Fractionated stereotactic irradiation by Cyberknife of choroid melanomas: repositioning validation, closed eyelids

International Nuclear Information System (INIS)

Horn, S.; Rezvoy, N.; Lacornerie, T.; Mirabel, X.; Labalette, P.; Lartigau, E.

2009-01-01

The fractionated stereotactic radiotherapy by Cyberknife is an option in the treatment of eyes tumors. The advantages of the Cyberknife in the choroid melanomas are in its infra-millimetric precision, to the automated repositioning on the skull bones and to the conformity brought by the stereotaxy. The objective of this study was to validate the quality of repositioning and the immobility of the eyes with closed eyelids. Conclusion: the reproducibility of the eye positioning with closed eyelids seems enough to consider the conservative treatment of choroid melanomas by fractionated stereotactic radiotherapy by Cyberknife without implementation of fiducials nor retrobulbar anaesthesia. (N.C.)

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

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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.

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

Directory of Open Access Journals (Sweden)

Martha M. Motomo Chojniak

2001-04-01

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

Malignant melanoma of the choroid in a naevus of Ota.

Science.gov (United States)

Singh, M; Kaur, B; Annuar, N M

1988-02-01

A rare case of choroidal malignant melanoma in a naevus of Ota is described. This is the first reported case from Asia outside the Japanese population. This case illustrates the need for close observation of all pigmented lesions of the eye.

Malignant melanoma of the choroid in a naevus of Ota.

OpenAIRE

Singh, M.; Kaur, B.; Annuar, N. M.

1988-01-01

A rare case of choroidal malignant melanoma in a naevus of Ota is described. This is the first reported case from Asia outside the Japanese population. This case illustrates the need for close observation of all pigmented lesions of the eye.

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

International Nuclear Information System (INIS)

Al-Wassia, Rolina; Dal Pra, Alan; Shun, Kitty; Shaban, Ahmed; Corriveau, Christine; Edelstein, Chaim; Deschenes, Jean; Ruo, Russel; Patrocinio, Horacio; Cury, Fabio L.B.; DeBlois, François; Shenouda, George

2011-01-01

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.

Prognostic value of nucleolar size and size pleomorphism in choroidal melanomas

DEFF Research Database (Denmark)

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

1993-01-01

Morphometric estimates of nucleolar size have been shown to possess a high prognostic value in patients with uveal melanomas. The authors investigated various quantitative estimators of the mean size and pleomorphism of nucleoli in choroidal melanomas from a consecutive series of 95 Danish patients...... of melanoma, and largest macroscopic tumor dimension (LTD), the following histomorphometric estimates were obtained: mean diameter of the 10 largest nucleoli (MLN), point-sampled mean nucleolar profile area (nucleolar ao) and the associated standard deviation of nucleolar ao, the volume-weighted mean...

Preliminary results of proton therapy in choroidal melanoma at the centre de proton therapy d'Orsay (C.P.O.): 464 initial cases

International Nuclear Information System (INIS)

Desjardins, L.; Levy, C.; D'hermies, F.; Frau, E.; Schlienger, P.; Habrand, J.L.; Mammar, H.; Schwartz, L.; Mazal, A.; Delacroix, S.; Nauraye, C.; Ferrand, R.; Asselain, B.

1997-01-01

Retrospective analysis of the treatment of choroidal melanoma with proton-therapy at the Centre de protontherapie d'Orsay, France. Between September 1991 and September 1995, 612 patients presenting with choroidal melanoma were treated by proton-therapy in Orsay. Following initial management of the first 464 patients, results were analyzed, as were results after a 1-year follow up for 305 patients, a 2-year follow-up for 169 patients, and a 3-year follow-up for 59 patients. Univariate analysis showed that the actuarial local recurrence rate was 5 %, the 3-year survival rate 88 %, and the overall metastatic rate 5%. The initial tumor volume was the most significant predictive factor for visual results and metastases. Multivariate analysis revealed that visual results were significantly related to the initial tumor volume, initial retinal detachment, and total dose delivered to the optic nerve and macula. Proton-therapy of choroidal melanoma allows in most cases conservation of the eye without modification of survival. Visual results mainly depend on the site and size of the tumor. (author)

Curie-therapy for the conservative treatment of 304 choroidal melanomas in the Catalonia Oncology Institute

International Nuclear Information System (INIS)

Riou, O.; Gutierrez, C.; Pera, J.; Martinez, E.; Caminal, J.M.; Modolell, I.; Navarro, V.; Guedea, F.

2011-01-01

The authors report an analysis of results obtained on 304 patients who have been treated by curie-therapy for a non-metastatic choroidal melanoma. They address the treatment (exclusive curie-therapy, local relapse, and adjuvant surgery), the treatment type (iodine-125 plate, ruthenium plate, and dose level), the survival, metastatic evolutions, toxicity occurrence, and vision quality. In most of the cases, curie-therapy results in ocular conservation and in an acceptable vision. Short communication

Estudo comparativo da flarefotometria em pacientes com melanoma maligno e nevo de coróide Comparative study of flare photometry in patients with choroidal malignant melanoma and choroidal nevus

Directory of Open Access Journals (Sweden)

Priscilla Luppi Ballalai

2002-01-01

Full Text Available Introdução: Os tumores malignos intra-oculares estão associados com um aumento do "flare" na câmara anterior, causado por uma quebra na barreira hemato-aquosa, que pode ocorrer por vários mecanismos. Estudos utilizando a flarefotometria confirmam o aumento do "flare" em olhos com tumores intra-oculares malignos e benignos. Objetivo: Avaliar a flarefotometria como auxiliar no diagnóstico diferencial de melanoma maligno e nevo de coróide, comparando-se com olhos contralaterais normais. Métodos: Foram avaliados olhos com melanoma maligno e olhos com nevo de coróide diagnosticados por meio de oftalmoscopia indireta e/ou ultra-sonografia. Os olhos normais contralaterais foram utilizados como controles. A flarefotometria foi realizada em todos os pacientes, sob midríase bilateral, utilizando equipamento Laser Flare Meter (FC 500, Kowa. Foram aplicados os testes de Wilcoxon, Mann-Whitney, e Spearman para análise estatística. Resultados: A média da flarefotometria nos olhos com melanoma maligno de coróide foi 17,1 ph/ms e nos olhos normais contralaterais foi 4,06 ph/ms. Nos olhos com nevo de coróide o valor da flarefotometria foi 6,12 ph/ms e nos olhos contralaterais normais foi 4,47 ph/ms. O valor da flarefotometria foi maior nos olhos com melanoma maligno e nevo quando comparado com os olhos contralaterais normais (pIntroduction: Malignant intraocular tumors are associated with an increase in the aqueous flare, caused by alterations of the blood-ocular barriers through various mechanisms. Several studies have demonstrated an ocular flare increase using flare photometry in eyes with benign and malignant tumors. Purpose: To evaluate flare photometry as an adjunct method in the differential diagnosis of choroidal malignant melanoma and choroidal nevus comparing to normal control eyes. Methods: Eyes with melanoma and nevus were diagnosed by indirect binocular ophthalmoscopy and/or ultrasound were evaluated. The fellow normal eyes were used

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

International Nuclear Information System (INIS)

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

2002-01-01

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

Trends in size and treatment of recently diagnosed choroidal melanoma, 1987-1997: findings from patients examined at collaborative ocular melanoma study (COMS) centers: COMS report no. 20.

Science.gov (United States)

2003-08-01

To describe time trends, from 1987 through 1997, (1) in size of choroidal melanoma among patients with recent diagnosis confirmed at a clinical center that participated in the Collaborative Ocular Melanoma Study (COMS) and (2) in choice of treatment by patients who did not enroll in one of the COMS randomized trials. Investigators at all COMS clinical centers (41 in the United States and 2 in Canada) agreed to report, in a masked fashion that did not include personal identifiers, all patients diagnosed as having choroidal melanoma during the accrual period for COMS randomized trials of radiotherapy. Information reported for patients who did not enroll in a COMS randomized trial included tumor dimensions, date of diagnosis, and initial treatment selected. Patients reported by centers that continued to report cases until 1997 and diagnosed as having choroidal melanoma no more than 1 year before evaluation at a participating COMS center contributed the data analyzed. Time trends in tumor size among patients reported and in elective treatment of patients not enrolled in COMS randomized trials. Of 8712 patients with choroidal melanoma examined, 6703 met criteria for analysis of time trend in tumor size and 4077 were analyzed for treatment trends over time. The number of cases with longest tumor basal diameter greater than 15.0 mm declined over time from 393 (30%) of 1330 cases reported in 1987 through 1989 to 345 (25%) of 1397 cases reported in 1996 or 1997. The proportion of patients eligible for COMS randomized trials who did not enroll and who elected enucleation remained stable over time for tumors of all sizes; the proportion of these patients who elected eye-conserving radiotherapy increased over time. Juxtapapillary tumors accounted for nearly half of the enucleations among ineligible patients who had tumors no larger than 15.0 mm in longest basal diameter. Among patients examined at COMS centers during 1987 through 1997, the trends observed for patients with

Preliminary results of proton therapy in choroidal melanoma at the centre de proton therapy d`Orsay (C.P.O.): 464 initial cases; Resultats preliminaires de la protontherapie du melanome de la choroide au centre de protontherapie d`Orsay (CPO): les 464 premiers cas

Energy Technology Data Exchange (ETDEWEB)

Desjardins, L.; Levy, C.; D`hermies, F.; Frau, E.; Schlienger, P.; Habrand, J.L.; Mammar, H.; Schwartz, L.; Mazal, A.; Delacroix, S.; Nauraye, C.; Ferrand, R.; Asselain, B. [Centre de protontherapie d`Orsay, 91 - Orsay (France)

1997-06-01

Retrospective analysis of the treatment of choroidal melanoma with proton-therapy at the Centre de protontherapie d`Orsay, France. Between September 1991 and September 1995, 612 patients presenting with choroidal melanoma were treated by proton-therapy in Orsay. Following initial management of the first 464 patients, results were analyzed, as were results after a 1-year follow up for 305 patients, a 2-year follow-up for 169 patients, and a 3-year follow-up for 59 patients. Univariate analysis showed that the actuarial local recurrence rate was 5 %, the 3-year survival rate 88 %, and the overall metastatic rate 5%. The initial tumor volume was the most significant predictive factor for visual results and metastases. Multivariate analysis revealed that visual results were significantly related to the initial tumor volume, initial retinal detachment, and total dose delivered to the optic nerve and macula. Proton-therapy of choroidal melanoma allows in most cases conservation of the eye without modification of survival. Visual results mainly depend on the site and size of the tumor. (author) 16 refs.

Investigation into the quantitative and qualitative characteristics of choroidal melanoma through magnetic resonance imaging and B-scan ultrasound.

Science.gov (United States)

Papayiannis, Vassilis; Tsaousis, Konstantinos T; Kouskouras, Constantinos A; Haritanti, Afroditi; Diakonis, Vasilios F; Tsinopoulos, Ioannis T

2017-01-01

To investigate the homogeneity and vascularity of choroidal melanoma through magnetic resonance imaging (MRI) and brightness modulation (B-mode) ultrasound scan and their correlation with dimensions of tumor, as well as to measure the sensitivity of both modalities in retinal detachment (RD) detection. This retrospective chart review included patients diagnosed with choroidal melanoma. All these patients underwent MRI scans using T2-weighted (T2-WI) and T1-weighted (T1-WI) sequences, before and after an intravenous injection of paramagnetic contrast material. The patients were also examined using a B-mode ultrasound scan, and the results from both modalities were compared (tumor homogeneity, tumor height, tumor base diameter, and tumor vascularity). Forty-two patients (mean age=65.33±12.51 years) with choroidal melanoma were included in the study. Homogeneity was confirmed in 16 patients through ultrasound scan, in 19 patients through T1-WI sequence, in 21 patients through T2-WI sequence, and in 25 patients through T1-WI sequence + contrast (gadolinium). Patients with homogenous tumors presented with lower ( P =0.0045) mean height than that of those with nonhomogenous tumors, whereas no statistically significant difference was found for base diameter measurements ( P =0.056). Patients with tumors of high vascularity presented with greater mean height ( P =0.000638) and greater mean base diameter compared with those with tumors of low vascularity ( P =0.019543). RD was detected in 26 patients through T1-WI sequence, in 13 patients through T2-WI sequence, in 26 patients through T1-WI sequence + contrast, and in 32 patients through ultrasound scan, which proved to be the most sensitive modality. The height of choroidal melanoma was positively correlated with tumor's homogeneity. Melanomas of greater height were found to be less homogenous, due to increased degeneration and higher occurrence of intratumoral hemorrhage. In addition, choroidal melanoma's height was also

Appearance of choroidal melanoma on high resolution MRI using 1.5 T and a dedicated surface coil in 200 consecutive patients

International Nuclear Information System (INIS)

Lemke, A.J.; Hosten, N.; Frenzel, D.; Richter, M.; Felix, R.; Bornfeld, N.; Bechrakis, N.E.

1998-01-01

Purpose: Choroidal melanomas usually present a characteristic appearance in MRI. Differing characteristics can cause problems in differential diagnosis between melanomas and other masses in the globe. The purpose of this study was to evaluate the appearance of choroidal melanomas with MRI in a large consecutive patient group. Methods: In a prospective study, 200 patients with choroidal melanomas were investigated with MRI using a 1.5 T scanner and a 5 cm surface coil. Both quantitative and qualitative evaluation of the resulting images was performed. Results: 78.5% of the melanomas presented with homogeneous signal intensities within the tumor due to a homogeneous pigmentation whereas 21.5% of the melanomas demonstrated a mixed pigmentation. Signal intensities of the homogeneous melanomas in the plain T 1 -WI were moderately or markedly hyperintense compared to the vitreous in 29.3% and moderately or markedly hypointense in the T 2 -WI in 37.1%. An accompanying retinal detachment was found in 65.5% and an extraocular growth in 7.0%. Conclusions: In 10% to 37% we observed the typical well known MR appearance, including homogenous high signal in the T 1 -WI and low signals in the T 2 -WI. For further differentiation, morphological criteria (e.g. shape, size, and position) were used, which are also discussed. (orig.) [de

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

Complications of cobalt plaque therapy of choroidal malanomas

International Nuclear Information System (INIS)

Char, D.H.; Lonn, L.I.; Margolis, L.W.

1977-01-01

We treated a small series of patients with choroidal melanomas with radioactive cobalt plaques. To assess the effectiveness of radiation, we performed radioactive phosphorus ( 32 P) uptake determinations before and after treatment. The 32 P results did not tumor destruction. In five of seven patients with posterior pole melanomas, radiation retinopathy developed after treatment with resultant decrease in vision

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

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Nouritza M. Torossian

2015-01-01

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

Outcomes of Proton Radiation Therapy for Peripapillary Choroidal Melanoma at the BC Cancer Agency

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Tran, Eric, E-mail: etran2@bccancer.bc.ca [Radiation Therapy Program, BC Cancer Agency and University of British Columbia, Vancouver, British Columbia (Canada); Ma, Roy [Radiation Therapy Program, BC Cancer Agency and University of British Columbia, Vancouver, British Columbia (Canada); Paton, Katherine [Department of Ophthalmology and Visual Sciences, Vancouver Hospital Eye Care Centre and University of British Columbia, Vancouver, British Columbia (Canada); Blackmore, Ewart [TRIUMF, Vancouver, British Columbia (Canada); Pickles, Tom [Radiation Therapy Program, BC Cancer Agency and University of British Columbia, Vancouver, British Columbia (Canada)

2012-08-01

Purpose: To report toxicity, local control, enucleation, and survival rates for patients with peripapillary choroidal melanoma treated with proton therapy in Canada. Methods and Materials: We performed a retrospective analysis of patients with peripapillary choroidal melanoma ({<=}2 mm from optic disc) treated between 1995 and 2007 at the only Canadian proton therapy facility. A prospective database was updated for follow-up information from a chart review. Descriptive and actuarial data are presented. Results: In total, 59 patients were treated. The median age was 59 years. According to the 2010 American Joint Committee on Cancer TNM classification, there were 20 T1 tumors (34%), 28 T2 tumors (48%), and 11 T3 tumors (19%). The median tumor diameter was 11.4 mm, and the median thickness was 3.5 mm. Median follow-up was 63 months. Nineteen patients received 54 cobalt gray equivalents (CGE) and forty patients received 60 CGE, each in 4 fractions. The 5-year actuarial local control rate was 91% (T1, 100%; T2, 93%; and T3, 59%) (p = 0.038). There was a suggestive relationship between local control and dose. The local control rate was 97% with 60 CGE and 83% with 54 CGE (p = 0.106). The metastasis-free survival rate was 82% and related to T stage (T1, 94%; T2, 84%; and T3, 47%) (p < 0.001). Twelve patients died, including eleven with metastases. The 5-year actuarial rate of neovascular glaucoma was 31% (23% for T1-T2 and 68% for T3, p < 0.001), and that of enucleation was 0% for T1, 14% for T2, and 72% for T3 (p < 0.001). Radiation retinopathy (74%) and optic neuropathy (64%) were common within-field effects. Conclusions: Proton therapy provides excellent local control with acceptable toxicity while conserving the globe in 80% of cases. These results are consistent with other single-institution series using proton radiotherapy, and toxicity rates were acceptable. T3 tumors carry a higher rate of both local recurrence and metastasis.

Outcomes of Proton Radiation Therapy for Peripapillary Choroidal Melanoma at the BC Cancer Agency

International Nuclear Information System (INIS)

Tran, Eric; Ma, Roy; Paton, Katherine; Blackmore, Ewart; Pickles, Tom

2012-01-01

Purpose: To report toxicity, local control, enucleation, and survival rates for patients with peripapillary choroidal melanoma treated with proton therapy in Canada. Methods and Materials: We performed a retrospective analysis of patients with peripapillary choroidal melanoma (≤2 mm from optic disc) treated between 1995 and 2007 at the only Canadian proton therapy facility. A prospective database was updated for follow-up information from a chart review. Descriptive and actuarial data are presented. Results: In total, 59 patients were treated. The median age was 59 years. According to the 2010 American Joint Committee on Cancer TNM classification, there were 20 T1 tumors (34%), 28 T2 tumors (48%), and 11 T3 tumors (19%). The median tumor diameter was 11.4 mm, and the median thickness was 3.5 mm. Median follow-up was 63 months. Nineteen patients received 54 cobalt gray equivalents (CGE) and forty patients received 60 CGE, each in 4 fractions. The 5-year actuarial local control rate was 91% (T1, 100%; T2, 93%; and T3, 59%) (p = 0.038). There was a suggestive relationship between local control and dose. The local control rate was 97% with 60 CGE and 83% with 54 CGE (p = 0.106). The metastasis-free survival rate was 82% and related to T stage (T1, 94%; T2, 84%; and T3, 47%) (p < 0.001). Twelve patients died, including eleven with metastases. The 5-year actuarial rate of neovascular glaucoma was 31% (23% for T1–T2 and 68% for T3, p < 0.001), and that of enucleation was 0% for T1, 14% for T2, and 72% for T3 (p < 0.001). Radiation retinopathy (74%) and optic neuropathy (64%) were common within-field effects. Conclusions: Proton therapy provides excellent local control with acceptable toxicity while conserving the globe in 80% of cases. These results are consistent with other single-institution series using proton radiotherapy, and toxicity rates were acceptable. T3 tumors carry a higher rate of both local recurrence and metastasis.

Dosimetric and Late Radiation Toxicity Comparison Between Iodine-125 Brachytherapy and Stereotactic Radiation Therapy for Juxtapapillary Choroidal Melanoma

Energy Technology Data Exchange (ETDEWEB)

Krema, Hatem, E-mail: htmkrm19@yahoo.com [Department of Ocular Oncology, Princess Margaret Hospital/University Health Network, University of Toronto, Toronto, Ontario (Canada); Heydarian, Mostafa [Department of Radiation Medicine, Princess Margaret Hospital/University Health Network, University of Toronto, Toronto, Ontario (Canada); Beiki-Ardakani, Akbar [Department of Radiation Oncology, Princess Margaret Hospital/University Health Network, University of Toronto, Toronto, Ontario (Canada); Weisbrod, Daniel [Department of Ocular Oncology, Princess Margaret Hospital/University Health Network, University of Toronto, Toronto, Ontario (Canada); Xu, Wei [Department of Biostatistics, Princess Margaret Hospital/University Health Network, University of Toronto, Toronto, Ontario (Canada); Laperriere, Normand J.; Sahgal, Arjun [Department of Radiation Oncology, Princess Margaret Hospital/University Health Network, University of Toronto, Toronto, Ontario (Canada)

2013-07-01

Purpose: To compare the dose distributions and late radiation toxicities for {sup 125}I brachytherapy (IBT) and stereotactic radiation therapy (SRT) in the treatment of juxtapapillary choroidal melanoma. Methods: Ninety-four consecutive patients with juxtapapillary melanoma were reviewed: 30 have been treated with IBT and 64 with SRT. Iodine-125 brachytherapy cases were modeled with plaque simulator software for dosimetric analysis. The SRT dosimetric data were obtained from the Radionics XKnife RT3 software. Mean doses at predetermined intraocular points were calculated. Kaplan-Meier estimates determined the actuarial rates of late toxicities, and the log–rank test compared the estimates. Results: The median follow-up was 46 months in both cohorts. The 2 cohorts were balanced with respect to pretreatment clinical and tumor characteristics. Comparisons of radiation toxicity rates between the IBT and SRT cohorts yielded actuarial rates at 50 months for cataracts of 62% and 75% (P=.1), for neovascular glaucoma 8% and 47% (P=.002), for radiation retinopathy 59% and 89% (P=.0001), and for radiation papillopathy 39% and 74% (P=.003), respectively. Dosimetric comparisons between the IBT and SRT cohorts yielded mean doses of 12.8 and 14.1 Gy (P=.56) for the lens center, 17.6 and 19.7 Gy (P=.44) for the lens posterior pole, 13.9 and 10.8 Gy (P=.30) for the ciliary body, 61.9 and 69.7 Gy (P=.03) for optic disc center, and 48.9 and 60.1 Gy (P<.0001) for retina at 5-mm distance from tumor margin, respectively. Conclusions: Late radiation-induced toxicities were greater with SRT, which is secondary to the high-dose exposure inherent to the technique as compared with IBT. When technically feasible, IBT is preferred to treat juxtapapillary choroidal melanoma.

Neovascular Glaucoma After Stereotactic Radiotherapy for Juxtapapillary Choroidal Melanoma: Histopathologic and Dosimetric Findings

International Nuclear Information System (INIS)

Fernandes, Bruno F.; Weisbrod, Daniel; Yuecel, Yeni H.; Follwell, Matthew; Krema, Hatem; Heydarian, Mostafa; Xu Wei; Payne, David; McGowan, Hugh; Simpson, Ernest R.; Laperriere, Normand; Sahgal, Arjun

2011-01-01

Purpose: Enucleation after stereotactic radiotherapy (SRT) for juxtapapillary choroidal melanoma may be required because of tumor progression (TP) or the development of intractable radiation-induced neovascular glaucoma (NVG). We compare pathologic changes and dosimetric findings in those eyes enucleated secondary to NVG as opposed to TP to better understand potential mechanisms. Methods and Materials: Patients with juxtapapillary choroidal melanoma treated with SRT (70 Gy in 5 fractions, alternate days over a total of 10 days) at the Princess Margaret Hospital, Toronto, Ontario, Canada, who underwent enucleation between 1998 and 2006 were selected. We correlated dosimetric data based on the patient's original SRT treatment plan with histopathologic findings in the retina, optic nerve head, and anterior chamber. A dedicated ocular pathologist reviewed each case in a blinded fashion. Results: Ten eyes in ten patients were enucleated after SRT. Six were enucleated secondary to NVG and four secondary to because of TP. Aggressive tumor features such as invasion of the sclera and epithelioid cell type were observed predominantly in the TP group. Retinal damage was more predominant in the NVG group, as were findings of radiation-related retinal vascular changes of fibrinoid necrosis and hyalinization. No conclusive radiation-related effects were found in the anterior chamber. The maximum point dose and dose to 0.1 cc were lower for the anterior chamber as compared with the dose to the tumor, retina, and optic nerve head. The mean 0.1-cc doses to the retina were 69.4 Gy and 73.5 Gy and to the anterior chamber were 4.9 Gy and 17.3 Gy for the NVG group and tumor progression group, respectively. Conclusions: Our findings suggest that NVG is due to radiation damage to the posterior chamber of the eye rather than primary radiation damage to the anterior segment.

Investigation into the quantitative and qualitative characteristics of choroidal melanoma through magnetic resonance imaging and B-scan ultrasound

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Papayiannis V

2017-08-01

Full Text Available Vassilis Papayiannis,1 Konstantinos T Tsaousis,2,3 Constantinos A Kouskouras,4 Afroditi Haritanti,4 Vasilios F Diakonis,5 Ioannis T Tsinopoulos2 1Department of Radiology, Papageorgiou General Hospital, 2Department of Ophthalmology, Aristotle University of Thessaloniki, Thessaloniki, Greece; 3John A Moran Eye Center, University of Utah, Salt Lake City, UT, USA; 4Department of Radiology, AHEPA Aristotle University Hospital of Thessaloniki, Thessaloniki, Greece; 5Bascom Palmer Eye Institute, Miller School of Medicine, University of Miami, Miami, FL, USA Objective: To investigate the homogeneity and vascularity of choroidal melanoma through magnetic resonance imaging (MRI and brightness modulation (B-mode ultrasound scan and their correlation with dimensions of tumor, as well as to measure the sensitivity of both modalities in retinal detachment (RD detection.Materials and methods: This retrospective chart review included patients diagnosed with choroidal melanoma. All these patients underwent MRI scans using T2-weighted (T2-WI and T1-weighted (T1-WI sequences, before and after an intravenous injection of paramagnetic contrast material. The patients were also examined using a B-mode ultrasound scan, and the results from both modalities were compared (tumor homogeneity, tumor height, tumor base diameter, and tumor vascularity.Results: Forty-two patients (mean age =65.33±12.51 years with choroidal melanoma were included in the study. Homogeneity was confirmed in 16 patients through ultrasound scan, in 19 patients through T1-WI sequence, in 21 patients through T2-WI sequence, and in 25 patients through T1-WI sequence + contrast (gadolinium. Patients with homogenous tumors presented with lower (P=0.0045 mean height than that of those with nonhomogenous tumors, whereas no statistically significant difference was found for base diameter measurements (P=0.056. Patients with tumors of high vascularity presented with greater mean height (P=0.000638 and

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

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

1992-08-01

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

Use of iodine-125 brachytherapy in treatment of choroidal melanomas, technic and preliminary analysis of 78 patients

International Nuclear Information System (INIS)

Quetin, P.; Schumacher, C.; Schraub, S.; Meyer, L.; Polto, F.; Sahel, J.; Magnenet, P.; Andres, E.

2001-01-01

Purpose. - Iodine 125 curietherapy is one of the conservative treatments of uveal melanoma. The technique used to achieve these results was simplified through the physical characteristics of the radioelement and the optimized-dosimetry program employed. Patients and methods. - 78 patients with choroidal melanoma were treated with iodine 125. About 100 Gy were delivered to the superior pole of the tumour. The minimal length of follow-up was 17 months and the average, 67 months. Results. -There was 88% local control, leading to lowered visual acuity in 76 % of the cases. Radiation retinopathy, directly related to proximity to the macula, is the principle etiology. Seven patients died of hepatic metastasis, five patients were enucleated. Four patients were further treated with proton-therapy to make up for non-control locally. Conclusion. -One dose of 100 Gy to the superior pole of the tumor seemed to lead to good local control, with the exception of complications related to proximity to the macula and the optic nerve. In this attempt to optimize irradiation, the time lapse between any benefit in local control derived from irradiation and post-therapeutic complications observed remains insufficient to evaluate any relationship. (authors)

Stereotactic radiotherapy for choroidal melanoma: analysis of eye movement during treatment

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Souza, Felipe Marques Lucas de; Gonçalves, Odair Dias; Cardoso, Simone Coutinho, E-mail: felipemlucas@poli.ufrj.br [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil); Batista, Delano V.S. [Instituto de Radioproteção e Dosimetria (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil)

2017-07-01

This study aims to analyze the eye’s movement during radiotherapy treatment for choroidal melanoma, as well as the methodology used in the repositioning of the patient between treatments sessions. For this purpose, the procedures used by the hospital staff were analyzed on site and videos were recorded during the treatments. The methodology for the fixation of the eye is correct in its objective. However, the repositioning needs improvements in its reproducibility. It is recommended the study to fix the eye by the healthy eye and the feasibility study for the development of a software that assists in patient repositioning. (author)

Stereotactic radiotherapy for choroidal melanoma: analysis of eye movement during treatment

International Nuclear Information System (INIS)

Souza, Felipe Marques Lucas de; Gonçalves, Odair Dias; Cardoso, Simone Coutinho; Batista, Delano V.S.

2017-01-01

This study aims to analyze the eye’s movement during radiotherapy treatment for choroidal melanoma, as well as the methodology used in the repositioning of the patient between treatments sessions. For this purpose, the procedures used by the hospital staff were analyzed on site and videos were recorded during the treatments. The methodology for the fixation of the eye is correct in its objective. However, the repositioning needs improvements in its reproducibility. It is recommended the study to fix the eye by the healthy eye and the feasibility study for the development of a software that assists in patient repositioning. (author)

Stereotactic radiotherapy for choroidal melanoma: analysis of eye movement during treatment

Science.gov (United States)

Souza, F. M. L.; Gonçalves, O. D.; Batista, D. V. S.; Cardoso, S. C.

2018-03-01

This study aims to analyse the eye’s movement during radiotherapy treatment for choroidal melanoma, as well as the methodology used in the repositioning of the patient between treatments sessions. For this purpose, the procedures used by the hospital staff were analysed on site and videos were recorded during the treatments. The methodology for the fixation of the eye is correct in its objective. However, the repositioning needs improvements in its reproducibility. It is recommended the study to fix the eye by the healthy eye and the feasibility study for the development of a software that assists in patient repositioning.

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

Fractionated stereotactic irradiation by Cyberknife of choroid melanomas: repositioning validation, closed eyelids; Irradiation stereotaxique fractionnee par Cyberknife des melanomes choroidiens: validation du repositionnement, paupieres fermees

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Horn, S.; Rezvoy, N.; Lacornerie, T.; Mirabel, X.; Labalette, P.; Lartigau, E. [Centre Oscar-Lambret, Service de Radiotherapie, 59 - Lille (France)

2009-10-15

The fractionated stereotactic radiotherapy by Cyberknife is an option in the treatment of eyes tumors. The advantages of the Cyberknife in the choroid melanomas are in its infra-millimetric precision, to the automated repositioning on the skull bones and to the conformity brought by the stereotaxy. The objective of this study was to validate the quality of repositioning and the immobility of the eyes with closed eyelids. Conclusion: the reproducibility of the eye positioning with closed eyelids seems enough to consider the conservative treatment of choroid melanomas by fractionated stereotactic radiotherapy by Cyberknife without implementation of fiducials nor retrobulbar anaesthesia. (N.C.)

Tratamento conservador ocular dos melanomas de coróide com braquiterapia utilizando placas de iodo-125 Conservative treatment of choroidal melanomas using iodine brachytherapy

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Antônio Cássio Assis Pellizzon

2004-08-01

Full Text Available OBJETIVO: Avaliar, retrospectivamente, o resultado do tratamento conservador do melanoma de coróide, por meio de braquiterapia, usando placas episclerais de iodo-125 (modelo 6711, Amershan. MATERIAIS E MÉTODOS: Foram avaliados 49 pacientes portadores de melanoma de coróide tratados no Hospital do Câncer, São Paulo, SP, de março de 2001 a janeiro de 2003. Os seguintes parâmetros foram analisados e correlacionados ao controle local e sobrevida: sexo, idade, dimensões da lesão, tempo de tratamento e doses no ápice e base das lesões. RESULTADOS: Com diâmetro máximo da base do tumor de 17 mm e altura máxima de 12 mm, observamos que as doses na base do tumor variaram de 213 a 463 Gy (mediana de 347 Gy e no ápice, de 51 a 250 Gy (mediana de 91 Gy. As taxas de preservação ocular, sobrevida livre de doença e conservação ocular, atuariais em dois anos, foram de 96%, 93,5% e 96,3%, respectivamente. Através de análise univariada, o único fator prognóstico para controle local nesta análise foi a altura do tumor menor que 6 mm (p = 0,0348. CONCLUSÃO: A braquiterapia levou a uma taxa bastante satisfatória de controle local, confirmando que a altura do tumor é um dos fatores prognósticos importantes desse parâmetro.OBJECTIVE: To retrospectively evaluate the results of conservative therapy using episcleral iodine-125 (model 6711, Amershan plaque for brachytherapy of choroidal melanoma. MATERIALS AND METHODS: We evaluated 49 patients with choroidal melanoma treated at "Hospital do Câncer", São Paulo, Brazil, from March 2001 to January 2003. The following clinical parameters were analyzed and correlated with local control and survival rate: gender, age, lesion dimension, treatment duration, as well as doses in apex and base of the tumors. RESULTS: The maximum diameter and height of the base of the tumors treated were 17 mm and 12 mm, respectively. Doses at those points ranged from 213 to 463 Gy (median: 347 Gy and 51 to 250 Gy

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

International Nuclear Information System (INIS)

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

2013-01-01

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

PRIMARY CHOROIDAL MALIGNANT LYMPHOMA:REPORT OF A CASE AND REVIEW OF LITERATURE

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F. Asadi Amoli

2006-06-01

Full Text Available Non-Hodgkin lymphoma (NHL is one of the masquerade syndromes of malignant melanoma that can occur with two main patterns of presentations in the eye: metastatic involvement of uveal tract, and primary involvement of retina. We report ophthalmic, imaging and histopathological findings in the first case diagnosed as primary choroidal NHL without central nervous system or systemic involvement. A 37-year-old woman presented with the complaint of severe visual loss in her right eye. Significant ocular finding included light perception of vision (LP, 2+ APD, 2+ cells in vitreous and intraocular pressure of 46 mmHg. Fundoscopic examination revealed exudative retinal detachment. Ocular echography showed choroidal thickening in addition to retinal detachment. MRI showed semilunar shape lesion in the posterior right globe suggesting choroidal melanoma. Systemic work-up could not reveal any underlying cause. The patient underwent enucleation with clinical suggestion of choroidal melanoma. Result of histological examination showed NHL (diffuse large Bcell type of choroid. Immunohistochemical staining showed negative staining for HMB-45 and CD3, positive staining for LCA, and CD20. Multiple periodic lumbar puncture, bone marrow biopsies and MRI were unremarkable. No recurrence of tumor in systemic work-up was noted during the 36-months follow-up. Primary choroidal NHL is one of the causes of generalized thickening of choroid and should be considered in differential diagnosis of malignant melanoma. It is recommended to perform fine needle biopsy before performing surgery in any patient who has had an atypical malignant melanoma. This is, so far as we know, the first case diagnosed as primary choroidal NHL.

Surgery with radioguided location of a liver metastasis of melanoma choroid: case report

International Nuclear Information System (INIS)

Moreno, Marcelo; Miranda, Mario Henrique Furlanetto

2015-01-01

Introduction: The use of radioguided occult lesion localization prior to surgical excision is increasing, mainly due to the development of new probes and the use of PET-CT. Case report: A 70-year-old male who presented with a metastatic lesion in his liver from a choroidal melanoma. This was located using PET-CT and subsequently located with a low-energy intraoperative gamma probe during the laparotomy. Conclusion: The present case shows that it is possible to excise a hepatic metastasis utilizing the principles of radioguided surgery, even in centers without access to high energy probes. (author)

Immunohistochemistry of a choroidal melanoma: nestin, CD34 and CD117÷c-kit labeling.

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Vrapciu, Alexandra Diana; Rusu, Mugurel Constantin; Voinea, Liliana Mary

2014-01-01

In a case of choroidal melanoma (CM) in a 70-year-old male patient, was firstly aimed at studying the processes of angiogenesis by use of nestin and CD34 antibodies. Anti-CD117÷c-kit antibodies were further considered for their progenitor cells specificity. Choroidal melanoma was histopathologically confirmed. Nestin-positive endothelia were found in the CM and the adjacent retina, but not in endothelia elsewhere in that eye. Nestin-positive non-pigmentary cells were found within the CM. Filopodia-projecting endothelial tip cells (ETCs), nestin- and CD34-positive were found in the CM. CD34-positive ETCs were also found in the iridial stroma. There were found two different immune patterns of the retinal Müller cells (MCs). They were nestin-positive in the retina adjacent to the tumor, but negative in any other part of retina. On the other hand, CD117÷c-kit antibodies labeled MCs as follows: (a) discontinuously, or continuously, in the retina adjacent to the CM; (b) only the inner segments of the MCs were labeled in the retina unrelated to the CM. While nestin could be a reliable marker for retinal damage, the CD117÷c-kit phenotype of MCs still needs further investigations. Antiangiogenic therapy appears as a good choice for tumor therapy.

Comparison of parameters affecting GNP-loaded choroidal melanoma dosimetry; Monte Carlo study

Science.gov (United States)

Sharabiani, Marjan; Asadi, Somayeh; Barghi, Amir Rahnamai; Vaezzadeh, Mehdi

2018-04-01

The current study reports the results of tumor dosimetry in the presence of gold nanoparticles (GNPs) with different sizes and concentrations. Due to limited number of works carried out on the brachytherapy of choroidal melanoma in combination with GNPs, this study was performed to determine the optimum size and concentration for GNPs which contributes the highest dose deposition in tumor region, using two phantom test cases namely water phantom and a full Monte Carlo model of human eye. Both water and human eye phantoms were simulated with MCNP5 code. Tumor dosimetry was performed for a typical point photon source with an energy of 0.38 MeV as a high energy source and 103Pd brachytherapy source with an average energy of 0.021 MeV as a low energy source in water phantom and eye phantom respectively. Such a dosimetry was done for different sizes and concentrations of GNPs. For all of the diameters, increase in concentration of GNPs resulted in an increase in dose deposited in the region of interest. In a certain concentration, GNPs with larger diameters contributed more dose to the tumor region, which was more pronounced using eye phantom. 100 nm was reported as the optimum size in order to achieve the highest energy deposition within the target. This work investigated the optimum parameters affecting macroscopic dose enhancement in GNP-aided brachytherapy of choroidal melanoma. The current work also had implications on using low energy photon sources in the presence of GNPs to acquire the highest dose enhancement. This study is conducted through four different sizes and concentrations of GNPs. Considering the sensitivity of human eye tissue, in order to report the precise optimum parameters affecting radiosensitivity, a comprehensive study on a wide range of sizes and concentrations are required.

Dose rate effect of 125I irradiation on normal rabbit eyes and experimental choroidal melanoma

International Nuclear Information System (INIS)

Yang, C.M.; Olsen, K.R.; Schwade, J.G.; Houdek, P.V.; Markoe, A.M.; Pisciotta, V.; Xiaodong Wu

1993-01-01

The dose rate effect of radiation by 125 I plaque on choroidal melanoma and normal intraocular tissue was studied. In the first part of the experiment, high activity plaques (HAP) and low activity plagues (LAP) were implanted on rabbit eyes with experimental Greene choroidal melanoma to deliver a total dose of 10 000 cGy to the tumor apex. The mean dose rate calculated at 0.5 mm from the inner sclera in eight eyes with high activity plaques was 3341.5 cGy hr -1 while that in ten eyes with low activity plaques was 239.9 cGy hr -1 . For tumors less than 1.0 mm in height, both groups showed complete tumor regression at the tumor implantation site after plaque treatment. For tumours more than 1.0 mm in height, two out of two eyes in the low activity plaque group and one of four eyes in the high activity plaque group failed to show complete tumor regression. In the second part of the experiment, 125 I plaques were implanted on the sclera of 12 normal rabbits' eyes. Six received high dose rate plaque treatment, while the other six received low dose rate plaque treatment. Clinical and histologic examinations demonstrated more damaging effects to the normal chorioretinal tissues at the plaque implantation site in the high dose rate plaque group. These results suggest that high dose rate plaques are more effective than low dose rate plaques when tumor height is statistically controlled. (Author)

Iodine-125 radiation of posterior uveal melanoma

International Nuclear Information System (INIS)

Packer, S.

1987-01-01

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

Iodine-125 radiation of posterior uveal melanoma

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Packer, S.

1987-12-01

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

Ruthenium therapy of choroidal melanomas of the posterior pole

International Nuclear Information System (INIS)

Langmann, G.; Faschinger, C.; Langmann, A.; Poier, E.

1992-01-01

The indications for conservative treatment of intraocular melanomas of the posterior pole with radioactive plaques are controversial. Melanomas located at the macula or adjacent to the fovea are regarded as relative contraindications for conservative treatment. Three melanomas of the macula have been treated at our department meanwhile. The tumor elevation ranged between 3.5 and 6 mm, the distance to the fovea between 0.5 and 2 dd. An average radiation dosage between 130 and 160 Gy was delivered to the apex of the tumors. The duration of observation was between 12 months to 4 years. The tumor regression was satisfactory in all 3 cases, additional photocoagulation was necessary in one case of incomplete tumor regression. Pretreatment visual acuity ranged between 0.8 and 0.1, posttreatment visual acuity between 0.8 and 0.25. In one case we observed a local radiation vasculopathy. General examination did not reveal any signs of metastases. (authors)

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

Science.gov (United States)

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

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

Remodelling of choroidal blood flow in radiation choroidopathy

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Kobayashi, Hideo; Muraoka, Kanemitsu; Takahashi, Kyoichi; Sutoh, Noriko [Gunma Univ., Maebashi (Japan). School of Medicine

1997-02-01

Two males, aged 68 and 34 years each, presented with radiation retinopathy. One had received radiation therapy to the whole brain for intracranial metastasis of lung carcinoma 29 months before. The other underwent surgery and radiation for melanoma of the upper eyelid 15 years before. When examined by indocyanine green angiography. both cases showed vasoocclusive changes in the choroid involving the choriocapillaris and major vessels in the affected fundus area. In one eye with severe retinal vascular lesions in the superior temporal quadrant, the vortex vein in the quadrant had obliterated. The venous blood in this quadrant was drained into the inferior temporal vortex vein crossing the presumed watershed zone temporal to the macula. Collaterals had formed between choroidal arteries and between choroidal veins. These cases illustrate that choroidal vascular lesions may be present in radiation retinopathy, that the former may be more pronounced than the latter and that choroidal vessels may undergo extensive remodelling to compensate for the disturbed choroidal circulation. (author)

Remodelling of choroidal blood flow in radiation choroidopathy

International Nuclear Information System (INIS)

Kobayashi, Hideo; Muraoka, Kanemitsu; Takahashi, Kyoichi; Sutoh, Noriko

1997-01-01

Two males, aged 68 and 34 years each, presented with radiation retinopathy. One had received radiation therapy to the whole brain for intracranial metastasis of lung carcinoma 29 months before. The other underwent surgery and radiation for melanoma of the upper eyelid 15 years before. When examined by indocyanine green angiography. both cases showed vasoocclusive changes in the choroid involving the choriocapillaris and major vessels in the affected fundus area. In one eye with severe retinal vascular lesions in the superior temporal quadrant, the vortex vein in the quadrant had obliterated. The venous blood in this quadrant was drained into the inferior temporal vortex vein crossing the presumed watershed zone temporal to the macula. Collaterals had formed between choroidal arteries and between choroidal veins. These cases illustrate that choroidal vascular lesions may be present in radiation retinopathy, that the former may be more pronounced than the latter and that choroidal vessels may undergo extensive remodelling to compensate for the disturbed choroidal circulation. (author)

RARE METASTASES OF MALIGNANT MELANOMA

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Marija Trenkić-Božinović

2014-09-01

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

Treating Melanoma Metastases with a Novel Photodynamic Approach

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2017-09-01

AWARD NUMBER: W81XWH-15-1-0270 TITLE: Treating Melanoma Metastases with a Novel Photodynamic Approach PRINCIPAL INVESTIGATOR: Jin Xie...Metastases with a Novel Photodynamic Approach 5a. CONTRACT NUMBER Treating Melanoma Metastases with a Novel Photodynamic Approach 5b. GRANT NUMBER...ligand and after systemic injection, home to tumors in the lung. X-ray of relatively low doses can then be applied externally to the lung area to

Surgery with radioguided location of a liver metastasis of melanoma choroid: case report; Cirurgia com localizacao radioguiada de uma metastase hepatica de melanoma de coroide: relato de caso

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Moreno, Marcelo; Miranda, Mario Henrique Furlanetto, E-mail: mmoreno@unochapeco.edu.br, E-mail: mirandamario@unochapeco.edu.br [Universidade Comunitaria da Regiao de Chapeco (UNOCHAPECO), SC (Brazil)

2015-04-15

Introduction: The use of radioguided occult lesion localization prior to surgical excision is increasing, mainly due to the development of new probes and the use of PET-CT. Case report: A 70-year-old male who presented with a metastatic lesion in his liver from a choroidal melanoma. This was located using PET-CT and subsequently located with a low-energy intraoperative gamma probe during the laparotomy. Conclusion: The present case shows that it is possible to excise a hepatic metastasis utilizing the principles of radioguided surgery, even in centers without access to high energy probes. (author)

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

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

2016-03-01

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

Enucleaton of the right eye due to large choroidal melanoma with simultaneous penetrating cornea transplantation from OD to OS (Case report).

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E. A. Korchuganova; A. Yu. Slonimskiy,; O. Yu. Yatsenko; M. Yu. Lerner

2013-01-01

There is presentation case report of 75‑year old woman with choroidal melanoma (T3N0M0) on the right eye and failed graft on the left pseudophakic eye with far advanced glaucoma and ARMD. No treatment was given to the leading eye with VA 0,2. VA of OS = 1 / ∞ pr.l.certa; PKP OS in 2008 for pseudophakic bullous keratopathy on the eye with far advanced glaucoma. IOP was normal after previous filtering surgery. After PKP VA = 0,04; clear graft during 2 years; then gradually opacification and vas...

Avaliação da área de melanomas amelanóticos de coróide em coelhos: modelo matemático An assessment of rabbit's choroidal amelanotic melanomas area: mathematical model

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Ayrton Roberto Branco Ramos

2002-09-01

Full Text Available Objetivo: Os métodos terapêuticos para o tratamento dos melanomas de coróide incluem a observação, a radioterapia, a cirurgia e a laserterapia. Para acompanhamento do crescimento tumoral, há necessidade de documentação e medida do tamanho desses tumores. O objetivo deste estudo é apresentar um modelo matemático simples e de baixo custo, para medida de áreas desses tumores do fundo de olho. Métodos: Utilizaram-se 25 olhos de coelhos pigmentados. Fragmentos de melanomas amelanóticos de hamster foram implantados cirurgicamente no espaço supracoroideo dos olhos dos animais. Quando os tumores atingiram 3 a 4 diâmetros papilares de tamanho realizaram-se as retinografias e angiografias fluorescentes com retinógrafo sem Imaginet, com foco fixo. Por meio de cálculos matemáticos verificaram-se as áreas reais dos tumores. Resultados: Foi possível verificar as áreas reais dos tumores e na análise da comparação dos valores das médias obtidas para os tumores, verificou-se que não existiu diferença estatisticamente significativa entre eles (p= 0,717. Conclusões: Concluiu-se neste estudo, que com o uso de retinógrafo sem Imaginet, foi possível medir com acurácia e segurança, por meio de cálculo matemático, a área de melanomas amelanóticos de hamster implantados no espaço supracoroídeo de coelhos.Purpose: Methods of management for choroidal melanomas include basically observation, radiotherapy, surgery, and laser therapy. A reliable measure of the size of the tumor is very important to follow tumor growth. The purpose of this experimental study is to verify the reliability of a low-cost mathematical model to measure areas of tumors of the fundus. Methods: Twenty-five eyes of pigmented rabbits were used in this study. Experimental Greene hamster amelanotic choroidal melanomas were implanted into the suprachoroidal space. When the tumors reached 3 to 4 papillary diameters, we performed retinography and fluorescein angiograms

Ultrasonic characterisation of malignant melanoma of choroid

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John Sheila

1998-01-01

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

A pilot study to image the vascular network of small melanocytic choroidal tumors with speckle noise-free 1050-nm swept source optical coherence tomography (OCT choroidal angiography).

Science.gov (United States)

Maloca, Peter; Gyger, Cyrill; Hasler, Pascal W

2016-06-01

To visualize and measure the vascular network of melanocytic choroidal tumors with speckle noise-free swept source optical coherence tomography (SS-OCT choroidal angiography). Melanocytic choroidal tumors from 24 eyes were imaged with 1050-nm optical coherence tomography (Topcon DRI OCT-1 Atlantis). A semi-automated algorithm was developed to remove speckle noise and to extract and measure the volume of the choroidal vessels from the obtained OCT data. In all cases, analysis of the choroidal vessels could be performed with SS-OCT without the need for pupillary dilation. The proposed method allows speckle noise-free, structure-guided visualization and measurement of the larger choroidal vessels in three dimensions. The obtained data suggest that speckle noise-free OCT may be more effective at identifying choroidal structures than traditional OCT methods. The measured volume of the extracted choroidal vessels of Haller's layer and Sattler's layer in the examined tumorous eyes was on average 0.982463955 mm(3) /982463956 μm(3) (range of 0.209764406 mm(3) /209764405.9 μm(3)to 1.78105544 mm(3) /1781055440 μm(3)). Full thickness obstruction of the choroidal vasculature by the tumor was found in 18 cases (72 %). In seven cases (18 %), choroidal vessel architecture did not show pronounced morphological abnormalities (18 %). Speckle noise-free OCT may serve as a new illustrative imaging technology and enhance visualization of the choroidal vessels without the need for dye injection. OCT can be used to identify and evaluate the choroidal vessels of melanocytic choroidal tumors, and may represent a potentially useful tool for imaging and monitoring of choroidal nevi and melanoma.

Enucleaton of the right eye due to large choroidal melanoma with simultaneous penetrating cornea transplantation from OD to OS (Case report.

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E. A. Korchuganova

2013-01-01

Full Text Available There is presentation case report of 75‑year old woman with choroidal melanoma (T3N0M0 on the right eye and failed graft on the left pseudophakic eye with far advanced glaucoma and ARMD. No treatment was given to the leading eye with VA 0,2. VA of OS = 1 / ∞ pr.l.certa; PKP OS in 2008 for pseudophakic bullous keratopathy on the eye with far advanced glaucoma. IOP was normal after previous filtering surgery. After PKP VA = 0,04; clear graft during 2 years; then gradually opacification and vascularization occurred. VA dropped to light perception. Echography OD — tumor h 8,29 mm, d 21,77 mm. No ingrowth of tumor into anterior segment of the eye; VA OD = 0 (no light perception. Concerning the need to enucleate the right eye with large choroidal melanoma, the advantage of using corneal autograft from OD to OS, location of tumor in the posterior pole with no ingrowth in anterior segment, the decision was made to perform the following operation — to enucleate the right eye and transplant simultaneously corneal graft from OD on OS. Patient was discharged from the Ophthalmology Hospital with VA OS = 0,01, during next week VA improved to 0,02. 8,0 mm graft isclear, fixed with 8 interruptured and continious suture 10 / 0‑nylon. Anterior chamber — normal depth, atrophic iris, stable position of PC IOL. Optic nerve head is pale with subtotal deep glaucomatous excavation. Conclusion: presented case report demonstrates the rarepossibility to use cornea after enucleation the eye with large malignant tumor (located in the posterior pole for grafting in the only eye with failed vascularised graft. It was the only possibility for this patient to restore some vision.

