperineal resection (six patients), abdominoperineal resection with bilateral inguinal node dissection (one patient), abdominoperineal resection with liver resection (one patient) and posterior exenteration (one patient). In patients who underwent curative surgery, the median overall survival was 15 months and disease-free survival was nine months, with a two-year overall survival of 22%. Conclusions Anorectal melanoma is an aggressive disease with a poor prognosis. The majority of patients present with distant metastases. Prognosis depends on stage at presentation. Early diagnosis and surgical resection may improve the overall outcome. Newer modalities such as immunotherapy and targeted therapies such as anti-CTLA4 monoclonal antibody and anti-programmed cell death protein 1 monoclonal antibodies have radically changed the management of mucosal melanoma and may, in the future, improve the overall prognosis of anorectal melanoma.

  9. Use of the melanoma vaccine in 38 dogs: The South African experience.

    Science.gov (United States)

    McLean, Joanne L; Lobetti, Remo G

    2015-04-30

    The commercially available vaccine Oncept is indicated for the management of dogs with stage II or III oral melanoma after local control has been achieved. Survival times in dogs with both oral and digit melanoma have been shown to be significantly increased following vaccination. This retrospective study was designed to document the investigators' experiences with Oncept vaccine when used as an adjunct therapy for treatment of stage II-IV oral, digit and malignant melanoma of other sites after local control had been achieved in dogs presented to a South African specialist referral veterinary practice. Thirty-eight dogs diagnosed with melanoma (25 oral, 6 digit and 7 infiltrative at various other sites) underwent a combination of surgical excision and Oncept vaccination. At the end of the study period there were 16 live and 22 dead dogs; median survival time of the live dogs was 29 months (range 2-46 months) versus 8 months (range 2-16 months) for those that died from progressive disease. This study showed that by using a combination of surgical excision and vaccination with Oncept survival times in dogs with malignant melanoma of the oral cavity, digit and other sites can be increased significantly.

  10. 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

  11. 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.

  12. 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.

  13. Clinical features of 36 cases of amelanotic melanomas and considerations about the relationship between histologic subtypes and diagnostic delay.

    Science.gov (United States)

    Gualandri, L; Betti, R; Crosti, C

    2009-03-01

    Amelanotic melanomas (AM) are a difficult diagnostic challenge for clinicians. To consider the clinical presentation of AM, the histologic subtypes involved, the relationship with the diagnostic delay and the possible involvement in overall prognosis. Patients who were observed in our department to be affected by cutaneous melanomas were recorded. Sex, age, the clinical features, the site of presentation, the suspected diagnosis, the clinical course, the histological type, the Clark level and the Breslow thickness were recorded. AM were divided in three main clinical types: an erythematous macule or patch on sun-exposed skin, a dermal plaque or nodule without a particular epidermal change, an exophytic nodule. Only pure AM were considered. Histological subtypes considered were superficial spreading melanoma, nodular melanoma, and lentigo maligna melanoma. Diagnostic delay considered from when the patients first noticed the lesion on the site where the melanoma was diagnosed and when the physician or the patient first proposed the removal was recorded. The chi-squared test was used for statistical evaluation with P melanomas (7.2%) were collected. The most frequent morphology of clinical presentation was the papulo-nodular form, followed by the plaque form. Mean Breslow thickness of AM was 1.72 mm compared to 0.61 mm of pigmented cases. Nodular histotype was highly represented in AM (30.5% of cases) with respect to pigmented nodular melanomas (2.9%). The diagnostic delay did not differ between amelanotic and pigmented melanomas, nor between nodular AM and nodular pigmented melanomas. The great prevalence of clinical and histological nodular cases, the higher mean Breslow thickness (considered as the most important factor of prognosis) of AM compared with a not significant greater diagnostic delay may point out that a good percentage of AM have an intrinsic faster speed of growth with a worse prognosis irrespectively of the diagnostic performance. The importance of

  14. 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

  15. Detailed dosimetry and clinical outcome analysis for the argentine BNCT trials of cutaneous nodular melanomas

    International Nuclear Information System (INIS)

    Gonzalez, S.J.; Santa Cruz, G.A.; Casal, M.R.

    2006-01-01

    Three female patients with biopsy-proven nodular melanoma were treated to six separate sites as part of the Phase I/II BNCT clinical trial conducted at the Comision Nacional de Energia Atomica (CNEA) and the Instituto A. Roffo, Argentina. This work reports on the detailed dosimetry for the clinical trials, and presents a preliminary analysis to investigate the possible influence of tumor size and total equivalent dose on the observed local tumor response. Also, the appropriateness of applying 3.5 tumor-to-blood 10 B concentration ratio for the BPA compound in nodular melanoma cases is discussed. The statistical analysis showed that tumor response depends not only on the dose but also, and highly, on the tumor size. For these three patients, there was no significant difference between minimum and mean equivalent doses as explicative for tumor response. The collection of sixteen experimental-based tumor-to-blood ratios determined by CNEA in nodular melanoma patients derived an average value and standard deviation of 2.5 ± 0.6. This result suggests that a lower ratio could be more suitable for estimating the clinical dosimetry. It is also consistent with the worse tumor control rate in nodular melanomas observed by other researchers. (author)

  16. 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.

  17. Familial melanoma: clinical factors associated with germline CDKN2A mutations according to the number of patients affected by melanoma in a family.

    Science.gov (United States)

    Maubec, Eve; Chaudru, Valérie; Mohamdi, Hamida; Blondel, Christophe; Margaritte-Jeannin, Patricia; Forget, Sébastien; Corda, Eve; Boitier, Françoise; Dalle, Stéphane; Vabres, Pierre; Perrot, Jean-Luc; Lyonnet, Dominique Stoppa; Zattara, Hélène; Mansard, Sandrine; Grange, Florent; Leccia, Marie-Thérèse; Vincent-Fetita, Lynda; Martin, Ludovic; Crickx, Béatrice; Joly, Pascal; Thomas, Luc; Bressac-de Paillerets, Brigitte; Avril, Marie-Françoise; Demenais, Florence

    2012-12-01

    Features associated with an increased frequency of cyclin-dependent kinase inhibitor 2A (CDKN2A) mutations have been identified in families with 3 or more patients with cutaneous melanoma (CM). However, in families with 2 patients with CM, which represent the majority of familial melanoma, these factors have been rarely studied. We investigated association of 3 clinical features with the presence of a CDKN2A mutation in a family by extent of CM family clustering (2 vs ≥3 patients with CM among first-degree relatives in a family). We included 483 French families that comprised 387 families with 2 patients with CM (F2 families) and 96 families with 3 or more patients with CM (F3+ families). Three clinical factors were examined individually and in a joint analysis: median age at diagnosis younger than 50 years, and 1 or more patient in a family with multiple primary melanoma or with pancreatic cancer. The frequency of CDKN2A mutations was higher in F3+ families (32%) than in F2 families (13%). Although early age at melanoma diagnosis and occurrence of multiple primary melanoma in 1 or more patient were significantly associated with the risk of a CDKN2A mutation in F2 families, early age at melanoma diagnosis and occurrence of pancreatic cancer in a family were significantly associated with CDKN2A mutations in F3+ families. The study was not population based. This study shows that factors associated with CDKN2A mutations differ by extent of CM family clustering. It indicates that, in France, families with 2 patients with CM are eligible for genetic testing especially when there is an early age at CM diagnosis and/or 1 or more patients with multiple primary melanoma. Copyright © 2012 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  18. 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.

  19. Non melanoma skin cancer - etiopathogenesis, clinic, diagnostic and treatment

    International Nuclear Information System (INIS)

    Polakova, K.

    2009-01-01

    The incidence of non melanoma skin cancer has permanently increasing tendency in populations of European origin. The similar situation is in Slovakia too. It is the most frequent cancer in Caucasian. The UVR is considered as the most important factor for development of such diseases. UV exposure leads to the generation of alterations in nuclear genes such as the p53 tumour suppressor gene as well as in the other genome in the cell - namely mitochondrial DNA (mtDNA). Except traditional surgical treatment, noninvasive treatment modalities are increasingly used, namely for superficial lesions.Together with them, also markant development of new noninvasive diagnostic technologies was observed in the last decade.The shift from the older age groups to the younger ones, forced us to give increased attention to this problem. (author)

  20. Clinical study of noninvasive in vivo melanoma and nonmelanoma skin cancers using multimodal spectral diagnosis

    Science.gov (United States)

    Lim, Liang; Nichols, Brandon; Migden, Michael R.; Rajaram, Narasimhan; Reichenberg, Jason S.; Markey, Mia K.; Ross, Merrick I.; Tunnell, James W.

    2014-11-01

    The goal of this study was to determine the diagnostic capability of a multimodal spectral diagnosis (SD) for in vivo noninvasive disease diagnosis of melanoma and nonmelanoma skin cancers. We acquired reflectance, fluorescence, and Raman spectra from 137 lesions in 76 patients using custom-built optical fiber-based clinical systems. Biopsies of lesions were classified using standard histopathology as malignant melanoma (MM), nonmelanoma pigmented lesion (PL), basal cell carcinoma (BCC), actinic keratosis (AK), and squamous cell carcinoma (SCC). Spectral data were analyzed using principal component analysis. Using multiple diagnostically relevant principal components, we built leave-one-out logistic regression classifiers. Classification results were compared with histopathology of the lesion. Sensitivity/specificity for classifying MM versus PL (12 versus 17 lesions) was 100%;/100%;, for SCC and BCC versus AK (57 versus 14 lesions) was 95%;/71%, and for AK and SCC and BCC versus normal skin (71 versus 71 lesions) was 90%/85%. The best classification for nonmelanoma skin cancers required multiple modalities; however, the best melanoma classification occurred with Raman spectroscopy alone. The high diagnostic accuracy for classifying both melanoma and nonmelanoma skin cancer lesions demonstrates the potential for SD as a clinical diagnostic device.

  1. Genetic basis for clinical response to CTLA-4 blockade in melanoma.

    Science.gov (United States)

    Snyder, Alexandra; Makarov, Vladimir; Merghoub, Taha; Yuan, Jianda; Zaretsky, Jesse M; Desrichard, Alexis; Walsh, Logan A; Postow, Michael A; Wong, Phillip; Ho, Teresa S; Hollmann, Travis J; Bruggeman, Cameron; Kannan, Kasthuri; Li, Yanyun; Elipenahli, Ceyhan; Liu, Cailian; Harbison, Christopher T; Wang, Lisu; Ribas, Antoni; Wolchok, Jedd D; Chan, Timothy A

    2014-12-04

    Immune checkpoint inhibitors are effective cancer treatments, but molecular determinants of clinical benefit are unknown. Ipilimumab and tremelimumab are antibodies against cytotoxic T-lymphocyte antigen 4 (CTLA-4). Anti-CTLA-4 treatment prolongs overall survival in patients with melanoma. CTLA-4 blockade activates T cells and enables them to destroy tumor cells. We obtained tumor tissue from patients with melanoma who were treated with ipilimumab or tremelimumab. Whole-exome sequencing was performed on tumors and matched blood samples. Somatic mutations and candidate neoantigens generated from these mutations were characterized. Neoantigen peptides were tested for the ability to activate lymphocytes from ipilimumab-treated patients. Malignant melanoma exomes from 64 patients treated with CTLA-4 blockade were characterized with the use of massively parallel sequencing. A discovery set consisted of 11 patients who derived a long-term clinical benefit and 14 patients who derived a minimal benefit or no benefit. Mutational load was associated with the degree of clinical benefit (P=0.01) but alone was not sufficient to predict benefit. Using genomewide somatic neoepitope analysis and patient-specific HLA typing, we identified candidate tumor neoantigens for each patient. We elucidated a neoantigen landscape that is specifically present in tumors with a strong response to CTLA-4 blockade. We validated this signature in a second set of 39 patients with melanoma who were treated with anti-CTLA-4 antibodies. Predicted neoantigens activated T cells from the patients treated with ipilimumab. These findings define a genetic basis for benefit from CTLA-4 blockade in melanoma and provide a rationale for examining exomes of patients for whom anti-CTLA-4 agents are being considered. (Funded by the Frederick Adler Fund and others.).

  2. Transgressive first clinical experiences

    DEFF Research Database (Denmark)

    Jensen, Carsten Juul; Jeppesen, Lise Kofoed; Drachmann, Merete

    2014-01-01

    . The nursing students’ learning seems to be oriented towards socialization in the clinic as a workplace. This means that the nursing students seek to deal with overwhelming experiences concerning the naked bodies of patients and death, useful application of theoretical knowledge, the path from novice......This Study seeks to comprehend learning experiences of nursing students during their first clinical in-service placement. This Paper is part of a longitudinal development project interviewing the Student Nurse after each one of the five clinical in-service placements and then one year after...... graduation as a Nurse. The Study has a qualitative methodology, inspired by Michael Eraut’s thoughts on learning in the workplace. When the workplace perspective is applied, learning seems to be concentrated on actual situations which the Learner is in, in contrast to employing constructed concepts...

  3. Assessing response to chemotherapy in metastatic melanoma with FDG PET: Early experience.

    Science.gov (United States)

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

    2007-12-01

    The management of metastatic melanoma remains challenging with only modest response rates to chemotherapy but the need to identify the best re-staging techniques remains paramount. This study evaluates our early experience in the use of FDG PET-CT in the assessment of early response to chemotherapy in metastatic melanoma. FDG PET-CT was performed at baseline and following two or three cycles of combination or single agent chemotherapy in seven patients. Response was assessed visually as complete, partial metabolic response or progressive disease. There was intense FDG uptake in all metastases at baseline. Following two to three cycles of chemotherapy, there was a complete metabolic response (CMR) in one patient, partial metabolic response (PMR) in two patients and progressive metabolic disease (PMD) in the remaining three patients. Survival was 679 days in the single patient with a CMR, median of 206 and 129 days in the patients with PMR and PMD respectively. This pilot study demonstrates the potential use of FDG PET as a biomarker in early response assessment to chemotherapy in metastatic melanoma. PET-CT already plays in integral role in staging high risk melanoma patients and it may also have a promising role in assessing response to current and novel therapies. Further larger studies examining specific therapies and optimal timing are required.

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

    International Nuclear Information System (INIS)

    Laatikainen, L.; Tarkkanen, A.

    1987-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Laatikainen, L.; Tarkkanen, A.

    1987-01-01

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

  6. 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.

  7. Mutation Profile of B-Raf Gene Analyzed by fully Automated System and Clinical Features in Japanese Melanoma Patients.

    Science.gov (United States)

    Ide, Masaru; Koba, Shinichi; Sueoka-Aragane, Naoko; Sato, Akemi; Nagano, Yuri; Inoue, Takuya; Misago, Noriyuki; Narisawa, Yutaka; Kimura, Shinya; Sueoka, Eisaburo

    2017-01-01

    BRAF gene mutations have been observed in 30-50 % of malignant melanoma patients. Recent development of therapeutic intervention using BRAF inhibitors requires an accurate and rapid detection system for BRAF mutations. In addition, the clinical characteristics of the melanoma associated with BRAF mutations in Japanese patients have not been investigated on a large scale evaluation. We recently established quenching probe system (QP) for detection of an activating BRAF mutation, V600E and evaluated 113 melanoma samples diagnosed in Saga University Hospital from 1982 to 2011. The QP system includes fully automated genotyping, based on analysis of the probe DNA melting curve, which binds the target mutated site using a fluorescent guanine quenched probe. BRAF mutations were detected in 54 of 115 (47 %) including 51 of V600E and 3 of V600 K in Japanese melanoma cases. Among clinical subtypes of melanoma, nodular melanoma showed high frequency (12 of 15; 80 %) of mutation followed by superficial spreading melanoma (13 of 26; 50 %). The QP system is a simple and sensitive method to determine BRAF V600E mutation, and will be useful tool for patient-oriented therapy with BRAF inhibitors.

  8. 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

  9. 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.

  10. Pilot Trial of Selecting Molecularly-Guided Therapy for Patients with non-V600 BRAF Mutant Metastatic Melanoma: Experience of the SU2C/MRA Melanoma Dream Team

    Science.gov (United States)

    LoRusso, Patricia M.; Boerner, Scott A.; Pilat, Mary Jo; Forman, Karen M.; Zuccaro, Clarice Y.; Kiefer, Jeffrey A.; Liang, Winnie S.; Hunsberger, Sally; Redman, Bruce G.; Markovic, Svetomir N.; Sekulic, Aleksandar; Bryce, Alan H.; Joseph, Richard W.; Cowey, C. Lance; Fecher, Leslie Anne; Sosman, Jeffrey Alan; Chapman, Paul B.; Schwartz, Gary K.; Craig, David W.; Carpten, John D.; Trent, Jeffrey M.

    2017-01-01

    Targeted therapies and immunotherapies have led to significant improvements in the treatment of advanced cancers, including metastatic melanoma. However, new strategies are desperately needed to overcome therapeutic resistance to these agents, as well as to identify effective treatment approaches for cancer patients that fall outside major targetable mutational subtypes (e.g. non-V600 BRAF melanoma). One such strategy is to extend the paradigm of individually tailored, molecularly targeted therapy into a broader spectrum of melanoma patients, particularly those bearing tumors without commonly recognized therapeutic targets, as well as having failed or were ineligible for immunotherapy. In this non-treatment pilot study, next-generation sequencing (NGS) technologies were utilized, including whole genome and whole transcriptome sequencing, to identify molecular aberrations in patients with non-V600 BRAF Metastatic Melanoma (MM). This information was then rationally matched to an appropriate clinical treatment from a defined pharmacopeia. Five patients with advanced non-V600 BRAF MM were enrolled. We demonstrated successful performance of the following during a clinically relevant time period: patient tumor biopsy, quality DNA/RNA extraction, DNA/RNA-based sequencing for gene expression analysis, analysis utilizing a series of data integration methodologies, report generation, and tumor board review with formulated treatment plan. Streamlining measures were conducted based on the experiences of enrolling, collecting specimens, and analyzing the molecular signatures of patients. We demonstrated the feasibility of using NGS to identify molecular aberrations and generate an individualized treatment plan in this patient population. A randomized treatment study utilizing lessons learned from the conduct of this pilot study is currently underway. PMID:26063764

  11. An assessment of clinical pathways and missed opportunities for the diagnosis of nodular melanoma versus superficial spreading melanoma.

    Science.gov (United States)

    Cicchiello, Mark; Lin, Matthew J; Pan, Yan; McLean, Catriona; Kelly, John W

    2016-05-01

    Missed opportunities in the diagnosis of nodular melanoma (NM) carry high prognostic penalties due to the rapid rate of NM growth. To date, an assessment of the pathways to diagnosis of NM versus superficial spreading melanoma (SSM) specifically comparing numbers of opportunities missed to undertake biopsy has not been performed. A retrospective questionnaire of 120 patients (60 NM patients, age and sex matched to 60 SSM patients) from the Victorian Melanoma Service (VMS) database was undertaken to assess pathways to diagnosis. The numbers of opportunities missed to undertake a biopsy and doctor behaviour at such encounters were recorded. Diagnostic delay (overall, patient's and doctor's delay) in terms of time was assessed. Significant differences in opportunities missed to make a diagnosis of NM compared to SSM were found. In all, 43% of NM were biopsied at a first encounter compared to 70% of SSM. All SSM were diagnosed within three reviews. Overall, 33% of NM required at least three and up six reviews until biopsy. Patients with NM were more likely than those with SSM to be reassured that their lesions were benign. No significant differences in terms of time delay to diagnosis between NM and SSM were found. NM contributes disproportionately to melanoma mortality in Australia. Addressing earlier diagnosis of NM with renewed focus may make the biggest impact on the overall mortality of melanoma. The message that a period of observation is not appropriate for patients re-presenting with lesions of concern must be more effectively communicated. © 2015 The Australasian College of Dermatologists.

  12. Sentinel node biopsy for melanoma. Analysis of our experience (125 patients).

    Science.gov (United States)

    Soliveres Soliveres, Edelmira; García Marín, Andrés; Díez Miralles, Manuel; Nofuentes Riera, Carmen; Candela Gomis, Asunción; Moragón Gordon, Manuel; Antón Leal, María Ángeles; García García, Salvador

    2014-11-01

    The objective of this study is to analyze our experience in the use of sentinel node biopsy (SNB) in melanoma and identify the predictive factors of positive SNB and multiple drainage. Retrospective study of patients who underwent SNB for melanoma between August of 2000 and February of 2013. SNB was performed in 125 patients with a median of age of 55,6 (±15) years. The anatomic distribution was: 44 (35,2%) in legs, 24 (19,2%) in arms, 53 (42,4%) trunk and 3 (2,4%) in head and neck. The median Breslow index was 1,81 (0,45-5). Between 1 and 6 nodes were isolated. The drainage was unique in 98 (78,4%) and multiple in 27 (21,6%). The trunk was the localization of 25 (92,6%) nodes with multiple drainage. The definitive result of sentinel node (SN) was positive in 18 cases (7,1%). Breslow thickness (p=0,01) was statistically significant predictor of a positive SNB. The SNB allows patients to be selected for lymphadenectomy. Melanoma of the trunk was the principle location of multiple drainage. The only predictive factor of positive SNB was Breslow thickness. Copyright © 2013 AEC. Published by Elsevier Espana. All rights reserved.

  13. Stereotactic Fractionated Radiotherapy in the Treatment of Juxtapapillary Choroidal Melanoma: The McGill University Experience

    Energy Technology Data Exchange (ETDEWEB)

    Al-Wassia, Rolina; Dal Pra, Alan; Shun, Kitty; Shaban, Ahmed [Department of Oncology, Division of Radiation Oncology, Montreal General Hospital, McGill University Health Centre, Montreal, Quebec (Canada); Corriveau, Christine [Department of Ophthalmology, Notre Dame Hospital, Centre Hospitalier de l' Universite de Montreal, Montreal, Quebec (Canada); Edelstein, Chaim; Deschenes, Jean [Department of Ophthalmology, McGill University Health Centre, Montreal, Quebec (Canada); Ruo, Russel; Patrocinio, Horacio [Department of Medical Physics, Montreal General Hospital, McGill University Health Centre, Montreal, Quebec (Canada); Cury, Fabio L.B. [Department of Oncology, Division of Radiation Oncology, Montreal General Hospital, McGill University Health Centre, Montreal, Quebec (Canada); DeBlois, Francois [Department of Medical Physics, Jewish General Hospital, McGill University, Montreal, Quebec (Canada); Shenouda, George, E-mail: george.shenouda@muhc.mcgill.ca [Department of Oncology, Division of Radiation Oncology, Montreal General Hospital, McGill University Health Centre, Montreal, Quebec (Canada)

    2011-11-15

    Purpose: To report our experience with linear accelerator-based stereotactic fractionated radiotherapy in the treatment of juxtapapillary choroidal melanoma. Methods and Materials: We performed a retrospective review of 50 consecutive patients diagnosed with juxtapapillary choroidal melanoma and treated with linear accelerator-based stereotactic fractionated radiotherapy between April 2003 and December 2009. Patients with small to medium sized lesions (Collaborative Ocular Melanoma Study classification) located within 2 mm of the optic disc were included. The prescribed radiation dose was 60 Gy in 10 fractions. The primary endpoints included local control, enucleation-free survival, and complication rates. Results: The median follow-up was 29 months (range, 1-77 months). There were 31 males and 29 females, with a median age of 69 years (range, 30-92 years). Eighty-four percent of the patients had medium sized lesions, and 16% of patients had small sized lesions. There were four cases of local progression (8%) and three enucleations (6%). Actuarial local control rates at 2 and 5 years were 93% and 86%, respectively. Actuarial enucleation-free survival rates at 2 and 5 years were 94% and 84%, respectively. Actuarial complication rates at 2 and 5 years were 33% and 88%, respectively, for radiation-induced retinopathy; 9.3% and 46.9%, respectively, for dry eye; 12% and 53%, respectively, for cataract; 30% and 90%, respectively, for visual loss [Snellen acuity (decimal equivalent), <0.1]; 11% and 54%, respectively, for optic neuropathy; and 18% and 38%, respectively, for neovascular glaucoma. Conclusions: Linear accelerator-based stereotactic fractionated radiotherapy using 60 Gy in 10 fractions is safe and has an acceptable toxicity profile. It has been shown to be an effective noninvasive treatment for juxtapapillary choroidal melanomas.

  14. 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.

  15. Clinical assessment of 67 Ga-citrate tumor scintigraphy in malignant melanoma

    International Nuclear Information System (INIS)

    Kosuda, Shigeru; Takagi, Yaeko; Kubo, Atsushi; Sanmiya, Toshikazu; Okano, Yoshiyuki.

    1984-01-01

    In a retrospective study of the value of 67 Ga-citrate scan in cases of malignant melanoma, 63 scans were obtained from 22 patients. The overall sensitivity, specificity and accuracy of the 67 Ga-citrate scan for detection of affected patients were excellent, that is, 85.7%, 100%, 95.2%, respectively. Of the 92 lesions of grossly or pathologically proven melanoma, 65 (70.7%) were detected by routine 67 Ga-citrate scan. The smallest lesion that could be detected was the nodular skin metastasis of 4 mm in diameter. Many patients with positive 67 Ga-citrate scan showed elevations of erythrocyte sedimentation rate, C-reactive protain, lactic dehydrogenase and increased levels of alpha-2 globulin in serum total protain. The life expectancy of patients with an abnormal scan was shorter than that of patients with a normal scan. 67 Ga-citrate whole body scan reliably revealed the extent of malignant melanoma, and is of value in clinical management. (author)

  16. Clinical assessment of /sup 67/Ga-citrate tumor scintigraphy in malignant melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Kosuda, Shigeru (National Hospital of Okura, Tokyo (Japan)); Takagi, Yaeko; Kubo, Atsushi; Sanmiya, Toshikazu; Okano, Yoshiyuki

    1984-07-01

    In a retrospective study of the value of /sup 67/Ga-citrate scan in cases of malignant melanoma, 63 scans were obtained from 22 patients. The overall sensitivity, specificity and accuracy of the /sup 67/Ga-citrate scan for detection of affected patients were excellent, that is, 85.7%, 100%, 95.2%, respectively. Of the 92 lesions of grossly or pathologically proven melanoma, 65 (70.7%) were detected by routine /sup 67/Ga-citrate scan. The smallest lesion that could be detected was the nodular skin metastasis of 4 mm in diameter. Many patients with positive /sup 67/Ga-citrate scan showed elevations of erythrocyte sedimentation rate, C-reactive protein, lactic dehydrogenase and increased levels of alpha-2 globulin in serum total protein. The life expectancy of patients with an abnormal scan was shorter than that of patients with a normal scan. /sup 67/Ga-citrate whole body scan reliably revealed the extent of malignant melanoma, and is of value in clinical management.

  17. 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.

  18. 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.

  19. Clinical presentation, histology, and prognoses of malignant melanoma in ethnic Chinese: A study of 522 consecutive cases

    Directory of Open Access Journals (Sweden)

    Han Mei

    2011-02-01

    Full Text Available Abstract Background Malignant melanoma is a rare disease in Asia, and knowledge on its characteristics and clinical outcome in Asian patients is limited. The purpose of this observational study was to determine the clinical presentation and outcome of patients with melanoma in China. Methods A database was prospectively established for the purpose of this analysis. The elements of the database included basic demographic data of patients and prognosticators previously reported in literature, as well as follow-up data including clinical outcome after treatment. Medical record of all patients with pathologically diagnosed malignant melanoma consulted in our center since 2006 were retrieved and reviewed. No patient was excluded in this study. Statistical analyses including survival and multivariate analyses of factors associated with survival were respectively performed by Kaplan-Meier method and Cox proportional hazard model. Results A total of 522 consecutive and nonselected cases were evaluated. There were 218 cases (41.8% of acral lentiginous melanoma (ALM, 118 (22.6% of mucosal melanoma (MCM, 103 (19.7% of nodular melanoma (NM, 33 (6.3% of superficial spreading melanoma (SSM, and others were Lentigo maligna melanoma or unclassifiable disease. The proportion of patients with clinical stage I, II, III, and IV diseases were 6.1%, 55.9%, 25.1%, and 12.8%, respectively. Among the 357 cases of cutaneous melanoma, 234 patients (65.5% had ulceration. The 5-year overall survival rate of all 522 patients was 41.6%, and the median survival time was 3.92 years (95% CI, 3.282 to 4.558. Five-year survival rates of patients with stage I, II, III, and IV diseases were 94.1%, 44.0%, 38.4% and 4.6% respectively (P Conclusions Prognoses of patients with malignant melanoma diagnosed in China were suboptimal, and most patients were diagnosed with locally advanced disease (i.e., stage II or above. ALM and MCM are the two most commonly diagnosed pathological subtypes

  20. Clinical presentation, histology, and prognoses of malignant melanoma in ethnic Chinese: A study of 522 consecutive cases

    Science.gov (United States)

    2011-01-01

    Background Malignant melanoma is a rare disease in Asia, and knowledge on its characteristics and clinical outcome in Asian patients is limited. The purpose of this observational study was to determine the clinical presentation and outcome of patients with melanoma in China. Methods A database was prospectively established for the purpose of this analysis. The elements of the database included basic demographic data of patients and prognosticators previously reported in literature, as well as follow-up data including clinical outcome after treatment. Medical record of all patients with pathologically diagnosed malignant melanoma consulted in our center since 2006 were retrieved and reviewed. No patient was excluded in this study. Statistical analyses including survival and multivariate analyses of factors associated with survival were respectively performed by Kaplan-Meier method and Cox proportional hazard model. Results A total of 522 consecutive and nonselected cases were evaluated. There were 218 cases (41.8%) of acral lentiginous melanoma (ALM), 118 (22.6%) of mucosal melanoma (MCM), 103 (19.7%) of nodular melanoma (NM), 33 (6.3%) of superficial spreading melanoma (SSM), and others were Lentigo maligna melanoma or unclassifiable disease. The proportion of patients with clinical stage I, II, III, and IV diseases were 6.1%, 55.9%, 25.1%, and 12.8%, respectively. Among the 357 cases of cutaneous melanoma, 234 patients (65.5%) had ulceration. The 5-year overall survival rate of all 522 patients was 41.6%, and the median survival time was 3.92 years (95% CI, 3.282 to 4.558). Five-year survival rates of patients with stage I, II, III, and IV diseases were 94.1%, 44.0%, 38.4% and 4.6% respectively (P melanoma diagnosed in China were suboptimal, and most patients were diagnosed with locally advanced disease (i.e., stage II or above). ALM and MCM are the two most commonly diagnosed pathological subtypes. Clinical staging and presence of ulceration was significantly

  1. 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.

  2. 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

  3. Primary ovarian malignant melanoma

    Directory of Open Access Journals (Sweden)

    Kostov Miloš

    2010-01-01

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

  4. [Ocular melanomas : An update].

    Science.gov (United States)

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

    2017-11-01

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

  5. Small nodular melanoma: the beginning of a life-threatening lesion. A clinical study on 11 cases.

    Science.gov (United States)

    Bono, Aldo; Tolomio, Elena; Carbone, Antonino; Moglia, Daniele; Crippa, Federica; Tomatis, Stefano; Santinami, Mario

    2011-01-01

    Because of its high thickness, nodular melanoma often bears a poor prognosis. Thus, an earlier diagnosis of this type of lesion while it is still thin would be an important step in secondary prevention. The principal aim of the present study was to better define the initial clinical features of nodular melanoma to allow an early diagnosis. A secondary aim was to establish the prognosis of this type of lesion. We retrospectively studied and illustrated the clinical features of 11 small (nodular melanomas seen and treated during a 10-year period. Prognostic characteristics of the various lesions were also described. The results of the study help to describe a small nodular melanoma as a dark and/or pink/red raised lesion, which may be evenly or unevenly colored, with well-defined borders, that often appears de novo. A correct clinical diagnosis was made in 7 of the cases. During a median follow-up of 6 years, none of the patients had local or distant relapses. Detection of small nodular melanoma is feasible by accurate visual inspection, provided that physicians are aware of this type of lesion and maintain the index of suspicion at a high level to bring about curative surgery.

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

    International Nuclear Information System (INIS)

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

    2010-01-01

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

  7. Sentinel Node Tumor Load Assessment in Melanoma: Dilemmas and Clinical Management

    NARCIS (Netherlands)

    A.C.J. van Akkooi (Alexander)

    2011-01-01

    textabstractMalignant Melanoma is the most aggressive form of skin cancer. Worldwide, the incidence of melanoma has risen sharply of the past three decades. On the 1st of January 2007, there were nearly 800,000 people alive in the USA alone, who were diagnosed with a melanoma. This increase is

  8. Malignant melanoma of the oral cavity. Review of the literature and experience in a Peruvian Population.

    Science.gov (United States)

    Guevara-Canales, J-O; Gutiérrez-Morales, M-M; Sacsaquispe-Contreras, S-J; Sánchez-Lihón, J; Morales-Vadillo, R

    2012-03-01

    To determine the epidemiological profile of malignant melanoma cases treated at the National Institute for Neoplastic Diseases "Dr. Eduardo Caceres Graziani" (INEN) over the period 1952 to 2008. All clinical records with complete data of patients presenting a histopathological diagnosis of malignant melanoma of the oral cavity were reviewed. Data such as age, gender, location, tumor size, disease length, presence of metastasis, treatment received and year of admission were recorded. During the study period 97 cases were found. The average age of patients was 52.85±1.6 years old mostly between 50 and 59 years old; the predominant gender was the female. The most common location was the palate and there was 58.8% of cases with a tumor size bigger than or equal to 4 cm. The length of the disease in 38.1% of the cases was longer than a year and in great part of the cases (69.1%) there was no metastasis. The treatment of choice was the surgery plus radiotherapy in 38.1% of the cases. According to the admission date it was also noted that the number of cases is increasing. The results of this study demonstrate a late diagnosis and an increasing frequency of this neoplasia in the oral cavity.

  9. Sentinel Node Tumor Load Assessment in Melanoma: Dilemmas and Clinical Management

    OpenAIRE

    Akkooi, Alexander

    2011-01-01

    textabstractMalignant Melanoma is the most aggressive form of skin cancer. Worldwide, the incidence of melanoma has risen sharply of the past three decades. On the 1st of January 2007, there were nearly 800,000 people alive in the USA alone, who were diagnosed with a melanoma. This increase is characterized largely by an increase in thin melanomas (1 mm or less; T1 tumors). Prognosis of American Joint Committee on Cancer (AJCC) stage I / II ranges between 95% for T1 and 45% for T4 melanomas.

  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. Incidence trends and clinical-pathological characteristics of invasive cutaneous melanoma from 1980 to 2010 in the Canton of Zurich, Switzerland.

    Science.gov (United States)

    Minini, Remo; Rohrmann, Sabine; Braun, Ralph; Korol, Dimitri; Dehler, Silvia

    2017-04-01

    The aims of this paper are to describe the incidence trends of invasive cutaneous melanoma in the Canton of Zurich and to evaluate clinical and pathological factors such as cancer subtype, localization, age and Breslow thickness. A retrospective analysis was carried out with data from the population-based Cancer Registry of Zurich and Zug located in Zurich. A total of 8469 cases in 8034 different patients of invasive cutaneous melanoma were registered for the period 1980-2010 in the Canton of Zurich. Incidence trends were age standardized to the European standard population. Joinpoint regression was used to compute changes in incidence and mortality rates, measured as the annual percent change (APC). The most common subtypes of cutaneous melanoma were superficial spreading melanoma (SSM, 41.1%), followed by nodular melanoma (16.5%), lentigo maligna melanoma (13.5%), acral-lentiginous melanoma (5.0%) and other types of melanoma (2.8%); 21.1% were melanoma not otherwise specified. The trunk was the most frequent location (30.8%), followed by the lower limb and hip (26.4%) and the upper limb and shoulder (22.8%). Statistically significantly increasing incidence trends were observed for both men (APC=3.0%) and women (APC=2.1%). Incidences of SSM and melanoma not otherwise specified were the histological subtypes for which a significant increase in incidence was observed (APC for the period 1980-2010=3.2% for both). In terms of Breslow thickness, thin melanomas (0.01-1.00 mm) showed an increasing incidence. The incidence of melanoma increased in both men and women between 1980 and 2010. In terms of the different subtypes and Breslow thickness, increasing incidences of the SSM and of thin melanomas (0.01-1.00 mm) were observed. These observations are in agreement with other studies from Southern and Western Switzerland as well as other European countries and the USA.

  12. Malignant Melanoma

    Directory of Open Access Journals (Sweden)

    Eshini Perera

    2013-12-01

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

  13. Uveal Melanoma

    International Nuclear Information System (INIS)

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

    2011-01-01

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

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

    Directory of Open Access Journals (Sweden)

    K. V. Avakyan

    2017-01-01

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

  15. Clinical attachment: a learning experience

    African Journals Online (AJOL)

    2012-08-03

    Aug 3, 2012 ... A clinical attachment is an opportunity for doctors from South Sudan to experience the hospital and clinical practice in a setting different from their own. What they learn in the attachment will help them improve their medical practice on their return. I attended a clinical attachment in Oral and Maxillofacial ...

  16. Favorable outcome in clinically stage II melanoma patients is associated with the presence of activated tumor infiltrating T-lymphocytes and preserved MHC class I antigen expression

    NARCIS (Netherlands)

    Houdt, van I.S.; Sluijter, B.J.; Moesbergen, L.M.; Vos, de W.M.; Gruijl, T.D.; Molenkamp, B.G.; Eertwegh, van den A.J.; Hooijberg, E.; Leeuwen, van P.A.; Meijer, C.J.; Oudejans, J.J.

    2008-01-01

    In this study we investigated whether the presence of specific populations of tumor infiltrating lymphocytes (TILs) in diagnostic primary melanoma biopsies are related to outcome in clinically stage II melanoma patients. Moreover, we investigated whether the presence of TILs correlates with

  17. Favorable outcome in clinically stage II melanoma patients is associated with the presence of activated tumor infiltrating T-lymphocytes and preserved MHC class I antigen expression.

    NARCIS (Netherlands)

    Houdt, I.S. van; Sluijter, B.J.; Moesbergen, L.M.; Vos, W.M. de; Gruijl, T.D. de; Molenkamp, B.G.; Eertwegh, A.J. van den; Hooijberg, E.; Leeuwen, P.A.M. van; Meijer, C.J.; Oudejans, J.J.

    2008-01-01

    In this study we investigated whether the presence of specific populations of tumor infiltrating lymphocytes (TILs) in diagnostic primary melanoma biopsies are related to outcome in clinically stage II melanoma patients. Moreover, we investigated whether the presence of TILs correlates with

  18. Added clinical value of 'true' whole body F-FDG PET/CT imaging in patients with malignant melanoma

    International Nuclear Information System (INIS)

    Kovacs, Julie C.

    2009-01-01

    Full text: Accurate and reliable staging of disease extent in patients with malignant melanoma is essential to ensure appropriate treatment planning. The detection of recurrent or residual malignancy after primary treatment allows for early intervention and optimises patient survival. FDG PET/CT is indicated for surveillance of malignant melanoma due to its high sensitivity and specificity for soft-tissue or nodal recurrences and metastases. It has been claimed that routinely scanning lower extremities and skull in addition to 'eyes to thigh' images in PET/CT evaluation of metastatic melanoma is warranted. Whole-body PET/CT scan reports in patients with melanoma scanned from April 2005 to December 2008 were retrospectively reviewed. PET abnormalities in the brain/scalp and lower extremities were tabulated by location and whether they were 'expected'. Findings were correlated with pathology, other imaging studies and clinical follow-up. 94 PET/CT examinations in 268 patients with melanoma were included. 9 of 294 (3.1 %) scans showed brain/scalp abnormalities, with only 4 (1.3%) showing unexpected abnormalities. 24 of 294 (8.1 %) scans showed lower extremity abnormalities, with only 5 (1.6%) showing unexpected abnormalities. In no case was an unexpected solitary malignant lesion identified in the brain/scalp or lower extremities. In patients with no known or suspected primary or metastatic melanoma involving the head or lower extremities, inclusion of these regions on PET/CT is of low yield and appears to seldom offer significant additional benefit, as detection of additional metastases in these patients is unlikely to change clinical management. Routine 'eyes to thighs' images is adequate for this subset of patients.

  19. Integrated NY-ESO-1 antibody and CD8+ T-cell responses correlate with clinical benefit in advanced melanoma patients treated with ipilimumab.

