Chaim Edelstein

Immunohistochemical expression of phospho-akt in uveal melanoma

The aim of this study was to evaluate the immunohistochemical expression of phospho-Akt and its possible association with clinicopathological features in uveal melanoma. Thirty-four enucleated eyes from 34 patients with choroidal melanoma were included in the study. Patients were divided into two groups based on the treatment received: (1) primary enucleation (n=18); (2) radiotherapy, either external beam or brachytherapy, and enucleation (n=16). Clinicopathological data were obtained. The minimum follow-up time was 72 months. Immunohistochemistry for phospho-Akt was performed using an anti-phospho-Akt (Ser 473) rabbit antibody. The association of phospho-Akt with clinicopathological parameters was investigated in each patient group separately. Phospho-Akt immunostaining was cytoplasmic in both groups. In the primary enucleation group, 10 tumours were phospho-Akt positive (55.5%). Patients with phospho-Akt-positive tumours were older (average 70.8 years versus 59 years, P=0.01) and phospho-Akt immunoreactivity was significantly associated with a higher risk of metastatic disease (Kaplan–Meier analysis, P=0.02). In the radiotherapy and enucleation group, nine tumours were phospho-Akt positive (56.2%). The absence of phospho-Akt expression was correlated with male gender (P=0.02). The following conclusions can be drawn from this study: (1) phospho-Akt immunoexpression was detected in 55.5% of uveal melanomas treated with primary enucleation and in 56.2% of uveal melanomas treated with radiotherapy and enucleation; (2) the association of phospho-Akt immunoexpression with clinicopathological features, including prognosis, merits further study.

STEREOTACTIC FRACTIONATED RADIOTHERAPY IN THE TREATMENT OF JUXTAPAPILLARY CHOROIDAL MELANOMA: THE MCGILL UNIVERSITY EXPERIENCE

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.

The risk of other primary cancer in patients with uveal melanoma: a retrospective cohort study of a Canadian population.

BACKGROUND The incidence of second primary malignant tumours has doubled during the last 2 decades. These tumours now represent the sixth most common group of cancers. Many authors have described the presence of multiple primary cancers in patients with uveal melanoma. However, no studies have been performed using Canadian data. The purpose of this study was to describe the occurrence of other primary cancers diagnosed before or after uveal melanoma and to calculate the incidence of subsequent primary cancer in a Canadian cohort with uveal melanoma. METHODS We conducted a retrospective study of a cohort of patients with uveal melanoma diagnosed between 1990 and 2002 at a university-affiliated centre in Montreal. We reviewed medical records to identify patients in whom other, unrelated primary malignant disease had been diagnosed. We used the standardized incidence ratio to calculate the risk of development of a second, unrelated cancer following the diagnosis of uveal melanoma. RESULTS A total of 129 cases of uveal melanoma were diagnosed. Eighteen patients (14%) also had a diagnosis of an unrelated primary cancer. In nine patients the other cancer had been diagnosed first, and in nine patients the other tumour had been diagnosed after the uveal melanoma. There was no increased risk of development of any particular form of cancer studied for females or males. INTERPRETATION In our Canadian cohort, statistical analysis showed no increased risk of a second cancer, overall or by organ site, in male or female patients with uveal melanoma. As uveal melanoma is a rare type of cancer, analyses of a much larger cohort may be needed to accurately estimate the risk of development of a second primary cancer in patients with uveal melanoma.

New prognostic factors in uveal melanomas: potential molecular targets for therapy.

Even with advances in the diagnosis and local treatment of uveal melanoma, there has been no significant change in the survival rates of these patients in the last decades. Metastatic disease still occurs at the same frequency, and no systemic therapy is currently offered to patients after local eye treatment. Therefore, experimental and clinical research has been focused on the metastatic cascade in order to elucidate its underlying mechanisms at the molecular level. As a result, new prognostic factors in uveal melanoma have been described that also serve as molecular targets for the development of novel treatments. These prognostic factors/molecular targets, such as membrane receptors, enzymes, cytokines, cytoskeleton components, oncogenes, tumour suppressor genes, cell-cycle proteins and nuclear antigens, are reviewed in this article.

Retinal capillary hemangioma in von Hippel-Lindau disease

Retinal capillary hemangioma (RCH) is a benign vascular tumour that often presents a diagnostic dilemma. It was first described by Fuchs, in 1882.1 In this report, we present a case of unilateral vision loss as the initial manifestation of von Hippel–Lindau (VHL) disease and a summary of the ocular and systemic clinical features and the differential diagnosis of RCH, along with the treatment options, as determined from a literature review.

Choroidal melanoma: clinical presentation and differential diagnosis.

Choroidal melanoma represents a diagnostic challenge in ophthalmology owing to the varied presenting symptoms and signs coupled with a wide variety of masquerading lesions. In this article the authors review the clinical presentation and differential diagnosis of this malignant neoplasm.

Intraoperative Sonographically Assisted Radioactive Iodine 125 Plaque Brachytherapy for Choroidal Melanoma Visual Acuity Outcome

The purpose of this study was to present a retrospective series of cases from a single Canadian academic center assessing visual acuity outcomes after intraoperative sonographically assisted iodine 125 (125I) plaque brachytherapy treatment.