Enucleaton of the right eye due to large choroidal melanoma with simultaneous penetrating cornea transplantation from OD to OS (Case report.

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E. A. Korchuganova

2014-07-01

Full Text Available There is presentation case report of 75‑year old woman with choroidal melanoma (T3N0M0 on the right eye and failed graft on the left pseudophakic eye with far advanced glaucoma and ARMD. No treatment was given to the leading eye with VA 0,2. VA of OS = 1 / ∞ pr.l.certa; PKP OS in 2008 for pseudophakic bullous keratopathy on the eye with far advanced glaucoma. IOP was normal after previous filtering surgery. After PKP VA = 0,04; clear graft during 2 years; then gradually opacification and vascularization occurred. VA dropped to light perception. Echography OD — tumor h 8,29 mm, d 21,77 mm. No ingrowth of tumor into anterior segment of the eye; VA OD = 0 (no light perception. Concerning the need to enucleate the right eye with large choroidal melanoma, the advantage of using corneal autograft from OD to OS, location of tumor in the posterior pole with no ingrowth in anterior segment, the decision was made to perform the following operation — to enucleate the right eye and transplant simultaneously corneal graft from OD on OS. Patient was discharged from the Ophthalmology Hospital with VA OS = 0,01, during next week VA improved to 0,02. 8,0 mm graft isclear, fixed with 8 interruptured and continious suture 10 / 0‑nylon. Anterior chamber — normal depth, atrophic iris, stable position of PC IOL. Optic nerve head is pale with subtotal deep glaucomatous excavation. Conclusion: presented case report demonstrates the rarepossibility to use cornea after enucleation the eye with large malignant tumor (located in the posterior pole for grafting in the only eye with failed vascularised graft. It was the only possibility for this patient to restore some vision.

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

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

2018-01-19

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

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

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

2001-12-01

Purpose. - Iodine 125 curietherapy is one of the conservative treatments of uveal melanoma. The technique used to achieve these results was simplified through the physical characteristics of the radioelement and the optimized-dosimetry program employed. Patients and methods. - 78 patients with choroidal melanoma were treated with iodine 125. About 100 Gy were delivered to the superior pole of the tumour. The minimal length of follow-up was 17 months and the average, 67 months. Results. -There was 88% local control, leading to lowered visual acuity in 76 % of the cases. Radiation retinopathy, directly related to proximity to the macula, is the principle etiology. Seven patients died of hepatic metastasis, five patients were enucleated. Four patients were further treated with proton-therapy to make up for non-control locally. Conclusion. -One dose of 100 Gy to the superior pole of the tumor seemed to lead to good local control, with the exception of complications related to proximity to the macula and the optic nerve. In this attempt to optimize irradiation, the time lapse between any benefit in local control derived from irradiation and post-therapeutic complications observed remains insufficient to evaluate any relationship. (authors)

Film dosimetry analyses on the effect of gold shielding for Iodine-125 eye plaque therapy for choroidal melanoma

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Wu, A. (Department of Radiation Oncology, University of Pittsburgh, School of Medicine, Joint Radiation Oncology Center and Pittsburgh Cancer Institute, Pittsburgh, PA (USA)); Krasin, F. (Department of Radiation Oncology, Tufts University School of Medicine, New England Medical Center, Boston, MA (USA))

1990-09-01

One of the methods currently being used to treat choroidal melanoma employs an episcleral plaque containing I-125 radioactive seeds. However, comprehensive dosimetry studies on the plaque are scarce and controversial. For this work, we use film to study the dosimetry outside the lip of the gold shield of the eye plaque. This lip around the gold shield was made to protect the critical structures behind and adjacent to the lesion. Since the changes of energy spectrum of I-125 in tissue are negligible, film dosimetry seems to be a logical choice because of high spatial resolution required around the lip of the gold plaque. For this study, we first established an H and D curve with dose expressed in a unit of specific dose rate constant. This avoids absolute dose measurements. All film density measurements are made with a 1-mm aperture scan, normalized to the density at the prescription point for tumor of 3--5-mm apical height, i.e., 5 mm from the interior surface of sclera, and converted to percentage isodose curves. With a gold shield, it is found that when the plaque is placed against the optical nerve, the optical disk and macula, located at 2 mm outside the lip, on the exterior surface of sclera, may receive 85% of the prescription dose for a 12-mm plaque and 58% for a 16-mm plaque. For tumors of 8-mm apical height, the optical nerve would receive more than the prescription dose.

Combination therapy of low-fluence photodynamic therapy and intravitreal ranibizumab for choroidal neovascular membrane in choroidal osteoma

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Rodney J Morris

2011-01-01

Full Text Available Choroidal osteoma is an unusual form of intraocular calcification seen in otherwise healthy eyes. It is a benign idiopathic osseous tumor of the choroid, typically seen in young females. Choroidal neovascular membrane (CNVM is a complication seen in one-third of these patients and carries a poor visual outcome. We report a case of a 25-year-old hyperthyroid female with choroidal osteoma and subfoveal CNVM in her left eye which was successfully treated using low-fluence photodynamic therapy (PDT with verteporfin followed by a single injection of intravitreal ranibizumab.

Long-term Results of the UCSF-LBNL Randomized Trial: Charged Particle With Helium Ion Versus Iodine-125 Plaque Therapy for Choroidal and Ciliary Body Melanoma

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Mishra, Kavita K., E-mail: Kavita.mishra@ucsf.edu [Department of Radiation Oncology, University of California-San Francisco, San Francisco, California (United States); Quivey, Jeanne M.; Daftari, Inder K. [Department of Radiation Oncology, University of California-San Francisco, San Francisco, California (United States); Lawrence Berkeley National Laboratory, Berkeley, California (United States); Weinberg, Vivian [Department of Radiation Oncology, University of California-San Francisco, San Francisco, California (United States); Cole, Tia B. [The Tumori Foundation, San Francisco, California (United States); Patel, Kishan [Department of Radiation Oncology, University of California-San Francisco, San Francisco, California (United States); Castro, Joseph R.; Phillips, Theodore L. [Department of Radiation Oncology, University of California-San Francisco, San Francisco, California (United States); Lawrence Berkeley National Laboratory, Berkeley, California (United States); Char, Devron H. [The Tumori Foundation, San Francisco, California (United States); Department of Ophthalmology, University of California-San Francisco, San Francisco, California (United States); Department of Ophthalmology, Stanford University, Palo Alto, California (United States)

2015-06-01

Purpose: Relevant clinical data are needed given the increasing national interest in charged particle radiation therapy (CPT) programs. Here we report long-term outcomes from the only randomized, stratified trial comparing CPT with iodine-125 plaque therapy for choroidal and ciliary body melanoma. Methods and Materials: From 1985 to 1991, 184 patients met eligibility criteria and were randomized to receive particle (86 patients) or plaque therapy (98 patients). Patients were stratified by tumor diameter, thickness, distance to disc/fovea, anterior extension, and visual acuity. Tumors close to the optic disc were included. Local tumor control, as well as eye preservation, metastases due to melanoma, and survival were evaluated. Results: Median follow-up times for particle and plaque arm patients were 14.6 years and 12.3 years, respectively (P=.22), and for those alive at last follow-up, 18.5 and 16.5 years, respectively (P=.81). Local control (LC) for particle versus plaque treatment was 100% versus 84% at 5 years, and 98% versus 79% at 12 years, respectively (log rank: P=.0006). If patients with tumors close to the disc (<2 mm) were excluded, CPT still resulted in significantly improved LC: 100% versus 90% at 5 years and 98% versus 86% at 12 years, respectively (log rank: P=.048). Enucleation rate was lower after CPT: 11% versus 22% at 5 years and 17% versus 37% at 12 years, respectively (log rank: P=.01). Using Cox regression model, likelihood ratio test, treatment was the most important predictor of LC (P=.0002) and eye preservation (P=.01). CPT was a significant predictor of prolonged disease-free survival (log rank: P=.001). Conclusions: Particle therapy resulted in significantly improved local control, eye preservation, and disease-free survival as confirmed by long-term outcomes from the only randomized study available to date comparing radiation modalities in choroidal and ciliary body melanoma.

Single institutional retrospective analysis: treatment of choroidal melanomas with cobalt-60 brachytherapy Análise retrospectiva uni-institucional: tratamento de melanomas de coróide com braquiterapia utilizando cobalto-60

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Antônio Cássio Assis Pellizzon

2004-06-01

Full Text Available PURPOSE: To evaluate the outcome of patients with choroidal melanoma treated with conservative therapy with brachytherapy (episcleral Co-60 plaque therapy at the "Hospital do Cancer" São Paulo, Brazil. METHODS: We evaluated 102 patients consecutively treated from January, 1999 to June, 1999. Median age, maximum tumor base diameter and apex size were 55.5 years, 9.75 mm and 5 mm, respectively. Doses at the base of the tumor, including 1 mm of sclera, ranged from 157 to 487 Gy (median 284.5 Gy and to the apex from 37 to 220 Gy (median 106 Gy. RESULTS: The crude eye preservation rate with conservative therapy alone was 78.5%. Five-year overall actuarial survival rate was 92.2% and eye conservation rate was 78%. Side effects were mostly an uncomplicated retinopathy in 39/102 patients (38.2%; macular degeneration or scarring led to poor central vision in 31/102 patients (30.3% of cases. CONCLUSION: Our experience with cobalt-60 plaque brachytherapy achieved a satisfactory rate of local tumor control, despite the oversized base diameters of treated tumors.OBJETIVOS: Para avaliar o resultado de tratamento pacientes portadores de melanoma de coróide tratados com braquiterapia (placas episclerais de Co-60 no Hospital do Câncer, São Paulo, Brasil. MÉTODOS: Foram avaliados 108 pacientes tratados consecutivamente de janeiro de 1995 a junho de 1999, com idade mediana de 55,5 anos, diâmetro da base do tumor e altura máximos 9,75 mm e 5 mm, respectivamente. As doses na base do tumor, incluindo 1 mm de esclera variaram de 157 a 487 Gy (mediana 284,5 Gy e para o ápice de 37 até 220 Gy (mediana 106 Gy. RESULTADOS: A taxa de preservação ocular foi 78,5%, com sobrevida atuarial global em cinco anos, e a taxa de conservação ocular atuarial foram 92,2% e 78%, respectivamente. Os principais efeitos colaterais relacionados ao tratamento foram retinopatia em 39/102 (38,2% pacientes e degeneração macular, levando a déficit visual central em 31/102 (30

Novel low-kVp beamlet system for choroidal melanoma

International Nuclear Information System (INIS)

Esquivel, Carlos Jr; Fuller, Clifton D; Waggener, Robert G; Wong, Adrian; Meltz, Martin; Blough, Melissa; Eng, Tony Y; Thomas, Charles R Jr

2006-01-01

Treatment of choroidal melanoma with radiation often involves placement of customized brachytherapy eye-plaques. However, the dosimetric properties inherent in source-based radiotherapy preclude facile dose optimization to critical ocular structures. Consequently, we have constructed a novel system for utilizing small beam low-energy radiation delivery, the Beamlet Low-kVp X-ray, or 'BLOKX' system. This technique relies on an isocentric rotational approach to deliver dose to target volumes within the eye, while potentially sparing normal structures. Monte Carlo N-Particle (MCNP) transport code version 5.0(14) was used to simulate photon interaction with normal and tumor tissues within modeled right eye phantoms. Five modeled dome-shaped tumors with a diameter and apical height of 8 mm and 6 mm, respectively, were simulated distinct positions with respect to the macula iteratively. A single fixed 9 × 9 mm 2 beamlet, and a comparison COMS protocol plaque containing eight I-125 seeds (apparent activity of 8 mCi) placed on the scleral surface of the eye adjacent to the tumor, were utilized to determine dosimetric parameters at tumor and adjacent tissues. After MCNP simulation, comparison of dose distribution at each of the 5 tumor positions for each modality (BLOKX vs. eye-plaque) was performed. Tumor-base doses ranged from 87.1–102.8 Gy for the BLOKX procedure, and from 335.3–338.6 Gy for the eye-plaque procedure. A reduction of dose of at least 69% to tumor base was noted when using the BLOKX. The BLOKX technique showed a significant reduction of dose, 89.8%, to the macula compared to the episcleral plaque. A minimum 71.0 % decrease in dose to the optic nerve occurred when the BLOKX was used. The BLOKX technique allows more favorable dose distribution in comparison to standard COMS brachytherapy, as simulated using a Monte Carlo iterative mathematical modeling. Future series to determine clinical utility of such an approach are warranted

Multifocal choroiditis as the first sign of systemic sarcoidosis associated with pembrolizumab

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Qu-Knafo Lise

2017-04-01

Conclusions and importance: Pembrolizumab is an immune checkpoint inhibitor therapy used in the treatment of metastatic melanoma. We report a pembrolizumab-associated sarcoidosis revealed by a panuveitis with multifocal choroiditis. Physicians should be aware of the potential inflammatory and autoimmune disease that may be induced by immunomodulatory therapies.

The clinical role of immunoscintigraphy for the detection of ocular melanoma

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

1996-12-01

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

Long-term Results of Carbon Ion Radiation Therapy for Locally Advanced or Unfavorably Located Choroidal Melanoma: Usefulness of CT-based 2-Port Orthogonal Therapy for Reducing the Incidence of Neovascular Glaucoma

International Nuclear Information System (INIS)

Toyama, Shingo; Tsuji, Hiroshi; Mizoguchi, Nobutaka; Nomiya, Takuma; Kamada, Tadashi; Tokumaru, Sunao; Mizota, Atsushi; Ohnishi, Yoshitaka; Tsujii, Hirohiko

2013-01-01

Purpose: To determine the long-term results of carbon ion radiation therapy (C-ion RT) in patients with choroidal melanoma, and to assess the usefulness of CT-based 2-port irradiation in reducing the risk of neovascular glaucoma (NVG). Methods and Materials: Between January 2001 and February 2012, a total of 116 patients with locally advanced or unfavorably located choroidal melanoma received CT-based C-ion RT. Of these patients, 114 were followed up for more than 6 months and their data analyzed. The numbers of T3 and T2 patients (International Union Against Cancer [UICC], 5th edition) were 106 and 8, respectively. The total dose of C-ion RT varied from 60 to 85 GyE, with each dose given in 5 fractions. Since October 2005, 2-port therapy (51 patients) has been used in an attempt to reduce the risk of NVG. A dose-volume histogram analysis was also performed in 106 patients. Results: The median follow-up was 4.6 years (range, 0.5-10.6 years). The 5-year overall survival, cause-specific survival, local control, distant metastasis-free survival, and eye retention rates were 80.4% (95% confidence interval 89.0%-71.8%), 82.2% (90.6%-73.8%), 92.8% (98.5%-87.1%), 72.1% (81.9%-62.3%), and 92.8% (98.1%-87.5%), respectively. The overall 5-year NVG incidence rate was 35.9% (25.9%-45.9%) and that of 1-port group and 2-port group were 41.6% (29.3%-54.0%) and 13.9% (3.2%-24.6%) with statistically significant difference (P<.001). The dose-volume histogram analysis showed that the average irradiated volume of the iris-ciliary body was significantly lower in the non-NVG group than in the NVG group at all dose levels, and significantly lower in the 2-port group than in the 1-port group at high dose levels. Conclusions: The long-term results of C-ion RT for choroidal melanoma are satisfactory. CT-based 2-port C-ion RT can be used to reduce the high-dose irradiated volume of the iris-ciliary body and the resulting risk of NVG

Long-term Results of Carbon Ion Radiation Therapy for Locally Advanced or Unfavorably Located Choroidal Melanoma: Usefulness of CT-based 2-Port Orthogonal Therapy for Reducing the Incidence of Neovascular Glaucoma

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Toyama, Shingo [Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan); Department of Heavy Particle Therapy and Radiation Oncology, Faculty of Medicine, Saga University, Saga (Japan); Tsuji, Hiroshi, E-mail: h_tsuji@nirs.go.jp [Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan); Mizoguchi, Nobutaka; Nomiya, Takuma; Kamada, Tadashi [Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan); Tokumaru, Sunao [Department of Heavy Particle Therapy and Radiation Oncology, Faculty of Medicine, Saga University, Saga (Japan); Mizota, Atsushi [Department of Ophthalmology, Teikyo University School of Medicine, Tokyo (Japan); Ohnishi, Yoshitaka [Department of Ophthalmology, Wakayama Medical University, Wakayama (Japan); Tsujii, Hirohiko [Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan)

2013-06-01

Purpose: To determine the long-term results of carbon ion radiation therapy (C-ion RT) in patients with choroidal melanoma, and to assess the usefulness of CT-based 2-port irradiation in reducing the risk of neovascular glaucoma (NVG). Methods and Materials: Between January 2001 and February 2012, a total of 116 patients with locally advanced or unfavorably located choroidal melanoma received CT-based C-ion RT. Of these patients, 114 were followed up for more than 6 months and their data analyzed. The numbers of T3 and T2 patients (International Union Against Cancer [UICC], 5th edition) were 106 and 8, respectively. The total dose of C-ion RT varied from 60 to 85 GyE, with each dose given in 5 fractions. Since October 2005, 2-port therapy (51 patients) has been used in an attempt to reduce the risk of NVG. A dose-volume histogram analysis was also performed in 106 patients. Results: The median follow-up was 4.6 years (range, 0.5-10.6 years). The 5-year overall survival, cause-specific survival, local control, distant metastasis-free survival, and eye retention rates were 80.4% (95% confidence interval 89.0%-71.8%), 82.2% (90.6%-73.8%), 92.8% (98.5%-87.1%), 72.1% (81.9%-62.3%), and 92.8% (98.1%-87.5%), respectively. The overall 5-year NVG incidence rate was 35.9% (25.9%-45.9%) and that of 1-port group and 2-port group were 41.6% (29.3%-54.0%) and 13.9% (3.2%-24.6%) with statistically significant difference (P<.001). The dose-volume histogram analysis showed that the average irradiated volume of the iris-ciliary body was significantly lower in the non-NVG group than in the NVG group at all dose levels, and significantly lower in the 2-port group than in the 1-port group at high dose levels. Conclusions: The long-term results of C-ion RT for choroidal melanoma are satisfactory. CT-based 2-port C-ion RT can be used to reduce the high-dose irradiated volume of the iris-ciliary body and the resulting risk of NVG.

Invasão do nervo óptico por melanoma peripapilar: relato de caso Optic nerve invasion by juxtapapillary melanoma: case report

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Eduardo Ferrari Marback

2003-06-01

Full Text Available Tumores pigmentados localizados sobre o disco óptico são raros e representam desafio diagnóstico. Paciente masculino, 60 anos, apresenta baixa da acuidade visual no olho esquerdo devido à lesão pigmentada que cobre o disco óptico. Foi indicada a enucleação com recusa pelo paciente. O quadro evoluiu com descolamento de retina. Examinado em outro serviço teve indicação de vitrectomia também recusada. Retorna aos nossos cuidados; feita a enucleação o diagnóstico anatomopatológico revelou melanoma maligno da coróide com invasão pós-laminar do nervo óptico. A importância prognóstica da invasão do nervo óptico por melanoma da coróide ainda não está totalmente esclarecida. Embora raro, tumor pigmentado cobrindo o nervo óptico pode representar melanoma maligno. O diagnóstico diferencial destes casos é geralmente difícil, porém seu reconhecimento à ultra-sonografia ocular é patente e descolamento de retina associado é sinal de atividade tumoral. Os riscos de disseminação da doença exigem atenção na suspeita diagnóstica e conduta precisa.Small-pigmented lesions over the optic disc are very rare and may represent a diagnostic challenge. To report a case of a small malignant choroidal melanoma invading the optic nerve. A 60-year-old male presents with low vision in the left eye due to a small, pigmented lesion over the optic disc. At first the patient refused enucleation. One month later, after further drop in visual acuity, the patient was seen at another service, diagnosed as having a retinal detachment, and pars plana vitrectomy was proposed but also refused by the patient. Returning to our service, the eye was enucleated and a final diagnosis of choroidal melanoma with post-laminar optic nerve invasion was made. Although rare, pigmented lesions over the optic disc may represent a malignant melanoma. The prognostic significance of optic nerve invasion by choroidal melanoma is not clear yet. The differential

Changes of subfoveal choroidal thickness after treated by Ranibizumab for choroidal neovascularization secondary to pathologic myopia

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Jian-Shu Yuan

2016-05-01

Full Text Available AIM:To observe the change of subfoveal choroidal thickness(SFCTafter intravitreal injections of anti-vascular endothelial growth factor monoclonal antibody Ranibizumab in patients with choroidal neovascularization(CNVsecondary to pathologic myopia(PMand to research the relation between visual acuity and SFCT.METHODS:This was a prospective, contrast, open-label study.Fifty pathologic myopia patients with CNV(50 eyeswere recruited in this study. Before the injection,best-corrected visual acuity detected by visual chart from Early Treatment of Diabetic Retinopathy Study(ETDRS,non-contact tonometer,ophthalmoscope,fundus photography, fundus fluorescein angiograph(FFAand optical coherence tomography(OCTexamination were necessary. All affected eye were treated with intravitreal ranibizumab 0.05mL. Following up for 12mo, the changes of visual acuity and SFCT were compared before and after treatment, also the relation between them. RESULTS:All eyes received an average of 2.47±2.23 injections,the final vision of follow-up increased by 13.62±8.98 letters than that before(t=6.69,Pt=0.95, P>0.05.While after 6 and 12mo,the differences were significant(t=2.34, 2.61; PPP>0.05.There were no serious systemic or local side effects during the follow up.CONCLUSION:Intravitreal ranibizumab for CNV secondary to pathologic myopia is safe and can improve the visual acuity.Intravitreal injections of ranibizumab can induce SFCT reduction for CNV secondary to pathologic myopia.We hypothesized that increase of SFCT may be one of evaluation index for CNV activity.

Rhegmatogenous Retinal Detachment Associated with Choroidal Detachment

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L. Sh. Bilandarli

2017-01-01

this pathology. Correct early diagnosis of “retino-choroidal dеtаchment” is complicated by several factors: sluggish pupil dilation, exacerbated by the presence of posterior synechiaes, clouding environments with the presence of cellular elements, choroidal dеtаchment, masking the retinal tears. Rhegmatogenous retino–choridal dеtаchment should be differentiated from a number of pathologies. The most obvious sign of “retinyl choroidal” dеtаchment is severe generalized inflammation leading to an erroneous diagnosis of uveitis. A particular problem is the differentiation with syndrome of uveal effusion, choroidal melanoma. Retino-choroidal dеtаchment is a rare pathology that requires timely and correct diagnosis of pathogenically based treatment.

Enhanced-Depth Imaging Optical Coherence Tomography of the Human Choroid In Vivo Compared With Histology After Enucleation

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Li, Xiao Qiang; Heegaard, Steffen; Kiilgaard, Jens Folke

2016-01-01

PURPOSE: This study compared in vivo enhanced-depth imaging optical coherence tomography (EDI-OCT) with ex vivo histology of the choroid in human eyes. METHODS: Three eyes in three patients with advanced iris melanoma without posterior segment involvement underwent EDI-OCT less than 24 hours prior...... to enucleation and, in one eye, immediately after enucleation. Following fixation in 4% buffered formaldehyde and paraffin embedding, serial sections of the whole eye were cut horizontally, mounted, stained with hematoxylin-eosin and digitized. Alignment between histology and EDI-OCT was made on landmarks...... and subfoveal choroid thickness reduced to 56%, 45%, and 56%, respectively, of its in vivo thickness on EDI-OCT. CONCLUSIONS: There were no identifiable discrepancies in choroidal structural patterns between clinical EDI-OCT and histologic sections except that after enucleation and histologic fixation choroidal...

Our Treatment Results of Circumscribed and Diffuse Choroidal Hemangiomas

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Esra Savku

2013-08-01

Full Text Available Purpose: To discuss our treatment results of choroidal hemangiomas. Material and Method: The records of 39 cases of choroidal hemangioma followed up at our clinic between July 1999–October 2012 were reviewed retrospectively. Asymptomatic cases were followed up. Symptomatic cases with subretinal fluid and impaired vision received treatment. Results: Mean age of the 39 patients was 44 (12-80 years. Thirty-five of 39 cases had circumscribed choroidal hemangioma, and 4 cases had diffuse choroidal hemangioma. Sturge-Weber syndrome was present in 3 cases with diffuse choroidal hemangioma. Cases with circumscribed choroidal hemangioma and minimal subretinal fluid were treated with TTT in 11 cases, PDT in 12 cases, and PDT+TTT in 1 case. Cases with circumscribed choroidal hemangioma and excessive subretinal fluid were treated with Ru-106 plaque radiotherapy in 1 case, Ru-106 plaque radiotherapy+TTT in 1 case, EBRT in 3 cases, and TTT+EBRT in 1 case. One painful blind eye with neovascular glaucoma and complicated cataract was enucleated. Cases with diffuse choroidal hemangioma and excessive subretinal fluid were treated with Ru-106 plaque radiotherapy+TTT in 1 case and EBRT in 1 case. Ahmed glaucoma valve implantation and FAKO emulsification were applied to a case with neovascular glaucoma and complicated cataract. Complete resorption of subretinal fluid was achieved in 23 (72% of treated 32 cases. When mean initial tumor thickness was 2.6 mm (0.5-6, mean final tumor thickness was 1.4 mm (0-6. When mean initial visual acuity (LogMAR was 1.5 (0-3, mean final visual acuity was 1.1 (0-3. No recurrence was observed. Discussion: The amount of the subretinal fluid determines the method of treatment in circumscribed choroidal hemangioma. While TTT and PDT are effective treatment modalities for minimal subretinal fluid, plaque radiotherapy and EBRT are applied in cases with excessive subretinal fluid. Combination therapies may be necessary according to the

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

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

2014-01-01

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

Choroidal Thinning Associated With Hydroxychloroquine Retinopathy.

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Ahn, Seong Joon; Ryu, So Jung; Joung, Joo Young; Lee, Byung Ro

2017-11-01

To investigate choroidal thickness in patients using hydroxychloroquine (HCQ) and compare choroidal thickness between eyes with and without HCQ retinopathy. Retrospective case series. Setting: Institutional. We included 124 patients with systemic lupus erythematosus or rheumatoid arthritis who were treated with HCQ. The patients were divided into an HCQ retinopathy group and a control group, according to the presence or absence of HCQ retinopathy. Total choroidal thickness and choriocapillaris-equivalent thickness were measured manually by 2 independent investigators using swept-source optical coherence tomography (SS-OCT; DRI-OCT, Topcon Inc, Tokyo, Japan). These measurements were made at the fovea and at nasal and temporal locations 0.5, 1.5, and 3 mm from the fovea. Medium-to-large vessel layer thickness was calculated accordingly. The thicknesses were compared between the HCQ retinopathy and control groups. We performed correlation analyses between choroidal thicknesses and details regarding HCQ use. Total choroidal thickness and choriocapillaris-equivalent thickness. Choroidal thicknesses were significantly decreased (P < .05) in the HCQ retinopathy group compared to the control group, except at the temporal choroid 1.5 mm from the fovea. Choriocapillaris-equivalent thicknesses were significantly different in all choroidal locations between the groups. In contrast, the medium-to-large vessel layer thickness was only significantly different at a few locations. The cumulative dose/body weight was significantly correlated with subfoveal choroidal and choriocapillaris-equivalent thicknesses (both P = .001). The association between presence of HCQ retinopathy and choroidal thicknesses was also statistically significant after adjusting for age, diagnosis for HCQ use, refractive errors, and duration of HCQ use (P = .001 and P = .003 for subfoveal choroidal and choriocapillaris-equivalent thickness, respectively). These results all suggest that HCQ retinopathy is

Uveal melanoma: Estimating prognosis

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Swathi Kaliki

2015-01-01

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

Comparison of conventional color fundus photography and multicolor imaging in choroidal or retinal lesions.

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Muftuoglu, Ilkay Kilic; Gaber, Raouf; Bartsch, Dirk-Uwe; Meshi, Amit; Goldbaum, Michael; Freeman, William R

2018-04-01

Our purpose was to compare the characteristics of the retinal and choroidal lesions including choroidal nevus, choroidal melanoma and congenital hypertrophy of the retina pigment epithelium using conventional color fundus photography (CFP) and multicolor imaging (MCI). The paired images of patients with retinal or choroidal lesions were assessed for the visibility of lesion's border, halo and drusen using a grading scale (0-2). The area of the lesion was measured on both imaging modalities. The same grading was also done on the individual color channels of MCI for a further evaluation. Thirty-three eyes of 33 patients were included. There were no significant differences in the mean border, drusen and halo visibility scores between the two imaging modalities (p = 0.12, p = 0.70, p = 0.35). However, the mean area of the lesion was significantly smaller on MCI than that on CFP (14.9±3.3 versus 18.7±3.4 mm 2 , p = 0.01). The appearance of choroidal and/ or retinal lesions on MCI may be different than that on CFP. Though MCI can provide similar information with CFP for the features of retinal and/ or choroidal lesions including border, halo and drusen; the infrared light reflection on MCI underestimates the extent of the choroidal lesion by 33%.

Role of Tc-99M(V) DMSA for imaging of ocular melanoma developing in graves' patients treated with radioiodine

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Bandopadhyaya, G.P.; Barai, S.; Bal, C.S.

2004-01-01

The melanoma originates from the melanocytes, which are embryologically derived from neural crest. The melanoma of choroids in adults is a very common type primary ocular malignancy, where the tyrosine, an immediate precursor common for both melanin and thyroid hormone synthesis is involved. The neurogenic origins of melanoma and medullary thyroid carcinoma have also been shown to have certain common metabolites, receptors and the receptor binding proteins. Several radiolabelled derivatives either in the form of melanin metabolites or melanin binding agents including receptors/ receptor-binding proteins like somatostatin, calcitonin and other monoclonal antibodies, protein receptors (S-100, myelin basic protein, Leu-7, glial fibrillary acidic protein, HMB-45) etc. have been tried to evaluate/diagnose melanoma, staging or post therapeutic effects. However their cost of production, tedious synthetic and radiolabelling processes and the availability of certain cyclotron produced isotopes were not favorable or patient friendly. Moreover post-therapeutic assessments in melanoma patients were not encouraging. Because of the chelating properties of Tc-99m (V) Dimercaptosuccinic acid with Calcium ion, uptake by neurogenic tumors including ocular retinoblastoma, medullary thyroid carcinoma, pituitary adenoma etc has been demonstrated. Since MTC and Melanoma have the common neural crest origin and producing some common metabolites, receptors/receptor proteins and at the same time Tc-99m (V) DMSA was used in pre and post therapeutic assessment of Medullary thyroid carcinoma extensively. We therefore decided to use Tc-99m (v) DMSA for the assessment of melanoma developed in thyrotoxicosis patients who underwent radioiodine therapy more than 15 years back. The DMSA kits were prepared locally and labeled with Tecnetium-99m at pentavalent state. After the quality control each patients were injected a dose of 10mCi of Tc-99m labeled DMSA.The whole body images were taken after two

Immunological correlates of treatment and response in stage IV malignant melanoma patients treated with Ipilimumab

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

2016-01-01

Introduction: Ipilimumab is effective in the treatment of metastatic malignant melanoma, but few biomarkers reliably predict treatment response. Methods: Patients were treated with Ipilimumab for metastatic malignant melanoma. Blood and serum samples were collected before and during treatment. Mo...

Treatment with cyclosporine A in serpiginous choroiditis: A case report

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Kovačević Dragana

2012-03-01

Full Text Available Serpiginous choroiditis is a rare clinical entity. The clinical course of serpiginous choroiditis is very variable, there is no universal marker of treatment success, and even among experts there is debate about what is the most appropriate treatment. The aim of this paper is to describe a case of serpiginous choroiditis treated with Cyclosporine A at a tertiary uveitis referral centre.

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

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

2017-10-01

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

Intensity-Modulated Radiotherapy Triggers Onset of Bullous Pemphigoid in a Patient with Advanced Melanoma Treated with Nivolumab

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Kayo Tanita

2018-02-01

Full Text Available Since the efficacy of ipilimumab on nivolumab-resistant advanced melanoma is extremely low, additional supportive therapy for anti-PD-1 antibody therapy-resistant advanced melanoma is needed. Although several supportive therapies that enhance the antitumor immune response of anti-PD-1 antibodies have already been reported, unexpected immune-related adverse events were detected at the same time. In this report, we describe a patient with advanced melanoma treated with nivolumab followed by intensity-modulated radiotherapy, which might have triggered bullous pemphigoid (BP. Although several cases of BP developing in anti-PD-1 antibody-treated patients have already been reported, in this report, we shed light on the possible pathogenesis of BP developing in a patient treated with nivolumab through M2 macrophages.

Polypoidal Choroidal Vasculopathy Associated with Optic Disc Coloboma

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Yumiko Nakano

2018-01-01

Full Text Available Purpose: To report a case of polypoidal choroidal vasculopathy associated with optic disc coloboma. Methods: Case report. Results: A 50-year-old woman presented with optic disc coloboma and retinochoroidal coloboma associated with subretinal hemorrhage and serous retinal detachment (SRD in her left eye. Optical coherence tomography (OCT confirmed SRD at the macula and showed a sharply elevated retinal epithelial detachment at the choroidal excavation. OCT also revealed choroidal cavitation along the temporal side of the optic coloboma. Fluorescein angiography showed hyperfluorescent dye leakage and indocyanine green angiography revealed polypoidal lesions. We diagnosed polypoidal choroidal vasculopathy (PCV. PCV was located at the end of the choroidal cavitation. Her left eye was treated with an intraocular injection of the anti-vascular endothelial growth factor aflibercept (2 mg. Photodynamic therapy was performed using the standard protocol 1 week after the intravitreal application of aflibercept. One month after the combined treatment, OCT showed completely resolved SRD and her symptoms disappeared. Her best-corrected visual acuity remained stable and no recurrence was found during a 12-month follow-up period. Conclusion: PCV associated with optic disc coloboma has not been previously reported. The morphological abnormality of choroidal cavitation and choroidal excavation connecting with optic disc coloboma may contribute to the development of PCV in this case.

Dose–response of critical structures in the posterior eye segment to hypofractioned stereotactic photon radiotherapy of choroidal melanoma

International Nuclear Information System (INIS)

Dunavoelgyi, Roman; Georg, Dietmar; Zehetmayer, Martin; Schmidt-Erfurth, Ursula; Pötter, Richard; Dörr, Wolfgang; Dieckmann, Karin

2013-01-01

Purpose: To identify modifying factors and dose–/volume–response relationships for the retina and optic nerve related to highly conformal hypofractionated radiotherapy. Patients and methods: Seventy-three patients undergoing hypofractionated stereotactic photon radiotherapy of choroidal melanoma were included in this retrospective study. The volumes of the optic nerve receiving doses of more than 7.5 or 12 Gy, respectively, were defined. Optic nerve circumference included in the 30%, 40%, 50%, or 80% isodose (ON % ) and retina included in 30% or 40% were determined as quantal effects. Univariate and multivariate analyses were performed for clinical variables as well as probit analysis to define EDx (doses where a positive response is expected in x% of the cases). Results: Median follow-up was 90.0 (interquartile range 69.0–98.0) months. Fifty-two (71%) and 49 (67%) patients developed radiation retinopathy and optic neuropathy (any grade). Age, length of follow-up and diabetes were significant parameters regarding retinopathy. Optic neuropathy was significantly influenced by age, length of follow-up, and ON 30 . The probability of optic neuropathy (any grade and grade ⩾2) significantly increases with the dose (p ranges from 0.0126 to 0.0211). Conclusion: Treatment planning should aim at minimizing encompassing isodoses particularly in the low dose region, without compromising PTV coverage

Optic nerve invasion of uveal melanoma

DEFF Research Database (Denmark)

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

2007-01-01

in Denmark between 1942 and 2001 were reviewed (n=157). Histopathological characteristics and depth of optic nerve invasion were recorded. The material was compared with a control material from the same period consisting of 85 cases randomly drawn from all choroidal/ciliary body melanomas without optic nerve...... juxtapapillary tumors invading the optic nerve because of simple proximity to the nerve. A neurotropic subtype invades the optic nerve and retina in a diffuse fashion unrelated to tumor size or location. Udgivelsesdato: 2007-Jan...

Popliteal lymphadenectomy for treating metastatic melanoma: case report

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Sergio Renato Pais Costa

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

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

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

2003-01-01

the characteristic properties of malignant melanoma. However, the transplanted cells demonstrated vimentin reactivity, whereas the primary tumour cells were negative for vimentin. It can be concluded that a new experimental model of malignant uveal melanoma with tumours that were easy to observe and access...... model. Tumour tissue blocks (2 x 2 x 2 mm) from enucleated eyes with choroidal malignant melanoma were transplanted subcutaneously into the flanks of nude mice. The growing tumours were measured and serially transplanted. The tumour samples were investigated by histology, immunohistochemistry....... The transplanted tumour cells were epithelioid and slightly larger than the primary tumour cells and had prominent nucleoli. However, the transplanted tumour retained a morphological appearance similar to that of the primary tumour. Immunohistochemical examinations demonstrated that the cells preserved...

Radiotherapy of choroidal metastases

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Hoogenhout, J; Gasteren, J J.M. van; Brink, H M.A.; Verbeek, A M; Beex, L V.A.M.

1989-05-01

With binocular indirect ophthalmoscopy, fluorescin angiography and ultrasonography 68 choroidal metastases in 52 eyes of 39 patients were diagnosed. The primary tumors were mainly breast cancer (81%) and lung cancer (10%). After radiation treatment the visual acuity improved in 17 eyes (38%), stabilized in 15 eyes (33%), whereas in 13 eyes (29%) deterioration could not be prevented (seven eyes unknown). Regression of the lesions or its accompanying secondary retinal detachment was seen in 78% of the eyes treated. Acute transient side effects of radiation therapy were keratoconjunctivitis (nine patients) and acute glaucoma in one patient. No cataractous changes of the lens were observed in the post radiation period (one to 42 months). Irradiation of choroidal metastases can contribute to improvement of the quality of life with a treatment scheme of 30 Gy in ten daily fractions.

Four cases of facial melanoma treated by BNCT with 10B-p-boronophenylalanine

International Nuclear Information System (INIS)

Fukuda, H.; Mishima, Y.; Hiratsuka, J.; Kobayashi, T.; Karashima, H.; Yoshino, K.; Tsuru, K.; Araki, K.; Ichihashi, M.

2000-01-01

We treated four cases of facial melanoma by BNCT with 10 B-paraboronophenylalanine · fructose complex (BPA). The patients received 180 to 200 mg BPA/kg-BW intravenously for 3 to 5 hours. One to two hours after the end of BPA administration, they were irradiated with a thermal neutron beam at the Kyoto University Reactor (KUR). The local control of the tumors was good and complete regression was achieved in all cases. The acute and subacute skin reactions ranged from dry desquamation to erosion and were within tolerable limits. After 2 to 3 months, the skin recovered from damage with slight pigmentation or depigmentation and without serious functional or cosmetic problems. Our results indicate BNCT of facial melanoma is promising not only for tumor cure but also for good QOL of the patients, although surgery is the standard and first choice for the treatment of malignant melanoma. (author)

Bevacizumab inhibits proliferation of choroidal endothelial cells by regulation of the cell cycle.

Science.gov (United States)

Rusovici, Raluca; Patel, Chirag J; Chalam, Kakarla V

2013-01-01

The purpose of this study was to evaluate cell cycle changes in choroidal endothelial cells treated with varying doses of bevacizumab in the presence of a range of concentrations of vascular endothelial growth factor (VEGF). Bevacizumab, a drug widely used in the treatment of neovascular age-related macular degeneration, choroidal neovascularization, and proliferative diabetic retinopathy, neutralizes all isoforms of VEGF. However, the effect of intravitreal administration of bevacizumab on the choroidal endothelial cell cycle has not been established. Monkey choroidal endothelial (RF/6A) cells were treated with VEGF 50 ng/mL and escalating doses of bevacizumab 0.1-2 mg/mL for 72 hours. Cell cycle changes in response to bevacizumab were analyzed by flow cytometry and propidium iodide staining. Cell proliferation was measured using the WST-1 assay. Morphological changes were recorded by bright field cell microscopy. Bevacizumab inhibited proliferation of choroidal endothelial cells by stabilization of the cell cycle in G0/G1 phase. Cell cycle analysis of VEGF-enriched choroidal endothelial cells revealed a predominant increase in the G2/M population (21.84%, P, 0.01) and a decrease in the G0/G1 phase population (55.08%, P, 0.01). Addition of escalating doses of bevacizumab stabilized VEGF-enriched cells in the G0/G1 phase (55.08%, 54.49%, 56.3%, and 64% [P, 0.01]) and arrested proliferation by inhibiting the G2/M phase (21.84%, 21.46%, 20.59%, 20.94%, and 16.1% [P, 0.01]). The increase in G0/G1 subpopulation in VEGF-enriched and bevacizumab-treated cells compared with VEGF-enriched cells alone was dose-dependent. Bevacizumab arrests proliferation of VEGF-enriched choroidal endothelial cells by stabilizing the cell cycle in the G0/G1 phase and inhibiting the G2/M phase in a dose-dependent fashion.

Spontaneous Regression of Choroidal Neovascularization in a Patient with Pattern Dystrophy

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Anastasios Anastasakis

2016-01-01

Full Text Available Purpose. To present a case of a patient with pattern dystrophy (PD associated choroidal neovascularization (CNV that resolved spontaneously without treatment. Methods. A 69-year-old male patient was referred to our unit, for evaluation of a recent visual loss (metamorphopsias in his left eye. Fundus examination, fundus autofluorescence imaging, and fluorescein angiography showed a choroidal neovascular membrane in his left eye. Since visual acuity was satisfactory the patient elected observation. Clinical examination and OCT testing were repeated at 6 and 12 months after presentation. Results. Visual acuity remained stable at the level of 0.9 (baseline BCVA during the follow-up period (12 months. Repeat OCT testing showed complete spontaneous regression of the choroidal neovascular membrane without evidence of intra- or subretinal fluid in both follow-up visits. Conclusions. Spontaneous regression of choroidal neovascularization can occur in patients with retinal dystrophies and associated choroidal neovascular membranes. The decision to treat or observe these patients relies strongly on the presenting visual acuity, since, in isolated instances, spontaneous resolution of choroidal neovascularization may occur.

Peripapillary Choroidal Neovascularization Associated with Optic Nerve Head Drusen Treated with Anti-VEGF Agents

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Norman A. Saffra

2015-02-01

Full Text Available Optic nerve head drusen can be associated with peripapillary choroidal neovascularization, in both the pediatric and adult population. These membranes can involve the macula, causing significant visual loss. Herein, we present a case that required treatment with an anti-VEGF agent. The patient failed to respond to the initial agent, but subsequently responded to a change of agent. Adult patients with macular degeneration involving peripapillary choroidal neovascularization associated with optic nerve head drusen may require individualized treatment plans.

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

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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.

Feasibility of Proton Beam Therapy for Ocular Melanoma Using a Novel 3D Treatment Planning Technique

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Hartsell, William F., E-mail: whartsell@chicagocancer.org [Northwestern Medicine Chicago Proton Center, Proton Collaborative Group, Warrenville, Illinois (United States); Kapur, Rashmi [Retina Consultants, Des Plaines, Illinois (United States); Hartsell, Siobhan O' Connor; Sweeney, Patrick [Northwestern Medicine Chicago Proton Center, Warrenville, Illinois (United States); Lopes, Caitlin [Rush Medical College, Chicago, Illinois (United States); Duggal, Amanda [Northwestern Medicine Chicago Proton Center, Warrenville, Illinois (United States); Cohen, Jack [Department of Ophthalmology, Rush University, Chicago, Illinois (United States); Chang, John [Northwestern Medicine Chicago Proton Center, Proton Collaborative Group, Warrenville, Illinois (United States); Polasani, Rajeev S. [Northwestern Medicine Central DuPage Hospital, Winfield, Illinois (United States); Dunn, Megan [Northwestern Medicine Chicago Proton Center, Proton Collaborative Group, Warrenville, Illinois (United States); Pankuch, Mark [Northwestern Medicine Chicago Proton Center, Proton Collaborative Group, Warrenville, Illinois (United States)

2016-05-01

Purpose: We evaluated sparing of normal structures using 3-dimensional (3D) treatment planning for proton therapy of ocular melanomas. Methods and Materials: We evaluated 26 consecutive patients with choroidal melanomas on a prospective registry. Ophthalmologic work-up included fundoscopic photographs, fluorescein angiography, ultrasonographic evaluation of tumor dimensions, and magnetic resonance imaging of orbits. Three tantalum clips were placed as fiducial markers to confirm eye position for treatment. Macula, fovea, optic disc, optic nerve, ciliary body, lacrimal gland, lens, and gross tumor volume were contoured on treatment planning compute tomography scans. 3D treatment planning was performed using noncoplanar field arrangements. Patients were typically treated with 3 fields, with at least 95% of planning target volume receiving 50 GyRBE in 5 fractions. Results: Tumor stage was T1a in 10 patients, T2a in 10 patients, T2b in 1 patient, T3a in 2 patients, T3b in 1 patient, and T4a in 2 patients. Acute toxicity was mild. All patients completed treatment as planned. Mean optic nerve dose was 10.1 Gy relative biological effectiveness (RBE). Ciliary body doses were higher for nasal (mean: 11.4 GyRBE) than temporal tumors (5.8 GyRBE). Median follow-up was 31 months (range: 18-40 months). Six patients developed changes which required intraocular bevacizumab or corticosteroid therapy, but only 1 patient developed neovascular glaucoma. Five patients have since died: 1 from metastatic disease and 4 from other causes. Two patients have since required enucleation: 1 due to tumor and 1 due to neovascular glaucoma. Conclusions: 3D treatment planning can be used to obtain appropriate coverage of choroidal melanomas. This technique is feasible with relatively low doses to anterior structures, and appears to have acceptable rates of local control with low risk of enucleation. Further evaluation and follow-up is needed to determine optimal dose-volume relationships for

Feasibility of Proton Beam Therapy for Ocular Melanoma Using a Novel 3D Treatment Planning Technique

International Nuclear Information System (INIS)

Hartsell, William F.; Kapur, Rashmi; Hartsell, Siobhan O'Connor; Sweeney, Patrick; Lopes, Caitlin; Duggal, Amanda; Cohen, Jack; Chang, John; Polasani, Rajeev S.; Dunn, Megan; Pankuch, Mark

2016-01-01

Purpose: We evaluated sparing of normal structures using 3-dimensional (3D) treatment planning for proton therapy of ocular melanomas. Methods and Materials: We evaluated 26 consecutive patients with choroidal melanomas on a prospective registry. Ophthalmologic work-up included fundoscopic photographs, fluorescein angiography, ultrasonographic evaluation of tumor dimensions, and magnetic resonance imaging of orbits. Three tantalum clips were placed as fiducial markers to confirm eye position for treatment. Macula, fovea, optic disc, optic nerve, ciliary body, lacrimal gland, lens, and gross tumor volume were contoured on treatment planning compute tomography scans. 3D treatment planning was performed using noncoplanar field arrangements. Patients were typically treated with 3 fields, with at least 95% of planning target volume receiving 50 GyRBE in 5 fractions. Results: Tumor stage was T1a in 10 patients, T2a in 10 patients, T2b in 1 patient, T3a in 2 patients, T3b in 1 patient, and T4a in 2 patients. Acute toxicity was mild. All patients completed treatment as planned. Mean optic nerve dose was 10.1 Gy relative biological effectiveness (RBE). Ciliary body doses were higher for nasal (mean: 11.4 GyRBE) than temporal tumors (5.8 GyRBE). Median follow-up was 31 months (range: 18-40 months). Six patients developed changes which required intraocular bevacizumab or corticosteroid therapy, but only 1 patient developed neovascular glaucoma. Five patients have since died: 1 from metastatic disease and 4 from other causes. Two patients have since required enucleation: 1 due to tumor and 1 due to neovascular glaucoma. Conclusions: 3D treatment planning can be used to obtain appropriate coverage of choroidal melanomas. This technique is feasible with relatively low doses to anterior structures, and appears to have acceptable rates of local control with low risk of enucleation. Further evaluation and follow-up is needed to determine optimal dose-volume relationships for

Role of echography in diagnostic dilemma in choroidal masses

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Kopal N Mithal

2014-01-01

Full Text Available Purpose: To evaluate the role of echography in diagnosis and management of a diverse array of choroidal masses. Materials and Methods: Sixty-two cases of clinically suspected choroidal masses were prospectively analyzed with B-scan (10 Hz, A-scan, and ultrasound biomicroscopy (UBM (50 Hz after a meticulous history and ocular examination. Ancillary investigations and systemic evaluation were also done. Results: Based on clinical suspicion, acoustic features, response to treatment, and other ancillary tests combined together, the various masses were differentiated. The cases included in the study were as follows: n = 10 malignant melanomas, n = 16 metastasis and infiltrations, n = 9 hemangioma, n = 7 tuberculoma, n = 8 nonspecific inflammatory masses, n = 2 disciform plaques, n = 4 macular cysts or retinoschisis, n = 2 Coat′s disease, n = 1 melanocytoma, and n = 2 osteomas. Ultrasonography (USG alone could identify n = 51 lesions, while UBM in combination with USG was needed in remaining 11 masses. Conclusion: Standardized echography is an important adjunct in the diagnosis and management of eyes with intraocular masses. A better understanding of the clinicopathological and echographic picture of the diverse lesions can help in detection, differentiation, diagnosis, proposing a therapeutic approach, and also monitoring response to treatment. Echography is essential to evaluate tumors for extrascleral and anterior segment extension.

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

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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.

Choroidal vasculature characteristics based choroid segmentation for enhanced depth imaging optical coherence tomography images

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Chen, Qiang; Niu, Sijie [School of Computer Science and Engineering, Nanjing University of Science and Technology, Nanjing 210094 (China); Yuan, Songtao; Fan, Wen, E-mail: fanwen1029@163.com; Liu, Qinghuai [Department of Ophthalmology, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029 (China)

2016-04-15

Purpose: In clinical research, it is important to measure choroidal thickness when eyes are affected by various diseases. The main purpose is to automatically segment choroid for enhanced depth imaging optical coherence tomography (EDI-OCT) images with five B-scans averaging. Methods: The authors present an automated choroid segmentation method based on choroidal vasculature characteristics for EDI-OCT images with five B-scans averaging. By considering the large vascular of the Haller’s layer neighbor with the choroid-sclera junction (CSJ), the authors measured the intensity ascending distance and a maximum intensity image in the axial direction from a smoothed and normalized EDI-OCT image. Then, based on generated choroidal vessel image, the authors constructed the CSJ cost and constrain the CSJ search neighborhood. Finally, graph search with smooth constraints was utilized to obtain the CSJ boundary. Results: Experimental results with 49 images from 10 eyes in 8 normal persons and 270 images from 57 eyes in 44 patients with several stages of diabetic retinopathy and age-related macular degeneration demonstrate that the proposed method can accurately segment the choroid of EDI-OCT images with five B-scans averaging. The mean choroid thickness difference and overlap ratio between the authors’ proposed method and manual segmentation drawn by experts were −11.43 μm and 86.29%, respectively. Conclusions: Good performance was achieved for normal and pathologic eyes, which proves that the authors’ method is effective for the automated choroid segmentation of the EDI-OCT images with five B-scans averaging.