    Science.gov (United States)

    Yuan, Jianda; Adamow, Matthew; Ginsberg, Brian A; Rasalan, Teresa S; Ritter, Erika; Gallardo, Humilidad F; Xu, Yinyan; Pogoriler, Evelina; Terzulli, Stephanie L; Kuk, Deborah; Panageas, Katherine S; Ritter, Gerd; Sznol, Mario; Halaban, Ruth; Jungbluth, Achim A; Allison, James P; Old, Lloyd J; Wolchok, Jedd D; Gnjatic, Sacha

    2011-10-04

    Ipilimumab, a monoclonal antibody against cytotoxic T lymphocyte antigen 4 (CTLA-4), has been shown to improve survival in patients with advanced metastatic melanoma. It also enhances immunity to NY-ESO-1, a cancer/testis antigen expressed in a subset of patients with melanoma. To characterize the association between immune response and clinical outcome, we first analyzed NY-ESO-1 serum antibody by ELISA in 144 ipilimumab-treated patients with melanoma and found 22 of 140 (16%) seropositive at baseline and 31 of 144 (22%) seropositive following treatment. These NY-ESO-1-seropositive patients had a greater likelihood of experiencing clinical benefit 24 wk after ipilimumab treatment than NY-ESO-1-seronegative patients (P = 0.02, relative risk = 1.8, two-tailed Fisher test). To understand why some patients with NY-ESO-1 antibody failed to experience clinical benefit, we analyzed NY-ESO-1-specific CD4(+) and CD8(+) T-cell responses by intracellular multicytokine staining in 20 NY-ESO-1-seropositive patients and found a surprising dissociation between NY-ESO-1 antibody and CD8 responses in some patients. NY-ESO-1-seropositive patients with associated CD8(+) T cells experienced more frequent clinical benefit (10 of 13; 77%) than those with undetectable CD8(+) T-cell response (one of seven; 14%; P = 0.02; relative risk = 5.4, two-tailed Fisher test), as well as a significant survival advantage (P = 0.01; hazard ratio = 0.2, time-dependent Cox model). Together, our data suggest that integrated NY-ESO-1 immune responses may have predictive value for ipilimumab treatment and argue for prospective studies in patients with established NY-ESO-1 immunity. The current findings provide a strong rationale for the clinical use of modulators of immunosuppression with concurrent approaches to favor tumor antigen-specific immune responses, such as vaccines or adoptive transfer, in patients with cancer.

  20. EXPERIENCE OF SUCCESSFUL ACNEFORM ERUPTIONS TREATMENT IN PATIENT WITH MULTIPLE MELANOMA

    Directory of Open Access Journals (Sweden)

    O. V. Minkina

    2016-01-01

    Full Text Available Objective: to describe the results of the joint monitoring and diversified treatment of oncologists and dermatologists those patient with multiple recurrent melanoma who received over a long period a targeted anti-cancer therapy, which was complicated by side-effect as widespread acneform rush, resistant to traditional treatment. Patient A., born in 1988, was followed up and got a treatment more than 2 years in oncology out-patient clinic diagnosed with “Melanoma of the front surface of the left leg T2bN0M0 IIA”. Subsequently, the patient was verified metastasis in the inginal lymph nodes, in the soft tissues of the hips, to liver. Acute adverse reaction has developed in a short time after getting the anti-tumor target therapy as generalized acneform rush and itching of the skin. Skin symptoms accompanied by pronounced psychological and emotional stress, therefore, dermatologists have been invited to provide additional medical assistance to this patient. Due to the fact that subsequent traditional anti-acne algorithms of topical and oral treatment was not such effective, there was made a decision to use an alternative supporting external therapy, which did not have similar examples of usage previously. Results. External application of tacrolimus ointment in combination with other drugs and then as a mono-therapy, allows us in a rather short period achieve a stable and pronounced regression of skin pathological lesions, to return to the previously cancelled initial drug dose of the anti-tumor target therapy, to change significantly components of the patient’s quality of life. Conclusion. The search for additional and alternative treatment approaches for similar patients, as in our case, remains relevant for specialists and patients themselves. This case is an example of alternative approach to the tacrolimus topical application in patient with drug-mediated acneform rush.

  1. Dendritic cell vaccination for metastatic melanoma: a 14-year monoinstitutional experience.

    Science.gov (United States)

    de Rosa, Francesco; Ridolfi, Laura; Fiammenghi, Laura; Petrini, Massimiliano; Granato, Anna M; Ancarani, Valentina; Pancisi, Elena; Soldati, Valentina; Cassan, Serena; Bulgarelli, Jenny; Framarini, Massimo; Tauceri, Francesca; Migliori, Giuseppe; Brolli, Claudia; Gentili, Giorgia; Petracci, Elisabetta; Nanni, Oriana; Riccobon, Angela; Ridolfi, Ruggero; Guidoboni, Massimo

    2017-08-01

    Although immunomodulating antibodies are highly effective in metastatic melanoma, their toxicity, related to the activation of T lymphocytes, can be severe. Anticancer vaccines promote a fairly specific response and are very well tolerated, but their effectiveness has yet to be demonstrated. We have been treating patients with advanced melanoma with an autologous dendritic cell vaccine since 2001; to better characterize the safety and efficacy of our product, we designed a retrospective study on all of our patients treated with the vaccine to date. We retrospectively reviewed both case report forms of patients included in clinical trials and medical records of those treated within a compassionate use program. Response was assessed according to the Response Evaluation Criteria In Solid Tumors criteria and toxicity has been graded according to CTCAE 4.0. Although the response rate has been rather low, the median overall survival of 11.4 months and the 1-year survival rate of 46.9% are encouraging, especially considering the fact that data were obtained in a heavily pretreated population and only about one quarter of the patients had received ipilimumab and/or BRAF inhibitors. Multivariate analysis confirmed that the development of an immune response was significantly correlated with a better prognosis (hazard ratio 0.54; P=0.019). The adverse events observed were generally mild and self-limiting. Our analysis confirms the excellent tolerability of our vaccine, making it a potential candidate for combination therapies. As efficacy seems largely restricted to immunoresponsive patients, future strategies should aim to increase the number of these patients.

  2. 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

  3. CASE REPORT: NODULAR MELANOMA

    Directory of Open Access Journals (Sweden)

    Tina Zupančič

    2015-05-01

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

  4. 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.

  5. 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

  6. [Experience in the treatment of cutaneous in-transit melanoma metastases and satellitosis with intralesional interleukin-2].

    Science.gov (United States)

    Dehesa, L A; Vilar-Alejo, J; Valerón-Almazán, P; Carretero, G

    2009-09-01

    Although metastatic melanoma has a poor prognosis, cutaneous metastases represent a special case given their ready accessibility, making it possible for dermatologists to apply local treatment. We report our experience with intralesional treatment with interleukin (IL) 2 in 7 patients with cutaneous metastases from malignant melanoma. A total of 244 lesions in 7 patients with satellitosis and/or cutaneous metastases from malignant melanoma were treated with intralesional IL-2 twice a week. The maximum dose in each patient ranged from 3 to 18 million units per session, according to the number and size of lesions. Complete or partial remission was achieved in almost all lesions (95.9 % and 3.7 %, respectively).Only 1 lesion (0.4 %) -the largest and located subcutaneously- did not respond to intralesional treatment and required alcoholization and subsequent surgical removal to achieve cure. All partial responses occurred in subcutaneous lesions larger than 2 cm. Treatment was well tolerated with only a few mild side effects (grade 1-2). IL-2 may be an effective and well-tolerated treatment option in patients with satellitosis and cutaneous metastases from melanoma. Lesions smaller than 2 cm and located in the epidermis or superficial dermis respond better than those larger than 2 cm or located in the subcutaneous cellular tissue. More studies are necessary to establish appropriate doses and regimens.

  7. Palliative radiotherapy for recurrent and metastatic malignant melanoma: prognostic factors for tumor response and long-term outcome: a 20-year experience

    International Nuclear Information System (INIS)

    Seegenschmiedt, M. Heinrich; Keilholz, Ludwig; Altendorf-Hofmann, Annelore; Urban, Anna; Schell, Hermann; Hohenberger, Werner; Sauer, Rolf

    1999-01-01

    Purpose: Radiotherapy is used as a 'last resort' for patients with advanced cutaneous malignant melanoma. We have analyzed our 20-year clinical experience with respect to different endpoints and prognostic factors in patients with locally advanced, recurrent, or metastatic malignant melanoma. Methods: From 1977 to 1995, 2,917 consecutive patients were entered in the melanoma registry of our hospital. Radiotherapy was indicated in 121 patients (56 females, 65 males) for palliative reasons in advanced malignant melanoma stages UICC IIB/III/IV. The histology of the primary lesion was nodular in 51 patients, superficial spreading in 35, acral-lentiginous in 8, and lentigo maligna melanoma in 4 patients. Eleven patients had primary or recurrent lesions which were either not eligible for surgery or had residual disease (R2) after resection of a primary or recurrent lesion (UICC IIB); 57 patients had lymph node (n = 33) or in-transit metastases (n = 24) (UICC III), and 53 had distant organ metastases (7 M1a; 46 M1b) (UICC IV). Time from first diagnosis to on-study radiotherapy averaged 19 (median: 18; range: 3-186) months. In most cases, conventional RT was applied with 2-6 Gy single fractions up to a median total radiation dose of 48 (mean: 45; range: 20-66) Gy. Results: At 3 months follow-up, complete response (CR) was achieved in 7 (64%) and overall response [complete (CR) and partial response (PR)] in all (100%) UICC IIB patients, in 25 (44%) and 44 (77%) of 57 UICC III patients, and in 9 (17%) and 26 (49%) of 53 UICC IV patients. Tumor progression during radiotherapy occurred in 25 (21%) patients. Patients with CR survived longer (median: 40 months) than those without CR (median 10 months) (p < 0.01). At last follow-up (Dec 31, 1996), 26 patients were still alive: 6 (55%) UICC IIB, 17 (30%) UICC III, and 3 (6%) UICC IV patients (p < 0.01). Univariate analysis revealed the following prognostic factors for complete response and long-term survival: UICC stage (p < 0

  8. Assessing student clinical learning experiences.

    Science.gov (United States)

    Nehyba, Katrine; Miller, Susan; Connaughton, Joanne; Singer, Barbara

    2017-08-01

    This article describes the use of an activity worksheet and questionnaire to investigate the learning experience of students on clinical placement. The worksheet measures the amount of time students spend in different learning activities, and the questionnaire explores student satisfaction and preferred learning activities. An activity worksheet and questionnaire … investigate[d] the learning experiences of students on clinical placement METHODS: The activity worksheet and questionnaire were used in a cohort pilot study of physiotherapy students on clinical placement. The activity worksheet provides details of the amount of time students engage in a range of clinical and non-clinical tasks while on placement, such as time spent treating patients, working individually, working with their peers and engaging in reflective practice. In combination with the questionnaire results, it allows clinicians to gain an understanding of the clinical learning environment experienced by their students. The data collected using these tools provide a description of the students' activities while undertaking the clinical placement. This information may guide the refinement of the clinical experience, and offers an opportunity to individualise learning activities to match students' needs and preferences. © 2016 John Wiley & Sons Ltd and The Association for the Study of Medical Education.

  9. Primary Anorectal Melanoma: An Update

    Directory of Open Access Journals (Sweden)

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

    2012-01-01

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

  10. The melanomas: a synthesis of epidemiological, clinical, histopathological, genetic, and biological aspects, supporting distinct subtypes, causal pathways, and cells of origin

    Science.gov (United States)

    Whiteman, David C.; Pavan, William J; Bastian, Boris C.

    2012-01-01

    Summary Converging lines of evidence from varied scientific disciplines suggest that cutaneous melanomas comprise biologically distinct subtypes that arise through multiple causal pathways. Understanding the respective relationships of each subtype with etiologic factors such as UV radiation and constitutional factors is the first necessary step toward developing refined prevention strategies for the specific forms of melanoma. Furthermore, classifying this disease precisely into biologically distinct subtypes is the key to developing mechanism- based treatments, as highlighted by recent discoveries. In this review, we outline the historical developments that underpin our understanding of melanoma heterogeneity, and we do this from the perspectives of clinical presentation, histopathology, epidemiology, molecular genetics, and developmental biology. We integrate the evidence from these separate trajectories to catalog the emerging major categories of melanomas and conclude with important unanswered questions relating to the development of melanoma and its cells of origin. PMID:21707960

  11. [MALIGNANT MELANOMA--THE INFLUENCE OF HORMONAL FACTORS ON THE PROGRESSION AND PROGNOSIS. COMPARATIVE ANALYSIS BASED ON TWO CLINICAL CASES].

    Science.gov (United States)

    Trayanova, E; Trayanov, I; Chokoeva, A; Tchernev, G

    2015-01-01

    Malignant melanoma is the most aggressive form of skin cancer showing extremely high metastatic rate and leading to high levels of lethality. The continually growing incidence of malignant melanoma in the world and his difficult early diagnosis are the occasion for numerous studies. The individual risk for malignant transformation of melanocytes is determined by a number of etiologic factors--endogenous and exogenous. Ultraviolet radiation has a leading role in the group of exogenous factors. Within the group of endogenous factors, besides the well-known photo type skin, as well as genes mutations, are added and the sex hormones, with their significant prognostic importance. The differences, which are observed in the progression and prognosis of malignant melanoma in pre- and postmenopausal women, and men, have defined this cutaneous neoplasma as hormone-dependent tumor. We present two seemingly similar clinical cases of 52 year old woman and 53-year-old man diagnosed with malignant melanomas, developed on the basis of pigmented lesions located on the upper back, as we attempt a comparative analysis on etiopathogenetic factors led to radically different course and prognosis of the disease in these two patients.

  12. A prospective multicenter cohort study of cutaneous melanoma: clinical staging and potential associations with HIF-1α and VEGF expressions.

    Science.gov (United States)

    Martínez-García, Miguel Ángel; Riveiro-Falkenbach, Erica; Rodríguez-Peralto, José L; Nagore, Eduardo; Martorell-Calatayud, Antonio; Campos-Rodríguez, Francisco; Farré, Ramón; Hernández Blasco, Luis; Bañuls Roca, Jose; Chiner Vives, Eusebi; Sánchez-de-la-Torre, Alicia; Abad Capa, Jorge; Montserrat, Josep Maria; Almendros, Isaac; Pérez-Gil, Amalia; Cabriada Nuño, Valentin; Cano-Pumarega, Irene; Corral Peñafiel, Jaime; Diaz Cambriles, Trinidad; Mediano, Olga; Dalmau Arias, Joan; Gozal, David

    2017-12-01

    Melanoma is a highly prevalent cancer that is associated with substantial mortality. Although clinical staging procedures can serve as relatively robust prognostic indicators, we aimed to determine whether assessments of the abundance of hypoxia inducible factor-1α (HIF-1α) or vascular endothelial growth factor (VEGF) in postexcisional melanoma tumor tissues may enable more accurate determination of tumor aggressiveness. We carried out a multicenter prospective study, in which we systematically evaluated 376 consecutive patients diagnosed with melanoma, and performed histochemical assessments for both HIF-1α and VEGF immunoreactivity in the tumor biopsies. Multivariate analyses showed that higher HIF-1α expression, but not high VEGF, were associated significantly and independently with increased tumor aggressiveness as derived from several well-established aggressiveness criteria. A limitation of this study was that this was a descriptive prospective study lacking a post-hoc verification arm. Thus, the presence of increased numbers of positively labeled HIF-1α cells in melanoma tumors may potentially serve as an indicator of tumor phenotype and prognosis, and accordingly guide therapy.

  13. Distribution of thermal neutron dose in nodular melanoma. Preclinical test by using animals and analysis of human clinical data

    International Nuclear Information System (INIS)

    Hiratsuka, Junichi; Karashima, Hiroshi; Fukuda, Hiroshi; Honda, Chihiro; Wadabayashi, Nobutoshi; Furubayashi, Toru; Kanda, Keiji; Mishima, Yutaka.

    1995-01-01

    There is the thermal neutron capture therapy that uses the thermal neutrons from nuclear reactors for the radiation treatment of malignant tumors, and because it can irradiate high LET radiation in large amount limiting to diseased parts, now the clinical research is in progress as an effective treatment. In the case of malignant melanoma, boron neutron capture treatment was attempted in 18 cases so far, and the local suppression was obtained in most cases. Recently, nodular melanoma was treated by the BNCT, but it was very difficult to forecast the dose distribution inside a tumor. The data on the thermal neutron dose distribution in this human case was compared with the preclinical test on the pig having spontaneous melanoma, and the countermeasures of hereafter were investigated. The objects and the methods of the preclinical test and the human medical irradiation, and the results of dose distribution in both cases and the countermeasures to nodular melanoma are reported. The factors that exert influence to the dose in depth are pointed out. (K.I.)

  14. Distribution of thermal neutron dose in nodular melanoma. Preclinical test by using animals and analysis of human clinical data

    Energy Technology Data Exchange (ETDEWEB)

    Hiratsuka, Junichi [Kawasaki Medical School, Kurashiki, Okayama (Japan); Karashima, Hiroshi; Fukuda, Hiroshi; Honda, Chihiro; Wadabayashi, Nobutoshi; Furubayashi, Toru; Kanda, Keiji; Mishima, Yutaka

    1995-03-01

    There is the thermal neutron capture therapy that uses the thermal neutrons from nuclear reactors for the radiation treatment of malignant tumors, and because it can irradiate high LET radiation in large amount limiting to diseased parts, now the clinical research is in progress as an effective treatment. In the case of malignant melanoma, boron neutron capture treatment was attempted in 18 cases so far, and the local suppression was obtained in most cases. Recently, nodular melanoma was treated by the BNCT, but it was very difficult to forecast the dose distribution inside a tumor. The data on the thermal neutron dose distribution in this human case was compared with the preclinical test on the pig having spontaneous melanoma, and the countermeasures of hereafter were investigated. The objects and the methods of the preclinical test and the human medical irradiation, and the results of dose distribution in both cases and the countermeasures to nodular melanoma are reported. The factors that exert influence to the dose in depth are pointed out. (K.I.).

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. Clinicopathological features and clinical outcomes associated with TP53 and BRAFNon-V600mutations in cutaneous melanoma patients.

    Science.gov (United States)

    Kim, Dae Won; Haydu, Lauren E; Joon, Aron Y; Bassett, Roland L; Siroy, Alan E; Tetzlaff, Michael T; Routbort, Mark J; Amaria, Rodabe N; Wargo, Jennifer A; McQuade, Jennifer L; Kemnade, Jan; Hwu, Patrick; Woodman, Scott E; Roszik, Jason; Kim, Kevin B; Gershenwald, Jeffrey E; Lazar, Alexander J; Davies, Michael A

    2017-04-15

    BRAF V600 , NRAS, TP53, and BRAF Non-V600 are among the most common mutations detected in non-acral cutaneous melanoma patients. Although several studies have identified clinical and pathological features associated with BRAF V600 and NRAS mutations, limited data are available regarding the correlates and significance of TP53 and BRAF Non-V600 mutations. This study analyzed the patient demographics, primary tumor features, and clinical outcomes of a large cohort of non-acral cutaneous melanoma patients who had undergone clinically indicated molecular testing (n = 926). The prevalence of BRAF V600 , NRAS, TP53, and BRAF Non-V600 mutations was 43%, 21%, 19%, and 7%, respectively. The presence of a TP53 mutation was associated with older age (P = .019), a head and neck primary tumor site (P = .0001), and longer overall survival (OS) from the diagnosis of stage IV disease in univariate (P = .039) and multivariate analyses (P = .015). BRAF Non-V600 mutations were associated with older age (P = .005) but not with primary tumor features or OS from stage IV. Neither TP53 nor BRAF Non-V600 mutations correlated significantly with OS with frontline ipilimumab treatment, and the TP53 status was not significantly associated with outcomes with frontline BRAF inhibitor therapy. Eleven patients with BRAF Non-V600 mutations were treated with a BRAF inhibitor. Three patients were not evaluable for a response because of treatment cessation for toxicities; the remaining patients had disease progression as the best response to therapy. These results add to the understanding of the clinical features associated with TP53 and BRAF Non-V600 mutations in advanced cutaneous melanoma patients, and they support the rationale for evaluating the prognostic significance of TP53 in other cohorts of melanoma patients. Cancer 2017;123:1372-1381. © 2016 American Cancer Society. © 2016 American Cancer Society.

  1. Risk factors for presumptive melanoma in skin cancer screening: American Academy of Dermatology National Melanoma/Skin Cancer Screening Program experience 2001-2005.

    Science.gov (United States)

    Goldberg, Matthew S; Doucette, John T; Lim, Henry W; Spencer, James; Carucci, John A; Rigel, Darrell S

    2007-07-01

    Since its inception in 1985, the American Academy of Dermatology (AAD) National Melanoma/Skin Cancer Screening Program has strived to enhance early detection of cutaneous malignant melanoma (MM) by providing nationwide skin cancer education campaigns in combination with free skin cancer screenings. To analyze the AAD screening data from 2001 to 2005 in order to identify factors associated with MM detection, and thereby derive a model of increased likelihood for MM detection through visual skin examinations at screenings. Patients completed a standardized AAD pre-screening form with historical and phenotypic information. Clinicians then recorded suspected clinical findings noted at visual skin examination. Statistical analyses were conducted using SPSS 14 (SPSS Inc., Chicago, Ill). Five factors, which can be remembered with the acronym HARMM, independently increased the likelihood of suspected MM being found in the 362,804 persons screened: History of previous melanoma (odds ratio [OR] = 3.3; 95% confidence interval [CI], 2.9-3.8); Age over 50 (OR = 1.2; 95% CI, 1.1-1.3); Regular dermatologist absent (OR = 1.4; 95% CI, 1.3-1.5); Mole changing (OR = 2.0; 95% CI, 1.9-2.2); and Male gender (OR = 1.4; 95% CI, 1.3-1.5). Individuals at highest risk (4 or 5 factors) comprised only 5.8% of the total population, yet accounted for 13.6% of presumptive MM findings, and were 4.4 times (95% CI, 3.8-5.1) more likely to be diagnosed with suspected MM than individuals at lowest risk (0 or 1 factor). Receipt of a total skin examination at screening independently increased the likelihood for identifying suspected MM (OR = 1.4; 95% CI, 1.3-1.6). However, significantly fewer screenees in the highest risk group versus those in the lowest risk group underwent total skin examinations (53.7% vs 62.5%). Risk factors studied limited to variables collected in screenee enrollment form. A higher-risk subgroup of the skin cancer screening population can be identified through assessment of MM

  2. Reproducibility of the clinical criteria (ABCDE rule) and dermatoscopic features (7FFM) for the diagnosis of malignant melanoma.

    Science.gov (United States)

    Benelli, C; Roscetti, E; Dal Pozzo, V

    2001-01-01

    Dermatoscopy improves the sensitivity and the specificity in the diagnosis of melanoma. Although the reproducibility of dermatoscopic features has been the subject of research, no study up to now has compared the reproducibility of dermatoscopic features to the reproducibility of the clinical criteria of the ABCDE rule. For this reason we decided to examine the reproducibility of the clinical ABCDE rule and of our diagnostic dermatoscopic method 7FFM, as well as of the individual criteria of both. A total of 73 dermatologists attended three dermatoscopic courses and examined a set of clinical and dermatoscopic slides of 50 pigmented skin tumors. Agreement % and K value for a kappa statistical analysis have been calculated to evaluate inter-rater reliability. The clinical and the dermatoscopic methods showed similar values of concordance: clinical score 2 mean agreement = 68%, mean K = 0.44; clinical score 3 mean agreement = 73%, mean K = 0.61; 7FFM mean agreement = 83%, mean K = 0.64. The clinical criteria A, B, and C and the dermatoscopic features of our method presented similar values of concordance as well: clinical criteria mean K range 0.35-0.25, dermatoscopic features mean K range 0.62-0.25. The dermatoscopic features of our method 7FFM show a good reproducibility after a short training program, similar to the reproducibility of the clinical criteria of the ABCDE rule for the diagnosis of melanoma.

  3. 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...

  4. Clinical significance of intronic variants in BRAF inhibitor resistant melanomas with altered BRAF transcript splicing

    OpenAIRE

    Pupo, Gulietta M.; Boyd, Suzanah C.; Fung, Carina; Carlino, Matteo S.; Menzies, Alexander M.; Pedersen, Bernadette; Johansson, Peter; Hayward, Nicholas K.; Kefford, Richard F.; Scolyer, Richard A.; Long, Georgina V.; Rizos, Helen

    2017-01-01

    Alternate BRAF splicing is the most common mechanism of acquired resistance to BRAF inhibitor treatment in melanoma. Recently, alternate BRAF exon 4?8 splicing was shown to involve an intronic mutation, located 51 nucleotides upstream of BRAF exon 9 within a predicted splicing branch point. This intronic mutation was identified in a single cell line but has not been examined in vivo. Herein we demonstrate that in three melanomas biopsied from patients with acquired resistance to BRAF inhibito...

  5. GMP production of pDERMATT for vaccination against melanoma in a phase I clinical trial.

    Science.gov (United States)

    Quaak, S G L; van den Berg, J H; Toebes, M; Schumacher, T N M; Haanen, J B A G; Beijnen, J H; Nuijen, B

    2008-10-01

    For the treatment of melanoma DNA vaccines are a promising therapeutic approach. In our institute a plasmid encoding a melanoma-associated epitope (MART-1) and an immunostimulatory sequence (tetanus toxin fragment-c) termed pDERMATT was developed. In a phase I study the plasmid will be administered intradermally using a newly developed tattoo strategy to assess the toxicity and efficacy of inducing tumor-specific T-cell immunity. To facilitate this study a Good Manufacturing Practice (GMP)-compliant plasmid manufacturing process was set up and a pharmaceutical dosage form was developed. Each batch resulted in approximately 200mg plasmid DNA of a high purity >90% supercoiled DNA, an A260/280 ratio 1.80-1.95, undetectable or extremely low residual endotoxins, Escherichia coli host cell protein, RNA, and DNA. In the manufacturing process no animal derived enzymes like RNase or potentially harmful organic solvents are used. After sterile filtration the concentration of the plasmid solution is approximately 1.1mg/mL. For the scheduled phase I study a concentration of 5mg/mL is desired, and further concentration of the solution is achieved by lyophilisation. The formulation solution is composed of 1mg/mL pDERMATT and 20mg/mL sucrose in Water for Injections. Upon reconstitution with a five times smaller volume an isotonic sucrose solution containing 5mg/mL pDERMATT is obtained. Lyophilised pDERMATT is sterile with >90% supercoiled DNA, an A260-280 ratio 1.80-1.95, content 90-110% of labeled, and residual water content <2% (w/w). The product yields the predicted profile upon restriction-enzyme digestion, is highly immunogenic as confirmed in an in vivo mouse model, and stable for at least six months at 5 degrees C. We have not only developed a reproducible process to manufacture pharmaceutical grade plasmid DNA but also a stable dosage form for the use in clinical trials.

  6. Melanoma and non-melanoma skin cancers in hairy cell leukaemia: a SEER population analysis and the 30-year experience at Memorial Sloan Kettering Cancer Center

    Science.gov (United States)

    Watts, Justin M; Kishtagari, Ashwin; Hsu, Meier; Lacouture, Mario E; Postow, Michael A; Park, Jae H; Stein, Eytan M; Teruya-Feldstein, Julie; Abdel-Wahab, Omar; Devlin, Sean M; Tallman, Martin S

    2016-01-01

    Few studies have examined melanoma and non-melanoma skin cancer (NMSC) incidence rates after a diagnosis of hairy cell leukaemia (HCL). We assessed 267 HCL patients treated at Memorial Sloan Kettering Cancer Center (MSKCC) and Surveillance, Epidemiology and End Results (SEER) data for melanoma and NMSC incidence rates after HCL. Incidence data from MSKCC patients demonstrated a 10-year combined melanoma and NMSC skin cancer rate of 11.3%, melanoma 4.4% and NMSC 6.9%. Molecular analysis of skin cancers from MSKCC patients revealed activating RAS mutations in 3/9 patients, including one patient with melanoma. Of 4,750 SEER patients with HCL, 55 (1.2%) had a subsequent diagnosis of melanoma. Standardized incidence ratios (SIRs) did not show that melanoma was more common in HCL patients versus the general population (SIR 1.3, 95% CI 0.78–2.03). Analysis of SEER HCL patients diagnosed before and after 1990 (approximately before and after purine analogue therapy was introduced) showed no evidence of an increased incidence after 1990. A better understanding of any potential association between HCL and skin cancer is highly relevant given ongoing trials using BRAF inhibitors, such as vemurafenib, for relapsed HCL, as RAS-mutant skin cancers could be paradoxically activated in these patients. PMID:26115047

  7. Discordancy in BRAF mutations among primary and metastatic melanoma lesions: clinical implications for targeted therapy.

    Science.gov (United States)

    Bradish, Joshua R; Richey, Justin D; Post, Kristin M; Meehan, Kari; Sen, Joyashree D; Malek, Amanda J; Katona, Terrence M; Warren, Simon; Logan, Theodore F; Fecher, Leslie A; Cheng, Liang

    2015-04-01

    Systemic targeted molecular therapy, in the form of a selective BRAF inhibitor with or without a MEK inhibitor, is a standard treatment for patients with BRAF V600 mutation-positive melanoma with unresectable stage III and IV disease. Patients with BRAF mutation-negative primary tumors may manifest BRAF mutation-positive metastatic disease. It is unclear whether all metastatic lesions carry the same BRAF mutation status found in the primary tumor and if discordancy exists, in what frequency it occurs. Primary and matched metastatic lesions in 25 melanoma patients were tested for the BRAF V600E/Ec, V600K, V600D, and V600R mutations using a BRAF RGQ PCR kit (Qiagen). Four patients (16%) had discrepancies between their primary and metastatic melanoma BRAF status. Of these patients, 2 (8%) had BRAF mutation-positive primary melanomas with BRAF mutation-negative metastatic lesions and 2 (8%) patient had BRAF mutation-negative melanoma with a BRAF mutation-positive metastatic lesion. In summary, discordancy of BRAF mutation status is not an infrequent finding between primary and metastatic melanoma. It may be prudent in previously negative patients to determine BRAF mutation status of new metastatic tumors for proper allocation of BRAF inhibitor therapy. Discordant BRAF status may have a role in the varying patterns of response and inevitable resistance seen with BRAF inhibitor therapies.

  8. A Review of the Aetiopathogenesis and Clinical and Histopathological Features of Oral Mucosal Melanoma

    Directory of Open Access Journals (Sweden)

    Liviu Feller

    2017-01-01

    Full Text Available Oral mucosal melanoma is an uncommon, usually heavily melanin-pigmented, but occasionally amelanotic aggressive tumour with a poor prognosis. Despite radical surgery, radiotherapy, or chemotherapy, local recurrence and distant metastasis are frequent. Microscopical examination is essential for diagnosis, and routine histological staining must be supplemented by immunohistochemical studies. The aetiology is unknown, the pathogenesis is poorly understood, and the 5-year survival rate rarely exceeds 30%. In most cases, oral mucosal melanoma arises from epithelial melanocytes in the basal layer of the epithelium and less frequently from immature melanocytes arrested in the lamina propria. In both cases the melanocytes undergo malignant transformation, invade deeper tissues, and metastasize to regional lymph nodes and to distant sites. Very rarely metastasis from skin melanoma may give rise to oral mucosal melanoma that may be mistaken for primary oral mucosal melanoma. The pathogenesis of oral mucosal melanoma is complex involving multiple interactions between cytogenetic factors including dysregulation of the cKit signalling pathways, cell cycle, apoptosis, and cell-to-cell interactions on the one hand and melanin itself, melanin intermediates, and local microenvironmental agents regulating melanogenesis on the other hand. The detailed mechanisms that initiate the malignant transformation of oral melanocytes and thereafter sustain and promote the process of melanomagenesis are unknown.

  9. Baseline gut microbiota predicts clinical response and colitis in metastatic melanoma patients treated with ipilimumab.

    Science.gov (United States)

    Chaput, N; Lepage, P; Coutzac, C; Soularue, E; Le Roux, K; Monot, C; Boselli, L; Routier, E; Cassard, L; Collins, M; Vaysse, T; Marthey, L; Eggermont, A; Asvatourian, V; Lanoy, E; Mateus, C; Robert, C; Carbonnel, F

    2017-06-01

    Ipilimumab, an immune checkpoint inhibitor targeting CTLA-4, prolongs survival in a subset of patients with metastatic melanoma (MM) but can induce immune-related adverse events, including enterocolitis. We hypothesized that baseline gut microbiota could predict ipilimumab anti-tumor response and/or intestinal toxicity. Twenty-six patients with MM treated with ipilimumab were prospectively enrolled. Fecal microbiota composition was assessed using 16S rRNA gene sequencing at baseline and before each ipilimumab infusion. Patients were further clustered based on microbiota patterns. Peripheral blood lymphocytes immunophenotypes were studied in parallel. A distinct baseline gut microbiota composition was associated with both clinical response and colitis. Compared with patients whose baseline microbiota was driven by Bacteroides (cluster B, n = 10), patients whose baseline microbiota was enriched with Faecalibacterium genus and other Firmicutes (cluster A, n = 12) had longer progression-free survival (P = 0.0039) and overall survival (P = 0.051). Most of the baseline colitis-associated phylotypes were related to Firmicutes (e.g. relatives of Faecalibacterium prausnitzii and Gemmiger formicilis), whereas no colitis-related phylotypes were assigned to Bacteroidetes. A low proportion of peripheral blood regulatory T cells was associated with cluster A, long-term clinical benefit and colitis. Ipilimumab led to a higher inducible T-cell COStimulator induction on CD4+ T cells and to a higher increase in serum CD25 in patients who belonged to Faecalibacterium-driven cluster A. Baseline gut microbiota enriched with Faecalibacterium and other Firmicutes is associated with beneficial clinical response to ipilimumab and more frequent occurrence of ipilimumab-induced colitis. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  10. A unifying approach to the clinical diagnosis of melanoma including "D" for "Dark" in the ABCDE criteria.

    Science.gov (United States)

    Goldsmith, Stuart M

    2014-10-01

    Current clinical approaches to melanoma diagnosis have not been associated with a decrease in mortality from this cancer. The components of the new approach presented are, first, a screening examination to look for any lesion that stands out because of being dark, different, or changing; second, when a single lesion is recognized to be of concern for any reason, that lesion is then evaluated in more detail utilizing the ABCDE criteria, with the "D" signifying "Dark" and not "6 mm Diameter" in this mnemonic; and, third, additional discussion of the "ugly duckling" sign and of the recognition of nodular melanomas. Since the Georgia Society of Dermatology and Dermatologic Surgery was the first state or national society to endorse this approach, I refer to it as the Georgia approach.

  11. 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...

  12. Eight Years' Experience of Sentinel Lymph Node Biopsy in Melanoma Using Lymphoscintigraphy and Gamma Probe Detection After Radiocolloid Mapping.

    Science.gov (United States)

    Pham Dang, Nathalie; Cassier, Sophie; Mulliez, Aurélien; Mansard, Sandrine; DʼIncan, Michel; Barthélémy, Isabelle

    2017-02-01

    Isosulfan blue dye peripheral injection is used in preoperative sentinel lymph node (SLN) identification alone or, to increase sensitivity, in conjunction with radiocolloid mapping. However, isosulfan blue dye has certain drawbacks and limitations. This study assesses the authors' experience of SLN biopsy using only radiocolloid tracer. Between 2000 and 2008, 218 patients underwent SLN biopsy with radiocolloid mapping, preoperative localization by lymphoscintigraphy and intraoperative confirmation by gamma probe in primary malignant cutaneous melanoma. Mean Breslow index was 2.1 mm. The SLN biopsy success rate was above 98% at all sites and 87% in head and neck locations. The 5-year overall survival rate was 90% and that of 5-year disease-free survival was 80%. False-negative rate, with a mean follow-up time of 41 months, was 5.5%. Sentinel lymph node biopsy can be successfully performed in patients with melanoma using only radiocolloid tracer without blue dye staining. In circumstances where blue dye cannot be used such as head and neck tumors, allergic reactions and pregnancy, radiocolloid tracer mapping alone is not a loss of chance for patients with melanoma.

  13. 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

  14. Results after beta-irradiation (106Ru/106Rh) of choroidal melanomas. Twenty years' experience

    International Nuclear Information System (INIS)

    Lommatzsch, P.K.

    1987-01-01

    For two decades, from 1964 to 1984, 309 patients suffering from choroidal melanoma were treated with 106 Ru/ 106 Rh applications, following confirmation of diagnosis by a variety of tests. A total of 216 patients (69.9%) were treated successfully and have been under observation for a mean period of 6.7 years after irradiation. 188 patients were followed for more than five years. Results indicate that enucleation for choroidal melanoma, especially in cases of eyes with good vision, may no longer be the standard treatment for this disease. This appears particularly true inasmuch as almost 50% of all patients with large choroidal melanomas who have enucleation die from metastases within 5 years of the operation. Therefore, conservative methods such as photocoagulation, irradiation, and microsurgical excision have been used with more or less success to destroy tumor and save a functioning eye

  15. Uveal melanoma: estimating prognosis.

    Science.gov (United States)

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

    2015-02-01

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

  16. 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.

  17. Prediction of Sentinel Node Status and Clinical Outcome in a Melanoma Centre

    Directory of Open Access Journals (Sweden)

    Vera Teixeira

    2013-01-01

    Full Text Available Background. Sentinel lymph node biopsy (SLNB is a standard procedure for patients with localized cutaneous melanoma. The National Comprehensive Cancer Network (NCCN Melanoma Panel has reinforced the status of the sentinel lymph node (SLN as an important prognostic factor for melanoma survival. We sought to identify predictive factors associated with a positive SLNB and overall survival in our population. Methods. We performed a retrospective chart review of 221 patients who have done a successful SLNB for melanoma between 2004 and 2010 at our department. Univariate and multivariate analyses were done. Results. The SLNB was positive in 48 patients (21.7%. Univariate analysis showed that male gender, increasing Breslow thickness, tumor type, and absence of tumor-infiltrating lymphocytes were significantly associated with a positive SLNB. Multivariate analysis confirmed that Breslow thickness and the absence of tumor-infiltrating lymphocytes are independently predictive of SLN metastasis. The 5-year survival rates were 53.1% for SLN positive patients and 88.2% for SLN negative patients. Breslow thickness and the SLN status independently predict overall survival. Conclusions. The risk factors for a positive SLNB are consistent with those found in the previous literature. In addition, the SLN status is a major determinant of survival, which highlights its importance in melanoma management.

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

    Science.gov (United States)

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

    2015-01-01

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

  19. Use of Ruthenium-106 Brachytherapy for Iris Melanoma: The Scottish Experience.

    Science.gov (United States)

    Agraval, Umiya; Sobti, Manvi; Russell, Heather C; Lockington, David; Ritchie, Diana; Cauchi, Paul; Kemp, Ewan G; Chadha, Vikas

    2018-01-01

    To analyse long-term outcomes of ruthenium-106 ( 106 Ru) plaque brachytherapy for the treatment of iris melanoma. We retrospectively reviewed medical records of 19 consecutive patients with pure iris melanoma treated with 106 Ru plaque brachytherapy between 1998 and 2016 at the Scottish Ophthalmic Oncology Service, Glasgow. The iris melanoma was treated with a ruthenium plaque placed on the corneal surface to deliver a surface dose of 555 Gy. We analysed vision preservation, local tumour control, radiation-related complications, eye retention rates, symptomatic metastasis and melanoma-related mortality. The mean largest basal diameter of the lesions was 3.50±1.42 mm (range 1.6-6.5 mm), and the mean maximum height was 1.47±0.65 mm (range 0.7-2.8 mm). The tumour control and eye retention were 100% at a mean follow-up of 62 months (range 6-195 months). A 62% reduction in tumour height was observed on ultrasonography. Complications included cataract (68%), dry eye (47%), uveitis (37%) and scleral thinning (5%). At the final follow-up visit, the mean loss of Snellen visual acuity was 1.11±2.90 lines and vision of 6/9 or better was maintained in 53% of patients. None of the patients had evidence of symptomatic metastasis (non-imaged) or melanoma-related mortality. 106 Ru plaque treatment for iris melanoma was highly effective a high tumour control, no tumour recurrences and a relatively a low complication rate. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  20. Clinical Characteristics of Malignant Melanoma in Southwest China: A Single-Center Series of 82 Consecutive Cases and a Meta-Analysis of 958 Reported Cases.