Choroidal vasculature characteristics based choroid segmentation for enhanced depth imaging optical coherence tomography images

International Nuclear Information System (INIS)

Chen, Qiang; Niu, Sijie; Yuan, Songtao; Fan, Wen; Liu, Qinghuai

2016-01-01

Purpose: In clinical research, it is important to measure choroidal thickness when eyes are affected by various diseases. The main purpose is to automatically segment choroid for enhanced depth imaging optical coherence tomography (EDI-OCT) images with five B-scans averaging. Methods: The authors present an automated choroid segmentation method based on choroidal vasculature characteristics for EDI-OCT images with five B-scans averaging. By considering the large vascular of the Haller’s layer neighbor with the choroid-sclera junction (CSJ), the authors measured the intensity ascending distance and a maximum intensity image in the axial direction from a smoothed and normalized EDI-OCT image. Then, based on generated choroidal vessel image, the authors constructed the CSJ cost and constrain the CSJ search neighborhood. Finally, graph search with smooth constraints was utilized to obtain the CSJ boundary. Results: Experimental results with 49 images from 10 eyes in 8 normal persons and 270 images from 57 eyes in 44 patients with several stages of diabetic retinopathy and age-related macular degeneration demonstrate that the proposed method can accurately segment the choroid of EDI-OCT images with five B-scans averaging. The mean choroid thickness difference and overlap ratio between the authors’ proposed method and manual segmentation drawn by experts were −11.43 μm and 86.29%, respectively. Conclusions: Good performance was achieved for normal and pathologic eyes, which proves that the authors’ method is effective for the automated choroid segmentation of the EDI-OCT images with five B-scans averaging.

Orbital melanocytoma: When a tumor becomes a relieving surprise

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Haytham E. Nasr

2018-06-01

Full Text Available Purpose: Melanocytomas are rare pigmented tumors that arise form melanocytes and have been reported in the central nervous system. Orbital melanocytomas “also known as blue nevus” are rarely reported. The occurrence of choroidal melanoma and orbital melanocytomas has never been described. Observations: This is a case of orbital melanocytoma in a 34 year old female who presented with left proptosis and ecchymosis. She has the right eye enucleated to treat a large choroidal melanoma, 6 years earlier. Orbital metastasis was suspected. After orbital imaging and systemic evaluation, incisional biopsy was planned yet the mass could be totally excised and it turned out to be melanocytoma. The condition was not associated with nevus of Ota and the patient is not known to have any predisposing condition for melanocytic lesions. Conclusion and importance: Melanocytoma and malignant melanoma share the same cell of origin. The benign course, the well differentiated cells, absence of anaplasia and the positive reaction to Human Melanoma Black-45 (HMB-45 and S-100 proteins established the diagnosis of the former. Such diagnosis was a relief for this one eyed patient.(HMB-45:human melanoma black-45. Keywords: Orbit, Melanocytoma, Choroidal melanoma, HMB-45, S-100

Correlation between choroidal thickness and macular hole

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Li-Li Wang

2018-01-01

Full Text Available AIM:To explore the correlation between choroidal thickness and macular hole, and to provide a theoretical basis for diagnosis and treatment of macular hole. METHODS: This study included 40 cases of monocular idiopathic macular hole patients who were treated in ophthalmology of our hospital from June 2015 to June 2016 and 40 cases of healthy people. Sicked eyes of idiopathic macular hole patients(40 eyeswere set as the Group A, uninjured side eyes(40 eyeswere set as the Group B, eyes of 40 cases of healthy people(40 normal eyeswere set as the Group C. Choroidal thickness of macular fovea, macular fovea 1mm, 3mm at 9 points, 4 directions in the upper, lower, nasal and temporal regions were measured through coherent optical tomography of enhanced deep imaging(enhanced depth image optical coherence tomography, EDI-OCT. They were recorded as SFCT, SCT1mm, SCT3mm, ICT1mm, ICT3mm, NCT1mm, NCT3mm, TCT1mm, TCT3mm, and correlation analysis between SFCT and age was analyzed. RESULTS: Average SFCT of Group A, B had no significant difference, data of the Group C was significantly higher than those of the Group A, B, there was statistical significance(P1mm, SCT3mm, ICT1mm, ICT3mm, NCT1mm, NCT3mm, TCT1mm, TCT3mm of the Group A, B had no significant difference(P>0.05, and choroidal thickness at each point of the Group C was significantly higher than that of Group A and B, there was statistical significance(Pr=-0.065, P=0.148; r=-0.057, P=0.658, SFCT of the Group C was negatively correlated with age(r=-0.343, P=0.041. CONCLUSION: The pathogenesis of idiopathic macular hole may be related to the sharp decrease of choroidal thickness, choroidal thickness of uninjured side eyes reduces more sharply than normal population and choroidal vascular metabolism reduces may be pathogenic.

Proton or photon irradiation for hemangiomas of the choroid? A retrospective comparison

International Nuclear Information System (INIS)

Hoecht, Stefan; Wachtlin, Joachim; Bechrakis, Nikolaos E.; Schaefer, Christiane; Heufelder, Jens; Cordini, Dino; Kluge, Heinz; Foerster, Michael; Hinkelbein, Wolfgang

2006-01-01

Purpose: The aim of this study was to compare, on a retrospective basis, the results of therapy in patients with uveal hemangioma treated with photon or proton irradiation at a single center. Methods and Materials: From 1993 to 2002 a total of 44 patients were treated. Until 1998 radiotherapy was given with 6 MV photons in standard fractionation of 2.0 Gy 5 times per week. In 1998 proton therapy became available and was used since then. A dose of 20 to 22.5 Cobalt Gray Equivalent (CGE) 68 MeV protons was given on 4 consecutive days. Progressive symptoms or deterioration of vision were the indications for therapy. Results: Of the 44 patients treated, 36 had circumscribed choroidal hemangiomas and 8 had diffuse choroidal hemangiomas (DCH) and Sturge-Weber syndrome. Of the patients, 19 were treated with photons with a total dose in the range of 16 to 30 Gy. A total of 25 patients were irradiated with protons. All patients with DCH but 1 were treated with photons. Stabilization of visual acuity was achieved in 93.2% of all patients. Tumor thickness decreased in 95.4% and retinal detachment resolved in 92.9%. Late effects, although generally mild or moderate, were frequently detected. In all, 40.9% showed radiation-induced optic neuropathy, maximum Grade I. Retinopathy was found in 29.5% of cases, but only 1 patient experienced more than Grade II severity. Retinopathy and radiation-induced optic neuropathy were reversible in some of the patients and in some resolved completely. No differences could be detected between patients with circumscribed choroidal hemangiomas treated with protons and photons. Treatment was less effective in DCH patients (75%). Conclusions: Radiotherapy is effective in treating choroidal hemangiomas with respect to visual acuity and tumor thickness but a benefit of proton therapy could not be detected. Side effects are moderate but careful monitoring for side effects should be part of the follow-up procedures

Choroidal osteoma: US and CT findings

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Kim, Dong Hun; Park, Sang Woo [Armed Forces Kwangju Hospital, Kwangju (Korea, Republic of); Kim, Jeong Hun [Seoul National University College of Medicine, Seoul (Korea, Republic of)

2003-02-01

The purpose of this study was to evaluate US and CT features of choroidal osteoma. US and CT scans of seven cases of choroidal osteoma occurring in six patients were retrospectively analyzed. We analysed US and CT findings with particular attention to the location, size, and shape of calcification associated with choroidal osteoma, and sought the possible cause of the tumor, if any. None of six patients had any possible cause related to choroidal osteoma. All of seven cases of choroidal osteoma were manifested as calcified mass which were located in the posterior wall of the eyeball near the juxtapapillary region. Calcification ranged in size from 1 to 2 cm and had curvilinear shape. Both US and CT were equally useful to evaluate choroidal osteoma. By depicting the characteristic calcification, US and CT are useful imaging modalities in evaluating choroidal osteoma.

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...

Metastatic melanoma of mesentery

International Nuclear Information System (INIS)

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

2004-01-01

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

Thyroxine transport in choroid plexus

International Nuclear Information System (INIS)

Dickson, P.W.; Aldred, A.R.; Menting, J.G.; Marley, P.D.; Sawyer, W.H.; Schreiber, G.

1987-01-01

The role of the choroid plexus in thyroid hormone transport between body and brain, suggested by strong synthesis and secretion of transthyretin in this tissue, was investigated in in vitro and in vivo systems. Rat choroid plexus pieces incubated in vitro were found to accumulate thyroid hormones from surrounding medium in a non-saturable process. At equilibrium, the ratio of thyroid hormone concentration in choroid plexus pieces to that in medium decreased upon increasing the concentration of transthyretin in the medium. Fluorescence quenching of fluorophores located at different depths in liposome membranes showed maximal hormone accumulation in the middle of the phospholipid bilayer. Partition coefficients of thyroxine and triiodothyronine between lipid and aqueous phase were about 20,000. After intravenous injection of 125 I-labeled thyroid hormones, choroid plexus and parts of the brain steadily accumulated 125 I-thyroxine, but not [ 125 I]triiodothyronine, for many hours. The accumulation of 125 I-thyroxine in choroid plexus preceded that in brain. The amount of 125 I-thyroxine in non-brain tissues and the [ 125 I]triiodothyronine content of all tissues decreased steadily beginning immediately after injection. A model is proposed for thyroxine transport from the bloodstream into cerebrospinal fluid based on partitioning of thyroxine between choroid plexus and surrounding fluids and binding of thyroxine to transthyretin newly synthesized and secreted by choroid plexus

Safety and Efficacy of Radiation Therapy in Advanced Melanoma Patients Treated With Ipilimumab

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Qin, Rosie [School of Medicine, Duke University Medical Center, Durham, North Carolina (United States); Olson, Adam [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Singh, Bhavana [Department of Medicine, Duke University Medical Center, Durham, North Carolina (United States); Thomas, Samantha; Wolf, Steven [Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, North Carolina (United States); Bhavsar, Nrupen A. [Department of Medicine, Duke University Medical Center, Durham, North Carolina (United States); Hanks, Brent A. [Division of Medical Oncology, Duke University Medical Center, Durham, North Carolina (United States); Salama, Joseph K. [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Salama, April K.S., E-mail: april.salama@duke.edu [Division of Medical Oncology, Duke University Medical Center, Durham, North Carolina (United States)

2016-09-01

Purpose: Ipilimumab and radiation therapy (RT) are standard treatments for advanced melanoma; preclinical models suggest the potential for synergy. However, limited clinical information exists regarding safety and optimal timing of the combination. Methods and Materials: We reviewed the records of consecutive patients with unresectable stage 3 or 4 melanoma treated with ipilimumab. Patients were categorized as having received RT or not. Differences were estimated between these 2 cohorts. Results: We identified 88 patients treated with ipilimumab. At baseline, the ipilimumab-plus-RT group (n=44) had more unfavorable characteristics. Despite this, overall survival, progression-free survival, and both immune-related and non–immune-related toxicity were not statistically different (P=.67). Patients who received ipilimumab before RT had an increased duration of irradiated tumor response compared with patients receiving ipilimumab after RT (74.7% vs 44.8% at 12 months; P=.01, log-rank test). In addition, patients receiving ablative RT had non–statistically significantly improved median overall survival (19.6 vs 10.2 months), as well as 6-month (95.1% vs 72.7%) and 12-month (79.7% vs 48.5%) survival rates, compared with those treated with conventionally fractionated RT. Conclusions: We found that both ablative and conventionally fractionated RT can be safely administered with ipilimumab without a clinically apparent increase in toxicity. Patients who received ipilimumab before RT had an increased duration of irradiated tumor response.

Transport across the choroid plexus epithelium.

Science.gov (United States)

Praetorius, Jeppe; Damkier, Helle Hasager

2017-06-01

The choroid plexus epithelium is a secretory epithelium par excellence. However, this is perhaps not the most prominent reason for the massive interest in this modest-sized tissue residing inside the brain ventricles. Most likely, the dominant reason for extensive studies of the choroid plexus is the identification of this epithelium as the source of the majority of intraventricular cerebrospinal fluid. This finding has direct relevance for studies of diseases and conditions with deranged central fluid volume or ionic balance. While the concept is supported by the vast majority of the literature, the implication of the choroid plexus in secretion of the cerebrospinal fluid was recently challenged once again. Three newer and promising areas of current choroid plexus-related investigations are as follows: 1 ) the choroid plexus epithelium as the source of mediators necessary for central nervous system development, 2 ) the choroid plexus as a route for microorganisms and immune cells into the central nervous system, and 3 ) the choroid plexus as a potential route for drug delivery into the central nervous system, bypassing the blood-brain barrier. Thus, the purpose of this review is to highlight current active areas of research in the choroid plexus physiology and a few matters of continuous controversy. Copyright © 2017 the American Physiological Society.

Intravitreal bevacizumab associated with photodynamic therapy in a case of polypoidal choroidal vasculopathy associated with choroidal nevus: A case report.

Science.gov (United States)

Rangel, Carlos M; Villota, Eva; Fernández-Vega González, Álvaro; Sanchez-Avila, Ronald M

2017-12-01

Report the clinical findings and management of a case of polypoidal choroidal vasculopathy associated with choroidal nevus which received combination therapy. Decreased visual acuity in a woman with polypoidal choroidal vasculopathy and choroidal nevus. Polypoidal choroidal vasculopathy and choroidal nevus. The initial visual acuity was 0.5. After the first treatment with photodynamic therapy, exudation and bleeding appeared around the lesion. After this, the patient received 3 doses of intravitreal bevacizumab. After treatment with combination therapy, visual acuity, clinical and imaging findings improved, with no recurrence of exudation and bleeding. Intravitreal bevacizumab as an adjunctive treatment after photodynamic therapy is a good option for patients with polypoidal choroidal vasculopathy associated with choroidal nevus. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

VEGF-production by CCR2-dependent macrophages contributes to laser-induced choroidal neovascularization.

Directory of Open Access Journals (Sweden)

Torsten A Krause

Full Text Available Age-related macular degeneration (AMD is the most prevalent cause of blindness in the elderly, and its exsudative subtype critically depends on local production of vascular endothelial growth factor A (VEGF. Mononuclear phagocytes, such as macrophages and microglia cells, can produce VEGF. Their precursors, for example monocytes, can be recruited to sites of inflammation by the chemokine receptor CCR2, and this has been proposed to be important in AMD. To investigate the role of macrophages and CCR2 in AMD, we studied intracellular VEGF content in a laser-induced murine model of choroidal neovascularisation. To this end, we established a technique to quantify the VEGF content in cell subsets from the laser-treated retina and choroid separately. 3 days after laser, macrophage numbers and their VEGF content were substantially elevated in the choroid. Macrophage accumulation was CCR2-dependent, indicating recruitment from the circulation. In the retina, microglia cells were the main VEGF+ phagocyte type. A greater proportion of microglia cells contained VEGF after laser, and this was CCR2-independent. On day 6, VEGF-expressing macrophage numbers had already declined, whereas numbers of VEGF+ microglia cells remained increased. Other sources of VEGF detectable by flow cytometry included in dendritic cells and endothelial cells in both retina and choroid, and Müller cells/astrocytes in the retina. However, their VEGF content was not increased after laser. When we analyzed flatmounts of laser-treated eyes, CCR2-deficient mice showed reduced neovascular areas after 2 weeks, but this difference was not evident 3 weeks after laser. In summary, CCR2-dependent influx of macrophages causes a transient VEGF increase in the choroid. However, macrophages augmented choroidal neovascularization only initially, presumably because VEGF production by CCR2-independent eye cells prevailed at later time points. These findings identify macrophages as a relevant source

Knockdown of the placental growth factor gene inhibits laser induced choroidal neovascularization in a murine model.

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Nourinia, Ramin; Soheili, Zahra-Soheila; Ahmadieh, Hamid; Akrami, Hassan; Rezaei Kanavi, Mozhgan; Samiei, Shahram

2013-01-01

To evaluate the effect of placental growth factor (PlGF) gene knockdown in a murine model of laser-induced choroidal neovascularization. Choroidal neovascularization was induced in the left eyes of 11 mice by infrared laser. Small interfering RNA (siRNA, 20 picomoles/10 μl) corresponding to PlGF mRNA was administered intravitreally by Hamilton syringe in all subjects. One month later, fluorescein angiography and histolologic examination were performed. No leakage was apparent in the 11 eyes treated with siRNA cognate to PlGF. The results of histological evaluation were consistent with angiographic findings showing absence of choroidal neovascularization. Knockdown of the PlGF gene can inhibit the growth of laser-induced choroidal neovascularization in mice.

Intranasal melanoma treated with radiation therapy in three dogs.

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Davies, Owen; Spencer, Sarah; Necova, Slavomira; Holmes, Emma; Taylor, Angela; Blackwood, Laura; Lara-Garcia, Ana

2017-12-01

Three dogs were investigated for chronic unilateral nasal discharge. In all cases CT imaging showed an intranasal mass causing turbinate lysis and no evidence of metastasis. Cytology in cases 1 (a 14-year-old neutered male crossbreed dog) and 2 (a five-year-old neutered male German Shepherd dog) demonstrated a pleomorphic cell population with variable intracellular pigment suspicious of melanocytic neoplasia. Histopathology with immunohistochemistry (Melan-A and vimentin, plus PNL-2 in one case) confirmed the diagnosis of melanoma in all dogs. All dogs were treated with megavoltage radiotherapy using linear accelerators. Cases 1 and 3 (a nine-year-old neutered female beagle dog) received a hypofractionated (4 × 8 Gy) protocol and case 2 received a definitive (12 × 4 Gy) protocol. Complete remission was demonstrated on repeat CT scan five months after diagnosis in case 1 and seven months in case 2. Stable disease was documented on CT at four months for case 3; however, clinical signs in this dog remained controlled for 10 months in total. Case 1 died of unrelated causes five months after diagnosis, case 2 was euthanased due to the development of seizures 13 months after diagnosis, and case 3 was lost to follow-up 12 months after diagnosis. Melanoma should be considered as a rare differential diagnosis for primary nasal neoplasia in the dog and radiation therapy can be used as effective local therapy.

Pediatric Melanoma and Drug Development

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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.

Supra choroidal buckling in managing myopic vitreoretinal interface disorders: 1-year data.

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El Rayes, Ehab N

2014-01-01

To evaluate the efficacy of supra choroidal buckling procedure using a supra choroidal catheter, as a new approach in treating myopic vitreomacular interface disorders specially in difficult cases of myopic traction maculopathy with or without macular hole retinal detachment in posterior staphyloma depending on the concept of indenting the choroid only, from a 1-year data study. A newly developed supra choroidal catheter was used to deliver stabilized, cross-linked, long-acting hyaluronic acid as a filler in the supra choroidal space in the area of the staphyloma forming a choroidal indenting effect. Before the injection, pars plana vitrectomy was performed without internal limiting membrane peeling to avoid the risk of break of the roof of foveal detachment in case of foveoschisis. This indentation was used to treat 11 patients with myopic foveoschisis and 12 patients with myopic macular hole retinal detachment, 5 of whom had failed primary repair by vitrectomy before inclusion in this trial. Clinical and optical coherence tomographic evaluations of these patients were performed over 1-year follow-up. Retinal layer restoration was achieved in all 11 eyes with myopic foveoschisis. This was gradual over a period of 2 to 6 weeks postoperatively. No recurrence over the 12-month follow-up was observed. Visual acuity improved by 1 line or more in 9 eyes (81.8%). Of the 12 eyes, 10 with macular hole detachment (83%) showed closure of the holes in association with the resolution of the detachment; 2 eyes showed resolution of the detachment and flatting of the edge of the holes but with incomplete closure on optical coherence tomography. Eight eyes (66.6%) showed improvement in visual acuity by 1 or more lines with no recurrence of retinal detachment over the 12-month follow-up period. The indentation effect was sufficient over the 12-month follow-up period. The indentation effect achieved by supra choroidal approach can be used as a method of managing myopic foveoschisis

Choroidal thickness in traumatic optic neuropathy.

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Lee, Ju-Yeun; Eo, Doo-Ri; Park, Kyung-Ah; Oh, Sei Yeul

2017-12-01

To examine the choroidal thickness in patients with indirect traumatic optic neuropathy (TON) Methods: Patients with unilateral traumatic optic neuropathy over a period of 4 years were included in this study. Horizontal and vertical enhanced-depth imaging (EDI) from spectral-domain optical coherence tomography (SD-OCT) scans of the fovea were obtained in patients with unilateral TON within 2 weeks of injury. The main outcome measure was the choroidal thickness at nine locations. The choroidal thickness was compared between affected and unaffected eyes in the TON group, and the mean difference in the choroidal thickness in both eyes was compared between TON and control groups. A total of 16 patients and 20 control subjects were included. The choroidal thickness at horizontal, vertical and average subfoveal, inner temporal, and outer inferior locations was significantly thicker (13-23%) in affected eyes than in unaffected fellow eyes (p = 0.042, 0.046, 0.024, 0.013, 0.018, and 0.027, respectively). The mean difference value between choroidal thickness measurements in both eyes was significantly larger in the TON group than in the control group at the horizontal, vertical and average subfoveal, inner temporal, inner nasal, inner superior, inner inferior, and outer superior locations (p = 0.001, 0.011,  0.05). Eyes affected by TON showed a regionally thicker choroid than unaffected fellow eye. This thick choroid might be due to impaired blood circulation and vascular remodeling of the optic nerve head and choroid. These results help to better understand the pathophysiology of TON.

Long-term disease-free survival in advanced melanomas treated with nitrosoureas: mechanisms and new perspectives.

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Durando, Xavier; Thivat, Emilie; D'Incan, Michel; Sinsard, Anne; Madelmont, Jean-Claude; Chollet, Philippe

2005-11-15

Median survival of metastatic malignant melanoma is 6.0 to 7.5 months, with a 5-year survival of approximately 6.0%. Although long-term complete remissions are rare, few reports describe cases after chemotherapy. Fifty-three patients with metastatic melanoma were treated with Cystemustine, a chloroethyl nitrosourea (CENU) (60 or 90 mg/m2). We describe 5 cases, presenting with complete response with long-term disease-free survival of long-term remission of 14, 12, 9, 7 and 6 years after Cystemustine therapy alone. Long-term survival has already been described in literature, but in all cases they have been obtained after chemotherapy associated with or followed by surgery. But despite these noteworthy and encouraging but also rare results, it appears essential to increase Cystemustine efficiency.

Quantitative analysis of genes regulating sensitivity to heavy ion irradiation in cultured cell lines of malignant choroid melanoma

International Nuclear Information System (INIS)

Kumagai, Ken; Adachi, Nanao; Nimura, Yoshinori

2004-01-01

As a treatment strategy for malignant melanoma, heavy ion irradiation has been planned in National Institute of Radiological Sciences (NIRS). However, the molecular biology of the malignant melanoma cell after irradiation of heavy ion is still unknown. In this study, we used resistant and sensitive cell lines of malignant melanoma to study the effects of heavy ion irradiation. Furthermore, gene expression profiling of early response genes for heavy ion irradiation was carried out on these cell lines using microarray technology. (author)

Quantitative analysis of genes regulating sensitivity to heavy ion irradiation in cultured cell lines of malignant choroid melanoma

International Nuclear Information System (INIS)

Kumagai, Ken; Nimura, Yoshinori; Kato, Masaki; Seki, Naohiko; Miyahara, Nobuyuki; Aoki, Mizuho; Shino, Yayoi; Furusawa, Yoshiya; Mizota, Atsushi

2005-01-01

As a treatment strategy for malignant melanoma, heavy ion irradiation has been planned in National Institute of Radiological Sciences (NIRS). However, the molecular biology of the malignant melanoma cell after irradiation of heavy ion is still unknown. In this study, we used resistant and sensitive cell lines of malignant melanoma to study the effects of heavy ion irradiation. Furthermore, gene expression profiling of early response genes for heavy ion irradiation was carried out on these cell lines using microarray technology. (author)

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

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Guillaume Sarrabayrouse

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

Gold nanoparticle-based brachytherapy enhancement in choroidal melanoma using a full Monte Carlo model of the human eye.

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Asadi, Somayeh; Vaez-zadeh, Mehdi; Masoudi, S Farhad; Rahmani, Faezeh; Knaup, Courtney; Meigooni, Ali S

2015-09-08

The effects of gold nanoparticles (GNPs) in 125I brachytherapy dose enhancement on choroidal melanoma are examined using the Monte Carlo simulation technique. Usually, Monte Carlo ophthalmic brachytherapy dosimetry is performed in a water phantom. However, here, the compositions of human eye have been considered instead of water. Both human eye and water phantoms have been simulated with MCNP5 code. These simulations were performed for a fully loaded 16 mm COMS eye plaque containing 13 125I seeds. The dose delivered to the tumor and normal tissues have been calculated in both phantoms with and without GNPs. Normally, the radiation therapy of cancer patients is designed to deliver a required dose to the tumor while sparing the surrounding normal tissues. However, as the normal and cancerous cells absorbed dose in an almost identical fashion, the normal tissue absorbed radiation dose during the treatment time. The use of GNPs in combination with radiotherapy in the treatment of tumor decreases the absorbed dose by normal tissues. The results indicate that the dose to the tumor in an eyeball implanted with COMS plaque increases with increasing GNPs concentration inside the target. Therefore, the required irradiation time for the tumors in the eye is decreased by adding the GNPs prior to treatment. As a result, the dose to normal tissues decreases when the irradiation time is reduced. Furthermore, a comparison between the simulated data in an eye phantom made of water and eye phantom made of human eye composition, in the presence of GNPs, shows the significance of utilizing the composition of eye in ophthalmic brachytherapy dosimetry Also, defining the eye composition instead of water leads to more accurate calculations of GNPs radiation effects in ophthalmic brachytherapy dosimetry.

Gene expression of panaxydol-treated human melanoma cells using radioactive cDNA microarrays

International Nuclear Information System (INIS)

Cho, Joong Youn; Yu, Su Jin; Soh, Jeong Won; Kim, Meyoung Kon

2001-01-01

Polyacetylenic alcohols derived from Panax ginseng have been studied to be an anticancer reagent previously. One of the Panax ginseng polyacetylenic alcohols, i.e., panaxydol, has been studied to possess an antiproliferative effect on human melanoma cell line (SK-MEL-1). In ths study, radioactive cDNA microarrays enabled an efficient approach to analyze the pattern of gene expression (3.194 genes in a total) simultaneously. The bioinformatics selection of human cDNAs, which is specifically designed for immunology, apoptosis and signal transduction, were arrayed on nylon membranes. Using with 33 P labeled probes, this method provided highly sensitive gene expression profiles of our interest including apoptosis, cell proliferation, cell cycle, and signal transduction. Gene expression profiles were also classified into several categories in accordance with the duration of panaxydol treatment. Consequently, the gene profiles of our interest were significantly up (199 genes, > 2.0 of Z-ratio) or down-(196 genes, < 2.0 of Z-ratio) regulated in panaxydol-treated human melanoma cells

Gene expression of panaxydol-treated human melanoma cells using radioactive cDNA microarrays

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Cho, Joong Youn; Yu, Su Jin; Soh, Jeong Won; Kim, Meyoung Kon [College of Medicine, Korea Univ., Seoul (Korea, Republic of)

2001-07-01

Polyacetylenic alcohols derived from Panax ginseng have been studied to be an anticancer reagent previously. One of the Panax ginseng polyacetylenic alcohols, i.e., panaxydol, has been studied to possess an antiproliferative effect on human melanoma cell line (SK-MEL-1). In ths study, radioactive cDNA microarrays enabled an efficient approach to analyze the pattern of gene expression (3.194 genes in a total) simultaneously. The bioinformatics selection of human cDNAs, which is specifically designed for immunology, apoptosis and signal transduction, were arrayed on nylon membranes. Using with {sup 33}P labeled probes, this method provided highly sensitive gene expression profiles of our interest including apoptosis, cell proliferation, cell cycle, and signal transduction. Gene expression profiles were also classified into several categories in accordance with the duration of panaxydol treatment. Consequently, the gene profiles of our interest were significantly up (199 genes, > 2.0 of Z-ratio) or down-(196 genes, < 2.0 of Z-ratio) regulated in panaxydol-treated human melanoma cells.

Corpus vitreum, retina og chorioidea biopsi

DEFF Research Database (Denmark)

Scherfig, Erik Christian Høegh

2002-01-01

oftalmology, biopsy, choroid, corpus vitreum, retina, malignant melanoma, biopsy technic, retinoblastoma......oftalmology, biopsy, choroid, corpus vitreum, retina, malignant melanoma, biopsy technic, retinoblastoma...

Knockdown of the Placental Growth Factor Gene Inhibits Laser Induced Choroidal Neovascularization in a Murine Model

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Ramin Nourinia

2013-01-01

Full Text Available Purpose: To evaluate the effect of placental growth factor (PlGF gene knockdown in a murine model of laser-induced choroidal neovascularization. Methods: Choroidal neovascularization was induced in the left eyes of 11 mice by infrared laser. Small interfering RNA (siRNA, 20 picomoles/10 μl corresponding to PlGF mRNA was administered intravitreally by Hamilton syringe in all subjects. One month later, fluorescein angiography and histolologic examination were performed. Results: No leakage was apparent in the 11 eyes treated with siRNA cognate to PlGF. The results of histological evaluation were consistent with angiographic findings showing absence of choroidal neovascularization. Conclusion: Knockdown of the PlGF gene can inhibit the growth of laser-induced choroidal neovascularization in mice.

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

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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.

Long-term disease-free survival in advanced melanomas treated with nitrosoureas: mechanisms and new perspectives

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Sinsard Anne

2005-11-01

Full Text Available Abstract Background Median survival of metastatic malignant melanoma is 6.0 to 7.5 months, with a 5-year survival of ~6.0%. Although long-term complete remissions are rare, few reports describe cases after chemotherapy. Fifty-three patients with metastatic melanoma were treated with Cystemustine, a chloroethyl nitrosourea (CENU (60 or 90 mg/m2. Case presentation We describe 5 cases, presenting with complete response with long-term disease-free survival of long-term remission of 14, 12, 9, 7 and 6 years after Cystemustine therapy alone. Conclusion Long-term survival has already been described in literature, but in all cases they have been obtained after chemotherapy associated with or followed by surgery. But despite these noteworthy and encouraging but also rare results, it appears essential to increase cystemustine efficiency.

Clinical applications of choroidal imaging technologies

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Jay Chhablani

2015-01-01

Full Text Available Choroid supplies the major blood supply to the eye, especially the outer retinal structures. Its understanding has significantly improved with the advent of advanced imaging modalities such as enhanced depth imaging technique and the newer swept source optical coherence tomography. Recent literature reports the findings of choroidal changes, quantitative as well as qualitative, in various chorioretinal disorders. This review article describes applications of choroidal imaging in the management of common diseases such as age-related macular degeneration, high myopia, central serous chorioretinopathy, chorioretinal inflammatory diseases, and tumors. This article briefly discusses future directions in choroidal imaging including angiography.

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.

Diffuse choroidal haemangioma in Sturge-Weber syndrome treated with photodynamic therapy under general anaesthesia

NARCIS (Netherlands)

Huiskamp, EA; Muskens, RPHM; Ballast, A; Hooymans, JMM

Purpose: To report the treatment outcome of photodynamic therapy with verteporfin (PDT) for exudative retinal detachment associated with diffuse choroidal haemangioma in Sturge-Weber syndrome. Methods: An interventional case report of a 12-year-old girl with Sturge-Weber syndrome who developed an

Transport across the choroid plexus epithelium

DEFF Research Database (Denmark)

Praetorius, Jeppe; Damkier, Helle Hasager

2017-01-01

The choroid plexus epithelium is a secretory epithelium par excellence. However, this is perhaps not the most prominent reason for the massive interest in this modest-sized tissue residing inside the brain ventricles. Most likely, the dominant reason for extensive studies of the choroid plexus...... is the identification of this epithelium as the source of the majority of intraventricular cerebrospinal fluid. This finding has direct relevance for studies of diseases and conditions with deranged central fluid volume or ionic balance. While the concept is supported by the vast majority of the literature......, the implication of the choroid plexus in secretion of the cerebrospinal fluid was recently challenged once again. Three newer and promising areas of current choroid plexus-related investigations are as follows: 1) the choroid plexus epithelium as the source of mediators necessary for central nervous system...

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

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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

Poster - 30: Use of a Hazard-Risk Analysis for development of a new eye immobilization tool for treatment of choroidal melanoma

International Nuclear Information System (INIS)

Prooijen, Monique van; Breen, Stephen

2016-01-01

Purpose: Our treatment for choroidal melanoma utilizes the GTC frame. The patient looks at a small LED to stabilize target position. The LED is attached to a metal arm attached to the GTC frame. A camera on the arm allows therapists to monitor patient compliance. To move to mask-based immobilization we need a new LED/camera attachment mechanism. We used a Hazard-Risk Analysis (HRA) to guide the design of the new tool. Method: A pre-clinical model was built with input from therapy and machine shop personnel. It consisted of an aluminum frame placed in aluminum guide posts attached to the couch top. Further development was guided by the Department of Defense Standard Practice - System Safety hazard risk analysis technique. Results: An Orfit mask was selected because it allowed access to indexes on the couch top which assist with setup reproducibility. The first HRA table was created considering mechanical failure modes of the device. Discussions with operators and manufacturers identified other failure modes and solutions. HRA directed the design towards a safe clinical device. Conclusion: A new immobilization tool has been designed using hazard-risk analysis which resulted in an easier-to-use and safer tool compared to the initial design. The remaining risks are all low probability events and not dissimilar from those currently faced with the GTC setup. Given the gains in ease of use for therapists and patients as well as the lower costs for the hospital, we will implement this new tool.

Poster - 30: Use of a Hazard-Risk Analysis for development of a new eye immobilization tool for treatment of choroidal melanoma

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Prooijen, Monique van; Breen, Stephen [Princess Margaret Cancer Centre, Princess Margaret Hospital-UHN (Canada)

2016-08-15

Purpose: Our treatment for choroidal melanoma utilizes the GTC frame. The patient looks at a small LED to stabilize target position. The LED is attached to a metal arm attached to the GTC frame. A camera on the arm allows therapists to monitor patient compliance. To move to mask-based immobilization we need a new LED/camera attachment mechanism. We used a Hazard-Risk Analysis (HRA) to guide the design of the new tool. Method: A pre-clinical model was built with input from therapy and machine shop personnel. It consisted of an aluminum frame placed in aluminum guide posts attached to the couch top. Further development was guided by the Department of Defense Standard Practice - System Safety hazard risk analysis technique. Results: An Orfit mask was selected because it allowed access to indexes on the couch top which assist with setup reproducibility. The first HRA table was created considering mechanical failure modes of the device. Discussions with operators and manufacturers identified other failure modes and solutions. HRA directed the design towards a safe clinical device. Conclusion: A new immobilization tool has been designed using hazard-risk analysis which resulted in an easier-to-use and safer tool compared to the initial design. The remaining risks are all low probability events and not dissimilar from those currently faced with the GTC setup. Given the gains in ease of use for therapists and patients as well as the lower costs for the hospital, we will implement this new tool.

Peripapillary retinal nerve fiber layer and choroidal thickness in cirrhosis patients

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M.Orcun Akdemir

2015-12-01

Full Text Available ABSTRACT Purpose: To evaluate the effect of cirrhosis on peripapillary retinal nerve fiber layer and choroidal thickness with enhanced depth imaging optical coherence tomography. Methods: This cross sectional, single center study was undertaken at Bulent Ecevit University Ophthalmology department with the participation of internal medicine, Gastroenterology department. Patients who were treated with the diagnosis of cirrhosis (n=75 were examined in the ophthalmology clinic. Age and sex matched patients (n=50 who were healthy and met the inclusion, exclusion criteria were included in the study. Complete ophthalmological examination included visual acuity with Snellen chart, intraocular pressure measurement with applanation tonometry, biomicroscopy of anterior and posterior segments, gonioscopy, axial length measurement, visual field examination, peripapillary retinal nerve fiber layer, central macular and subfoveal choroidal thickness measurements. Results: The difference between intraocular pressure values was not statistically significant between cirrhosis and control group (p=0.843. However, mean peripapillary retinal nerve fiber layer thickness was significantly thinner in cirrhosis group in all regions (p<0.001 and subfoveal choroidal thickness was significantly thinner in cirrhosis group also (p<0.001. Moreover, central macular thickness of cirrhosis group was significantly thicker than the control group (p=0.001. Conclusion: Peripapillary retinal nerve fiber layer and subfoveal choroidal thickness was significantly thinner in cirrhosis patients.

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.

The Choroidal Eye Oximeter - An instrument for measuring oxygen saturation of choroidal blood in vivo

Science.gov (United States)

Laing, R. A.; Danisch, L. A.; Young, L. R.

1975-01-01

The Choroidal Eye Oximeter is an electro-optical instrument that noninvasively measures the oxygen saturation of choroidal blood in the back of the human eye by a spectrophotometric method. Since choroidal blood is characteristic of blood which is supplied to the brain, the Choroidal Eye Oximeter can be used to monitor the amount of oxygen which is supplied to the brain under varying external conditions. The instrument consists of two basic systems: the optical system and the electronic system. The optical system produces a suitable bi-chromatic beam of light, reflects this beam from the fundus of the subject's eye, and onto a low-noise photodetector. The electronic system amplifies the weak composite signal from the photodetector, computes the average oxygen saturation from the area of the fundus that was sampled, and displays the value of the computed oxygen saturation on a panel meter.

Peptides in melanoma therapy.

Science.gov (United States)

Mocellin, Simone

2012-01-01

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

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

Presumed choroidal metastasis of Merkel cell carcinoma

International Nuclear Information System (INIS)

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

1990-01-01

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

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

Pachychoroid neovasculopathy in extramacular choroidal neovascularization

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Gupta MP

2016-07-01

Full Text Available Mrinali Patel Gupta, Irene Rusu, Carly Seidman, Anton Orlin, Donald J D’Amico, Szilard Kiss Department of Ophthalmology, Weill Cornell Medicine, New York-Presbyterian Hospital, New York, NY, USA Purpose: To review a series of extramacular choroidal neovascular membranes (CNVMs in the context of their choroidal features, as determined by optical coherence tomography (OCT.Methods: Patients with extramacular CNVMs were identified from a tertiary care center through a review of records. The charts and cases were reviewed using multimodal imaging including fundus photography, OCT, fluorescein angiography (FA, and indocyanine angio­graphy (ICG.Results: Of six patients with extramacular CNVMs evaluated in this series, four patients (66.7% exhibited pachychoroidopathy on OCT imaging under or adjacent to the extramacular CNVM. All four of these patients also exhibited pachychoroidopathy in the macular OCT distant from the CNVM.Conclusion: Pachychoroidopathy is implicated in some cases of extramacular CNVMs. This represents the first report, to our knowledge, of pachychoroidopathy in extramacular CNVM. Keywords: choroidal neovascularization, pachychoroidopathy, pachychoroid neovasculopathy, peripheral disciform lesions, extramacular choroidal neovascularization, polypoidal choroidal vasculopathy

Transconjunctival drainage of serous and hemorrhagic choroidal detachment.

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Rezende, Flávio A; Kickinger, Mônica C; Li, Gisèle; Prado, Renata F; Regis, Luiz Gustavo T

2012-02-01

To describe a novel surgical technique for drainage of bullous serous and hemorrhagic choroidal detachments. A prospective, consecutive case series of 6 eyes with serous and/or hemorrhagic choroidal detachments secondary to intraocular surgery was documented to evaluate the feasibility of using the 25-gauge and 20-gauge transconjunctival trocar/cannula systems to drain choroidal detachments. Two eyes had expulsive hemorrhagic choroidal detachments and 4 eyes had serous choroidal detachments after glaucoma surgeries. A 25-gauge infusion line was placed in the anterior chamber. A 20-gauge (in eyes with hemorrhagic choroidal detachments) or a 25-gauge (in eyes with serous detachments) trocar/cannula system was inserted into the suprachoroidal space 7.0 mm from limbus. After drainage, the cannulas were removed and no sutures were placed. Pars plana vitrectomy was performed only in eyes with concomitant pathology that demanded the additional procedure. The primary outcome measure was presence of choroidal detachment at 1 week, 2 weeks, and 1 month postoperatively. Secondary outcome measures were visual acuity at 6 months and intraocular pressure at 1 week and 1, 3, and 6 months postoperatively. Drainage of hemorrhagic choroidal detachments resulted in resolution of the detachments by 1 month postoperatively. In eyes with serous detachments, resolution was achieved by 1 week postdrainage. In both groups, intraocular pressure increased to at least 10 mmHg by postoperative Week 1. The visual acuity improved in all eyes. No complications related to the transconjunctival technique were noted. Transconjunctival drainage of serous and hemorrhagic choroidal detachments seems to be a feasible and simple surgical option with minimal scleral and conjunctival damage. Pars plana vitrectomy may not be necessary when draining choroidal detachments in this manner.

Functional and Genetic Analysis of Choroid Plexus Development in Zebrafish

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Hannah Elizabeth Henson

2014-11-01

Full Text Available The choroid plexus, an epithelial-based structure localized in the brain ventricle, is the major component of the blood-cerebrospinal fluid barrier. The choroid plexus produces the cerebrospinal fluid and regulates the components of the cerebrospinal fluid. Abnormal choroid plexus function is associated with neurodegenerative diseases, tumor formation in the choroid plexus epithelium, and hydrocephaly. In this study, we used zebrafish (Danio rerio as a model system to understand the genetic components of choroid plexus development. We generated an enhancer trap line, Et(cp:EGFPsj2, that expresses enhanced green fluorescent protein (EGFP in the choroid plexus epithelium. Using immunohistochemistry and fluorescent tracers, we demonstrated that the zebrafish choroid plexus possesses brain barrier properties such as tight junctions and transporter activity. Thus, we have established zebrafish as a functionally relevant model to study choroid plexus development. Using an unbiased approach, we performed a forward genetic dissection of the choroid plexus to identify genes essential for its formation and function. Using Et(cp:EGFPsj2, we isolated 10 recessive mutant lines with choroid plexus abnormalities, which were grouped into five classes based on GFP intensity, epithelial localization, and overall choroid plexus morphology. We also mapped the mutation for two mutant lines to chromosomes 4 and 21, respectively. The mutants generated in this study can be used to elucidate specific genes and signaling pathways essential for choroid plexus development, function, and/or maintenance and will provide important insights into how these genetic mutations contribute to disease.

Linac-based radiosurgery of cerebral melanoma metastases. Analysis of 122 metastases treated in 64 patients

International Nuclear Information System (INIS)

Herfarth, K.K.; Pirzkall, A.; Izwekowa, O.; Wannenmacher, M.; Thilmann, C.; Debus, J.; Delorme, S.; Hofmann, U.; Schadendorf, D.; Zierhut, D.

2003-01-01

Purpose: Stereotactic radiosurgery is an alternative option to neurosurgical excision in the management of patients with brain metastases. We retrospectively analyzed patients with brain metastases of malignant melanoma who were treated at our institution for outcome and prognostic factors. Patients and Methods: 64 patients with 122 cerebral metastases were treated with stereotactic radiosurgery between 1986 and 2000. Twelve patients (19%) showed neurologic symptoms at the time of treatment, and 46 patients (72%) had extracerebral tumor manifestation at that time. The median dose to the 80% isodose line, prescribed to encompass the tumor margin, was 20 Gy (range, 15-22 Gy). Results: Neurologic symptoms improved in five of twelve symptomatic patients. 41 patients remained asymptomatic or unchanged in their neurologic symptoms. Only five patients (8%) temporarily worsened neurologically after therapy despite no signs of tumor progression. With a mean follow-up time of 9.4 months, actuarial local control was 81% after 1 year. There was a statistically significant dose and size dependency of local tumor control. Median actuarial survival after treatment was 10.6 months. Patients without extracerebral tumor manifestation showed a superior survival (p = 0.04). Conclusions: Despite high local tumor control rates, the prognosis of patients with cerebral metastases of malignant melanoma remains poor. Stereotactic radiosurgery has the potential of stabilizing or improving neurologic symptoms in these patients in a palliative setting. (orig.)

Why choroid vessels appear dark in clinical OCT images

Science.gov (United States)

Kirby, Mitchell A.; Li, Chenxi; Choi, Woo June; Gregori, Giovanni; Rosenfeld, Philip; Wang, Ruikang

2018-02-01

With the onset of clinically available spectral domain (SD-OCT) and swept source (SS-OCT) systems, clinicians are now easily able to recognize sub retinal microstructure and vascularization in the choroidal and scleral regions. As the bloodrich choroid supplies nutrients to the upper retinal layers, the ability to monitor choroid function accurately is of vital importance for clinical assessment of retinal health. However, the physical appearance of the choroid blood vessels (darker under a healthy Retinal Pigmented Epithelium (RPE) compared to regions displaying an RPE atrophic lesion) has led to confusion within the OCT ophthalmic community. The differences in appearance between each region in the OCT image may be interpreted as different vascular patterns when the vascular networks are in fact very similar. To explain this circumstance, we simulate light scattering phenomena in the RPE and Choroid complexes using the finite difference time domain (FDTD) method. The simulation results are then used to describe and validate imaging features in a controlled multi-layered tissue phantom designed to replicate human RPE, choroid, and whole blood microstructure. Essentially, the results indicate that the strength of the OCT signal from choroidal vasculature is dependent on the health and function of the RPE, and may not necessarily directly reflect the health and function of the choroidal vasculature.

Autofluorescence of choroidal nevus in 64 cases.

Science.gov (United States)

Shields, Carol L; Pirondini, Cesare; Bianciotto, Carlos; Materin, Miguel A; Harmon, Sarah A; Shields, Jerry A

2008-10-01

To describe the autofluorescence features of choroidal nevi. Noncomparative case series. Sixty-four consecutive patients. Correlation of fundus photography with autofluorescence photography. Autofluorescence features of choroidal nevus and overlying retinal pigment epithelium (RPE). The mean patient age was 62 years. The choroidal nevus was a mean of 5 mm from the optic disk and foveola. The mean tumor basal dimension was 5.0 mm and mean tumor thickness was 1.0 mm. The choroidal nevus showed hypoautofluorescence in 56%, isoautofluorescence in 19%, and hyperautofluorescence in 25%. The autofluorescence features appeared unaffected by tumor thickness, but increasing tumor base and disrupted overlying RPE appeared to produce slightly brighter autofluorescence. Nevi located in the macular region showed darker hypoautofluorescence than those outside the macular region. Overlying RPE hyperplasia, atrophy, and fibrous metaplasia were generally hypoautofluorescent. Drusen, subretinal fluid, and orange pigment were generally hyperautofluorescent. The brightest hyperautofluorescence was found with orange pigment. Choroidal nevus shows little intrinsic autofluorescence. Overlying RPE alterations show dramatic autofluorescence ranging from dark hypoautofluorescence of RPE atrophy to bright hyperautofluorescence of orange pigment.

Metastatic melanoma patients treated with dendritic cell vaccination, Interleukin-2 and metronomic cyclophosphamide

DEFF Research Database (Denmark)

Ellebaek, Eva; Engell-Noerregaard, Lotte; Iversen, Trine Zeeberg

2012-01-01

Dendritic cells (DC) are the most potent antigen presenting cells and have proven effective in stimulation of specific immune responses in vivo. Competing immune inhibition could limit the clinical efficacy of DC vaccination. In this phase II trial, metronomic Cyclophosphamide and a Cox-2 inhibitor...... have been added to a DC vaccine with the intend to dampen immunosuppressive mechanisms. Twenty-eight patients with progressive metastatic melanoma were treated with autologous DCs pulsed with survivin, hTERT, and p53-derived peptides (HLA-A2(+)) or tumor lysate (HLA-A2(-)). Concomitantly the patients...... were treated with IL-2, Cyclophosphamide, and Celecoxib. The treatment was safe and tolerable. Sixteen patients (57 %) achieved stable disease (SD) at 1st evaluation and 8 patients had prolonged SD (7-13.7 months). The median OS was 9.4 months. Patients with SD had an OS of 10.5 months while patients...

Changes in visual acuity in patients with malignant melanoma of the uvea treated with stereotactic radiosurgery (presentation)

International Nuclear Information System (INIS)

Mackova, K.; Waczultkova, I.; Furdova, Ad.; Furdova, Al.

2013-01-01

The goal was to assess the changes in visual acuity before and after 6 months of treatment, depending on the dose in risk structures (lens, optic nerve). This is a retrospective study of 19 patients group treated in 2011. The average age of the group was (57.3 ± 12.4) years (31-73 years). The analysis of the studied group did not demonstrate dependence of the tumour presence on gender. Higher prevalence of tumours was observed in the elderly population. Considered relationship of worse diagnosis with higher age (r = 0.39; p = 0.13) we could not prove to be significant due to the small group of patients. The median of melanoma volume was 0.77 cm 3 (0.11 to 1.76 cubic centimetres). The mean dose applied to melanoma was 37.34 Gy (Gy 36.74 to 44.65).

Histopathological study of malignant melanoma in highlanders ...

African Journals Online (AJOL)

Histopathological study of malignant melanoma in highlanders. AZ Mohammed, AN Manasseh, BM Mandong, ST Edino. Abstract. Background:Malignant melanoma is a fatal skin cancer that is curable when detected and treated early. Recent reports indicate a rising incidence globally. This study aims at identifying the ...

Choroidal Round Hyporeflectivities in Geographic Atrophy.

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Eleonora Corbelli

Full Text Available In geographic atrophy (GA, choroidal vessels typically appear on structural optical coherence tomography (OCT as hyperreflective round areas with highly reflective borders. We observed that some GA eyes show choroidal round hyporeflectivities with highly reflective borders beneath the atrophy, and futher investigated the charcteristcs by comparing structural OCT, indocyanine green angiography (ICGA and OCT angiography (OCT-A.Round hyporeflectivities were individuated from a pool of patients with GA secondary to non-neovascular age-related macular degeneration consecutively presenting between October 2015 and March 2016 at the Medical Retina & Imaging Unit of the University Vita-Salute San Raffaele. Patients underwent a complete ophthalmologic examination including ICGA, structural OCT and OCT-A. The correspondence between choroidal round hyporeflectivities beneath GA on structural OCT and ICGA and OCT-A imaging were analyzed.Fifty eyes of 26 consecutive patients (17 females and 9 males; mean age 76.8±6.2 years with GA were included. Twenty-nine round hyporeflectivities have been found by OCT in choroidal layers in 21 eyes of 21 patients (42.0%; estimated prevalence of 57.7%. All 29 round hyporeflectivities showed constantly a hyperreflective border and a backscattering on structural OCT, and appeared as hypofluorescent in late phase ICGA and as dark foci with non detectable flow in the choroidal segmentation of OCT-A. Interestingly, the GA area was greater in eyes with compared to eyes without round hyporeflectivities (9.30±5.74 and 5.57±4.48mm2, respectively; p = 0.01.Our results suggest that most round hyporeflectivities beneath GA may represent non-perfused or hypo-perfused choroidal vessels with non-detectable flow.

Choroidal Round Hyporeflectivities in Geographic Atrophy.