    Science.gov (United States)

    Yu, Jia; Luo, Xue; Huang, Hui; Zhai, Zhifang; Shen, Zhu; Lin, Hui

    2016-01-01

    The present study determined the clinical characteristics and prognostic factors in patients with malignant melanoma based on a series of 82 cases from January 2009 to December 2014 in Southwest Hospital and a meta-analysis (including 12 articles) involving 958 patients in China. The database elements included basic demographic data and prognosticators which were extracted from medical records. Statistical analyses of survival, and multivariate analyses of factors associated with survival were performed using the Kaplan-Meier method, and the Cox proportional hazard model, respectively. Literatures were identified through systematic searches in PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure (CNKI) and Weipu database (VIP) database for the period from inception to December 2015. The meta-analysis was conducted using R 3.1.1 meta-analysis software. In this series of 82 cases, the median age of the patients was 57.50 years. Melanoma was located in the foot in 79% of patients. Sixty-one patients (74.4%) were classified as stage II-III. Thirty-two patients (39.0%) had acral malignant melanoma, and 31 patients (37.8%) had nodular malignant melanoma. The clinical characteristics of melanoma were similar to those in areas outside southwest China (from results of the meta-analysis). The median survival time was 29.50 months. The 1-year, 3-year, and 5-year survival rates were 84.1%, 39.0% and 10.9%, respectively. COX regression following multi-factor analysis showed that ulcer, tumor boundary and lymph node metastasis were associated with prognosis. The clinical characteristics of melanoma in Chinese were different from those in Caucasians. Ulcer, tumor margins, and lymph node metastasis were significantly associated with prognosis. Immune therapy may prolong the median survival time of patients with acral melanoma, nodular melanoma, or stage I-III disease, although these differences were not statistically significant.

  1. Clinical Characteristics of Malignant Melanoma in Southwest China: A Single-Center Series of 82 Consecutive Cases and a Meta-Analysis of 958 Reported Cases.

    Directory of Open Access Journals (Sweden)

    Jia Yu

    Full Text Available The present study determined the clinical characteristics and prognostic factors in patients with malignant melanoma based on a series of 82 cases from January 2009 to December 2014 in Southwest Hospital and a meta-analysis (including 12 articles involving 958 patients in China.The database elements included basic demographic data and prognosticators which were extracted from medical records. Statistical analyses of survival, and multivariate analyses of factors associated with survival were performed using the Kaplan-Meier method, and the Cox proportional hazard model, respectively. Literatures were identified through systematic searches in PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure (CNKI and Weipu database (VIP database for the period from inception to December 2015. The meta-analysis was conducted using R 3.1.1 meta-analysis software.In this series of 82 cases, the median age of the patients was 57.50 years. Melanoma was located in the foot in 79% of patients. Sixty-one patients (74.4% were classified as stage II-III. Thirty-two patients (39.0% had acral malignant melanoma, and 31 patients (37.8% had nodular malignant melanoma. The clinical characteristics of melanoma were similar to those in areas outside southwest China (from results of the meta-analysis. The median survival time was 29.50 months. The 1-year, 3-year, and 5-year survival rates were 84.1%, 39.0% and 10.9%, respectively. COX regression following multi-factor analysis showed that ulcer, tumor boundary and lymph node metastasis were associated with prognosis.The clinical characteristics of melanoma in Chinese were different from those in Caucasians. Ulcer, tumor margins, and lymph node metastasis were significantly associated with prognosis. Immune therapy may prolong the median survival time of patients with acral melanoma, nodular melanoma, or stage I-III disease, although these differences were not statistically significant.

  2. The Skin Cancer Objective Structured Clinical Examination (SCOSCE): A multi-institutional collaboration to develop and validate a clinical skills assessment for melanoma.

    Science.gov (United States)

    Garg, Amit; Biello, Katie; Hoot, Joyce W; Reddy, Shalini B; Wilson, Lindsay; George, Paul; Robinson-Bostom, Leslie; Belazarian, Leah; Domingues, Erik; Powers, Jennifer; Jacob, Reza; Powers, Michael; Besen, Justin; Geller, Alan C

    2015-12-01

    Assessing medical students on core skills related to melanoma detection is challenging in the absence of a well-developed instrument. We sought to develop an objective structured clinical examination for the detection and evaluation of melanoma among medical students. This was a prospective cohort analysis of student and objective rater agreement on performance of clinical skills and assessment of differences in performance across 3 schools. Kappa coefficients indicated excellent agreement for 3 of 5 core skills including commenting on the presence of the moulage (k = 0.87, 95% confidence interval 0.77-0.96), obtaining a history for the moulage (k = 0.84, 95% confidence interval 0.74-0.94), and making a clinical impression (k = 0.80, 95% confidence interval 0.68-0.92). There were no differences in performance across schools with respect to 3 of 5 core skills: commenting on the presence of the moulage (P = .15), initiating a history (P = .53), and managing the suspicious lesion (P value range .07-.17). Overall, 54.2% and 44.7% of students commented on the presence of the moulage and achieved maximum performance of core skills, respectively, with no difference in performance across schools. Limitations include overall sample size of students and schools. The Skin Cancer Objective Structured Clinical Examination represents a potentially important instrument to measure students' performance on the optimal step-by-step evaluation of a melanoma. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  3. Cellular heterogeneity in vertical growth phase melanoma.

    Science.gov (United States)

    Laga, Alvaro C; Murphy, George F

    2010-12-01

    Melanoma growing as a tumorigenic nodule is one of the most virulent neoplasms to which the flesh is heir. At a considerably small tumor size, it incurs significant risk for widespread metastatic dissemination. There are no effective means of surgical intervention, chemical therapy, or immunologic therapy for advanced and metastatic melanoma. To review the literature and highlight recent cardinal advances in the understanding of melanoma vertical growth, with specific emphasis on how its recognition and characterization may be applied to diagnostic practice and development of novel investigative approaches. Literature review, archival material, personal experience, and research collaborators. The study of tumorigenic melanoma, both in primary lesions and in metastases, is the key to the eventual eradication of this highly virulent neoplasm that may disseminate widely when only occupying the volume of a grain of rice. Morphology often provides the first insight into structure and function. A growing database using meticulous and inclusive criteria to define tumor stem cells in the context of clinically relevant models now indicates that the key to melanoma heterogeneity may reside in a small subpopulation with the ability to self-renew and form tumors despite most cells present being significantly less virulent. Hopefully, from these insights into melanoma tumor progression from radial growth phase to heterogeneous and tumorigenic vertical growth phase will come additional answers to how smart therapies may be developed that specifically target those vertical growth phase cells that most pertain to patient survival.

  4. Clinical Relevance of Detection of Lymphovascular Invasion in Primary Melanoma Using Endothelial Markers D2-40 and CD34

    Science.gov (United States)

    Rose, Amy E.; Christos, Paul J.; Lackaye, Dan; Shapiro, Richard L.; Berman, Russell; Mazumdar, Madhu; Kamino, Hideko; Osman, Iman; Darvishian, Farbod

    2013-01-01

    Immunohistochemistry (IHC) using endothelial markers may facilitate the detection of lymphovascular invasion (LVI) in primary melanoma; however, the clinical implications of enhanced detection are unknown. We evaluated whether the use of lymphatic endothelial marker D2-40 and panvascular marker CD34 increases LVI positivity relative to routine histology alone and then evaluated the prognostic relevance of LVI detected using these markers in terms of disease-free (DFS) and overall survival (OS). A total of 246 primary melanomas were assessed for LVI using D2-40, CD34, and routine histology. Associations between LVI positivity and clinicopathologic variables, DFS, and OS were compared using univariate and multivariate analyses. The use of endothelial markers increased the rate of LVI positivity (18% using D2-40 and/or CD34 vs. 3% by routine histology, P nodular subtype) compared with LVI detected by routine histology (thickness and ulceration only). In a multivariate model controlling for stage, LVI detected using IHC markers remained a significant marker of both reduced DFS [hazard ratio (HR), 2.01; 95% confidence interval (CI): 1.27–3.18; P = 0.003] and OS (HR, 2.08; 95% CI: 1.25–3.46; P = 0.005). Results show that D2-40 and CD34 increase the detection of LVI in primary melanoma and that cases missed by routine histology have prognostic relevance. PMID:21881483

  5. Histological Types of Polypoid Cutaneous Melanoma II

    OpenAIRE

    Knežević, Fabijan; Duančić, Vjekoslav; Šitić, Sanda; Horvat-Knežević, Anica; Benković, Vesna; Ramić, Snježana; Kostović, Krešimir; Ramljak, Vesna; Velemir Vrdoljak, Danko; Stanec, Mladen; Božović, Angelina

    2007-01-01

    The aim of this study was to ascertain which histological types of melanoma can clinically and morphologically appear as polypoid melanomas. In 645 cases of primary cutaneous melanoma we have analyzed criteria for diagnosis of polypoid cutaneous melanoma and afterwards we have analyzed growth phase in each polypoid melanoma, histological type of atypical melanocytes, the number of epidermal ridges which are occupied by atypical melanocytes, and distribution according to age, sex a...

  6. 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

  7. Genital melanoma: prognosis factors and treatment modality.

    Science.gov (United States)

    Ferraioli, Domenico; Lamblin, Gery; Mathevet, Patrice; Hetu, Jessika; Berakdar, Isabelle; Beurrier, Frederic; Chopin, Nicolas

    2016-11-01

    Genital melanoma is a rare pathology. We present the experience of two comprehensive cancer centers in Lyon (France) in the management of genital melanoma in order to identify prognostic factors and optimal treatments. Between April 1992 and Mars 2014, 16 patients with a primary genital melanoma were referred to our department. Nine patients presented a vaginal melanoma, six vulvar melanomas and only one cervical melanoma. The median dimension of the lesion was 33.7 mm (5-100 mm). The AJCC stage ranged from IB to IIIC. 12 cases were the classic dark-blue flat melanoma and the other 4 cases were an atypical amelanotic tumor. Wide local surgery was performed in nine patients. A radical surgery was performed in six patients. In the large cervical melanoma, radiotherapy was performed as first-line treatment. In all the patients regional lymph node staging was performed. Adjuvant treatment was realized in nine patients. Two patients are alive without recurrence. Only one patient was lost to the first follow-up. The other 13 patients experienced a rapid recurrence. The median disease-free survival and the median overall survival were 11.8 months (2-49 m) and of 30.4 m (11-144 m), respectively. The disease-free survival and overall survival could be linked to a clinical presentation (Breslow thickness and morphology of lesion) associated to the early diagnosis. In our small series, the most important prognosis factor remains the tumor thickness. These rare lesions should be treated in experienced centers in order to improve their prognostic.

  8. 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.

  9. Management of Melanoma Families

    Directory of Open Access Journals (Sweden)

    Wilma Bergman

    2010-04-01

    Full Text Available In this review we have aimed to focus on the clinical management of familial melanoma patients and their relatives. Along this line three major topics will be discussed: (1 management/screening of familial melanoma families: what is advised and what is the evidence thereof; (2 variability of families worldwide with regard to clinical phenotype, including cancer spectrum and likelihood of finding germline mutations and (3 background information for clinicians on the molecular biology of familial melanoma and recent developments in this field.

  10. Role of radiotherapy in melanoma management

    International Nuclear Information System (INIS)

    Strojan, Primoz

    2010-01-01

    In melanoma, radiotherapy has generally been considered as a palliative treatment option indicated only for advanced cases or disseminated disease. In the 70s of the previous century, the technological advances in radiotherapy, linked to rapid development of computer sciences, resulted in restored interest for radiotherapy in melanoma management. Although a fundamental lack of well designed prospective and/or randomized clinical trials critically influenced the integration of radiotherapy into treatment strategies in melanoma, radiotherapy was recently recognized as an indispensable part in the multidisciplinary management of patients with melanoma. Altogether, approximately 23% of melanoma patients should receive at least one course of radiotherapy during the course of the disease. In this review, radiobiological properties of melanoma that govern the decisions for the fractionation patterns used in the treatment of this disease are described. Moreover, the indications for irradiation and the results of pertinent clinical studies from the literature, creating a rationale for the use of radiotherapy in the management of this disease, are reviewed and a brief description of radiotherapy techniques is given. Basic treatment modality in melanoma is surgery. However, whenever surgery is not radical or there are adverse prognostic factors identified on histopathological examination of resected tissue specimen, it needs to be supplemented. Also, in patients with unresectable disease or in those not being suitable for major surgery or who refuse proposed surgical intervention, other effective mode(s) of therapy need to be implemented. From this perspective, supported by clinical experiences and literature results, radiotherapy is a valuable option: it is effective and safe, in curative and palliative setting

  11. Primary dermal melanoma: a West Australian cohort.

    Science.gov (United States)

    Teow, James; Chin, Olivia; Hanikeri, Mark; Wood, Benjamin A

    2015-09-01

    The objectives of this study were to identify a subgroup of patients with putative primary dermal melanoma after thorough multidisciplinary clinical and histological evaluation, and to describe the clinical, histological and selected molecular features of these lesions. The records of the Western Australian Melanoma Advisory Service were searched for potential cases of primary dermal melanoma. The clinical and histological features were reviewed, immunohistochemical assessment was performed and clinical outcomes recorded. Eighteen cases of putative primary dermal melanoma with available clinical data were identified. Two of 12 cases in which further histological sections could be obtained were excluded because of the presence of findings suggesting an epidermal origin on these further sections. In one additional case, such origin could not be histologically excluded. Median follow-up period for the remaining cases was 68 months. Confirmed primary dermal melanoma accounts for 0.87% of cases of melanoma referred to a subspecialist melanoma advisory service. These cases show significant histological overlap with dermal/subcutaneous metastases of melanoma, but display a relatively good prognosis, with a 5-year survival of 87.5%. Our results support the recognition of a distinct group of melanoma that mimics metastatic melanoma, but is associated with a relatively favourable outcome. The group of putative primary dermal melanoma is likely to be heterogenous, including cases of primary nodular melanoma in which epidermal connection has not been identified, metastatic melanoma with an occult primary lesion and true primary dermal melanoma. © 2015 Royal Australasian College of Surgeons.

  12. Clinical, Molecular, and Immune Analysis of Dabrafenib-Trametinib Combination Treatment for BRAF Inhibitor-Refractory Metastatic Melanoma: A Phase 2 Clinical Trial.

    Science.gov (United States)

    Chen, Guo; McQuade, Jennifer L; Panka, David J; Hudgens, Courtney W; Amin-Mansour, Ali; Mu, Xinmeng Jasmine; Bahl, Samira; Jané-Valbuena, Judit; Wani, Khalida M; Reuben, Alexandre; Creasy, Caitlyn A; Jiang, Hong; Cooper, Zachary A; Roszik, Jason; Bassett, Roland L; Joon, Aron Y; Simpson, Lauren M; Mouton, Rosalind D; Glitza, Isabella C; Patel, Sapna P; Hwu, Wen-Jen; Amaria, Rodabe N; Diab, Adi; Hwu, Patrick; Lazar, Alexander J; Wargo, Jennifer A; Garraway, Levi A; Tetzlaff, Michael T; Sullivan, Ryan J; Kim, Kevin B; Davies, Michael A

    2016-08-01

    Combined treatment with dabrafenib and trametinib (CombiDT) achieves clinical responses in only about 15% of patients with BRAF inhibitor (BRAFi)-refractory metastatic melanoma in contrast to the higher response rate observed in BRAFi-naïve patients. Identifying correlates of response and mechanisms of resistance in this population will facilitate clinical management and rational therapeutic development. To determine correlates of benefit from CombiDT therapy in patients with BRAFi-refractory metastatic melanoma. Single-center, single-arm, open-label phase 2 trial of CombiDT treatment in patients with BRAF V600 metastatic melanoma resistant to BRAFi monotherapy conducted between September 2012 and October 2014 at the University of Texas MD Anderson Cancer Center. Key eligibility criteria for participants included BRAF V600 metastatic melanoma, prior BRAFi monotherapy, measurable disease (RECIST 1.1), and tumor accessible for biopsy. Patients were treated with dabrafenib (150 mg, twice daily) and trametinib (2 mg/d) continuously until disease progression or intolerance. All participants underwent a mandatory baseline biopsy, and optional biopsy specimens were obtained on treatment and at disease progression. Whole-exome sequencing, reverse transcription polymerase chain reaction analysis for BRAF splicing, RNA sequencing, and immunohistochemical analysis were performed on tumor samples, and blood was analyzed for levels of circulating BRAF V600. The primary end point was overall response rate (ORR). Progression-free survival (PFS) and overall survival (OS) were secondary clinical end points. A total of 28 patients were screened, and 23 enrolled. Among evaluable patients, the confirmed ORR was 10%; disease control rate (DCR) was 45%, and median PFS was 13 weeks. Clinical benefit was associated with duration of prior BRAFi therapy greater than 6 months (DCR, 73% vs 11% for ≤6 months; P = .02) and decrease in circulating BRAF V600 at day 8 of cycle 1 (DCR, 75

  13. 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...

  14. Experimenting with clinical networks: the Australasian experience.

    Science.gov (United States)

    Cunningham, Frances C; Morris, Andrew D; Braithwaite, Jeffrey

    2012-01-01

    Australian states have embraced clinical networking as a mechanism for managing, organising and improving the quality of care. Using these individualised state approaches to clinical networks, in this paper the authors aim to examine this Australasian "experimentation" and present lessons for other health systems. The paper draws on current knowledge from the literature on clinical networks. The 2010 Inaugural Australasian Clinical Networks Conference also serves as a primary resource, as well as the authors' extensive discussions with policy-makers, managers and clinicians in Australasian systems. Key themes from the literature include: network type (mandated or natural, and hybrids); network purpose; the importance of network objectives; drivers of network success and barriers; the need for consumer engagement; and the difficulty of evaluating network effectiveness. Policy challenges include the establishment of networks for some specialty areas and not others; how to develop common standards across networks; and the need for performance metrics to assess network impact on patient outcomes. Australian networks report difficulties with achieving greater involvement of rural clinicians and indigenous populations, and with private sector clinical engagement. There are challenges too with implementation, at service level, of models of care and recommendations. Clinical networks are becoming a fundamental vehicle for clinical improvement and change across complex organisational and professional boundaries. How to nurture and sustain effective clinical networks is of import to every health system and the authors invite stakeholders in health systems to network and share their empirical research on clinical networks to assist with distinguishing the evidence from the rhetoric.

  15. CYP24A1 Expression Inversely Correlates with Melanoma Progression: Clinic-Pathological Studies

    Directory of Open Access Journals (Sweden)

    Anna A. Brożyna

    2014-10-01

    Full Text Available The major role of 24-hydroxylase (CYP24A1 is to maintain 1,25-dihydroxyvitamin D3 (1,25(OH2D3 homeostasis. Recently, it has been discovered that CYP24A1 also catalyses the hydroxylation of 20(OHD3, producing dihydroxy-derivatives that show very effective antitumorigenic activities. Previously we showed a negative correlation of vitamin D receptor (VDR and CYP27B1 expression with progression, aggressiveness and overall or disease-free survivals of skin melanomas. Therefore, we analyzed CYP24A1 expression in relation to clinicopathomorphological features of nevi, skin melanomas and metastases. In melanocytic tumors, the level of CYP24A1 was higher than in the normal epidermis. The statistically highest mean CYP24A1 level was found in nevi and early stage melanomas. With melanoma progression, CYP24A1 levels decreased and in advanced stages were comparable to the normal epidermis and metastases. Furthermore, the CYP24A1 expression positively correlated with VDR and CYP27B1, and negatively correlated with mitotic activity. Lower CYP24A1 levels correlated with the presence of ulceration, necrosis, nodular type and amelanotic phenotypes. Moreover, a lack of detectable CYP24A1 expression was related to shorter overall and disease-free survival. In conclusion, the local vitamin D endocrine system affects melanoma behavior and an elevated level of CYP24A1 appears to have an important impact on the formation of melanocytic nevi and melanomagenesis, or progression, at early stages of tumor development.

  16. Melanoma genetics

    DEFF Research Database (Denmark)

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

    2015-01-01

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

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

    International Nuclear Information System (INIS)

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

    1988-01-01

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

  18. [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.

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

    Directory of Open Access Journals (Sweden)

    Furdová A

    2017-01-01

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

  20. 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...

  1. Immune Parameters in The Prognosis and Therapy Monitoring of Cutaneous Melanoma Patients: Experience, Role, and Limitations

    Directory of Open Access Journals (Sweden)

    Monica Neagu

    2013-01-01

    Full Text Available Cutaneous melanoma is an immune-dependent aggressive tumour. Up to our knowledge, there are no reports regarding immune parameters monitoring in longitudinal followup of melanoma patients. We report a followup for 36 months of the immune parameters of patients diagnosed in stages I–IV. The circulatory immune parameters comprised presurgery and postsurgery immune circulating peripheral cells and circulating intercommunicating cytokines. Based on our analysis, the prototype of the intratumor inflammatory infiltrate in a melanoma with good prognosis is composed of numerous T cells CD3+, few or even absent B cells CD20+, few or absent plasma cells CD138+, and present Langerhans cells CD1a+ or langerin+. Regarding circulatory immune cells, a marker that correlates with stage is CD4+/CD8+ ratio, and its decrease clearly indicates a worse prognosis of the disease. Moreover, even in advanced stages, patients that have an increased overall survival rate prove the increase of this ratio. The decrease in the circulating B lymphocytes with stage is balanced by an increase in circulating NK cells, a phenomenon observed in stage III. Out of all the tested cytokines in the followup, IL-6 level correlated with the patient’s survival, while in our study, IL-8, IL-10, and IL-12 did not correlate statistically in a significant way with overall survival, or relapse-free survival.

  2. Review of clinical studies on dendritic cell-based vaccination of patients with malignant melanoma: assessment of correlation between clinical response and vaccine parameters

    DEFF Research Database (Denmark)

    Engell-Noerregaard, Lotte; Hansen, Troels Holz; Andersen, Mads Hald

    2009-01-01

    which in the disseminated stage have a very poor prognosis and only limited treatment options with moderate effectiveness. Herein we describe the results of a focused search of recently published clinical studies on dendritic cell vaccination in melanoma and review different vaccine parameters which...... schedules among the published studies, which were not considered in order to be able to process and group the data....... are frequently claimed to have a possible influence on clinical response. These parameters include performance status, type of antigen, DC maturation status, route of vaccine administration, use of adjuvant, and vaccine induced immune response. In total, 38 articles found through Medline search, have been...

  3. Ipilimumab in the real world: the UK expanded access programme experience in previously treated advanced melanoma patients.

    Science.gov (United States)

    Ahmad, Saif S; Qian, Wendi; Ellis, Sarah; Mason, Elaine; Khattak, Muhammad A; Gupta, Avinash; Shaw, Heather; Quinton, Amy; Kovarikova, Jarmila; Thillai, Kiruthikah; Rao, Ankit; Board, Ruth; Nobes, Jenny; Dalgleish, Angus; Grumett, Simon; Maraveyas, Anthony; Danson, Sarah; Talbot, Toby; Harries, Mark; Marples, Maria; Plummer, Ruth; Kumar, Satish; Nathan, Paul; Middleton, Mark R; Larkin, James; Lorigan, Paul; Wheater, Matthew; Ottensmeier, Christian H; Corrie, Pippa G

    2015-10-01

    Before licensing, ipilimumab was first made available to previously treated advanced melanoma patients through an expanded access programme (EAP) across Europe. We interrogated data from UK EAP patients to inform future clinical practice. Clinicians registered in the UK EAP provided anonymized patient data using a prespecified variable fields datasheet. Data collected were baseline patient characteristics, treatment delivered, toxicity, response, progression-free survival and overall survival (OS). Data were received for 193 previously treated metastatic melanoma patients, whose primary sites were cutaneous (82%), uveal (8%), mucosal (2%), acral (3%) or unknown (5%). At baseline, 88% of patients had a performance status (PS) of 0-1 and 20% had brain metastases. Of the patients, 53% received all four planned cycles of ipilimumab; the most common reason for stopping early was disease progression, including death from melanoma. Toxicity was recorded for 171 patients, 30% of whom experienced an adverse event of grade 3 or higher, the most common being diarrhoea (13%) and fatigue (9%). At a median follow-up of 23 months, the median progression-free survival and OS were 2.8 and 6.1 months, respectively; the 1-year and 2-year OS rates were 31 and 14.8%, respectively. The 2-year OS was significantly lower for patients with poorer PS (P<0.0001), low albumin concentrations (P<0.0001), the presence of brain metastases (P=0.007) and lactate dehydrogenase levels more than two times the upper limit of normal (P<0.0001) at baseline. These baseline characteristics are negative predictors of benefit from ipilimumab and should be taken into consideration before prescription.

  4. Clinical guidelines for the recognition of melanoma of the foot and nail unit

    Directory of Open Access Journals (Sweden)

    Turner Richard J

    2010-11-01

    Full Text Available Abstract Malignant melanoma is a life threatening skin tumour which may arise on the foot. The prognosis for the condition is good when lesions are diagnosed and treated early. However, lesions arising on the soles and within the nail unit can be difficult to recognise leading to delays in diagnosis. These guidelines have been drafted to alert health care practitioners to the early signs of the disease so an early diagnosis can be sought.

  5. Clinical guidelines for the recognition of melanoma of the foot and nail unit.

    Science.gov (United States)

    Bristow, Ivan R; de Berker, David Ar; Acland, Katharine M; Turner, Richard J; Bowling, Jonathan

    2010-11-01

    Malignant melanoma is a life threatening skin tumour which may arise on the foot. The prognosis for the condition is good when lesions are diagnosed and treated early. However, lesions arising on the soles and within the nail unit can be difficult to recognise leading to delays in diagnosis. These guidelines have been drafted to alert health care practitioners to the early signs of the disease so an early diagnosis can be sought.

  6. Clinical value of imaging methods for postoperative management of patients with malignant melanoma

    International Nuclear Information System (INIS)

    Ishii, Takayuki; Fujimoto, Akihide; Takehara, Kazuhiko; Hatta, Naohito

    2008-01-01

    In the postoperative management of patients with malignant melanoma, CT and MRI are both used for screening of recurrent disease more frequently in Japan than in other countries. We evaluated the usefulness of various imaging methods during the postoperative period by retrospective analysis of 142 patients with Stage I-III malignant melanoma. Metastases were found in 44 of 142 patients (31%) during the follow-up period. In 28 cases, the metastases were detected by a routine physical examination, but by imaging tests including CT, MRI, Ga/Tc scintigraphy and positron emission tomography (PET) in 16 cases. Elevated serum markers including 5-S-cysteinyldopa (5-SCD), melanoma inhibitory activity (MIA) and lactate dehydrogenase (LDH) were observed in 24%, 72%, and 12% of patients who developed metastases, respectively. There was no significant difference in overall survival rate between in patients with metastasis detected by a routine physical examination and in patients with metastasis detected by imaging methods (p=0.27). In contrast, there was a significantly longer overall survival rate in patients with operable metastasis compared with those with inoperable metastasis (p=0.001). Patients with operable stage IV disease showed a longer overall survival rate than did patients with inoperable disease (p=0.07). The results suggest that early detection of melanoma metastases may improve the survival rate of patients. However, frequent systemic evaluation by imaging methods is strongly discouraged due to costs and effects. An adequate follow-up schedule should be justified according to the risk of each patient. (author)

  7. Recombinant interleukin-2-based treatments for advanced melanoma: the experience of the European Organization for Research and Treatment of Cancer Melanoma Cooperative Group

    NARCIS (Netherlands)

    Keilholz, U.; Stoter, G.; Punt, C. J.; Scheibenbogen, C.; Lejeune, F.; Eggermont, A. M.

    1997-01-01

    This article reviews the currently available data on phase II and III trials regarding the efficacy of recombinant interleukin-2 (rIL-2)-based regimens in the treatment of stage IV melanoma, and discusses the rationale and outcome of past and currently ongoing rIL-2-based chemo-immunotherapy phase

  8. 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

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

    Science.gov (United States)

    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

    2016-11-01

    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. 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. 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. 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 potential to be even more effective in combination with

  10. Rapid and clinically significant response to masitinib in the treatment of mucosal primary esophageal melanoma with somatic KIT exon 11 mutation involving brain metastases: A case report.

    Science.gov (United States)

    Prosvicova, Jarmila; Lukesova, Sarka; Kopecky, Jindrich; Grim, Jiri; Papik, Zdenek; Kolarova, Renata; Navratilova, Blanka; Dubreuil, Patrice; Agopian, Julie; Mansfield, Colin; Moussy, Alan; Hermine, Olivier

    2015-12-01

    Malignant melanoma in the gastrointestinal tract may be primary or metastatic. Mucosal melanoma is a quite rare and aggressive disease, growing hidden and diagnosed with a certain delay which makes treatment difficult. The authors present the first patient with c-kit exon 11 mutated primary esophageal melanoma treated with oral tyrosine kinase inhibitor masitinib. A 55-year-old-man presented with esophageal melanoma metastising into visceral organs and to the brain. The patient showed objective and clinical significant therapeutic response to masitinib. After initiation of masitinib, dysphagia and odynophagia disappeared within 1 week. Following 1 month of treatment, computed tomography showed a regression in the number and size of brain metastatic lesions and regression in visceral lesions. This therapeutic response, despite the aggressive disease on treatment initiation, effectively enabled the patient to have 6 months of quality life. This report corroborates the plausibility of treating advanced melanoma carrying a mutation of KIT with masitinib. It also raises the question of masitinib treatment beyond progression. Additionally, the observed masitinib treatment effect on the brain suggests accumulation of therapeutically relevant concentration of masitinib in the central nervous system. This observation has possible ramifications for treatment of intracranial neoplasms.

  11. Proton beam radiotherapy of choroidal melanoma: The Liverpool-Clatterbridge experience

    International Nuclear Information System (INIS)

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

    2005-01-01

    Purpose To report on outcomes after proton beam radiotherapy of choroidal melanoma using a 62-MeV cyclotron in patients considered unsuitable for other forms of conservative therapy. Methods and Materials A total of 349 patients with choroidal melanoma referred to the Liverpool Ocular Oncology Centre underwent proton beam radiotherapy at Clatterbridge Centre for Oncology (CCO) between January 1993 and December 2003. Four daily fractions of proton beam radiotherapy were delivered, with a total dose of 53.1 proton Gy, and with lateral and distal safety margins of 2.5 mm. Outcomes measured were local tumor recurrence; ocular conservation; vision; and metastatic death according to age, gender, eye, visual acuity, location of anterior and posterior tumor margins, quadrant, longest basal tumor dimension, tumor height, extraocular extension, and retinal invasion. Results The 5-year actuarial rates were 3.5% for local tumor recurrence, 9.4% for enucleation, 79.1% for conservation of vision of counting fingers or better, 61.1% for conservation of vision of 20/200 or better, 44.8% for conservation of vision of 20/40 or better, and 10.0% for death from metastasis. Conclusion Proton beam radiotherapy with a 62 MeV cyclotron achieves high rates of local tumor control and ocular conservation, with visual outcome depending on tumor size and location

  12. The Danish Melanoma Database

    DEFF Research Database (Denmark)

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

    2016-01-01

    AIM OF DATABASE: The aim of the database is to monitor and improve the treatment and survival of melanoma patients. STUDY POPULATION: All Danish patients with cutaneous melanoma and in situ melanomas must be registered in the Danish Melanoma Database (DMD). In 2014, 2,525 patients with invasive......-node-metastasis stage. Information about the date of diagnosis, treatment, type of surgery, including safety margins, results of lymphoscintigraphy in patients for whom this was indicated (tumors > T1a), results of sentinel node biopsy, pathological evaluation hereof, and follow-up information, including recurrence......, nature, and treatment hereof is registered. In case of death, the cause and date are included. Currently, all data are entered manually; however, data catchment from the existing registries is planned to be included shortly. DESCRIPTIVE DATA: The DMD is an old research database, but new as a clinical...

  13. Superficial melanomas of oral mucous membranes.

    Science.gov (United States)

    Regezi, J A; Hayward, J R; Pickens, T N

    1978-05-01

    In accordance with microscopic and clinical criteria established for superficial melanomas of the skin (superficial spreading melanoma, lentigo maligna melanoma, acral-lentiginous melanoma), three oral lesions have been evaluated. The literature on oral melanomas has also been reviewed, with special attention given to those cases that had pre-existing melanosis. One patient with a diagnosis of superficial spreading melanoma eventually died of his untreated lesion 11 years after its first appearance. Two patients had lesions diagnosed as acral-lentiginous melanoma (a group which also includes volar and subungual melanomas) that exhibited aggressive, recurrent behavior. These lesions had microsocpic features similar to lentigo maligna melanoma but did not behave in a manner consistent with that diagnosis. Electron microscopic study of one acral-lentiginous melanoma demonstrated malenosomes and premelanosomes that were like those seen in normal melanocytes and nevus cells. The superficial or radial growth phase of many oral melanomas has apparently gone unrecognized. Melanosis has been reported to be a common feature of invasive oral melanomas but has not generally been related to the natural history of these lesions. Oral lesions with a prolonged intra-epithelial or radial growth phase would be expected to have a better prognosis than nodular melanomas, but meaningful survival data are not available because of the infrequency with which oral melanomas have been subclassified.

  14. Melanoma do aparelho ungueal Nail apparatus melanoma

    Directory of Open Access Journals (Sweden)

    Ignez Regina dos Santos Muri Mendonça

    2004-10-01

    Full Text Available O melanoma do aparelho ungueal é apresentação relativamente rara dessa neoplasia, muitas vezes diagnosticada como nevo juncional, hematoma subungueal ou mesmo onicomicose. Esse fato leva a um atraso no diagnóstico e, conseqüentemente, na instituição da terapêutica específica, contribuindo para agravar o prognóstico de uma doença que por si só já é muito agressiva. Os autores relatam um caso de melanoma no primeiro quirodáctilo esquerdo de uma paciente negra com evolução de um ano, ressaltando a importância de avaliar certos critérios clínicos para obter o diagnóstico em fases mais precoces da doença.Nail apparatus melanoma is a rare presentation of melanoma and may be misdiagnosed as junctional nevus, subungual hematoma or onychomycosis. This fact often leads initially to inappropriate treatment and significant delays in appropriately managing such an aggressive disease. The authors report a case of melanoma on the left thumb of a black patient evolving for a year. Emphasis was placed on the importance of assessing certain clinical characteristics in order to reach an early diagnosis.

  15. Clinical Concept Mapping as Preparation for Student Nurses' Clinical Experiences.

    Science.gov (United States)

    Baugh, Nancy G.; Mellott, Karen G.

    1998-01-01

    Clinical concept mapping promotes critical thinking and prepares nursing students for clinical experience by helping them organize patient data and view patients holistically. It aids their assessment of what they know and what they still need to learn. (SK)

  16. Clinical Predictors of Regression of Choroidal Melanomas after Brachytherapy: A Growth Curve Model.

    Science.gov (United States)

    Rashid, Mamunur; Heikkonen, Jorma; Singh, Arun D; Kivelä, Tero T

    2018-02-27

    To build multivariate models to assess correctly and efficiently the contribution of tumor characteristics on the rate of regression of choroidal melanomas after brachytherapy in a way that adjusts for confounding and takes into account variation in tumor regression patterns. Modeling of longitudinal observational data. Ultrasound images from 330 of 388 consecutive choroidal melanomas (87%) irradiated from 2000 through 2008 at the Helsinki University Hospital, Helsinki, Finland, a national referral center. Images were obtained with a 10-MHz B-scan during 3 years of follow-up. Change in tumor thickness and cross-sectional area were modeled using a polynomial growth-curve function in a nested mixed linear regression model considering regression pattern and tumor levels. Initial tumor dimensions, tumor-node-metastasis (TNM) stage, shape, ciliary body involvement, pigmentation, isotope, plaque size, detached muscles, and radiation parameters were considered as covariates. Covariates that independently predict tumor regression. Initial tumor thickness, largest basal diameter, ciliary body involvement, TNM stage, tumor shape group, break in Bruch's membrane, having muscles detached, and radiation dose to tumor base predicted faster regression, whether considering all tumors or those that regressed in a pattern compatible with exponential decay. Dark brown pigmentation was associated with slower regression. In multivariate modeling, initial tumor thickness remained the predominant and robust predictor of tumor regression (P future analyses efficiently without matching. Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

  17. Mucosal melanoma of the nose and paranasal sinuses, a contemporary experience from the M. D. Anderson Cancer Center.

    Science.gov (United States)

    Moreno, Mauricio A; Roberts, Dianna B; Kupferman, Michael E; DeMonte, Franco; El-Naggar, Adel K; Williams, Michelle; Rosenthal, David S; Hanna, Ehab Y

    2010-05-01

    Sinonasal mucosal melanoma is a rare disease associated with a very poor prognosis. Because most of the series extend retrospectively several decades, we sought to determine prognostic factors and outcomes with recent treatment modalities. A retrospective chart review of 58 patients treated for sinonasal melanoma at a tertiary cancer center between 1993 and 2004. The patients were retrospectively staged according to the sinonasal American Joint Committee on Cancer (AJCC) staging system. Demographic, clinical and pathological parameters were identified and correlated with outcomes. There were 35 males and 23 females with a median age of 63 years; 56 patients were treated surgically and 33 received radiation therapy. According to Ballantyne's clinical staging system, 88% of the patients presented with stage I (local) disease. Classification by the AJCC staging classified yielded 27% of the patients with T1, 33% with T2, 21% with T3, and 19% with T4. T-stage and the degree of tumor pigmentation were associated with a worse survival (P = .0096 and P = .018, respectively), while pseudopapillary architecture was associated with a higher locoregional failure (P = .0144). Postoperative radiation therapy improved locoregional control when a total dose greater than 54 Gy was used (P = .0215), but did not affect overall survival. Tumor stage according to sinonasal AJCC staging system is an effective outcome predictor and should be the staging system of choice. Postoperative radiation therapy improves locoregional control when a higher dose and standard fractionations are used. Histological features such as pigmentation and pseudopapillary architecture are associated with worse outcome. (c) 2010 American Cancer Society.

  18. [Melanoma and Human Papillomaviruses: Is There an Outlook for Study?].

    Science.gov (United States)

    Volgareva, G M; Mikhaylova, I N; Golovina, D A

    2016-01-01

    Melanoma is one of the most aggressive human malignant tumors. Its incidence and mortality are growing steadily. Ultraviolet irradiation is the main risk factor for melanoma involved in melanomagenesis. The probability of viral etiology of melanoma has been discussed. Human papillomaviruses (HPV) have been mentioned among candidates for its etiologic agents because some HPV types are the powerful carcinogens causing cervical cancer and other cancers. The review analyses the literature data on the association of melanoma with HPV Several groupsfound HPVin skin melanomas as well as in mucosa; viruses of high oncogenic risk were detected in some cases. For some organs the etiological role of high-risk HPV as inducers of invasive carcinomas is confirmed. These organs require special mention: cervix uteri, vulva, vagina, penis, anal region, and oral cavity. However in the majority of the studies in which viral DNA-positive melanomas were found, testing for viral genome expression was not done while this is the fact of primary importance. HPVare found in normal skin and mucous membranes thus creating justifiable threat of tumor specimen contamination with viral DNA in vivo. There are limited data on aggravation of the disease prognosis in papillomavirus-positive melanomas. However, any systematic observation of a sizeable patient group distinguished by that tumor type has not been performed yet. Viral E6 and E7 oncogenes of high-risk papillomaviruses were shown to be able to transform normal human melanocytes in vitro experiments. Thus, we can assume the presence of the association of melanoma with oncogenic HPV. The clinical significance of this problem is indisputable under the conditions of the steady increase in melanoma incidence and mortality rates in Russia and abroad. The problem requires further study.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2007-03-15

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

  20. 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...... patients received a total of 161 vaccinations. Treatment was well tolerated and quality of life measurements did not vary much across time. One patient experienced partial response [5%; 95% confidence interval (CI), 1-24%] and seven achieved stable disease (35%; 95% CI, 18-57%), one of whom also achieved...

  1. FDG PET scans as evaluation of clinical response to dendritic cell vaccination in patients with malignant melanoma

    DEFF Research Database (Denmark)

    Engell-Noerregaard, Lotte; Hendel, Helle W; Johannesen, Helle H

    2013-01-01

    . In this study it is investigated whether FDG-PET might add information on the efficacy of immune therapy. MATERIALS AND METHODS: In a retrospective analysis data from patients with advanced progressive melanoma, treated with DC vaccinations and evaluated by PET/CT scans at baseline as well as after 6...... vaccinations were analysed. If a patient achieved stable disease according to RECIST, additional vaccinations were given. The PET scans were evaluated according to EORTC guidelines. RESULTS: PET/CT scans from 13 patients were evaluated. According to RECIST 3 patients achieved stable disease and 10 patients...... PET scans to the CT evaluation of patients treated with DC vaccines, a more detailed picture of the single lesions was found. This seems to improve the clinical evaluation of the treatment. The lack of correlation between the PET and CT scans suggests that some of the increases in target lesions seen...

  2. The Danish Melanoma Database

    Directory of Open Access Journals (Sweden)

    Hölmich Lr

    2016-10-01

    Full Text Available Lisbet Rosenkrantz Hölmich,1 Siri Klausen,2 Eva Spaun,3 Grethe Schmidt,4 Dorte Gad,5 Inge Marie Svane,6,7 Henrik Schmidt,8 Henrik Frank Lorentzen,9 Else Helene Ibfelt10 1Department of Plastic Surgery, 2Department of Pathology, Herlev-Gentofte Hospital, University of Copenhagen, Herlev, 3Institute of Pathology, Aarhus University Hospital, Aarhus, 4Department of Plastic and Reconstructive Surgery, Breast Surgery and Burns, Rigshospitalet – Glostrup, University of Copenhagen, Copenhagen, 5Department of Plastic Surgery, Odense University Hospital, Odense, 6Center for Cancer Immune Therapy, Department of Hematology, 7Department of Oncology, Herlev-Gentofte Hospital, University of Copenhagen, Herlev, 8Department of Oncology, 9Department of Dermatology, Aarhus University Hospital, Aarhus, 10Registry Support Centre (East – Epidemiology and Biostatistics, Research Centre for Prevention and Health, Glostrup – Rigshospitalet, University of Copenhagen, Glostrup, Denmark Aim of database: The aim of the database is to monitor and improve the treatment and survival of melanoma patients.Study population: All Danish patients with cutaneous melanoma and in situ melanomas must be registered in the Danish Melanoma Database (DMD. In 2014, 2,525 patients with invasive melanoma and 780 with in situ tumors were registered. The coverage is currently 93% compared with the Danish Pathology Register.Main variables: The main variables include demographic, clinical, and pathological characteristics, including Breslow’s tumor thickness, ± ulceration, mitoses, and tumor–node–metastasis stage. Information about the date of diagnosis, treatment, type of surgery, including safety margins, results of lymphoscintigraphy in patients for whom this was indicated (tumors > T1a, results of sentinel node biopsy, pathological evaluation hereof, and follow-up information, including recurrence, nature, and treatment hereof is registered. In case of death, the cause and date

  3. Malignant Melanoma in African-Americans: A Population-Based Clinical Outcomes Study Involving 1106 African-American Patients from the Surveillance, Epidemiology, and End Result (SEER) Database (1988-2011).

    Science.gov (United States)

    Mahendraraj, Krishnaraj; Sidhu, Komal; Lau, Christine S M; McRoy, Georgia J; Chamberlain, Ronald S; Smith, Franz O

    2017-04-01

    Malignant melanoma accounts for 75% of all skin cancer deaths and is potentially curable if identified early. Although melanoma is rare in African-Americans (AA), it is associated with a worse prognosis than in Caucasians. This study examines the demographic, pathologic, and clinical factors impacting AA melanoma outcomes.Data for 1106 AA and 212,721 Caucasian cutaneous melanoma patients were abstracted from the Surveillance, Epidemiology, and End Result (SEER) database (1988-2011). Data were grouped on the basis of histological subtypes: "Superficial Spreading" (SS), "Nodular" (NM), "Lentigo Maligna" (LM), "Acral Lentiginous" (AL), and "Not otherwise specified" (NOS).Cutaneous malignant melanoma occurs most commonly in the sixth and seventh decade of life. Caucasian patients presented most commonly with trunk melanomas (34.5%), while lower extremity melanomas were more common in AAs (56.1%), P melanoma on the lower extremities, and with deeper and more advanced stage lesions. AAs have higher cancer-specific mortality for NM and LM than Caucasians. Melanoma education for AA patients and health care providers is needed to increase disease awareness, facilitate early detection, and promote access to effective treatment.

  4. BIOFILM AND OUR CLINICAL EXPERIENCE.

    Science.gov (United States)

    Rucigaj, Tanja Planinsek

    2016-03-01

    Bacteria organized in biofilms are insensitive to the usual treatment with dressings or antibiotics. Most successful is surgical debridement to remove their colonies, but this option may not be possible in all environments. Dressings with silver and other antiseptics are often the only tools available to nurses at patient homes or to dermatologists at outpatient clinics. In our clinical studies conducted several years ago, we demonstrated that dressings with antiseptics were an effective tool in daily clinical practice to remove bacteria/biofilms from chronic wounds.

  5. 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

  6. 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

  7. Histopathological findings concerning ocular melanomas.

    Science.gov (United States)

    Costache, Mariana; Pătraşcu, Oana Maria; Dumitru, Adrian; Costache, Diana; Voinea, Liliana Mary; Simionescu, Olga; Sajin, Maria

    2014-01-01

    Ocular melanoma is rare in clinical practice. In this study, we present three cases of ocular melanoma surgically removed in the Department of Ophthalmology of the Emergency University Hospital of Bucharest, Romania, and diagnosed in the Department of Pathology of the same hospital using conventional histopathological techniques and immunohistochemical tests.

  8. Radioimmunoscintigraphy in ocular melanoma

    International Nuclear Information System (INIS)

    Kovacs, J.; Chatterton, B.E.; Muecke, J.; Penglis, S.

    1999-01-01

    Full text: Malignant choroidal melanoma is one of the most common primary intraocular neoplasms. Despite significant advances in indirect ophthalmology, ultrasound, computed tomography (CT), magnetic resonance imaging (MRI) and fluoroescein angiography, choroidal melanomas may be difficult to distinguish from other malignant and non-malignant eye lesions. Radioimmunoscintigraphy (RIS) with 99 Tc m -labelled monoclonal antibody F(ab')2 fragments was performed on three patients (2 females, 1 male) who were suspected of having a choroidal melanoma. Patients were injected with 240-420 MBq Technemab-K-1 and scanned 6 and 22 h post-injection. Both planar and single photon emission tomographic (SPET) imaging were performed. RIS was faintly positive in one patient in whom the diagnosis of choroidal melanoma was confirmed by enucleation of the left eye. In the other two patients, immunoscintigraphy was negative. One patient had a benign choroidal haemangioma and the other an amelanotic melanoma. This was confirmed on clinical follow-up. These preliminary results indicate that this procedure may have utility for choroidal melanoma

  9. Thin melanoma.

    Science.gov (United States)

    Elder, David E

    2011-03-01

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

  10. Ubiquitination in melanoma pathogenesis and treatment.

    Science.gov (United States)

    Ma, Jinyuan; Guo, Weinan; Li, Chunying

    2017-06-01

    Melanoma is one of the most aggressive skin cancers with fiercely increasing incidence and mortality. Since the progressive understanding of the mutational landscape and immunologic pathogenic factors in melanoma, the targeted therapy and immunotherapy have been recently established and gained unprecedented improvements for melanoma treatment. However, the prognosis of melanoma patients remains unoptimistic mainly due to the resistance and nonresponse to current available drugs. Ubiquitination is a posttranslational modification which plays crucial roles in diverse cellular biological activities and participates in the pathogenesis of various cancers, including melanoma. Through the regulation of multiple tumor promoters and suppressors, ubiquitination is emerging as the key contributor and therefore a potential therapeutic target for melanoma. Herein, we summarize the current understanding of ubiquitination in melanoma, from mechanistic insights to clinical progress, and discuss the prospect of ubiquitination modification in melanoma treatment. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  11. 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.

  12. Ocular Melanoma

    Science.gov (United States)

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

  13. Malignant melanoma

    NARCIS (Netherlands)

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

    2003-01-01

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

  14. [CROATIAN SOCIETY FOR MEDICAL ONCOLOGY CLINICAL GUIDELINES FOR DIAGNOSIS, TREATMENT AND FOLLOW-UP OF PATIENTS WITH MELANOMA].

    Science.gov (United States)

    Herceg, Davorin; Buzina, Daska Stulhofer; Ceović, Romana; Dotlić, Snjezana; Ilić, Ivana; Orehovec, Sanda Smuđ; Herceg, Gordana Horvatić; Mijatović, Davor; Separović, Robert; Silovski, Tajana; Vrbanec, Damir

    2016-01-01

    Melanoma in the Western world has an increasing incidence. One of the most important factor for the increase in incidence is sporadic, uncontrolled exposure to the sun. The basis for the treatment of primary melanoma is surgical treatment. Treatment of metastatic disease of melanoma in recent years experienced significant changes. BRAF and MEK inhibitors, immunotherapy with programmed cell-death immune checkpoint inhibitors (anti-PD-1-antibodies) are new options for the treatment of metastatic disease. A mulitidisiplinary team of Croatian Society for Medical Oncology provides recommendations for diagnosis, treatment and follow-up of melanoma primarily driven to the discovery of new drugs and therapeutic options, that change the prognosis of patients with metastatic melanoma.

  15. 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

  16. [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

  17. Pediatric Melanoma and Drug Development

    Directory of Open Access Journals (Sweden)

    Klaus Rose

    2018-03-01

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

  18. Oral mucosal melanoma: conservative treatment including laser surgery.

    Science.gov (United States)

    Luna-Ortiz, Kuauhyama; Campos-Ramos, Eunice; Pasche, Philippe; Mosqueda-Taylor, Adalberto

    2011-05-01

    To discuss the convenience of laser surgery as optimal treatment for melanoma of the oral mucosa. A retrospective evaluation of four patients with primary oral melanomas treated at a single Cancer Institution in Mexico City. Two patients were treated with resection of the melanoma with CO2 laser together with extraction of the involved dental organs and curettage of the alveolar walls. These two cases had melanoma in situ with multiple isolated foci. The third patient had a lesion with vertical growth, who was submitted to partial maxillectomy along with selective dissection of bilateral neck levels I-V with a negative report and the fourth patient had a history of oral nodular melanoma and presented with lymph node metastasis. According to follow-up status, there was no distant metastasis in any of the patients reported here. In our experience, conservative management with CO2 laser is adequate for melanomas of the oral mucosa with extraction of the dental organs and curettage of the alveoli to achieve complete surgical resection microscopically without sacrifice of the quality of life. Management of the neck is controversial. We recommend selective therapeutic resection of the neck only if it is found to be clinically positive. Elective dissection has not shown to have an impact in overall survival.

  19. Human Papillomaviruses and Non-Melanoma Skin Cancer: Basic Virology and Clinical Manifestations

    Directory of Open Access Journals (Sweden)

    Ingo Nindl

    2007-01-01

    Full Text Available Human papillomaviruses (HPV infect cutaneous and mucosal epithelia and induce benign and malignant lesions. Non-melanoma skin cancer (NMSC, encompassing basal cell carcinoma and squamous cell carcinoma (SCC, is the most frequent cancer in the Caucasian population, and the incidence has increased dramatically worldwide. Ultraviolet (UV radiation is a major risk factor for NMSC, and cutaneous HPV is also considered to play an active role during the pathogenesis of these cancers. The first evidence for the involvement of HPV in NMSC was reported in patients with Epidermodysplasia verruciformis (EV. HPV types detected in skin tumours of these patients are referred to as EV/cutaneous HPV types belonging to the beta- and gamma-papillomaviruses (PV. Epidemiological studies have shown a higher risk of several EV/cutaneous HPV types for NMSC. Furthermore, in vitro and animal models show transforming properties of some PV types. The anti-apoptotic activities, and the delay of DNA repair mechanism caused by some EV/cutaneous HPV E6 proteins in response to UV-induced mutations, may lead to the persistence of DNA-damaged keratinocytes. Thus, specific EV/cutaneous HPV types as co-factors in association with UV-radiation and the immune system seem to be involved in the early pathogenesis of cutaneous SCC.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2007-12-15

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

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

    International Nuclear Information System (INIS)

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

    2007-01-01

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

  2. The initial experience of electronic brachytherapy for the treatment of non-melanoma skin cancer

    Directory of Open Access Journals (Sweden)

    Bhatnagar Ajay

    2010-09-01

    Full Text Available Abstract Background Millions of people are diagnosed with non-melanoma skin cancers (NMSC worldwide each year. While surgical approaches are the standard treatment, some patients are appropriate candidates for radiation therapy for NMSC. High dose rate (HDR brachytherapy using surface applicators has shown efficacy in the treatment of NMSC and shortens the radiation treatment schedule by using a condensed hypofractionated approach. An electronic brachytherapy (EBT system permits treatment of NMSC without the use of a radioactive isotope. Methods Data were collected retrospectively from patients treated from July 2009 through March 2010. Pre-treatment biopsy was performed to confirm a malignant cutaneous diagnosis. A CT scan was performed to assess lesion depth for treatment planning, and an appropriate size of surface applicator was selected to provide an acceptable margin. An HDR EBT system delivered a dose of 40.0 Gy in eight fractions twice weekly with 48 hours between fractions, prescribed to a depth of 3-7 mm. Treatment feasibility, acute safety, efficacy outcomes, and cosmetic results were assessed. Results Thirty-seven patients (mean age 72.5 years with 44 cutaneous malignancies were treated. Of 44 lesions treated, 39 (89% were T1, 1 (2% Tis, 1 (2% T2, and 3 (7% lesions were recurrent. Lesion locations included the nose for 16 lesions (36.4%, ear 5 (11%, scalp 5 (11%, face 14 (32%, and an extremity for 4 (9%. Median follow-up was 4.1 months. No severe toxicities occurred. Cosmesis ratings were good to excellent for 100% of the lesions at follow-up. Conclusions The early outcomes of EBT for the treatment of NMSC appear to show acceptable acute safety and favorable cosmetic outcomes. Using a hypofractionated approach, EBT provides a convenient treatment schedule.

  3. Biologic and clinical characteristics of adolescent and young adult cancers: Acute lymphoblastic leukemia, colorectal cancer, breast cancer, melanoma, and sarcoma.

    Science.gov (United States)

    Tricoli, James V; Blair, Donald G; Anders, Carey K; Bleyer, W Archie; Boardman, Lisa A; Khan, Javed; Kummar, Shivaani; Hayes-Lattin, Brandon; Hunger, Stephen P; Merchant, Melinda; Seibel, Nita L; Thurin, Magdalena; Willman, Cheryl L

    2016-04-01

    Adolescent and young adult (AYA) patients with cancer have not attained the same improvements in overall survival as either younger children or older adults. One possible reason for this disparity may be that the AYA cancers exhibit unique biologic characteristics, resulting in differences in clinical and treatment resistance behaviors. This report from the biologic component of the jointly sponsored National Cancer Institute and LiveStrong Foundation workshop entitled "Next Steps in Adolescent and Young Adult Oncology" summarizes the current status of biologic and translational research progress for 5 AYA cancers; colorectal cancer breast cancer, acute lymphoblastic leukemia, melanoma, and sarcoma. Conclusions from this meeting included the need for basic biologic, genomic, and model development for AYA cancers as well as translational research studies to elucidate any fundamental differences between pediatric, AYA, and adult cancers. The biologic questions for future research are whether there are mutational or signaling pathway differences (for example, between adult and AYA colorectal cancer) that can be clinically exploited to develop novel therapies for treating AYA cancers and to develop companion diagnostics. © 2016 American Cancer Society.

  4. 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.

  5. Clinical psychologists' experiences of NHS organisational change

    OpenAIRE

    Colley, Rich; Eccles, Fiona; Hutton, Cheryl

    2015-01-01

    Organisational-change experiences of eight clinical psychologists working in the NHS were captured. Three themes revealed the challenges they experienced and how their knowledge and skills have helped them understand, cope with, and respond to change.

  6. Targeted Therapy for Melanoma

    International Nuclear Information System (INIS)

    Quinn, Thomas; Moore, Herbert

    2016-01-01

    The research project, entitled ''Targeted Therapy for Melanoma,'' was focused on investigating the use of kidney protection measures to lower the non-specific kidney uptake of the radiolabeled Pb-DOTA-ReCCMSH peptide. Previous published work demonstrated that the kidney exhibited the highest non-target tissue uptake of the 212Pb/203 Pb radiolabeled melanoma targeting peptide DOTA-ReCCMSH. The radiolabeled alpha-melanocyte stimulating hormone (α-MSH) peptide analog DOTA-Re(Arg 11 )CCMSH, which binds the melanocortin-1 receptor over-expressed on melanoma tumor cells, has shown promise as a PRRT agent in pre-clinical studies. High tumor uptake of 212 Pb labeled DOTA-Re(Arg 11 )CCMSH resulted in tumor reduction or eradication in melanoma therapy studies. Of particular note was the 20-50% cure rate observed when melanoma mice were treated with alpha particle emitter 212 Pb. However, as with most PRRT agents, high radiation doses to the kidneys where observed. To optimize tumor treatment efficacy and reduce nephrotoxicity, the tumor to kidney uptake ratio must be improved. Strategies to reduce kidney retention of the radiolabeled peptide, while not effecting tumor uptake and retention, can be broken into several categories including modification of the targeting peptide sequence and reducing proximal tubule reabsorption.

  7. 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.

  8. The Immunology of Melanoma.

    Science.gov (United States)

    Ko, Jennifer S

    2017-09-01

    The relatively high DNA mutational burden in melanoma allows for the creation of potentially "foreign," immune-stimulating neoantigens, and leads to its exceptional immunogenicity. Brisk tumor-infiltrating lymphocytes, a marker of immune editing, confer improved overall survival in melanoma, possibly due to reduced sentinel lymph node spread. Meanwhile, T-cell-stimulating drugs, so-called T-cell checkpoint inhibitors, which reverse peripheral tolerance-dependent tumor escape, have demonstrated unparalleled clinical success in metastatic melanoma. Markers to predict response to immunotherapy are currently imperfect, and the subject of intense research, which will guide the future of ancillary pathologic testing in this setting. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Case studies of skin melanoma

    Directory of Open Access Journals (Sweden)

    A. V. Kozlova

    2015-01-01

    Full Text Available Skin melanoma is a malignant tumor originating in the cells of the melanocytic system, which is characterized by an aggressive clinical course, significant metastatic potential and unfavorable prognosis. These features of the tumor stipulate the need to improve measures to optimize early diagnosis of tumors. The article presents cases of pigmented skin melanoma to demonstrate the variability of clinical manifestations of this tumor requiring dermatologist skills in the differential diagnostics of neoplasms.

  10. 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.

    2011-01-01

    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. PMID:21460252

  11. Oral mucosal melanoma: A case report

    Directory of Open Access Journals (Sweden)

    Ramlal Gantala

    2017-01-01

    Full Text Available Malignant melanoma is most deadly of all primary skin cancers. Over 90% of melanomas occur on the skin. Half of such melanomas occur in the oral cavity, followed by nasal cavity (44% and sinuses (8%. In the oral cavity, the most frequent sites of occurrence are hard palate and maxillary gingiva. Mucosal melanomas represent a diagnostic challenge than the more common cutaneous melanomas because oral melanomas demonstrate significant heterogeneity in morphological features, developmental process, and biological behaviour. This case report highlights an exophytic, lobulated oral malignant melanoma involving maxillary gingiva and is presented to reemphasize the fact that any pigmented lesion in the oral cavity should be examined with suspicion; proper investigation should be carried out to rule out any untoward experiences later.

  12. A unifying approach to the clinical diagnosis of melanoma including “D” for “Dark” in the ABCDE criteria

    Science.gov (United States)

    Goldsmith, Stuart M.

    2014-01-01

    Current clinical approaches to melanoma diagnosis have not been associated with a decrease in mortality from this cancer. The components of the new approach presented are, first, a screening examination to look for any lesion that stands out because of being dark, different, or changing; second, when a single lesion is recognized to be of concern for any reason, that lesion is then evaluated in more detail utilizing the ABCDE criteria, with the “D” signifying “Dark” and not “6 mm Diameter” in this mnemonic; and, third, additional discussion of the “ugly duckling” sign and of the recognition of nodular melanomas. Since the Georgia Society of Dermatology and Dermatologic Surgery was the first state or national society to endorse this approach, I refer to it as the Georgia approach. PMID:25396093

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

    Science.gov (United States)

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

    2014-01-01

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

  14. Analysis of the Clinical and Histopathological Patterns of 100 Consecutive Cases of Primary Cutaneous Melanoma and Correlation with Staging

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    Kyung Wook Nam

    2015-11-01

    Full Text Available BackgroundThis study analyzed 100 consecutive patients with primary cutaneous melanoma over the course of 13 years to determine whether epidemiological differences correspond to different stages of the disease. We also investigated whether epidemiological characteristics affected the survival rate. Our results were compared with those of selected descriptive studies of melanoma in other East Asian populations, in order to determine whether cutaneous melanoma patterns are similar in East Asian populations.MethodsThe patients' medical records were reviewed retrospectively, and we analyzed the relationship of epidemiological characteristics to staging and survival rate. Additionally, papers from Hong Kong and Japan describing these phenomena in East Asian populations were subjected to a statistical comparison.ResultsThe ratio of males to females was 1:1.8, and the foot was the most frequent tumor site (49%. Acral lentiginous melanoma occurred most frequently (55%. Nodular melanoma was associated with a higher stage. Stage III-IV tumors with Clark levels of IV-V were significantly associated with a low survival rate. A statistical analysis of comparable papers reported in Hong Kong and Japan showed similar results with regard to age, tumor location, and histopathological subtypes.ConclusionsThis study provides the first full epidemiological description of 100 consecutive cases of primary cutaneous melanoma in Korea, with results similar to those observed in other East Asian populations. Corresponding to previous findings, nodular melanoma tended to occur at a higher stage than other types, and tumors with high Clark levels and high stages showed a lower survival rate.

  15. 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.

  16. Effectiveness of Integrated Simulation and Clinical Experiences Compared to Traditional Clinical Experiences for Nursing Students.

    Science.gov (United States)

    Curl, Eileen D; Smith, Sheila; Ann Chisholm, Le; McGee, Leah Anne; Das, Kumar

    2016-01-01

    The focus of this research study was the evaluation of the effectiveness of using high-fidelity simulations to replace 50 percent of traditional clinical experiences in obstetrics, pediatrics, critical care, and mental health nursing. Increasing student admissions to nursing programs require additional clinical learning opportunities to accommodate extra students. Three schools with associate degree nursing programs partnered to identify, implement, and evaluate a creative solution to this dilemma. The resulting quasi-experimental study investigated if substituting half of the conventional clinical experiences with simulations was as effective as traditional clinical activities in obstetrics, pediatrics, mental health, and critical care. One hour of simulation counted for two hours of clinical time. RESULTS Findings indicated combining simulations with conventional clinical experiences resulted in significantly higher scores on the pre-graduation exit exam than traditional clinical experiences alone. Findings have implications for articulation and basic students in associate degree nursing programs.

  17. MC1R variation and melanoma risk in relation to host/clinical and environmental factors in CDKN2A positive and negative melanoma patients.

    Science.gov (United States)

    Ghiorzo, Paola; Bonelli, Luigina; Pastorino, Lorenza; Bruno, William; Barile, Monica; Andreotti, Virginia; Nasti, Sabina; Battistuzzi, Linda; Grosso, Marco; Bianchi-Scarrà, Giovanna; Queirolo, Paola

    2012-09-01

    Host, environmental and genetic factors differently modulate cutaneous melanoma (CM) risk across populations. Currently, the main genetic risk determinants are germline mutations in the major known high-risk susceptibility genes, CDKN2A and CDK4, and variants of the low-risk gene MC1R, which is key in the pigmentation process. This case-control study aimed at investigating the influence of the main host and environmental risk factors and of MC1R variation on CM risk in 390 CDKN2A-negative and 49 CDKN2A-positive Italian individuals. Multivariate analysis showed that MC1R variation, number of nevi and childhood sunburns doubled CM risk in CDKN2A-negative individuals. In CDKN2A-positive individuals, family history of CM and presence of atypical nevi, rather than MC1R status, modified risk (20.75- and 2.83-fold, respectively). Occupational sun exposure increased CM risk (three to sixfold) in both CDKN2A-negative and CDKN2A-positive individuals, reflecting the occupational habits of the Ligurian population and the geographical position of Liguria. © 2012 John Wiley & Sons A/S.

  18. 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.

  19. 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.

  20. The clinical experiences of dyslexic healthcare students

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    Murphy, Fred [Directorate of Radiography, School of Health Care Professions, University of Salford, Allerton Building, Salford, Greater Manchester M6 6PU (United Kingdom)], E-mail: f.j.murphy@salford.ac.uk

    2009-11-15

    This paper reflects on the experiences of healthcare students with dyslexia in order to raise awareness of the potential challenges for dyslexic student radiographers and their clinical educators. With widening participation policies it is likely that the number of student radiographers with specific learning difficulties such as dyslexia will continue to increase. A review of the literature associated with dyslexia in healthcare education was performed in order to provide an overview of the current position. Although Higher Education Institutions (HEIs) have embraced the support and learning opportunities for dyslexic students at university, evidence would suggest that this is not reflected in the clinical departments. The current literature strongly suggests that since the risk of errors with clinical information is far more significant within the clinical placement, there is an immediate requirement for greater understanding, robust support and risk assessment systems. This review considers the problems experienced by dyslexic students, coping strategies they employ and the possible implications for clinical radiography education.

  1. The clinical experiences of dyslexic healthcare students

    International Nuclear Information System (INIS)

    Murphy, Fred

    2009-01-01

    This paper reflects on the experiences of healthcare students with dyslexia in order to raise awareness of the potential challenges for dyslexic student radiographers and their clinical educators. With widening participation policies it is likely that the number of student radiographers with specific learning difficulties such as dyslexia will continue to increase. A review of the literature associated with dyslexia in healthcare education was performed in order to provide an overview of the current position. Although Higher Education Institutions (HEIs) have embraced the support and learning opportunities for dyslexic students at university, evidence would suggest that this is not reflected in the clinical departments. The current literature strongly suggests that since the risk of errors with clinical information is far more significant within the clinical placement, there is an immediate requirement for greater understanding, robust support and risk assessment systems. This review considers the problems experienced by dyslexic students, coping strategies they employ and the possible implications for clinical radiography education.

  2. Physiotherapy clinical educators' perceptions and experiences of clinical prediction rules.

    Science.gov (United States)

    Knox, Grahame M; Snodgrass, Suzanne J; Rivett, Darren A

    2015-12-01

    Clinical prediction rules (CPRs) are widely used in medicine, but their application to physiotherapy practice is more recent and less widespread, and their implementation in physiotherapy clinical education has not been investigated. This study aimed to determine the experiences and perceptions of physiotherapy clinical educators regarding CPRs, and whether they are teaching CPRs to students on clinical placement. Cross-sectional observational survey using a modified Dillman method. Clinical educators (n=211, response rate 81%) supervising physiotherapy students from 10 universities across 5 states and territories in Australia. Half (48%) of respondents had never heard of CPRs, and a further 25% had never used CPRs. Only 27% reported using CPRs, and of these half (51%) were rarely if ever teaching CPRs to students in the clinical setting. However most respondents (81%) believed CPRs assisted in the development of clinical reasoning skills and few (9%) were opposed to teaching CPRs to students. Users of CPRs were more likely to be male (pphysiotherapy (pphysiotherapy clinical practice. Copyright © 2015 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

  3. Nursing students’ experiences of clinical education setting

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    Rahnama M

    2015-08-01

    Full Text Available Background and Objective: Appropriate clinical environment has an important role in preparing students to use learned knowledge in practice through providing learning opportunities. Since the students’ experiences in the clinical setting affect on quality of their learning, the current study aimed to explain the experiences of nursing students concerning clinical education setting. Materials and Method: The current study was conducted based on conventional content analysis. Sampling was done purposively and the participants were 13 last year nursing students in Zabol Nursing and Midwifery School in 2013-2014. Data collection was done through in-depth semi-structured interviews. Data analysis was conducted through qualitative content analysis approach. Results: Based on the results, five major categories including threats, vision, dual forces, mindset and students’ action to clinical education and also10 subcategorie were identified. Conclusion: Since the formation of students’ experiences in these environments is one of the predictive factors in achieving their learning and in facilitating the professionalization process, thus the attention of managers in clinical settings is very important for decreasing the threats and concerns for students. In this way, the marred prospects of profession can be recovered through the meeting students’ expectations, attractiveness of the profession can be increased and the positive belief, actions and feelings can be created in students.

  4. Epidemiologic study of clinically amyopathic dermatomyositis and anti-melanoma differentiation-associated gene 5 antibodies in central Japan

    Science.gov (United States)

    2011-01-01

    Introduction Several reports have found the onset or activity of inflammatory myopathies to show spatial clustering and seasonal association. We recently detected autoantibodies against melanoma differentiation-associated gene 5 (MDA-5) in more than 20% of patients with dermatomyositis. Anti-MDA-5 antibodies were associated with the presence of rapidly progressive interstitial lung disease in clinically amyopathic dermatomyositis (CADM). The present study aims to assess the growing prevalence of CADM and the geographical incidence of anti-MDA-5-positive patients. Methods We reviewed medical charts and examined the presence of anti-MDA-5 antibodies in 95 patients, including 36 CADM patients. Sera were obtained from 1994 through 2011. Statistical analyses were performed to assess whether CADM development and the presence of anti-MDA-5 antibodies were associated with various parameters, including age at disease onset, season of onset, annual positivity, and population of resident city. Results Tertiles based on the year when the sera were collected showed increasing tendencies of CADM and anti-MDA-5-positive patients among all of the dermatomyositis patients. From 1994 to 2010, the relative prevalence of CADM and anti-MDA-5 antibody-positive patients significantly increased. Interestingly, the presence of anti-MDA-5 antibodies in 26 patients was inversely associated with the population of their city of residence. Conclusions This is the first study to examine the distribution of anti-MDA-5-positive dermatomyositis phenotypes in Japan. Regional differences in the incidences of these phenotypes would suggest that environmental factors contribute to the production of antibodies against MDA-5, which triggers innate antiviral responses. PMID:22192091

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

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    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

  6. Planning a study abroad clinical experience.

    Science.gov (United States)

    Wright, Dolores J

    2010-05-01

    Not only is globalization expanding areas of human activity, it is also influencing the variety of educational offerings in universities. Therefore, globalization must be considered by nurse educators as they reevaluate ways of preparing nursing students to meet the health care needs of populations they currently serve and will care for in the future. Study abroad programs have been encouraged to be part of the college experience in the United States for more than 30 years; however, these programs have been relatively lacking in nursing education. Most of the study abroad programs described in the nursing literature are research-based or first-person accounts of an experience and provide little information about planning a study abroad program. This article describes a study abroad learning experience for senior nursing students and discusses the issues such as student selection, student safety, and available clinical experiences that need to be considered before undertaking such an endeavor.

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

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    Rodrigo Souza Dias

    2007-04-01

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

  8. Malignant Melanoma of the Foot

    Science.gov (United States)

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

  9. 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.

  10. 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.

  11. First year clinical tutorials: students' learning experience.

    Science.gov (United States)

    Burgess, Annette; Oates, Kim; Goulston, Kerry; Mellis, Craig

    2014-01-01

    Bedside teaching lies at the heart of medical education. The learning environment afforded to students during clinical tutorials contributes substantially to their knowledge, thinking, and learning. Situated cognition theory posits that the depth and breadth of the students' learning experience is dependent upon the attitude of the clinical teacher, the structure of the tutorial, and the understanding of tutorial and learning objectives. This theory provides a useful framework to conceptualize how students' experience within their clinical tutorials impacts their knowledge, thinking, and learning. The study was conducted with one cohort (n=301) of students who had completed year 1 of the medical program at Sydney Medical School in 2013. All students were asked to complete a three-part questionnaire regarding their perceptions of their clinical tutor's attributes, the consistency of the tutor, and the best features of the tutorials and need for improvement. Both quantitative and qualitative data were collected and analyzed using descriptive statistics. The response rate to the questionnaire was 88% (265/301). Students perceived that their tutors displayed good communication skills and enthusiasm, encouraged their learning, and were empathetic toward patients. Fifty-two percent of students reported having the same communications tutor for the entire year, and 28% reported having the same physical examination tutor for the entire year. Students would like increased patient contact, greater structure within their tutorials, and greater alignment of teaching with the curriculum. Situated cognition theory provides a valuable lens to view students' experience of learning within the clinical environment. Our findings demonstrate students' appreciation of clinical tutors as role models, the need for consistency in feedback, the importance of structure within tutorials, and the need for tutors to have an understanding of the curriculum and learning objectives for each

  12. First year clinical tutorials: students’ learning experience

    Science.gov (United States)

    Burgess, Annette; Oates, Kim; Goulston, Kerry; Mellis, Craig

    2014-01-01

    Background Bedside teaching lies at the heart of medical education. The learning environment afforded to students during clinical tutorials contributes substantially to their knowledge, thinking, and learning. Situated cognition theory posits that the depth and breadth of the students’ learning experience is dependent upon the attitude of the clinical teacher, the structure of the tutorial, and the understanding of tutorial and learning objectives. This theory provides a useful framework to conceptualize how students’ experience within their clinical tutorials impacts their knowledge, thinking, and learning. Methods The study was conducted with one cohort (n=301) of students who had completed year 1 of the medical program at Sydney Medical School in 2013. All students were asked to complete a three-part questionnaire regarding their perceptions of their clinical tutor’s attributes, the consistency of the tutor, and the best features of the tutorials and need for improvement. Both quantitative and qualitative data were collected and analyzed using descriptive statistics. Results The response rate to the questionnaire was 88% (265/301). Students perceived that their tutors displayed good communication skills and enthusiasm, encouraged their learning, and were empathetic toward patients. Fifty-two percent of students reported having the same communications tutor for the entire year, and 28% reported having the same physical examination tutor for the entire year. Students would like increased patient contact, greater structure within their tutorials, and greater alignment of teaching with the curriculum. Conclusion Situated cognition theory provides a valuable lens to view students’ experience of learning within the clinical environment. Our findings demonstrate students’ appreciation of clinical tutors as role models, the need for consistency in feedback, the importance of structure within tutorials, and the need for tutors to have an understanding of the

  13. The relationship between occupational sun exposure and non-melanoma skin cancer: clinical basics, epidemiology, occupational disease evaluation, and prevention.

    Science.gov (United States)

    Fartasch, Manigé; Diepgen, Thomas Ludwig; Schmitt, Jochen; Drexler, Hans

    2012-10-01

    The cumulative effect of solar ultraviolet (UV) radiation is responsible for the worldwide increase in non-melanoma skin cancer, a category that includes squamous cell carcinoma and its precursors (the actinic keratoses) as well as basal-cell carcinoma. Non-melanoma skin cancer is the most common type of cancer in areas of the world with a light-skinned population. The occupational exposure to UV radiation is high in many outdoor occupations; recent studies suggest that persons working in such occupations are more likely to develop non-melanoma skin cancer. On the basis of a selective review of the literature, we present the current state of knowledge about occupational and non-occupational UV exposure and the findings of meta-analyses on the association of outdoor activity with non-melanoma skin cancer. We also give an overview of the current recommendations for prevention and for medicolegal assessment. Recent meta-analyses have consistently documented a significantly higher risk of squamous cell carcinoma of the skin among persons who work outdoors (odds ratio [OR] 1.77, 95% confidence interval [CI] 1.40-2.22, pmelanoma skin cancer in persons with high occupational exposure to UV radiation should be reported as an occupational disease under § 9, paragraph 2 of the Seventh Book of the German Social Code (Sozialgesetzbuch, SGB VII). Preventive measures are urgently needed for persons with high occupational exposure to UV radiation.

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

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    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.

  15. 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

  16. Melanoma and non-melanoma skin cancers in hairy cell leukaemia: a Surveillance, Epidemiology and End Results population analysis and the 30-year experience at Memorial Sloan Kettering Cancer Center.

    Science.gov (United States)

    Watts, Justin M; Kishtagari, Ashwin; Hsu, Meier; Lacouture, Mario E; Postow, Michael A; Park, Jae H; Stein, Eytan M; Teruya-Feldstein, Julie; Abdel-Wahab, Omar; Devlin, Sean M; Tallman, Martin S

    2015-10-01

    Few studies have examined melanoma and non-melanoma skin cancer (NMSC) incidence rates after a diagnosis of hairy cell leukaemia (HCL). We assessed 267 HCL patients treated at Memorial Sloan Kettering Cancer Center (MSKCC) and Surveillance, Epidemiology and End Results (SEER) data for melanoma and NMSC incidence rates after HCL. Incidence data from MSKCC patients demonstrated a 10-year combined melanoma and NMSC skin cancer rate of 11·3%, melanoma 4·4% and NMSC 6·9%. Molecular analysis of skin cancers from MSKCC patients revealed activating RAS mutations in 3/9 patients, including one patient with melanoma. Of 4750 SEER patients with HCL, 55 (1·2%) had a subsequent diagnosis of melanoma. Standardized incidence ratios (SIRs) did not show that melanoma was more common in HCL patients versus the general population (SIR 1·3, 95% CI 0·78-2·03). Analysis of SEER HCL patients diagnosed before and after 1990 (approximately before and after purine analogue therapy was introduced) showed no evidence of an increased incidence after 1990. A better understanding of any potential association between HCL and skin cancer is highly relevant given ongoing trials using BRAF inhibitors, such as vemurafenib, for relapsed HCL, as RAS-mutant skin cancers could be paradoxically activated in these patients. © 2015 John Wiley & Sons Ltd.

  17. First year clinical tutorials: students’ learning experience

    Directory of Open Access Journals (Sweden)

    Burgess A

    2014-11-01

    Full Text Available Annette Burgess,1 Kim Oates,2 Kerry Goulston,2 Craig Mellis1 1Central Clinical School, Sydney Medical School, The University of Sydney, Sydney, NSW, Australia; 2Sydney Medical School, The University of Sydney, Sydney, NSW, Australia Background: Bedside teaching lies at the heart of medical education. The learning environment afforded to students during clinical tutorials contributes substantially to their knowledge, thinking, and learning. Situated cognition theory posits that the depth and breadth of the students' learning experience is dependent upon the attitude of the clinical teacher, the structure of the tutorial, and the understanding of tutorial and learning objectives. This theory provides a useful framework to conceptualize how students' experience within their clinical tutorials impacts their knowledge, thinking, and learning. Methods: The study was conducted with one cohort (n=301 of students who had completed year 1 of the medical program at Sydney Medical School in 2013. All students were asked to complete a three-part questionnaire regarding their perceptions of their clinical tutor's attributes, the consistency of the tutor, and the best features of the tutorials and need for improvement. Both quantitative and qualitative data were collected and analyzed using descriptive statistics. Results: The response rate to the questionnaire was 88% (265/301. Students perceived that their tutors displayed good communication skills and enthusiasm, encouraged their learning, and were empathetic toward patients. Fifty-two percent of students reported having the same communications tutor for the entire year, and 28% reported having the same physical examination tutor for the entire year. Students would like increased patient contact, greater structure within their tutorials, and greater alignment of teaching with the curriculum. Conclusion: Situated cognition theory provides a valuable lens to view students' experience of learning within the

  18. 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.

  19. 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.

  20. A phase II trial of stereotactic body radiotherapy with concurrent anti-PD1 treatment in metastatic melanoma: evaluation of clinical and immunologic response.