Science.gov (United States)

Corbelli, Eleonora; Sacconi, Riccardo; De Vitis, Luigi Antonio; Carnevali, Adriano; Rabiolo, Alessandro; Querques, Lea; Bandello, Francesco; Querques, Giuseppe

2016-01-01

In geographic atrophy (GA), choroidal vessels typically appear on structural optical coherence tomography (OCT) as hyperreflective round areas with highly reflective borders. We observed that some GA eyes show choroidal round hyporeflectivities with highly reflective borders beneath the atrophy, and futher investigated the charcteristcs by comparing structural OCT, indocyanine green angiography (ICGA) and OCT angiography (OCT-A). Round hyporeflectivities were individuated from a pool of patients with GA secondary to non-neovascular age-related macular degeneration consecutively presenting between October 2015 and March 2016 at the Medical Retina & Imaging Unit of the University Vita-Salute San Raffaele. Patients underwent a complete ophthalmologic examination including ICGA, structural OCT and OCT-A. The correspondence between choroidal round hyporeflectivities beneath GA on structural OCT and ICGA and OCT-A imaging were analyzed. Fifty eyes of 26 consecutive patients (17 females and 9 males; mean age 76.8±6.2 years) with GA were included. Twenty-nine round hyporeflectivities have been found by OCT in choroidal layers in 21 eyes of 21 patients (42.0%; estimated prevalence of 57.7%). All 29 round hyporeflectivities showed constantly a hyperreflective border and a backscattering on structural OCT, and appeared as hypofluorescent in late phase ICGA and as dark foci with non detectable flow in the choroidal segmentation of OCT-A. Interestingly, the GA area was greater in eyes with compared to eyes without round hyporeflectivities (9.30±5.74 and 5.57±4.48mm2, respectively; p = 0.01). Our results suggest that most round hyporeflectivities beneath GA may represent non-perfused or hypo-perfused choroidal vessels with non-detectable flow.

[Krypton laser photocoagulation at low power setting for age-related macular degeneration complicated with subfoveal choroidal neovascularization].

Science.gov (United States)

Zhang, Cheng-fen; Jia, Yan; Li, Zhi-qing; Du, Hong; Han, Bao-ling

2004-12-01

To evaluate the efficacy of krypton laser photocoagulation for treatment of age-related macular degeneration (AMD) complicated with mainly subfoveal classic choroidal neovascularization (CNV). Seventeen eyes of 17 cases, aged 50 - 74 years (averaged 60.8 years) with mainly subfoveal classic choroidal neovascularization were treated with krypton laser at lower power setting. The treatment was completed in one session. Another course of treatment was given 4 weeks later if there was active leakage demonstrated at the CNV area. Visual acuity, anterior segment and fundus examination, perimetry test, fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA) were performed before and after treatment. The follow-up period was 3.5 years on average (1 - 8 years). There was no immediately decrease of visual acuity after treatment. All treated eyes showed absorption of hemorrhages and/or exudates and diminished leakages. Visual acuity was stable in 8 eyes; improved in 6 eyes (>/= 2 lines), and decreased in 3 eyes (Krypton laser photocoagulation at low power setting is an effective treatment for AMD with mainly classic subfoveal choroidal neovascularization.

BILATERAL CHOROIDAL EXCAVATION IN JUVENILE LOCALIZED SCLERODERMA.

Science.gov (United States)

Franklin, Mackenzie L; Day, Shelley

2018-01-01

To describe a case of bilateral choroidal excavation in a patient with juvenile localized scleroderma. Case report. An asymptomatic 12-year-old boy with localized scleroderma presented for examination and was found to have bilateral areas of choroidal excavation temporal to the fovea. Previous reports of ocular complications of localized scleroderma have primarily described adnexal and anterior segment changes. This is the second report of choroidal changes in a patient with localized scleroderma, and the first in a pediatric patient.

Psammoma bodies - friends or foes of the aging choroid plexus.

Science.gov (United States)

Jovanović, Ivan; Ugrenović, Sladjana; Vasović, Ljiljana; Petrović, Dragan; Cekić, Sonja

2010-06-01

Psammoma bodies are structures classified in the group of dystrophic calcifications, which occur in some kind of tumors and in choroid plexus during the aging process. Despite early discovery of their presence in choroid plexus stroma, mechanisms responsible for their formation remained unclear. Their presence in some kind of tumors was even more extensively studied, but significant breakthrough in the field of their etiology was not attained, too. However, till today correlation between their presence in tumors and aging is not established. Also, there are not any data about structural differences between ones found in tumors and ones found in choroid plexus. This might points to the assumption that besides the aging, some other causes might be involved in their formation in choroid plexus. Furthermore, it is contradictory that forms, like psammoma bodies, present in such malignant formations as tumors, represent quite benign phenomenon in choroid plexus. Literature data and the results of our previous researches revealed that there might be connections between, these, on the first sight quite different processes. Firstly, psammoma bodies are present in stroma of tumors with predominantly papillomatous morphology, which is present in choroid plexus, too. Initial forms of psammoma bodies might be formed in fibrovascular core of choroid plexus villi, similarly like in tumors papillae of papillary thyroid cancer. Their further growth leads to the progressive destruction of both tumors papillae and choroidal villi. Choroid plexus stroma is characterized by the fenestrated blood vessels presence, which are similar to newly formed vessels in tumors. This makes it vulnerable to the noxious agents from circulation. It can contain lymphocytes, macrophages, dendritic cells and myofibroblasts in cases with psammoma bodies, similarly to tumors stroma which is in activated, proinflammatory state. So, all these facts can suggest that similar processes can lead to psammoma

Nivolumab in the treatment of malignant melanoma: review of the literature

Directory of Open Access Journals (Sweden)

Mashima E

2015-08-01

Full Text Available Emi Mashima, Akiha Inoue, Yumiko Sakuragi, Takashi Yamaguchi, Natsuko Sasaki, Yoko Hara, Daisuke Omoto, Shun Ohmori, Sanehito Haruyama, Yu Sawada, Manabu Yoshioka, Daisuke Nishio, Motonobu Nakamura Department of Dermatology, University of Occupational and Environmental Health, Kitakyushu, Japan Abstract: Nivolumab was developed as a monoclonal antibody against programmed death receptor-1, an immune checkpoint inhibitor which negatively regulates T-cell proliferation and activation. Intravenous administration of nivolumab was approved for the treatment of unresectable malignant melanoma in 2014 in Japan. When advanced melanoma patients were treated with nivolumab, median overall survival became longer. Overall survival rate was significantly better in nivolumab-treated melanoma patients than dacarbazine-treated melanoma patients. Nivolumab had an acceptable long-term tolerability profile, with 22% of patients experiencing grade 3 or 4 adverse events related to the drug. Therefore, nivolumab can become an alternative therapy for advanced malignant melanoma. Keywords: monoclonal antibody, PD-1, PD-L1

[Combined use of irradiation and DNA tumor vaccine to treat canine oral malignant melanoma: a pilot study].

Science.gov (United States)

Herzog, A; Buchholz, J; Ruess-Melzer, K; Lang, J; Kaser-Hotz, B

2013-02-01

Melanoma is the most common oral tumor in dogs, characterized by rapid growth, local invasion, and high metastatic rate. The goal of this study was to evaluate the combination of radiation therapy and DNA tumor vaccine. We hypothesized, that the concurrent use would not increase toxicity. Nine dogs with oral melanoma were treated with 4 fractions of 8 Gray at 7-day intervals. The vaccine was given 4 times every 14 days, beginning at the first radiation fraction. Local acute radiation toxicities were assessed according to the VRTOG toxicity scoring scheme over a time period of 7 weeks. In none of the evaluated dogs, mucositis, dermatitis and conjunctivitis exceeded grade 2. In 3 dogs mild fever, lethargy, and local swelling at the injection site were seen after vaccine application. In conclusion, the concurrent administration of radiation therapy and vaccine was well tolerated in all dogs.

Radiation biology of malignant melanoma

International Nuclear Information System (INIS)

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

1986-01-01

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

Alpha particles for treatment of disseminated melanoma

International Nuclear Information System (INIS)

Link, E.M.

2010-01-01

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

Monoclonal Antibody Therapy in Treating Patients With Ovarian Epithelial Cancer, Melanoma, Acute Myeloid Leukemia, Myelodysplastic Syndrome, or Non-Small Cell Lung Cancer

Science.gov (United States)

2013-01-09

Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Recurrent Melanoma; Recurrent Non-small Cell Lung Cancer; Recurrent Ovarian Epithelial Cancer; Stage IV Melanoma; Stage IV Non-small Cell Lung Cancer

A new animal model of choroidal neovascularization

DEFF Research Database (Denmark)

Kiilgaard, Jens Folke; Andersen, Mads Varis Nis; Wiencke, Anne

2005-01-01

The purpose of this study was to evaluate the ability of different methods to induce choroidal neovascularization (CNV) in the domestic pig.......The purpose of this study was to evaluate the ability of different methods to induce choroidal neovascularization (CNV) in the domestic pig....

Is a diagnostic CT of the brain indicated in patients with choroidal metastases before radiotherapy?

International Nuclear Information System (INIS)

Bottke, D.; Wiegel, T.; Hoecht, S.; Hinkelbein, W.; Kreusel, K.M.

2005-01-01

Background and purpose: there is no evidence in the literature about the incidence of synchronous brain metastases in patients with choroidal metastases. This is of major importance, because the radiation fields of choroidal metastases and, later on, brain metastases, if treated consecutively, are partly overlapping, thus potentially increasing the rate of late side effects such as brain necrosis. The goal of this study was to determine the frequency of synchronous brain metastases. Patients and methods: 50 patients with choroidal metastases were enrolled into a study of the ''Arbeitsgemeinschaft Radiologische Onkologie'' of the German Cancer Society (ARO 95-08) with standardized 40 Gy radiotherapy, 2 Gy single dose. All patients were staged before treatment with a computed tomography of the brain (CCT). No patient showed clinical signs of brain metastases. Results: 13 out of 50 patients (26%) had brain metastases in the CCT leading to radiotherapy of the brain and choroidal metastases in one volume. Conclusion: a CCT is indicated at the diagnosis of choroidal metastases for screening of synchronous brain metastases. The incidence is about 25%, and the diagnosis of brain metastases results in a different target volume: the whole brain including the posterior parts of the eyes compared to the posterior parts of the eyes alone. Therefore, the risk of late side effects could be reduced compared with an additional later radiotherapy of the whole brain with partly overlapping fields. (orig.)

IQGAP1 is an oncogenic target in canine melanoma.

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Becky H Lee

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

A case of malignant melanoma of the maxilla treated by adoptive immunotherapy after fast neutron therapy

International Nuclear Information System (INIS)

Morifuji, Masayo; Ohishi, Masamichi; Higuchi, Yoshinori; Ozeki, Satoru; Tashiro, Hideo

1992-01-01

A 77-year-old male patient with malignant melanoma was treated by fast neutron therapy and immunotherapy. Total dose of fast neutron applied to the primary lesion was 1905 cGy per 21 fractionation for 46 days. For adoptive immunotherapy, lymphocytes were collected from the peripheral blood drawn from the patient 2 days after the injection of cyclophosphamide. T cells were further purified by passing the lymphocytes through nylon wool. Cytotoxic T cells were induced by incubating the T cells mixed with allogeneic malignant melanoma cells and a small number of patient's adherent cells, and activated with recombinant interleukin-2 (γ IL-2). Our patient and the patient from whom stimulating melanoma cells were derived shared A locous 24 and B locous 51 of MHC class I antigens in common. Thus prepared cytotoxic T cells were inoculated to the patient via the maxillary artery, 3 to 4 times a week for one month. Total amount of cells transferred was 5.6 x 10 8 (97% lymphocytes). Primary lesion reduced markedly by the therapies. During adoptive immunotherapy, increase in natural killer cells and decrease in both suppressor/inducer T-cells and macrophages were observed. However, lung metastases appeared 3 months after adoptive immunotherapy. While the nonspecific immunotherapy (OK-432 injection) was being conducted thereafter, growth of the metastatic lesions of the lung was kept gentle but became obvious after the suspension of the treatment. (author)

Retinal sensitivity and choroidal thickness in high myopia.

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Zaben, Ahmad; Zapata, Miguel Á; Garcia-Arumi, Jose

2015-03-01

To estimate the association between choroidal thickness in the macular area and retinal sensitivity in eyes with high myopia. This investigation was a transversal study of patients with high myopia, all of whom had their retinal sensitivity measured with macular integrity assessment microperimetry. The choroidal thicknesses in the macular area were then measured by optical coherence tomography, and statistical correlations between their functionality and the anatomical structuralism, as assessed by both types of measurements, were analyzed. Ninety-six eyes from 77 patients with high myopia were studied. The patients had a mean age ± standard deviation of 38.9 ± 13.2 years, with spherical equivalent values ranging from -6.00 diopter to -20.00 diopter (8.74 ± 2.73 diopter). The mean central choroidal thickness was 159.00 ± 50.57. The mean choroidal thickness was directly correlated with sensitivity (r = 0.306; P = 0.004) and visual acuity but indirectly correlated with the spherical equivalent values and patient age. The mean sensitivity was not significantly correlated with the macular foveal thickness (r = -0.174; P = 0.101) or with the overall macular thickness (r = 0.103; P = 0.334); furthermore, the mean sensitivity was significantly correlated with visual acuity (r = 0.431; P < 0.001) and the spherical equivalent values (r = -0.306; P = 0.003). Retinal sensitivity in highly myopic eyes is directly correlated with choroidal thickness and does not seem to be associated with retinal thickness. Thus, in patients with high myopia, accurate measurements of choroidal thickness may provide more accurate information about this pathologic condition because choroidal thickness correlates to a greater degree with the functional parameters, patient age, and spherical equivalent values.

Clinical Profile and Outcome of Serpiginous Choroiditis in a Uveitis ...

African Journals Online (AJOL)

tulyasys

around the optic disc and then gradually spread in a serpentine manner toward the macula and peripheral fundus. It can be classified into typical (peripapillary geographic paern), serpiginous macular choroiditis and atypical (ampiginous choroiditis). Serpiginous choroiditis is very rare in our environment; work in this area ...

Melanoma stem cells in experimental melanoma are killed by radioimmunotherapy

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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

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

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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.

MR imaging in the evaluation of macular degeneration and intraocular tumorlike conditions

International Nuclear Information System (INIS)

Mafee, M.F.; Peyman, G.A.; Cohen, S.B.; Capek, V.

1987-01-01

The MR characteristics of malignant uveal melanoma and choroidal hematoma have been described. This paper reports on MR imaging and CT examinations of patients who had macular degeneration, retinal and subretinal masses (hematoma, dense scar), choroidal metastases, choroidal nevus, and choroidal leiomyoma. Several diagnostically helpful MR findings were noted. Posterior hyaloid detachment with associated retinal detachment and subretinal hematoma in patients with macular degeneration demonstrated by MR imaging. Associated liquefaction of the vitreous in our patients with macular degeneration was seen as hyperintensity of the involved vitreous. Hematomas, metastases, and nevi may be confused with uveal melanoma. Choroidal leiomyoma had characteristic high signal intensity in both T1- and T2-weighted images

Systemic Immune-Inflammation Index and Circulating T-Cell Immune Index Predict Outcomes in High-Risk Acral Melanoma Patients Treated with High-Dose Interferon

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Jiayi Yu

2017-10-01

Full Text Available High-dose interferon alfa-2b (IFN-α-2b improves the survival of patients with high-risk melanoma. We aimed to identify baseline peripheral blood biomarkers to predict the outcome of acral melanoma patients treated with IFN-α-2b. Pretreatment baseline parameters and clinical data were assessed in 226 patients with acral melanoma. Relapse-free survival (RFS and overall survival (OS were assessed using the Kaplan-Meier method, and multivariate Cox regression analyses were applied after adjusting for stage, lactate dehydrogenase (LDH, and ulceration. Univariate analysis showed that neutrophil-to-lymphocyte ratio ≥2.35, platelet-to-lymphocyte ratio ≥129, systemic immune-inflammation index (SII ≥615 × 109/l, and elevated LDH were significantly associated with poor RFS and OS. The SII is calculated as follows: platelet count × neutrophil count/lymphocyte count. On multivariate analysis, the SII was associated with RFS [hazard ratio (HR=1.661, 95% confidence interval (CI: 1.066-2.586, P=.025] and OS (HR=2.071, 95% CI: 1.204-3.564, P=.009. Additionally, we developed a novel circulating T-cell immune index (CTII calculated as follows: cytotoxic T lymphocytes/(CD4+ regulatory T cells × CD8+ regulatory T cells. On univariate analysis, the CTII was associated with OS (HR=1.73, 95% CI: 1.01-2.94, P=.044. The SII and CTII might serve as prognostic indicators in acral melanoma patients treated with IFN-α-2b. The indexes are easily obtainable via routine tests in clinical practice.

Choroidal Excavation in Eye with Normal Tension Glaucoma

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Kazunobu Asao

2014-05-01

Full Text Available Purpose: To report the case of an eye with normal tension glaucoma and a choroidal excavation. Methods: This is an observational case report. Results: A 59-year-old woman with normal tension glaucoma had a choroidal excavation in the left eye. Her best-corrected visual acuity and intraocular pressure were within normal limits and had been stable for 5 years. Fundus examination showed a small white lesion inferior to the macula and a nerve fiber layer defect at the inferior edge of the optic disc. Humphrey Field Analyzer (HFA showed visual field defects corresponding to the nerve fiber layer defect with C30-2, and a central scotoma superior to the macula with C10-2. Optical coherence tomography (OCT showed a 150-µm deep choroidal excavation. Disruptions of the IS/OS line were detected only in the area inferior to the choroidal excavation. During the 5 months of follow-up, her best-corrected visual acuity remained at 1.0 and the IOP ranged from 12 to 14 mm Hg in the left eye. The fundus and OCT images did not deteriorate and the choroidal excavation did not enlarge. Conclusions: The disruption of the inner/outer segment (IS/OS line was detected only at the area surrounding the choroidal excavation. OCT examinations are useful in assessing the area of the residual IS/OS line, and HFA can be used to estimate the residual central visual field.

Management of melanoma brain metastases in the era of targeted therapy.

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Shapiro, Daniela Gonsalves; Samlowski, Wolfram E

2011-01-01

Disseminated metastatic disease, including brain metastases, is commonly encountered in malignant melanoma. The classical treatment approach for melanoma brain metastases has been neurosurgical resection followed by whole brain radiotherapy. Traditionally, if lesions were either too numerous or surgical intervention would cause substantial neurologic deficits, patients were either treated with whole brain radiotherapy or referred to hospice and supportive care. Chemotherapy has not proven effective in treating brain metastases. Improvements in surgery, radiosurgery, and new drug discoveries have provided a wider range of treatment options. Additionally, recently discovered mutations in the melanoma genome have led to the development of "targeted therapy." These vastly improved options are resulting in novel treatment paradigms for approaching melanoma brain metastases in patients with and without systemic metastatic disease. It is therefore likely that improved survival can currently be achieved in at least a subset of melanoma patients with brain metastases.

Management of Melanoma Brain Metastases in the Era of Targeted Therapy

International Nuclear Information System (INIS)

Shapiro, D. G.; Samlowski, W. E.; Samlowski, W. E.; Samlowski, W. E.; Samlowski, W. E.

2011-01-01

Disseminated metastatic disease, including brain metastases, is commonly encountered in malignant melanoma. The classical treatment approach for melanoma brain metastases has been neurosurgical resection followed by whole brain radiotherapy. Traditionally, if lesions were either too numerous or surgical intervention would cause substantial neurologic deficits, patients were either treated with whole brain radiotherapy or referred to hospice and supportive care. Chemotherapy has not proven effective in treating brain metastases. Improvements in surgery, radiosurgery, and new drug discoveries have provided a wider range of treatment options. Additionally, recently discovered mutations in the melanoma genome have led to the development of "targeted therapy."These vastly improved options are resulting in novel treatment paradigms for approaching melanoma brain metastases in patients with and without systemic metastatic disease. It is therefore likely that improved survival can currently be achieved in at least a subset of melanoma patients with brain metastases.

Sarcoid granuloma of the choroid.

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Marcus, D F; Bovino, J A; Burton, T C

1982-12-01

Two patients were found to have macular choroidal granulomas associated with systemic sarcoidosis. This unusual fundus picture was documented by serial fundus photography and fluorescein angiography. Both patients had a similar clinical picture of decreased vision, chorioretinal granulomas, and overlying neurosensory detachments. Staining of the inflammatory mass with fluorescein and leakage of dye into the neurosensory space was typical. Lymph node biopsies were performed to substantiate the diagnosis. Both patients responded promptly to systemic corticosteroid therapy with dramatic improvement in visual acuity and resolution of the choroidal lesions.

Bilateral choroidal osteomas associated with fatal systemic illness.

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Kline, L B; Skalka, H W; Davidson, J D; Wilmes, F J

1982-02-01

An 11-year-old black boy complained of intermittent occipital headaches with nausea and projectile vomiting. Previous skin and lung biopsy specimens were interpreted as histiocytosis X. Cranial computed tomographic scanning disclosed a mass lesion in the region of the choroid plexus of the left lateral ventricle. This was surgically removed but proved nondiagnostic despite extensive histologic examination. An ophthalmologic evaluation showed discrete, elevated, yellow-white choroidal tumors in both maculas. The ophthalmoscopic appearance, as well as ultrasonography and computed tomography, led to the diagnosis of choroidal osteomas.

Standardized precision radiotherapy in choroidal metastases

International Nuclear Information System (INIS)

Nylen, U.; Kock, E.; Lax, I.; Lundell, G.; Trampe, E. af; Wilking, N.

1994-01-01

Metastases in the choroid of the eye are frequent in patients with disseminated malignancy. We here report the results using the precision radiotherapy technique described by Schipper et al. to treat 14 of 17 consecutive patients (21 eyes) with symptoms from such metastases. A beam defining collimator was used and a lateral field was given with the treated eye individually fixed. Varying fractionations and doses were used. The biologically effective dose for early effects (BED 3 ) was 47 to 90 Gy and for late effects (BED 10 ) 28 to 59 Gy. In 14 eyes (82%) the metastases regressed completely. The visual acuity was stabilized or improved in all patients and none needed local surgery. Three patients developed signs of radiation retinopathy, but only in one case the visual function was compromized. With this standardized technique no individualized dose planning was needed, the risk of radiation cataract was minimized and a dry eye avoided. (orig.)

Unilateral solitary choroid metastasis from breast cancer: Rewarding results of external radiotherapy

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Nirmala S

2008-01-01

Full Text Available Intraocular metastatic tumor is the commonest intraocular malignancy in adults, with uveal tract the commonest site. In nearly 85% of cases the choroid is the afflicted site due to its vascularity. Breast and lung are the common primaries. In breast primaries, this could be the first metastatic disease. This condition should always be kept in mind in patients with visual symptoms. Fundus examination, ultrasonography and CT/MRI of the orbit help in diagnosis. Early recognition and timely treatment can save the visual function thus imparting good quality of life to the patient. External beam radiotherapy is a good local form of treatment. Hormone therapy in hormone receptor positive tumors can have additional benefits. Here we report a case of unilateral solitary choroid metastasis in a case of breast cancer treated with external beam radiotherapy.

Targeted Therapy for Melanoma

International Nuclear Information System (INIS)

Quinn, Thomas; Moore, Herbert

2016-01-01

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

Targeted Therapy for Melanoma

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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.

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

Science.gov (United States)

2018-05-15

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

Low-dose radiation therapy for choroidal neovascularization in age-related macular degeneration

International Nuclear Information System (INIS)

Matsuhashi, Hideaki; Takahashi, Daisuke; Mariya, Yasushi; Tarusawa, Nobuko; Yoshimoto, Hiroshi; Matsuyama, Shuichi; Noda, Yasuko.

1996-01-01

The efficacy of low-dose radiation was evaluated in the treatment of eyes with subfoveal or juxtafoveal choroidal neovascularization in age-related macular degeneration. Ten eyes of ten patients received a total dose of 14 Gy of 10 MV X-rays in seven fractions and the mean follow-up time was 12 months (range 9-18 months). Thirteen control eyes of thirteen patients were followed for an average of 18 months (range 12-24 months). Visual acuity was improved in 2 eyes (20%), unchanged in 3 eyes (30%), and deteriorated in 5 eyes (50%) of treated patients, and it was improved in no eyes (0%), unchanged in 5 eyes (32%), and deteriorated in 8 eyes (50%) of the control patients at their last follow-up examinations. Funduscopic and angiographic findings were improved in 3 eyes (30%), unchanged in 2 eyes (20%), and deteriorated in 5 eyes (50%) of treated patients, and they were improved in no eyes (0%), unchanged in 5 eyes (32%), and deteriorated in 8 eyes (50%) of the control patients. These results suggested that low-dose radiation is beneficial for the management of subfoveal or juxtafoveal choroidal neovascularization in age-related macular degeneration. (author)

Low-dose radiation therapy for choroidal neovascularization in age-related macular degeneration

Energy Technology Data Exchange (ETDEWEB)

Matsuhashi, Hideaki; Takahashi, Daisuke; Mariya, Yasushi; Tarusawa, Nobuko; Yoshimoto, Hiroshi; Matsuyama, Shuichi [Hirosaki Univ., Aomori (Japan). School of Medicine; Noda, Yasuko

1996-10-01

The efficacy of low-dose radiation was evaluated in the treatment of eyes with subfoveal or juxtafoveal choroidal neovascularization in age-related macular degeneration. Ten eyes of ten patients received a total dose of 14 Gy of 10 MV X-rays in seven fractions and the mean follow-up time was 12 months (range 9-18 months). Thirteen control eyes of thirteen patients were followed for an average of 18 months (range 12-24 months). Visual acuity was improved in 2 eyes (20%), unchanged in 3 eyes (30%), and deteriorated in 5 eyes (50%) of treated patients, and it was improved in no eyes (0%), unchanged in 5 eyes (32%), and deteriorated in 8 eyes (50%) of the control patients at their last follow-up examinations. Funduscopic and angiographic findings were improved in 3 eyes (30%), unchanged in 2 eyes (20%), and deteriorated in 5 eyes (50%) of treated patients, and they were improved in no eyes (0%), unchanged in 5 eyes (32%), and deteriorated in 8 eyes (50%) of the control patients. These results suggested that low-dose radiation is beneficial for the management of subfoveal or juxtafoveal choroidal neovascularization in age-related macular degeneration. (author)

ASSOCIATION OF DRUSEN VOLUME WITH CHOROIDAL PARAMETERS IN NONNEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

Science.gov (United States)

Balasubramanian, Siva; Lei, Jianqin; Nittala, Muneeswar G; Velaga, Swetha B; Haines, Jonathan; Pericak-Vance, Margaret A; Stambolian, Dwight; Sadda, SriniVas R

2017-10-01

The choroid is thought to be relevant to the pathogenesis of nonneovascular age-related macular degeneration, but its role has not yet been fully defined. In this study, we evaluate the relationship between the extent of macular drusen and specific choroidal parameters, including thickness and intensity. Spectral domain optical coherence tomography images were collected from two distinct, independent cohorts with nonneovascular age-related macular degeneration: Amish (53 eyes of 34 subjects) and non-Amish (40 eyes from 26 subjects). All spectral domain optical coherence tomography scans were obtained using the Cirrus HD-OCT with a 512 × 128 macular cube (6 × 6 mm) protocol. The Cirrus advanced retinal pigment epithelium analysis tool was used to automatically compute drusen volume within 3 mm (DV3) and 5 mm (DV5) circles centered on the fovea. The inner and outer borders of the choroid were manually segmented, and the mean choroidal thickness and choroidal intensity (i.e., brightness) were calculated. The choroidal intensity was normalized against the vitreous and nerve fiber layer reflectivity. The correlation between DV and these choroidal parameters was assessed using Pearson and linear regression analysis. A significant positive correlation was observed between normalized choroidal intensity and DV5 in the Amish (r = 0.42, P = 0.002) and non-Amish (r = 0.33, P = 0.03) cohorts. Also, DV3 showed a significant positive correlation with normalized choroidal intensity in both the groups (Amish: r = 0.30, P = 0.02; non-Amish: r = 0.32, P = 0.04). Choroidal thickness was negatively correlated with normalized choroidal intensity in both Amish (r = -0.71, P = 0.001) and non-Amish (r = -0.43, P = 0.01) groups. Normalized choroidal intensity was the most significant constant predictor of DV in both the Amish and non-Amish groups. Choroidal intensity, but not choroidal thickness, seems to be associated with drusen volume in Amish and non-Amish populations. These

Retinopathy of prematurity: inflammation, choroidal degeneration, and novel promising therapeutic strategies.

Science.gov (United States)

Rivera, José Carlos; Holm, Mari; Austeng, Dordi; Morken, Tora Sund; Zhou, Tianwei Ellen; Beaudry-Richard, Alexandra; Sierra, Estefania Marin; Dammann, Olaf; Chemtob, Sylvain

2017-08-22

Retinopathy of prematurity (ROP) is an important cause of childhood blindness globally, and the incidence is rising. The disease is characterized by initial arrested retinal vascularization followed by neovascularization and ensuing retinal detachment causing permanent visual loss. Although neovascularization can be effectively treated via retinal laser ablation, it is unknown which children are at risk of entering this vision-threatening phase of the disease. Laser ablation may itself induce visual field deficits, and there is therefore a need to identify targets for novel and less destructive treatments of ROP. Inflammation is considered a key contributor to the pathogenesis of ROP. A large proportion of preterm infants with ROP will have residual visual loss linked to loss of photoreceptor (PR) and the integrity of the retinal pigment epithelium (RPE) in the macular region. Recent studies using animal models of ROP suggest that choroidal degeneration may be associated with a loss of integrity of the outer retina, a phenomenon so far largely undescribed in ROP pathogenesis. In this review, we highlight inflammatory and neuron-derived factors related to ROP progression, as well, potential targets for new treatment strategies. We also introduce choroidal degeneration as a significant cause of residual visual loss following ROP. We propose that ROP should no longer be considered an inner retinal vasculopathy only, but also a disease of choroidal degeneration affecting both retinal pigment epithelium and photoreceptor integrity.

Anti-vascular endothelial growth factors for choroidal neovascularization secondary to choroidal osteoma: Long-term results

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T Lekha

2015-01-01

Full Text Available Choroidal osteoma is an uncommon benign osseous intraocular tumor typically seen unilaterally in young women. Visual loss can occur due to choroidal neovascularization (CNV complicating osteoma. We report a rare case of bilateral choroidal osteoma with secondary CNV in a young male and the long-term results following anti-vascular endothelial growth factor (VEGF therapy. A 30-year-old male with history of defective vision in both eyes since several years and recent worsening in the right eye (RE since 2 months was found to have bilateral macular osteoma with CNV in the RE based on clinical evaluation, fluorescein angiography, optical coherence tomography, and ultrasonography. Intravitreal injection of ranibizumab at monthly intervals for three doses resulted in resolution of CNV and remained stable for 5 years. Recurrent CNV detected 6 years later responded to an injection of intravitreal bevacizumab and has remained stable till date. Anti-VEGF therapy stabilized the secondary CNV in our patient for 7 years with satisfactory structural and functional outcome, demonstrating the long-term efficacy of this modality of treatment.

MACULAR CHOROIDAL VOLUME CHANGES AFTER INTRAVITREAL BEVACIZUMAB FOR EXUDATIVE AGE-RELATED MACULAR DEGENERATION.

Science.gov (United States)

Palkovits, Stefan; Seidel, Gerald; Pertl, Laura; Malle, Eva M; Hausberger, Silke; Makk, Johanna; Singer, Christoph; Osterholt, Julia; Herzog, Sereina A; Haas, Anton; Weger, Martin

2017-12-01

To evaluate the effect of intravitreal bevacizumab on the macular choroidal volume and the subfoveal choroidal thickness in treatment naïve eyes with exudative age-related macular degeneration. The macular choroidal volume and the subfoveal choroidal thickness were measured using enhanced depth imaging optical coherence tomography. After a screening examination, each patient received 3 monthly intravitreal injections of 1.25 mg bevacizumab. One month after the third injection was a final assessment. Forty-seven patients with a mean age of 80 ± 6.4 years were included. The macular choroidal volume decreased significantly from median 4.1 mm (interquartile range 3.4-5.9) to median 3.9 mm (interquartile range 3.1-5.6) between the baseline and final examination (difference -0.46 mm, 95% confidence interval: -0.57 to 0.35, P macular choroidal volume at baseline and subfoveal choroidal thickness at baseline were not associated with the response to treatment. The macular choroidal volume and the subfoveal choroidal thickness decreased significantly after 3 monthly bevacizumab injections for exudative age-related macular degeneration.

Choroidal thickness in Malaysian eyes with full-thickness macular holes

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Chew Y Tan

2018-02-01

Full Text Available AIM: To compare choroidal thickness at the macula in eyes with unilateral idiopathic full-thickness macular holes(FTMHwith that of unaffected fellow eyes, and eyes of normal control patients.METHODS: Cross-sectional study. Thirty patients with unilateral idiopathic FTMH and thirty age, sex, and race-matched controls were recruited. Axial lengths were measured using laser interferometry. Enhanced depth imaging optical coherence tomography images were obtained using Heidelberg spectral-domain optical coherence tomography. Choroidal thickness was measured at the fovea, and at 1 mm and 2 mm nasally, temporally, superiorly and inferiorly from the center of the fovea. Statistical analysis was performed using independent and paired t-tests, chi-square tests, and Pearson correlation tests(PRESULTS: The mean subfoveal choroidal thickness was 201.0±44.0 μm in the FTMH group, 225.3±51.4 μm in the fellow eye group and 262.3±70.3 μm in the control group. The choroid was thinner in FTMH eyes at all locations when compared to control eyes(PPP>0.05. Choroidal thickness was generally highest subfoveally and lowest nasally. Subfoveal choroidal thickness was negatively correlated with age(r=-0.278, P=0.032, and axial length(r=-0.328, P=0.011.CONCLUSION: Choroidal thickness is lower in both eyes of patients with unilateral FTMH compared to healthy control eyes.

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...

CHANGES IN CHOROIDAL THICKNESS IN AND OUTSIDE THE MACULA AFTER HEMODIALYSIS IN PATIENTS WITH END-STAGE RENAL DISEASE.

Science.gov (United States)

Chang, In Boem; Lee, Jeong Hyun; Kim, Jae Suk

2017-05-01

To evaluate changes in choroidal thickness in and outside the macula as a result of hemodialysis (HD) in patients with end-stage renal disease. Patients with end-stage renal disease treated with maintenance HD in the Dialysis Unit of Sanggye Paik Hospital, Seoul, South Korea, were included in this study. The choroidal thickness was measured in and outside the macula before and after HD (paired t-test). Choroidal thickness in the macula was measured at the foveal center and 1.5 mm temporal to the foveal center and outside the macula was measured at superior, inferior, and nasal area 3.5 mm from the optic disk margin. Peripapillary retinal nerve fiber layer thickness, intraocular pressure, central corneal thickness, and systemic parameters such as serum osmolarity and blood pressure (BP) were measured before and after HD (paired t-test). We divided patients into two groups, diabetic and nondiabetic groups to compare the changes in choroidal thickness. Patients with diabetes were subdivided into two groups: severe retinal change group and moderate retinal change group (Mann-Whitney test). Pearson's correlation test was used to evaluate the correlations between choroidal thickness and changes in serum osmolarity, BP, and body weight loss. Choroidal thickness and peripapillary retinal nerve fiber layer thickness were measured using spectral-domain optical coherence tomography. Fifty-four eyes of 31 patients with end-stage renal disease were included. After HD, the mean intraocular pressure was significantly decreased from 14.8 ± 2.5 mmHg to 13.0 ± 2.6 mmHg (P macula.

Choroidal metastasis from early rectal cancer: Case report and literature review.

Science.gov (United States)

Tei, Mitsuyoshi; Wakasugi, Masaki; Akamatsu, Hiroki

2014-01-01

Choroidal metastasis from colorectal cancer is rare, and there have been no reported cases of such metastasis from early colorectal cancer. We report a case of choroidal metastasis from early rectal cancer. A 61 year-old-man experienced myodesopsia in the left eye 2 years and 6 months after primary rectal surgery for early cancer, and was diagnosed with left choroidal metastasis and multiple lung metastases. Radiotherapy was initiated for the left eye and systemic chemotherapy is initiated for the multiple lung metastases. The patient is living 2 years and 3 months after the diagnosis of choroidal metastasis without signs of recurrence in the left eye, and continues to receive systemic chemotherapy for multiple lung metastases. Current literatures have few recommendations regarding the appropriate treatment of choroidal metastasis from colorectal cancer, but an aggressive multi-disciplinary approach may be effective in local regression. This is the first report of choroidal metastasis from early rectal cancer. We consider it important to enforce systemic chemotherapy in addition to radiotherapy for choroidal metastasis from colorectal cancer. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Plaque Brachytherapy for Uveal Melanoma: A Vision Prognostication Model

International Nuclear Information System (INIS)

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

2012-01-01

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

Plaque Brachytherapy for Uveal Melanoma: A Vision Prognostication Model

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

2012-11-01

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

Ranibizumab in the treatment of choroidal neovascularization on the border of an inferior staphyloma associated with tilted disc syndrome

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Luis Arias

2010-03-01

Full Text Available Luis Arias1,2, Jordi Monés21Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat, Barcelona; 2Institut de la Màcula i de la Retina, Centro Médico Teknon, BarcelonaPurpose: To describe a case of choroidal neovascularization (CNV on the border of an inferior staphyloma associated with tilted disc syndrome treated with intravitreal ranibizumab.Patients: Observational case report.Methods: A patient with CNV on the border of an inferior staphyloma associated with tilted disc syndrome was imaged using fluorescein angiography, autofluorescence and spectral domain optical coherence tomography, and treated with intravitreal injections of ranibizumab. Results: The patient received 3 ranibizumab injections during the 9-month follow-up. The visual acuity improved from 20/40 to 20/32 and the foveal thickness reduced from 470 microns to 248 microns. The angiograms showed resolution of leakage associated with CNV. There were no adverse events.Conclusion: Intravitreal ranibizumab is an efficacious and safe treatment in the management of choroidal neovascularization on the border of an inferior staphyloma associated with tilted disc syndrome.Keywords: intravitreal ranibizumab, choroidal neovascularization, tilted disc syndrome, inferior staphyloma

Retinal and choroidal expression of BMP-2 in lens-induced myopia and recovery from myopia in guinea pigs.

Science.gov (United States)

Li, Honghui; Wu, Juan; Cui, Dongmei; Zeng, Junwen

2016-03-01

The present study investigated the retinal and choroidal expression of bone morphogenetic protein-2 (BMP-2) in myopia and in myopia recovery in a guinea pig model. For this investigation, two groups of guinea pigs, lens‑induced myopia and recovery from myopia, were used, and defocused myopia was induced the guinea pigs wearing ‑4.00 D lenses on the right eyes for 3 weeks, with the left eyes serving as the contralateral. In the following week, the lenses of the guinea pigs in the recovery group were removed, and the refractive power and axial length were measured. The expression of BMP‑2 in the eyeballs was observed using immunohistochemistry and analyzed using Western blot analysis. After 3 weeks, the eyes acquired relative myopia and longer axial lengths in the two groups of guinea pigs. After 1 week without lenses in the recovery group, the myopia and axial lengths regressed. Immunofluorescence staining showed that BMP‑2 was expressed in the posterior retina, RPE, choroid and sclera. The expression of BMP‑2 decreased in the myopic retina of the guinea pigs. Following the regression of myopia in the recovery group, no difference in the expression of BMP‑2 was observed between the recovered treated eyes and the contralateral eyes. The choroidal expression level of BMP‑2 in the treated eyes showed no significant changes in either group. Therefore, BMP‑2 may be involved in the development of myopia, however, it does not have a primary role in the retinal and choroidal signals regulating scleral remodeling.

Choroidal thickness in Chinese patients with non-arteritic anterior ischemic optic neuropathy.

Science.gov (United States)

Jiang, Libin; Chen, Lanlan; Qiu, Xiujuan; Jiang, Ran; Wang, Yaxing; Xu, Liang; Lai, Timothy Y Y

2016-08-31

Non-arteritic anterior ischemic optic neuropathy (NA-AION) is one of the most common types of ischemic optic neuropathy. Several recent studies suggested that abnormalities of choroidal thickness might be associated with NA-AION. The main objective of this case-control study was to evaluate whether choroidal thickness is an ocular risk factor for the development of NA-AION by evaluating the peripapillary and subfoveal choroidal thicknesses in affected Chinese patients. Forty-four Chinese patients with unilateral NA-AION were recruited and compared with 60 eyes of 60 normal age and refractive-error matched control subjects. Peripapillary and subfoveal choroidal thicknesses were measured by enhanced depth imaging optical coherence tomography. Choroidal thicknesses of eyes with NA-AION and unaffected fellow eyes were compared with normal controls. Choroidal thicknesses of NA-AION eyes with or without optic disc edema were also compared. The correlation between choroidal thickness and retinal nerve fiber layer (RNFL) thickness, logMAR best-corrected visual acuity (BCVA), and the mean deviation (MD) of Humphrey static perimetry in NA-AION eyes were analyzed. The peripapillary choroidal thicknesses at the nasal, nasal inferior and temporal inferior segments in NA-AION eyes with optic disc edema were significantly thicker compared with that of normal subjects (P optic disc edema and normal eyes (all P > 0.05). No significant correlation between choroidal thickness and RNFL thickness, logMAR BCVA and perimetry MD was found in eyes affected by NA-AION (all P > 0.05). Increase in peripapillary choroid thickness in some segments was found in NA-ION eyes with optic disc edema. However, our findings do not support the hypothesis that choroidal thickness is abnormal in Chinese patients with NA-AION compared with normal subjects with similar age and refractive error status.

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

International Nuclear Information System (INIS)

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

1994-01-01

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

Baseline Biomarkers for Outcome of Melanoma Patients Treated with Pembrolizumab

NARCIS (Netherlands)

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

2016-01-01

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

Evaluation of Immune-Related Response Criteria and RECIST v1.1 in Patients With Advanced Melanoma Treated With Pembrolizumab.

Science.gov (United States)

Hodi, F Stephen; Hwu, Wen-Jen; Kefford, Richard; Weber, Jeffrey S; Daud, Adil; Hamid, Omid; Patnaik, Amita; Ribas, Antoni; Robert, Caroline; Gangadhar, Tara C; Joshua, Anthony M; Hersey, Peter; Dronca, Roxana; Joseph, Richard; Hille, Darcy; Xue, Dahai; Li, Xiaoyun Nicole; Kang, S Peter; Ebbinghaus, Scot; Perrone, Andrea; Wolchok, Jedd D

2016-05-01

We evaluated atypical response patterns and the relationship between overall survival and best overall response measured per immune-related response criteria (irRC) and Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) in patients with advanced melanoma treated with pembrolizumab in the phase Ib KEYNOTE-001 study (clinical trial information: NCT01295827). Patients received pembrolizumab 2 or 10 mg/kg every 2 weeks or every 3 weeks. Atypical responses were identified by using centrally assessed irRC data in patients with ≥ 28 weeks of imaging. Pseudoprogression was defined as ≥ 25% increase in tumor burden at week 12 (early) or any assessment after week 12 (delayed) that was not confirmed as progressive disease at next assessment. Response was assessed centrally per irRC and RECIST v1.1. Of the 655 patients with melanoma enrolled, 327 had ≥ 28 weeks of imaging follow-up. Twenty-four (7%) of these 327 patients had atypical responses (15 [5%] with early pseudoprogression and nine [3%] with delayed pseudoprogression). Of the 592 patients who survived ≥ 12 weeks, 84 (14%) experienced progressive disease per RECIST v1.1 but nonprogressive disease per irRC. Two-year overall survival rates were 77.6% in patients with nonprogressive disease per both criteria (n = 331), 37.5% in patients with progressive disease per RECIST v1.1 but nonprogressive disease per irRC (n = 84), and 17.3% in patients with progressive disease per both criteria (n = 177). Atypical responses were observed in patients with melanoma treated with pembrolizumab. Based on survival analysis, conventional RECIST might underestimate the benefit of pembrolizumab in approximately 15% of patients; modified criteria that permit treatment beyond initial progression per RECIST v1.1 might prevent premature cessation of treatment. © 2016 by American Society of Clinical Oncology.

Current treatments for radiation retinopathy

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Giuliari, Gian Paolo; Simpson, E. Rand (Princess Margaret Hospital, Univ. of Toronto, Dept. of Ophthalmology and Vision Sciences, Toronto (Canada)), e-mail: gpgiuliari@gmail.com; Sadaka, Ama (Schepens Eye Research Inst., Boston, MA (United States)); Hinkle, David M. (Massachusetts Eye Research and Surgery Institution, Cambridge, MA (United States))

2011-01-15

Background. To review the currently available therapeutic modalities for radiation retinopathy (RR), including newer investigational interventions directed towards specific aspects of the pathophysiology of this refractory complication. Methods. A review of the literature encompassing the pathogenesis of RR and the current therapeutic modalities available was performed. Results. RR is a chronic and progressive condition that results from exposure to any source of radiation. It might be secondary to radiation treatment of intraocular tumors such as choroidal melanomas, retinoblastomas, and choroidal metastasis, or from unavoidable exposure to excessive radiation from the treatment of extraocular tumors like cephalic, nasopharyngeal, orbital, and paranasal malignancies. After the results of the Collaborative Ocular Melanoma Study, most of the choroidal melanomas are being treated with plaque brachytherapy increasing by that the incidence of this radiation complication. RR has been reported to occur in as many as 60% of eyes treated with plaque radiation, with higher rates associated with larger tumors. Initially, the condition manifests as a radiation vasculopathy clinically seen as microaneurysms and telangiectasis, with posterior development of retinal hard exudates and hemorrhages, macular edema, neovascularization and tractional retinal detachment. Regrettably, the management of these eyes remains limited. Photodynamic therapy, laser photocoagulation, oral pentoxyphylline and hyperbaric oxygen have been attempted as treatment modalities with inconclusive results. Intravitreal injections of anti-vascular endothelial growth factor such as bevacizumab, ranibizumab and pegaptanib sodium have been recently used, also with variable results. Discussion. RR is a common vision threatening complication following radiation therapy. The available therapeutic options are limited and show unsatisfactory results. Further large investigative studies are required for developing

Measurement of Choroidal Perfusion and Thickness Following Systemic Sildenafil (Viagra®)

Science.gov (United States)

Kim, David Y.; Silverman, Ronald H.; Chan, R.V. Paul; Khanifar, Aziz A.; Rondeau, Mark; Lloyd, Harriet; Schlegel, Peter; Coleman, D. Jackson

2011-01-01

Objective To demonstrate anatomic and physiologic changes in the human choroid following systemic sildenafil citrate (ViagraR) using enhanced depth imaging spectral domain-optical coherence tomography (EDI-OCT) and swept-scan high frequency digital ultrasound. Methods Seven healthy male subjects (mean age 32.7 years) were evaluated at baseline and two hours after ingesting 50 mg of sildenafil. Swept-scan high frequency digital ultrasound and EDI-OCT were utilized to measure choroidal perfusion and thickness, respectively. Results were read by masked observers. The Wilcoxon signed-rank test and t-test were used to analyze differences in choroidal flow and thickness at baseline and two hours after ingestion of sildenafil. Results Two hours following sildenafil, increased choroidal perfusion was observed in 11 of 12 eyes measured by swept-scan high frequency digital ultrasound. The mean increase was 3.46 (±2.00) times baseline with a range of 0.47 to 7.80 times baseline (p=0.004). Increased choroidal thickness was observed in 12 of 12 eyes measured with EDI-OCT. The average choroidal thickness increased by 11.6% temporal to the fovea, 9.3% nasal to the fovea, and 10.7% underneath the fovea (p<0.001 for all values). Conclusions Choroidal perfusion and thickness both increase in response to systemic sildenafil. These changes could secondarily affect retinal function, explain previously reported clinical symptoms, and potentially be a useful adjunct for treatment of ocular diseases that would benefit from increased choroidal blood flow. PMID:22974308

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

DEFF Research Database (Denmark)

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

2011-01-01

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

Radiogenic late effects in the eye after therapeutic application of beta radiation

International Nuclear Information System (INIS)

Lommatzsch, P.; Neumeister, K.

1978-01-01

Beta irradiation with 90 Sr/ 90 Y is used to treat epibulbar tumours (carcinoma, melanoma) and irradiation with 106 Ru/ 106 Rh is used to treat intra-ocular tumours (melanoma, retinoblastoma). Two studies have been carried out. Since 1960, 185 patients with epibulbar pigment tumours and 15 patients with conjunctiva carcinomas have been treated with 90 Sr/ 90 Y-applicators and observed for several years. The dose applied was 10,000 to 20,000 rads at the focus depending on the type and extent of the tumour. Apart from teleangiectasias of the conjunctiva, there were only a few cases of severe radio-induced complications such as keratopathies and secondary glaucoma, which were regarded as the lesser evil in comparison with the main disease. The radiation cataract after beta irradiation remains peripheral and does not impair vision. So far 39 patients with choroid melanomas and 22 children with retinoblastomas have been observed for more than 5 years after beta irradiation with 106 Ru/ 106 Rh. The dose applied at the sclera surface was 40,000 to 100,000 rads for 4 to 8 days. In 39 patients with successfully irradiated choroid melanomas, radio-induced late complications developed such as macula degeneration, opticus atrophy and retinal-vessel ablations, which may impair vision. In the 22 children irradiated, only 7 cases of late complications with impaired functions could be observed. Whereas radiation-induced late damage after beta irradiation of the front section of the eye is of small clinical importance, especially in older patients, intra-ocular tumours with radio-induced late damage in the retinal vessel and capillary system have to be expected after high-dose beta irradiation

Bilateral choroidal neovascularization response to unilateral intravitreal Ranibizumab injection in a patient with angioid streaks

Directory of Open Access Journals (Sweden)

Otacílio de Oliveira Maia Júnior

2013-08-01

Full Text Available Report of a 48 year-old male with bilateral decrease in vision due to choroidal neovascularization secondary to angioid streaks. Best corrected visual acuity was 20/80 in the right eye and counting fingers at 2 meters on the left eye. Patient underwent intravitreal injection of Ranibizumab (Lucentis in the eye with worse visual acuity. Fifteen days after treatment patient reported better visual acuity on the fellow eye, which was measured to be 20/25. Treatment result was evaluated with visual acuity and optical coherence tomography. The effect of ranibizumab was observed in the treated eye, but the fellow eye had complete resolution of the choroidal neovascularization complex. This result may be a response to systemic absorption of the medication.

Effect of DETOX as an adjuvant for melanoma vaccine.

Science.gov (United States)

Schultz, N; Oratz, R; Chen, D; Zeleniuch-Jacquotte, A; Abeles, G; Bystryn, J C

1995-04-01

The identification of effective adjuvants is critical for tumor vaccine development. Towards this end, we examined whether the immunogenicity of a melanoma vaccine could be potentiated by DETOX, an adjuvant consisting of monophosphoryl lipid A (MPL) and purified mycobacterial cell-wall skeleton (CWS). Nineteen patients with resected stage III melanoma were immunized with a polyvalent melanoma antigen vaccine (40 micrograms) admixed with DETOX, q3 wks x 4. Seven patients received vaccine + low-dose DETOX (10 micrograms MPL + 100 micrograms CWS) and 12 received vaccine + high-dose DETOX (20 micrograms MPL + 200 micrograms CWS). A non-randomized control group of 35 patients was treated similarly with 40 micrograms vaccine + alum. One week after the fourth vaccine immunization, melanoma antibodies were increased over baseline in 7/7 (100%) patients treated with vaccine + low-dose DETOX, 8/12 (67%) patients treated with vaccine + high-dose DETOX, and in 4/19 (21%) of vaccine + alum patients. For the entire DETOX group, the antibody response rate was 15/19 (79%) compared 4/19 (21%) in the alum group (p or = 15 mm increase in DTH response over baseline) was induced in 50% of the entire DETOX group versus in 47% of the alum group. Median disease-free (DF) survival for the entire DETOX group was 17.8 months compared with 32.1 months in the alum group (p DETOX markedly potentiated antibody but had little effect on DTH responses to melanoma vaccine immunization. It did not appear to improve disease-free survival in comparison to alum in this non-randomized study.

Long-Term Metastatic Risk after Biopsy of Posterior Uveal Melanoma

DEFF Research Database (Denmark)

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

2018-01-01

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

Seven Non-melanoma Features to Rule Out Facial Melanoma

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Philipp Tschandl

2017-08-01

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

Diffuse choroid plexus hyperplasia: an under-diagnosed cause of hydrocephalus in children?

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Aziz, Azian Abd.; Coleman, Lee [Royal Children' s Hospital Melbourne, Department of Medical Imaging, Parkville, Victoria (Australia); Morokoff, Andrew; Maixner, Wirginia [Royal Children' s Hospital Melbourne, Department of Neurosurgery, Parkville (Australia)

2005-08-01

Hydrocephalus is a common neurological disorder in children and the result of a variety of causes. However, with the advancement of imaging modalities, particularly MRI, previously reported rarer causes of hydrocephalus in children are now being more readily appreciated. We report an 11-year-old boy with diffuse villous hyperplasia of the choroid plexus. He had a ventriculo-peritoneal (VP) shunt in-situ and a prior diagnosis from infancy of congenital aqueduct stenosis as the cause of his hydrocephalus. His current presentation was with further shunt dysfunction. CT and MRI demonstrated enlarged choroid plexuses but did not confirm aqueduct stenosis. CSF overproduction was demonstrated from the externalized ventricular drain. The enlarged choroid plexuses were surgically resected and histology confirmed choroid plexus hyperplasia. Identification of choroid plexus hyperplasia is important since the neurosurgical management of hydrocephalus is not VP shunt insertion, but resection of the hyperplastic choroid plexus. (orig.)

Diffuse choroid plexus hyperplasia: an under-diagnosed cause of hydrocephalus in children?

International Nuclear Information System (INIS)

Aziz, Azian Abd.; Coleman, Lee; Morokoff, Andrew; Maixner, Wirginia

2005-01-01

Hydrocephalus is a common neurological disorder in children and the result of a variety of causes. However, with the advancement of imaging modalities, particularly MRI, previously reported rarer causes of hydrocephalus in children are now being more readily appreciated. We report an 11-year-old boy with diffuse villous hyperplasia of the choroid plexus. He had a ventriculo-peritoneal (VP) shunt in-situ and a prior diagnosis from infancy of congenital aqueduct stenosis as the cause of his hydrocephalus. His current presentation was with further shunt dysfunction. CT and MRI demonstrated enlarged choroid plexuses but did not confirm aqueduct stenosis. CSF overproduction was demonstrated from the externalized ventricular drain. The enlarged choroid plexuses were surgically resected and histology confirmed choroid plexus hyperplasia. Identification of choroid plexus hyperplasia is important since the neurosurgical management of hydrocephalus is not VP shunt insertion, but resection of the hyperplastic choroid plexus. (orig.)

Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes in Advanced Melanoma Patients

OpenAIRE

Mélanie Saint-Jean; Anne-Chantal Knol; Christelle Volteau; Gaëlle Quéreux; Lucie Peuvrel; Anabelle Brocard; Marie-Christine Pandolfino; Soraya Saiagh; Jean-Michel Nguyen; Christophe Bedane; Nicole Basset-Seguin; Amir Khammari; Brigitte Dréno

2018-01-01

Immunotherapy for melanoma includes adoptive cell therapy with autologous tumor-infiltrating lymphocytes (TILs). This monocenter retrospective study was undertaken to evaluate the efficacy and safety of this treatment of patients with advanced melanoma. All advanced melanoma patients treated with TILs using the same TIL expansion methodology and same treatment interleukin-2 (IL-2) regimen between 2009 and 2012 were included. After sterile intralesional excision of a cutaneous or subcutaneous ...

Choroid plexus carcinoma. A case report

International Nuclear Information System (INIS)

Strojan, P.; Jereb, B.; Popovic, M.; Surlan, K.

2004-01-01

Background. The opinions on the value of adjuvant therapy in choroid plexus carcinomas vary. The aim of present report is to present a case of successful therapy of this rare tumor. Result. A fourteen-year-old girl with third ventricle tumor had non-radical surgery and adjuvant chemotherapy and irradiation. She is alive with no evidence of disease 8.5 years after diagnosis. The role of adjuvant therapy in the context of literature data is discussed. Conclusion. For choroids plexus carcinomas, adjuvant multiagent chemotherapy and craniospinal radiotherapy following surgery should be considered. (author)

Evaluation of focal choroidal excavation in the macula using swept-source optical coherence tomography.

Science.gov (United States)

Lim, F P M; Loh, B K; Cheung, C M G; Lim, L S; Chan, C M; Wong, D W K

2014-09-01

To evaluate imaging findings of patients with focal choroidal excavation (FCE) in the macula using swept-source optical coherence tomography (SS-OCT) and correlate it clinically. Prospective observational case series. Eleven consecutive patients (12 eyes) with FCE were described. Data on demographics and clinical presentation were collected and imaging findings (including color photography, fundus autofluorescence imaging, fluorescein angiography, indocyanine green angiography, spectral-domain optical coherence tomography, and SS-OCT) were analyzed. The primary diagnosis was epiretinal membrane (two eyes), choroidal neovascularization (one eye), polypoidal choroidal vasculopathy (three eyes), central serous chorioretinopathy (one eye), and dry age-related macular degeneration (two eyes). Eleven out of 12 of the lesions were conforming. One presented with a non-conforming lesion that progressed to a conforming lesion. One eye had multiFCE and two had two overlapping choroidal excavations. Using the SS-OCT, we found the choroid to be thinned out at the area of FCE but sclera remained normal. The choroidal tissue beneath the FCE was abnormal, with high internal reflectivity and poor visualization of choroidal vessels. There was loss of contour of the outer choroidal boundary that appeared to be pulled inward by this abnormal choroidal tissue. A suprachoroidal space was noted beneath this choroidal tissue and the choroidal-scleral interface was smooth. Repeat SS-OCT 6 months after presentation showed the area of excavation to be stable in size. FCE can be associated with epiretinal membrane, central serous chorioretinopathy, and age-related macular degeneration. The choroid was thinned out in the area of FCE.

Correlation between clinical and histological features in a pig model of choroidal neovascularization

DEFF Research Database (Denmark)

Lassota, Nathan; Kiilgaard, Jens Folke; Prause, Jan Ulrik

2006-01-01

To analyse the histological changes in the retina and the choroid in a pig model of choroidal neovascularization (CNV) and to correlate these findings with fundus photographic and fluorescein angiographic features.......To analyse the histological changes in the retina and the choroid in a pig model of choroidal neovascularization (CNV) and to correlate these findings with fundus photographic and fluorescein angiographic features....

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

Science.gov (United States)

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

2018-01-01

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

Choroidal thickness in eyes with different degrees of myopia

Directory of Open Access Journals (Sweden)

Yuriy Sergeyevich Astakhov

2013-12-01

Full Text Available 66 healthy people (124 eyes with different degrees of myopia and emmetropia were examined using enhanced depth imaging optical coherence tomography (EDI-OCT using the “Spectralis OCT”. It was found that the choroid in subjects with medium and high degrees of myopia was significantly thinner than that in the control group. In the study, a negative correlation was found between the subfoveal choroidal thickness and the degree of myopia (r = -0.75, p < 0.0001. It was also found that the subfoveal choroidal thickness decreased for each diopter of myopia by approximately 18.03 μm.

Beals–Hecht syndrome and choroidal neovascularization

Directory of Open Access Journals (Sweden)

Roberto Gallego-Pinazo

2010-07-01

Full Text Available Roberto Gallego-Pinazo1, Ruth López-Lizcano1, José María Millán2,3, J Fernando Arevalo5, J Luis Mullor6, Manuel Díaz-Llopis1,3,41Department of Ophthalmology, 2Department of Genetics, Unit of Experimental Opthalmology, Hospital Universitario La Fe, Valencia, Spain; 3Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER, Valencia, Spain; 4Faculty of Medicine, University of Valencia, Valencia, Spain; 5Retina and Vitreous Service, Clínica Oftalmológica Centro Caracas, Caracas, Venezuela; 6Unit of Experimental Opthalmology, Fundación Parala Investigación del Hospital La Fe, Valencia, SpainPurpose: To describe a case of choroidal neovascularization (CNV in a female diagnosed with Beals–Hecht syndrome.Methods: A retrospective, interventional case is described in a 26-year-old female complaining of metamorphopsia and visual loss in her left eye (counting fingers. The fluorescein angiogram and the optical coherence tomography supported the diagnosis of CNV. Intravitreal ranibizumab was administered.Results: After the third intravitreal ranibizumab, her visual acuity improved to 0.8 and the morphology of the macular area was restored.Conclusions: To our knowledge this is the first report of CNV in Beals–Hecht syndrome treated with ranibizumab. Self-monitoring by periodically performing Amsler grid test is strongly recommended in these patients in order to achieve an early diagnosis of eventual CNV and avoid visual acuity loss.Keywords: Beals–Hecht syndrome, connective tissue disease, choroidal neovascularization, ranibizumab

Vulvar melanoma - Is there a role for sentinel lymph node biopsy?

NARCIS (Netherlands)

de Hullu, JA; Hollema, H; Hoekstra, HJ; Piers, DA; Mourits, MJE; Aalders, JG; van der Zee, AGJ

2002-01-01

BACKGROUND. The objective of this study was to evaluate the author's recent, preliminary experience with the sentinel lymph node procedure in patient with vulvar melanoma and to compare this experience with treatment and follow-up of patients with vulvar melanomas who were treated previously at

Fundus autofluorescence in serpiginouslike choroiditis.

Science.gov (United States)

Gupta, Amod; Bansal, Reema; Gupta, Vishali; Sharma, Aman

2012-04-01

To report the fundus autofluorescence characteristics in serpiginouslike choroiditis. Twenty-nine patients with presumed tubercular serpiginouslike choroiditis between November 2008 and January 2010 underwent fundus autofluorescence imaging during the acute stage and at regular intervals till the lesions healed. All patients received antitubercular therapy with oral corticosteroids. The autofluorescence images were compared with color fundus photography and fundus fluorescein angiography. The main outcome measure was fundus autofluorescence characteristics of lesions during the course of the disease. The pattern of fundus autofluorescence changed as the lesions evolved from the acute to the healed stage. In acute stage, the lesions showed an ill-defined halo of increased autofluorescence (hyperautofluorescence), giving it a diffuse, amorphous appearance (Stage I, acute). As the lesions began to heal, a thin rim of decreased autofluorescence (hypoautofluorescence) surrounded the lesion, defining its edges. The lesions showed predominantly hyperautofluorescence with stippled pattern (Stage II, subacute). With further healing, the hypoautofluorescence progressed and the lesion appeared predominantly hypoautofluorescent with stippled pattern (Stage III, nearly resolved). On complete healing, the lesions became uniformly hypoautofluorescent (Stage IV, completely resolved). Fundus autofluorescence highlighted the areas of disease activity and was a quick imaging tool for monitoring the course of lesions in serpiginouslike choroiditis.

The patterns of melanoma presentation in Rijeka region.

Science.gov (United States)

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

2013-01-01

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

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

Quantitative HRMAS proton total correlation spectroscopy applied to cultured melanoma cells treated by chloroethyl nitrosourea: demonstration of phospholipid metabolism alterations.

Science.gov (United States)

Morvan, Daniel; Demidem, Aicha; Papon, Janine; Madelmont, Jean Claude

2003-02-01

Recent NMR spectroscopy developments, such as high-resolution magic angle spinning (HRMAS) probes and correlation-enhanced 2D sequences, now allow improved investigations of phospholipid (Plp) metabolism. Using these modalities we previously demonstrated that a mouse-bearing melanoma tumor responded to chloroethyl nitrosourea (CENU) treatment in vivo by altering its Plp metabolism. The aims of the present study were to investigate whether HRMAS proton total correlation spectroscopy (TOCSY) could be used as a quantitative technique to probe Plp metabolism, and to determine the Plp metabolism response of cultured B16 melanoma cells to CENU treatment in vitro. The exploited TOCSY signals of Plp derivatives arose from scalar coupling among the protons of neighbor methylene groups within base headgroups (choline and ethanolamine). For strongly expressed Plp derivatives, TOCSY signals were compared to saturation recovery signals and demonstrated a linear relationship. HRMAS proton TOCSY was thus used to provide concentrations of Plp derivatives during long-term follow-up of CENU-treated cell cultures. Strong Plp metabolism alteration was observed in treated cultured cells in vitro involving a down-regulation of phosphocholine, and a dramatic and irreversible increase of phosphoethanolamine. These findings are discussed in relation to previous in vivo data, and to Plp metabolism enzymatic involvement. Copyright 2003 Wiley-Liss, Inc.

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

Energy Technology Data Exchange (ETDEWEB)

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

2001-06-01

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

Baseline Tumor Size Is an Independent Prognostic Factor for Overall Survival in Patients With Melanoma Treated With Pembrolizumab.

Science.gov (United States)

Joseph, Richard W; Elassaiss-Schaap, Jeroen; Kefford, Richard F; Hwu, Wen-Jen; Wolchok, Jedd D; Joshua, Anthony Michael; Ribas, Antoni; Hodi, F Stephen; Hamid, Omid; Robert, Caroline; Daud, Adil I; Dronca, Roxana S; Hersey, Peter; Weber, Jeffrey S; Patnaik, Amita; de Alwis, Dinesh P; Perrone, Andrea M; Zhang, Jin; Kang, Soonmo Peter; Ebbinghaus, Scot W; Anderson, Keaven M; Gangadhar, Tara

2018-04-23

To assess the association of baseline tumor size (BTS) with other baseline clinical factors and outcomes in pembrolizumab-treated patients with advanced melanoma in KEYNOTE-001 (NCT01295827). BTS was quantified by adding the sum of the longest dimensions of all measurable baseline target lesions. BTS as a dichotomous and continuous variable was evaluated with other baseline factors using logistic regression for objective response rate (ORR) and Cox regression for overall survival (OS). Nominal P values with no multiplicity adjustment describe the strength of observed associations. Per central review by RECIST v1.1, 583 of 655 patients had baseline measurable disease and were included in this post hoc analysis. Median BTS was 10.2 cm (range, 1-89.5). Larger median BTS was associated with Eastern Cooperative Oncology Group performance status 1, elevated lactate dehydrogenase (LDH), stage M1c disease, and liver metastases (with or without any other sites) (all P ≤ 0.001). In univariate analyses, BTS below the median was associated with higher ORR (44% vs 23%; P BTS below the median remained an independent prognostic marker of OS (P BTS below the median and PD-L1-positive tumors were independently associated with higher ORR and longer OS. BTS is associated with many other baseline clinical factors but is also independently prognostic of survival in pembrolizumab-treated patients with advanced melanoma. Copyright ©2018, American Association for Cancer Research.

Evaluation of focal choroidal excavation in the macula using swept-source optical coherence tomography

Science.gov (United States)

Lim, F P M; Loh, B K; Cheung, C M G; Lim, L S; Chan, C M; Wong, D W K

2014-01-01

Purpose To evaluate imaging findings of patients with focal choroidal excavation (FCE) in the macula using swept-source optical coherence tomography (SS-OCT) and correlate it clinically. Methods Prospective observational case series. Eleven consecutive patients (12 eyes) with FCE were described. Data on demographics and clinical presentation were collected and imaging findings (including color photography, fundus autofluorescence imaging, fluorescein angiography, indocyanine green angiography, spectral-domain optical coherence tomography, and SS-OCT) were analyzed. Results The primary diagnosis was epiretinal membrane (two eyes), choroidal neovascularization (one eye), polypoidal choroidal vasculopathy (three eyes), central serous chorioretinopathy (one eye), and dry age-related macular degeneration (two eyes). Eleven out of 12 of the lesions were conforming. One presented with a non-conforming lesion that progressed to a conforming lesion. One eye had multiFCE and two had two overlapping choroidal excavations. Using the SS-OCT, we found the choroid to be thinned out at the area of FCE but sclera remained normal. The choroidal tissue beneath the FCE was abnormal, with high internal reflectivity and poor visualization of choroidal vessels. There was loss of contour of the outer choroidal boundary that appeared to be pulled inward by this abnormal choroidal tissue. A suprachoroidal space was noted beneath this choroidal tissue and the choroidal–scleral interface was smooth. Repeat SS-OCT 6 months after presentation showed the area of excavation to be stable in size. Conclusion FCE can be associated with epiretinal membrane, central serous chorioretinopathy, and age-related macular degeneration. The choroid was thinned out in the area of FCE. PMID:24946847

Radiopharmaceuticals targeting melanoma

Energy Technology Data Exchange (ETDEWEB)

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

2008-02-15

specific localisation of the radioactivity was noticed in mice bearing A.375 human amelanotic tumour. In competition experiments,uptake of {sup 123}I-M..E.L.037 in brain, lung, heart and kidney, organs known to contain s-receptors, was not significantly different in haloperidol treated animals compared to controls. Therefore,reduction of uptake in tumour and eyes of the pigmented mice bearing the B.16 F.0 tumour suggested that the mechanism of tumour uptake was likely due to an interaction with melanin.These findings suggested that {sup 123}I-M.E.L.037, which displays a rapid and very high tumour uptake, appeared to be a promising imaging agent for detection of most melanoma tumours with the potential for development as a therapeutic agent in melanoma tumour proliferation. (authors)

Macular Choroidal Small-Vessel Layer, Sattler's Layer and Haller's Layer Thicknesses: The Beijing Eye Study.

Science.gov (United States)

Zhao, Jing; Wang, Ya Xing; Zhang, Qi; Wei, Wen Bin; Xu, Liang; Jonas, Jost B

2018-03-13

To study macular choroidal layer thickness, 3187 study participants from the population-based Beijing Eye Study underwent spectral-domain optical coherence tomography with enhanced depth imaging for thickness measurements of the macular small-vessel layer, including the choriocapillaris, medium-sized choroidal vessel layer (Sattler's layer) and large choroidal vessel layer (Haller's layer). In multivariate analysis, greater thickness of all three choroidal layers was associated (all P  0.05) associated with the prevalence of open-angle glaucoma or diabetic retinopathy. There was a tendency (0.07 > P > 0.02) toward thinner choroidal layers in chronic angle-closure glaucoma. The ratio of small-vessel layer thickness to total choroidal thickness increased (P layer and Haller's layer thickness to total choroidal thickness decreased. A higher ratio of small-vessel layer thickness to total choroidal thickness was significantly associated with a lower prevalence of AMD (early type, intermediate type, late geographic type). Axial elongation-associated and aging-associated choroidal thinning affected Haller's and Sattler's layers more markedly than the small-vessel layer. Non-exudative and exudative AMD, except for geographic atrophy, was associated with slightly increased choroidal thickness.

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.

Treatment of age-related subfoveal choroidal neovascularization by low-dose external radiation. A preliminary study

Energy Technology Data Exchange (ETDEWEB)

Harino, Seiyo; Oshima, Yusuke; Tsujikawa, Kaoru; Oh, Ami; Sugimoto, Kiyoshi [Yodogawa Christian Hospital, Osaka (Japan); Murayama, Shigeyuki; Inoue, Toshihiko

1997-04-01

We applied low dose external beam radiation (6MV) to 17 eyes of 17 patients (Mean age 70.9 years, range 58-85) who had subfoveal choroidal neovascularization associated with age-related macular degeneration. None of the cases were suitable for photocoagulation according to the Macular Photo-coagulation Study protocol, and no feeding vessels underlying choroidal neovascular membrane could be detected. Corrected visual acuity ranged from 0.02 to 0.6 before treatment. The patients were divided into two groups. One group of 11 eyes was treated with 10 Gy and the other group of 6 eyes with 21 Gy. Mean follow up period was 347{+-}89 (mean{+-}standard deviation) days in the 10 Gy group and 312{+-}100 days in the 21 Gy group. We evaluated the outcome as `effective` if no progression in neovascular membrane was found by ophthalmoscopic and angiographic examination. Only 3 eyes (21%) of patients in the 10 Gy group and 2 eyes (33%) in 21 Gy group showed any effect. Although the rate of progression in choroidal neovascular membrane was significantly smaller in the 10 and 21 Gy group than in the controls, the corrected visual acuity in the treated group was not improved over that of the controls. No serious complications were seen. Only one case showed a stabilized neovascular membrane in the control group of 7 patients. Although the present results seem to be worse than those in previous reports, the efficacy of this treatment still needs to be evaluated because no beneficial strategies in the treatment of subfoveal neovascularization have been established. (author)

Prevalence of left-sided melanomas in an Irish population.

LENUS (Irish Health Repository)

de Blacam, C

2012-02-01

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

Prevalence of left-sided melanomas in an Irish population.

LENUS (Irish Health Repository)

de Blacam, C

2011-04-17

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

Microneurosurgical management of anterior choroid artery aneurysms.

Science.gov (United States)

Lehecka, Martin; Dashti, Reza; Laakso, Aki; van Popta, Jouke S; Romani, Rossana; Navratil, Ondrej; Kivipelto, Leena; Kivisaari, Riku; Foroughi, Mansoor; Kokuzawa, Jouji; Lehto, Hanna; Niemelä, Mika; Rinne, Jaakko; Ronkainen, Antti; Koivisto, Timo; Jääskelainen, Juha E; Hernesniemi, Juha

2010-05-01

Anterior choroid artery aneurysms (AChAAs) constitute 2%-5% of all intracranial aneurysms. They are usually small, thin walled with one or several arteries originating at their base, and often associated with multiple aneurysms. In this article, we review the practical microsurgical anatomy, the preoperative imaging, surgical planning, and the microneurosurgical steps in the dissection and the clipping of AChAAs. This review, and the whole series on intracranial aneurysms (IAs), are mainly based on the personal microneurosurgical experience of the senior author (J.H.) in two Finnish centers (Helsinki and Kuopio) that serve, without patient selection, the catchment area in Southern and Eastern Finland. These two centers have treated more than 10,000 patients with IAs since 1951. In the Kuopio Cerebral Aneurysm Database of 3005 patients with 4253 IAs, 831 patients (28%) had altogether 980 internal carotid artery (ICA) aneurysms, of whom 95 patients had 99 (2%) AChAAs. Ruptured AChAAs, found in 39 patients (41%), with median size of 6 mm (range = 2-19 mm), were associated with intracerebral hematoma (ICH) in only 1 (3%) patient. Multiple aneurysms were seen in 58 (61%) patients. The main difficulty in microneurosurgical management of AChAAs is to preserve flow in the anterior choroid artery originating at the base and often attached to the aneurysm dome. This necessitates perfect surgical strategy based on preoperative knowledge of 3 dimensional angioarchitecture and proper orientation during the microsurgical dissection. Copyright © 2010 Elsevier Inc. All rights reserved.

Response of melanoma tumor phospholipid metabolism to chloroethyle nitrosourea: a high resolution proton NMR spectroscopy study.

Science.gov (United States)

Morvan, Daniel; Demidem, Aïcha; Madelmont, Jean-Claude

2003-07-01

Phospholipid metabolism is tightly involved in tumor growth regulation and tumor cell survival. The response of phospholipid metabolism to chloroethyle nitrosourea treatment is investigated in a murine B16 melanoma model. Measurements of phospholipid derivatives are performed on intact tumor tissue samples using one- and two-dimensional proton NMR spectroscopy. During the tumor growth inhibition phase under treatment, tumors overexpress phosphocholine, phosphoethanolamine, glycerophosphocholine and glycerophosphoethanolamine, whereas phosphatidylcholine and phosphatidylethanolamine levels are maintained to control levels. During re-growth, which remained quantitatively much below control growth, chloroethyle nitrosourea-treated melanoma tumors overexpress phosphocholine and phosphoethanolamine only. In treated melanoma, phosphatidylcholine levels show an inverse relationship with tumor growth rates. In conclusion, chloroethyle nitrosourea-treated melanoma tumors maintain their phosphatidylcholine levels and exhibit transformed phospholipid metabolism phenotype, by mechanisms that could participate in tumor cell survival.

Swept-Source Optical Coherence Tomographic Findings of Choroidal Osteoma

Directory of Open Access Journals (Sweden)

Yuki Hayashi

2014-07-01

Full Text Available Purpose: To report the morphologic features of a choroidal osteoma using swept-source optical coherence tomography (SS-OCT and fundus autofluorescence (FAF. Methods: Two eyes of two cases with a choroidal osteoma were studied using SS-OCT and FAF. Results: The location of the tumor was circumpapillary without macular involvement in case 1 and juxtapapillary with macular involvement in case 2. Both cases had a mixture of calcified and decalcified areas, and a concomitant choroidal neovascularization was found in case 2. The FAF images showed decreased autofluorescence in the central decalcified regions and relatively preserved fluorescence in marginal calcified regions in both cases. SS-OCT revealed a normal inner retina and an abnormal outer retina in both cases, and subretinal fluid in case 2. The calcified regions appeared sponge-like and were multilayered in case 2. A lamellar reflective pattern was observed in the decalcified regions in case 1, and hyperreflective mound-like areas were observed in both cases. SS-OCT demonstrated hyperreflective areas above Bruch's membrane accompanied by disruption of Bruch's membrane in case 1. The chorioscleral border was visible in both cases. Conclusions: The FAF pattern in the calcified and decalcified areas of the choroidal osteoma may correspond to the different stage of tumor evolution. The SS-OCT findings indicate that choroidal osteomas can have characteristic reflective patterns and alterations of the overlying retina.

ADAM15 expression is downregulated in melanoma metastasis compared to primary melanoma

International Nuclear Information System (INIS)

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

2010-01-01

Research highlights: → Strong ADAM15 expression is found in normal melanocytes. → ADAM15 expression is significantly downregulated in patients with melanoma metastasis. → TGF-β can downregulate ADAM15 expression in melanoma cells. → Overexpression of ADAM15 in melanoma cells inhibits migration, proliferation and invasion of melanoma cells. → Conclusion: ADAM15 represents an tumor suppressor protein in melanoma. -- Abstract: In a mouse melanoma metastasis model it has been recently shown that ADAM15 overexpression in melanoma cells significantly reduced the number of metastatic nodules on the lung. Unfortunately, the expression of ADAM15 in human melanoma tissue has not been determined so far. In our study, we characterized the expression of ADAM15 in tissue micro-arrays of patients with primary melanoma with melanoma metastasis. ADAM15 was expressed in melanocytes and endothelial cells of benign nevi and melanoma tissue. Importantly, ADAM15 was significantly downregulated in melanoma metastasis compared to primary melanoma. We further demonstrate that IFN-γ and TGF-β downregulate ADAM15 protein levels in melanoma cells. To investigate the role of ADAM15 in melanoma progression, we overexpressed ADAM15 in melanoma cells. Importantly, overexpression of ADAM15 in melanoma cells reduced the migration, invasion and the anchorage dependent and independent cell growth of melanoma cells. In summary, the downregulation of ADAM15 plays an important role in melanoma progression and ADAM15 act as a tumorsuppressor in melanoma.

ADAM15 expression is downregulated in melanoma metastasis compared to primary melanoma

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

2010-10-22

Research highlights: {yields} Strong ADAM15 expression is found in normal melanocytes. {yields} ADAM15 expression is significantly downregulated in patients with melanoma metastasis. {yields} TGF-{beta} can downregulate ADAM15 expression in melanoma cells. {yields} Overexpression of ADAM15 in melanoma cells inhibits migration, proliferation and invasion of melanoma cells. {yields} Conclusion: ADAM15 represents an tumor suppressor protein in melanoma. -- Abstract: In a mouse melanoma metastasis model it has been recently shown that ADAM15 overexpression in melanoma cells significantly reduced the number of metastatic nodules on the lung. Unfortunately, the expression of ADAM15 in human melanoma tissue has not been determined so far. In our study, we characterized the expression of ADAM15 in tissue micro-arrays of patients with primary melanoma with melanoma metastasis. ADAM15 was expressed in melanocytes and endothelial cells of benign nevi and melanoma tissue. Importantly, ADAM15 was significantly downregulated in melanoma metastasis compared to primary melanoma. We further demonstrate that IFN-{gamma} and TGF-{beta} downregulate ADAM15 protein levels in melanoma cells. To investigate the role of ADAM15 in melanoma progression, we overexpressed ADAM15 in melanoma cells. Importantly, overexpression of ADAM15 in melanoma cells reduced the migration, invasion and the anchorage dependent and independent cell growth of melanoma cells. In summary, the downregulation of ADAM15 plays an important role in melanoma progression and ADAM15 act as a tumorsuppressor in melanoma.

Ocular Melanoma

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

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

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2018-04-26

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

Efficient adenovector CD40 ligand immunotherapy of canine malignant melanoma.

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

2008-05-01

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

Communication about melanoma and risk reduction after melanoma diagnosis.

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

2017-12-01

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

Vitamin D and melanoma: state of the art and possible therapeutic uses.

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Paolino, Giovanni; Moliterni, Elisa; Corsetti, Paola; Didona, Dario; Bottoni, Ugo; Calvieri, Stefano; Mattozzi, Carlo

2017-12-15

Despite the presence of several studies in literature, the real connection between vitamin D serological levels, vitamin D receptor and melanoma remains unclear, probably because of the complex correlation between vitamin D and melanoma. Indeed, UV radiations are not reported as the main risk factor for melanoma in non-sun-exposed, while systemic immunosuppression, anatomical and physiological features may contribute to malignancy. Therefore, the correlation between melanoma cells in sun- exposed areas and vitamin D, as well as vitamin D receptor could be different from the one in melanoma of sun-shielded sites. These differences may also explain the controversial results reported in the literature regarding the correlation between melanoma and vitamin D, as well as the different outcomes in melanoma patients treated with vitamin D as adjuvant therapy. The aim of this review is to highlight the most recent findings about vitamin D and melanoma, focusing on the anatomic site of the primary tumor as well as on the possible therapeutic uses of vitamin D in melanoma patients.

High accuracy of family history of melanoma in Danish melanoma cases

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

2015-01-01

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

Choroidal metastasis from early rectal cancer: Case report and literature review

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Mitsuyoshi Tei

2014-01-01

CONCLUSION: This is the first report of choroidal metastasis from early rectal cancer. We consider it important to enforce systemic chemotherapy in addition to radiotherapy for choroidal metastasis from colorectal cancer.

Real-time in vivo micromorphology and histopathology of choroidal osteoma using enhanced depth imaging

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Rameez Hussain

2015-01-01

Full Text Available Choroidal osteoma is a usually unilateral benign tumor of the choroid composed of mature bone. Optical coherence tomography (OCT has been used to image osteoma for several years. With the advent of enhanced depth imaging (EDI feature of spectral-domain OCT (SD-OCT, better visualization of the morphology of choroidal lesions has been possible. Herein we present a case of choroidal osteoma in a 45-year-old woman, wherein in vivo morphology of the choroidal osteoma had been visualized using EDI technique of SD-OCT before and after performing photodynamic therapy. EDI OCT has proven to be a valuable noninvasive imaging modality, almost comparable to histopathological examination, for diagnosing choroidal osteomas and for providing an insight into the in vivo micromorphological changes occurring during the course of the disease.

MULTIFOCAL CHOROIDITIS IN DISSEMINATED SPOROTRICHOSIS IN PATIENTS WITH HIV/AIDS.

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Biancardi, Ana L; Freitas, Dayvison F S; Valviesse, Vitor R G de A; Andrade, Hugo B; de Oliveira, Manoel M E; do Valle, Antonio C F; Zancope-Oliveira, Rosely M; Galhardo, Maria C G; Curi, Andre L L

2017-01-01

In this article, the authors describe multifocal choroiditis related to disseminated sporotrichosis in patients with HIV/AIDS. We conducted a retrospective observational study of three patients infected with HIV who presented with disseminated sporotrichosis characterized by cutaneous lesions, multifocal choroiditis, and other manifestations, including osteomyelitis and involvement of the bone marrow, larynx, pharynx, and nasal and oral mucosa. Five eyes of three patients with HIV/AIDS showed multifocal choroiditis related to disseminated sporotrichosis. The CD4 counts ranged from 25 to 53 mm. All patients were asymptomatic visually. The ocular disease was bilateral in two patients. The lesion size ranged from 1/3 to 2 disc diameters. None of the patients had vitritis. Of the 12 lesions, 9 were localized in the posterior pole (Zone 1) and 3 were localized in the mild periphery (Zone 2). Multifocal choroiditis due to disseminated sporotrichosis can occur in profoundly immunosuppressed patients with HIV/AIDS.

Interocular Symmetry in Macular Choroidal Thickness in Children

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Christiane Al-Haddad

2014-01-01

Full Text Available Objective. To report interocular differences in choroidal thickness in children using spectral domain optical coherence tomography (SD-OCT and correlate findings with biometric data. Methods. This observational cross-sectional study included 91 (182 eyes healthy children aged 6 to 17 years with no ocular abnormality except refractive error. After a comprehensive eye exam and axial length measurement, high definition macular scans were performed using SD-OCT. Two observers manually measured the choroidal thickness at the foveal center and at 1500 µm nasally, temporally, inferiorly, and superiorly. Interocular differences were computed; correlations with age, gender, refractive error, and axial length were performed. Results. Mean age was 10.40 ± 3.17 years; mean axial length and refractive error values were similar between fellow eyes. There was excellent correlation between the two observers’ measurements. No significant interocular differences were observed at any location. There was only a trend for right eyes to have higher values in all thicknesses, except the superior thickness. Most of the choroidal thickness measurements correlated positively with spherical equivalent but not with axial length, age, or gender. Conclusion. Choroidal thickness measurements in children as performed using SD-OCT revealed a high level of interobserver agreement and consistent interocular symmetry. Values correlated positively with spherical equivalent refraction.

Interocular symmetry in macular choroidal thickness in children.

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Al-Haddad, Christiane; El Chaar, Lama; Antonios, Rafic; El-Dairi, Mays; Noureddin, Baha'

2014-01-01

Objective. To report interocular differences in choroidal thickness in children using spectral domain optical coherence tomography (SD-OCT) and correlate findings with biometric data. Methods. This observational cross-sectional study included 91 (182 eyes) healthy children aged 6 to 17 years with no ocular abnormality except refractive error. After a comprehensive eye exam and axial length measurement, high definition macular scans were performed using SD-OCT. Two observers manually measured the choroidal thickness at the foveal center and at 1500 µm nasally, temporally, inferiorly, and superiorly. Interocular differences were computed; correlations with age, gender, refractive error, and axial length were performed. Results. Mean age was 10.40 ± 3.17 years; mean axial length and refractive error values were similar between fellow eyes. There was excellent correlation between the two observers' measurements. No significant interocular differences were observed at any location. There was only a trend for right eyes to have higher values in all thicknesses, except the superior thickness. Most of the choroidal thickness measurements correlated positively with spherical equivalent but not with axial length, age, or gender. Conclusion. Choroidal thickness measurements in children as performed using SD-OCT revealed a high level of interobserver agreement and consistent interocular symmetry. Values correlated positively with spherical equivalent refraction.

Fever and the use of paracetamol during IL-2-based immunotherapy in metastatic melanoma

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Køstner, Anne Helene; Ellegaard, Mai-Britt Bjørklund; Christensen, Ib Jarle

2015-01-01

effective antitumor immune response. The purpose of this retrospective study was to examine the potential role of the IL-2-induced fever in melanoma patients treated with or without paracetamol in two consecutive cohorts. One hundred and seventy-nine patients with metastatic melanoma treated with a modified...... decrescendo regimen of IL-2 and Interferon (IFN) between 2004 and 2010 were retrospectively studied. 87 patients treated before 2007 received paracetamol as part of the treatment schedule, and 92 patients treated after 2007 did not receive paracetamol routinely. Body temperature was analyzed as dichotomized...

Radiation therapy for small choroidal neovascularization in age-related macular degeneration

International Nuclear Information System (INIS)

Matsuhashi, Hideaki; Noda, Yasuko; Takahashi, Daisuke; Mariya, Yasushi

2000-01-01

The purpose of this study was to evaluate the effects of radiation therapy on age-related macular degeneration with subfoveal or juxtafoveal choroidal neovascularization ≤1 disc area. Fourteen patients (14 eyes) received a total radiation dose of 10-20 Gy in 5-10 fractions. The mean follow-up time was 22 months. Ten patients (10 eyes) in a control group were followed up for an average of 16 months without treatment. At a 12-month posttreatment examination, funduscopic and angiographic findings showed improvement in 7 eyes (50%), no change in 1 eye (7%), and deterioration in 6 eyes (43%) among the treated patients. The same findings demonstrated improvement in 1 eye (10%), no change in 2 eyes (20%), and deterioration in 7 eyes (70%) among the control patients. This difference was determined to be statistically significant between the two groups by the Mann-Whitney U-test. Visual acuity had improved in 4 eyes (29%), was unchanged in 6 eyes (43%), and had declined in 4 eyes (29%), among the treated patients. Among the control patients, visual acuity had improved in none of the eyes (0%), was unchanged in 6 eyes (60%), and had declined in 4 eyes (40%). The difference in visual acuity between the two groups was not statistically significant. Radiation therapy inhibited small choroidal neovascularization, as seen by funduscopy and angiography, but its effectiveness in improving visual prognosis was not always evident. (author)

Radiation therapy for small choroidal neovascularization in age-related macular degeneration

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Matsuhashi, Hideaki; Noda, Yasuko; Takahashi, Daisuke; Mariya, Yasushi [Hirosaki Univ., Aomori (Japan). School of Medicine

2000-12-01

The purpose of this study was to evaluate the effects of radiation therapy on age-related macular degeneration with subfoveal or juxtafoveal choroidal neovascularization {<=}1 disc area. Fourteen patients (14 eyes) received a total radiation dose of 10-20 Gy in 5-10 fractions. The mean follow-up time was 22 months. Ten patients (10 eyes) in a control group were followed up for an average of 16 months without treatment. At a 12-month posttreatment examination, funduscopic and angiographic findings showed improvement in 7 eyes (50%), no change in 1 eye (7%), and deterioration in 6 eyes (43%) among the treated patients. The same findings demonstrated improvement in 1 eye (10%), no change in 2 eyes (20%), and deterioration in 7 eyes (70%) among the control patients. This difference was determined to be statistically significant between the two groups by the Mann-Whitney U-test. Visual acuity had improved in 4 eyes (29%), was unchanged in 6 eyes (43%), and had declined in 4 eyes (29%), among the treated patients. Among the control patients, visual acuity had improved in none of the eyes (0%), was unchanged in 6 eyes (60%), and had declined in 4 eyes (40%). The difference in visual acuity between the two groups was not statistically significant. Radiation therapy inhibited small choroidal neovascularization, as seen by funduscopy and angiography, but its effectiveness in improving visual prognosis was not always evident. (author)

Cell Behaviors during Closure of the Choroid Fissure in the Developing Eye

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Gaia Gestri

2018-02-01

Full Text Available Coloboma is a defect in the morphogenesis of the eye that is a consequence of failure of choroid fissure fusion. It is among the most common congenital defects in humans and can significantly impact vision. However, very little is known about the cellular mechanisms that regulate choroid fissure closure. Using high-resolution confocal imaging of the zebrafish optic cup, we find that apico-basal polarity is re-modeled in cells lining the fissure in proximal to distal and inner to outer gradients during fusion. This process is accompanied by cell proliferation, displacement of vasculature, and contact between cells lining the choroid fissure and periocular mesenchyme (POM. To investigate the role of POM cells in closure of the fissure, we transplanted optic vesicles onto the yolk, allowing them to develop in a situation where they are depleted of POM. The choroid fissure forms normally in ectopic eyes but fusion fails in this condition, despite timely apposition of the nasal and temporal lips of the retina. This study resolves some of the cell behaviors underlying choroid fissure fusion and supports a role for POM in choroid fissure fusion.

Components in aqueous Hibiscus rosa-sinensis flower extract inhibit in vitro melanoma cell growth

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Karina H. Goldberg

2017-01-01

Full Text Available Skin cancer is extremely common, and melanoma causes about 80% of skin cancer deaths. In fact, melanoma kills over 50 thousand people around the world each year, and these numbers are rising. Clearly, standard treatments are not effectively treating melanoma, and alternative therapies are needed to address this problem. Hibiscus tea has been noted to have medicinal properties, including anticancer effects. Extracts from Hibiscus have been shown to inhibit the growth of a variety of cancer cells. In particular, recent studies found that polyphenols extracted from Hibiscus sabdariffa by organic solvents can inhibit melanoma cell growth. However, effects of aqueous extracts from Hibiscus rosa-sinesis flowers, which are commonly used to make traditional medicinal beverages, have not been examined on melanoma cells. Here, we report that aqueous H. rosa-sinesis flower extract contains compounds that inhibit melanoma cell growth in a dose dependent manner at concentrations that did not affect the growth of nontransformed cells. In addition, these extracts contain low molecular weight growth inhibitory compounds below 3 kD in size that combine with larger compounds to more effectively inhibit melanoma cell growth. Future work should identify these compounds, and evaluate their potential to prevent and treat melanoma and other cancers.

Requirement for Innate Immunity and CD90+ NK1.1− Lymphocytes to Treat Established Melanoma with Chemo-Immunotherapy

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Moskalenko, Marina; Pan, Michael; Fu, Yichun; de Moll, Ellen H.; Hashimoto, Daigo; Mortha, Arthur; Leboeuf, Marylene; Jayaraman, Padmini; Bernardo, Sebastian; Sikora, Andrew G.; Wolchok, Jedd; Bhardwaj, Nina; Merad, Miriam; Saenger, Yvonne

2015-01-01

We sought to define cellular immune mechanisms of synergy between tumor-antigen–targeted monoclonal antibodies and chemotherapy. Established B16 melanoma in mice was treated with cytotoxic doses of cyclophosphamide in combination with an antibody targeting tyrosinase-related protein 1 (αTRP1), a native melanoma differentiation antigen. We find that Fcγ receptors are required for efficacy, showing that antitumor activity of combination therapy is immune mediated. Rag1−/− mice deficient in adaptive immunity are able to clear tumors, and thus innate immunity is sufficient for efficacy. Furthermore, previously treated wild-type mice are not significantly protected against tumor reinduction, as compared with mice inoculated with irradiated B16 alone, consistent with a primarily innate immune mechanism of action of chemo-immunotherapy. In contrast, mice deficient in both classical natural killer (NK) lymphocytes and nonclassical innate lymphocytes (ILC) due to deletion of the IL2 receptor common gamma chain IL2γc−/−) are refractory to chemo-immunotherapy. Classical NK lymphocytes are not critical for treatment, as depletion of NK1.1+ cells does not impair antitumor effect. Depletion of CD90+NK1.1− lymphocytes, however, both diminishes therapeutic benefit and decreases accumulation of macrophages within the tumor. Tumor clearance during combination chemo-immunotherapy with monoclonal antibodies against native antigen is mediated by the innate immune system. We highlight a novel potential role for CD90+NK1.1− ILCs in chemo-immunotherapy. PMID:25600438

Successful Treatment of Nivolumab-Resistant Multiple In-Transit Melanomas with Ipilimumab and Topical Imiquimod

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Taku Fujimura

2018-01-01

Full Text Available Simultaneous or sequential, planned administration of ipilimumab could significantly enhance the antitumor effects of nivolumab in advanced melanoma patients. On the other hand, the efficacy of ipilimumab for nivolumab-resistant advanced melanoma is extremely poor. Therefore, additional supportive therapy for anti-PD-1 antibody therapy-resistant advanced melanoma has been widely investigated. In this report, we describe a case of multiple in-transit melanomas developing in a nivolumab-resistant patient successfully treated with ipilimumab in combination with imiquimod. Our present case suggested a possible therapy for nivolumab-resistant multiple in-transit melanomas using ipilimumab in combination with topical imiquimod.

Choroidal thickness in patients with fibromyalgia and correlation with disease severity

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Mahmut Oguz Ulusoy

2018-01-01

Full Text Available Purpose: To evaluate and compare choroidal thickness in patients with fibromyalgia (FM and healthy controls. Methods: In this prospective, cross-sectional study, forty eyes of 40 patients with FM and 40 eyes of 40 age- and sex-matched healthy subjects were enrolled. FM was diagnosed according to the American College of Rheumatology criteria. The choroidal thickness measurements of the subjects were obtained using spectral-domain optical coherence tomography (RTVue-100, Optovue. Widespread pain index (WPI, symptom severity scale (SSS, and fibromyalgia impact questionnaire (FIQ scores were recorded. The choroidal thickness measurements of the groups were compared, and correlations among the WPI, SSS, and FIQ scores and these measurements were calculated. Results: Choroidal thicknesses at 1500 μm nasally were 198.5 ± 46.7 μm and 306.3 ± 85.4 μm; at 1000 μm nasally were 211.7 ± 50.2 μm and 310.05 ± 87.26 μm; at 500 μm nasally were 216 ± 55.05 μm and 311.5 ± 83.4 μm; at subfoveal region were 230.9 ± 58.4 μm and 332.4 ± 91.3 μm; at 500 μm temporally 227.5 ± 58.1 μm and 318.15 ± 92.3 μm; at 1000 μm temporally 224.5 ± 57.07 μm and 315.1 ± 84.2 μm; at 1500 μm temporally 212.5 ± 56.08 μm and 312.9 ± 87.8 μm in the FM and control groups, respectively (P < 0.001. Choroidal thicknesses were thinner at all measurement location, except temporal 1000 and 1500 in patients with FIQ score ≥50 than in FIQ score <50. Conclusion: The results of this study demonstrated that choroidal thickness decreases in patients with FM and correlated with disease activity. This choroidal changes might be related with the alterations in autonomic nervous system functioning. Further studies are needed to evaluate the etiopathologic relationship between choroidal thickness and FM.

X-ray induced dysplasia in the developing telencephalic choroid plexus of mice exposed in utero

International Nuclear Information System (INIS)

Heinzmann, U.

1982-01-01

Pregnant NMRI-mice were X-irradiated with single doses of 0.95 Gy (100 R) and 1.9 Gy (200 R) on day of gestation (dg) 12. For sampling, anesthetized animals were perfused with buffered glutaraldehyde solution or fixed by immersion in Karnovsky solution. LM, SEM, and TEM studies were carried out on brains prenatally and up to the age of 20 months to follow the radiation effects on the developing lateral choroid plexus. Radiation-induced changes were found using all three methods and at all stages studied. The normally sickle-shaped and stretched choroid plexus is shortened and irregular, and the dome-shaped plexus cells are flattened. Their superficial fine structures, i.e., the microvilli and cilia, are altered. Three stages of severity can be distinguished and the internal hydromicrocephalus increases from stage I to III. Intercellular spaces of the treated plexus epithelium are often dilated, but the tight junctions at the ventricular surface seem to be intact. The interstitium shows large dilations in comparison with the controls. Thus, gross changes and alterations in the fine structure can be induced in the choroid plexus by doses of 0.95 Gy and 1.9 Gy, which persist throughout postnatal life

3H-dextran method for measurements of the blood volume in the rat choroid

International Nuclear Information System (INIS)

Matsusaka, Toshihiko; Morimoto, Kazuhiro; Kikkawa, Yoshizo.

1980-01-01

A new method was developed using 3 H-dextran for measuring the blood volume in the choroid. Under pentobarbital-anesthesia, albino rats weighing 200 grams were perfused through the left ventricle with a 2.5 percent glutaraldehyde solution containing the radioactive dextran. The procedure allowed exchange of the choroidal blood with the 3 H-dextran solution with a simultaneous fixation of the choroid. The blood volume in the choroid was calculated from the radioactivity count, which is estimated to be 1.690 x 10 -4 ml per mg wet weight and 5.070 x 10 -4 ml per mg dry weight. Epinephrine subconjunctivally injected diminished the blood volume in the choroid by 68 percent. Pretreatment with lidocaine almost nullified the effect of epinephrine. Applicability of this method to the analytical study of the choroidal circulation is discussed. (author)

A Proinflammatory Function of Toll-Like Receptor 2 in the Retinal Pigment Epithelium as a Novel Target for Reducing Choroidal Neovascularization in Age-Related Macular Degeneration.

Science.gov (United States)

Feng, Lili; Ju, Meihua; Lee, Kei Ying V; Mackey, Ashley; Evangelista, Mariasilvia; Iwata, Daiju; Adamson, Peter; Lashkari, Kameran; Foxton, Richard; Shima, David; Ng, Yin Shan

2017-10-01

Current treatments for choroidal neovascularization, a major cause of blindness for patients with age-related macular degeneration, treat symptoms but not the underlying causes of the disease. Inflammation has been strongly implicated in the pathogenesis of choroidal neovascularization. We examined the inflammatory role of Toll-like receptor 2 (TLR2) in age-related macular degeneration. TLR2 was robustly expressed by the retinal pigment epithelium in mouse and human eyes, both normal and with macular degeneration/choroidal neovascularization. Nuclear localization of NF-κB, a major downstream target of TLR2 signaling, was detected in the retinal pigment epithelium of human eyes, particularly in eyes with advanced stages of age-related macular degeneration. TLR2 antagonism effectively suppressed initiation and growth of spontaneous choroidal neovascularization in a mouse model, and the combination of anti-TLR2 and antivascular endothelial growth factor receptor 2 yielded an additive therapeutic effect on both area and number of spontaneous choroidal neovascularization lesions. Finally, in primary human fetal retinal pigment epithelium cells, ligand binding to TLR2 induced robust expression of proinflammatory cytokines, and end products of lipid oxidation had a synergistic effect on TLR2 activation. Our data illustrate a functional role for TLR2 in the pathogenesis of choroidal neovascularization, likely by promoting inflammation of the retinal pigment epithelium, and validate TLR2 as a novel therapeutic target for reducing choroidal neovascularization. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Involvement of ER stress and activation of apoptotic pathways in fisetin induced cytotoxicity in human melanoma.