    Science.gov (United States)

    De Wolf, Katrien; Kruse, Vibeke; Sundahl, Nora; van Gele, Mireille; Chevolet, Ines; Speeckaert, Reinhart; Brochez, Lieve; Ost, Piet

    2017-01-31

    Antibodies blocking programmed cell death 1 (PD-1) have encouraging responses in patients with metastatic melanoma. Response to anti-PD-1 treatment requires pre-existing CD8+ T cells that are negatively regulated by PD-1-mediated adaptive immune resistance. Unfortunately, less than half of melanoma tumours have these characteristics. Combining anti-PD-1 treatment with other immunomodulating treatments to activate CD8+ T cells is therefore of vital importance to increase response rates and long-term survival benefit in melanoma patients. Both preclinical and retrospective clinical data support the hypothesis that radiotherapy increases the response rates to anti-PD-1 treatment by stimulating the accumulation and activation of CD8+ T cells in the tumour microenvironment. Combining radiotherapy with a PD-1 blocking antibody might therefore increase response rates and even induce long-term survival. The current phase II study will be testing these hypotheses and aims to improve local and distant tumour responses by exploiting the pro-immunogenic effects of radiotherapy in addition to anti-PD-1 treatment. The trial will be conducted in patients with metastatic melanoma. Nivolumab or pembrolizumab, both antibodies that target PD-1, will be administrated according to the recommended dosing schedule. Prior to the 2nd cycle, radiotherapy will be delivered in three fractions of 8 Gy to the largest FDG-avid metastatic lesion. The primary endpoint is the proportion of patients with a partial or complete response in non-irradiated metastases according to RECIST v1.1. Secondary endpoints include response rate according to immune related response criteria, metabolic response, local control and survival. To identify peripheral blood biomarkers, peripheral blood mononuclear cells and serum samples will be collected prospectively before, during and after treatment and subjected to flow cytometry and cytokine measurement. The current phase II trial aims at exploring the suggested

  1. Melanoma risk prediction models

    Directory of Open Access Journals (Sweden)

    Nikolić Jelena

    2014-01-01

    only present in melanoma patients and thus were strongly associated with melanoma. The percentage of correctly classified subjects in the LR model was 74.9%, sensitivity 71%, specificity 78.7% and AUC 0.805. For the ADT percentage of correctly classified instances was 71.9%, sensitivity 71.9%, specificity 79.4% and AUC 0.808. Conclusion. Application of different models for risk assessment and prediction of melanoma should provide efficient and standardized tool in the hands of clinicians. The presented models offer effective discrimination of individuals at high risk, transparent decision making and real-time implementation suitable for clinical practice. A continuous melanoma database growth would provide for further adjustments and enhancements in model accuracy as well as offering a possibility for successful application of more advanced data mining algorithms.

  2. Melanoma epidemiology, prognosis and trends in Latvia.

    Science.gov (United States)

    Azarjana, K; Ozola, A; Ruklisa, D; Cema, I; Rivosh, A; Azaryan, A; Pjanova, D

    2013-11-01

    Melanoma incidence and mortality rates are increasing worldwide within the white population. Clinical and histological factors have been usually used for the prognosis and assessment of the risk for melanoma. The aim of the study was to describe the clinical and histopathological features of the cutaneous melanoma (CM) in the Latvian population, to test the association between melanoma features and patient survival, and to assess the time trends for melanoma incidence. We undertook a descriptive, retrospective analysis of archive data of 984 melanoma patients treated at the largest oncological hospital of Latvia, Riga East University Hospital Latvian Oncology Centre (LOC), between 1998 and 2008. Cox proportional hazards model was used to analyse patient survival and autoregressive models were applied to detect trends in melanoma incidence over time for various categories of melanoma. The study showed a significant ascending trend in melanoma incidence in Latvia during the time period from 1998 to 2008 (ß = 1.83, 95% CI = 1.15-2.91, P = 0.011). Nodular melanoma was the most common tumour subtype with a frequency of 39.2%. Ulceration was present in 45.2% of melanomas. The mean Breslow thickness was 6.0 mm (6.8 mm) and no significant decline in median Breslow thickness was observed during the study period (P = 0.609). A better overall prognosis was detected for females in comparison with males (HR = 1.49; 95% CI = 1.22-1.81; P Latvia with the majority of melanomas diagnosed at late stages with poor prognosis for survival. © 2012 The Authors Journal of the European Academy of Dermatology and Venereology © 2012 European Academy of Dermatology and Venereology.

  3. Checkpoint Inhibitors Hold Promise for Rare Melanoma

    Science.gov (United States)

    Patients with a rare form of melanoma, called desmoplastic melanoma, may be particularly likely to benefit from immune checkpoint inhibitors, a new study shows. As this Cancer Currents post explains, an NCI-sponsored clinical trial is already testing one such drug, pembrolizumab (Keytruda) in patients with this cancer.

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

    Science.gov (United States)

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

    2012-12-01

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

  5. Melanoma Exosomes Enable Tumor Tolerance in Lymph Nodes

    OpenAIRE

    Hood, Joshua L.

    2016-01-01

    Melanoma preferentially spreads via lymph nodes. Melanoma exosomes can induce angiogenesis and immune suppression. However, a role for melanoma exosomes in facilitating tumor tolerance in lymph nodes has not been considered. Herein, the hypothesis that melanoma exosome mediated induction of vascular endothelial cell (VEC) derived TNF-α results in lymphatic endothelial cell (LEC) mediated tumor tolerance is explored. To support this hypothesis, experiments involving ex vivo lymph node associat...

  6. Nodular melanoma is less likely than superficial spreading melanoma to be histologically associated with a naevus.

    Science.gov (United States)

    Pan, Yan; Adler, Nikki R; Wolfe, Rory; McLean, Catriona A; Kelly, John W

    2017-10-16

    To determine the frequency of naevus-associated melanoma among superficial spreading and nodular subtypes; and to investigate associations between naevus-associated melanoma and other clinico-pathological characteristics. Cross-sectional study of all patients with nodular and superficial spreading melanomas diagnosed between 1994 and 2015 at the Victorian Melanoma Service, Melbourne. Clinical and pathological characteristics of naevus-associated and de novo melanomas were assessed in univariable and multivariable logistic regression analyses. Of 3678 primary melanomas, 1360 (37.0%) were histologically associated with a naevus and 2318 (63.0%) were de novo melanomas; 71 of 621 nodular (11.4%) and 1289 of 3057 superficial spreading melanomas (42.2%) were histologically associated with a naevus. In multivariable analyses, the odds of being associated with a naevus were higher for melanomas located on the trunk (v head and neck: adjusted odds ratio [OR], 2.27; 95% CI, 1.73-2.96; P melanomas (adjusted OR, 0.68; 95% CI, 0.48-0.97; P = 0.035), and older age (patients 70 years or older v patients under 30 at diagnosis: adjusted OR, 0.28; 95% CI, 0.20-0.40; P melanomas as for nodular melanomas (adjusted OR, 3.05; 95% CI, 2.24-4.17; P Melanomas are most likely to arise in the absence of a pre-existing naevus, particularly nodular melanomas. Public health campaigns should therefore emphasise the detection of suspicious de novo lesions, as well as of changing lesions.

  7. 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

  8. 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.

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

    African Journals Online (AJOL)

    Isolated pancreatic metastasis from malignant melanoma (IPMMM) is rare because most melanoma patients already have a widespread disease at diagnosis. No adjuvant systemic treatment is known to be effi cient in this setting. Experience with pancreatic resection for IPMMM is limited and controversial. We report here ...

  10. 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

  11. A Clinical Study of a Cell-Based MAGE-A3 Active Immunotherapy in Advanced Melanoma Patients

    Directory of Open Access Journals (Sweden)

    Vincenzo Russo, Francesca Lunghi, Raffaella Fontana, Marco Bregni

    2011-01-01

    Full Text Available In this bi-institutional study, twenty-three stage IIIC-IV MAGE-A3+ melanoma patients were vaccinated with M3TK-GML biweekly at three dose levels, with a subsequent phase of vaccinations at the maximum dose level. Anti-MAGE-A3 and anti-TK T cells were assessed by in vitro assay and delayed-type hypersensitivity skin testing.

  12. Stages of Intraocular (Uveal) Melanoma

    Science.gov (United States)

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

  13. Clinical experience with PACS: Digital radiology

    International Nuclear Information System (INIS)

    Hruby, W.; Mosser, H.; Urban, M.; Krampla, W.; Ammann, M.; Mayrhofer, R.; Kaissas, K.

    1994-01-01

    We present our experience during the first 21 months of using hospital-wide network technology and digital archiving in connection with digital radiology in the Radiology Department at the SMZO/Danube hospital in Vienna. This means digital generation, archiving and distribution of radiographs as well as monitor reporting embedded in HIS and RIS. The clinical use of PACS demands full integration of all subsystems and modalities in a digital way, as was first realized at the Danube Hospital. With this approach, a reduction in radiation dose, improved communication and thus a reduction in the length of hospital stay and health care cost are attained. (orig.) [de

  14. Melanoma of the Hand: Current Practice and New Frontiers

    Directory of Open Access Journals (Sweden)

    John Brad Turner

    2014-03-01

    Full Text Available Melanoma of the hand represents a complicated clinical entity. Anatomic features of the hand create challenges in successful management of melanoma not encountered elsewhere in the body. The objectives of this article are to outline current standards for managing melanoma of the hand including diagnosis, surgical, and chemotherapeutic management. Particular emphasis will be placed on currently debated topics of the role of sentinel lymph node biopsy, the role of Mohs micrographic surgery, tissue sparing management of subungual melanoma, and the consideration of melanoma of the hand as a distinct entity based on clinical and molecular studies.

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

    Science.gov (United States)

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

    2016-04-01

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

  16. Genomic characterisation of acral melanoma cell lines.

    Science.gov (United States)

    Furney, Simon J; Turajlic, Samra; Fenwick, Kerry; Lambros, Maryou B; MacKay, Alan; Ricken, Gerda; Mitsopoulos, Costas; Kozarewa, Iwanka; Hakas, Jarle; Zvelebil, Marketa; Lord, Christopher J; Ashworth, Alan; Reis-Filho, Jorge S; Herlyn, Meenhard; Murata, Hiroshi; Marais, Richard

    2012-07-01

    Acral melanoma is a rare melanoma subtype with distinct epidemiological, clinical and genetic features. To determine if acral melanoma cell lines are representative of this melanoma subtype, six lines were analysed by whole-exome sequencing and array comparative genomic hybridisation. We demonstrate that the cell lines display a mutation rate that is comparable to that of published primary and metastatic acral melanomas and observe a mutational signature suggestive of UV-induced mutagenesis in two of the cell lines. Mutations were identified in oncogenes and tumour suppressors previously linked to melanoma including BRAF, NRAS, KIT, PTEN and TP53, in cancer genes not previously linked to melanoma and in genes linked to DNA repair such as BRCA1 and BRCA2. Our findings provide strong circumstantial evidence to suggest that acral melanoma cell lines and acral tumours share genetic features in common and that these cells are therefore valuable tools to investigate the biology of this aggressive melanoma subtype. Data are available at: http://rock.icr.ac.uk/collaborations/Furney_et_al_2012/. © 2012 John Wiley & Sons A/S.

  17. Nodular skin melanomas and dermatoscopic diagnostic therein

    Directory of Open Access Journals (Sweden)

    M. V. Zhuchkov

    2016-01-01

    Full Text Available Aim. The study of dermatoscopic pattern characteristics of nodular melanoma with the use of modified Kittler’s pattern analysis. Materials and methods. Clinical and dermatoscopis images of 127 patients with histologically distinctive nodular form of skin melanoma were examined. Nonpolarized dermoscopy of nodular melanoma foci was carried out to patients. Interpretation of obtained dermatoscopic images was performed with the use of pattern analysis modified by Harold Kittler. Main results. The two most important dermatoscopic features of nodular melanoma that distinguish it from other clinical types of this malignant tumor were revealed in our investigation: 1 the prevalence of dermatoscopis images with one pattern (structureless; 2 the prevalence of “grey dots, circles, clods” and “black peripheral dots and clods” as main features of nodular melanoma.

  18. 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

    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...... 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....... 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...

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

    Science.gov (United States)

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

    2016-06-01

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

  20. Clinical Scale Zinc Finger Nuclease-mediated Gene Editing of PD-1 in Tumor Infiltrating Lymphocytes for the Treatment of Metastatic Melanoma.

    Science.gov (United States)

    Beane, Joal D; Lee, Gary; Zheng, Zhili; Mendel, Matthew; Abate-Daga, Daniel; Bharathan, Mini; Black, Mary; Gandhi, Nimisha; Yu, Zhiya; Chandran, Smita; Giedlin, Martin; Ando, Dale; Miller, Jeff; Paschon, David; Guschin, Dmitry; Rebar, Edward J; Reik, Andreas; Holmes, Michael C; Gregory, Philip D; Restifo, Nicholas P; Rosenberg, Steven A; Morgan, Richard A; Feldman, Steven A

    2015-08-01

    Programmed cell death-1 (PD-1) is expressed on activated T cells and represents an attractive target for gene-editing of tumor targeted T cells prior to adoptive cell transfer (ACT). We used zinc finger nucleases (ZFNs) directed against the gene encoding human PD-1 (PDCD-1) to gene-edit melanoma tumor infiltrating lymphocytes (TIL). We show that our clinical scale TIL production process yielded efficient modification of the PD-1 gene locus, with an average modification frequency of 74.8% (n = 3, range 69.9-84.1%) of the alleles in a bulk TIL population, which resulted in a 76% reduction in PD-1 surface-expression. Forty to 48% of PD-1 gene-edited cells had biallelic PD-1 modification. Importantly, the PD-1 gene-edited TIL product showed improved in vitro effector function and a significantly increased polyfunctional cytokine profile (TNFα, GM-CSF, and IFNγ) compared to unmodified TIL in two of the three donors tested. In addition, all donor cells displayed an effector memory phenotype and expanded approximately 500-2,000-fold in vitro. Thus, further study to determine the efficiency and safety of adoptive cell transfer using PD-1 gene-edited TIL for the treatment of metastatic melanoma is warranted.

  1. Clear cells in acral melanoma.

    Science.gov (United States)

    Schmuth, M; Spötl, L; Zelger, B; Weinlich, G; Zelger, B

    2001-01-01

    Acral melanoma may present clinically and histologically with atypical features causing a delay in proper diagnosis. The aim of the present study was to assess the frequency of a histological variant with clear cell changes. Clinical information, hematoxylin & eosin stained paraffin sections and immunohistochemical staining profiles were reviewed in 49 cases of acral melanoma. Twenty-one (43%) specimens contained tumor cells with clear cell changes in focal areas, whereas in 7 (14%) specimens clear cells were the major tumor constituting cells. The tumor thickness ranged from melanoma in situ to 14 mm. Immunohistochemistry demonstrated weak staining for S100 and HMB45 as well as strong positivity for Melan A and NK1C3. Recognition of clear cell features is important since differential diagnosis includes a variety of other clear cell malignancies, among them metastasis from renal cell carcinoma, clear cell sarcoma and hidradenocarcinoma.

  2. Dermoscopy of Nodular Melanoma: Review of the Literature and Report of 3 Cases.

    Science.gov (United States)

    Đorđević Brlek, Zorica; Jurakić Tončić, Ružica; Radoš, Jaka; Marinović, Branka

    2016-08-01

    Nodular melanoma is the most aggressive subtype of melanoma, with rapid growth rate and metastatic potential. It is usually diagnosed at a locally advanced stage (Breslow thickness Nodular melanoma often does not fit the classic clinical ABCD criteria, but rather the EFG rule or 3 Cs criteria. Missing the diagnosis of nodular melanoma is a dermatologist's worst nightmare, especially since nodular melanomas can have a non-alarming clinical appearance and imitate a wide range of benign lesions. All evolving nodular lesions, despite their size, symmetry, and color, which cannot be confidently diagnosed as benign, should be excised in order to rule out nodular melanoma. Almost all melanoma-specific dermoscopic criteria are described in context of superficial spreading melanoma. Thus, physicians are not familiar and aware enough of dermoscopic features for early detection of nodular melanomas. Herein we present 3 cases of nodular melanomas from our Department and give a review of the current literature.

  3. Other targeted drugs in melanoma.

    Science.gov (United States)

    González-Cao, María; Rodón, Jordi; Karachaliou, Niki; Sánchez, Jesús; Santarpia, Mariacarmela; Viteri, Santiago; Pilotto, Sara; Teixidó, Cristina; Riso, Aldo; Rosell, Rafael

    2015-10-01

    Targeted therapy drugs are developed against specific molecular alterations on cancer cells. Because they are "targeted" to the tumor, these therapies are more effective and better tolerated than conventional therapies such as chemotherapy. In the last decade, great advances have been made in understanding of melanoma biology and identification of molecular mechanisms involved in malignant transformation of cells. The identification of oncogenic mutated kinases involved in this process provides an opportunity for development of new target therapies. The dependence of melanoma on BRAF-mutant kinase has provided an opportunity for development of mutation-specific inhibitors with high activity and excellent tolerance that are now being used in clinical practice. This marked a new era in the treatment of metastatic melanoma and much research is now ongoing to identify other "druggable" kinases and transduction signaling networking. It is expected that in the near future the spectrum of target drugs for melanoma treatment will increase. Herein, we review the most relevant potential novel drugs for melanoma treatment based on preclinical data and the results of early clinical trials.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    Riechardt, Aline I; Karle, Bettina; Cordini, Dino; Heufelder, Jens; Budach, Volker; Joussen, Antonia M; Gollrad, Johannes

    2017-11-01

    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.

  6. Long-term Survival with Ipilimumab: Experience from a National Expanded Access Program for Patients with Melanoma.

    Science.gov (United States)

    Krajsová, Ivana; Arenberger, Petr; Lakomý, Radek; Kubala, Eugen; Březinová, Ivana; Poprach, Alexandr; Šťastný, Marek; Mužík, Jan; Melichar, Bohuslav

    2015-11-01

    Evaluation of efficacy and safety of ipilimumab in patients with advanced, refractory melanoma enrolled into a national ipilimumab Expanded Access Program. Adult patients with advanced/metastatic refractory melanoma were eligible for study inclusion. Ipilimumab was administered up to a total of four doses. One hundred and ninety-six patients were analyzed. Full ipilimumab induction was administered to 66.8% of patients. Median overall survival (OS) in the entire cohort was 7.5 months. Median OS for patients after four doses of ipilimumab was significantly longer than for patients with fewer doses (12.3 months vs. 2.0 months respectively; p<0.001). Median OS for patients with objective tumor response was 42.3 months. Normal baseline serum lactate dehydrogenase (LDH) and C-reactive protein (CRP) levels, and the number of affected organs correlated with improved OS. The number of affected organs and combination of baseline LDH and CRP levels could potentially serve as predictors for both treatment response and OS. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  7. [Skin cancer and sun radiation: peruvian experience in the prevention and early detection of skin cancer and melanoma].

    Science.gov (United States)

    Sordo, Carlos; Gutiérrez, César

    2013-03-01

    The excessive exposure to sun radiation, especially to ultraviolet radiation (UV), has led to various diseases, in particular to skin cancer. In 1995, the Peruvian Dermatological Association conducted the first "Campaign for Education, Prevention and Early Detection of Skin Cancer and Melanoma" called "Mole's Day". The Ministry of Health has turned it into an official event, and the Health Social Security (EsSalud) also participates. This is a free campaign that takes place every year nationwide. 118,092 people attended from 1995 to 2011 in 76 sites distributed in 18 cities throughout the country. A cutaneous lesion were malignancy was suspected was identified in 2.8% of people attending, out of which 64.9% corresponded to basal cell carcinoma, 26.7% to cutaneous melanoma, and 8.4% to squamous cell carcinoma. These campaigns are highly important not only because of the assistance given, but also because of the educational activities aimed at promoting a prevention culture in favor of the most vulnerable populations. Finally, we believe it is important to continue educating the population on skin cancer prevention, to build awareness among the authorities so that they actively participate in the performance of these activities, and to ask all physicians to coordinately join this initiative, in order to continue growing, and to improve all that has been attained for the benefit of our country.

  8. Obesity as a risk factor for malignant melanoma and non-melanoma skin cancer.

    Science.gov (United States)

    Karimi, K; Lindgren, T H; Koch, C A; Brodell, Robert T

    2016-09-01

    The dramatic increases in incidence of both obesity and many cancers including skin cancer emphasize the need to better understand the pathophysiology of both conditions and their connections. Melanoma is considered the fastest growing cancer and rates of non-melanoma skin cancer have also increased over the last decade. The molecular mechanisms underlying the association between obesity and skin cancer are not clearly understood but emerging evidence points to changes in the tumor microenvironment including aberrant cell signaling and genomic instability in the chronic inflammatory state many obese individuals experience. This article reviews the literature linking obesity to melanoma and non-melanoma skin cancer.

  9. Dermoscopy of Nodular Melanoma: Review of the Literature and Report of 3 Cases

    OpenAIRE

    Zorica Đorđević Brlek; Ružica Jurakić Tončić; Jaka Radoš; Branka Marinović

    2016-01-01

    Nodular melanoma is the most aggressive subtype of melanoma, with rapid growth rate and metastatic potential. It is usually diagnosed at a locally advanced stage (Breslow thickness <2 mm) and is therefore associated with a poor prognosis. Nodular melanoma often does not fit the classic clinical ABCD criteria, but rather the EFG rule or 3 Cs criteria. Missing the diagnosis of nodular melanoma is a dermatologist’s worst nightmare, especially since nodular melanomas can have a non-alarming cl...

  10. Progression of cutaneous melanoma: implications for treatment

    Science.gov (United States)

    Leong, Stanley P. L.; Mihm, Martin C.; Murphy, George F.; Hoon, Dave S. B.; Kashani-Sabet, Mohammed; Agarwala, Sanjiv S.; Zager, Jonathan S.; Hauschild, Axel; Sondak, Vernon K.; Guild, Valerie; Kirkwood, John M.

    2015-01-01

    The survival rates of melanoma, like any type of cancer, become worse with advancing stage. Spectrum theory is most consistent with the progression of melanoma from the primary site to the in-transit locations, regional or sentinel lymph nodes and beyond to the distant sites. Therefore, early diagnosis and surgical treatment before its spread is the most effective treatment. Recently, new approaches have revolutionized the diagnosis and treatment of melanoma. Genomic profiling and sequencing will form the basis for molecular taxonomy for more accurate subgrouping of melanoma patients in the future. New insights of molecular mechanisms of metastasis are summarized in this review article. Sentinel lymph node biopsy has become a standard of care for staging primary melanoma without the need for a more morbid complete regional lymph node dissection. With recent developments in molecular biology and genomics, novel molecular targeted therapy is being developed through clinical trials. PMID:22892755

  11. From Melanocyte to Metastatic Malignant Melanoma

    Directory of Open Access Journals (Sweden)

    Bizhan Bandarchi

    2010-01-01

    Full Text Available Malignant melanoma is one of the most aggressive malignancies in human and is responsible for almost 60% of lethal skin tumors. Its incidence has been increasing in white population in the past two decades. There is a complex interaction of environmental (exogenous and endogenous, including genetic, risk factors in developing malignant melanoma. 8–12% of familial melanomas occur in a familial setting related to mutation of the CDKN2A gene that encodes p16. The aim of this is to briefly review the microanatomy and physiology of the melanocytes, epidemiology, risk factors, clinical presentation, historical classification and histopathology and, more in details, the most recent discoveries in biology and genetics of malignant melanoma. At the end, the final version of 2009 AJCC malignant melanoma staging and classification is presented.

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

    Science.gov (United States)

    2015-06-25

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

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

    Science.gov (United States)

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

    2014-01-01

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

  14. Emerging targeted therapies for melanoma.

    Science.gov (United States)

    Johnson, Douglas B; Pollack, Megan H; Sosman, Jeffrey A

    2016-06-01

    Melanoma is an aggressive cutaneous malignancy associated with poor response to traditional therapies. Recent regulatory approval for immune checkpoint inhibitors and agents targeting mutated BRAF has led to a tremendous expansion of effective treatment options for patients with advanced melanoma. Unfortunately, primary or acquired resistance develops in most patients, highlighting the need for additional therapies. Numerous genetic and other molecular features of this disease may provide effective targets for therapy development. This article reviews available melanoma treatments, including immune and molecularly-targeted therapies. We then discuss agents in development, with a focus on targeted (rather than immune) therapies. In particular, we discuss agents that block mitogen-activated protein kinase (MAPK) signaling, as well as other emerging approaches such as antibody-drug conjugates, cell-cycle targeting, and novel genetically-informed clinical trials. Despite the incredible advances in melanoma therapeutics over the last several years, a clear need to develop more effective therapies remains. Molecularly-targeted therapy approaches will likely remain a cornerstone of melanoma treatment in parallel to immune therapy strategies.

  15. Choroidal melanoma in a dog.

    Science.gov (United States)

    Miwa, Yasutsugu; Matsunaga, Satoru; Kato, Kumiko; Ogawa, Hiroyuki; Nakayama, Hiroyuki; Tsujimoto, Saori; Sasaki, Nobuo

    2005-08-01

    A 7-year-old intact female golden Retriever was referred for evaluation of an intraorbital mass of the left eye. Based on ophthalmoscopy, ultrasonography and magnetic resonance imaging (MRI), the tentative diagnosis was made as an intraocular neoplasia, especially choroidal melanoma. The orbital exenteration of the affected eye was performed. The mass was histologically diagnosed as malignant choroidal melanoma. No signs of recurrence and metastasis were detected by thoracic radiographs, blood examinations and MR images, and the dog was clinically healthy for 23 months after operation.

  16. Malignant melanoma at a scientific laboratory

    Energy Technology Data Exchange (ETDEWEB)

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

    1985-11-15

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

  17. 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

  18. 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...

  19. Modulith SL20--development and clinical experience.

    Science.gov (United States)

    Köhrmann, K U; Henkel, T O; Potempa, D; Rassweiler, J; Heine, G; Alken, P

    1993-01-01

    A third generation lithotripter was developed incorporating the advantages of high disintegrative efficacy, anaesthesia-free treatment, combined sonographic and fluoroscopic localization system as well as a multifunctional table for interdisciplinary use. The shock wave generator consists of a cylindrical-shaped electromagnetic coil with a paraboloid reflector. The waves are coupled by means of a water cushion and an impedance adapted foil in which the patient is comfortably positioned. Stones are localized by an in-line ultrasound probe or fluoroscopically by the integrated C-arm. Preclinical trials using the in-vitro stone model demonstrated the superior disintegrative capacity. The in-vivo animal studies evaluated the dose-dependent and reversible kidney trauma, which was comparable to that induced by other lithotripters. The clinical evaluation of the Modulith SL since 1988 was divided into three phases with different technical equipment. It was indicated that sonographic stone localization enables treatment of nearly all kidney stones and 12% of the ureteric calculi. As preference was given to in situ disintegration of all ureteral stones, X-ray targeting became necessary. By increasing the generator voltage in the third phase together with advanced experience, the disintegration rate (94%) was improved. The number of auxiliary measures after ESWL (11%) and treatment time (average 39 min) was decreased. Eighty-eight percent of our patients were stone-free at follow-up. The experience demonstrated that this lithotripter is also easy to handle for gallbladder stones and highly effective (82%) in treatment of endoscopically non-extractable bile duct stones.

  20. 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

  1. Skin cancer and melanoma

    International Nuclear Information System (INIS)

    Moylan, D.J.

    1991-01-01

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

  2. 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.

  3. Experimental boron neutron capture therapy for melanoma: Systemic delivery of boron to melanotic and amelanotic melanoma

    International Nuclear Information System (INIS)

    Coderre, J.A.; Glass, J.D.; Micca, P.; Greenberg, D.; Packer, S.

    1990-01-01

    The boron-containing melanin precursor analogue p-boronophenylalanine (BPA) has previously been shown to selectively deliver boron to pigmented murine melanomas when administered in a single intragastric dose. If boron neutron capture therapy is to become a clinically useful method of radiation therapy for human malignant melanoma, the boron carrier must be capable of delivering useful amounts of boron to remote tumor sites (metastases) and to poorly pigmented melanomas. The authors have now determined the ability of BPA to accumulate in several nonpigmented melanoma models including human melanoma xenografts in nude mice. The absolute amount of boron in the nonpigmented melanomas was about 50% of the observed in the pigmented counterparts but was still selectively concentrated in the tumor relative to normal tissues in amounts sufficient for effective neutron capture therapy. Single intragastric doses of BPA resulted in selective localization of boron in the amelanotic Greene melanoma carried in the anterior chamber of the rabbit eye and in a pigmented murine melanoma growing in the lungs. The ratio of the boron concentration in these tumors to the boron concentration in the immediately adjacent normal tissue was in the range of 3:1 to 4:1. These distribution studies support the proposal that boron neutron capture therapy may be useful as a regional therapy for malignant melanoma

  4. Decontamination and decorporation: the clinical experience

    International Nuclear Information System (INIS)

    Poda, G.A.

    1979-01-01

    Decontamination and decorporation are quite interrelated when dealing with a contaminated person. Some clinical experiences from a transuranium production facility are offered. Skin decontamination is accomplished by washing with detergent and water. Stubborn cases are treated with sodium hypochlorite followed by rinsing, and emery cloth is used on more stubborn nail or finger pad contamination. If inhaled, the usual skin cleansing followed by nasal douche with normal saline decontaminates reachable areas and one of the DTPA salts given via aerosol both decontaminates and decorporates the inner recesses. Saline laxative reduces the time inhaled, and ingested particles remain in the gastro-intestinal tract. Conservatism prevails in general, but most persons found to have inhaled contamination are given a single chelation within the hour of discovery and if subsequently found to have over 10% M.P.P.B. of a soluble actinide are offered further chelation. Single dose chelation has been found to be relatively innocuous and usually sufficient. The longest case of chelation therapy spanned 2-1/4 years and encompassed 123 doses of CaNa-DTPA

  5. Transmyocardial laser revascularization. Early clinical experience

    Directory of Open Access Journals (Sweden)

    Oliveira Sérgio Almeida de

    1999-01-01

    Full Text Available OBJECTIVE: To analyze the initial clinical experience of transmyocardial laser revascularization (TMLR in patients with severe diffuse coronary artery disease. METHODS: Between February, 1998 and February, 1999, 20 patients were submitted to TMLR at the Heart Institute (InCor, University of São Paulo Medical School, Brazil, isolated or in association with conventional coronary artery bypass graft (CABG. All patients had severe diffuse coronary artery disease, with angina functional class III/IV (Canadian Cardiovascular Society score unresponsive to medical therapy. Fourteen patients were submitted to TMLR as the sole therapy, whereas 6 underwent concomitant CABG. Fifty per cent of the patients had either been previously submitted to a CABG or to a percutaneous transluminal coronary angioplasty (PTCA. Mean age was 60 years, ranging from 45 to 74 years. RESULTS: All patients had three-vessel disease, with normal or mildly impaired left ventricular global function. Follow-up ranged from 1 to 13 months (mean 6.6 months, with no postoperative short or long term mortality. There was significant symptom improvement after the procedure, with 85% of the patients free of angina, and the remaining 15 % of the patients showing improvement in functional class, as well as in exercise tolerance. CONCLUSION: This novel technique can be considered a low risk alternative for a highly selected group of patients not suitable for conventional revascularization procedures.

  6. 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.

  7. Association of MC1R variants and risk of melanoma in melanoma-prone families with CDKN2A mutations.

    Science.gov (United States)

    Goldstein, Alisa M; Landi, Maria Teresa; Tsang, Shirley; Fraser, Mary C; Munroe, David J; Tucker, Margaret A

    2005-09-01

    Major risk factors for melanoma include many nevi, especially dysplastic nevi, fair pigmentation, freckling, poor tanning ability, and germ line mutations in the CDKN2A, CDK4, or MC1R genes. We evaluated the relationship between MC1R and melanoma risk in CDKN2A melanoma-prone families with extensive clinical and epidemiologic data. We studied 395 subjects from 16 American CDKN2A families. Major melanoma risk factors were assessed by clinical examination or questionnaire; MC1R was sequenced. Odds ratios were estimated by unconditional and conditional logistic regression models. We examined the distribution of MC1R variants and median ages at melanoma diagnosis in multiple primary melanoma (MPM) and single primary melanoma (SPM) patients. Presence of multiple MC1R variants was significantly associated with melanoma, even after adjustment for major melanoma risk factors. All 40 MPM patients had at least one MC1R variant; 65% of MPM patients versus only 17% of SPM patients had at least two MC1R variants (P MC1R variants increased (P = 0.010 and P = 0.008, respectively). In contrast, no significant reduction in age at melanoma diagnosis was observed for SPM patients (P = 0.91). The current study suggests that the presence of multiple MC1R variants is associated with the development of multiple melanoma tumors in patients with CDKN2A mutations. Additional studies are needed to confirm these findings and to explore the mechanisms that may contribute to this relationship.

  8. A new understanding in the epidemiology of melanoma.

    Science.gov (United States)

    Erdei, Esther; Torres, Salina M

    2010-11-01

    The incidence of melanoma is continuing to increase worldwide. UV exposure is a known risk factor for melanoma. Geographic location is known to influence UV exposure and the distribution of the incidence of melanoma. Furthermore, epidemiologic data suggest that gender and genetics may influence the distribution of melanoma on the body surface and histopathologic characteristics of the lesion. This article describes what is known about the impact of gender, ethnicity and geography on the progression of melanoma. Advanced-stage cutaneous melanoma has a median survival time of less than 1 year. Surgical removal, radiotherapy, chemotherapy, targeted therapies and a variety of immunotherapies have been utilized in the treatment of melanoma. Current treatment strategies and the results of recent clinical trials are also discussed in this article.

  9. Defining the dermoscopic characteristics of fast-growing cutaneous melanomas.

    Science.gov (United States)

    Tejera-Vaquerizo, Antonio; Arias-Santiago, Salvador; Nagore, Eduardo; Martín-Cuevas, Paula; Orgaz-Molina, Javier; Traves, Victor; Herrera-Acosta, Enrique; Naranjo-Sintes, Ramón; Guillén, Carlos; Herrera-Ceballos, Enrique

    2015-06-01

    A high growth rate in melanomas has been associated with a more aggressive phenotype and worse survival. The aim of this study was to define the dermoscopic characteristics associated with this type of cutaneous melanoma. We carried out a retrospective study of 132 cutaneous melanomas, analyzing certain clinical characteristics and the most important dermoscopic variables related to the melanomas. Fast-growing melanomas were considered to be those with a growth rate of more than 0.5 mm per month. Fast-growing melanomas more often lacked an atypical network, were symmetrical, presented ulceration, and were hypopigmented. The dermoscopic vascular pattern often showed atypical irregular vessels and milky-red areas. The association of these two is a specific characteristic. Fast-growing melanomas have a characteristic phenotype and dermoscopy can be useful for their identification.

  10. Detection of desmoplastic melanoma with dermoscopy and reflectance confocal microscopy.

    Science.gov (United States)

    Maher, N G; Solinas, A; Scolyer, R A; Puig, S; Pellacani, G; Guitera, P

    2017-12-01

    Desmoplastic melanoma (DM) is frequently misdiagnosed clinically and often associated with melanoma in situ (MIS). To improve the detection of DM using dermoscopy and reflectance confocal microscopy (RCM). A descriptive analysis of DM dermoscopy features and a case-control study within a melanoma population for RCM feature evaluation was performed blindly, using data obtained between 2005 and 2015. After retrospectively identifying all DM cases with RCM data over the study period (n = 16), a control group of non-DM melanoma patients with RCM data, in a ratio of at least 3 : 1, was selected. The control group was matched by age and primary tumour site location, divided into non-DM invasive melanomas (n = 27) and MIS (n = 27). Invasive melanomas were selected according to the melanoma subtypes associated with the DM cases. The main outcomes were the frequency of melanoma-specific features on dermoscopy for DM; and the odds ratios of RCM features to distinguish DM from MIS and/or other invasive melanomas; or MIS from the combined invasive melanoma group. At least one of the 14 melanoma-specific features evaluated on dermoscopy was found in 100% of DMs (n = 15 DM with dermoscopy). Known RCM melanoma predictors were commonly found in the DMs, such as pagetoid cells (100%) and cell atypia (100%). The RCM feature of spindle cells in the superficial dermis was more common in DM compared with the entire melanoma control group (OR 3.82, 95% CI 1.01-14.90), and particularly compared to MIS (OR 5.48, 95% CI 1.11-32.36). Nucleated cells in the dermis and the RCM correlate of dermal inflammation were also significant RCM features favouring DM over MIS, as well as invasive melanoma over MIS. Dermoscopy and RCM may be useful tools for the identification of DM. Certain RCM features may help distinguish DM from MIS and other invasive melanomas. Larger studies are warranted. © 2017 European Academy of Dermatology and Venereology.

  11. 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

  12. Melanoma Brain Metastasis: Mechanisms, Models, and Medicine

    Science.gov (United States)

    Kircher, David A.; Silvis, Mark R.; Cho, Joseph H.; Holmen, Sheri L.

    2016-01-01

    The development of brain metastases in patients with advanced stage melanoma is common, but the molecular mechanisms responsible for their development are poorly understood. Melanoma brain metastases cause significant morbidity and mortality and confer a poor prognosis; traditional therapies including whole brain radiation, stereotactic radiotherapy, or chemotherapy yield only modest increases in overall survival (OS) for these patients. While recently approved therapies have significantly improved OS in melanoma patients, only a small number of studies have investigated their efficacy in patients with brain metastases. Preliminary data suggest that some responses have been observed in intracranial lesions, which has sparked new clinical trials designed to evaluate the efficacy in melanoma patients with brain metastases. Simultaneously, recent advances in our understanding of the mechanisms of melanoma cell dissemination to the brain have revealed novel and potentially therapeutic targets. In this review, we provide an overview of newly discovered mechanisms of melanoma spread to the brain, discuss preclinical models that are being used to further our understanding of this deadly disease and provide an update of the current clinical trials for melanoma patients with brain metastases. PMID:27598148

  13. Treatment Option Overview (Melanoma)

    Science.gov (United States)

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

  14. General Information about Melanoma

    Science.gov (United States)

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

  15. Stages of Melanoma

    Science.gov (United States)

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

  16. Melanoma - neck (image)

    Science.gov (United States)

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

  17. 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.

  18. Melanoma International Foundation

    Science.gov (United States)

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

  19. PIM kinases as therapeutic targets against advanced melanoma

    Science.gov (United States)

    Shannan, Batool; Watters, Andrea; Chen, Quan; Mollin, Stefan; Dörr, Markus; Meggers, Eric; Xu, Xiaowei; Gimotty, Phyllis A.; Perego, Michela; Li, Ling; Benci, Joseph; Krepler, Clemens; Brafford, Patricia; Zhang, Jie; Wei, Zhi; Zhang, Gao; Liu, Qin; Yin, Xiangfan; Nathanson, Katherine L.; Herlyn, Meenhard; Vultur, Adina

    2016-01-01

    Therapeutic strategies for the treatment of metastatic melanoma show encouraging results in the clinic; however, not all patients respond equally and tumor resistance still poses a challenge. To identify novel therapeutic targets for melanoma, we screened a panel of structurally diverse organometallic inhibitors against human-derived normal and melanoma cells. We observed that a compound that targets PIM kinases (a family of Ser/Thr kinases) preferentially inhibited melanoma cell proliferation, invasion, and viability in adherent and three-dimensional (3D) melanoma models. Assessment of tumor tissue from melanoma patients showed that PIM kinases are expressed in pre- and post-treatment tumors, suggesting PIM kinases as promising targets in the clinic. Using knockdown studies, we showed that PIM1 contributes to melanoma cell proliferation and tumor growth in vivo; however, the presence of PIM2 and PIM3 could also influence the outcome. The inhibition of all PIM isoforms using SGI-1776 (a clinically-available PIM inhibitor) reduced melanoma proliferation and survival in preclinical models of melanoma. This was potentiated in the presence of the BRAF inhibitor PLX4720 and in the presence of PI3K inhibitors. Our findings suggest that PIM inhibitors provide promising additions to the targeted therapies available to melanoma patients. PMID:27448973

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

    Science.gov (United States)

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

    2016-08-01

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

  1. Ocular melanoma: an overview of the current status

    Science.gov (United States)

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

    2013-01-01

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

  2. 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.

  3. Patient Experiences with the Preoperative Assessment Clinic (PEPAC): validation of an instrument to measure patient experiences

    NARCIS (Netherlands)

    Edward, G. M.; Lemaire, L. C.; Preckel, B.; Oort, F. J.; Bucx, M. J. L.; Hollmann, M. W.; de Haes, J. C. J. M.

    2007-01-01

    Background. Presently, no comprehensive and validated questionnaire to measure patient experiences of the preoperative assessment clinic (PAC) is available. We developed and validated the Patient Experiences with the Preoperative Assessment Clinic (PEPAC) questionnaire, which can be used for

  4. Nodular Melanoma Mimicking Keratoacanthoma: Lessons to learn.

    Science.gov (United States)

    Muthupalaniappen, Leelavathi; Das, Srijit; Md Nor, Norazirah; Ali, Siti A M

    2012-08-01

    A 67-year-old man of Chinese descent presented with a painless nodular lesion that had been present on his right forearm for the previous 3 months. A single, well-defined, dome-shaped, firm nodule with a central keratin plug surrounded by erythema was noted. Keratoacanthoma with secondary bacterial infection was suspected and the patient underwent an excision biopsy. Biopsy of the nodule and immunohistochemical staining supported a diagnosis of nodular malignant melanoma. It should be noted both that nodular malignant melanoma may present with a wide variety of clinical appearances, and that the lack of melanin pigment in nodular malignant melanoma may hinder the diagnosis of this aggressive tumour.