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Syed, Deeba N; Lall, Rahul K; Chamcheu, Jean Christopher; Haidar, Omar; Mukhtar, Hasan

2014-12-01

The prognosis of malignant melanoma remains poor in spite of recent advances in therapeutic strategies for the deadly disease. Fisetin, a dietary flavonoid is currently being investigated for its growth inhibitory properties in various cancer models. We previously showed that fisetin inhibited melanoma growth in vitro and in vivo. Here, we evaluated the molecular basis of fisetin induced cytotoxicity in metastatic human melanoma cells. Fisetin treatment induced endoplasmic reticulum (ER) stress in highly aggressive A375 and 451Lu human melanoma cells, as revealed by up-regulation of ER stress markers including IRE1α, XBP1s, ATF4 and GRP78. Time course analysis indicated that the ER stress was associated with activation of the extrinsic and intrinsic apoptotic pathways. Fisetin treated 2-D melanoma cultures displayed autophagic response concomitant with induction of apoptosis. Prolonged treatment (16days) with fisetin in a 3-D reconstituted melanoma model resulted in inhibition of melanoma progression with significant apoptosis, as evidenced by increased staining of cleaved Caspase-3 in the treated constructs. However, no difference in the expression of autophagic marker LC-3 was noted between treated and control groups. Fisetin treatment to 2-D melanoma cultures resulted in phosphorylation and activation of the multifunctional AMP-activated protein kinase (AMPK) involved in the regulation of diverse cellular processes, including autophagy and apoptosis. Silencing of AMPK failed to prevent cell death indicating that fisetin induced cytotoxicity is mediated through both AMPK-dependent and -independent mechanisms. Taken together, our studies confirm apoptosis as the primary mechanism through which fisetin inhibits melanoma cell growth and that activation of both extrinsic and intrinsic pathways contributes to fisetin induced cytotoxicity.

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

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

2010-06-01

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

Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes in Advanced Melanoma Patients

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Mélanie Saint-Jean

2018-01-01

Full Text Available Immunotherapy for melanoma includes adoptive cell therapy with autologous tumor-infiltrating lymphocytes (TILs. This monocenter retrospective study was undertaken to evaluate the efficacy and safety of this treatment of patients with advanced melanoma. All advanced melanoma patients treated with TILs using the same TIL expansion methodology and same treatment interleukin-2 (IL-2 regimen between 2009 and 2012 were included. After sterile intralesional excision of a cutaneous or subcutaneous metastasis, TILs were produced according to a previously described method and then infused into the patient who also received a complementary subcutaneous IL-2 regimen. Nine women and 1 man were treated for unresectable stage IIIC (n=4 or IV (n=6 melanoma. All but 1 patient with unresectable stage III melanoma (1st line had received at least 2 previous treatments, including anti-CTLA-4 antibody for 4. The number of TILs infused ranged from 0.23 × 109 to 22.9 × 109. Regarding safety, no serious adverse effect was reported. Therapeutic responses included a complete remission, a partial remission, 2 stabilizations, and 6 progressions. Among these 4 patients with clinical benefit, 1 is still alive with 9 years of follow-up and 1 died from another cause after 8 years of follow-up. Notably, patients treated with high percentages of CD4 + CD25 + CD127lowFoxp3+ T cells among their TILs had significantly shorter OS. The therapeutic effect of combining TILs with new immunotherapies needs further investigation.

Synchronous high-risk melanoma and lymphoid neoplasia.

LENUS (Irish Health Repository)

Cahill, R A

2012-02-03

Large population-based studies have shown a significant association between melanoma and lymphoid neoplasia, particularly non-Hodgkin\\'s lymphoma (NHL) and chronic lymphocytic leukaemia (CLL), that is independent of any treatment received for the initial tumour. This study examines the presentation, diagnosis, treatment and progress of three patients who developed advanced melanoma concurrently with a lymphoid neoplasm (one NHL, two CLLs), in order to illustrate their association, discuss common aetiological factors and examine possible therapeutic options. As it is the melanoma rather than the lymphoid neoplasm that represents the bigger threat to overall survival, initial treatment should be targeted towards this cancer. However, because of the interplay between the diseases and the possible side-effects of the various treatments, the choice of adjuvant therapy requires careful consideration. Immunosuppression associated with chemotherapy may permit a more aggressive course for the melanoma, while locoregional radiotherapy is contraindicated following lymph node dissections. As immunotherapy is of benefit in the treatment of melanoma and has also been recently shown to be effective in the management of lymphoid neoplasia, we instituted interferon-alpha as adjuvant therapy for these patients, thereby utilizing a single agent to treat the dual pathologies. The three patients have now been followed-up for 6 months without evidence of disease recurrence or progression.

Automatic segmentation of the choroid in enhanced depth imaging optical coherence tomography images.

Science.gov (United States)

Tian, Jing; Marziliano, Pina; Baskaran, Mani; Tun, Tin Aung; Aung, Tin

2013-03-01

Enhanced Depth Imaging (EDI) optical coherence tomography (OCT) provides high-definition cross-sectional images of the choroid in vivo, and hence is used in many clinical studies. However, the quantification of the choroid depends on the manual labelings of two boundaries, Bruch's membrane and the choroidal-scleral interface. This labeling process is tedious and subjective of inter-observer differences, hence, automatic segmentation of the choroid layer is highly desirable. In this paper, we present a fast and accurate algorithm that could segment the choroid automatically. Bruch's membrane is detected by searching the pixel with the biggest gradient value above the retinal pigment epithelium (RPE) and the choroidal-scleral interface is delineated by finding the shortest path of the graph formed by valley pixels using Dijkstra's algorithm. The experiments comparing automatic segmentation results with the manual labelings are conducted on 45 EDI-OCT images and the average of Dice's Coefficient is 90.5%, which shows good consistency of the algorithm with the manual labelings. The processing time for each image is about 1.25 seconds.

Xenogeneic murine tyrosinase DNA vaccine for malignant melanoma of the digit of dogs.

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Manley, C A; Leibman, N F; Wolchok, J D; Rivière, I C; Bartido, S; Craft, D M; Bergman, P J

2011-01-01

Malignant melanoma of dogs is a highly aggressive neoplasm and is the 2nd most common digit tumor. Metastatic disease is a common sequela for which few effective treatment options exist. Studies show that xenogeneic tyrosinase DNA vaccination yields immune responses and prolongation of survival in dogs with oral malignant melanoma. Describe clinical findings and tumor characteristics of a cohort of dogs with digit malignant melanoma, and evaluate the prognostic utility of a proposed staging system. Determine if a novel xenogeneic DNA vaccine is safe and potentially effective for treatment of dogs with digit melanoma. Fifty-eight dogs with digit malignant melanoma treated at the Animal Medical Center between 2004 and 2007. Retrospective, medical records review of dogs with digit melanoma treated with xenogeneic DNA vaccine. Overall median survival time (MST) for dogs treated with loco-regional control and xenogeneic DNA vaccine was 476 days with a 1-year survival rate of 63%. MST for dogs presenting with metastasis was 105 days versus 533 days for dogs presenting without metastasis (P dogs in the latter group were alive at 2 and 3 years. A proposed staging system proved prognostic with stages I-IV dogs surviving >952, >1,093, 321, and 76 days, respectively. The xenogeneic murine tyrosinase DNA vaccine was safe and appears effective when used in conjunction with local and regional disease control. The proposed staging system was prognostic in this study and future studies might benefit from utilizing this staging system. Copyright © 2010 by the American College of Veterinary Internal Medicine.

Real-world treatment patterns and outcomes among metastatic cutaneous melanoma patients treated with ipilimumab.

Science.gov (United States)

Mohr, P; Ascierto, P; Arance, A; McArthur, G; Hernaez, A; Kaskel, P; Shinde, R; Stevinson, K

2018-06-01

There is a scarcity of real-world data on treatment patterns and outcomes among advanced melanoma patients treated with immunotherapies including ipilimumab, an anti-CTLA-4 antibody approved since 2011. To evaluate ipilimumab and postipilimumab treatment patterns and outcomes among patients with advanced melanoma in Australia, Germany, Italy and Spain, following regulatory approval. Retrospective multicentre, multinational, observational chart review study. Data were extracted from the start of ipilimumab therapy until the end of at least 40 weeks of follow-up, or death. Data from 371 patients (Australia, 103; Germany, 152; Italy, 76; Spain, 40) were analysed. Mean age was 65 years; 62% were male. Eastern Cooperative Oncology Group performance status (ECOG PS) was 0 or 1 for 94%. In 67%, ipilimumab was initially received as second-line or later therapy. Patients received on average 3.4 ipilimumab doses. The ipilimumab-refractory cohort comprised of 226 patients. Of these, 17% in Australia, 47% in Germany, 29% in Italy and 14% in Spain received another antimelanoma treatment after ipilimumab including chemotherapy in 26% and BRAF/other kinase inhibitors in 11%. Ipilimumab-refractory patients who received postipilimumab treatment showed a 40% reduced hazard of dying than those not receiving treatment after ipilimumab (HR 0.60; 95% CI 0.43-0.83), after adjustment for potential confounders. During the time observed, ipilimumab was mainly used as second-line or later therapy. A significant proportion of patients received postipilimumab therapy, most of which was chemotherapy. Nevertheless, overall survival following progression on ipilimumab treatment remained poor, highlighting the need for research to develop more effective end-of-life treatment options. © 2017 European Academy of Dermatology and Venereology.

Idiopathic polypoidal choroidal vasculopathy in Thai patients with clinical and angiographic choroidal neovascularization

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Bhoomibunchoo C

2017-02-01

Full Text Available Chavakij Bhoomibunchoo,1 Yosanan Yospaiboon,1 Somanus Thoongsuwan,2 Duangnate Rojanaporn,3 Nawat Watanachai,4 Pichai Jirarattanasopa,5 Nattapon Wongcumchang,6 Atchara Amphornphruet,7 Sritatath Vongkulsiri,8 Eakkachai Arayangkoon9 1Department of Ophthalmology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 2Department of Ophthalmology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, 3Department of Ophthalmology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, 4Department of Ophthalmology, Faculty of Medicine, Chiang Mai University, Chiang Mai, 5Department of Ophthalmology, Faculty of Medicine, Prince of Songkla University, Songkhla, 6Department of Ophthalmology, Faculty of Medicine, Thammasat University, Pathum Thani, 7Department of Ophthalmology, Rajavithi Hospital, Bangkok, 8Department of Ophthalmology, Phramongkutklao Hospital, Bangkok, 9Department of Ophthalmology, Mettapracharak Hospital, Nakhon Pathom, Thailand Objective: This study aimed to study the prevalence and characteristics of idiopathic polypoidal choroidal vasculopathy (IPCV in Thai patients with clinical and angiographic choroidal neovascularization (CNV.Patients and methods: A consecutive case study of 140 patients presenting with CNV was conducted in nine large referral eye centers throughout Thailand. The demographic data, fundus photographs, fundus fluorescein angiography and indocyanine green angiography of the patients were analyzed.Results: Of 129 patients with clinical and angiographic CNV, IPCV was diagnosed in 100 patients (77.52%, idiopathic CNVs in 16 patients (12.40% and age-related macular degeneration (AMD in 12 patients (9.30%. Of the 107 eyes with IPCV, 90 eyes (84.11% had both branching venous networks (BVNs and polypoidal lesions. Most IPCV patients (93% had unilateral involvement and were at a younger age than AMD patients. In all, 79 eyes (73.83% had lesions found in the macular area, 14 eyes (13.08% in the

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

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Jinah Kim

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

Multifocal choroiditis following simultaneous hepatitis A, typhoid, and yellow fever vaccination

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Escott S

2013-02-01

Full Text Available Sarah Escott, Ahmad B Tarabishy, Frederick H DavidorfHavener Eye Institute, The Ohio State University, Columbus, OH, USAAbstract: The paper describes the first reported case of multifocal choroiditis following simultaneous hepatitis-A, typhoid, and yellow fever vaccinations. A 33-year-old male developed sudden onset of flashing lights and floaters in his right eye 3 weeks following hepatitis A, typhoid, and yellow fever vaccinations. Fundus examination and angiography confirmed the presence of multiple peripheral chorioretinal lesions. These lesions demonstrated characteristic morphologic changes over a period of 8 weeks which were consistent with a diagnosis of self-resolving multifocal choroiditis. Vaccine-induced intraocular inflammation has been described infrequently. We demonstrate the first case of self-resolving multifocal choroiditis following simultaneous administration of hepatitis A, yellow fever, and typhoid immunizations.Keywords: multifocal choroiditis, vaccination, hepatitis A, typhoid, yellow fever

Stereotactic Radiofrequency Ablation for Metastatic Melanoma to the Liver

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Bale, Reto, E-mail: reto.bale@i-med.ac.at; Schullian, Peter [Medical University Innsbruck, Department of Radiology, Section of Interventional Oncology - Microinvasive Therapy (SIP) (Austria); Schmuth, Matthias [Medical University Innsbruck, Department of Dermatology (Austria); Widmann, Gerlig; Jaschke, Werner [Medical University Innsbruck, Department of Radiology, Section of Interventional Oncology - Microinvasive Therapy (SIP) (Austria); Weinlich, Georg [Medical University Innsbruck, Department of Dermatology (Austria)

2016-08-15

PurposeTo evaluate the outcome of patients with melanoma liver metastasis treated with stereotactic radiofrequency ablation (SRFA).Material and MethodFollowing IRB approval, a retrospective evaluation of the treatment of 20 patients with 75 melanoma liver metastases was performed.ResultsA median number of 2 lesions (range 1–14) per patient with a median size of 1.7 cm (range 0.5–14.5 cm) were treated. 67 lesions were <3 cm (89.3 %) and 8 lesions were >3 cm (10.7 %). Per patient a median of 1 ablation session was performed (range: 1–4) totaling 34 sessions. There were no procedure-related deaths and all major complications (n = 3) could be easily treated by pleural drainages. The primary and secondary success rates were 89.3 and 93.3 %, respectively. The overall local recurrence rate was 13.3 %. Four of ten local recurrences were re-treated successfully by SRFA. During follow-up, 9/20 patients developed extrahepatic metastatic disease and 10/20 had liver recurrence at any location. The median OS from the date of SRFA was 19.3 months, with an OS of 64, 41, and 17 % at 1, 3, and 5 years, with no significant difference for patients with cutaneous and ocular melanoma. The median DFS after SRFA for all 20 patients was 9.5 months, with 37, 9, and 0 % at 1, 3, and 5 years.ConclusionsDue to the high local curative potential and the promising long-term survival rates associated with minimal morbidity and mortality, radiofrequency ablation seems to be an attractive alternative to resection in patients with melanoma liver metastases.

A Case of Primary Subglottic Malignant Melanoma with a Successful Surgical Treatment

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Shahzad Ahmad

2014-01-01

Full Text Available Primary subglottic malignant melanoma is a very rare and underdiagnosed neoplasm. We are reporting a case of primary malignant melanoma of subglottic mucosa in a 78-year-old woman who presented to our hospital with shortness of breath and hoarseness of voice. Laryngoscopy and excisional biopsy along with immunoreactivity to S-100 and human melanoma black-45 (HMB-45 confirmed the diagnosis. The patient was treated with laryngectomy followed by radiotherapy. Five years following surgical treatment, she continues to be asymptomatic. To our knowledge, there is only one reported case of primary malignant melanoma of subglottic mucosa in the medical literatures.

Transscleral sustained vasohibin-1 delivery by a novel device suppressed experimentally-induced choroidal neovascularization.

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Hideyuki Onami

Full Text Available We established a sustained vasohibin-1 (a 42-kDa protein, delivery device by a novel method using photopolymerization of a mixture of polyethylene glycol dimethacrylate, triethylene glycol dimethacrylate, and collagen microparticles. We evaluated its effects in a model of rat laser-induced choroidal neovascularization (CNV using a transscleral approach. We used variable concentrations of vasohibin-1 in the devices, and used an enzyme-linked immunosorbent assay and Western blotting to measure the released vasohibin-1 (0.31 nM/day when using the 10 μM vasohibin-1 delivery device [10VDD]. The released vasohibin-1 showed suppression activity comparable to native effects when evaluated using endothelial tube formation. We also used pelletized vasohibin-1 and fluorescein isothiocyanate-labeled 40 kDa dextran as controls. Strong fluorescein staining was observed on the sclera when the device was used for drug delivery, whereas pellet use produced strong staining in the conjunctiva and surrounding tissue, but not on the sclera. Vasohibin-1 was found in the sclera, choroid, retinal pigment epithelium (RPE, and neural retina after device implantation. Stronger immunoreactivity at the RPE and ganglion cell layers was observed than in other retinal regions. Significantly lower fluorescein angiography (FA scores and smaller CNV areas in the flat mounts of RPE-choroid-sclera were observed for the 10VDD, VDD (1 μM vasohibin-1 delivery device, and vasohibin-1 intravitreal direct injection (0.24 μM groups when compared to the pellet, non-vasohibin-1 delivery device, and intravitreal vehicle injection groups. Choroidal neovascularization can be treated with transscleral sustained protein delivery using our novel device. We offer a safer sustained protein release for treatment of retinal disease using the transscleral approach.

Characteristics of choroidal neovascularization in the complications of age-related macular degeneration prevention trial.

Science.gov (United States)

Maguire, Maureen G; Alexander, Judith; Fine, Stuart L

2008-09-01

To describe the characteristics of incident choroidal neovascularization (CNV) in observed and treated eyes in the Complications of Age-related Macular Degeneration Prevention Trial (CAPT). Cross-sectional descriptive study within a multicenter, randomized clinical trial. Patients who developed CNV during CAPT follow-up. Inclusion criteria for CAPT specified bilateral large drusen (>or=10 drusen at least 125 micro), visual acuity >or=20/40 in each eye, and age >or=50. Exclusion criteria included CNV and geographic atrophy >1 Macular Photocoagulation Study (MPS) disc area or within 500 micro of the foveal center. One eye of each person was selected randomly for low-intensity laser treatment and the contralateral eye was observed. Fluorescein angiography was performed at baseline, annually for >or=5 years, and whenever there were symptoms of CNV. Trained readers at the CAPT Photograph Reading Center assessed color stereo photographs and angiogram negatives to identify CNV. Choroidal neovascularization was classified by type (predominantly classic CNV, minimally classic CNV, occult only CNV, or scar), location, and area. Visual acuity was measured by certified examiners. Symmetry of characteristics between eyes of bilaterally affected patients was examined. Choroidal neovascularization developed in 282 eyes of 225 patients. At the time of detection, 192 (68%) of the lesions were occult only, 153 (54%) were subfoveal, and 157 (56%) were or=20/40 in 123 (69%) of 179 eyes with visual acuity measured at the time of detection. Choroidal neovascularization developed in both eyes in 57 patients (25%) during CAPT follow-up. Lesions in eyes of bilaterally affected patients were no more similar to each other than affected eyes in 2 different patients. When patients are monitored closely, many CNV lesions can be detected outside of the fovea and when they are relatively small. Early detection may lead to improved long-term visual acuity.

Multimodal imaging of choroidal nodules in neurofibromatosis type-1

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Vinod Kumar

2018-01-01

Full Text Available Choroidal nodules in neurofibromatosis type-1 are common and are best imaged with near-infrared reflectance (NIR imaging. The authors describe swept-source optical coherence tomography angiography (SSOCTA of choroidal nodules. These nodules are seen as hyperflow areas on SSOCTA and correlate well to bright patches on NIR imaging. The utility of multicolor scanning laser imaging in detecting these abnormalities is also described.

Gene expression in SK-Mel-28 human melanoma cells treated with the snake venom jararhagin.

Science.gov (United States)

Klein, Anelise; Capitanio, Juliana Silva; Maria, Durvanei Augusto; Ruiz, Itamar Romano Garcia

2011-01-01

Alternative approaches to improve the treatment of advanced melanomas are highly needed. The disintegrin domain of metalloproteinases binds integrin receptors on tumor cells, blocking migration, invasion, and metastatization. Previous studies showed that jararhagin, from the Bothrops jararaca snake venom, induces changes in the morphology and viability of SK-Mel-28 human melanoma cells, and decreases the number of metastases in mice injected with pre-treated cells. The purpose of this study was to evaluate the molecular effects of jararhagin on SK-Mel-28 cells and fibroblasts, concerning the expression of integrins, cadherins, caspases, and TP53 genes. Sub-toxic doses of jararhagin were administered to confluent cells. RT-PCR was performed following extraction of total RNA. Jararhagin treatments induced similar morphological alterations in both normal and tumor cells, with higher IC50 values for fibroblasts. Integrin genes were downregulated in untreated cells, except for ITGA6a,b, ITGAv, and ITGB3 which were highly expressed in SK-Mel-28. The integrin expression profiles were not affected by the toxin. However, jararhagin 30ng/μl upregulated genes TP53, CDKN1A, CDKN2A, CASP3, CASP5, CASP6, CASP8, and E-CDH in SK-Mel-28, and genes ITGB6, ITGB7, CASP3, TP53, and CDKN1B in fibroblasts. Appropriate jararhagin concentration can have apoptotic and suppressant effects on SK-Mel-28 cells, rather than on fibroblasts, and can be used to develop potential anti-cancer drugs. Copyright © 2010 Elsevier Ltd. All rights reserved.

Intraocular (Eye) Melanoma—Health Professional Version

Science.gov (United States)

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

Alteration of choroidal thickness in patients with obstructive sleep apnea hyponea syndrome

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Jing-Bo Wang

2018-02-01

Full Text Available AIM:To analyze the choroidal thickness alteration in patients with obstructive sleep apnea hypopnea syndrome(OSAHS. METHODS: Seventeen patients who were diagnosed with OSAHS initially and 31 healthy individuals were enrolled. Enhanced depth imaging choriodal scans were obtained by spectral-domain optical coherence tomography. Choroidal thickness of subfovea, 2mm superior, inferior, nasal and temporal to the fovea were measured and statistically analyzed. RESULTS: Subfoveal choroidal thickness of the control group and the OSAHS group was 323.58±58.63μm and 316.82±46.43μm respectively, and the difference was unsignificant(t=0.409, P=0.684. Choroidal thickness at 2mm superior to the fovea of the control group and the OSAHS group was 318.29±56.89μm and 314.29±59.8μm respectively, and the difference was unsignificant(t=0.229, P=0.820. Choroidal thickness at 2mm inferior to the fovea of the control group and the OSAHS group was 308.42±54.95μm and 291.65±55.37μm respectively, and the difference was not significant(t=1.009, P=0.318. Choroidal thickness at 2mm temporal to the fovea of the control group and the OSAHS group was 308.23±54.62μm and 302.76±46.97μm respectively, and the difference was not significant(t=0.347, P=0.730. Choroidal thickness at 2mm nasal to the fovea of the control group and the OSAHS group was 266.23±58.10μm and 277.12±63.99μm respectively, and the difference was not significant(t=-0.599, P=0.552. There were no significant differences among subgroups after grading based on the severity of sleep apnea hypopnea index and blood oxygen concentration. CONCLUSION: Compared with healthy individuals, choroidal thickness of patients with OSAHS decreases slightly(except for the location of 2mm nasal to the fovea, but the alteration is not significant. The severity of OSAHS has no effect on the choroidal thickness for the patients first diagnosis of OSAHS.

Intravitreal itraconazole inhibits laser-induced choroidal neovascularization in rats.

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Jeong Hun Bae

Full Text Available Choroidal neovascularization (CNV is a major cause of severe visual loss in patients with age-related macular degeneration (AMD. Recently, itraconazole has shown potent and dose-dependent inhibition of tumor-associated angiogenesis. We evaluated the anti-angiogenic effect of itraconazole in a rat model of laser-induced CNV. After laser photocoagulation in each eye to cause CNV, right eyes were administered intravitreal injections of itraconazole; left eyes received balanced salt solution (BSS as controls. On day 14 after laser induction, fluorescein angiography (FA was used to assess abnormal vascular leakage. Flattened retinal pigment epithelium (RPE-choroid tissue complex was stained with Alexa Fluor 594-conjugated isolectin B4 to measure the CNV area and volume. Vascular endothelial growth factor receptor 2 (VEGFR2 mRNA and protein expression was determined 1, 4, 7, and 14 days after intravitreal injection by quantitative RT-PCR or Western blot. VEGF levels were analyzed by enzyme-linked immunosorbent assay (ELISA. Intravitreal itraconazole significantly reduced leakage from CNV as assessed by FA and CNV area and volume on flat mounts compared with intravitreal BSS (p = 0.002 for CNV leakage, p<0.001 for CNV area and volume. Quantitative RT-PCR showed significantly lower expression of VEGFR2 mRNA in the RPE-choroid complexes of itraconazole-injected eyes than those of BSS-injected eyes on days 7 and 14 (p = 0.003 and p = 0.006. Western blots indicated that VEGFR2 was downregulated after itraconazole treatment. ELISA showed a significant difference in VEGF level between itraconazole-injected and BSS-injected eyes on days 7 and 14 (p = 0.04 and p = 0.001. Our study demonstrated that intravitreal itraconazole significantly inhibited the development of laser-induced CNV in rats. Itraconazole had anti-angiogenic activity along with the reduction of VEGFR2 and VEGF levels. Itraconazole may prove beneficial for treating CNV as an alternative or

Management of advanced melanoma

International Nuclear Information System (INIS)

Nathanson, L.

1986-01-01

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

[Central aleolar choroidal dystrophy in sibilings coexisting with alopecia].

Science.gov (United States)

Brydak-Godowska, Joanna; Dróbecka-Brydak, Ewa; Paćkowska, Maria; Kecik, Dariusz

2007-01-01

Central areolar choroidal dystrophy is localized in macular region and is characterized by atrophy of pigment epithelium, photoreceptors and choriocapillaris. This paper presents the history of two sibilings at the age of 23 and 30, with central aleolar choroidal dystrophy coexisting with alopecia. The results of erg, eog and fluorescein angiography are presented. The results of therapy for glaucoma associated with the Sturge-Weber syndrome are often disappointing.

Choroidal neovascular membrane

OpenAIRE

Bhatt Nitul; Diamond James; Jalali Subhadra; Das Taraprasad

1998-01-01

Choroidal neovascular membrane in the macular area is one of the leading causes of severe visual loss. Usually a manifestation in elderly population, it is often associated with age-related macular degeneration. The current mainstay of management is early diagnosis, usually by fundus examination, aided by angiography and photocoagulation in selected cases. Various other modalities of treatment including surgery are being considered as alternate options, but with limited success. The purpose o...

Choroid-Plexus-Derived Otx2 Homeoprotein Constrains Adult Cortical Plasticity

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Julien Spatazza

2013-06-01

Full Text Available Brain plasticity is often restricted to critical periods in early life. Here, we show that a key regulator of this process in the visual cortex, Otx2 homeoprotein, is synthesized and secreted globally from the choroid plexus. Consequently, Otx2 is maintained in selected GABA cells unexpectedly throughout the mature forebrain. Genetic disruption of choroid-expressed Otx2 impacts these distant circuits and in the primary visual cortex reopens binocular plasticity to restore vision in amblyopic mice. The potential to regulate adult cortical plasticity through the choroid plexus underscores the importance of this structure in brain physiology and offers therapeutic approaches to recovery from a broad range of neurodevelopmental disorders.

Risk of invasive melanoma in patients with rheumatoid arthritis treated with biologics

DEFF Research Database (Denmark)

Mercer, Louise K; Askling, Johan; Raaschou, Pauline

2017-01-01

-specific general population of each register as reference, age, sex and calendar year standardised incidence ratios (SIRs) of invasive histology-confirmed cutaneous melanoma were calculated within each register. Pooled SIR and incidence rate ratios (IRRs) comparing biologic cohorts to biologic-naïve were...... calculated across countries by taking the size of the register into account. RESULTS: Overall 130 315 RA patients with a mean age of 58 years contributing 579 983 person-years were available for the analysis and 287 developed a first melanoma. Pooled SIRs for biologic-naïve, TNFi and rituximab...... with TNF inhibitors (TNFi), other biologic disease modifying drugs and non-biologic therapy. METHODS: Eleven biologic registers from nine European countries participated in this collaborative project. According to predefined exposure definitions, cohorts of patients with RA were selected. Using the country...

/sup 3/H-dextran method for measurements of the blood volume in the rat choroid

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Matsusaka, T [Osaka Prefectural Center for Adult Diseases (Japan); Morimoto, K; Kikkawa, Y

1980-01-01

A new method was developed using /sup 3/H-dextran for measuring the blood volume in the choroid. Under pentobarbital-anesthesia, albino rats weighing 200 grams were perfused through the left ventricle with a 2.5 percent glutaraldehyde solution containing the radioactive dextran. The procedure allowed exchange of the choroidal blood with the /sup 3/H-dextran solution with a simultaneous fixation of the choroid. The blood volume in the choroid was calculated from the radioactivity count, which is estimated to be 1.690 x 10/sup -4/ ml per mg wet weight and 5.070 x 10/sup -4/ ml per mg dry weight. Epinephrine subconjunctivally injected diminished the blood volume in the choroid by 68 percent. Pretreatment with lidocaine almost nullified the effect of epinephrine. Applicability of this method to the analytical study of the choroidal circulation is discussed.

Radiation therapy for small choroidal neovascularization in age-related macular degeneration

Energy Technology Data Exchange (ETDEWEB)

Matsuhashi, Hideaki; Noda, Yasuko; Takahashi, Daisuke; Mariya, Yasushi [Hirosaki Univ., Aomori (Japan). School of Medicine

1999-06-01

Radiation therapy for age-related macular degeneration with subfoveal or juxtafoveal choroidal neovascularization smaller than or equal to 1 disc area was evaluated. Fourteen eyes received a total radiation dose of 10-20 Gy in 5-10 fractions. The mean follow-up time was 22 months. Ten eyes in a control group were followed for an average of 16 months without any treatment. At a 12-month follow-up examination, funduscopic and angiographic findings had improved in 7 eyes (50%), were unchanged in 1 eye (7%) and, had deteriorated in 6 eyes (43%) among the treated patients. The same findings had improved in 1 eye (10%), were unchanged in 2 eyes (20%), and had deteriorated in 7 eyes (70%) among the control patients. There was a statistically significant difference by Mann-Whitney U test between the two groups. Visual acuity had improved in 4 eyes (29%), was unchanged in 6 eyes (43%), and had declined in 4 eyes (29%) among the treated patients. Among the control patients visual acuity had improved in none of the eyes (0%), was unchanged in 6 eyes (60%), and had declined in 4 eyes (40%). The difference between the two groups was not statistically significant. Of the 7 cases whose fundus had improved by 12 months, 4 cases maintained a favorable status through the following 2 years. Radiation therapy had an inhibitory effect on small choroidal neovascularization when viewed by funduscopy and angiography, but, the efficacy for visual prognosis was not always identified. (author)

Phase II study of 4'-(9-acridinylamino) methanesulfon-m- anisidide (AMSA) in metastatic melanoma.

Science.gov (United States)

Legha, S S; Hall, S W; Powell, K C; Burgess, M A; Benjamin, R S; Gutterman, J U; Bodey, G P

1980-01-01

A phase II study of AMSA in previously treated patients with metastatic malignant melanoma was conducted. The dose schedule of AMSA was 40 mg/m2/day for 3 days repeated at 3-week intervals. Among the 30 evaluable patients, one achieved a complete response, one a partial response, and four had minor responses. Side effects included mild nausea and vomiting and moderate degree of myelosuppression. AMSA has poor activity against previously treated metastatic melanoma.

Treatment of cutaneous melanoma: current approaches and future prospects

International Nuclear Information System (INIS)

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

2010-01-01

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

Vascular endothelial growth factor regulates melanoma cell adhesion and growth in the bone marrow microenvironment via tumor cyclooxygenase-2

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Crende Olatz

2011-08-01

Full Text Available Abstract Background Human melanoma frequently colonizes bone marrow (BM since its earliest stage of systemic dissemination, prior to clinical metastasis occurrence. However, how melanoma cell adhesion and proliferation mechanisms are regulated within bone marrow stromal cell (BMSC microenvironment remain unclear. Consistent with the prometastatic role of inflammatory and angiogenic factors, several studies have reported elevated levels of cyclooxygenase-2 (COX-2 in melanoma although its pathogenic role in bone marrow melanoma metastasis is unknown. Methods Herein we analyzed the effect of cyclooxygenase-2 (COX-2 inhibitor celecoxib in a model of generalized BM dissemination of left cardiac ventricle-injected B16 melanoma (B16M cells into healthy and bacterial endotoxin lipopolysaccharide (LPS-pretreated mice to induce inflammation. In addition, B16M and human A375 melanoma (A375M cells were exposed to conditioned media from basal and LPS-treated primary cultured murine and human BMSCs, and the contribution of COX-2 to the adhesion and proliferation of melanoma cells was also studied. Results Mice given one single intravenous injection of LPS 6 hour prior to cancer cells significantly increased B16M metastasis in BM compared to untreated mice; however, administration of oral celecoxib reduced BM metastasis incidence and volume in healthy mice, and almost completely abrogated LPS-dependent melanoma metastases. In vitro, untreated and LPS-treated murine and human BMSC-conditioned medium (CM increased VCAM-1-dependent BMSC adherence and proliferation of B16M and A375M cells, respectively, as compared to basal medium-treated melanoma cells. Addition of celecoxib to both B16M and A375M cells abolished adhesion and proliferation increments induced by BMSC-CM. TNFα and VEGF secretion increased in the supernatant of LPS-treated BMSCs; however, anti-VEGF neutralizing antibodies added to B16M and A375M cells prior to LPS-treated BMSC-CM resulted in a

Objective evaluation of choroidal melanin contents with polarization-sensitive optical coherence tomography

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Miura, Masahiro; Makita, Shuichi; Yasuno, Yoshiaki; Ikuno, Yasushi; Uematsu, Sato; Iwasaki, Takuya; Goto, Hiroshi

2018-02-01

We non-invasively evaluated choroidal melanin contents in human eyes with PS-OCT. We calculated the percentage area of low DOPU in the choroidal interstitial stroma for Vogt-Koyanagi- Harada disease with sunset glow fundus, without sunset glow fundus, control group and tessellated fundus with high myopia. The mean percentage area of low DOPU in the sunset group was significantly lower than the other groups. PS-OCT provides an in vivo objective evaluation of choroidal melanin loss in vivo human eyes.

Risk of non-melanoma skin cancer in myasthenia patients treated with azathioprine

DEFF Research Database (Denmark)

Pedersen, E G; Pottegård, A; Hallas, J

2014-01-01

The association between use of azathioprine and risk of non-melanoma skin cancer (NMSC) in patients with myasthenia was evaluated in a nationwide setting. Treatment of autoimmune myasthenia frequently involves long-term exposure to immunosuppressants, including azathioprine. Use of azathioprine...

Pregnancy and melanoma.

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

2016-10-01

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

Changes in Retinal and Choroidal Vascular Blood Flow after Oral Sildenafil: An Optical Coherence Tomography Angiography Study

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David Berrones

2017-01-01

Full Text Available Purpose. To describe changes in the retina and choroidal flow by optical coherence tomography angiography (OCT-A after a single dose of oral sildenafil. Method. A case-control study. Patients in the study group received 50 mg of oral sildenafil. Patients in the control group received a sham pill. Retinal and choroidal images were obtained at baseline (before pill ingestion and 1 hour after ingestion. Central macular and choroidal thickness, choroidal and outer retina flow, and the retinal and choroidal vascular density were compared using a Mann-Whitney U test. Results. Twenty eyes were enrolled into the study group and 10 eyes in the control group. There was a significant difference in central choroidal thickness and outer retina blood flow between groups after 1 hour of sildenafil ingestion (p<0.01. There were no differences in central macular thickness, choroidal flow, and retinal vascular density among groups. Conclusions. A single dose of oral sildenafil increases choroidal thickness, probably due to sildenafil-induced vasodilation.

Development and Testing of a 212Pb/212Bi Peptide for Targeting Metastatic Melanoma

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Fisher, Darrell R.

2012-10-25

The purpose of this project is to develop a new radiolabeled peptide for imaging and treating metastatic melanoma. The immunoconjugate consists of a receptor-specific peptide that targets melanoma cells. The beta-emitter lead-212 (half-life = 10.4 hours) is linked by coordination chemistry to the peptide. After injection, the peptide targets melanoma receptors on the surfaces of melanoma cells. Lead-212 decays to the alpha-emitter bismuth-212 (half-life = 60 minutes). Alpha-particles that hit melanoma cell nuclei are likely to kill the melanoma cell. For cancer cell imaging, the lead-212 is replaced by lead-203 (half-life = 52 hours). Lead-203 emits 279 keV photons (80.1% abundance) that can be imaged and measured for biodistribution analysis, cancer imaging, and quantitative dosimetry.

Choroidal Thickness Analysis in Patients with Usher Syndrome Type 2 Using EDI OCT.

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Colombo, L; Sala, B; Montesano, G; Pierrottet, C; De Cillà, S; Maltese, P; Bertelli, M; Rossetti, L

2015-01-01

To portray Usher Syndrome type 2, analyzing choroidal thickness and comparing data reported in published literature on RP and healthy subjects. Methods. 20 eyes of 10 patients with clinical signs and genetic diagnosis of Usher Syndrome type 2. Each patient underwent a complete ophthalmologic examination including Best Corrected Visual Acuity (BCVA), intraocular pressure (IOP), axial length (AL), automated visual field (VF), and EDI OCT. Both retinal and choroidal measures were measured. Statistical analysis was performed to correlate choroidal thickness with age, BCVA, IOP, AL, VF, and RT. Comparison with data about healthy people and nonsyndromic RP patients was performed. Results. Mean subfoveal choroidal thickness (SFCT) was 248.21 ± 79.88 microns. SFCT was statistically significant correlated with age (correlation coefficient -0.7248179, p patients (p = 0.2138). Conclusions. Our study demonstrated in vivo choroidal thickness reduction in patients with Usher Syndrome type 2. These data are important for the comprehension of mechanisms of disease and for the evaluation of therapeutic approaches.

Role of optical coherence tomography angiography in myopic choroidal neovascularization after intravitreal injections of Ranibizumab

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Meng Cai

2017-10-01

Full Text Available AIM: To investigate the change of myopic choroidal neovascularization treated by ranibizumab and evaluate their value in monitoring the effect of anti- vascular endothelial growth factor(VEGFtherapy.METHODS: The study enrolled 30 patients(30 eyesdiagnosed with myopic choroidal neovascularization. All affected eyes were treated with intravitreal ranibizumab 0.05mL(10mg/mL. Best corrected visual acuity(BCVA, non-contact tonometer, ophthalmoscope, fundus fluorescein angiograph(FFAand OCTA were evaluated monthly until 6mo. The changes of BCVA and central macular thickness(CMTwere compared at 1, 3 and 6mo after treatment.RESULTS: All patients received an average of 1.70±0.65 injections. BCVA was 0.96±0.17(LogMARbefore therapy, and BCVA 1, 3 and 6mo after treatment respectively improved by 0.23±0.09, 0.34±0.07, 0.38±0.11. The differences were significant(t=5.461, 8.191, 8.894; Pt=12.007, 13.360, 9.531; PCONCLUSION: Intravitreal ranibizumab for CNV secondary to pathologic myopia is effective and safe; OCTA is a noninvasive and time-saving new technology, and it also is a promising tool for clinicians to make preliminary diagnosis and assess treatment efficacy in the follow-up visits.

Five years of proton therapy of tumours of the eye at Hahn-Meitner Institute, Berlin

International Nuclear Information System (INIS)

Heufelder, J.; Cordini, D.; Heese, J.; Homeyer, H.; Kluge, H.; Morgenstern, H.; Fuchs, H.; Hoecht, S.; Nausner, M.; Hinkelbein, W.; Bechrakis, N.E.; Foerster, M.H.

2004-01-01

Eye tumors (choroidal melanomas, iris melanomas, and choroidal hemangiomas) are being treated with 68 MeV protons since 1998 at the Ion Beam Laboratory of the Hahn-Meitner Institute of Berlin (Germany's first proton therapy center), in cooperation with the Charite University Hospital in Berlin, Campus Benjamin Franklin. The proton beam, generated via a combination of Van de Graaff accelerator and cyclotron, is prepared by passive shaping for conformal tumor irradiation. A digital X-ray verification of the tumor location with the patient in sitting position limits the position uncertainties to a maximum of 0,3 mm. The treatment planning is performed using the program EYEPLAN. OCTOPUS, a CT-based planning program developed in cooperation with the German Cancer Research Center of Heidelberg, is under pre-clinical testing. Thus far, more than 400 patients have been irradiated. The first results are comparable to those obtained in other proton therapy centers. At the end of 2002, the University Hospital of Essen has also become a cooperation partner of the Hahn-Meitner Institute. (orig.) [de

An Unusual Case of Unilateral Multifocal Choroiditis in a Young Male

African Journals Online (AJOL)

Multifocal choroiditis is a vision‑threatening disease causing inflammation at the level of retinal pigment epithelium and outer retina. We present a unique case of unilateral multifocal choroiditis in a young nonmyopic male and its subsequent course. The patient developed visual loss due to the sub‑retinal neovascular ...

Choroidal Thickness Analysis in Patients with Usher Syndrome Type 2 Using EDI OCT

Directory of Open Access Journals (Sweden)

L. Colombo

2015-01-01

Full Text Available To portray Usher Syndrome type 2, analyzing choroidal thickness and comparing data reported in published literature on RP and healthy subjects. Methods. 20 eyes of 10 patients with clinical signs and genetic diagnosis of Usher Syndrome type 2. Each patient underwent a complete ophthalmologic examination including Best Corrected Visual Acuity (BCVA, intraocular pressure (IOP, axial length (AL, automated visual field (VF, and EDI OCT. Both retinal and choroidal measures were measured. Statistical analysis was performed to correlate choroidal thickness with age, BCVA, IOP, AL, VF, and RT. Comparison with data about healthy people and nonsyndromic RP patients was performed. Results. Mean subfoveal choroidal thickness (SFCT was 248.21±79.88 microns. SFCT was statistically significant correlated with age (correlation coefficient −0.7248179, p<0.01. No statistically significant correlation was found between SFCT and BCVA, IOP, AL, VF, and RT. SFCT was reduced if compared to healthy subjects (p<0.01. No difference was found when compared to choroidal thickness from nonsyndromic RP patients (p=0.2138. Conclusions. Our study demonstrated in vivo choroidal thickness reduction in patients with Usher Syndrome type 2. These data are important for the comprehension of mechanisms of disease and for the evaluation of therapeutic approaches.

Choroid plexus transport: gene deletion studies

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Keep Richard F

2011-11-01

Full Text Available Abstract This review examines the use of transporter knockout (KO animals to evaluate transporter function at the choroid plexus (the blood-CSF barrier; BCSFB. Compared to the blood-brain barrier, there have been few such studies on choroid plexus (CP function. These have primarily focused on Pept2 (an oligopeptide transporter, ATP-binding cassette (ABC transporters, Oat3 (an organic anion transporter, Svct2 (an ascorbic acid transporter, transthyretin, ion transporters, and ion and water channels. This review focuses on the knowledge gained from such studies, both with respect to specific transporters and in general to the role of the CP and its impact on brain parenchyma. It also discusses the pros and cons of using KO animals in such studies and the technical approaches that can be used.

[Acute dyspnea in malignant melanoma].

Science.gov (United States)

Franzen, A M; Günzel, T

2011-09-01

Metastases to the larynx are rare. The current article presents the case of a 75-year-old patient with a history of shortness of breath due to a supraglottic exophytic lesion that was identified as a metastasis of a cutaneous melanoma treated 2.5 years previously. As a result of our medline analysis we found approximately 30 cases of metastatic melanoma to the larynx published to date. Primary tumors are always cutaneous in origin and spread over the whole integument of trunk and extremities. The time interval between diagnosis of the primary and the laryngeal metastasis is often several years. In most reports a supraglottic exophytic, red coloured lesion is described. Diagnosis can only be proven by histological examination. Laryngeal metastasis is usually an indication of tumor dissemination and always has a fatal prognosis.

Choroidal Thickness Changes in the Acute Attack Period in Patients with Familial Mediterranean Fever.

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Gundogan, Fatih C; Akay, Fahrettin; Uzun, Salih; Ozge, Gokhan; Toyran, Sami; Genç, Halil

2016-01-01

The aim of this study was to evaluate choroidal thickness changes during acute attacks of familial Mediterranean fever (FMF). Fifty patients with FMF and 50 healthy controls were included. Choroidal thickness of each participant was measured at the foveola and horizontal nasal and temporal quadrants at 500-µm intervals to 1,500 µm from the foveola using spectral-domain optical coherence tomography. White blood cell count, erythrocyte sedimentation rate (ESR) and serum levels of fibrinogen and C-reactive protein (CRP) were evaluated. The clinical findings (peritonitis, arthritis and pleuritis) were noted. Choroidal thickness was significantly thicker at all measurement points in FMF patients compared to healthy controls during an acute attack (p 0.05). Increased choroidal thickness in the acute phase of FMF is possibly related to the inflammatory edematous changes in the choroid. © 2015 S. Karger AG, Basel.

Structural changes of the choroid in sarcoid- and tuberculosis-related granulomatous uveitis

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Mehta, H; Sim, D A; Keane, P A; Zarranz-Ventura, J; Gallagher, K; Egan, C A; Westcott, M; Lee, R W J; Tufail, A; Pavesio, C E

2015-01-01

Aim The aim of this study is to characterise the choroidal features of patients diagnosed with sarcoid- and tuberculosis (TB)-associated granulomatous uveitis using spectral domain optical coherence tomography (OCT). Methods Twenty-seven patients (27 eyes) diagnosed with sarcoid- (13 eyes) and TB (14 eyes)-related uveitis were included in this retrospective, cross-sectional study. Over a six-month period, patients diagnosed with sarcoid and TB granulomatous uveitis were scanned using enhanced depth imaging OCT. Clinical and demographical characteristics were recorded, including the method of diagnosis, disease activity, site of inflammation (anterior or posterior), treatments, and visual acuity (VA). Manual segmentation of the choroidal layers was performed using custom image analysis software. Results The main outcome measure was OCT-derived thickness measurements of the choroid and choroidal sublayers (Haller's large vessel and Sattler's medium vessel layers) at the macula region. The ratio of Haller's large vessel to Sattler's medium vessel layer was significantly different at the total macula circle in eyes diagnosed with TB uveitis (1.47 (=140.71/95.72 μm)) compared with sarcoid uveitis (1.07 (=137.70/128.69 μm)) (P=0.001). A thinner choroid was observed in eyes with a VA ≥0.3 LogMAR (Snellen 6/12; 198.1 μm (interquartile range (IQR)=147.0–253.4 μm) compared with those with VA uveitis, and choroidal thickening may be a feature of active granulomatous uveitis. PMID:26021867

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

Science.gov (United States)

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

2015-11-01

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

Ultrasound-mediated interferon β gene transfection inhibits growth of malignant melanoma

International Nuclear Information System (INIS)

Yamaguchi, Kazuki; Feril, Loreto B.; Tachibana, Katsuro; Takahashi, Akira; Matsuo, Miki; Endo, Hitomi; Harada, Yoshimi; Nakayama, Juichiro

2011-01-01

Highlights: → Successful ultrasound-mediated transfection of melanoma (C32) cells with IFN-β genes both in vitro and in vivo. → Ultrasound-mediated IFN-β transfection inhibited proliferation of melanoma cells in vitro. → Ultrasound-mediated IFN-β transfection inhibited melanoma tumor growth in vivo. -- Abstract: We investigated the effects of ultrasound-mediated transfection (sonotransfection) of interferon β (IFN-β) gene on melanoma (C32) both in vitro and in vivo. C32 cells were sonotransfected with IFN-β in vitro. Subcutaneous C32 tumors in mice were sonicated weekly immediately after intra-tumor injection with IFN-β genes mixed with microbubbles. Successful sonotransfection with IFN-β gene in vitro was confirmed by ELISA, which resulted in C32 growth inhibition. In vivo, the growth ratio of tumors transfected with IFN-β gene was significantly lower than the other experimental groups. These results may lead to a new method of treatment against melanoma and other hard-to-treat cancers.

Effect of Qi Ming Granule on the choroidal circulation in diabetic patients

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Ke-Jun Li

2016-03-01

Full Text Available AIM:To investigate the effect of a Chinese medicine(Qi Ming granuleon the retinal and choroidal circulation in diabetes patients. METHODS: According to the results of fundus fluorescein angiography(FFA, all the 45 diabetes patients were divided into no diabetic retinopathy(NDRgroup and nonproliferative diabetic retinopathy(NPDRgroup. All subjects were examined by FFA and indocyanine green angiography(ICGAat the same time. After taken Qi Ming granule for 3mo, all subjects were examined by the same method. FFA and ICGA were used to evaluate the retinal and choroidal circulation and their features. The key points were filling time for the retinal and choroidal circulation before and after treatments. The accuracy data was used to evaluate the effect.RESULTS: After taken Qi Ming granule for 3mo, there were significant decrease of the retina and the choroid filling time in NDR and NPDR groups. The occurrence rate of various abnormal angiographic features were significantly decreased. CONCLUSION: Qi Ming granule can accelerate the blood flow of retina and choroid, improve the blood circulation in diabetes patients, and delay the occurrence and development of diabetic retinopathy.

Elevated serum IGF-1 level enhances retinal and choroidal thickness in untreated acromegaly patients.

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Zhang, Xia; Ma, Jin; Wang, Yuhan; Li, Lüe; Gao, Lu; Guo, Xiaopeng; Xing, Bing; Zhong, Yong

2018-03-01

1) To compare the retinal, choroidal, Haller's layer, and Sattler's/choriocapillaris thicknesses of untreated acromegaly patients without chiasm compression or diabetes mellitus and healthy controls. 2) To evaluate the correlations of retinal and choroidal thicknesses with serum growth hormone (GH) and insulin-like growth factor 1 (IGF) burden. This prospective, case-control study included 27 untreated acromegaly patients and 27 sex-matched and age-matched controls. Subfoveal choroidal, Haller's layer and Sattler's/choriocapillaris thicknesses were determined by enhanced-depth imaging optical coherence tomography (EDI-OCT). Foveal and macular retinal thicknesses were determined with SD-OCT. GH and IGF-1 burdens were defined as the product of disease duration and treatment-naïve serum GH and IGF-1 levels. Compared with healthy controls, patients with acromegaly exhibited significantly increased foveal retinal (p = 0.003), subfoveal choroidal (p IGF-1 level (p = 0.03) and IGF-1 burden (p = 0.009). No significant correlations were detected between choroidal thickness and GH burden (p = 0.44). Retinal thickness was not significantly correlated with any factor. The choroidal thickness of acromegaly patients was greater than that of healthy controls and was significantly correlated with disease duration, IGF-1 level and IGF-1 burden, indicating that excessive serum IGF-1 and its exposure time have a combined effect on choroidal thickness.

Dye-enhanced diode laser photocoagulation of choroidal neovascularizations

Science.gov (United States)

Klingbeil, Ulrich; Puliafito, Carmen A.; McCarthy, Dan; Reichel, Elias; Olk, Joseph; Lesiecki, Michael L.

1994-06-01

Dye-enhanced diode laser photocoagulation, using the dye indocyanine green (ICG), has shown some potential in the treatment of choroidal neovascularizations (CNV). A diode laser system was developed and optimized to emit at the absorption maximum of ICG. In a clinical study at two retinal centers, more than 70 patients, the majority of which had age-related macular degeneration, were treated. Eighteen cases with ill-defined subfoveal CNV were followed an average of 11 months after laser treatment. The results show success in resolving the CNV with an average long-term preservation of visual function equal to or superior to data provided by the Macular Photocoagulation Study for confluent burns of low intensity applied to the CNV. Details of the technique and discussion of the controversies inherent in such a treatment strategy will be presented.

Massive choroidal hemorrhage after intravitreal administration of bevacizumab (Avastin® for AMD followed by controlateral sympathetic ophthalmia

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Dimitrios Brouzas

2009-08-01

Full Text Available Dimitrios Brouzas, Chryssanthi Koutsandrea, Marilita Moschos, Spiros Papadimitriou, Ioannis Ladas, Michael Apostolopoulos1st Eye Department , University of Athens, Athens, GreecePurpose: To report a severe ocular complication initiated ten days after intravitreal administration of bevacizumab (Avastin®, in a patient with exudative age-related macular degeneration (AMD.Patients and method: Case report.Results: Ten days after intravitreal injection of 1.25 mg Avastin®, the patient manifested acute loss of vision with excruciating pain. An extensive choroidal detachment was evident in close contact with the lens, which necessitated an emergency sclerotomy with reconstruction of the anterior chamber. Four months later, the eye proceeded to phthisis bulbi. Five months after the injection, the patient complained of mild pain, photophobia, and visual acuity deterioration from the fellow eye. The diagnosis of sympathetic ophthalmia was suggested and treated with intravitreal injections of triamcinolone acetonide every three months with good response, complicated by elevation of intraocular pressure which we managed with Ahmet valve implantation.Conclusion: Serious ocular complications after intravitreal of Avastin® can not be excluded, including massive choroidal hemorrhage and sympathetic ophthalmia of the fellow eye.Keywords: Avastin® complication, intravitreal injection, choroidal detachment, Phthisis bulbi, sympathetic ophthalmia

Olbrzymi brodawczak splotu naczyniówkowego – opis przypadku = Giant choroid plexus papilloma – case report

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Kamila Woźniak

2016-08-01

cylindrical shape of the cells resting on the basilar membrane. The authors present a case of clinical patient operating treated in the Department of Neurosurgery, Neurotraumatology and Pediatric Neurosurgery, Dr Antoni Jurasz University Hospital No.1 in Bydgoszcz histopathological diagnosed with choroid plexus papilloma.   Key words: choroid plexus papilloma, cancer, central nervous system, neurosurgery.

Choroidal metastasis of a minor salivary gland adenoid cystic carcinoma: A case report.

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Portilla Blanco, R R; Roberts Martínez-Aguirre, I; Pontón Méndez, P; Zarzosa Martín, M E; Pérez-Salvador García, E

2018-03-21

A 61-year-old man with a lower lip minor salivary gland adenoid cystic carcinoma, suffered from a unilateral progressive visual acuity loss due to choroidal metastasis. Adenoid cystic carcinoma is a rare primary tumour with significant metastatic potential. Our patient presented with a unilateral choroidal metastasis. According to the current literature, 8 cases of choroidal metastasis of salivary gland adenoid cystic carcinoma have been reported. This is the second case reported of choroidal metastasis with origin in a minor salivary gland, and the first one with origin in the minor salivary glands of the lower lip. Copyright © 2018 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

Symptomatic bilateral xanthogranuloma of the choroid plexus

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Selin Tural Emon

2017-01-01

Full Text Available Xanthogranulomas (XGRs of the choroid plexus are rare, asymptomatic, and benign lesions usually found incidentally. Here, we present a case of a 47-year-old male with bilateral XGR of the choroid plexus with periventricular edema and discuss our case in relation to a review of existing literature pertaining to the radiology of XGRs. To the best of our knowledge, this is the first reported case of bilateral trigonal XGR causing brain edema without ventricular dilatation. Despite the fact that they can cause hydrocephalus, XGRs are silent and benign lesions. Although the etiopathology of XGRs remains poorly understood, enhanced imaging analyses may provide additional information regarding edema and focal white matter signal changes.

Malignant melanoma in 63 dogs (2001-2011): the effect of carboplatin chemotherapy on survival.

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Brockley, L K; Cooper, M A; Bennett, P F

2013-01-01

The aim of the study was to compare the effect of carboplatin chemotherapy on the survival of canine patients diagnosed with malignant melanoma after loco-regional control or as a sole therapy. A retrospective study of 63 dogs with oral, digital or cutaneous malignant melanoma treated with surgery and/or chemotherapy was undertaken. Dogs were grouped based on the anatomical site of melanoma development. For oral melanoma, dogs were subclassified into two groups: loco-regional control and gross disease. All patients in the digital and cutaneous groups had achieved loco-regional control with surgery. Comparisons between survival data for each group at each anatomical site were then made. Within the loco-regional control groups survival time was compared between those treated with and without chemotherapy post surgery. For the oral melanoma patients with gross disease survival was compared between those treated with chemotherapy and palliative therapy. The toxicity of carboplatin chemotherapy was evaluated overall. The overall median survival times for patients with oral, digital and cutaneous melanoma were 389, 1,350 days and not reached (with a median follow-up of 776 days) respectively. Median survival time was defined as "not reached" when less than 50% of the subjects died of the disease at the end of the follow-up period, or at the time they were lost to follow-up. The addition of chemotherapy to surgery did not confer a survival benefit in the loco-regional control setting when assessing survival for each anatomical site. For oral melanoma patients with gross disease there was no difference between survival of patients treated with chemotherapy and palliative intent therapy. There was however an improvement in survival in the three dogs that responded to chemotherapy (978 days; p=0.039) compared to the eight non-responders (147 days). On univariate and multivariate analysis, anatomic location was the only variable that was significantly related to survival (p=0

Taurine uptake by human retinal pigment epithelium: implications for the transport of small solutes between the choroid and the outer retina.

Science.gov (United States)

Hillenkamp, Jost; Hussain, Ali A; Jackson, Timothy L; Cunningham, Joanna R; Marshall, John

2004-12-01

To characterize the Michaelis-Menten kinetics of the taurine transporter (TT) in retinal pigment epithelium (RPE) freshly isolated from human donor eyes. To identify the rate limiting compartment in the pathway of taurine delivery from the choroidal blood supply to the outer retina composed by Bruch's-choroid (BC) and the RPE in the human older age group. In human donor samples (4 melanoma-affected eyes, and 14 control eyes; age range, 62-93 years), radiochemical techniques were used to determine the RPE taurine accumulation at various exogenous concentrations. The transport capability of human RPE was obtained from a kinetic analysis of the high-affinity carrier over a substrate concentration of 1 to 60 microM taurine. Uptake of taurine into human RPE at a taurine concentration of 1 microM was independent of donor age (P > 0.05) and averaged at 2.83 +/- 0.27 (SEM) pmol/10 minutes per 6-mm trephine. Taurine transport by human RPE was mediated by a high-affinity carrier of K(m) 50 microM and V(max) of 267 pmol/10 minutes per 5-mm disc. In human donor RPE, uptake of taurine remained viable in the age range 62 to 93 years. Taurine transport rates in the RPE were lower than across the isolated BC complex, and thus the data suggest that the former compartment houses the rate-limiting step in the delivery of taurine to the outer retina.

CD147 silencing inhibits tumor growth by suppressing glucose transport in melanoma.

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Su, Juan; Gao, Tianyuan; Jiang, Minghao; Wu, Lisha; Zeng, Weiqi; Zhao, Shuang; Peng, Cong; Chen, Xiang

2016-10-04

Melanoma is a very malignant disease and there are still no effective treatments. CD147 participates in the carcinogenesis of multiple human cancers and GLUT-1, as a glucose transporter, is associated with tumor growth. However, the function of CD147 and GLUT-1 in melanoma have not been completely understood. Thus, in this study we investigated the expression of CD147 and GLUT-1 in melanoma tissue, which were overexpressed compared with that in nevus tissue. In addition, CD147 and GLUT-1 were co-localized in the cytoplasm of human melanoma A375 cells. Immunoprecipitation proved that CD147 interacted with GLUT-1 at D105-199. Silencing CD147 by specific siRNA could downregulate GLUT-1 level via inhibiting PI3K/Akt signaling and decrease glucose uptake in A375 cells. In vivo experiments also supported that CD147 knockdown suppressed the tumor growth in melanoma subcutaneous mice model, observed by micro PET/CT. Our results could help validate CD147 as a new therapeutic target for treating melanoma.

WITHDRAWN: Chemoimmunotherapy versus chemotherapy for metastatic malignant melanoma.

Science.gov (United States)

Sasse, Andre D; Sasse, Emma C; Clark, Luciana Go; Clark, Otavio Augusto Camara

2018-02-06

-analysis, with a total of 2625 participants. We found evidence of an increase of objective response rates in people treated with chemoimmunotherapy, in comparison with people treated with chemotherapy. Nevertheless, the impact of these increased response rates was not translated into a survival benefit. We found no difference in survival to support the addition of immunotherapy to chemotherapy in the systemic treatment of metastatic melanoma, with a hazard ratio of 0.89 (95% CI 0.72 to 1.11, P = 0.31). Additionally, we found increased hematological and non-hematological toxicities in people treated with chemoimmunotherapy. We failed to find any clear evidence that the addition of immunotherapy to chemotherapy increases survival of people with metastatic melanoma. Further use of combined immunotherapy and chemotherapy should only be done in the context of clinical trials.

Targeted alpha therapy for melanoma : from bench to bedside

International Nuclear Information System (INIS)

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

2001-01-01

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

Neovascular glaucoma after helium ion irradiation for uveal melanoma

International Nuclear Information System (INIS)

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

1986-01-01

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

Specific Detection of Serum Antibodies against BKPyV, A Small DNA Tumour Virus, in Patients Affected by Choroidal Nevi

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Silvia Pietrobon

2017-10-01

Full Text Available Ocular or choroidal nevus (CN is a rare benign neoplastic lesion of the eye. The cause of CN onset/progression, which arises from the transformation of ocular melanocytes, is not known. A fraction of CN patients may develop uveal melanoma. The objective of this study was to investigate the association between CN and BK polyomavirus (BKPyV, a small DNA tumor virus. Serum IgG antibodies which react with BKPyV antigens were analyzed. An indirect E.L.I.S.A. using synthetic peptides that mimic BKPyV antigens was employed. Serum antibodies against BKPyV were also investigated by haemagglutination inhibition (HAI assay. Sera were from CN patients and healthy subject (HS were the control. A statistically significant higher prevalence of antibodies against BKPyV capsid protein antigens in serum samples from CN patients was detected, compared to HS, using two independent techniques, indirect E.L.I.S.A. and HAI (87.3% CN vs. 62.1% HS and 91.5% CN vs. 64.4% HS, respectively; p < 0.005. Our data suggest an association exists between CN and BKPyV indicating that this small DNA tumor virus could be responsible in the onset of this benign neoplastic lesion affecting eye melanocytes. This investigation reports the association between choroidal nevi and BKPyV infection for the first time. These data are innovative in this field and may represent a starting point for further investigation into the putative role of BKPyV in CN onset/progression.

Primary malignant melanoma

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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.

[Choroidal neovascularization followed in a patient with "Multiple Evanescent White Dot Syndrome" (MEWDS) -- a case report].

Science.gov (United States)

Löw, U; Palmowski, A M; Weich, C-M; Ruprecht, K W

2004-12-01

Since the description of the "multiple evanescent white dot syndrome" (MEWDS) by Jampol et al, choroiditis has been in the focus of interest. But the classical type of MEWDS was an exceptional case in clinical routine. A 48-year-old female presented to our hospital with a sudden unilateral visual acuity decrease and an extension of the blind spot. Ophthalmoscopy and fluorescein angiography revealed typical multiple grey-white chorioretinal patches of the same stage with lesion areas of about 100 - 200 microm compatible with the diagnose of MEWDS. Although visual acuity increased continuously the patient developed a classical choroidal neovascularization within 4 weeks. She was treated with PDT and visual acuity as well as the ophthalmoscopic diagnosis remained stable. In spite of visual improvement in MEWDS, regular control is recommended. In addition we propose to consider the diagnosis of MEWDS if an enlargement of the blind spot and CNV without lesions of the retinal pigment epithelium are diagnosed.

Management of peripheral polypoidal choroidal vasculopathy with intravitreal bevacizumab and indocyanine green angiography-guided laser photocoagulation

Directory of Open Access Journals (Sweden)

Pukhraj Rishi

2012-01-01

Full Text Available A 69-year-old lady presented with complaints of decreased vision in left eye since one month. Best Corrected Visual Acuity (BCVA was 6/18 in that eye. Fundus examination revealed non-central geographic atrophy and soft drusens at macula in both eyes. Temporal periphery of left eye revealed subretinal exudates with altered sub-RPE hemorrhage mimicking peripheral exudative hemorrhagic chorioretinopathy (PEHCR. Fundus Fluorescein Angiogram showed window defects at macula and blocked fluorescence at temporal periphery in left eye. However, Indocyanine green angiography (ICGA revealed active peripheral choroidal polyps. The patient was successfully treated with intravitreal bevacizumab and ICGA-guided laser photocoagulation. 27 months after laser treatment, BCVA improved to 6/9. Rationale of consecutive anti-vascular endothelial growth factor (VEGF treatment followed by more definitive laser photocoagulation is that anti-VEGF aids in resolution of subretinal fluid, thus making the polyp more amenable to focal laser photocoagulation which stabilizes the choroidal vasculature and prevents further leakage.

Automated choroid segmentation based on gradual intensity distance in HD-OCT images.

Science.gov (United States)

Chen, Qiang; Fan, Wen; Niu, Sijie; Shi, Jiajia; Shen, Honglie; Yuan, Songtao

2015-04-06

The choroid is an important structure of the eye and plays a vital role in the pathology of retinal diseases. This paper presents an automated choroid segmentation method for high-definition optical coherence tomography (HD-OCT) images, including Bruch's membrane (BM) segmentation and choroidal-scleral interface (CSI) segmentation. An improved retinal nerve fiber layer (RNFL) complex removal algorithm is presented to segment BM by considering the structure characteristics of retinal layers. By analyzing the characteristics of CSI boundaries, we present a novel algorithm to generate a gradual intensity distance image. Then an improved 2-D graph search method with curve smooth constraints is used to obtain the CSI segmentation. Experimental results with 212 HD-OCT images from 110 eyes in 66 patients demonstrate that the proposed method can achieve high segmentation accuracy. The mean choroid thickness difference and overlap ratio between our proposed method and outlines drawn by experts was 6.72µm and 85.04%, respectively.

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

NARCIS (Netherlands)

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

2009-01-01

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

Enhanced Depth SD-OCT Images Reveal Characteristic Choroidal Changes in Patients With Vogt-Koyanagi-Harada Disease.

Science.gov (United States)

Li, Mei; Liu, Qiuhui; Luo, Yan; Li, Yonghao; Lin, Shaofen; Lian, Ping; Yang, Qiufen; Li, Xiaofang; Liu, Xialin; Sadda, SriniVas; Lu, Lin

2016-11-01

To identify characteristic choroidal changes of patients with Vogt-Koyanagi-Harada (VKH) disease at different stages. Fifty-four patients with VKH in the acute uveitic or convalescent stages, 24 patients with central serous chorioretinopathy (CSC), and 54 normal participants were enrolled in this prospective, observational study. Enhanced depth imaging spectral-domain optical coherence tomography scans were captured for all subjects to allow for comparison of choroidal morphological findings. Numerous round or oval hyperreflective profiles with hyporeflective cores, corresponding to choroidal vessels, were observed in the choroid of control participants and patients with CSC; whereas the numbers of these profiles were markedly decreased in the choroid of VKH patients in both the acute uveitic and convalescent stages. A reduction in vascular profiles in the choroid is observed in VKH and may aid in the differentiation with disorders such as CSC. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:1004-1012.]. Copyright 2016, SLACK Incorporated.

Assessment of Choroidal Microstructure and Subfoveal Thickness Change in Eyes With Different Stages of Age-Related Macular Degeneration.

Science.gov (United States)

Lu, Linna; Xu, Shiqiong; He, Fangling; Liu, Yan; Zhang, Yidan; Wang, Jing; Wang, Zhiliang; Fan, Xianqun

2016-03-01

Age-related macular degeneration (AMD) is a major cause of irreversible blindness. Choroidal structural changes seem to be inevitable in AMD pathogenesis. Our study revealed associated choroidal microstructural changes in AMD eyes.The aim of the study was to compare choroidal microstructural changes in eyes with AMD of different stages.The study was a retrospective, cross-sectional case series.The participants comprised of 32 age-matched normal eyes as controls, and 26 fellow uninvolved eyes of intermediate/late AMD, 29 of early AMD, 28 of intermediate AMD, and 39 of late AMD.All subjects underwent comprehensive ophthalmologic examination. The choroid images, including subfoveal choroidal thickness, percentage of Sattler layer area, and en face images of the choroid, were obtained using spectral-domain optical coherence tomography.The main outcome measures were subfoveal choroidal thickness changes, percentage of Sattler layer area changes, and en face images of the choroid in AMD eyes.One hundred fifty-four eyes of 96 individuals with mean age of 67.1±9.2 years were included. The mean subfoveal choroidal thickness was 295.4 ± 56.8 μm in age-matched normal eyes, 306.7 ± 68.4 μm in fellow uninvolved eyes with AMD, 293.8 ± 80.4 μm in early AMD, 215.6 ± 80.4 μm in intermediate AMD, and 200.4 ± 66.6 μm in late AMD (F = 14.2, all P < 0.001). Choroidal thickness was greater in early AMD eyes than in intermediate/late AMD eyes (P < 0.001). Mean percentage of Sattler layer area in each group showed a similar tendency. Microstructure of the choroid showed reduced vascular density of Sattler layer areas in late AMD eyes compared with normal eyes.Decreasing subfoveal choroidal thickness and percentage of Sattler layer area were demonstrated in the progression of AMD. The choroidal change was related to atrophy of the microstructural changes of underlying capillaries and medium-sized vessels.

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

Energy Technology Data Exchange (ETDEWEB)

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

2011-12-15

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

Choroid metastasis of papillary thyroid carcinoma. Color doppler ultrasound study

International Nuclear Information System (INIS)

Ganado, T.; Torre, S. de la; Contreras, E.; Hernandez, J.

1997-01-01

The most common causes of intraocular metastases are breast and lung cancers, although many other neoplasms can metastasize to the eye. Most of the metastases are located in the posterior pole and the choroid is more often involved than the retina. We present a case of a choroidal metastasis from a papillary carcinoma of the thyroid, associated with a massive subretinal hemorrhage. Findings with color Doppler ultrasound are emphasized. (Author) 9 refs

Waardenburg syndrome: iris and choroidal hypopigmentation: findings on anterior and posterior segment imaging.

Science.gov (United States)

Shields, Carol L; Nickerson, Stephanie J; Al-Dahmash, Saad; Shields, Jerry A

2013-09-01

Waardenburg syndrome typically manifests with congenital iris pigmentary abnormalities, but careful inspection can reveal additional posterior uveal pigmentary abnormalities. To demonstrate iris and choroidal hypopigmentation in patients with Waardenburg syndrome. Retrospective review of 7 patients referred for evaluation of presumed ocular melanocytosis. To describe the clinical and imaging features of the anterior and posterior uvea. In all patients, the diagnosis of Waardenburg syndrome was established. The nonocular features included white forelock in 4 of 7 (57%), tubular nose in 5 of 6 (83%), and small nasal alae in 5 of 6 (83%) patients. In 2 patients, a hearing deficit was documented on audiology testing. Family history of Waardenburg syndrome was elicited in 5 of 7 (71%) patients. Ocular features (7 patients) included telecanthus in 5 (71%), synophrys in 2 (29%), iris hypopigmentation in 5 (71%), and choroidal hypopigmentation in 5 (71%) patients. No patient had muscle contractures or Hirschsprung disease. Visual acuity was 20/20 to 20/50 in all patients. Iris hypopigmentation in 8 eyes was sector in 6 (75%) and diffuse (complete) in 2 (25%). Choroidal hypopigmentation in 9 eyes (100%) showed a sector pattern in 6 (67%) and a diffuse pattern in 3 (33%). Anterior segment optical coherence tomography revealed the hypopigmented iris to be thinner and with shallower crypts than the normal iris. Posterior segment optical coherence tomography showed a normal retina in all patients, but the subfoveal choroid in the hypopigmented region was slightly thinner (mean, 197 μm) compared with the opposite normal choroid (243 μm). Fundus autofluorescence demonstrated mild hyperautofluorescence (scleral unmasking) in hypopigmented choroid and no lipofuscin abnormality. Waardenburg syndrome manifests hypopigmentation of the iris and choroid with imaging features showing a slight reduction in the thickness of the affected tissue.

The choroid plexus in normal full-term neonate : a study of morphological variety on sonography

International Nuclear Information System (INIS)

Lee, Young Seok; Kim, Ji Hye

1999-01-01

The purpose of this study was to evaluate the sonographic features of normal choroid plexus, thus helping avoid misinterpretations such as intraventricular hemorrhage or abnormality. Posterior coronal, parasagittal, and oblique sagittal scans of 400 choroid plexus in normal full-term neonates(100 girls, 100 boys) were reviewed with special attention to coronal configuration, glomus patterns, and the shape of anterior ends. Sonographic features were classified as follows ; tubular(type 1), posterior clubbing(type 2), mid-bulging(type 3), or double choroidal pattern(type 4), as seen on posterior coronal scans; crescent(type 1), superior notching(type 2), dorsal bulging(type 3), or inferior notching(type 4), as seen on parasagittal scans; and anterior tapering(type 1) and clubbing shape (type 2) on oblique parasagittal scans. Maximal diameters of the choroid plexus on posterior coronal scan and the glomus on parasagittal scan were measured. All sonographic measurements of normal choroid plexus were statistically analysed according to gender and side. Four hundred normal choroid plexus were classified as 293 cases(73%) of tubular pattern(type 1), 50 cases(13%) of posterior bulging(type 2), 44 cases (11%) of mid-bulging(type 3) and 13 cases(3%) of double choroidal pattern (type 4) as seen on posterior coronal scans ; 263 cases(66%) of crescent shape(type 1), 70 cases(17%) of superior notching (type 2), 38 cases(9%) of dorsal bulging(type 3), and 29 cases(7%) of inferior notching(type 4), as seen on parasagittal scans; and 233 cases(58%) of anterior tapering(type 1) and 167 cases(42%) of anterior clubbing (type 2), as seen on oblique parasagittal scans. Maximal diameters of the choroid plexus on posterior coronal scan were 7.17±0.12 mm (95% confidence interval [CI]) on the right side and 7.13±0.19 mm (95% CI) on the left side, and 8.13±0.24(95% CI) mm on the right and 8.57±0.29 mm on the left side glomus on parasagittal scan. There were no significant statistical

The choroid plexus in normal full-term neonate : a study of morphological variety on sonography

Energy Technology Data Exchange (ETDEWEB)

Lee, Young Seok [Dankook Univ. Hospital, Seoul (Korea, Republic of); Kim, Ji Hye [Chunganggil Hospital, Seoul (Korea, Republic of)

1999-04-01

The purpose of this study was to evaluate the sonographic features of normal choroid plexus, thus helping avoid misinterpretations such as intraventricular hemorrhage or abnormality. Posterior coronal, parasagittal, and oblique sagittal scans of 400 choroid plexus in normal full-term neonates(100 girls, 100 boys) were reviewed with special attention to coronal configuration, glomus patterns, and the shape of anterior ends. Sonographic features were classified as follows ; tubular(type 1), posterior clubbing(type 2), mid-bulging(type 3), or double choroidal pattern(type 4), as seen on posterior coronal scans; crescent(type 1), superior notching(type 2), dorsal bulging(type 3), or inferior notching(type 4), as seen on parasagittal scans; and anterior tapering(type 1) and clubbing shape (type 2) on oblique parasagittal scans. Maximal diameters of the choroid plexus on posterior coronal scan and the glomus on parasagittal scan were measured. All sonographic measurements of normal choroid plexus were statistically analysed according to gender and side. Four hundred normal choroid plexus were classified as 293 cases(73%) of tubular pattern(type 1), 50 cases(13%) of posterior bulging(type 2), 44 cases (11%) of mid-bulging(type 3) and 13 cases(3%) of double choroidal pattern (type 4) as seen on posterior coronal scans ; 263 cases(66%) of crescent shape(type 1), 70 cases(17%) of superior notching (type 2), 38 cases(9%) of dorsal bulging(type 3), and 29 cases(7%) of inferior notching(type 4), as seen on parasagittal scans; and 233 cases(58%) of anterior tapering(type 1) and 167 cases(42%) of anterior clubbing (type 2), as seen on oblique parasagittal scans. Maximal diameters of the choroid plexus on posterior coronal scan were 7.17{+-}0.12 mm (95% confidence interval [CI]) on the right side and 7.13{+-}0.19 mm (95% CI) on the left side, and 8.13{+-}0.24(95% CI) mm on the right and 8.57{+-}0.29 mm on the left side glomus on parasagittal scan. There were no significant

Surgical treatment of iris and ciliary body melanoma: follow-up of a 25-year series of patients

DEFF Research Database (Denmark)

Klauber, Stefan; Jensen, Peter K; Prause, Jan U

2010-01-01

Purpose: To evaluate outcome of surgical resection of iris and irido-ciliary melanomas. Method: Retrospective analysis of all cases treated in Denmark 1975-1999 with clinical follow-up in 2002 and death certificate analysis in 2008. A quality of life questionnaire was completed at follow-up. Resu......Purpose: To evaluate outcome of surgical resection of iris and irido-ciliary melanomas. Method: Retrospective analysis of all cases treated in Denmark 1975-1999 with clinical follow-up in 2002 and death certificate analysis in 2008. A quality of life questionnaire was completed at follow...... time. However, none had changed job as a consequence of the surgical treatment. Only two patients were emotionally affected by the diagnosis of iris melanoma. Conclusion: Resection of small iris and irido-ciliary melanomas is a safe and efficient procedure, provided that strict diagnostic and surgical...

Primary ovarian malignant melanoma

Directory of Open Access Journals (Sweden)

Kostov Miloš

2010-01-01

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

Burden of Melanoma

NARCIS (Netherlands)

C. Holterhues (Cynthia)

2011-01-01

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

Choroidal findings in dome-shaped macula in highly myopic eyes: a longitudinal study.

Science.gov (United States)

Viola, Francesco; Dell'Arti, Laura; Benatti, Eleonora; Invernizzi, Alessandro; Mapelli, Chiara; Ferrari, Fabio; Ratiglia, Roberto; Staurenghi, Giovanni; Barteselli, Giulio

2015-01-01

To describe choroidal findings in dome-shaped macula associated with high myopia using fluorescein angiography (FA), indocyanine green angiography (ICGA), and spectral-domain optical coherence tomography (SD OCT), and to elucidate the mechanism and natural course of serous retinal detachment (RD) associated with dome-shaped macula. Retrospective, observational case series. We reviewed longitudinal imaging results of 52 highly myopic eyes with dome-shaped macula. Changes on FA and ICGA were assessed. Retinal, choroidal, and scleral thicknesses and bulge height were measured on SD OCT. Serous RD was the most common abnormality associated with dome-shaped macula, detected by SD OCT in 44% of the cases with no associated choroidal neovascularization. Significant differences in the proportion of eyes with pinpoint leakage on FA (P macula was likely caused by choroidal vascular changes, similar to central serous chorioretinopathy, but specifically confined in the inward bulge of the staphyloma and secondary to excessive scleral thickening. Serous retinal detachment showed fluctuating changes over time, with alternating active and inactive stages. Angiographic findings in dome-shaped macula suggest the choroid as a target for possible treatment strategies. Copyright © 2015 Elsevier Inc. All rights reserved.

Dark adaptation in relation to choroidal thickness in healthy young subjects

DEFF Research Database (Denmark)

Munch, Inger Christine; Altuntas, Cigdem; Li, Xiao Qiang

2016-01-01

a sensitivity of 5.0 × 10-3 cd/m2 (time to rod intercept) and the slope (rod adaptation rate). The choroid was imaged using enhanced-depth imaging spectral-domain optical coherence tomography (EDI-OCT). Results: The time to the rod intercept was 7.3 ± 0.94 (range 5.1 - 10.2) min. Choroidal thickness 2.5° above...

Comparison of choroidal thickness using swept-source and spectral-domain optical coherence tomography in normal Indian eyes.

Science.gov (United States)

Narendran, Siddharth; Manayath, George; Venkatapathy, Narendran

2018-01-01

Choroidal thickness measurements are reported to differ between spectral-domain optical coherence tomography (SD-OCT) and swept-source OCT (SS-OCT). The aim of this study was to assess the comparability of choroidal thickness measurements using SS-OCT and SD-OCT devices among normal participants. This was a prospective study of 31 (62 eyes) normal participants. Choroidal imaging was performed sequentially with the Spectralis OCT (SD-OCT) and the deep range imaging OCT (DRI OCT-1) (SS-OCT) using standardized imaging protocols. The subfoveal choroidal thickness (SFChT) was measured manually by two masked retinal specialists. Paired t -tests and intraclass correlation coefficients (ICCs) were used to compare the measurements. The mean SFChT was 319.5 μm and 325.3 μm for DRI OCT-1 and Spectralis OCT, respectively ( P = 0.001), with a mean difference of 5.9 with ICC of 0.97. The mean difference in choroidal thickness between the OCT devices was larger among eyes with choroidal thickness > 350 μm compared with eyes with thinner choroids (8.0 μm vs. 4.7 μm). SFChT measurements are comparable between DRI OCT-1 and Spectralis OCT. The variability between the devices increases in thicker choroids.

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

Science.gov (United States)

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

2015-01-01

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

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

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

2012-08-01

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

TNF-α mediates choroidal neovascularization by upregulating VEGF expression in RPE through ROS-dependent β-catenin activation.

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Wang, Haibo; Han, Xiaokun; Wittchen, Erika S; Hartnett, M Elizabeth

2016-01-01

Inflammation, oxidative stress, and angiogenesis have been proposed to interact in age-related macular degeneration. It has been postulated that external stimuli that cause oxidative stress can increase production of vascular endothelial growth factor (VEGF) in retinal pigment epithelial (RPE) cells. In this study, we tested the hypothesis that the inflammatory cytokine, tumor necrosis factor alpha (TNF-α), contributed to choroidal neovascularization (CNV) by upregulating VEGF in RPE through intracellular reactive oxygen species (ROS)-dependent signaling and sought to understand the mechanisms involved. In a murine laser-induced CNV model, 7 days after laser treatment and intravitreal neutralizing mouse TNF-α antibody or isotype immunoglobulin G (IgG) control, the following measurements were made: 1) TNF-α protein and VEGF protein in RPE/choroids with western blot, 2) CNV volume in RPE/choroidal flatmounts, and 3) semiquantification of oxidized phospholipids stained with E06 antibody within CNV with immunohistochemistry (IHC). In cultured human RPE cells treated with TNF-α or PBS control, 1) ROS generation was measured using the 2',7'-dichlorodihydrofluorescein diacetate (DCFDA) fluorescence assay, and 2) NOX4 protein and VEGF protein or mRNA were measured with western blot or quantitative real-time PCR in cells pretreated with apocynin or nicotinamide adenine dinucleotide phosphate-oxidase (NADPH) inhibitor, VAS 2870, or transfected with p22phox siRNA, and each was compared to its appropriate control. Western blots of phosphorylated p65 (p-p65), total p65 and β-actin, and quantitative real-time PCR of VEGF mRNA were measured in human RPE cells treated with TNF-α and pretreatment with the nuclear factor kappa B inhibitor, Bay 11-7082 or control. Western blots of β-catenin, VEGF, and p22phox and coimmunoprecipitation of β-catenin and T-cell transcriptional factor were performed in human RPE cells treated with TNF-α following pretreatment with �

Choroidal neovascular membrane

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Bhatt Nitul

1998-01-01

Full Text Available Choroidal neovascular membrane in the macular area is one of the leading causes of severe visual loss. Usually a manifestation in elderly population, it is often associated with age-related macular degeneration. The current mainstay of management is early diagnosis, usually by fundus examination, aided by angiography and photocoagulation in selected cases. Various other modalities of treatment including surgery are being considered as alternate options, but with limited success. The purpose of this review is to briefly outline the current concepts and the management strategy from a clinician′s viewpoint.

Choroidal neovascular membrane.

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Bhatt, N S; Diamond, J G; Jalali, S; Das, T

1998-06-01

Choroidal neovascular membrane in the macular area is one of the leading causes of severe visual loss. Usually a manifestation in elderly population, it is often associated with age-related macular degeneration. The current mainstay of management is early diagnosis, usually by fundus examination, aided by angiography and photocoagulation in selected cases. Various other modalities of treatment including surgery are being considered as alternate options, but with limited success. The purpose of this review is to briefly outline the current concepts and the management strategy from a clinician's viewpoint.

The synthetic parasite-derived peptide GK1 increases survival in a preclinical mouse melanoma model.

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Pérez-Torres, Armando; Vera-Aguilera, Jesús; Hernaiz-Leonardo, Juan Carlos; Moreno-Aguilera, Eduardo; Monteverde-Suarez, Diego; Vera-Aguilera, Carlos; Estrada-Bárcenas, Daniel

2013-11-01

The therapeutic efficacy of a synthetic parasite-derived peptide GK1, an immune response booster, was evaluated in a mouse melanoma model. This melanoma model correlates with human stage IIb melanoma, which is treated with wide surgical excision; a parallel study employing a surgical treatment was carried out as an instructive goal. C57BL/6 mice were injected subcutaneously in the flank with 2×10(5) B16-F10 murine melanoma cells. When the tumors reached 20 mm3, mice were separated into two different groups; the GK1 group, treated weekly with peritumoral injections of GK1 (10 μg/100 μL of sterile saline solution) and the control group, treated weekly with an antiseptic peritumoral injection of 100 μL of sterile saline solution without further intervention. All mice were monitored daily for clinical appearance, tumor size, and survival. Surgical treatment was performed in parallel when the tumor size was 20 mm3 (group A), 500 mm3 (group B), and >500 mm3 (group C). The GK1 peptide effectively increased the mean survival time by 9.05 days, corresponding to an increase of 42.58%, and significantly delayed tumor growth from day 3 to 12 of treatment. In addition, tumor necrosis was significantly increased (pcancers remains to be determined, and surgical removal remains a challenge for any new experimental treatment of melanoma in mouse models.

SCLERAL AND CHOROIDAL THICKNESS IN SECONDARY HIGH AXIAL MYOPIA.

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Shen, Ling; You, Qi Sheng; Xu, Xiaolin; Gao, Fei; Zhang, Zhibao; Li, Bin; Jonas, Jost B

2016-08-01

To assess differences in scleral and choroidal thickness between eyes with secondary high axial myopia caused by congenital glaucoma, eyes with primary high axial myopia, and nonhighly myopic eyes. The study consisted of 301 Chinese individuals with a mean age of 23.9 ± 22.6 years and mean axial length of 24.8 ± 4.2 mm. It included the "secondary highly myopic group" (SHMG) because of congenital glaucoma (n = 20 eyes; axial length >26.0 mm), the "primary highly myopic group" (PHMG) (n = 73; axial length >26.0 mm), and the remaining nonhighly myopic group (NHMG). The secondary highly myopic group versus the primary highly myopic group had significantly thinner sclera in the pars plana region (343 ± 71 μm versus 398 ± 83 μm; P = 0.006), whereas scleral thickness in other regions did not differ significantly between both highly myopic groups and was significantly thinner in both highly myopic groups than in the NHMG. Mean total scleral volume did not differ significantly (P > 0.20) between any group (SHMG: 659 ± 106 μm; PHMG: 667 ± 128 μm; NHMG: 626 ± 135 μm). Choroidal thickness was significantly thinner in both highly myopic groups than in the NHMG, with no significant differences between both highly myopic groups. Choroidal volume did not differ significantly (P > 0.40) between any of the groups (SHMG: 43 ± 12 μm; PHMG: 43 ± 13 μm; NHMG: 46 ± 17 μm). In secondary high axial myopia, the sclera gets thinner anterior and posterior to the equator; whereas in primary high axial myopia, scleral thinning is predominantly found posterior to the equator. Because volume of sclera and choroid did not differ between any group, scleral and choroidal thinning in myopia may be due to a rearrangement of tissue and not due to the new formation of tissue.

In vivo retinal optical coherence tomography at 1030 nm with enhanced penetration into the choroid

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Unterhuber, A.; Povazay, B.; Hermann, B.; Sattmann, H.; Michels, S.; Sacu, S.; Ahlers, C.; Scholda, C.; Chavez-Pirson, A.; Schmidt-Erfurth, U.; Fercher, Adolf F.; Drexler, W.

2005-08-01

In vivo retinal imaging with ~ 8 μm axial resolution at 1030 nm is demonstrated for the first time, enabling enhanced penetration into the choroid. A new high power, broad bandwidth light source based on amplified spontaneous emission (NP Photonics, λc = 1030 nm, Δλ= 50 nm, Pout = 25 mW) has been interfaced to a time domain ophthalmic OCT system. In vivo retinal OCT tomograms performed at 800 nm are compared to those achieved at 1030 nm. Retinal OCT at longer wavelengths, e.g. 1030 nm significantly improves the visualization of the retinal pigment epithelium/choriocapillaris/choroid interface and might therefore provide new insight into choroidal/choriocapillary changes in age-related macular degeneration and other diseases of the retinal pigment epithelium (RPE)-choroid complex. 1030 nm OCT could also become a valuable tool in monitoring treatment effects on the choroids as in Verteporfin therapy.

Retrospective analysis of drug utilization, health care resource use, and costs associated with IFN therapy for adjuvant treatment of malignant melanoma

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Zhang Y

2015-07-01

Full Text Available ≥Ying Zhang,1 Trong Kim Le,1 James W Shaw,2 Srividya Kotapati31Center for Observational Research and Data Sciences, Worldwide Health Economics and Outcomes Research, Bristol-Myers Squibb Research and Development, Hopewell, NJ, USA; 2Worldwide Health Economics and Outcomes Research, Bristol-Myers Squibb Research and Development, Princeton, NJ, USA; 3Worldwide Health Economics and Outcomes Research, Bristol-Myers Squibb Research and Development, Wallingford Center, CT, USABackground: This study examines real-world drug utilization patterns, health care resource use, and costs among patients receiving adjuvant treatment with IFN versus patients receiving no treatment ("observation" for malignant melanoma following surgery.Methods: A retrospective cohort study was conducted using administrative claims from Truven Health Analytics (MarketScan® to identify all adjuvant melanoma patients (aged ≥18 years diagnosed between June 2007 and June 2011 who had a lymph node dissection (ie, index surgery and were treated with IFN or subsequently observed. Health care resource use and costs of services were converted to 2012 US dollars and were evaluated and compared using multivariable regression.Results: Of 1,999 eligible subjects with melanoma surgery claims, 179 (9.0% were treated with IFN and 1,820 (91.0% were observed. The median duration (days and number of doses of IFN therapy were 73 and 36, respectively. Among IFN-treated patients, only 10.6% completed ≥80% of maintenance therapy. The total average cost for patients treated with IFN was US$60,755±$3,972 (n=179; significantly higher than for patients undergoing observation ($31,641±$2,471; P<0.0001. Similar trends were observed when evaluating total cost components, including melanoma-related and non-melanoma–related medical costs. Among the melanoma-related medical costs, outpatient services, including office visits and laboratory testing, represented between 33% and 53% of total costs and

Primary Culture of Choroid Plexuses from Neonate Rats Containing Progenitor Cells Capable of Differentiation

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Sheng-Li Huang

2013-12-01

Full Text Available Background: The choroid plexuses, which could secrete a number of neurotrophins, have recently been used in transplantation in central nervous system diseases. Aims: To study the mechanism of nerve regeneration in the central nervous system by grafting choroid plexus tissues. Study Design: Animal experimentation. Methods: The choroid plexuses from the lateral ventricles of neonatal rats were cultured in adherent culture, and immunocytochemical methods were used to analyse the progenitor cells on days 2, 6, and 10 after seeding. Results: Expression of both nestin and glial fibrillary acidic protein was observed in small cell aggregates on day 2 in primary culture. Most of the nestin-positive cells on day 6 were immunoreactive to glial fibrillary acidic protein antibody. No cells expressing nestin or glial fibrillary acidic protein were seen on day 10. Conclusion: These experimental results indicate that the choroid plexus contains a specific cell population – progenitor cells. Under in vitro experimental conditions, the progenitor cells differentiated into choroid plexus epithelial cells but did not form neurons or astrocytes.

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

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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.

Ciliary body melanoma with optic nerve invasion.

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

1990-01-01

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

Total body topical 5-fluorouracil for extensive non-melanoma skin cancer

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van Ruth, Serge; Jansman, Frank G. A.; Sanders, Cornelis J.

Background Topical 5-fluorouracil 5% cream is one of the treatment modalities for non-melanoma skin cancer (NMSC). There is a lack of suitable therapies to treat patients with extensive NMSC. In this paper we report two patients with extensive NMSC treated by total body application of topical

Comparison of outcomes between overlapping-spot and single-spot photodynamic therapy for circumscribed choroidal hemangioma

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Zhao-An Su

2014-02-01

Full Text Available AIM:To compare the efficacy and safety of photodynamic therapy (PDT with overlapping multiple spots and single spot for treating circumscribed choroidal hemangioma.METHODS:Twenty-two patients (22 eyes with symptomatic circumscribed choroidal hemangioma received PDT treatment. Fourteen patients received overlapping spots (two to three spots PDT, whereas eight patients received single-spot PDT. Laser was used at 50J/cm2 for 83s in the overlapping-spot group and 50J/cm2 for 166s in the single-spot group. Clinical examination, funduscopy, fluorescein angiography, and ultrasonography were performed at baseline and after treatment.RESULTS:The mean follow-up time was 28.5±8.0 months in the overlapping-spot group and 27.0±5.0 months in the single-spot group. Nine patients (64.2% had their vision improved over two lines on the Snellen chart, and five patients showed stable visual acuity in the overlapping-spot group. The mean thickness of tumor decreased from 2.7±0.8mm to 1.2±0.9mm, and the mean greatest tumor linear dimension decreased from 7.4±1.5mm to 4.5±3.5mm after treatment. In the single-spot group, two patients (25% had their vision improved over two lines on the Snellen chart, and six patients had unchanged stable vision. The mean tumor thickness in this group decreased from 2.5±0.7mm to 1.4±1.0mm, and the mean greatest tumor linear dimension decreased from 7.2±1.3mm to 4.7±3.6mm. No significant differences in visual improvement and tumor regression were found between the two groups.CONCLUSION: Overlapping-spot PDT under appropriate treatment parameters and strategies is as effective and safe as single-spot PDT for treating symptomatic circumscribed choroidal hemangioma. Improved or stabilized visual acuity was achieved as a result of tumor regression.

Phase I/II Study of Metastatic Melanoma Patients Treated with Nivolumab Who Had Progressed after Ipilimumab.

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Weber, Jeffrey; Gibney, Geoffrey; Kudchadkar, Ragini; Yu, Bin; Cheng, Pingyan; Martinez, Alberto J; Kroeger, Jodie; Richards, Allison; McCormick, Lori; Moberg, Valerie; Cronin, Heather; Zhao, Xiuhua; Schell, Michael; Chen, Yian Ann

2016-04-01

The checkpoint inhibitor nivolumab is active in patients with metastatic melanoma who have failed ipilimumab. In this phase I/II study, we assessed nivolumab's safety in 92 ipilimumab-refractory patients with unresectable stage III or IV melanoma, including those who experienced grade 3-4 drug-related toxicity to ipilimumab. We report long-term survival, response duration, and biomarkers in these patients after nivolumab treatment (3 mg/kg) every 2 weeks for 24 weeks, then every 12 weeks for up to 2 years, with or without a multipeptide vaccine. The response rate for ipilimumab-refractory patients was 30% (95% CI, 21%-41%). The median duration of response was 14.6 months, median progression-free survival was 5.3 months, and median overall survival was 20.6 months, when patients were followed up for a median of 16 months. One- and 2-year survival rates were 68.4% and 31.2%, respectively. Ipilimumab-naïve and ipilimumab-refractory patients showed no significant difference in survival. The 21 patients with prior grade 3-4 toxicity to ipilimumab that was managed with steroids tolerated nivolumab well, with 62% (95% CI, 38%-82%) having complete or partial responses or stabilized disease at 24 weeks. High numbers of myeloid-derived suppressor cells (MDSC) were associated with poor survival. Thus, survival and long-term safety were excellent in ipilimumab-refractory patients treated with nivolumab. Prior grade 3-4 immune-related adverse effects from ipilimumab were not indicative of nivolumab toxicities, and patients had a high overall rate of remission or stability at 24 weeks. Prospectively evaluating MDSC numbers before treatment could help assess the expected benefit of nivolumab. ©2016 American Association for Cancer Research.

Characterization of CD8+ T-Cell Responses in the Peripheral Blood and Skin Injection Sites of Melanoma Patients Treated with mRNA Electroporated Autologous Dendritic Cells (TriMixDC-MEL

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Daphné Benteyn

2013-01-01

Full Text Available Treatment of melanoma patients with mRNA electroporated dendritic cells (TriMixDC-MEL stimulates T-cell responses against the presented tumor-associated antigens (TAAs. In the current clinical trials, melanoma patients with systemic metastases are treated, requiring priming and/or expansion of preexisting TAA-specific T cells that are able to migrate to both the skin and internal organs. We monitored the presence of TAA-specific CD8+ T cells infiltrating the skin at sites of intradermal TriMixDC-MEL injection (SKILs and within the circulation of melanoma patients treated in two clinical trials. In 10 out of fourteen (71% patients screened, CD8+ T cells recognizing any of the four TAA presented by TriMixDC-MEL cellular vaccine were found in both compartments. In total, 30 TAA-specific T-cell responses were detected among the SKILs and 29 among peripheral blood T cells, of which 24 in common. A detailed characterization of the antigen specificity of CD8+ T-cell populations in four patients indicates that the majority of the epitopes detected were only recognized by CD8+ T cells derived from either skin biopsies or peripheral blood, indicating that some compartmentalization occurs after TriMix-DC therapy. To conclude, functional TAA-specific CD8+ T cells distribute both to the skin and peripheral blood of patients after TriMixDC-MEL therapy.

Characterization of CD8+ T-cell responses in the peripheral blood and skin injection sites of melanoma patients treated with mRNA electroporated autologous dendritic cells (TriMixDC-MEL).

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Benteyn, Daphné; Van Nuffel, An M T; Wilgenhof, Sofie; Corthals, Jurgen; Heirman, Carlo; Neyns, Bart; Thielemans, Kris; Bonehill, Aude

2013-01-01

Treatment of melanoma patients with mRNA electroporated dendritic cells (TriMixDC-MEL) stimulates T-cell responses against the presented tumor-associated antigens (TAAs). In the current clinical trials, melanoma patients with systemic metastases are treated, requiring priming and/or expansion of preexisting TAA-specific T cells that are able to migrate to both the skin and internal organs. We monitored the presence of TAA-specific CD8(+) T cells infiltrating the skin at sites of intradermal TriMixDC-MEL injection (SKILs) and within the circulation of melanoma patients treated in two clinical trials. In 10 out of fourteen (71%) patients screened, CD8(+) T cells recognizing any of the four TAA presented by TriMixDC-MEL cellular vaccine were found in both compartments. In total, 30 TAA-specific T-cell responses were detected among the SKILs and 29 among peripheral blood T cells, of which 24 in common. A detailed characterization of the antigen specificity of CD8(+) T-cell populations in four patients indicates that the majority of the epitopes detected were only recognized by CD8(+) T cells derived from either skin biopsies or peripheral blood, indicating that some compartmentalization occurs after TriMix-DC therapy. To conclude, functional TAA-specific CD8(+) T cells distribute both to the skin and peripheral blood of patients after TriMixDC-MEL therapy.

Dabrafenib Plus Trametinib Approved for Melanoma, Thyroid Cancer

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FDA recently approved the combination of dabrafenib (Taflinar) and trametinib (Mekinist) to treat some patients with melanoma and anaplastic thyroid cancer whose tumors have a mutation in the BRAF gene. As this Cancer Currents blog post explains, this is the first treatment approved specifically for anaplastic thyroid

Anti-vascular endothelial growth factor therapy for the treatment of myopic choroidal neovascularization

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Tan CS

2017-09-01

Full Text Available Colin S Tan,1,2 SriniVas R Sadda3 1National Healthcare Group Eye Institute, Tan Tock Seng Hospital, Singapore; 2Fundus Image Reading Center, National Healthcare Group Eye Institute, Singapore; 3Doheny Eye Institute, University of California Los Angeles, CA, USA Abstract: Myopic choroidal neovascularization (CNV is a sight-threatening condition which occurs in eyes with myopia, particularly in those with pathologic myopia. It is the most common cause of CNV among patients younger than 50 years. Hemorrhage and exudation from the CNV lesion may eventually result in scarring or chorioretinal atrophy. While myopic CNV was previously treated with focal laser photocoagulation or photodynamic therapy (PDT, the current treatment of choice is anti-vascular endothelial growth factor (VEGF agents. Many studies have demonstrated the efficacy of intravitreal anti-VEGF agents in the treatment of myopic CNV. The RADIANCE study reported that intravitreal ranibizumab was superior to PDT in eyes with myopic CNV (at 3 months, both groups receiving intravitreal ranibizumab gained 10.5 and 10.6 letters vs 2.2 letters among patients receiving PDT. In addition, the study demonstrated similar visual outcomes in eyes treated on the basis of visual acuity stabilization or disease activity criteria. Other clinical studies have provided evidence for the efficacy of ranibizumab and aflibercept in the treatment of myopic CNV. This review addresses the epidemiology, pathophysiology, and imaging characteristics of myopic CNV, and discusses the evidence for the efficacy of anti-VEGF agents as compared to laser photocoagulation and PDT. Keywords: myopic choroidal neovascularization, ranibizumab, anti-vascular endothelial growth factor

Choroidal thickness and biometric markers for the screening of lacquer cracks in patients with high myopia.

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Nan-Kai Wang

Full Text Available OBJECTIVES: Validation of choroidal thickness and other biometrics measured by spectral domain optical coherence tomography (SD-OCT in predicting lacquer cracks formation in highly myopic eyes. METHODS: Patients with a refractive error worse than -8 diopters and moderate myopic maculopathy were recruited into two groups based on the presence or absence of lacquer cracks (36 eyes without and 33 eyes with lacquer cracks. Choroidal thickness, refractive error, and axial length were measured and subjected to receiver operating characteristic curve analysis to identify the optimal cutoff values at predicting lacquer crack formation. The width of the retinal pigment epithelium (RPE, RPE to the inner segment/outer segment line, RPE to the external limiting membrane were also measured and compared to the subfoveal choroidal thickness to assess their relationships as potential markers of lacquer crack formation. RESULTS: Lacquer crack is associated with decreased choroidal thickness, lower best-corrected visual acuity, longer axial length and higher refractive errors. Choroidal thickness has the strongest association with lacquer crack formation versus axial length and refractive error. In eyes with lacquer cracks, stellate lacquer cracks are associated with thinner choroidal thickness compared to eyes with linear lacquer cracks. Subfoveal choroidal thickness less than the width of the retinal pigment epithelium to the inner segment/outer segment line is also associated with lacquer crack formation (sensitivity 78.8%, specificity 88.3%, and accuracy 81.2%. CONCLUSIONS: This study suggests that choroidal thickness and other SD-OCT measurements could be employed clinically to predict the development and severity of lacquer cracks in patients with high myopia.