  5. Drug effects on melanoma

    NARCIS (Netherlands)

    Koomen, Elsje Rosalie

    2010-01-01

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

  6. Burden of Melanoma

    NARCIS (Netherlands)

    C. Holterhues (Cynthia)

    2011-01-01

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

  7. 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...

  8. Cutaneous melanoma in women

    Directory of Open Access Journals (Sweden)

    Mi Ryung Roh, MD

    2017-03-01

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

  9. 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.

  10. Dermoscopic features of melanomas associated with MC1R variants in Spanish CDKN2A mutation carriers.

    Science.gov (United States)

    Cuéllar, F; Puig, S; Kolm, I; Puig-Butille, J; Zaballos, P; Martí-Laborda, R; Badenas, C; Malvehy, J

    2009-01-01

    The presence of at least one MC1R gene variant is associated with a reduction in age at melanoma diagnosis in families with CDKN2A mutations. To describe dermoscopic features of early melanoma in CDKN2A gene mutation-positive Spanish individuals and to evaluate the possibility of a correlation between particular dermatoscopic pattern and MC1R gene variants. Patients in whom a melanoma was diagnosed during specific follow up of high-risk individuals carrying CDKN2A mutations (with familial or personal history of previous melanoma) were included in this study. The decision to remove such melanomas was taken on the basis of history, clinical and dermoscopic evaluations including total body photography and digital dermoscopy. Of the nine patients included in this study, three were noncarriers of the red hair MC1R polymorphism, three patients had one red hair MC1R polymorphism and three patients had two red hair MC1R polymorphisms. On dermoscopic analysis of suspect melanocytic lesions we found that the mean +/- SD ABCD total dermoscopy score (TDS) was significantly higher in noncarriers of red hair MC1R polymorphisms than in carriers of two MC1R gene red hair variants (6.8 +/- 0.4 vs. 4.4 +/- 0.9; P = 0.014). Early melanomas in patients with two MC1R red hair variants may be difficult to diagnose definitively by dermoscopy because, in our limited experience, they show fewer colours and structures and have a lower TDS. In such melanomas, subtle atypical vessels and other changes detected by digital image follow up may be useful to confirm the diagnosis of melanoma. An integrated approach including clinical history and dermoscopic data (also considering additional information, such as the presence of atypical vessels) should be utilized in evaluating these high-risk patients. Further studies are necessary to confirm our suggestion.

  11. Recent developments in nanomedicine for melanoma treatment.

    Science.gov (United States)

    Tang, Jian-Qin; Hou, Xiao-Yang; Yang, Chun-Sheng; Li, Ya-Xi; Xin, Yong; Guo, Wen-Wen; Wei, Zhi-Ping; Liu, Yan-Qun; Jiang, Guan

    2017-08-15

    Melanoma is a most aggressive skin cancer with limited therapeutic options and its incidence is increasing rapidly in recent years. The discovery and application of new targeted therapy agents have shown significant benefits. However, adverse side-effects and resistance to chemotherapy remain formidable challenges in the clinical treatment of malignant melanoma. Nanotherapeutics offers an important prospect of overcoming these drawbacks. The anti-tumoral applications of nanomedicine are varied, including those in chemotherapy, RNA interference, photothermal therapy, and photodynamic therapy. Furthermore, nanomedicine allows delivery of the effector structures into the tumor site via passive or active targeting, thereby allowing increased therapeutic specificity and reduced side effects. In this review, we summarize the latest developments in the application of nanocarrier-mediated targeted drug delivery to melanoma and nanomedicine-related clinical trials in melanoma treatment. We also discuss existing problems and opportunities for future developments, providing direction and new thoughts for further studies. © 2017 UICC.

  12. Satisfaction and improvement of clinical experiment of student radiotechnologists

    International Nuclear Information System (INIS)

    Lyu, Kwang Yeul; Kim, Hyun Soo

    2006-01-01

    Clinical experiment is a set of experience to help student acquire technic, attitude and knowledge by participating in the clinical work. The radiotechnologists who are employed in departments of radiology serve as clinical instructors. Their responsibilities include teaching students them to become competent radiotechnologist. Clinical instructors often have no formal preparation in teaching student. The purpose of this study is to review some principals that will help clinical instructors support and foster the professional development of student radiotechnologists. The clinical instructor should be able to identify the qualities of instructor, the characteristics of feedback and use facilitation skills when is evaluated student performance. And the survey was performed to evaluate the satisfaction of student participated in clinical experiment, the purpose of this research is to fine the problems and improvements in clinical experiment of student radiotechnologist in Korea

  13. Usefulness of preoperative lymphoscintigraphy for the identification of sentinel lymph nodes in melanoma.

    Science.gov (United States)

    Morris, K T; Stevens, J S; Pommier, R F; Fletcher, W S; Vetto, J T

    2001-05-01

    The exact role of lymphoscintigraphy (LS) in the evaluation of sentinel lymph nodes (SLNs) in melanoma is controversial. We reviewed our experience with preoperative LS for the determination of the lymph node drainage pattern of clinically node negative primary melanomas, with attention to the rate of ambiguous drainage and the effect of previous wide local excision (WLE). The scans of 87 patients who underwent LS at our institution for evaluation of their primary melanomas from 1995 to the present were reviewed. Fourteen of the primary tumor sites were in the head and neck region, 41 were truncal, and 32 were in the extremities. The average tumor thickness was 2.6 mm. Nine of 14 (64%) head/neck lesions and 12 of 41 (29%) truncal lesions displayed ambiguous drainage, as compared with only 2 of 32 (6%) extremity lesions (P drainage scans and subsequent SLN biopsies are not contraindicated in the presence of a prior WLE.

  14. A Case of Melanoma Associated Leukoderma

    Directory of Open Access Journals (Sweden)

    Özer Arıcan

    2010-06-01

    Full Text Available Melanoma associated leukoderma is a rare disease characterized by hypopigmented or depigmented macules, which are usualy localized at distant sites from the primary malignant melonoma. Immunologic response to abnormal melanocytes is thought to be responsible for the physiopathology of the disease. A 34-year- old male patient with a facially localized melanoma associated leukoderma is presented and the clinical features, pathogenesis, differential diagnosis, treatment and follow-up of the disease are discussed with the recent literature.

  15. Extracutaneous melanomas: a primer for the radiologist

    OpenAIRE

    Keraliya, Abhishek R.; Krajewski, Katherine M.; Braschi-Amirfarzan, Marta; Tirumani, Sree Harsha; Shinagare, Atul B.; Jagannathan, Jyothi P.; Ramaiya, Nikhil H.

    2015-01-01

    Objective: The purpose of this article is to provide a comprehensive review of the imaging features of extracutaneous melanomas. Conclusion: Extracutaneous melanomas are clinically and biologically distinct from their more common cutaneous counterpart with higher frequency of metastatic disease and poorer overall prognosis. Complete surgical excision is the treatment of choice whenever possible; systemic therapy in the form of conventional chemotherapeutic agents as well as novel targeted age...

  16. Estrogen Receptor β Agonists Differentially Affect the Growth of Human Melanoma Cell Lines.

    Directory of Open Access Journals (Sweden)

    Monica Marzagalli

    Full Text Available Cutaneous melanoma is an aggressive malignancy; its incidence is increasing worldwide and its prognosis remains poor. Clinical observations indicate that estrogen receptor β (ERβ is expressed in melanoma tissues and its expression decreases with tumor progression, suggesting its tumor suppressive function. These experiments were performed to investigate the effects of ERβ activation on melanoma cell growth.Protein expression was analyzed by Western blot and immunofluorescence assays. Cell proliferation was assessed by counting the cells by hemocytometer. ERβ transcriptional activity was evaluated by gene reporter assay. Global DNA methylation was analyzed by restriction enzyme assay and ERβ isoforms were identified by qRT-PCR. We demonstrated that ERβ is expressed in a panel of human melanoma cell lines (BLM, WM115, A375, WM1552. In BLM (NRAS-mutant cells, ERβ agonists significantly and specifically inhibited cell proliferation. ERβ activation triggered its cytoplasmic-to-nuclear translocation and transcriptional activity. Moreover, the antiproliferative activity of ERβ agonists was associated with an altered expression of G1-S transition-related proteins. In these cells, global DNA was found to be hypomethylated when compared to normal melanocytes; this DNA hypomethylation status was reverted by ERβ activation. ERβ agonists also decreased the proliferation of WM115 (BRAF V600D-mutant cells, while they failed to reduce the growth of A375 and WM1552 (BRAF V600E-mutant cells. Finally, we could observe that ERβ isoforms are expressed at different levels in the various cell lines. Specific oncogenic mutations or differential expression of receptor isoforms might be responsible for the different responses of cell lines to ERβ agonists.Our results demonstrate that ERβ is expressed in melanoma cell lines and that ERβ agonists differentially regulate the proliferation of these cells. These data confirm the notion that melanoma is a

  17. 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.

  18. Comprehensive histopathological comparison of epidermotropic/dermal metastatic melanoma and primary nodular melanoma.

    Science.gov (United States)

    Skala, Stephanie L; Arps, David P; Zhao, Lili; Cha, Kelly B; Wang, Min; Harms, Paul W; Andea, Aleodor A; Fullen, Douglas R; Chan, May P

    2018-02-01

    Metastatic melanoma involving the epidermis and/or upper dermis may show significant histological overlap with primary cutaneous melanoma, especially the nodular subtype. Proper histopathological classification is crucial to appropriate staging and management, but is often challenging. The aim of this study was to identify helpful histopathological features for differentiating epidermotropic/dermal metastatic melanoma (EDMM) and primary nodular melanoma (PNM). A cohort of EDMMs (n = 74) and PNMs (n = 75) was retrospectively reviewed for various histopathological features, and the data were compared between groups by the use of univariate analysis. Features significantly associated with EDMM included a tumour size of 10 mm, ulceration, epidermal collarettes, a higher mitotic rate, necrosis, multiple phenotypes, significant pleomorphism, and lichenoid inflammation. In multivariate analysis, a logistic regression model including large tumour size, ulceration, prominent TIPs, lichenoid inflammation and epidermal collarettes was highly predictive of PNM. Six (8%) EDMMs from three patients showed an 'epidermal-only' or 'epidermal-predominant' pattern closely simulating in-situ or microinvasive melanoma. Two of these cases were tested by fluorescence in-situ hybridisation, which confirmed clonal relationships with their corresponding primary melanomas. This is the first comprehensive histopathological comparison of EDMM and PNM. Recognition of the above histopathological associations should aid in the correct classification and staging of cutaneous melanoma. Epidermotropic metastatic melanomas may occasionally show an epidermal-only/epidermal-predominant pattern; accurate diagnosis requires prudent clinical correlation and, when necessary, ancillary molecular tests. © 2017 John Wiley & Sons Ltd.

  19. 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 

  20. Clinical observation of panniculitis in two patients with BRAF-mutated metastatic melanoma treated with a combination of a BRAF inhibitor and a MEK inhibitor.

    Science.gov (United States)

    Galliker, Nadja A; Murer, Carla; Kamarashev, Jivko; Dummer, Reinhard; Goldinger, Simone M

    2015-04-01

    Treatment with selective BRAF or MEK inhibitors is frequently associated with cutaneous toxicities, including squamous cell carcinoma (SCC), papillomas and rash. These cutaneous adverse effects are typically observed at a lower incidence during combined BRAF and MEK inhibitor therapy. Two male patients with stage IV metastatic BRAF-mutated melanoma were treated with a combination of a selective BRAF inhibitor and a selective MEK inhibitor (dabrafenib and trametinib, or encorafenib (LGX818) and binimetinib (MEK162)) within two different clinical trials. Ten and 150 days after treatment start respectively, the patients developed painful nodules on the legs. In addition, one patient developed symmetrical articulation pain and intermittent fever episodes. Based on the clinical and histological presentation, erythema nodosum-like panniculitis was diagnosed in both cases. No other aetiology could be found. After receiving topical or oral steroid treatment and anti-inflammatory analgesics, the painful nodular lesions disappeared several weeks later. In one case, a rebound of the painful nodules was observed when the combination treatment (dabrafenib and trametinib) was resumed after a 1-week unscheduled treatment interruption. Panniculitis has previously been described in association with BRAF inhibitor treatment, but not MEK inhibitor treatment. Combination treatment is usually associated with a lower incidence of cutaneous adverse events (AEs), as compared to monotherapy. Panniculitis was observed in two patients during combined BRAF and MEK inhibitor treatment. These cases illustrate the need for further research in a larger patient population to identify a possible link between combined BRAF and MEK inhibitor treatment and the incidence of panniculitis.

  1. Intratumoral Approaches for the Treatment of Melanoma.

    Science.gov (United States)

    Bommareddy, Praveen K; Silk, Ann W; Kaufman, Howard L

    There have been significant advances in the immunotherapy of melanoma over the last decade. The tumor microenvironment is now known to promote an immune-suppressive milieu that can block effective immune-mediated tumor rejection. Several novel strategies designed to overcome local immunosuppression hold promise for treatment of melanoma and other cancers. These approaches include oncolytic viruses, plasmid DNA delivery, Toll-like receptor agonists, inflammatory dyes, cytokines, checkpoint inhibitors, immunomodulatory agents, and host and pathogenic cell-based vectors. In addition, there are several novel methods for local drug delivery, including direct injection, image-guided, electroporation, and nanodelivery techniques under study. The approval of talimogene laherparepvec (Imlygic), an attenuated, recombinant oncolytic herpesvirus, for melanoma treatment is the first intratumoral agent to receive regulatory approval for the treatment of patients with melanoma. This review will focus on the rationale for intratumoral treatment in melanoma, describe the clinical and safety data for some of the agents in clinical development, and provide a perspective for future clinical investigation with intratumoral approaches. Melanoma has been a paradigm tumor for progress in targeted therapy and immunotherapy and will likely also be the tumor to establish the therapeutic role of intratumoral treatment for cancer.

  2. [Systemic treatment of inoperable metastasized malignant melanoma].

    Science.gov (United States)

    Gutzmer, R; Rauschenberg, R; Meier, F

    2016-07-01

    The medical therapy of inoperable malignant melanoma has changed dramatically over the last few years. The purpose of this article is to summarize the current state of systemic medical treatment of malignant melanoma. Clinical studies and guidelines in the therapy of malignant melanoma are reviewed. Medical therapy of inoperable melanoma changed due to developments in immunotherapies (checkpoint inhibitors) and molecular-targeted therapies (BRAF and MEK inhibitors). Checkpoint inhibitors are antibodies administered as infusions every 2-3 weeks, blocking the checkpoints PD-1 or CTLA-4, thus, preventing downregulation of the immune system. BRAF and MEK inhibitors are small molecules, they are given orally and block a certain signaling pathway in tumor cells. The activation of this pathway has to be demonstrated by molecular analysis of tumor tissue first. This strategy is currently registered for 40-50 % of melanomas harboring a BRAF V600 mutation, while the combination of a BRAF plus MEK inhibitor has been proven more efficient than a BRAF inhibitor alone. A fascinating development has started in the melanoma field due to immunotherapeutic and molecular-targeted treatment strategies. The continuation of this development needs further clinical and translational studies. This includes particular clinical studies with the new substances in the adjuvant situation, and sequences and combinations in the metastatic setting. Translational studies are needed to develop biomarkers for response and side effects.

  3. Dengue fever outbreak: a clinical management experience

    International Nuclear Information System (INIS)

    Ahmed, S.; Illyas, M.

    2008-01-01

    To determine the frequency of dengue as a cause of fever and compare the clinical and haematological characteristics of Dengue-probable and Dengue-proven cases. All patients with age above 14 years, who were either hospitalized or treated in medical outdoor clinic due to acute febrile illness, were evaluated for clinical features of Dengue Fever (DF), Dengue haemorrhagic fever (DHF) and Dengue Shock Syndrome (DSS). Patients showing typical clinical features and haematological findings suggestive of Dengue fever (As per WHO criteria) were evaluated in detail for comparison of probable and confirmed cases of Dengue fever. All other cases of acute febrile illness, not showing clinical features or haematological abnormalities of Dengue fever, were excluded. The clinical and laboratory features were recorded on SPSS 11.0 programme and graded where required, for descriptive and statistical analysis. Out of 5200 patients with febrile illness, 107 (2%) presented with typical features of DF, 40/107 (37%) were Dengue-proven while 67/107 (63%) were Dengue-probable. Out of Dengue-proven cases, 38 were of DF and 2 were of DHF. Day 1 temperature ranged from 99-105 degreeC (mean 101 degree C). Chills and rigors were noticed in 86 (80%), myalgia in 67%, headache in 54%, pharyngitis in 35%, rash in 28%, and bleeding manifestations in 2% cases. Hepatomegaly in 1(0.5%), lymphadenopathy in 1 (0.5%) and splenomegaly in 12 (11.2%) cases. Leucopoenia (count 40 U/L in 57% cases. Frequency of clinically suspected dengue virus infection was 107 (2%), while confirmed dengue fever cases were 40 (0.8%) out of 5200 fever cases. Fever with chills and rigors, body aches, headache, myalgia, rash, haemorrhagic manifestations, platelet count, total leukocyte count, and ALT, are parameters to screen the cases of suspected dengue virus infection, the diagnosis cannot be confirmed unless supported by molecular studies or dengue specific IgM. (author)

  4. Tumor progression in uveal melanoma

    NARCIS (Netherlands)

    C.M. Mooij (Cornelia)

    1995-01-01

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

  5. Dermoscopy on subungual melanoma 

    Directory of Open Access Journals (Sweden)

    Grażyna Kamińska-Winciorek

    2013-05-01

    Full Text Available Subungual melanoma is a rare, but one of the diagnostically most difficult variants of melanoma. Unfortunately, due to its late detection, lack of an early reaction from the patient and diagnosis in advanced stages, subungual melanoma is deemed as a prognostically unfavorable variant of this malignancy. Diagnosis of subungual melanoma is very difficult to establish merely on the basis of clinical examination due to the resemblance of subungual hematoma to melanocytic nevus, fungal or bacterial infections. Dermoscopy seems to be the ideal diagnostic tool in the differential diagnosis of this life-threatening disease. Aims. To describe the basic aspects of dermoscopy of subungual melanoma and other conditions involving the nails. Methods. Review of medical database PubMed for the literature of the last 10 years on the dermoscopic patterns of subungual melanoma and other subungual diseases. Results. We collate the fundamental rules of performing dermoscopy in subungual melanoma, as well as basic dermoscopic features and diagnostic algorithms of selected subungual lesions requiring differentiation from melanoma. Conclusions. Dermoscopy is a safe, easily repeatable diagnostic method, and the knowledge of basic dermoscopic patterns of developing melanoma in subungual localization, along with the differential diagnosis of other diseases within the nail plate, will help not only dermatologists, but also the professionals of other specialties, such as surgeons, oncologists, orthopedists, and also general practitioners.

  6. 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

  7. Accumulating experience in a child abuse clinic

    African Journals Online (AJOL)

    Child Abuse and Neglect Clinic, Transvaal Memorial Institute for Child. Health and Development, and Department ... PH.. D. (Present address: Department of Paediatrics and Child Health, Medical University of Southern Africa, ..... common in children who suffer other kinds of stress, especially when there is potential for the.

  8. Emotional Intelligence in Intensive Clinical Experiences for Nursing Students

    Science.gov (United States)

    Zoromski, Lorraine M.

    2017-01-01

    This study looked for associations between measures of emotional intelligence in an intensive clinical experience for nursing students in their final semester of an associate's degree program. The theory of emotional labor was used to make connections between nursing clinical experience and emotional intelligence. Twenty nursing students from a…

  9. Intraoperative radiotherapy. Clinical experiences and results

    Energy Technology Data Exchange (ETDEWEB)

    Calvo, F.A.; Santos, M. (Clinica Universitaria, Dept. of Oncology, Service of Radiotherapy, Pamplona (Spain)); Brady, L.W. (Hahnemann Univ., Dept. of Radiation Oncology, Philadelphia, PA (United States)) (eds.)

    1992-01-01

    This monograph reports on the largest clinical series to date in which intraoperative radiation therapy (IORT) has been used in mulitdisciplinary treatment programs for tumors of various sites and differing histological sybtype. It represents the product of 5 years' intensive work by physicians active at a leading European institution. The findings are supplemented by a thorough review of the data presented worldwide during the last two decades. The results in this book are meticulously presented and focus on the most important features of clinical research reports based on phase I-II studies (toxicity, local tumor control, and survival data). The tumor sites and histologies analyzed are: head and neck cancer, lung cancer, gastric cancer, pancreatic cancer, colorectal cancer, bladder cancer, gynecologic cancer, soft tissue sarcomas of the extremities, retroperitoneal and other central soft issue sarcomas, Ewing's sarcoma, osteosarcoma, and intracranial tumors. (orig./MG) With 60 figs.

  10. Clinical Engineering: Experiences of assisted professional practices

    International Nuclear Information System (INIS)

    Langone, Luis; Vanetta, Marcos; Vazquez, Marcelo; Rotger, Viviana I; Olivera, Juan Manuel

    2007-01-01

    In the curricula of the Biomedical Engineering career of the Facultad de Ciencias Exactas y TecnologIa of the Universidad Nacional de Tucuman, Argenitna, there are the Assisted Professional Practices. Within this framework, the students have the possibility of performing practices in the clinic Sanatorio 9 de Julio. One of the objectives of these practices is to apply the concepts, methods and procedures studied along the career in the field work under real work conditions. From the point of view of the host institution, the objective is to improve the performance of the different services and areas applying the tools of Biomedical Engineering. The present work shows an example of such practices where an equipment preliminary analysis was made, its use and maintenance corresponding to the surgical unit of the clinic

  11. [Clinical experience with a new microfilled composite].

    Science.gov (United States)

    Grandini, R; Pagavino, G; Nardi, P

    1990-02-01

    The authors have investigated a new material for esthetic restoration for front teeth. It is a microfilled heterogene composite (Helio Progress) with spheridal prepolymer. The clinical trials were realized in cavities III, IV an V, in anomal y teeth and resin ceramic (with a pretreatment with silane). The results after 18 months have demonstrated the better characteristics of this material in relation with foreknown ones.

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

    Science.gov (United States)

    2016-05-06

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

  13. Epidemiology of uveal melanomas in Moscow

    Directory of Open Access Journals (Sweden)

    E. E. Grishina

    2017-01-01

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

  14. First Experience with OSCE as an Exit Clinical Examination for ...

    African Journals Online (AJOL)

    Background: The evaluation of clinical skills of surgical residents has long been viewed by surgical educators as problematic and the Objective Structured Clinical Examination (OSCE) is said to address the deficiencies of the traditional clinical examinations. Here, we report findings from evaluation of our first experience ...

  15. 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.

  16. Verrucous-Keratotic Malignant Melanoma (VKMM

    Directory of Open Access Journals (Sweden)

    Nikolay Damianov

    2017-07-01

    Full Text Available We report a patient with a verrucous keratotic variant of melanoma visiting the policlinic of Medical Institute of Ministry of Interior (MVR-Sofia, Department of Dermatology and Dermatologic surgery, with a keratotic verrucous lesion, located on the right thigh, partially deeply pigmented at upper right quadrant. The lesion had appeared three years ago before her presentation in the policlinic, and it had gradually enlarged and become darker in the last twelve months. The surface of the lesion was covered with thick hyperkeratotic lobules. The histologic evaluation revealed verrucous melanoma with a tumour thickness of 3 mm and Clark Level IV and focal ulceration. The tumour was staged as stage IIB (T3bN0M0. Sentinel lymph node biopsy was planned. Verrucous-keratotic forms of malignant melanoma occur more commonly in women and favour the extremities, but may be found on any anatomic site. Seventy-one percent of this melanoma type are situated on the upper and lower extremities. Although two-thirds of these neoplasms can be can be histologically graded according to the classification of Clark, one-third of these melanomas with marked verrucous hyperplasia and hyperkeratosis of the epidermis do not fit into his classification. Histological classification of patients with a verrucous keratotic type of melanoma may sometimes be extremely difficult. The marked papilliferous architecture of these lesions made an assessment of Breslow depth difficult. The presented case highlights the clinical existence and features of such benign-looking melanomas. It is therefore important for surgical pathologists to recognise this unusual variant of malignant melanoma, as it may be confused both clinically and pathologically with benign lesions.

  17. Aspirin and other NSAIDs as chemoprevention agents in melanoma

    Science.gov (United States)

    Goodman, James R.; Grossman, Douglas

    2014-01-01

    Melanoma incidence is increasing and, despite recent therapeutic advances, the prognosis for patients with metastatic disease remains poor. Thus early detection and chemoprevention are promising strategies for improving patient outcomes. Aspirin (ASA) and other non-steroidal anti-inflammatory drugs (NSAIDs) have demonstrated chemoprotective activity in several other cancers, and have been proposed as chemopreventive agents for melanoma. Throughout the last decade, however, a number of case-control, prospective, and interventional studies of NSAIDs and melanoma risk have yielded conflicting results. These inconsistent findings have led to uncertainty about the clinical utility of NSAIDs for melanoma chemoprevention. This mini-review highlights current knowledge of NSAID mechanisms of action and rationale for use in melanoma, provides a comparative review of outcomes and limitations of prior studies, and discusses the future challenges in demonstrating that these drugs are effective agents for mitigating melanoma risk. PMID:24694780

  18. Prognostic value of BRAF mutations in localized cutaneous melanoma.

    Science.gov (United States)

    Nagore, Eduardo; Requena, Celia; Traves, Víctor; Guillen, Carlos; Hayward, Nicholas K; Whiteman, David C; Hacker, Elke

    2014-05-01

    BRAF mutations are frequent in melanoma but their prognostic significance remains unclear. We sought to further evaluate the prognostic value of BRAF mutations in localized cutaneous melanoma. We undertook an observational retrospective study of 147 patients with localized invasive (stages I and II) cutaneous melanomas to determine the prognostic value of BRAF mutation status. After a median follow-up of 48 months, patients with localized melanomas with BRAF-mutant melanomas exhibited poorer disease-free survival than those with BRAF-wt genotype (hazard ratio 2.2, 95% confidence interval 1.1-4.3) even after adjustment for Breslow thickness, tumor ulceration, location, age, sex, and tumor mitotic rate. The retrospective design and the small number of events are limitations. Our findings suggest that reappraisal of clinical treatment approaches for patients with localized melanoma harboring tumors with BRAF mutation might be warranted. Copyright © 2013 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

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

    Science.gov (United States)

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

    2014-11-01

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

  20. [Richter syndrome: clinical characteristics and treatment experiences].

    Science.gov (United States)

    Li, Zeng-jun; Xu, Yan; Zhang, Pei-hong; Liu, Wei; Yi, Shu-hua; Zou, De-hui; Qi, Jun-yuan; Zhao, Yao-zhong; Qiu, Lu-gui

    2012-12-11

    To summarize the clinical characteristics of Richter syndrome and explore the methods of successful treatment and timely diagnosis. Five patients with Richter syndrome in the last three years (from January 2009 to December 2011) were analyzed retrospectively at our hospital, including their clinical features and therapy before and after transformation. There were 4 males and 1 female with a median age on a diagnosis of chronic lymphocytic leukemia (CLL) at 47 (44 - 68) years. The median duration from a diagnosis of CLL to transformation was 52 (5 - 90) months. As for cytogenetic abnormalities, 3/4 patients had 17p deletion by fluorescence in situ hybridization (FISH). The clinical manifestations on transformation included regional enlargement of lymph node (n = 2) and systemic enlargement of lymph nodes (n = 3). All diagnoses were confirmed by lymph node biopsy and all transformed into diffuse large B cell lymphoma (classical transformation). The subgroups were germinal center B-cell like (GCB) (n = 3) and non-GCB (n = 1). After transformation, one patient underwent sibling allo-stem cell transplantation and survived 24 months until April 2012. Another patient with auto-stem cell transplantation relapsed and died 12 months later. One patient lost the treatment opportunity due to worsening condition. Another 2 patients gained partial remission after therapy and survived 20 and 8 months respectively. Richter syndrome may occur during a late stage of CLL. Such a high-risk cytogenetic abnormality as del17p may be correlated with transformation. Early identification and optimal therapy may extend the survival of Richter syndrome. Allo-stem cell transplantation remains a curable option.

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

    International Nuclear Information System (INIS)

    Mishima, Yutaka; Ichihashi, Masamitsu; Nakanishi, Takafumi

    1985-01-01

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

  2. 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.

  3. Key points in the dermoscopic diagnosis of hypomelanotic melanoma and nodular melanoma.

    Science.gov (United States)

    Moloney, Fergal J; Menzies, Scott W

    2011-01-01

    Nodular melanoma (NM) and amelanotic/hypomelanotic melanoma (AHM) often present a challenge to the diagnosing clinician. A significant proportion of AHM are nodular in nature. Such tumors may lack features of asymmetry and altered peripheral pigmentation routinely observed in other melanoma subtypes. This lack of distinguishing clinical features can potentially result in delayed diagnosis or inappropriate treatment. This review highlights the key points in evaluating the range of lesions where AHM or NM are considered in the differential diagnosis and summarizes current evidence in relation to pigmented and vascular dermoscopic diagnostic criteria for both. © 2011 Japanese Dermatological Association.

  4. Decoding Melanoma Metastasis

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-12-30

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

  5. 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.

  6. Incidence of melanoma in organ transplant recipients in Alberta, Canada.

    Science.gov (United States)

    Tran, Mimi; Sander, Megan; Ravani, Pietro; Mydlarski, P Régine

    2016-10-01

    Many studies have documented the increased risk of non-melanoma skin cancers in organ transplant recipients (OTRs). However, the incidence of melanoma is less well defined. To date, there have been no studies on the incidence of melanoma in Canadian OTRs. Herein, we determine the incidence and clinical features of melanoma in a cohort of OTRs in Southern Alberta, Canada. We used the Southern Alberta Transplant database to identify kidney and liver transplant recipients between the years 2000 and 2012. This population was cross-referenced with the Alberta Cancer Registry for a diagnosis of melanoma. The clinical features of all cases were obtained, and the standardized incidence rate was calculated. We identified 993 OTR patients, representing 5955 person-years. Only one patient developed a melanoma post-transplant, and this was a nodular melanoma. The age-standardized incidence rate was 11 per 100 000 (0.6 per 5955), compared to 13.4 per 100 000 in the general Alberta population (incidence rate ratio of 1.29, with 95% confidence interval of 0.17 to 9.82). This is the first Canadian study to investigate the association between organ transplantation and melanoma. Our study did not identify an increased risk of developing a de novo melanoma post-transplant. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Expression of PIWIL3 in primary and metastatic melanoma.

    Science.gov (United States)

    Gambichler, Thilo; Kohsik, Christina; Höh, Ann-Kathrin; Lang, Kerstin; Käfferlein, Heiko U; Brüning, Thomas; Stockfleth, Eggert; Stücker, Markus; Dreißigacker, Max; Sand, Michael

    2017-03-01

    The PIWI-interacting RNA machinery in malignant melanoma (MM) has not been sufficiently studied. We aimed to investigate the PIWIL3 expression profiles in primary melanomas and metastases of MM including a correlation with clinical data. We studied 161 primary melanomas, 45 lymph node metastases, and 16 distant metastases of 183 patients with MM. We used immunohistochemistry to assess PIWIL3 protein expression in situ. The relationship between the immunoreactivity of PIWIL3 and clinical data was statistically evaluated. We observed a significantly (P = 0.000059) higher median immunoreactivity score in primary melanomas (4.9; range, 0.1-6), lymph node metastases (5.1; range, 3.3-6), and distant metastases (5.6; range, 4.5-6). PIWIL3 was expressed significantly higher (P = 0.0002) in primary nodular melanomas and acral melanomas (5.2; range, 3.4-6) when compared to other melanoma subtypes (4.7; range, 0.1-6). On univariate analysis, a significant positive correlation was observed between primary melanoma PIWIL3 expression and tumor thickness (r = 0.2; P = 0.014). On univariate and multivariate analysis, PIWIL3 did not prove to be an independent predictor for melanoma relapse or death. Our data indicate that PIWIL3 protein expression is elevated in more aggressive primary MM and metastatic disease. As also observed in other malignancies, PIWIL3 seems to play a role in MM progression.

  8. 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.

  9. Insomnia: clinical experience with zolpidem (sanval

    Directory of Open Access Journals (Sweden)

    Yakov Iosifovich Levin

    2010-01-01

    Full Text Available The paper describes the present view of the problem of insomnia and gives a classification of sleep disorders and basic methods for their drug and non-drug therapy. Emphasis is placed on the role of the objective sleep study - polysomnography. The use of the current hypnotics belonging to a three Zs group and the minimization of administration of benzodiazepines are most important in pharmacotherapy for insomnia. The results of a clinical polysomnographic study of the effect of Zolpidem (Sanval in patients with insomnia are presented. The subjective evaluation of the beneficial effect of a 10-day course of Sanval is confirmed by the objective studies of the sleep pattern undergoing positive changes in the most important indicators, such as the process of falling asleep, the time of intrasleep awakenings, and the duration of Δ-sleep. The high safety and good tolerability of Sanval permit the latter to be assessed as an effective agent for the treatment of insomnia.

  10. Cognitive development, clinical knowledge, and clinical experience related to diagnostic ability.

    Science.gov (United States)

    Aquilino, M L

    1997-01-01

    To examine the relationship among cognitive development, clinical knowledge, and clinical experience in nursing students. A survey of junior and senior baccalaureate nursing students from three Midwestern colleges (N = 55). Students' diagnostic ability increased as they gained clinical experience and clinical knowledge. However, students failed to identify many nursing diagnoses and demonstrated only moderate levels of cognitive development. Nurse educators and nursing students need to change their approaches to teaching and learning to enhance students' diagnostic ability and cognitive development.

  11. Cartap hydrochloride poisoning: A clinical experience.

    Science.gov (United States)

    Boorugu, Hari K; Chrispal, Anugrah

    2012-01-01

    Cartap hydrochloride, a nereistoxin analog, is a commonly used low toxicity insecticide. We describe a patient who presented to the emergency department with alleged history of ingestion of Cartap hydrochloride as an act of deliberate self-harm. The patient was managed conservatively. To our knowledge this is the first case report of Cartap hydrochloride suicidal poisoning. Cartap toxicity has been considered to be minimal, but a number of animal models have shown significant neuromuscular toxicity resulting in respiratory failure. It is hypothesized that the primary effect of Cartap hydrochloride is through inhibition of the [(3)H]-ryanodine binding to the Ca(2+) release channel in the sarcoplasmic reticulum in a dose-dependent manner and promotion of extracellular Ca(2+) influx and induction of internal Ca(2+) release. This results in tonic diaphragmatic contraction rather than paralysis. This is the basis of the clinical presentation of acute Cartap poisoning as well as the treatment with chelators namely British Anti Lewisite and sodium dimercaptopropane sulfonate.

  12. The European approach to in-transit melanoma lesions

    NARCIS (Netherlands)

    Hoekstra, H. J.

    The biological behavior of melanoma is unpredictable. Three to five per cent of melanoma patients will develop in-transit lesions and the median time to recurrence ranges between 13-16 months. At the time of recurrence the risk of occult nodal metastasis, with clinically negative regional lymph

  13. Percutaneous gastrostomy and gastroenterostomy: 2. Clinical experience.

    Science.gov (United States)

    van Sonnenberg, E; Wittich, G R; Cabrera, O A; Quinn, S F; Casola, G; Lee, A A; Princenthal, R A; Lyons, J W

    1986-03-01

    This report describes the authors' initial experience with percutaneous gastrostomy (PG) and gastroenterostomy (PGE) in 40 patients. Indications for PG and PGE included alimentation (35 patients) and small bowel decompression (five). Seldinger technique with air distension of the stomach via a nasogastric tube (20 patients) is a simple method to insert small (7-9 French) and firm catheters; tube exchanges for larger and softer catheters often are necessary by this method (23 procedures in 17 patients). Coaxial trocar technique (19 patients) permits initial insertion of softer and often larger catheters (9-14 French feeding tubes), which are less likely to clog or require exchange; the intragastric balloon support method facilitates trocar insertion. Now preferred is a system that uses 18-gauge needle puncture and allows coaxial insertion of a final soft feeding tube at the initial procedure. Small bowel catheter positioning (PGE) (31 patients) was more common than gastrostomy alone (8 patients); "downhill puncture" toward the gastric antrum assists direct guide-wire cannulation of the duodenum via the gastric puncture (12 patients). Five complications occurred; two were major and included catheter dislodgement in one patient. Another patient, who had a pharyngeal tumor, suffered profound respiratory difficulty from premedication and nasogastric tube malposition; patients with head and neck tumors present particular problems with nasogastric tube passage and airway monitoring. Inability to pass a nasogastric tube does not preclude PG and PGE, as direct puncture of the stomach is feasible.

  14. Review article: clinical experience with Prometheus.

    Science.gov (United States)

    Rifai, Kinan; Manns, Michael P

    2006-04-01

    Prometheus is a new extracorporeal liver support device which facilitates the combined removal of both albumin-bound and water-soluble toxins based upon the method of fractionated plasma separation and adsorption (FPSA). The pilot trial included 11 patients with acute-on-chronic liver failure and concomitant renal failure. Prometheus therapy was found to be safe except for a reversible decrease of blood pressure. In three patients, clotting of the secondary system occurred. Prometheus treatment significantly improved blood levels of protein-bound (conjugated bilirubin, bile acids, ammonia) and water-soluble (creatinine, urea) substances. Thus, Prometheus might be a new therapeutic option in patients with severe hepatorenal syndrome. Furthermore, there is some preliminary experience with Prometheus in the treatment of refractory cholestatic pruritus and in successful bridging to liver transplantation. In order to compare extraction capacities of Prometheus and the molecular adsorbent recirculating system (MARS), five patients were crossover-treated with both systems. Prometheus resulted in significantly higher reduction ratios of bilirubin, ammonia and urea. Another study closely monitored whether the device causes an unselective removal. Neither important cytokines nor coagulation factors were found to be removed. In conclusion, Prometheus seems to be a new therapeutic option in artificial liver support. A significant improvement of the biochemical milieu was already observed after two treatments. The potential to remove protein-bound and water-soluble substances has been shown without signs of a significant unselective removal.

  15. 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.

  16. Tinnitus: clinical experience of the psychosomatic connection

    Directory of Open Access Journals (Sweden)

    Salviati M

    2014-02-01

    the lack of coping capabilities can play a critical role in the clinical history of patients affected by severe tinnitus.Keywords: tinnitus, psychosomatics, stress, psychopathological dimensions, personality

  17. Vertigo in childhood: a clinical experience.

    Science.gov (United States)

    Erbek, Seyra H; Erbek, Selim S; Yilmaz, Ismail; Topal, Ozgul; Ozgirgin, Nuri; Ozluoglu, Levent N; Alehan, Fusun

    2006-09-01

    Vertigo in childhood is a complaint consisting of a wide spectrum of diagnoses. The aim of this study was to evaluate pediatric patients with vertigo with normal eardrum and middle ear findings and discuss the differential diagnoses. Patient records of 50 children under 18 years of age with vertigo as the chief complaint, examined at the Baskent University, Research and Application Centers at Konya and Adana otorhinolaryngology clinics between May 2003 and October 2005 were retrospectively reviewed. The questionnaires, laboratory tests including blood samples, audiological and vestibular tests, and final diagnoses were analyzed. Patients with perforated eardrums, otitis media with effusion, and acute upper respiratory tract infections were not included in the study. The study group consisted of 50 patients (33 females, 66%; 17 males, 34%), between 4 and 17 years of age (mean age, 11.5+/-3.9 years). Severe sensorineural hearing loss was present in one patient unilaterally (2%) and one patient bilaterally (2%). Bilateral low-frequency sensorineural hearing loss was present in one patient (2%). Electronystagmography revealed central vestibular abnormalities in three patients (6%). Canal paresis was established in six patients (12%). The Dix-Hallpike test was positive in six patients (12%). The most frequent cause of vertigo was migraine, occurring in 34% of patients (n=17). Other less-frequent etiologies of vertigo were benign paroxysmal vertigo (n=6; 12%), benign paroxysmal positional vertigo (n=6; 12%), psychogenic vertigo (n=5; 10%), epilepsy (n=3; 6%), metabolic disorders (n=3; 6%), vestibular neuritis (n=2; 4%), Meniere's disease (n=1; 2%), perilymphatic fistula (n=1; 2%), amblyopia (n=1; 2%), and unclassifiable (n=5; 10%). Migraine was found to be the most frequent presenting diagnosis in childhood vertigo, although several peripheral vestibular disorders also were diagnosed. Evaluation of vertigo in childhood should begin with a thorough neuro

  18. Ameloblastoma: Our clinical experience with 68 cases

    Directory of Open Access Journals (Sweden)

    Benjamin Fomete

    2014-01-01

    Full Text Available Introduction: In this environment, previous workers have reported on the challenges of managing large sized ameloblastoma of the jaws with less than adequate facilities. The aim of this review is to present the management of 68 cases of ameloblastoma with emphasis on surgical care. Materials and Methods: Retrospective survey of case notes of patients with histopathologic diagnosis of ameloblastoma (using the criteria of Barnes et al., 2005 seen between January 2006 and August 2010 at the Maxillofacial Unit, Ahmadu Bello University Teaching Hospital, Shika-Zaria, Nigeria was undertaken. Data collected includes histopathological diagnosis, age, gender, clinical information on site of lesion, form of intubation and surgical procedure performed. Results: Out of 94 patients, 68 with histological diagnosis of ameloblastoma (59 mandibular and 9 maxillary were operated within the study period. The remainder (26 was not treated in hospital. Among 68 patients treated, more were males (38 than females (30, giving a male to female ratio of 1.3:1. The age range was between 14 and 74 years (mean-standard deviation. The duration of the symptoms ranged from 7 months to 24 years, most were follicular ameloblastoma (n = 13 followed by acanthomatous type (n = 7. Endotracheal intubation was the most common (n = 55 followed by fiber optic laryngoscopy (n = 8. The surgical approach most used was extended Risdon with intraoral (n = 24 followed by extended Risdon with lip split and intraoral (n = 17. Segmental resection (en block formed the bulk of our procedures (n = 22 followed by subtotal mandibulectomy (n = 16. Conclusion: The treatment of ameloblastoma remains controversial. Its destructive nature has left patients with wide defects difficult to reconstruct.