Canine Choroid Plexus Tumor with Intracranial Dissemination Presenting as Multiple Cystic Lesions

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Trisha J. Oura

2013-01-01

Full Text Available A Miniature Pinscher developed acute blindness and behavioral changes. On magnetic resonance imaging (MRI, there were multiple small intra-axial cystic lesions, and primary differential diagnoses included primary or metastatic neoplasia and neurocysticercosis. These cystic lesions were subsequently diagnosed histopathologically as disseminated choroid plexus carcinoma. This is only the second documented description of this diagnosis in a dog, but both patients had very similar MRI findings. This patient adds to the literature about the MRI characteristics of choroid plexus tumors and indicates that choroid plexus tumor should be considered as a possible cause of small multifocal intra-axial cystic brain lesions in dogs, regardless of whether a primary intraventricular lesion is visible.

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

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

2010-07-01

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

Automated estimation of choroidal thickness distribution and volume based on OCT images of posterior visual section.

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Vupparaboina, Kiran Kumar; Nizampatnam, Srinath; Chhablani, Jay; Richhariya, Ashutosh; Jana, Soumya

2015-12-01

A variety of vision ailments are indicated by anomalies in the choroid layer of the posterior visual section. Consequently, choroidal thickness and volume measurements, usually performed by experts based on optical coherence tomography (OCT) images, have assumed diagnostic significance. Now, to save precious expert time, it has become imperative to develop automated methods. To this end, one requires choroid outer boundary (COB) detection as a crucial step, where difficulty arises as the COB divides the choroidal granularity and the scleral uniformity only notionally, without marked brightness variation. In this backdrop, we measure the structural dissimilarity between choroid and sclera by structural similarity (SSIM) index, and hence estimate the COB by thresholding. Subsequently, smooth COB estimates, mimicking manual delineation, are obtained using tensor voting. On five datasets, each consisting of 97 adult OCT B-scans, automated and manual segmentation results agree visually. We also demonstrate close statistical match (greater than 99.6% correlation) between choroidal thickness distributions obtained algorithmically and manually. Further, quantitative superiority of our method is established over existing results by respective factors of 27.67% and 76.04% in two quotient measures defined relative to observer repeatability. Finally, automated choroidal volume estimation, being attempted for the first time, also yields results in close agreement with that of manual methods. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

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

2018-05-01

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

Melanoma Therapy with Rhenium-Cyclized Alpha Melanocyte Stimulating Hormone Peptide Analogs

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Thomas P Quinn

2005-11-22

Malignant melanoma is the 6th most commonly diagnosed cancer with increasing incidence in the United States. It is estimated that 54,200 cases of malignant melanoma will be newly diagnosed and 7,600 cases of death will occur in the United States in the year 2003 (1). At the present time, more than 1.3% of Americans will develop malignant melanoma during their lifetime (2). The average survival for patients with metastatic melanoma is about 6-9 months (3). Moreover, metastatic melanoma deposits are resistant to conventional chemotherapy and external beam radiation therapy (3). Systematic chemotherapy is the primary therapeutic approach to treat patients with metastatic melanoma. Dacarbazine is the only single chemotherapy agent approved by FDA for metastatic melanoma treatment (5). However, the response rate to Dacarbazine is only approximately 20% (6). Therefore, there is a great need to develop novel treatment approaches for metastatic melanoma. The global goal of this research program is the rational design, characterization and validation of melanoma imaging and therapeutic radiopharmaceuticals. Significant progress has been made in the design and characterization of metal-cyclized radiolabeled alpha-melanocyte stimulating hormone peptides. Therapy studies with {sup 188}Re-CCMSH demonstrated the therapeutic efficacy of the receptor-targeted treatment in murine and human melanoma bearing mice (previous progress report). Dosimetry calculations, based on biodistribution data, indicated that a significant dose was delivered to the tumor. However, {sup 188}Re is a very energetic beta-particle emitter. The longer-range beta-particles theoretically would be better for larger tumors. In the treatment of melanoma, the larger primary tumor is usually surgically removed leaving metastatic disease as the focus of targeted radiotherapy. Isotopes with lower beta-energies and/or shorter particle lengths should be better suited for targeting metastases. The {sup 177}Lu

CHOROIDAL CHANGES ASSOCIATED WITH SEROUS MACULAR DETACHMENT IN EYES WITH STAPHYLOMA, DOME-SHAPED MACULA OR TILTED DISK SYNDROME.

Science.gov (United States)

Tan, Anna C S; Yzer, Suzanne; Freund, K Bailey; Dansingani, Kunal K; Phasukkijwatana, Nopasak; Sarraf, David

2017-08-01

To study the relationship of choroidal abnormalities with serous retinal detachment (SRD) in eyes with staphyloma, dome-shaped macula, or tilted disk syndrome. Group 1, 28 eyes of 20 patients with staphyloma/dome-shaped macula/tilted disk syndrome associated with SRD was compared with Group 2, 30 eyes of 20 patients, with staphyloma/dome-shaped macula/tilted disk syndrome but without SRD. Radial and en-face optical coherence tomography and choroidal analysis were performed. Group 1 had a thicker mean subfoveal choroidal thickness (161 μm vs. 92 μm, P 0.05) compared with eyes of Group 2. Focal abrupt changes in choroidal thickness were more commonly seen in Group 1 versus eyes in Group 2 (90% vs. 30%, P < 0.05) and this area of abrupt change was located within or at the edge of the SRD in 64% of eyes. Large choroidal vessels (pachyvessels) (82% located within the area of SRD) were always associated with the presence of SRD. An abrupt transition in choroidal thickness may be involved in the pathogenesis of SRD. In some cases, a radial scan pattern may better demonstrate mild SRD, choroidal contours and the focal choroidal variations than horizontal or vertical raster scan patterns.

Adoptive cell transfer in the treatment of metastatic melanoma

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Straten, Per thor; Becker, Jürgen C

2009-01-01

Adoptive cell therapy (ACT) for metastatic cancer is the focus of considerable research effort. Rosenberg's laboratory demonstrated a 50% response rate in stage IV melanoma patients treated with in vitro expanded tumor-infiltrating lymphocytes (TILs) and high-dose IL-2 administered after...

Long-term outcome after radiation therapy for subfoveal choroidal neovascularization associated with age-related macular degeneration

International Nuclear Information System (INIS)

Mandai, Michiko; Takahashi, Masayo; Miyamoto, Hideki; Hiroshiba, Naoko; Kimura, Hideya; Ogura, Yuichiro; Honda, Yoshihito; Sasai, Keisuke

2000-01-01

The purpose of this study was to investigate the long-term effect of low-dose radiation therapy on subfoveal choroidal neovascularization associated with age-related macular degeneration. The clinical course and visual outcome were compared retrospectively among two treated groups and a control group; 15 patients (15 eyes) received 10 Gy, another 15 patients (15 eyes) received 20 Gy. The control group consisted of 15 patients (15 eyes) without treatment. All patients were followed up for at least 18 months, and most were followed up for 3 years. The macula was irradiated with either 10 Gy in 5 fractions or with 20 Gy in 10 fractions after computed tomography (CT) simulation enabled real-time treatment planning from multiple CT slices. During the 3 years of follow-up, the lesions became better in 5 eyes, unchanged in 1, and worse in 9 with 10 Gy radiation; better in 7 eyes, unchanged in 1, and worse in 7 eyes with 20 Gy; and better in 1 eye and worse in 14 with no treatment. The difference between the groups treated with radiation and the control was statistically significant (P<.05). Visual acuity was also significantly better in the group receiving 20 Gy than in the control group up to 2 years after radiation (P<.01). Radiation may extend the period of good visual function substantially by reducing subfoveal choroidal neovascularization activity. (author)

Long-term outcome after radiation therapy for subfoveal choroidal neovascularization associated with age-related macular degeneration

Energy Technology Data Exchange (ETDEWEB)

Mandai, Michiko; Takahashi, Masayo; Miyamoto, Hideki; Hiroshiba, Naoko; Kimura, Hideya; Ogura, Yuichiro; Honda, Yoshihito; Sasai, Keisuke [Kyoto Univ. (Japan). Graduate School of Medicine

2000-10-01

The purpose of this study was to investigate the long-term effect of low-dose radiation therapy on subfoveal choroidal neovascularization associated with age-related macular degeneration. The clinical course and visual outcome were compared retrospectively among two treated groups and a control group; 15 patients (15 eyes) received 10 Gy, another 15 patients (15 eyes) received 20 Gy. The control group consisted of 15 patients (15 eyes) without treatment. All patients were followed up for at least 18 months, and most were followed up for 3 years. The macula was irradiated with either 10 Gy in 5 fractions or with 20 Gy in 10 fractions after computed tomography (CT) simulation enabled real-time treatment planning from multiple CT slices. During the 3 years of follow-up, the lesions became better in 5 eyes, unchanged in 1, and worse in 9 with 10 Gy radiation; better in 7 eyes, unchanged in 1, and worse in 7 eyes with 20 Gy; and better in 1 eye and worse in 14 with no treatment. The difference between the groups treated with radiation and the control was statistically significant (P<.05). Visual acuity was also significantly better in the group receiving 20 Gy than in the control group up to 2 years after radiation (P<.01). Radiation may extend the period of good visual function substantially by reducing subfoveal choroidal neovascularization activity. (author)

CD36 deficiency leads to choroidal involution via COX2 down-regulation in rodents.

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Marianne Houssier

2008-02-01

Full Text Available BACKGROUND: In the Western world, a major cause of blindness is age-related macular degeneration (AMD. Recent research in angiogenesis has furthered the understanding of choroidal neovascularization, which occurs in the "wet" form of AMD. In contrast, very little is known about the mechanisms of the predominant, "dry" form of AMD, which is characterized by retinal atrophy and choroidal involution. The aim of this study is to elucidate the possible implication of the scavenger receptor CD36 in retinal degeneration and choroidal involution, the cardinal features of the dry form of AMD. METHODS AND FINDINGS: We here show that deficiency of CD36, which participates in outer segment (OS phagocytosis by the retinal pigment epithelium (RPE in vitro, leads to significant progressive age-related photoreceptor degeneration evaluated histologically at different ages in two rodent models of CD36 invalidation in vivo (Spontaneous hypertensive rats (SHR and CD36-/- mice. Furthermore, these animals developed significant age related choroidal involution reflected in a 100%-300% increase in the avascular area of the choriocapillaries measured on vascular corrosion casts of aged animals. We also show that proangiogenic COX2 expression in RPE is stimulated by CD36 activating antibody and that CD36-deficient RPE cells from SHR rats fail to induce COX2 and subsequent vascular endothelial growth factor (VEGF expression upon OS or antibody stimulation in vitro. CD36-/- mice express reduced levels of COX2 and VEGF in vivo, and COX2-/- mice develop progressive choroidal degeneration similar to what is seen in CD36 deficiency. CONCLUSIONS: CD36 deficiency leads to choroidal involution via COX2 down-regulation in the RPE. These results show a novel molecular mechanism of choroidal degeneration, a key feature of dry AMD. These findings unveil a pathogenic process, to our knowledge previously undescribed, with important implications for the development of new therapies.

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

DEFF Research Database (Denmark)

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

2013-01-01

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

Simultaneous development of craniopharyngioma and choroid plexus carcinoma in the childhood -a clinical case

International Nuclear Information System (INIS)

Marinova, L.; Georgiev, R.; Mihaylova, I.

2014-01-01

We present a clinical case of 9 years old girl with concomitant brain tumors - choroid plexus carcinoma and craniopharyngioma diagnosed in 2009. After three operations, cranio-spinal irradiation with boost for the remaining tumor located in left ventricular trigonum to a total dose of 55 Gy and 7 courses chemotherapy, local tumor control was achieved for the choroid plexus carcinoma. Four years following the achievement of local tumor control of the choroid plexus carcinoma, an increase of the tumor formation located in the left side of the pituitary was reported. The diagnosis cystic craniopharyngeoma was found during the surgical operation. With this clinical case we would like to stress on the achieved local tumor control following the complex treatment of carcinoma of the choroid plexus, as well as on the slow growth of simultaneously diagnosed craniopharyngeoma. This case report raises the question of the genetic predisposition of the brain tumors in children, as well as possibility of malignant transformation of craniopharyngeoma following radiotherapy. The differential diagnosis of neuroectodermal brain tumors requires immunohistochemical analysis and if necessary genetic analysis. Key words: Complex treatment. Choroid plexus carcinoma. Craniopharyngioma. Radiotherapy. Malignant transformation. Simultaneity

External radiotherapy for circumscribed choroidal haemangiomas using a modified retinoblastoma technique

International Nuclear Information System (INIS)

Eide, N.; Syrdalen, P.; Tausjoe, J.; Tveraa, K.

1995-01-01

This report describes two cases of circumscribed choroidal haemangiomas involving the fovea, complicated by serous retinal detachment. Laser photocoagulation, generally accepted as the treatment of choice for choroidal haemangioma, was considered either to be of no visual benefit or a risk for jeopardizing vision further due to the subfoveolar lesions. Fractionated radiotherapy using a lens-sparing, modified retinoblastoma technique, was given, using circular fields of 15 mm diameter. The dose was 24 Gy in 8 fractions. In both eyes the retina reattached completely. The visual acuity improved markedly in the first, and was restored to the prior level in the second. Normalization of a high intraocular pressure was also achieved in the second case. We believe this method to be a reasonable and effective therapy for some choroidal haemangiomas after careful individual consideration. (au) 17 refs

Choroidal thickness in non-ocular Behçet's disease – A spectral-domain OCT study

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Aman Mittal

2017-09-01

Conclusion: This study demonstrates that BD may have subclinical manifestations in the choroid, resulting in thinning of the choroid relative to normal eyes, even without overt signs of ocular involvement.

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.

Morphological features of choroidal metastases: An OCT analysis

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Ludovico Iannetti

2013-01-01

Full Text Available The morphological characteristics and retinal changes of chroidal metastases using Spectral Domain OCT are described in a case with primary lung adenocarcinoma and secondary choroidal involvement.

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.

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.

Macular Choroidal Thickness in Myopic Eyes with and without a Dome-Shaped Macula: A Case-Control Study.

Science.gov (United States)

Soudier, Guillaume; Gaudric, Alain; Gualino, Vincent; Massin, Pascale; Nardin, Mathieu; Tadayoni, Ramin; Speeg-Schatz, Claude; Gaucher, David

2016-01-01

Dome-shaped macula (DSM) has recently been described with myopic staphyloma, which may cause decreased vision. The purpose of this study was to evaluate the choroidal thickness of eyes with and eyes without DSM. A total of 26 eyes with DSM were paired based on axial length with 26 eyes without DSM. All patients underwent spectral-domain OCT examination using the 7-line EDI (enhanced depth imaging) protocol. The mean choroidal thickness was measured using Early Treatment Diabetic Retinopathy Study (ETDRS) grid areas. Both nasal choroidal thickness and temporal choroidal thickness were significantly thinner in the DSM group (120.43 vs. 159.46 µm, p = 0.035, and 142.17 vs. 187.23 µm, p = 0.021, respectively). However, the mean central choroidal thickness did not differ (152.61 vs. 175.96 µm, p = 0.20). The ratio between central and peripheral choroidal thickness was very significantly elevated with DSM (1.18 ± 0.12 vs. 0.99 ± 0.09, p < 0.0001). Choroidal thickness decreases at the periphery but not in the macular area with DSM. DSM seems not to be due to an inward protrusion of the globe but due to macular anatomical preservation in a growing staphyloma. © 2016 S. Karger AG, Basel.

Boron neutron capture therapy induces cell cycle arrest and DNA fragmentation in murine melanoma cells

Energy Technology Data Exchange (ETDEWEB)

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

2011-12-15

The melanoma is a highly lethal skin tumor, with a high incidence. Boron Neutron Capture Therapy (BNCT) is a radiotherapy which combines Boron with thermal neutrons, constituting a binary system. B16F10 melanoma and L929 fibroblasts were treated with Boronophenylalanine and irradiated with thermal neutron flux. The electric potential of mitochondrial membrane, cyclin D1 and caspase-3 markers were analyzed. BNCT induced a cell death increase and cyclin D1 amount decreased only in B16F10 melanoma. Besides, there was not caspase-3 phosphorylation.

Choroidal thinning in high myopia measured by optical coherence tomography

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Ikuno Y

2013-05-01

Full Text Available Yasushi Ikuno, Satoko Fujimoto, Yukari Jo, Tomoko Asai, Kohji NishidaDepartment of Ophthalmology, Osaka University Graduate School of Medicine, Osaka, JapanPurpose: To investigate the rate of choroidal thinning in highly myopic eyes.Patients and methods: A retrospective observational study of 37 eyes of 26 subjects (nine males and 17 females, mean age 39.6 ± 7.7 years with high myopia but no pathologies who had undergone spectral domain optical coherence tomography and repeated the test 1 year later (1 ± 0.25 year at Osaka University Hospital, Osaka, Japan. Patients older than 50 years with visual acuity worse than 20/40 or with whitish chorioretinal atrophy involving the macula were excluded. Two masked raters measured the choroidal thicknesses (CTs at the foveda, 3 mm superiorly, inferiorly, temporally, and nasally on the images and averaged the values. The second examination was about 365 days after the baseline examination. The CT reduction per year (CTRPY was defined as (CT 1 year after - baseline CT/days between the two examinations × 365. The retinal thicknesses were also investigated.Results: The CTRPY at the fovea was −1.0 ± 22.0 µm (range –50.2 to 98.5 at the fovea, –6.5 ± 24.3 µm (range −65.8 to 90.2 temporally, –0.5 ± 22.3 µm (range –27.1 to 82.5 nasally, –9.7 ± 21.7 µm (range –40.1 to 60.1 superiorly, and –1.4 ± 25.5 µm (range –85.6 to 75.2 inferiorly. There were no significant differences in the CTRPY at each location (P = 0.34. The CT decreased significantly (P < 0.05 only superiorly. The superior CTRPY was negatively correlated with the axial length (P < 0.05. The retinal thickness at the fovea did not change. Stepwise analysis for CTRPY selected axial length (P = 0.04, R2 = 0.13 and age (P = 0.08, R2 = 0.21 as relevant factors.Conclusions: The highly myopic choroid might gradually thin and be affected by many factors. Location and axial length are key factors to regulate the rate of choroidal

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

Quercetin as an Emerging Anti-Melanoma Agent: A four-focus area therapeutic development strategy

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Zoey Harris

2016-10-01

Full Text Available Replacing current refractory treatments for melanoma with new prevention and therapeutic approaches is crucial in order to successfully treat this aggressive cancer form. Melanoma develops from neural crest cells, which express tyrosinase -- a key enzyme in the pigmentation pathway. The tyrosinase enzyme is highly active in melanoma cells and metabolizes polyphenolic compounds; tyrosinase expression thus makes a feasible a target for polyphenol-based therapies. For example, quercetin (3,3′,4′,5,7-pentahydroxyflavone is a highly ubiquitous and well-classified dietary polyphenol found in various fruits, vegetables and other plant products including onions, broccoli, kale, oranges, blueberries, apples, and tea. Quercetin has demonstrated anti-proliferative and pro-apoptotic activity in various cancer cell types. Quercetin is readily metabolized by tyrosinase into various compounds that promote anti-cancer activity; additionally, given that tyrosinase expression increases during tumorigenesis, and its activity is associated with pigmentation changes in both early- and late-stage melanocytic lesions, it suggests that quercetin can be used to target melanoma. In this review we explore the potential of Quercetin as an anti-melanoma agent utilizing and extrapolating on evidence from previous in vitro studies in various human malignant cell lines and propose a four-focus area strategy to develop quercetin as a targeted anti-melanoma compound for use as either a preventative or therapeutic agent. The four areas of focus include utilizing quercetin to i modulate cellular bioreduction potential and associated signaling cascades, ii affect transcription of relevant genes, iii regulate epigenetic processes, and iv develop effective combination therapies and delivery modalities/protocols. In general, quercetin could be used to exploit tyrosinase activity to prevent, and/or treat, melanoma with minimal additional side effects.

Malignant melanoma - a warning

International Nuclear Information System (INIS)

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

1990-01-01

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

Altered choroid plexus gene expression in major depressive disorder

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Cortney Ann Turner

2014-04-01

Full Text Available Given the emergent interest in biomarkers for mood disorders, we assessed gene expression in the choroid plexus, the region that produces cerebrospinal fluid (CSF, in individuals with major depressive disorder (MDD. Genes that are expressed in the choroid plexus (CP can be secreted into the CSF and may be potential biomarker candidates. Given that we have previously shown that fibroblast growth factor family members are differentially expressed in post-mortem brain of subjects with MDD and the CP is a known source of growth factors in the brain, we posed the question whether growth factor dysregulation would be found in the CP of subjects with MDD. We performed laser capture microscopy of the choroid plexus at the level of the hippocampus in subjects with MDD and psychiatrically normal controls. We then extracted, amplified, labeled and hybridized the cRNA to Illumina BeadChips to assess gene expression. In controls, the most highly abundant known transcript was transthyretin. Moreover, half of the 14 most highly expressed transcripts in controls encode ribosomal proteins. Using BeadStudio software, we identified 169 transcripts differentially expressed (p< 0.05 between control and MDD samples. Using pathway analysis we noted that the top network altered in subjects with MDD included multiple members of the transforming growth factor-beta (TGFβ pathway. Quantitative real-time PCR (qRT-PCR confirmed downregulation of several transcripts that interact with the extracellular matrix in subjects with MDD. These results suggest that there may be an altered cytoskeleton in the choroid plexus in MDD subjects that may lead to a disrupted blood-CSF-brain barrier.

Association of ABO blood groups and Rh factor with retinal and choroidal thickness.

Science.gov (United States)

Teberik, Kuddusi; Eski, Mehmet Tahir

2018-06-01

To evaluate if ABO blood group and Rh factor have an effect on retinal and choroidal thickness. This study was designed prospectively. Retinal nerve fiber layer, retinal, and choroidal thicknesses were measured with spectral-domain optical coherence tomography. Retinal and choroidal thickness measurements (one subfoveal, three temporal, and three nasal) were obtained at 500-μm intervals up to 1500 μm with the caliper system. In this study, 109 male and 151 female, 260 individuals in total were included. There were 125 subjects in group A, 29 in group B, 34 in group AB, and 72 in group O. Rh factor was positive in 194 subjects and negative in 66. There was no significant difference between the groups regarding age (p = 0.667). The groups did not show any statistical difference in retinal nerve fiber layer thickness. There was significant difference found for mean retinal thickness at temporal 1000 μm when four groups were compared (p = 0.037). No statistically significant difference was detected for the remaining retinal and choroidal sectoral regions. The groups did not statistically significantly differ concerning Rh factor (p > 0.05). Although we found a significant difference in retinal thickness in the temporal retina between group B with group A and group O, we suggest that both blood group and Rh factor have no effect on retinal and choroidal thickness.

Iodine 125-lysergic acid diethylamide binds to a novel serotonergic site on rat choroid plexus epithelial cells

International Nuclear Information System (INIS)

Yagaloff, K.A.; Hartig, P.R.

1985-01-01

125 I-Lysergic acid diethylamide ( 125 I-LSD) binds with high affinity to serotonergic sites on rat choroid plexus. These sites were localized to choroid plexus epithelial cells by use of a novel high resolution stripping film technique for light microscopic autoradiography. In membrane preparations from rat choroid plexus, the serotonergic site density was 3100 fmol/mg of protein, which is 10-fold higher than the density of any other serotonergic site in brain homogenates. The choroid plexus site exhibits a novel pharmacology that does not match the properties of 5-hydroxytryptamine-1a (5-HT1a), 5-HT1b, or 5-HT2 serotonergic sites. 125 I-LSD binding to the choroid plexus site is potently inhibited by mianserin, serotonin, and (+)-LSD. Other serotonergic, dopaminergic, and adrenergic agonists and antagonists exhibit moderate to weak affinities for this site. The rat choroid plexus 125 I-LSD binding site appears to represent a new type of serotonergic site which is located on non-neuronal cells in this tissue

[Melanoma in organ transplant patients].

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

2000-02-01

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

Gyrate atrophy of the choroid and retina with hyper-ornithinemia responsive to vitamin B6: a case report

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Javadzadeh Alireza

2007-06-01

Full Text Available Abstract Background Gyrate atrophy of the retina and choroid is a rare autosomal recessive inherited disease, characterized by progressive chorioretinal atrophy that results in progressive deterioration of peripheral and night vision and leading to blindness. Case presentation This report presents a case of a 28-year-old man consulting for a progressive fall of visual acuity with hemeralopia. Eye fundoscopy showed regions of confluent rounded chorioretinal atrophy. The visual field and retinal angiography were altered. A high level of plasma ornithine (629 nmol/mL was detected and a diagnosis of gyrate atrophy of the retina and choroid was made. The patient was treated with high dose Pyridoxine supplement (300 mg/d for 6 months and the ornithine level of his serum was successfully reduced. Conclusion The exact mechanism of chorioretinal atrophy in hyper-ornithinemia is not known and a small percentage of the affected people respond to Vitamin B6 supplementation.

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

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Goldenberg A

2015-08-01

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

Applications of nanotechnology for melanoma treatment, diagnosis, and theranostics

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Chen J

2013-07-01

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

En Face Optical Coherence Tomography Angiography Imaging Versus Fundus Photography in the Measurement of Choroidal Nevi.

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Lee, Michele D; Kaidonis, Georgia; Kim, Alice Y; Shields, Ryan A; Leng, Theodore

2017-09-01

Choroidal nevi are common benign intraocular tumors with a small risk of malignant transformation. This retrospective study investigates the use of en face spectral-domain optical coherence tomography angiography (SD-OCTA) in determining the clinical features and measurement of choroidal nevi. Patients with choroidal nevi were imaged with both OCTA and a fundus photography device. Greatest longitudinal dimension (GLD), perpendicular dimension (PD), and the GLD/PD ratio were assessed on each device. Inter-device variation and intra- and inter-rater reliability analyses were performed. Fourteen patients with choroidal nevi were included. No significant difference between the GLD/PD ratio as measured by all three devices was found (Chi-square = 2.8, 2 df, P = .247). Intraclass correlation coefficients were greater than 0.7 for repeated measures on all devices, suggesting good repeatability and reproducibility. This study demonstrated inter-device consistency and high intra- and inter-rater reliability when measuring choroidal nevi. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:741-747.]. Copyright 2017, SLACK Incorporated.

Choroidal thickness and myopia in relation to physical activity during childhood

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Lundberg, Kristian; Jacobsen, Nina; Vestergaard, Anders Højslet

Purpose: Decreasing physical activity (PA) has been suggested to be a driving force behind the rapid increase of myopia worldwide. The possible protective effects of PA might be through increased blood flow and subsequent change in thickness of the choroid. The purpose of this study......, L, M and V PA (2.31 µm/% (p=0.22), -3.99 µm/% (p=0.15), -5.43 µm/% (p=0.57) and -0.53 µm/% (p=0.95), respectively). Conclusions: We found no association between physical activity and the choroidal thickness, axial length or refractive error. However, the choroid was thinner in myopic eyes......±59 µm (3 mm zone), respectively. All CT measurements were thinner in myopic eyes (psex-adjusted linear regression there were no associations between PA and SE, AL or any CT measurements. There was no association between accumulated PA and the overall CT for SED...

Immunohistochemical detection of XIAP in melanoma.

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

2008-03-01

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

Genetics of familial melanoma

DEFF Research Database (Denmark)

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

2015-01-01

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

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

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Tchernev, Georgi; Chokoeva, Anastasiya Atanasova

2017-06-15

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

A retrospective analysis of 140 dogs with oral melanoma treated with external beam radiation.

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Proulx, David R; Ruslander, David M; Dodge, Richard K; Hauck, Marlene L; Williams, Laurel E; Horn, Birgitte; Price, G Sylvester; Thrall, Donald E

2003-01-01

Despite the early notion that canine oral malignant melanoma is radioresistant, recent data suggest that external beam radiotherapy is effective in local tumor control. However, optimal fractionation schedules have not been established. The high rate of regional and distant metastasis is another problem that has hindered long-term control. The role of chemotherapy in the management of canine oral melanoma has also not been determined. In this study, data from 140 dogs irradiated at North Carolina State University were evaluated with the following objectives: (1) to compare the efficacy of three radiation therapy protocols (36 Gy, 9 Gy x 4 fractions; 30 Gy, 10 Gy x 3 fractions; or >45 Gy, 2-4 Gy x 12-19 fractions) for the treatment of dogs with oral malignant melanoma, (2) to identify any host or tumor factors influencing prognosis, and (3) to determine the impact of systemic chemotherapy on treatment outcome. Information regarding response to therapy, disease progression, and survival were determined from the medical records or from information obtained by telephone or mail survey. Relationships between host, tumor, and treatment variables and outcome measures (response, time to first event, and survival) were evaluated using Fisher's exact test (response) and the Cox regression model (time to first event and survival). The median time to first event for the 140 dogs was 5.0 months (95% C.I., 4-6 months) and the median survival was 7.0 months (95% C.I., 6-9 months). In the univariate analysis, the following variables were associated with increased time to first event and survival: (1) rostral tumor sublocation; (2) lack of bone lysis observed on skull imaging, and (3) microscopic tumor burden. In a multivariate analysis of 111 dogs with complete data for these variables, tumor sublocation, bone lysis, and tumor volume were identified as joint predictors of time to first event (p oral malignant melanoma; however, the optimal fractionation scheme has yet to be

Helicoid peripapillary chorioretinal degeneration complicated by choroidal neovascularization.

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Triantafylla, Magdalini; Panos, Georgios D; Dardabounis, Doukas; Nanos, Panagiotis; Konstantinidis, Aristeidis

2016-02-15

Helicoid peripapillary chorioretinal degeneration (HPCD) is a hereditary disease of the fundus that is characterized by atrophic chorioretinal areas that appear early in life and expand gradually from the optic disc towards the macula and the periphery. We describe the case of an elderly man with a known diagnosis of HPCD who developed choroidal neovascular membrane (CNV) in both eyes during the course of the disease. The patient was treated with intravitreal injection of ranibizumab, to which he had excellent response. The CNV subsided with 2 injections in the right eye and 1 in the left. Two years after the initial diagnosis of CNV in the right eye, visual acuity was 5/10 OD and 9/10 OS. Helicoid peripapillary chorioretinal degeneration is rarely complicated by CNV as the fundus lacks the trigger factors that would sustain this process. Although rare, HPCD complicated by CNV can be seen bilaterally, but responds well to few ranibizumab injections.

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

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Dearbhaile Catherine Collins

2016-01-01

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

DYSPHONIA AS AN UNCOMMON PRESENTATION OF PONTOCEREBELLAR CHOROID PLEXUS PAPILLOMA.

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Rotim, Krešimir; Sajko, Tomislav; Zmajević, Marina; Šumonja, Ilijana; Grgić, Marko

2015-06-01

A case is presented of a patient with dysphonia, hearing loss and ataxia due to vestibulocochlear and vagal nerve compression by choroid plexus papilloma in the cerebellopontine angle. Choroid plexus papillomas are rare tumors usually arising in the lateral and fourth ventricle, and rarely found in the cerebellopontine angle, making the neuroimaging characteristics usually not sufficient for diagnosis. Patients usually present with headache and hydrocephalus but tumors in the cerebellopontine angle can cause vestibulocochlear dysfunction and cerebellar symptoms. Dysphonia along with hearing loss was a dominant symptom in the case presented. After complete surgical removal of the tumor, deterioration of dysphonia was noticed; it could be explained as peripheral vagal nerve neuropathy due to tumor compression and intraoperative manipulation. In this case report, we describe dysphonia as an uncommon presentation of a rare posterior fossa tumor. To our knowledge, a case of choroid plexus papilloma presenting with dysphonia has not been described before. Our case extends the differential diagnosis of dysphonia from the otorhinolaryngological to the neurosurgical field.

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

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

1985-01-01

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

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.)

Outer Retinal and Choroidal Evaluation in Multiple Evanescent White Dot Syndrome (MEWDS): An Enhanced Depth Imaging Optical Coherence Tomography Study.

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Fiore, Tito; Iaccheri, Barbara; Cerquaglia, Alessio; Lupidi, Marco; Torroni, Giovanni; Fruttini, Daniela; Cagini, Carlo

2018-01-01

To perform an analysis of optical coherence tomography (OCT) abnormalities in patients with MEWDS, during the acute and recovery stages, using enhanced depth imaging-OCT (EDI-OCT). A retrospective case series of five patients with MEWDS was included. EDI-OCT imaging was evaluated to detect retinal and choroidal features. In the acute phase, focal impairment of the ellipsoid zone and external limiting membrane, hyperreflective dots in the inner choroid, and full-thickness increase of the choroidal profile were observed in the affected eye; disappearance of these findings and restoration of the choroidal thickness (p = 0.046) was appreciated in the recovery phase. No OCT abnormalities were assessed in the unaffected eye. EDI-OCT revealed transient outer retinal layer changes and inner choroidal hyperreflective dots. A transient increased thickness of the whole choroid was also identified. This might confirm a short-lasting inflammatory involvement of the whole choroidal tissue in the active phase of MEWDS.

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

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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.

A natural product-like JAK2/STAT3 inhibitor induces apoptosis of malignant melanoma cells.

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Ke-Jia Wu

Full Text Available The JAK2/STAT3 signaling pathway plays a critical role in tumorigenesis, and has been suggested as a potential molecular target for anti-melanoma therapeutics. However, few JAK2 inhibitors were being tested for melanoma therapy. In this study, eight amentoflavone analogues were evaluated for their activity against human malignant melanoma cells. The most potent analogue, compound 1, inhibited the phosphorylation of JAK2 and STAT3 in human melanoma cells, but had no discernible effect on total JAK2 and STAT3 levels. A cellular thermal shift assay was performed to identify that JAK2 is engaged by 1 in cell lysates. Moreover, compound 1 showed higher antiproliferative activity against human melanoma A375 cells compared to a panel of cancer and normal cell lines. Compound 1 also activated caspase-3 and cleaved PARP, which are markers of apoptosis, and suppressed the anti-apoptotic Bcl-2 level. Finally, compound 1 induced apoptosis in 80% of treated melanoma cells. To our knowledge, compound 1 is the first amentoflavone-based JAK2 inhibitor to be investigated for use as an anti-melanoma agent.

Outcomes of dogs undergoing radiotherapy for treatment of oral malignant melanoma: 111 cases (2006-2012).

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Kawabe, Mifumi; Mori, Takashi; Ito, Yusuke; Murakami, Mami; Sakai, Hiroki; Yanai, Tokuma; Maruo, Kohji

2015-11-15

To evaluate the characteristics and outcomes of dogs with stage I, II, III, or IV oral malignant melanoma treated by various types of radiotherapy. Retrospective case series. 111 dogs. Medical records of dogs with oral malignant melanoma treated by radiotherapy (with or without adjunctive treatments) at a veterinary medical center between July 2006 and December 2012 were reviewed. Information regarding signalment, tumor location, disease stage, treatment protocols, adverse effects, and survival time were obtained from medical records and by telephone follow-up. Associations between variables of interest and outcome were analyzed. Dogs received orthovoltage x-ray (n = 68), megavoltage x-ray (39), or electron beam (4) radiotherapy. Adjunctive treatments included debulking surgery (n = 18), chemotherapy (39), or both (27). Median survival times for dogs with stage I, II, III, and IV melanoma were 758 days (n = 19), 278 days (24), 163 days (37), and 80 days (31), respectively, and differed significantly between dogs with stage I disease and those with all other disease stages. Among dogs with stage III melanoma, risk of death was significantly higher in those that received orthovoltage x-ray treatment than in those that received megavoltage x-ray treatment. Severe (primary or secondary) adverse effects were identified in 9 dogs. Median survival time was significantly longer for dogs with stage I oral malignant melanoma than for dogs with more advanced disease at the time of staging. The staging system used may be a useful tool for prognosis prediction in dogs undergoing similar treatment protocols for oral malignant melanomas.

Interleukins 1alpha and 1beta secreted by some melanoma cell lines strongly reduce expression of MITF-M and melanocyte differentiation antigens.

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Kholmanskikh, Olga; van Baren, Nicolas; Brasseur, Francis; Ottaviani, Sabrina; Vanacker, Julie; Arts, Nathalie; van der Bruggen, Pierre; Coulie, Pierre; De Plaen, Etienne

2010-10-01

We report that melanoma cell lines expressing the interleukin-1 receptor exhibit 4- to 10-fold lower levels of mRNA of microphthalmia-associated transcription factor (MITF-M) when treated with interleukin-1beta. This effect is NF-kappaB and JNK-dependent. MITF-M regulates the expression of melanocyte differentiation genes such as MLANA, tyrosinase and gp100, which encode antigens recognized on melanoma cells by autologous cytolytic T lymphocytes. Accordingly, treating some melanoma cells with IL-1beta reduced by 40-100% their ability to activate such antimelanoma cytolytic T lymphocytes. Finally, we observed large amounts of biologically active IL-1alpha or IL-1beta secreted by two melanoma cell lines that did not express MITF-M, suggesting an autocrine MITF-M downregulation. We estimate that approximately 13% of melanoma cell lines are MITF-M-negative and secrete IL-1 cytokines. These results indicate that the repression of melanocyte-differentiation genes by IL-1 produced by stromal cells or by tumor cells themselves may represent an additional mechanism of melanoma immune escape.

The risk of melanoma and hematologic cancers in patients with psoriasis.

Science.gov (United States)

Reddy, Shivani P; Martires, Kathryn; Wu, Jashin J

2017-04-01

The risk of melanoma and hematologic cancers in patients with psoriasis is controversial. We sought to assess the risk of melanoma and hematologic cancers in patients with psoriasis, and the association with different treatments. We used case-control and retrospective cohort designs to determine melanoma or hematologic cancer risk in patients with psoriasis. Risk with treatment type was assessed using Fisher exact test. Patients with psoriasis had 1.53 times greater risk of developing a malignancy compared with patients without psoriasis (P < .01). There were no significant differences in malignancy risk among patients treated with topicals, phototherapy, systemics, or biologic agents. Patients with psoriasis and malignancy did not have significantly worse survival than patients without psoriasis. It is possible that patients developed malignancy subsequent to the follow-up time included in the study. Patients with psoriasis may experience an elevated risk of melanoma and hematologic cancers, compared with the general population. The risk is not increased by systemic or biologic psoriasis therapies. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Is there a relationship between outer retinal destruction and choroidal changes in cone dystrophy?

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Onder Ayyildiz

Full Text Available ABSTRACT Purpose: The aim of the present study was to use enhanced depth imaging optical coherence tomography (EDI-OCT to investigate choroidal changes in patients with cone dystrophy (CD and to correlate these findings with clinical and electroretinography (ERG findings. Methods: This case-control study included 40 eyes of 20 patients with CD and 40 eyes of 40 age- and refraction-matched healthy individuals. Choroidal thickness (CT measurements were obtained under the foveal center and at 500 and 1,500 μm from the nasal and temporal regions to the center of the fovea, respectively. EDI-OCT and ERG data were analyzed, and the correlations of CT with the best-corrected visual acuity (BCVA and the central foveal thickness (CFT were evaluated. Results: The mean subfoveal CTs in the CD and control groups were 240.70 ± 70.78 and 356.18 ± 48.55 μm, respectively. The subfoveal CT was significantly thinner in patients with CD than in the controls (p<0.001. The patients with CD also had significantly thinner choroids than the controls at each measurement location relative to the fovea (p<0.001. The subfoveal CT in the CD group correlated with CFT (p=0.012, but no significant correlation was found between the subfoveal CT and BCVA or photopic ERG responses. Conclusions: The present study demonstrated a significant thinning of the choroid in patients with CD. EDI-OCT is a useful technique for describing the choroidal changes occurring in CD. Future studies investigating the association between choroidal changes and outer retinal destruction or the disease stage may provide a better understanding of the pathophysiology of CD.

Is there a relationship between outer retinal destruction and choroidal changes in cone dystrophy?

Science.gov (United States)

Ayyildiz, Onder; Ozge, Gokhan; Kucukevcilioglu, Murat; Ozgonul, Cem; Mumcuoglu, Tarkan; Durukan, Ali Hakan; Mutlu, Fatih Mehmet

2016-01-01

The aim of the present study was to use enhanced depth imaging optical coherence tomography (EDI-OCT) to investigate choroidal changes in patients with cone dystrophy (CD) and to correlate these findings with clinical and electroretinography (ERG) findings. This case-control study included 40 eyes of 20 patients with CD and 40 eyes of 40 age- and refraction-matched healthy individuals. Choroidal thickness (CT) measurements were obtained under the foveal center and at 500 and 1,500 μm from the nasal and temporal regions to the center of the fovea, respectively. EDI-OCT and ERG data were analyzed, and the correlations of CT with the best-corrected visual acuity (BCVA) and the central foveal thickness (CFT) were evaluated. The mean subfoveal CTs in the CD and control groups were 240.70 ± 70.78 and 356.18 ± 48.55 μm, respectively. The subfoveal CT was significantly thinner in patients with CD than in the controls (p<0.001). The patients with CD also had significantly thinner choroids than the controls at each measurement location relative to the fovea (p<0.001). The subfoveal CT in the CD group correlated with CFT (p=0.012), but no significant correlation was found between the subfoveal CT and BCVA or photopic ERG responses. The present study demonstrated a significant thinning of the choroid in patients with CD. EDI-OCT is a useful technique for describing the choroidal changes occurring in CD. Future studies investigating the association between choroidal changes and outer retinal destruction or the disease stage may provide a better understanding of the pathophysiology of CD.

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

International Nuclear Information System (INIS)

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

2002-01-01

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

Adeno-Associated Viral Vector-Mediated mTOR Inhibition by Short Hairpin RNA Suppresses Laser-Induced Choroidal Neovascularization

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Tae Kwann Park

2017-09-01

Full Text Available Choroidal neovascularization (CNV is the defining characteristic feature of the wet subtype of age-related macular degeneration (AMD and may result in irreversible blindness. Based on anti-vascular endothelial growth factor (anti-VEGF, the current therapeutic approaches to CNV are fraught with difficulties, and mammalian target of rapamycin (mTOR has recently been proposed as a possible therapeutic target, although few studies have been conducted. Here, we show that a recombinant adeno-associated virus-delivered mTOR-inhibiting short hairpin RNA (rAAV-mTOR shRNA, which blocks the activity of both mTOR complex 1 and 2, represents a promising therapeutic approach for the treatment of CNV. Eight-week-old male C57/B6 mice were treated with the short hairpin RNA (shRNA after generating CNV lesions in the eyes via laser photocoagulation. The recombinant adeno-associated virus (rAAV delivery vehicle was able to effectively transduce cells in the inner retina, and significantly fewer inflammatory cells and less extensive CNV were observed in the animals treated with rAAV-mTOR shRNA when compared with control- and rAAV-scrambled shRNA-treated groups. Presumably related to the reduction of CNV, increased autophagy was detected in CNV lesions treated with rAAV-mTOR shRNA, whereas significantly fewer apoptotic cells detected in the outer nuclear layer around the CNV indicate that mTOR inhibition may also have neuroprotective effects. Taken together, these results demonstrate the therapeutic potential of mTOR inhibition, resulting from rAAV-mTOR shRNA activity, in the treatment of AMD-related CNV. Keywords: retinal neovascularization, choroidal neovascularization, adeno-associated virus, mTOR, RNA interference, mTOR shRNA, autophagy

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

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

2009-12-01

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

Clinical radiobiology of malignant melanoma

International Nuclear Information System (INIS)

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

1989-01-01

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

Thick melanoma in Tuscany.

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

2017-03-14

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

Baseline β-catenin, programmed death-ligand 1 expression and tumour-infiltrating lymphocytes predict response and poor prognosis in BRAF inhibitor-treated melanoma patients.

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Massi, Daniela; Romano, Emanuela; Rulli, Eliana; Merelli, Barbara; Nassini, Romina; De Logu, Francesco; Bieche, Ivan; Baroni, Gianna; Cattaneo, Laura; Xue, Gongda; Mandalà, Mario

2017-06-01

The activation of oncogenic Wnt/β-catenin pathway in melanoma contributes to a lack of T-cell infiltration. Whether baseline β-catenin expression in the context of tumour-infiltrating lymphocytes (TILs) and programmed death ligand-1 (PD-L1) overexpression correlates with prognosis of metastatic melanoma patients (MMPs) treated with mitogen-activated protein kinase, MAPK inhibitor (MAPKi) monotherapy, however, has not been fully clarified. Sixty-four pre-treatment formalin-fixed and paraffin embedded melanoma samples from MMP treated with a BRAF inhibitor (n = 39) or BRAF and MEK inhibitors (n = 25) were assessed for presence of β-catenin, PD-L1, cluster of differentiation (CD)8, CD103 and forkhead box protein P3 (FOXP3) expression by immunohistochemistry, and results were correlated with clinical outcome. Quantitative assessment of mRNA transcripts associated with Wnt/β-catenin pathway and immune response was performed in 51 patients. We found an inverse correlation between tumoural β-catenin expression and the level of CD8, CD103 or forkhead box protein P3 (FOXP3) positivity in the tumour microenvironment (TME). By multivariate analysis, PD-L1 <5% (odds ratio, OR 0.12, 95% confidence interval, CI 0.03-0.53, p = 0.005) and the presence of CD8+ T cells (OR 18.27, 95%CI 2.54-131.52, p = 0.004) were significantly associated with a higher probability of response to MAPKi monotherapy. Responding patients showed a significantly increased expression of mRNA transcripts associated with adaptive immunity and antigen presentation. By multivariate analysis, progression-free survival (PFS) (hazards ratio (HR) = 0.25 95%CI 0.10-0.61, p = 0.002) and overall survival (OS) (HR = 0.24 95%CI 0.09-0.67, p = 0.006) were longer in patients with high density of CD8+ T cells and β-catenin <10% than those without CD8+ T cells infiltration and β-catenin ≥10%. Our findings provide evidence that in the context of MAPKi monotherapy, immune subsets in the (TME) and

RECURRENCE OF CHOROIDAL NEOVASCULARIZATION LESION ACTIVITY AFTER AFLIBERCEPT TREATMENT FOR AGE-RELATED MACULAR DEGENERATION.

Science.gov (United States)

Wakazono, Tomotaka; Yamashiro, Kenji; Oishi, Akio; Ooto, Sotaro; Tamura, Hiroshi; Akagi-Kurashige, Yumiko; Hata, Masayuki; Takahashi, Ayako; Tsujikawa, Akitaka; Yoshimura, Nagahisa

2017-11-01

To examine the recurrence rate of choroidal neovascularization (CNV) lesion activity in age-related macular degeneration (AMD) and associated factors after 1-year aflibercept treatment. Age-related macular degeneration eyes with 1-year aflibercept fixed-regimen treatment and a follow-up period of at least 18 months from the initial aflibercept injection for treatment-naive exudative AMD were retrospectively evaluated. The recurrence rate was examined. Age, gender, visual acuity, AMD subtype, greatest linear dimension, and retinal and choroidal thicknesses at the 12th month examination were compared between eyes with and without recurrence. Presence of remnant polyps and pigment epithelial detachment (PED) morphology were also compared in polypoidal choroidal vasculopathy (PCV) eyes. Of the 98 eyes studied, 69 displayed a dry macula at the 12th month examination; 43.7% exhibited recurrence during the subsequent 12-month period in Kaplan-Meier analysis. Although no factors associated with recurrence were detected in AMD, remnant polyps and pigment epithelial detachment morphology at the 12th month examination were significantly associated with recurrence in polypoidal choroidal vasculopathy (P = 0.018 and 0.048, respectively). Continuous, proactive treatment would be considered overtreatment for more than half of the AMD eyes that achieved a dry macula. Angiography and optical coherence tomography analyses may be useful for predicting recurrence in polypoidal choroidal vasculopathy eyes.

Late side effects of Ruthenium 106 therapy for uveal melanomas

International Nuclear Information System (INIS)

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

1994-01-01

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

A Phase II trial of 17-allylamino, 17-demethoxygeldanamycin (17-AAG, tanespimycin) in patients with metastatic melanoma.

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Pacey, Simon; Gore, Martin; Chao, David; Banerji, Udai; Larkin, James; Sarker, Sarah; Owen, Karen; Asad, Yasmin; Raynaud, Florence; Walton, Mike; Judson, Ian; Workman, Paul; Eisen, Tim

2012-02-01

A Phase II study to screen for anti-melanoma activity of the heat shock protein 90 (HSP90) inhibitor, 17-AAG (17-allylamino-17-demethoxygeldanamycin) was performed. The primary endpoint was the rate of disease stabilisation in patients with progressive, metastatic melanoma treated with 17-AAG. Secondary endpoints were to determine: the toxicity of 17-AAG, the duration of response(s), median survival and further study the pharmacokinetics and pharmacodynamics of 17-AAG. Patients with metastatic melanoma (progressive disease documented ≤6 months of entering study) were treated with weekly, intravenous 17-AAG. A Simon one sample two stage minimax design was used. A stable disease rate of ≥25% at 6 months was considered compatible with 17-AAG having activity. Fourteen patients (8 male: 6 female) were entered, eleven received 17-AAG (performance status 0 or 1). Median age was 60 (range 29-81) years. The majority (93%) received prior chemotherapy and had stage M1c disease (71%). Toxicity was rarely ≥ Grade 2 in severity and commonly included fatigue, headache and gastrointestinal disturbances. One of eleven patients treated with 17-AAG had stable disease for 6 months and median survival for all patients was 173 days. The study was closed prematurely prior to completion of the first stage of recruitment and limited planned pharmacokinetic and pharmacodynamic analyses. Some evidence of 17-AAG activity was observed although early study termination meant study endpoints were not reached. Stable disease rates can be incorporated into trials screening for anti-melanoma activity and further study of HSP90 inhibitors in melanoma should be considered.

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.

Animal type melanoma: a report of two cases

Directory of Open Access Journals (Sweden)

Mariângela Esther Alencar Marques

2010-08-01

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

Neural retina-specific Aldh1a1 controls dorsal choroidal vascular development via Sox9 expression in retinal pigment epithelial cells.

Science.gov (United States)

Goto, So; Onishi, Akishi; Misaki, Kazuyo; Yonemura, Shigenobu; Sugita, Sunao; Ito, Hiromi; Ohigashi, Yoko; Ema, Masatsugu; Sakaguchi, Hirokazu; Nishida, Kohji; Takahashi, Masayo

2018-04-03

VEGF secreted from retinal pigment epithelial (RPE) cells is responsible for the choroidal vascular development; however, the molecular regulatory mechanism is unclear. We found that Aldh1a1 -/- mice showed choroidal hypoplasia with insufficient vascularization in the dorsal region, although Aldh1a1, an enzyme that synthesizes retinoic acids (RAs), is expressed in the dorsal neural retina, not in the RPE/choroid complex. The level of VEGF in the RPE/choroid was significantly decreased in Aldh1a1 -/- mice, and RA-dependent enhancement of VEGF was observed in primary RPE cells. An RA-deficient diet resulted in dorsal choroidal hypoplasia, and simple RA treatment of Aldh1a1 -/- pregnant females suppressed choroid hypoplasia in their offspring. We also found downregulation of Sox9 in the dorsal neural retina and RPE of Aldh1a1 -/- mice and RPE-specific disruption of Sox9 phenocopied Aldh1a1 -/- choroidal development. These results suggest that RAs produced by Aldh1a1 in the neural retina directs dorsal choroidal vascular development via Sox9 upregulation in the dorsal RPE cells to enhance RPE-derived VEGF secretion. © 2018, Goto et al.

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

DEFF Research Database (Denmark)

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

2002-01-01

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

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

Science.gov (United States)

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

2010-06-01

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

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

Directory of Open Access Journals (Sweden)

Bradley Garman

2017-11-01