  19. 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

  20. Clinical surgical Experiences with 51-ileal pouches

    International Nuclear Information System (INIS)

    Puerta, Juan D; Castano, Rodrigo; Arismendi, Ivan R

    2004-01-01

    Restorative proctocolectomy and ileal pouch (IP) has become an established surgery for patients with chronic ulcerative colitis and poliposis syndromes. The authors report the results of 8-year experience of restorative proctocolectomy and IP. Chart review was performed for 51 patients undergoing IP from 1994 through 2002. Preoperative histopathologic diagnoses were ulcerative colitis (n=39), poliposis syndromes (n=10), 2 Crohn diseases and 1 patient with colorectal cancer and extended resection. Information was obtained regarding patient demographics, type and duration of diseases, previous operations, and indications for surgery. Early (within 30 days after surgery) and late complications were noted. Follow-up included an annual function, physical examination, and biopsies of the pouch and anal transitional zone when were indicated. Of the 51 patients (24 women) with mean follow-up time of 44,5 months (range 12 -108 months), histopathologic diagnoses of ulcerative colitis were changed for Crohn's disease in 2 patients. The overall mortality rate was 2% (1 patient) one death was related to perineal sepsis 45 months after ileal pouch. The overall morbidity rate was 65% (73 complications in 33 patients; early 39%; late 49%) the mean hospitalary stance was 8, 9 days (range 6-25 days). Small bowel obstruction, septic complication and reoperation rates were 36%, 22% and 26%, respectively. The most frequent late complication was pouchitis (31,8%). The ileal pouch was removed in 1 patient, and it is functional in 50 (98%). There was a satisfactory index with 82% with excellent-good results, and 16% and 2% with regular and bad results. Restorative proctocolectomy with an IP is a safe procedure, with low mortality and major morbidity rates. Although total morbidity rate is appreciable, functional results generally are good and patient satisfaction is acceptable

  1. Differences in clinical experiences of ADN and BSN students.

    Science.gov (United States)

    Oermann, M H

    1998-05-01

    Prior research has suggested that clinical experience for nursing students is stressful. Concern about making an error and harming the patient, limited knowledge and skills for practice, and difficulties in interacting with the teacher and others in the clinical setting are some of the stressors reported by students. Few studies have compared these stresses and the clinical experiences in general between students in associate degree (ADN) and baccalaureate (BSN) nursing programs. The purposes of this research were to compare the clinical experiences of ADN and BSN students at different levels in the programs and describe these experiences from the students' perspectives. As such, both quantitative and qualitative data were collected from 415 students in ADN and BSN programs in the Midwest. The ADN students reported significantly higher stress in clinical practice than BSN students (t = 2.16, p ADN and BSN students in clinical practice increased as they progressed through the programs. The semester prior to graduation was the most stressful time in terms of clinical practice for both ADN and BSN students. The instructor was the predominant stressor reported by students in ADN programs across all levels of the curriculum. Among BSN students, the most prevalent stresses were coping with demands associated with patient care and the clinical teacher. The findings highlight the important role of the clinical faculty in both types of nursing programs.

  2. Intention to Obtain Genetic Testing for Melanoma among Individuals at Low to Moderate Risk for Hereditary Melanoma

    Science.gov (United States)

    Vadaparampil, Susan T.; Azzarello, Lora; Pickard, Jennifer; Jacobsen, Paul B.

    2007-01-01

    Background: Melanoma is a serious skin cancer that has been on the rise in the United States. Some genetic component is apparent. Purpose: The purpose of this study was to identify demographic, clinical, attitudinal, and health belief factors associated with intention to obtain genetic testing for hereditary melanoma among unaffected first-degree…

  3. The good clinical nursing educator and the baccalaureate nursing clinical experience: attributes and praxis.

    Science.gov (United States)

    Hanson, Karla J; Stenvig, Thomas E

    2008-01-01

    Clinical education accounts for a significant portion of baccalaureate nursing (BSN) education. This study examined recent BSN program graduates' views about clinical nursing educator attributes that enhance the ability of the graduates to provide safe, effective patient care. In this descriptive study, 6 participants were interviewed using grounded theory techniques. The study framework blended the elements of cognitive field theory, the humanistic philosophy of teaching and learning, the gestalt theory of learning, and Hergenhahn's behavioral change model. Participants identified three attributes of a good clinical nursing educator: knowledge, interpersonal presentation, and teaching strategies. Analysis revealed that educator attributes and phases of the clinical experience process together form the foundation for clinical experience praxis. Educators can improve the clinical education experience by developing teaching strategies and evaluation tools that build on the positive attributes and phases of the clinical experience identified in this study.

  4. Treatment Options for Intraocular (Uveal) Melanoma

    Science.gov (United States)

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

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

    Science.gov (United States)

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

  6. General Information about Intraocular (Uveal) Melanoma

    Science.gov (United States)

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

  7. 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

  8. 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.

  9. Toxicity and morbility after isolated lower limb perfusion in 242 chemo-hyperthermal treatments for cutaneous melanoma: The experience of the Tuscan Reference Centre

    Directory of Open Access Journals (Sweden)

    Bechi Paolo

    2008-11-01

    Full Text Available Abstract Background The aim of this retrospective study was to assess the results concerning the regional and systemic toxicity and complications in 242 chemo-hyperthermal treatments (HILPs for lower limb melanoma. Patients and methods 60 HILPs (G-A were performed with mild HT plus L-PAM (10 mg/lt ± D-actimomycin; 74 HILPs (G-B with true HT (40–41.8°C plus L-PAM (10 mg/lt ± D-act; 108 HILPs (G-C with true HT plus L-PAM (10 mg/lt ± D-act plus L-PAM (5 mg/lt additional bolus. Results Limb toxicity was very low in G-A and in G-B; increasing toxicity (grade III = 37% in G-C; no grade IV statistical difference was registered in all three groups, with percentage values among 1.6% and 2.7%. Systemic toxicity showed itself only in the haemopoietic parameters. No differences were registered in G-B vs G-A group. In G-C vs G-B a significative increase of systemic toxicity was seen in grade 3 (p Conclusion These data suggested that the technical implementations reduced the occurrence and the severity of the side effects and complications. The essential requirement for HILP is the quality assurance of the procedures. Although higher regional and systemic toxicity were observed in the G-C group caused by L-PAM additional bolus, the safeness of the procedures under the true hyperthermal regimen and the time increase of the high L-PAM concentration have assured the treatment reliability along with the increased clinical efficacy expectations of the treatments.

  10. Primary orbital melanoma in association with cellular blue nevus.

    Science.gov (United States)

    El-Sawy, Tarek; Bakhoum, Mathieu F; Tetzlaff, Michael; Nasser, Qasiem J; Prieto, Victor G; Ivan, Doina; Sniegowski, Matthew C; Yin, Vivian T; Pan, Caroline; Durairaj, Vikram; Esmaeli, Bita

    2014-01-01

    To describe 3 cases of primary orbital melanoma associated with either known or subsequently discovered cellular blue nevus. The clinical records and surgical specimens of 3 patients who underwent orbital exenteration for primary orbital melanoma and who had a cellular blue nevus diagnosed before or after detection of the melanoma were retrospectively reviewed. All 3 patients presented with signs and symptoms of an orbital mass. Subsequent biopsy revealed invasive melanoma. One patient had a known history of congenital cellular blue nevus of the eyelid from which the orbital melanoma originated. The other 2 patients had no known history of cutaneous pigmentation or blue nevus. In these 2 patients, the cellular blue nevus was detected on pathologic review of the orbital exenteration specimen (1 patient) or surgical biopsy specimen (1 patient). All 3 patients underwent total body positron emission tomography/computed tomography, and in all 3 results were negative for other sites of disease involvement. In the 2 patients without a previously known nevus a total body skin check was negative for other primary melanoma lesions. All 3 patients underwent orbital exenteration followed by postoperative radiation therapy. Thorough evaluation of biopsy specimens of "primary" orbital melanoma is warranted to ensure identification of any associated blue nevus because blue nevi are precursor lesions for orbital melanoma, and the presence of a blue nevus would support a primary orbital melanoma rather than a metastatic lesion. Patients with a known blue nevus of the periocular skin and ocular adnexa should be monitored closely for signs of malignant transformation.

  11. 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.

  12. 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)

  13. Experiences of health science students during clinical placements at ...

    African Journals Online (AJOL)

    Background: Clinical placement is an essential component of training in health sciences because it is where theory and practice interface. Objective: To explore experiences of health sciences students during clinical placement in terms of supervision, challenges and coping strategies. Design: It was a cross sectional survey ...

  14. Traumatic stress and psychopathology: experiences of a trauma clinic

    African Journals Online (AJOL)

    Adele

    traumatic events were grouped according to Friedman's categorisation of traumatic exposure and experience2 as follows: Traumatic stress and psychopathology: experiences of a trauma clinic. U Subramaney. Division of Psychiatry, Department of Neurosciences, University of the Witwatersrand, and Centre for the Study of ...

  15. Staging of cutaneous melanoma

    NARCIS (Netherlands)

    P. Mohr (P.); A.M.M. Eggermont (Alexander); A. Hauschild (Axel); A. Buzaid (A.)

    2009-01-01

    textabstractThe American Joint Committee on Cancer (AJCC) staging of cutaneous melanoma is a continuously evolving system. The identification of increasingly more accurate prognostic factors has led to major changes in melanoma staging over the years, and the current system described in this review

  16. Bronchial malignant melanoma.

    Science.gov (United States)

    Weshler, Z; Sulkes, A; Kopolovitch, J; Leviatan, A; Shifrin, E

    1980-01-01

    We describe a case of malignant melanoma presenting initially as an endobronchial lesion located in the left main bronchus causing total atelectasis. This resolved with radiation therapy. Widespread metastases developed shortly thereafter. The differential diagnosis of primary and metastatic bronchial malignant melanoma is discussed. Other isolated case reports are reviewed.

  17. 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.

  18. Plasma 25-hydroxyvitamin D and risk of non-melanoma and melanoma skin cancer: a prospective cohort study.

    Science.gov (United States)

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

    2013-03-01

    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. melanoma skin cancer were 4.7 (0.96-23.3) for 25-OH-vitD ≥50 vs. melanoma skin cancer and 1.5% for melanoma skin cancer, in participants with age >60 years, 25-OH-vitD winter levels ≥50 nmol  l(-1), and performing outdoor exercise. In conclusion, we show that increasing levels of 25-OH-vitD are associated with increased risk of non-melanoma and melanoma skin cancer.

  19. Exploring Knowledge, Attitudes, and Practice Associated With Meditation Among Patients With Melanoma.

    Science.gov (United States)

    Russell, Lahiru; Orellana, Liliana; Ugalde, Anna; Milne, Donna; Krishnasamy, Meinir; Chambers, Richard; Livingston, Patricia M

    2017-03-01

    To explore the knowledge, attitudes, and practices associated with meditation among people with melanoma and investigate the relationship between perceived stress, trait mindfulness, and meditation. Factors associated with interest to participate in an online meditation program were also explored. A survey-based cross-sectional study of 291 patients attending a melanoma outpatient clinic assessed knowledge of meditation, attitudes toward meditation using Determinants of Meditation Practice Inventory (DMPI), and meditation experience. Perceived stress and trait mindfulness were measured using the Perceived Stressed Scale and Cognitive and Affective Mindfulness Scale, respectively. Participants who had tried meditation (43%) were likely to be younger, female, and have completed higher education or be employed. Perceived stress score was higher among women, younger participants, and those treated in the past year but did not differ by melanoma stage. Participants reported a good understanding of the potential benefits of meditation, but even among people with meditation experience, common misconceptions prevailed. The main barrier to meditation was a perceived lack of knowledge about meditation . Higher DMPI scores were associated with lower education, moderate to low access to service centers, or living in disadvantaged neighborhoods . Participants practicing meditation that involved self-reflection reported less stress and higher trait mindfulness compared with participants practicing another type of meditation. People interested in participating in an online meditation-based program reported higher perceived stress than those not interested. A meditation-based intervention teaching self-reflective practices, targeted at people with melanoma, may have the potential to assist them with managing their stress.

  20. A memory of an aesthetic experience transferred to clinical practice.

    Science.gov (United States)

    Wikström, Britt-Maj

    2003-03-01

    To examine the usefulness of writing about a memory of an aesthetic experience, and then transfer the aesthetic experience to a health care situation. The study was accomplished at two university colleges of health sciences in Sweden. It started with student nurses (N=291) writing about a memory of an aesthetic experience. Then they transferred the aesthetic experience to a purposeful clinical practice. The results showed that each student could report on a positive memory of an aesthetic experience. Embedded in each story was an aesthetic experience that was meaningful to the student. Domains of memory most frequently reported were music, work of art and nature. Themes derived from the aesthetic memory were happiness and awareness. The awareness theme comprized the value of aesthetic experiences for the patients, and for student nurses. The process of writing about a memory of an aesthetic experience provided an alternative model for nursing education that could improve patient care.

  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. Cutaneous manifestations associated with melanoma.

    Science.gov (United States)

    Vyas, Ritva; Selph, Jacqueline; Gerstenblith, Meg R

    2016-06-01

    Melanoma is a malignancy most commonly arising from the skin; therefore, primary melanoma characteristics are usually the first cutaneous manifestations of melanoma. Cutaneous metastases, which can occur locally or diffusely, are important to detect in a timely manner as treatments for advanced melanoma that impact survival are now available. Melanoma can be associated with local or diffuse pigmentation changes, including depigmentation associated with the leukodermas and hyperpigmentation associated with diffuse melanosis cutis. The leukodermas occur frequently, illustrate the immunogenic nature of melanoma, and may impact prognosis. Paraneoplastic syndromes in association with melanoma are rare, though can occur. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    International Nuclear Information System (INIS)

    Alsuhaibani Adel H

    2009-01-01

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

  4. The integrated role of ultrasonography in the diagnosis of soft tissue metastases from melanoma: preliminary report of a single-center experience and literature review.

    Science.gov (United States)

    Covarelli, Piero; Burini, Gloria; Barberini, Francesco; Caracappa, Daniela; Boselli, Carlo; Noya, Giuseppe; Castellani, Elisa; Rulli, Antonio

    2013-01-01

    Currently melanoma has the fastest growing incidence of all cancers in men and the second in women (after lung cancer) in Western countries. Since prognosis of skin melanoma is excellent in early stages but dramatically worsens in advanced stages, an early diagnosis is fundamental in granting patients a favorable outcome. Sentinel node (SN) biopsy represents the gold standard for accurately staging melanoma, but other tests are commonly endorsed both in the initial staging work-up and in the follow-up, such as ultrasonography, computed tomography (CT)-scan and positron emission tomography (PET)-CT. PET-CT, among others, has high sensitivity and specificity for the study of distant metastases, the assessment of soft tissues and lymph node involvement, and for the guidance of surgical biopsies. Ultrasonography (US) is a non-invasive procedure whose use has recently expanded in our service, both preoperatively, intraoperatively and postoperatively, thanks to its wide availability, low costs and easy and fast reproducibility; ultrasonography even surpassed the reliability of PET-CT or CT-scan in the seven cases presented herein. US is operator-dependent, and this is probably the major limitation of the procedure, together with lack of prospective studies validating its strength, but our preliminary study demonstrates that ultrasound can assume an important role in melanoma, both for staging and the follow-up of patients, especially with lymph nodal or subcutaneous involvement.

  5. Photodynamic Therapy in Melanoma - Where do we stand?

    Science.gov (United States)

    Baldea, Ioana; Giurgiu, Lorin; Teacoe, Ioana Diana; Olteanu, Diana Elena; Olteanu, Florin Catalin; Clichici, Simona; Filip, Gabriela Adriana

    2017-12-25

    Malignant melanoma is one of the most aggressive malignant tumors with unpredictable evolution. Photodynamic therapy has been successfully used as the first line or palliative therapy for the treatment of lung, esophageal, bladder, non melanoma skin and head and neck cancers. However, classical photodynamic therapy has shown some drawbacks that limit its clinical application in melanoma. The most important challenge is to overcome melanoma resistance, due to melanosomal trapping, presence of melanin, enhanced oxidative stress defense, defects in the apoptotic pathways, immune evasion, neoangiogenesis stimulation. In this review we considered: (1) main signaling molecular pathways deregulated in melanoma as potential targets for personalized therapy, including photodynamic therapy, (2) results of the clinical studies regarding the photodynamic therapy of melanoma, especially advanced metastatic stage, (3) progresses made in the design of anti-melanoma photosensitizers (4) inhibition of tumor neoangiogenesis, as well as (5) advantages of the derived therapies like photothermal therapy, sonodynamic therapy. Moreover, the possibility of combined therapeutical regimens, such as photodynamic therapy and immune stimulation or theranostic approaches may increase the potential beneficial role of photodynamic therapy as an adjuvant in melanoma treatment. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  6. Dermoscopic evaluation of nodular melanoma.

    Science.gov (United States)

    Menzies, Scott W; Moloney, Fergal J; Byth, Karen; Avramidis, Michelle; Argenziano, Giuseppe; Zalaudek, Iris; Braun, Ralph P; Malvehy, Josep; Puig, Susana; Rabinovitz, Harold S; Oliviero, Margaret; Cabo, Horacio; Bono, Riccardo; Pizzichetta, Maria A; Claeson, Magdalena; Gaffney, Daniel C; Soyer, H Peter; Stanganelli, Ignazio; Scolyer, Richard A; Guitera, Pascale; Kelly, John; McCurdy, Olivia; Llambrich, Alex; Marghoob, Ashfaq A; Zaballos, Pedro; Kirchesch, Herbert M; Piccolo, Domenico; Bowling, Jonathan; Thomas, Luc; Terstappen, Karin; Tanaka, Masaru; Pellacani, Giovanni; Pagnanelli, Gianluca; Ghigliotti, Giovanni; Ortega, Blanca Carlos; Crafter, Greg; Ortiz, Ana María Perusquía; Tromme, Isabelle; Karaarslan, Isil Kilinc; Ozdemir, Fezal; Tam, Anthony; Landi, Christian; Norton, Peter; Kaçar, Nida; Rudnicka, Lidia; Slowinska, Monika; Simionescu, Olga; Di Stefani, Alessandro; Coates, Elliot; Kreusch, Juergen

    2013-06-01

    Nodular melanoma (NM) is a rapidly progressing potentially lethal skin tumor for which early diagnosis is critical. To determine the dermoscopy features of NM. Eighty-three cases of NM, 134 of invasive non-NM, 115 of nodular benign melanocytic tumors, and 135 of nodular nonmelanocytic tumors were scored for dermoscopy features using modified and previously described methods. Lesions were separated into amelanotic/hypomelanotic or pigmented to assess outcomes. Predominantly hospital-based clinics from 5 continents. Sensitivity, specificity, and odds ratios for features/models for the diagnosis of melanoma. Nodular melanoma occurred more frequently as amelanotic/hypomelanotic (37.3%) than did invasive non-NM (7.5%). Pigmented NM had a more frequent (compared with invasive non-NM; in descending order of odds ratio) symmetrical pigmentation pattern (5.8% vs 0.8%), large-diameter vessels, areas of homogeneous blue pigmentation, symmetrical shape, predominant peripheral vessels, blue-white veil, pink color, black color, and milky red/pink areas. Pigmented NM less frequently displayed an atypical broadened network, pigment network or pseudonetwork, multiple blue-gray dots, scarlike depigmentation, irregularly distributed and sized brown dots and globules, tan color, irregularly shaped depigmentation, and irregularly distributed and sized dots and globules of any color. The most important positive correlating features of pigmented NM vs nodular nonmelanoma were peripheral black dots/globules, multiple brown dots, irregular black dots/globules, blue-white veil, homogeneous blue pigmentation, 5 to 6 colors, and black color. A model to classify a lesion as melanocytic gave a high sensitivity (>98.0%) for both nodular pigmented and nonnodular pigmented melanoma but a lower sensitivity for amelanotic/hypomelanotic NM (84%). A method for diagnosing amelanotic/hypomelanotic malignant lesions (including basal cell carcinoma) gave a 93% sensitivity and 70% specificity for NM. When

  7. 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.

  8. Safety and clinical effect of subcutaneous human interleukin-21 in patients with metastatic melanoma or renal cell carcinoma: a phase I trial

    DEFF Research Database (Denmark)

    Schmidt, Henrik; Brown, Janet; Mouritzen, Ulrik

    2010-01-01

    This phase I study in patients with metastatic melanoma (MM) and renal cell carcinoma (RCC) evaluated the safety and maximum tolerated dose (MTD), pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of s.c. treatment of human recombinant interleukin 21 (IL-21)....

  9. Clinical Signifıcance of Serum Ykl-40 (Chitinase-3-Like-1 Protein) as a Biomarker in Melanoma: an Analysis of 112 Turkish Patients

    Science.gov (United States)

    Erturk, Kayhan; Tas, Faruk; Serilmez, Murat; Bilgin, Elif; Yasasever, Vildan

    2017-05-01

    Background: Angiogenesis plays an essential role in tumor growth and serum levels of YKL-40 , a strong angiogenic factor that promotes tumor vessel development, has been found to be elevated in various cancers. We here investigated correlation between melanoma parameters and serum YKL-40 levels, to assess potential diagnostic, prognostic and predictive values. Material and Methods: Data for 112 pathologically confirmed cutaneous melanomas of any stage were examined retrospectively. ELISA assays were used to measure serum YKL-40 in plasma samples. Results: The baseline serum YKL-40 levels were significantly higher in patients than healthy controls (174.88 vs 120.10 ng/mL, p0.05), and furthermore there was no apparent prognostic influence on melanoma survival (HR: 1.568; 95% CI, 0.580-3.051; p=0.838). Conclusion: Serum YKL-40 can be useful for diagnosis of melanoma, but reliability in assessing prognosis is questionable. We believe that efforts should be made to understand the interaction between YKL-40 and the tumor environment, and establish whether it might be the target for treatment of malignancies. Creative Commons Attribution License

  10. 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

  11. An innovative educational clinical experience promoting geriatric exercise.

    Science.gov (United States)

    Manning, Kenneth M; McNeill, Darien L; Pinheiro, Sandro O; Heflin, Mitchell T; Valencia, Willy M; Lee, Cathy C; Castle, Steven C; Katzel, Leslie; Giffuni, Jamie; Morey, Miriam C

    2017-10-13

    Formal educational training in physical activity promotion is relatively sparse throughout the medical education system. The authors describe an innovative clinical experience in physical activity directed at medical clinicians on a geriatrics rotation. The experience consists of a single 2 1/2 hour session, in which learners are partnered with geriatric patients engaged in a formal supervised exercise program. The learners are guided through an evidence-based exercise regimen tailored to functional status. This experience provides learners with an opportunity to interact with geriatric patients outside the hospital environment to counterbalance the typical geriatric rotation in which geriatric patients are often seen in clinics or hospitals. In this experience, learners are exposed to fit and engaged geriatric patients successfully living in the community despite chronic or disabling conditions. A survey of 105 learners highlighted positive responses to the experience, with 96% of survey respondents indicating that the experience increased their confidence in their ability to serve as advocates for physical activity for older adults, and 89.5% of responders to a follow-up survey indicating that the experience changed their perception of geriatric patients. Modifications to the experience, implemented at partnering facilities are described. The positive feedback from this experience warrants consideration for implementation in other settings.

  12. Experiência de um ano de modelo de programa de prevenção contínua do melanoma na cidade de Jaú-SP, Brasil One year experience of a model for melanoma continuous prevention in the city of Jaú (São Paulo, Brazil

    Directory of Open Access Journals (Sweden)

    Ana Gabriela Salvio

    2011-08-01

    Full Text Available FUNDAMENTO: A incidência do melanoma aumentou nos últimos anos mais rapidamente do que qualquer outro câncer. Embora represente apenas 4% dos cânceres de pele, é o responsável por 60% das mortes por esta neoplasia. Isto torna o melanoma um problema de saúde pública. OBJETIVOS: O presente estudo propôs o desenvolvimento de um Programa Contínuo de Prevenção do Melanoma, por meio da realização da prevenção primária e do diagnóstico precoce desta neoplasia. MÉTODOS: Foi tomada como piloto uma cidade de aproximadamente 130.000 habitantes. Uma equipe de enfermagem esteve presente por cerca de 30 dias em cada um dos 13 postos de saúde da cidade de Jaú (SP, realizando orientações quanto ao autoexame da pele, fotoproteção e sinais precoces do melanoma. O paciente com lesão suspeita era encaminhado imediatamente ao hospital de referência para dermatoscopia e triagem médica, sendo excisada quando suspeita. RESULTADOS: Foram diagnosticados 4 casos de melanoma em fase inicial e 3 nevos displásicos. Dos entrevistados, 74% trabalham expostos ao sol, variando de meio período ao completo, e mais de 60% nunca fizeram uso de filtro solar. CONCLUSÃO: Este modelo de programa de prevenção é inédito, exclusivo e demonstrou ser eficaz na prevenção e diagnóstico precoce do melanoma em uma cidade de 130.000 habitantes do Estado de São Paulo. Com esclarecimento à população e orientação à equipe de saúde, realiza-se uma rápida triagem e identificam-se lesões suspeitas de melanoma para que, com o diagnóstico em suas fases iniciais, o paciente apresente melhor prognósticoBACKGROUND: Worldwide incidence of melanoma has increased in recent years faster than any other cancer. Although it represents only 4% of skin cancers it is nevertheless responsible for 60% of skin cancer deaths. This makes melanoma a public health problem. OBJECTIVES: The aim of this study was the development of a continuous program for melanoma prevention

  13. Student nurses’ experiences during clinical practice in the Limpopo Province

    Directory of Open Access Journals (Sweden)

    BT Mabuda

    2008-09-01

    Full Text Available A qualitative, exploratory, descriptive and contextual study was conducted to explore student nurses’ experiences during clinical practice at a nursing college in the Limpopo Province. Purposive sampling was used and phenomenological interviews were held with eleven (11 student nurses who were in their final year of the four year basic nursing programme. The interviews were analysed by using Tesch’s method of data analysis for qualitative research. The findings indicate that there are aspects which impact negatively on student nurses’ clinical learning experiences, such as lack of teaching and learning support, lack of opportunities for learning, poor theory-practice integration, and poor interpersonal relationships between the students, college tutors and ward staff. Recommendations to enhance the clinical learning experiences of student nurses were outlined.

  14. Retrospective Study of Metastatic Melanoma and Renal Cell Carcinoma to the Brain with Multivariate Analysis of Prognostic Pre-Treatment Clinical Factors

    Directory of Open Access Journals (Sweden)

    Ethan A. Ferrel

    2016-03-01

    Full Text Available Patients with brain metastasis from renal cell carcinoma (RCC or melanoma have historically had very poor prognoses of less than one year. Stereotactic radiosurgery (SRS can be an effective treatment for patients with these tumors. This study analyzes the effect of pretreatment prognostic factors on overall survival (OS for RCC and melanoma patients with metastasis to the brain treated with SRS. A total of 122 patients with brain metastases from either RCC or melanoma were grouped by age at brain metastasis diagnosis, whether they received whole brain radiation therapy (WBRT in addition to SRS, or they underwent surgical resection, Karnofsky Performance Score (KPS, number of brain metastases, and primary tumor. Median survival times for melanoma patients and RCC patients were 8.20 ± 3.06 and 12.70 ± 2.63 months, respectively. Patients with >5 metastases had a significantly shorter median survival time (6.60 ± 2.45 months than the reference group (1 metastasis, 10.70 ± 13.40 months, p = 0.024. Patients with KPS ≤ 60 experienced significantly shorter survival than the reference group (KPS = 90–100, with median survival times of 5.80 ± 2.46 months (p < 0.001 and 45.20 ± 43.52 months, respectively. We found a median overall survival time of 12.7 and 8.2 months for RCC and melanoma, respectively. Our study determined that a higher number of brain metastases (>5 and lower KPS were statistically significant predictors of a lower OS prognosis.

  15. Characterization of melanoma associated spongiform scleropathy

    DEFF Research Database (Denmark)

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

    2002-01-01

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

  16. Pre-clinical medical student experience in a pediatric pulmonary clinic

    Directory of Open Access Journals (Sweden)

    Thomas G. Saba

    2015-11-01

    Full Text Available Objective: Our objective was to evaluate the educational value of introducing pre-clinical medical students to pediatric patients and their families in a subspecialty clinic setting. Methods: First- and second-year medical students at the University of Michigan seeking clinical experience outside of the classroom attended an outpatient pediatric pulmonary clinic. Evaluation of the experience consisted of pre- and post-clinic student surveys and post-clinic parent surveys with statements employing a four-point Likert scale as well as open-ended questions. Results: Twenty-eight first-year students, 6 second-year students, and 33 parents participated in the study. Post-clinic statement scores significantly increased for statements addressing empathic attitudes, confidence communicating with children and families, comfort in the clinical environment, and social awareness. Scores did not change for statements addressing motivation, a sense of team membership, or confidence with career goals. Students achieved their goals of gaining experience interacting with patients, learning about pulmonary diseases, and observing clinic workflow. Parents felt that they contributed to student education and were not inconvenienced. Conclusions: Students identified several educational benefits of exposure to a single pediatric pulmonary clinic. Patients and families were not inconvenienced by the participation of a student. Additional studies are warranted to further investigate the value of this model of pre-clinical medical student exposure to subspecialty pediatrics.

  17. Ambulance clinical placements – A pilot study of students' experience

    Directory of Open Access Journals (Sweden)

    Adams Bridget

    2008-04-01

    Full Text Available Abstract Background Undergraduate paramedic students undertake clinical placements in a variety of locations. These placements are considered an essential element for paramedic pre-employment education. However, anecdotal evidence suggests some students have not had positive experiences on their emergency ambulance placements. The objective of this study was to identify the type of experiences had by students during ambulance clinical placements and to provide feedback to the ambulance services. Methods In this pilot study we employed a cross-sectional study methodology, using a convenience sample of undergraduate paramedic students available in semester one of 2007 to ascertain the students' views on their reception by on-road paramedics and their overall experience on emergency ambulance clinical placements. Ethics approval was granted. Results There were 77 students who participated in the survey, 64% were females, with 92% of students Conclusion This study demonstrates that for a small group of students, emergency ambulance clinical placements were not a positive experience clinically or educationally. Some qualified paramedics doubt if a number of female students can perform the physical role of a paramedic.

  18. Strategies to Improve the Efficacy of Dendritic Cell-Based Immunotherapy for Melanoma

    Directory of Open Access Journals (Sweden)

    Kristian M. Hargadon

    2017-11-01

    Full Text Available Melanoma is a highly aggressive form of skin cancer that frequently metastasizes to vital organs, where it is often difficult to treat with traditional therapies such as surgery and radiation. In such cases of metastatic disease, immunotherapy has emerged in recent years as an exciting treatment option for melanoma patients. Despite unprecedented successes with immune therapy in the clinic, many patients still experience disease relapse, and others fail to respond at all, thus highlighting the need to better understand factors that influence the efficacy of antitumor immune responses. At the heart of antitumor immunity are dendritic cells (DCs, an innate population of cells that function as critical regulators of immune tolerance and activation. As such, DCs have the potential to serve as important targets and delivery agents of cancer immunotherapies. Even immunotherapies that do not directly target or employ DCs, such as checkpoint blockade therapy and adoptive cell transfer therapy, are likely to rely on DCs that shape the quality of therapy-associated antitumor immunity. Therefore, understanding factors that regulate the function of tumor-associated DCs is critical for optimizing both current and future immunotherapeutic strategies for treating melanoma. To this end, this review focuses on advances in our understanding of DC function in the context of melanoma, with particular emphasis on (1 the role of immunogenic cell death in eliciting tumor-associated DC activation, (2 immunosuppression of DC function by melanoma-associated factors in the tumor microenvironment, (3 metabolic constraints on the activation of tumor-associated DCs, and (4 the role of the microbiome in shaping the immunogenicity of DCs and the overall quality of anti-melanoma immune responses they mediate. Additionally, this review highlights novel DC-based immunotherapies for melanoma that are emerging from recent progress in each of these areas of investigation, and it

  19. Strategies to Improve the Efficacy of Dendritic Cell-Based Immunotherapy for Melanoma.

    Science.gov (United States)

    Hargadon, Kristian M

    2017-01-01

    Melanoma is a highly aggressive form of skin cancer that frequently metastasizes to vital organs, where it is often difficult to treat with traditional therapies such as surgery and radiation. In such cases of metastatic disease, immunotherapy has emerged in recent years as an exciting treatment option for melanoma patients. Despite unprecedented successes with immune therapy in the clinic, many patients still experience disease relapse, and others fail to respond at all, thus highlighting the need to better understand factors that influence the efficacy of antitumor immune responses. At the heart of antitumor immunity are dendritic cells (DCs), an innate population of cells that function as critical regulators of immune tolerance and activation. As such, DCs have the potential to serve as important targets and delivery agents of cancer immunotherapies. Even immunotherapies that do not directly target or employ DCs, such as checkpoint blockade therapy and adoptive cell transfer therapy, are likely to rely on DCs that shape the quality of therapy-associated antitumor immunity. Therefore, understanding factors that regulate the function of tumor-associated DCs is critical for optimizing both current and future immunotherapeutic strategies for treating melanoma. To this end, this review focuses on advances in our understanding of DC function in the context of melanoma, with particular emphasis on (1) the role of immunogenic cell death in eliciting tumor-associated DC activation, (2) immunosuppression of DC function by melanoma-associated factors in the tumor microenvironment, (3) metabolic constraints on the activation of tumor-associated DCs, and (4) the role of the microbiome in shaping the immunogenicity of DCs and the overall quality of anti-melanoma immune responses they mediate. Additionally, this review highlights novel DC-based immunotherapies for melanoma that are emerging from recent progress in each of these areas of investigation, and it discusses current

  20. Comparative analysis of methods of preinvasive melanoma diagnostics

    Directory of Open Access Journals (Sweden)

    Kozlov S.V.

    2013-03-01

    Full Text Available The article discusses one of the problems of oncology — skin melanoma. The research objective is to study and to compare diagnostic methods of preinvasive melanoma including fluorescence diagnosis, dermatoscopy and microwave radiometry. Materials and Methods: The survey has used dermatoscope of Heine Delta 20 Company, the unit RTM-01-RES and the instrument of fluorescent diagnostics «Spectrum-Cluster.» The results suggest the possibility of early detection of melanoma with the use of dermatoscopy. The method may be applied to radiometry screening study. Fluorescence diagnostics is effective for the differential diagnosis of melanoma and melanocytic nevi. In conclusion it has been proved the need for an integrated approach to the diagnostics of melanoma of skin, depending on the different clinical situations.

  1. 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.

  2. 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.

  3. Melanoma exosomes enable tumor tolerance in lymph nodes.

    Science.gov (United States)

    Hood, Joshua L

    2016-05-01

    Melanoma preferentially spreads via lymph nodes. Melanoma exosomes can induce angiogenesis and immune suppression. However, a role for melanoma exosomes in facilitating tumor tolerance in lymph nodes has not been considered. Herein, the hypothesis that melanoma exosome mediated induction of vascular endothelial cell (VEC) derived tumor necrosis factor alpha (TNF-α) results in lymphatic endothelial cell (LEC) mediated tumor tolerance is explored. To support this hypothesis, experiments involving ex vivo lymph node associated VECs, LECs, dendritic cells and T lymphocytes are proposed based upon a previously established fluorescent exosome lymph node trafficking model. The implication of the hypothesis in the context of melanoma exosome mediated induction of tumor tolerance in lymph nodes is then discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. The 2017 complete overhaul of adjuvant therapies for high-risk melanoma and its consequences for staging and management of melanoma patients.

    Science.gov (United States)

    Eggermont, Alexander M M; Dummer, Reinhard

    2017-11-01

    The spectacular outcomes of the phase III trials regarding nivolumab versus ipilimumab in fully resected stage IIIB/C-IV and of the combination of dabrafenib (D) plus trametinib (T) in BRAF-mutant stage III patients demonstrate that effective treatments in advanced melanoma are also highly effective in the adjuvant setting. In 2016, an overall survival benefit with adjuvant high-dose ipilimumab was demonstrated, and the European Organisation for Research and Treatment of Cancer trial 1325 comparing pembrolizumab versus placebo will complete the picture in the early 2018. Toxicity profiles are in line with the experience in advanced melanoma, i.e. favourable for the anti-PD1 agents and for D + T and problematic for ipilimumab. The 2017 outcomes are practice changing and put an end to the use of interferon (IFN) and ipilimumab. In countries with only access to IFN, its use can be restricted to patients with ulcerated melanoma, based on the individual patient data meta-analysis recently published. Because of the results of the Melanoma Sentinel Lymph node Trial-2 (MSLT-2) trial, completion lymph node dissection (CLND) will decrease sharply, leading to a lack of optimal prognostic information. Prognosis in sentinel node-positive stage IIIA/B patients is extremely heterogeneous with 5-year survival rates varying from 90% to 40% and depends mostly on the number of positive nodes identified by CLND. This information is crucial for clinical decision-making. How to guarantee optimal staging information needs to be discussed urgently. Further improvements of adjuvant therapies will have to address all these questions as well as the exploration of neoadjuvant use of active drugs and combination approaches. Important paradigm shifts in the management of high-risk melanoma patients are upon us. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Antioxidants can increase melanoma metastasis in mice.

    Science.gov (United States)

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

    2015-10-07

    Antioxidants in the diet and supplements are widely used to protect against cancer, but clinical trials with antioxidants do not support this concept. Some trials show that antioxidants actually increase cancer risk and a study in mice showed that antioxidants accelerate the progression of primary lung tumors. However, little is known about the impact of antioxidant supplementation on the progression of other types of cancer, including malignant melanoma. We show that administration of N-acetylcysteine (NAC) increases lymph node metastases in an endogenous mouse model of malignant melanoma but has no impact on the number and size of primary tumors. Similarly, NAC and the soluble vitamin E analog Trolox markedly increased the migration and invasive properties of human malignant melanoma cells but did not affect their proliferation. Both antioxidants increased the ratio between reduced and oxidized glutathione in melanoma cells and in lymph node metastases, and the increased migration depended on new glutathione synthesis. Furthermore, both NAC and Trolox increased the activation of the small guanosine triphosphatase (GTPase) RHOA, and blocking downstream RHOA signaling abolished antioxidant-induced migration. These results demonstrate that antioxidants and the glutathione system play a previously unappreciated role in malignant melanoma progression. Copyright © 2015, American Association for the Advancement of Science.

  6. [Novel Adjuvant Therapy for Ocular Melanoma].

    Science.gov (United States)

    Bosch, Jacobus J; Heindl, Ludwig M

    2017-05-01

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

  7. Metastatic amelanotic nodular melanoma during pregnancy.

    Science.gov (United States)

    Jasaitiene, Daiva; Valiukeviciene, Skaidra; Makstiene, Jurgita; Juodzbaliene, Edita Brone

    2008-01-01

    This case report presents a very aggressive course of amelanotic nodular melanoma during pregnancy resulting in death five months after delivery. A 34 year-old Caucasian woman at 19th week of the second pregnancy was diagnosed having amelanotic nodular melanoma (tumor thickness - 2.5 mm) with metastases to the regional right inguinal lymph node. Amelanotic nodular melanoma represents malignant melanocytic tumor of the skin, which clinically mimics a variety of benign and malignant skin conditions and therefore commonly leads to delayed diagnosis. Though primary tumor was excised immediately, other treatment procedures as radical lymphadenectomy and chemotherapy were delayed, and immunotherapy was not given totally. At the 29th week of pregnancy, the woman via naturalem delivered a healthy female child, and the chemotherapy was started. Since pregnancy limits the prescription of immunotherapy and chemotherapy, the prognosis for melanoma during pregnancy detected later than in the second stage is poor and can be illustrated by our reported case. Such patients seems to be at higher risk to develop metastasis of melanoma in the internal organs and occasionally even in the fetus; therefore, they should be timely informed about that.

  8. 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

  9. Chronology of metastasis in cutaneous melanoma: growth rate model.

    Science.gov (United States)

    Tejera-Vaquerizo, Antonio; Nagore, Eduardo; Meléndez, Juan J; López-Navarro, Norberto; Martorell-Calatayud, Antonio; Herrera-Acosta, Enrique; Traves, Victor; Guillén, Carlos; Herrera-Ceballos, Enrique

    2012-04-01

    In humans, it is not possible to obtain experimental evidence of when a cancer begins to metastasize. The purpose of this study was to estimate the time of onset of metastatic dissemination in cutaneous melanoma using a model based on its growth rate (GR). The critical time of onset of metastatic dissemination below which no cases of fatal melanomas were seen may be described with a potential function in which this time is inversely proportional to the GR. The critical time of development beyond which a melanoma may metastasize presents great variation. This time was just 1 month for those melanomas with a fast GR, whereas it was over 5 years for those with a very slow GR. Quantitatively, the fastest-growing melanomas began metastasizing with a greater thickness than the slowest-growing melanomas. A correlation exists between the critical time of onset of metastatic potential and the GR of the melanoma. These results may well have relevance to the understanding of mechanisms of tumor dissemination and for the design of future studies on melanomas, irrespective of whether they are basic studies on biomolecular mechamisms or clinical studies.

  10. IRF4 rs12203592 functional variant and melanoma survival.

    Science.gov (United States)

    Potrony, Miriam; Rebollo-Morell, Aida; Giménez-Xavier, Pol; Zimmer, Lisa; Puig-Butille, Joan Anton; Tell-Marti, Gemma; Sucker, Antje; Badenas, Celia; Carrera, Cristina; Malvehy, Josep; Schadendorf, Dirk; Puig, Susana

    2017-04-15

    Inherited genetic factors may modulate clinical outcome in melanoma. Some low-to-medium risk genes in melanoma susceptibility play a role in melanoma outcome. Our aim was to assess the role of the functional IRF4 SNP rs12203592 in melanoma prognosis in two independent sets (Barcelona, N = 493 and Essen, N = 438). Genotype association analyses showed that the IRF4 rs12203592 T allele increased the risk of dying from melanoma in both sets (Barcelona: odds ratio [OR] = 6.53, 95% CI 1.38-30.87, Adj p = 0.032; Essen: OR = 1.68, 95% CI 1.04-2.72, Adj p = 0.035). Survival analyses only showed significance for the Barcelona set (hazard ratio = 4.58, 95% CI 1.11-18.92, Adj p = 0.036). This SNP was also associated with tumour localization, increasing the risk of developing melanoma in head or neck (OR = 1.79, 95% CI 1.07-2.98, Adj p = 0.032) and protecting from developing melanoma in the trunk (OR = 0.59, 95% CI 0.41-0.85, Adj p = 0.004). These findings suggest for the first time that IRF4 rs12203592 plays a role in the modulation of melanoma outcome and confirms its contribution to the localization of the primary tumour. © 2017 UICC.

  11. Nodular malignant melanoma - Secondary to carcinoma rectum

    Directory of Open Access Journals (Sweden)

    Chopra Adarsh

    1997-01-01

    Full Text Available A 45-year female presented with a sudden eruption of multiple brownish black nodular lesions since 5 months over the face, trunk and extremities which were clinically diagnosed as a case of nodular malignant melanoma. Histopathologically, they revealed the secondaries from carcinoma rectum.

  12. 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.

  13. 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

  14. 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.

  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. Primary leptomeningeal melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Aichner, F.; Schuler, G.

    1982-11-01

    A case of primary leptomeningeal melanoma is presented in which the diagnosis was made by ultrastructural demonstration of melanoma cells from the cerebrospinal fluid (CSF) at a time when cranial computed tomography (CT) still gave negative results. Later CT examinations documented the emergence of a tumor mass of the left temporoparietal lobe. This case clearly illustrates the complementary role of these investigational procedures for the diagnosis of cerebrospinal melanoma: leptomeningeal involvement, characterized by two-dimensional diffuse spread of melanoma tissue (''leptomeningeal melanomatosis''), is invisible with CT, but easily recognisable by CSF cytology; in contrast, nodular parenchymal tumor deposits can be readily detected by CT. Identification of pigmented cells recovered from the CSF requires ultrastructural confirmation.

  17. Estimating healthcare resource use associated with the treatment of metastatic melanoma in eight countries.

    Science.gov (United States)

    McKendrick, Jan; Gijsen, Merel; Quinn, Casey; Barber, Beth; Zhao, Zhongyun

    2016-06-01

    Objectives Studies reporting healthcare resourse use (HRU) for melanoma, one of the most costly cancers to treat, are limited. Using consistent, robust methodology, this study estimated HRU associated with the treatment of metastatic melanoma in eight countries. Methods Using published literature and clinician input, treatment phases were identified: active systemic treatment (pre-progression); disease progression; best supportive care (BSC)/palliative care; and terminal care. HRU elements were identified for each phase and estimates of the magnitude and frequency of use in clinical practice were obtained through country-specific Delphi panels, comprising healthcare professionals with experience in oncology (n = 8). Results Medical oncologists are the key care providers for patients with metastatic melanoma, although in Germany dermato-oncologists also lead care. During the active systemic treatment phase, each patient was estimated to require 0.83-2 consultations with a medical oncologist/month across countries; the median number of such assessments in 3 months was highest in Canada (range = 3.5-5) and lowest in France, the Netherlands and Spain (1). Resource use during the disease progression phase was intensive and similar across countries: all patients were estimated to consult with medical oncologists and 10-40% with a radiation oncologist; up to 40% were estimated to require a brain MRI scan. During the BSC/palliative care phase, all patients were estimated to consult with medical oncologists, and most to consult with a primary care physician (40-100%). Limitations Panelists were from centers of excellence, thus results may not reflect care within smaller hospitals; data obtained from experts may be less variable than data from broader clinical practice. Treatments for metastatic melanoma are continually emerging, thus some elements of our work could be superseded. Conclusions HRU estimates were substantial and varied across countries for some

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

    Science.gov (United States)

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

    2016-06-01

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

  19. 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.

  20. UVB: suscetibilidade no melanoma maligno UVB: susceptibility in malignant melanoma

    Directory of Open Access Journals (Sweden)

    Nilton Nasser

    2010-12-01

    Full Text Available FUNDAMENTOS: Está bem definido que a radiação ultravioleta provoca depleção imunológica na pele, permitindo o desenvolvimento de tumores cutâneos malignos. A maioria dos pacientes de cânceres da pele não melanomas são considerados UVB-suscetíveis. OBJETIVOS: Estudar a UVB-suscetibilidade nos pacientes com melanoma maligno e se este é um fator de risco para o desenvolvimento desse câncer. MÉTODOS: Foram selecionados 88 voluntários divididos em dois grupos: grupo-controle saudável (n=61 e grupo de portadores de melanoma (n=27, todos identificados de acordo com os critérios: tipo histológico, nível de invasão, fotótipos de pele, sexo e idade. A suscetibilidade à radiação ultravioleta B (UVB foi medida pela reação de hipersensibilidade ao contato com o difenciprone nos voluntários sensibilizados em áreas previamente irradiadas. RESULTADOS: A suscetibilidade à radiação UVB foi de 81,5% nos pacientes com melanoma maligno e de 31,2% no grupo-controle. O risco de um indivíduo desenvolver o melanoma maligno foi 9,7 vezes maior do que nos indivíduos UVB-resistentes. CONCLUSÕES: A UVB-suscetibilidade pode ser considerada um fator de risco importante para o desenvolvimento do melanoma maligno.BACKGROUND: It is well established that UV radiation provokes an immunological depletion in the skin, enabling the development of malignant cutaneous tumors. Most nonmelanoma skin cancer patients are considered to be UVB-susceptible. OBJECTIVE: To study the behavior of UVB- susceptibility in malignant melanoma (MM patients and whether this is a risk factor to the development of MM. METHODS: Eighty-eight volunteers were selected and divided into two groups: healthy control group (n = 61 and MM group (n = 27, which were identified according to the following clinical criteria: histopathological type, level of invasion, skin phototype, sex and age. Susceptibility to ultraviolet B (UVB radiation was measured by the onset of a contact

  1. Genetics of Melanoma

    Directory of Open Access Journals (Sweden)

    Janet eWangari-Talbot

    2013-01-01

    Full Text Available Genomic variation is a trend observed in various human diseases including cancer. Genetic studies have set out to understand how and why these variations result in cancer, why some populations are predisposed to the disease, and also how genetics affect drug responses. The melanoma incidence has been increasing at an alarming rate worldwide. The burden posed by melanoma has made it a necessity to understand the fundamental signaling pathways involved in this deadly disease. Signaling cascades such as MAPK and PI3K/AKT have been shown to be crucial in the regulation of processes that are commonly dysregulated during cancer development such as aberrant proliferation, loss of cell cycle control, impaired apoptosis and altered drug metabolism. Understanding how these and other oncogenic pathways are regulated has been integral in our challenge to develop potent anti-melanoma drugs. With advances in technology and especially in next generation sequencing, we have been able to explore melanoma genomes and exomes leading to the identification of previously unknown genes with functions in melanomagenesis such as GRIN2A and PREX2. The therapeutic potential of these novel candidate genes is actively being pursued with some presenting as druggable targets while others serve as indicators of therapeutic responses. In addition, the analysis of the mutational signatures of melanoma tumors continues to cement the causative role of UV exposure in melanoma pathogenesis. It has become distinctly clear that melanomas from sun exposed skin areas have distinct mutational signatures including C to T transitions indicative of UV-induced damage. It is thus necessary to continue spreading awareness on how to decrease the risk factors of developing the disease while at the same time working for a cure. Given the large amount of information gained from these sequencing studies, it is likely that in the future, treatment of melanoma will follow a highly personalized route

  2. Perforating metastatic melanoma

    Directory of Open Access Journals (Sweden)

    Takenobu Ohashi

    2015-01-01

    Full Text Available We describe a case of metastatic malignant melanoma on the thigh with comedo-like appearance, which histologically showed elimination of tumor cells. A 70 year-old man was diagnosed with a nodular type malignant melanoma involving the lower back with satellite lesions (stage IIIB, T4b N2c M0, Breslow’s tumor thickness; 10.3 mm, Clark’s level; IV.

  3. Disseminated malignant melanoma

    Directory of Open Access Journals (Sweden)

    Verma Kaushal

    1999-01-01

    Full Text Available A 25-year-old man had multiple asymptomatic, nodular lesions on the trunk, extremities and the face for 3 months. He also had left facial palsy with severe headache and vomiting. There were no other systemic or constitutional symptoms. Skin biopsy from a nodular lesion showed features of malignant melanoma, confirmed by Fontana Masson and S-100 protein staining. A diagnosis of disseminated malignant melanoma was made and the patient was treated symptomatically. The patient died in 4 months.

  4. Clinical experience with Repotin, a locally produced recombinant ...

    African Journals Online (AJOL)

    Clinical experience with Repotin, a locally produced recombinant human erythropoietin, in the treatment of anaemia of chronic renal failure in South Africa. C. R. Swanepoel, M. R. Moosa, G. F. Rowland, G. F. Rowland, B. P. Botha, A. J. Smart, R. Goodman, R. Schall, H. J. Keogh, E. H. Merrifield ...

  5. Clinical and laboratory experience of chorionic villous sampling in ...

    African Journals Online (AJOL)

    Background: Chorionic villous sampling is a first trimester invasive diagnosis procedure that was introduced in Nigeria <2 decades ago. Objective: The objective of the following study is to review experience with chorionic villous sampling in relation to clinical and laboratory procedures, including general characteristics of ...

  6. Early clinical experience: do students learn what we expect?

    NARCIS (Netherlands)

    Helmich, E.; Bolhuis, S.; Laan, R.F.J.M.; Koopmans, R.T.C.M.

    2011-01-01

    CONTEXT: Early clinical experience is thought to contribute to the professional development of medical students, but little is known about the kind of learning processes that actually take place. Learning in practice is highly informal and may be difficult to direct by predefined learning outcomes.

  7. Early clinical experience : do students learn what we expect?

    NARCIS (Netherlands)

    Helmich, Esther; Bolhuis, Sanneke; Laan, Roland; Koopmans, Raymond

    CONTEXT Early clinical experience is thought to contribute to the professional development of medical students, but little is known about the kind of learning processes that actually take place. Learning in practice is highly informal and may be difficult to direct by predefined learning outcomes.

  8. 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.

  9. A qualitative study of constructive clinical learning experiences.

    Science.gov (United States)

    van der Hem-Stokroos, H H; Daelmans, H E M; van der Vleuten, C P M; Haarman, H J Th M; Scherpbier, A J J A

    2003-03-01

    Little is known about the effectiveness of clinical education. A more educational structure is considered to be potentially beneficial. The following structured components were added to a surgical clerkship: logbooks, an observed student-patient encounter, individual appraisals, feedback on patient notes, and (case) presentations by students. The authors organized two focus-group sessions in which 19 students participated to explore their perceptions about effective clinical learning experiences and the newly introduced structured components. The analysis of the transcripts showed that observation and constructive feedback are key features of clinical training. The structured activities were appreciated and the results show the direction to be taken for further improvement. Learning experiences depended vastly on individual clinicians' educational qualities. Students experienced being on call, assisting in theatre and time for self-study as instructive elements. Recommended clerkship components are: active involvement of students, direct observation, selection of teachers, a positive learning environment and time for self-study.

  10. Fostering new relational experience: clinical process in couple psychotherapy.

    Science.gov (United States)

    Marmarosh, Cheri L

    2014-03-01

    One of the most critical goals for couple psychotherapy is to foster a new relational experience in the session where the couple feels safe enough to reveal more vulnerable emotions and to explore their defensive withdrawal, aggressive attacking, or blaming. The lived intimate experience in the session offers the couple an opportunity to gain integrative insight into their feelings, expectations, and behaviors that ultimately hinder intimacy. The clinical processes that are necessary include empathizing with the couple and facilitating safety within the session, looking for opportunities to explore emotions, ruptures, and unconscious motivations that maintain distance in the relationship, and creating a new relational experience in the session that has the potential to engender integrative insight. These clinical processes will be presented with empirical support. Experts from a session will be used to highlight how these processes influence the couple and promote increased intimacy. (PsycINFO Database Record (c) 2014 APA, all rights reserved).

  11. Using clinical caring journaling: nursing student and instructor experiences.

    Science.gov (United States)

    Kuo, Chien-Lin; Turton, Michael; Cheng, Su-Fen; Lee-Hsieh, Jane

    2011-06-01

    Journaling has been incorporated into many nursing courses as an active reflective teaching strategy that can facilitate the learning process, personal growth, and professional development of students. There is limited research support of journaling as an appropriate tool to promote reflection for the purpose of learning caring in nursing education. The aim of this study was to explore the experiences and perceptions of student nurses and instructors who use clinical caring journaling (CCJ) in their clinical practicum. Researchers used a descriptive qualitative research design. The study population was 880 senior student nurses and 90 clinical instructors from a nursing program at a university in Taiwan who used CCJ. After completion of 1 year of clinical practicum, 16 students and 7 instructors participated voluntarily in focus group interviews. Researchers used content analysis to sort interview data into themes. Six themes were categorized that encapsulated student and instructor experiences and perceptions regarding using CCJ in their clinical practicum. These themes were guiding caring behavior toward patients, enabling students' reflective caring abilities, building up students' self-confidence, increasing interaction between students and instructors, enhancing students' self-development, and overcoming writing difficulty. Research findings may serve as a reference for nursing educators to use CCJ strategy in student nurses' clinical practicum.

  12. 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

  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

    primary melanomas: 18 superficial spreading, 4 nodular, 3 lentigo malignant, and 9 unclassified. Twelve tumors were dermal melanoma metastases. The median thickness of the 25 measurable melanomas was 0.78 mm. The 5-year overall survival was 69%. At the closing date of the study 15 patients had died, 13......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...

  14. Detrimental effects of melanocortin-1 receptor (MC1R) variants on the clinical outcomes of BRAF V600 metastatic melanoma patients treated with BRAF inhibitors.

    Science.gov (United States)

    Guida, Michele; Strippoli, Sabino; Ferretta, Anna; Bartolomeo, Nicola; Porcelli, Letizia; Maida, Immacolata; Azzariti, Amalia; Tommasi, Stefania; Grieco, Claudia; Guida, Stefania; Albano, Anna; Lorusso, Vito; Guida, Gabriella

    2016-11-01

    Melanocortin-1 receptor (MC1R) plays a key role in skin pigmentation, and its variants are linked with a higher melanoma risk. The influence of MC1R variants on the outcomes of patients with metastatic melanoma (MM) treated with BRAF inhibitors (BRAFi) is unknown. We studied the MC1R status in a cohort of 53 consecutive BRAF-mutated patients with MM treated with BRAFi. We also evaluated the effect of vemurafenib in four V600 BRAF melanoma cell lines with/without MC1R variants. We found a significant correlation between the presence of MC1R variants and worse outcomes in terms of both overall response rate (ORR; 59% versus 95%, P = 0.011 univariate, P = 0.028 multivariate analysis) and progression-free survival (PFS) shorter than 6 months (72% versus 33%, P = 0.012 univariate, P = 0.027 multivariate analysis). No difference in overall survival (OS) was reported, probably due to subsequent treatments. Data in vitro showed a significant different phosphorylation of Erk1/2 and p38 MAPK during treatment, associated with a greater increase in vemurafenib IC50 in MC1R variant cell lines. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Early evolution of BRAFV600 status in the blood of melanoma patients correlates with clinical outcome and identifies patients refractory to therapy.

    Science.gov (United States)

    Gonzalez-Cao, Maria; Mayo de Las Casas, Clara; Jordana Ariza, Nuria; Manzano, Jose L; Molina-Vila, Miguel Á; Soriano, Virtudes; Puertolas, Teresa; Balada, Ariadna; Soria, Ainara; Majem, Margarita; Montagut, Clara; Muñoz, Eva; Rodriguez-Abreu, Delvys; Perez, Elisabeth; Garcia, Almudena; Cortes, Javier; Drozdowskyj, Ana; Karachaliou, Niki; Rosell, Rafael

    2018-02-23

    Serial analysis of BRAF mutations in circulating-free DNA (cfDNA) could be of prognostic value in melanoma patients. We collected blood samples from 63 advanced BRAFV600E/K melanoma patients and determined BRAFV600E/K status in cfDNA using a quantitative 5'-nuclease PCR-based assay. Levels of BRAF mutation in pre-cfDNAs were associated significantly with tumour burden, progression-free survival and overall survival. Changes in BRAF status in cfDNA after initiation of treatment (early-cfDNA) had a significant correlation with outcome. In patients with persistent BRAF mutations (n=12), progression-free survival and overall survival were 3.5 months [95% confidence interval (CI): 1.6-4.6] and 5.3 months (95% CI: 3.4-8.1) compared with 16.6 months (95% CI: 8.2-22.3) and 21.9 months (95% CI: 10.2-NR) in patients with BRAF negativization (n=16), and 15.1 months (95% CI: 2.3-NR) and NR (95% CI: 5.1-NR) in patients who maintained their initial negative status (n=12) (P<0.0001). The median duration of response in patients with radiological response, but persistence of BRAFV600 in early-cfDNA (n=5) was 4 months. Our study indicates that serial BRAF testing in the blood of advanced melanoma identifies patients refractory to therapy.

  16. Challenging clinical learning environments: experiences of undergraduate nursing students.

    Science.gov (United States)

    O'Mara, Linda; McDonald, Jane; Gillespie, Mary; Brown, Helen; Miles, Lynn

    2014-03-01

    Clinical learning is an essential component of becoming a nurse. However at times, students report experiencing challenging clinical learning environments (CCLE), raising questions regarding the nature of a challenging clinical learning environment, its impact on students' learning and how students might respond within a CCLE. Using an Interpretive Descriptive study design, researchers held focus groups with 54 students from two Canadian sites, who self-identified as having experienced a CCLE. Students defined a CCLE as affected by relationships in the clinical area and by the context of their learning experiences. CCLE decreased students' learning opportunities and impacted on them as persons. As students determined which relationships were challenging, they tapped other resources and they used strategies to rebuilt, reframe, redirect and/or retreat relative to the specific challenge. Relationships also acted as buffers to unsupportive practice cultures. Implications for practice and research are addressed. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. E-health stakeholders experiences with clinical modelling and standardizations.

    Science.gov (United States)

    Gøeg, Kirstine Rosenbeck; Elberg, Pia Britt; Højen, Anne Randorff

    2015-01-01

    Stakeholders in e-health such as governance officials, health IT-implementers and vendors have to co-operate to achieve the goal of a future-proof interoperable e-health infrastructure. Co-operation requires knowledge on the responsibility and competences of stakeholder groups. To increase awareness on clinical modeling and standardization we conducted a workshop for Danish and a few Norwegian e-health stakeholders' and made them discuss their views on different aspects of clinical modeling using a theoretical model as a point of departure. Based on the model, we traced stakeholders' experiences. Our results showed there was a tendency that stakeholders were more familiar with e-health requirements than with design methods, clinical information models and clinical terminology as they are described in the scientific literature. The workshop made it possible for stakeholders to discuss their roles and expectations to each other.

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

    Science.gov (United States)

    Shields, Jerry A; Shields, Carol L

    2015-02-01

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

  19. Metastatic melanoma – a review of current and future drugs

    Directory of Open Access Journals (Sweden)

    Tiago Rodrigues Velho

    2012-11-01

    Full Text Available Background: Melanoma is one of the most aggressive cancers, and it is estimated that 76,250 men and women will be diagnosed with melanoma of the skin in the USA in 2012. Over the last few decades many drugs have been developed but only in 2011 have new drugs demonstrated an impact on survival in metastatic melanoma.Methods: A systematic search of literature was conducted, and studies providing data on the effectiveness of current and/or future drugs used in the treatment of metastatic melanoma were selected for review. This review discusses the advantages and limitations of these agents, evaluating past, current and future clinical trials designed to overcome such limitations.Results: To date, there are four drugs approved by the Food and Drug Administration for melanoma (dacarbazine, interleukin-2, ipilimumab and vemurafenib. Despite efforts to develop new drugs, few of them have demonstrated any clinical benefits. Approved in 1975, dacarbazine remains the gold standard in chemotherapy, although ipilimumab and vemurafenib have raised many hopes in the last few years. Combining dacarbazine or other chemotherapy agents with new pharmacological agents may be a new way to achieve better clinical responses in patients with metastatic melanoma.Discussion: Advances in the molecular knowledge of melanoma have led to major improvements in the treatment of patients with metastatic melanoma, providing new targets and insights. However, heterogeneity amongst study populations, different approaches to treatment and the different melanoma types and localisations included in the trials makes their comparison difficult. New studies focusing on drugs developed in recent decades are warranted

  20. DNA methylation characteristics of primary melanomas with distinct biological behaviour.

    Directory of Open Access Journals (Sweden)

    Szilvia Ecsedi

    Full Text Available In melanoma, the presence of promoter related hypermethylation has previously been reported, however, no methylation-based distinction has been drawn among the diverse melanoma subtypes. Here, we investigated DNA methylation changes associated with melanoma progression and links between methylation patterns and other types of somatic alterations, including the most frequent mutations and DNA copy number changes. Our results revealed that the methylome, presenting in early stage samples and associated with the BRAF(V600E mutation, gradually decreased in the medium and late stages of the disease. An inverse relationship among the other predefined groups and promoter methylation was also revealed except for histologic subtype, whereas the more aggressive, nodular subtype melanomas exhibited hypermethylation as well. The Breslow thickness, which is a continuous variable, allowed for the most precise insight into how promoter methylation decreases from stage to stage. Integrating our methylation results with a high-throughput copy number alteration dataset, local correlations were detected in the MYB and EYA4 genes. With regard to the effects of DNA hypermethylation on melanoma patients' survival, correcting for clinical cofounders, only the KIT gene was associated with a lower overall survival rate. In this study, we demonstrate the strong influence of promoter localized DNA methylation changes on melanoma initiation and show how hypermethylation decreases in melanomas associated with less favourable clinical outcomes. Furthermore, we establish the methylation pattern as part of an integrated apparatus of somatic DNA alterations.

  1. A protein deep sequencing evaluation of metastatic melanoma tissues.

    Directory of Open Access Journals (Sweden)

    Charlotte Welinder

    Full Text Available Malignant melanoma has the highest increase of incidence of malignancies in the western world. In early stages, front line therapy is surgical excision of the primary tumor. Metastatic disease has very limited possibilities for cure. Recently, several protein kinase inhibitors and immune modifiers have shown promising clinical results but drug resistance in metastasized melanoma remains a major problem. The need for routine clinical biomarkers to follow disease progression and treatment efficacy is high. The aim of the present study was to build a protein sequence database in metastatic melanoma, searching for novel, relevant biomarkers. Ten lymph node metastases (South-Swedish Malignant Melanoma Biobank were subjected to global protein expression analysis using two proteomics approaches (with/without orthogonal fractionation. Fractionation produced higher numbers of protein identifications (4284. Combining both methods, 5326 unique proteins were identified (2641 proteins overlapping. Deep mining proteomics may contribute to the discovery of novel biomarkers for metastatic melanoma, for example dividing the samples into two metastatic melanoma "genomic subtypes", ("pigmentation" and "high immune" revealed several proteins showing differential levels of expression. In conclusion, the present study provides an initial version of a metastatic melanoma protein sequence database producing a total of more than 5000 unique protein identifications. The raw data have been deposited to the ProteomeXchange with identifiers PXD001724 and PXD001725.

  2. Treatment Options by Stage (Melanoma)

    Science.gov (United States)

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

  3. Intracerebral metastases from ocular melanoma.

    OpenAIRE

    Jones, D. R.; Scobie, I. N.; Sarkies, N. J.

    1988-01-01

    A blind painful eye may harbour an unsuspected malignant melanoma. We report a case of ocular melanoma that presented with confusion owing to direct extension via the optic nerve into the anterior cranial fossa.

  4. 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.

  5. Report from the II Melanoma Translational Meeting of the Spanish Melanoma Group (GEM)

    Science.gov (United States)

    Berrocal, Alfonso; Puig, Susana; Karachaliou, Niki; De Matos-Arruda, Leticia; Seoane, Joan; Escors, David; Alvarez, Carmen; Vaque, Jose Pedro; Prat, Aleix; Wellbrock, Claudia; Arozarena, Imanol; Marquez-Rodas, Ivan; Espinosa, Enrique; Molina, Migue Angel; Puertolas, Teresa; Juan-Otero, Manuel; Malagrida, Rosina; Jantus-Lewintre, Eloisa; Soriano, Virtudes; Arance, Ana; Manzano, Jose Luis; Lorigan, Paul; Gajewski, Thomas F.; Rosell, Rafael; Martin-Algarra, Salvador

    2017-01-01

    The II Melanoma Translational Meeting of the Spanish Melanoma Group (GEM) was held in Barcelona, Spain, at the Hospital Universitari Quiron-Dexeus on November 3rd, 2016. The conference featured leaders in the fields of oncology, immunology and dermatology, all working at both national and international levels on basic research with direct applications to the clinical setting. The objective was to present cutting edge research on melanoma, mainly from Spanish research groups, but also from some international groups, with the aim of generating a network for future national and international collaborations. During a single day, fifteen speakers, seven biologists and eight clinicians, with a special focus on translational research, outlined the main findings of their ongoing studies. The moderators in every session were recognized GEM oncologists who guided discussion from the clinical point of view regarding the preclinical data presented. Herein, we summarize the main topics discussed during the meeting.

  6. 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.

  7. 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...... nine haematoxylin and eosin (HE)-negatives, all of which were found by immunohistochemistry. The false negative rate for the SNB procedure was 4% (2/55). The complication rate was 6% after SNB and 29% after complete node dissection. In conclusion, SN status is a strong prognostic factor in melanoma...

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

    Science.gov (United States)

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

    2017-02-01

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

  9. Seven years experience with a computerized diabetes clinic database.

    Science.gov (United States)

    Flack, J R

    1995-01-01

    With the emergence of information technology applications in medicine, a computerized medical record system that could be used to : (1) maintain patients' clinical records over time, (2) communicate with referring practitioners, and (3) form the basis of a potential research database of information, was sought. In 1987, we developed such a clinical database to register patients attending our busy Diabetes Clinic, now seeing in excess of 300 new referrals and, on average, 3,000 clinic visits per year. Baseline demographic data, clinical history, and examination and investigation results are recorded. We also record diabetes therapy and other medication dosage and changes, monitor follow-up, assess health outcome information (such as stroke or amputation), and generate results, summaries, and reports to referring practitioners and other health professionals. We now have almost seven years of experience using the system. Initially established on a single PC with paper-based data collection and subsequent data entry (running as a DOS application), it is now established on a PC Local Area Network [LAN] with terminals in the clinic consultation rooms enabling direct data entry and allowing patients to view their results in graphic form on screen. From its inception, the Diabetes Clinic Database System has maintained patient demographic and clinical data (which facilitates efficient clinic management) with patient clinic lists and adhesive address labels generated from appropriate menus. Batch mode processing produces daily work sheets which facilitate the running of clinics as well as ad hoc, daily, and weekly reports for all patients (as required). This expedites correspondence with referring doctors. A quality assurance report to the clinic doctor highlights missing clinical information which must be obtained in order to ensure data completeness. The initial system was relatively inefficient in that it required data entry following patient consultation and provided no

  10. ORAL AMELANOTIC MELANOMA FEATURE ARTICLE

    African Journals Online (AJOL)

    hard palate (more than 40%) and the gingiva2. Melanomas arise from the uninhibited proliferation ... Malignant melanomas of the mucosal regions of the head and neck are extremely rare neoplasms accounting for less than 1% of .... head and neck region reported that amelanotic melanomas had a 20% survival at 3 years, ...

  11. Genetic Abnormalities in Uveal Melanoma

    NARCIS (Netherlands)

    N.C. Naus (Nicole)

    2001-01-01

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

  12. Mutuality: clinical and metapsychological potentials of a failed experiment.

    Science.gov (United States)

    Castillo Mendoza, Carlos Alberto

    2012-03-01

    Ferenczi's experiments with mutual analysis are often dismissed, without acknowledging the results obtained from them and his own cautionary remarks about their limits. Though ultimately failed, Ferenczi's experiments with mutual analysis were a source of clinical and metapsychological knowledge, despite the fact that he was unable to elaborate them in his lifetime. In this paper I connect mutuality to the development of the psyche, especially to the constitutive core of the intrapsychic. To understand the latter, it is necessary to take into account, among others, issues such as the common attribute, the mutual flux between the unconsciouses, the dialogue of unconsciouses, the maternal profundity, the primal relationship with the mother, and, above all, the primal unity between mother and child, which are fundamental for the emergence and development of the primary psychic forces. Incidences of rupture, distortion of the core of mutuality in the psychic life, its loss and disadjustment, by means of external traumatizing forces, and some clinical implications are described.

  13. Clinical experience with an HCG-radioreceptor-assay

    International Nuclear Information System (INIS)

    Anger, H.

    1979-01-01

    First experience in clinical work showed up that there was a diagnostic gap to be filled concerning disturbances in early pregnancy. The radioreceptorassay for HCG is very sensitive (0.2 IU/ml serum), the results show good reproducibility and the test is rapidly and easily to perform. Thus, more precise diagnostic results during complications in early pregnancy are available and new therapeutic possibilities may arise. (orig.) [de

  14. Hospice clinical experiences for nursing students: living to the fullest.

    Science.gov (United States)

    Spicer, Sherri; Heller, Rebecca; Troth, Sarah

    2015-01-01

    Preparing future nurses to provide appropriate care for patients and their families at the end of life can be a formidable challenge for nurse educators. Most nursing schools thread end-of-life concepts throughout the curriculum. Grand Canyon University includes a 40-hour hospice clinical as a component of a home healthcare practicum. Students' weekly written reflections reveal the depth of affective learning that occurs during this experience. Article includes hospice materials and resources.

  15. The Treatment of Melanoma Brain Metastases.

    Science.gov (United States)

    Kibbi, Nour; Kluger, Harriet

    2016-12-01

    Melanoma is the malignancy with the highest rate of dissemination to the central nervous system once it metastasizes. Until recently, the prognosis of patients with melanoma brain metastases (MBM) was poor. In recent years, however, the prognosis has improved due to high-resolution imaging that facilitates early detection of small asymptomatic brain metastases and early intervention with local modalities such as stereotactic radiosurgery. More recently, a number of systemic therapies have been approved by the Food and Drug Administration for metastatic melanoma, resulting in improved survival for many MBM patients. Registration trials for these newer therapies excluded patients with untreated brain metastases, and a number of studies specifically tailored to this population of patients have been conducted or are underway. Herein, we review contemporary locoregional and systemic therapies and describe the unique challenges posed by treatment of brain metastases, such as radionecrosis, cerebral edema, and pseudoprogression. Since the number of systemic and combined modality clinical trials has increased, we expect that the treatment landscape for patients with melanoma brain metastasis will change dramatically. In addition to ongoing clinical trials, which show great promise, we conclude that our understanding of intracranial metastasis remains quite limited. In addition to inter-disciplinary, multi-modality studies, bench-side work to better understand the process of cerebrotropism is needed to fuel more drug development and further improve outcomes.

  16. Malignant melanoma misdiagnosed as diabetic foot ulcer

    Science.gov (United States)

    Gao, Wei; Chen, Dawei; Ran, Xingwu

    2017-01-01

    Abstract Rationale: 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. Patient concerns: 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. Diagnoses: An incisional biopsy of the lesion revealed malignant melanoma. Interventions: The patient received wide excision, skin grafting as well as biotherapy. Outcomes: The lesion was healed and no other metastasis has been founded until now. Lessons: 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. PMID:28723771

  17. Sentinel node detection by lymphoscintigraphy and sentinel lymph node biopsy in vulvar melanoma

    International Nuclear Information System (INIS)

    Trifiro, Giuseppe; Travaini, Laura L.; Pacifici, Monica; Vertua, Andrea; Paganelli, Giovanni; Sanvito, Francesca; Sideri, Mario G.; Mallia, Andrew; Ferrari, Mahila E.; Maggioni, Angelo

    2010-01-01

    Vulvar melanoma is a rare malignant tumour. Its surgical excision is the mainstay of treatment whilst the surgical management of regional lymph nodes remains controversial; on the contrary elective inguinofemoral lymphadenectomy causes considerable morbidity. Lymphoscintigraphy (LS) and sentinel lymph node biopsy (SLNB) are accurate staging procedures of lymph node status in breast cancer and cutaneous melanoma patients. In this retrospective paper we report our experience of LS and SLNB in vulvar melanoma patients. Twenty-two consecutive patients with a diagnosis of vulvar melanoma were treated at our institute: patients with clinically positive groin nodes or with previous surgery on the primary tumour were excluded. Twelve were selected for our analysis. All patients underwent sentinel lymph node localization with LS the day before surgery and the surgical procedure of SLNB associated with radical surgery. Six patients had metastatic SLNB and in five of six (83.3%) it was the only positive node. In the other six patients SLNB was negative for metastatic disease. No skip metastases were observed. In SLNB negative patients the mean Breslow thickness was 2.06 mm (range: 0.60-7.10) and only one patient showed a high Breslow thickness (patient 8). In SLNB positive patients the mean Breslow thickness was 4.33 mm (1.8-6.0). Our data indicate that, even in vulvar melanoma, the sentinel lymph node pathological status predicts the pathological status of the remaining groin nodes and suggests that elective groin dissection can be spared in cases of a negative SLNB. Breslow thickness (<1 mm) was not predictive of negative nodes. (orig.)

  18. Clinical decision-making: physicians' preferences and experiences

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    White Martha

    2007-03-01

    Full Text Available Abstract Background Shared decision-making has been advocated; however there are relatively few studies on physician preferences for, and experiences of, different styles of clinical decision-making as most research has focused on patient preferences and experiences. The objectives of this study were to determine 1 physician preferences for different styles of clinical decision-making; 2 styles of clinical decision-making physicians perceive themselves as practicing; and 3 the congruence between preferred and perceived style. In addition we sought to determine physician perceptions of the availability of time in visits, and their role in encouraging patients to look for health information. Methods Cross-sectional survey of a nationally representative sample of U.S. physicians. Results 1,050 (53% response rate physicians responded to the survey. Of these, 780 (75% preferred to share decision-making with their patients, 142 (14% preferred paternalism, and 118 (11% preferred consumerism. 87% of physicians perceived themselves as practicing their preferred style. Physicians who preferred their patients to play an active role in decision-making were more likely to report encouraging patients to look for information, and to report having enough time in visits. Conclusion Physicians tend to perceive themselves as practicing their preferred role in clinical decision-making. The direction of the association cannot be inferred from these data; however, we suggest that interventions aimed at promoting shared decision-making need to target physicians as well as patients.

  19. 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.

  20. Melanoma cutâneo: características clínicas, epidemiológicas e histopatológicas no Hospital Universitário de Brasília entre janeiro de 1994 e abril de 1999 Cutaneous Melanoma: clinical, epidemiological and histopathological characteristics at the University Hospital of Brasília between January 1994 and April 1999

    Directory of Open Access Journals (Sweden)

    Ana Maria Costa Pinheiro

    2003-04-01

    Full Text Available FUNDAMENTOS: A incidência do melanoma cutâneo tem aumentado cerca de 4 a 6% anualmente. Esse tumor ocorre preferencialmente no sexo feminino, entre 30 e 79 anos de idade e predominantemente em indivíduos de cor branca. A forma anatomopatológica mais freqüente é a extensivo-superficial, e sua localização varia com o sexo. OBJETIVOS: O objetivo deste estudo foi avaliar as características clínicas, epidemiológicas e histológicas do melanoma cutâneo primário, no Hospital Universitário de Brasília, em um período de cinco anos. MATERIAL E MÉTODOS: Foi realizado estudo de revisão dos prontuários dos casos de melanoma cutâneo primário, do Hospital Universitário de Brasília, diagnosticados e tratados entre janeiro de 1994 e abril de 1999, totalizando 32 casos. Os pacientes foram analisados, caracterizando-se a distribuição do tumor por sexo, idade, cor da pele, topografia, sintomatologia, tipo de crescimento, nível de Clark, índice de Breslow e presença de metástases. A análise dos dados foi realizada por meio de estatística simples e pelo teste do qui-quadrado (chi2. RESULTADOS: Neste estudo há predomínio das lesões localizadas nos membros, correspondendo a 16 pacientes (50%. Em nove pacientes (45% a forma primária era do tipo nodular, e 17 pacientes (58,6% não apresentavam queixas. Pela correlação entre a presença ou não de metástases e o nível de Clark observou-se que os pacientes com nível de invasão até o subcutâneo (Clark V apresentaram risco relativo de 2,94 (1,24BACKGROUND: The incidence of cutaneous melanoma has increased at a rate of approximately 4 to 6% annually. This neoplasm occurs preferably in the female gender, between 30 and 79 years old and among Caucasian persons. The most common histopathological form is the extensive superficial one, and its location varies according to gender. OBJECTIVES: The objective of this study was to evaluate the clinical, epidemiological and histopathological

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1989-09-01

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