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PubMedDate not supplied

Management of porous polyethylene implant exposure in patients with retinoblastoma following enucleation.

BACKGROUND AND OBJECTIVE: To report the features and the management of porous polyethylene implant exposure in patients with retinoblastoma following enucleation. PATIENTS AND METHODS: The medical records of 33 patients (33 sockets) following enucleation and porous polyethylene implantation for retinoblastoma were reviewed. RESULTS: The mean age at enucleation was 24 months (range, 2 to 85 months). The exposure rate was 33% (11 cases), and the mean time from enucleation to exposure was 15 months (range, 7 to 29 months). One case was resolved only by supportive management, and the remaining 10 were successfully treated with a scleral patch graft and maintained well during a mean follow-up of 15 months after surgical repair. There was no statistical evidence that age, gender, implant size, or chemotherapy had an effect on implant exposure. CONCLUSIONS: Porous polyethylene implant exposure does not seem to be resolved by conservative management. We recommend early surgical management, such as scleral patch graft, as opposed to supportive management.

Antineoplastic Agents↗
PubMed2004

Nuclear and plasma membrane localization of SH3BP4 in retinal pigment epithelial cells.

PURPOSE: The SH3BP4 protein contains domains belonging to the Eps15-Homology (EH) network family of endocytosis proteins and a C-terminal death domain. The purpose of this study was to determine the expression of SH3BP4 in ARPE-19, Y79 and COS-7 cell lines and to determine SH3BP4 subcellular localization within ARPE-19 cells. METHODS: A chicken anti-human SH3BP4 antibody was generated that specifically immunostains SH3BP4 fusion proteins and a corresponding endogenous protein band at 120 kDa. Protein expression of SH3BP4 was determined using western analysis of multiple cell lines and dissected retinal tissue. Intracellular localization of both endogenous SH3BP4 and SH3BP4 fusion proteins were determined using subcellular fractionation and microscopy studies using ARPE-19 and COS-7 cells. RESULTS: The retinal pigment epithelial (RPE) cell line ARPE-19 was found to express SH3BP4 protein at more than 7 fold the levels in Y79 retinoblastoma cells and more than 2.5 fold the levels in COS-7 cells. Both the RPE and neural retinal layers of the eye were also found to express the SH3BP4 protein. SH3BP4 endogenous and fusion proteins were found to localize to both membrane and nuclear fractions but not the cytosol in subcellular fractionation experiments. Subsequent microscopy analyses show that SH3BP4 fusion proteins localize to the plasma membrane and the nuclear periphery. CONCLUSIONS: These studies show that SH3BP4 is expressed in the RPE and neural retina in vivo, and in ARPE-19, Y79, and COS-7 cell lines. Compared to other EH network and death domain proteins, SH3BP4 fusion proteins have an unusual intracellular localization to the plasma membrane and the nuclear periphery. The present demonstration of the suborganelle localization in conjunction with the unique domain combinations belonging to both endocytosis and cell death pathways suggests that SH3BP4 has physiological significance for RPE cells.

Adaptor Proteins, Signal Transducing↗
PubMedDate not supplied

[Delayed diagnosis in retinoblastoma].

OBJECTIVES: To identify the main symptoms of retinoblastoma and to determine the mean time between symptom onset and diagnosis (lag time). PATIENTS AND METHODS: We carried out a retrospective analysis of the patients diagnosed with retinoblastoma between January 1991 and June 2000, at the Pediatric Department of the Hospital do Cancer, Sao Paulo, Brazil. Statistical analyses performed were: Student's t test, ANOVA, Tukey-HSD test (honest significant differences), Levene's test, multiple regression, ROC curve, logistic regression, Kaplan-Meier, and log rank. RESULTS: 327 medical records (171 males) were reviewed. The mean age was 25 months. Localized disease was identified in 269 patients. The most frequent symptoms were leukocoria (79%), strabismus (10.7%) and tumor mass (3.4%). Mean lag time was 5.8 months. Patients older than 2 years old had longer lag time in comparison to infants (7.2 vs 4.7 months; p = 0.001). Lag time was longer among patients with strabismus (8.8 months) in comparison to patients with tumor mass (2.3 months) and leukocoria (5.6 months); p = 0.014. Patients with metastatic disease had longer lag time (10.6 months; p < 0.001). Lag time was influenced by advanced disease (OR = 3.25/CI = 1.61:6.55), metastatic disease (OR=3.52/ CI = 1.21:10.21) and strabismus (OR = 2.84/IC = 1.36:5.92). Five-year overall survival rates were higher among patients with localized disease (94.6% ) and among patients with lag time less than 6 months (91%), in comparison to patients with longer lag time (78%; p < 0.001). CONCLUSION: Most frequent symptoms of retinoblastoma were leukocoria, strabismus and tumor mass. Mean lag time was 5.8 months. Strabismus and advanced disease were associated to longer lag time. Patients with advanced disease and lag time longer than 6 months had worse prognosis.

Child↗
PubMed2005

A retrospective review of visual outcome and complications in the treatment of retinoblastoma.

The aim of this study was to look at the visual outcome and treatment complications of children diagnosed with Retinoblastoma during the years 1985-2003 inclusive. A retrospective review of all patients records was performed. Patient characteristics, treatment methods and complications were recorded. Twenty eight children presented to Temple street Hospital between 1985-2003. Six of these infants had bilateral tumours. The mean age at presentation was 23.7 months. Sixty-nine percent presented with Leucocoria, of these 33% also had a squint. The mean duration of symptoms was only known in 58% and this figure was approximately 19.8 months. Enucleation was performed in 24 eyes of 24 patients. Three patients required adjuvant chemotherapy post enucleation. Two eyes was treated with external beam radiation and one eye with plaque radiotherapy. One eye (second eye) was treated with systemic chemotherapy and radiation. Five eyes of three patients were treated with systemic chemotherapy followed by adjuvant Argon laser, cryotherapy and diode laser to each eye.The complications of each treatment group was recorded. The visual outcome in the salvaged eyes was favourable. There were no deaths recorded. Though chemotherapy with adjuvant local treatments provide adequate treatment for early tumours, enucleation still plays a major role in the treatment of Retinoblastoma. The total eye salvage rate in this study was 29% with an enucleation rate of 90% in unilateral cases and 33% in bilateral cases. Sixty-six percent of bilateral eyes affected were salvaged. Seventy-one percent of tumours were diagnosed after a parent noticed a gross abnormality of the eye. This highlights the possible need for screening for retinoblastoma in the infant population.

Chemotherapy, Adjuvant↗
PubMedDate not supplied

Evolution of a retinoma case in 21 years.

A 35-year-old man was observed during a 21-year period with fundus color photography, fluorescein angiography, and B-scan ultrasonography for a presumed retinoma detected in his left eye during routine ophthalmoscopy in 1982. The patient was a carrier of the 13q14 retinoblastoma gene. His retinal lesion remained stable during the follow-up period without signs of malignant transformation. Retinomas are most commonly observed in patients with retinoblastoma and their relatives. In this case, none of the patient's parents, siblings, or children had evidence of a retinal tumor. Photographic documentation of the nonprogressive nature of this presumed retinoma is provided and demonstrates the absence of growth.

Adolescent↗
PubMed2005

Bilateral Coats' disease with unusual presentation--a case report.

Coats' disease is a well-known ocular disorder, characterized by idiopathic retinal telangiectasia, retinal exudation and retinal detachment. We report on a boy who first presented at the age of 2 years with Coats' disease and secondary neovascular glaucoma. The differential diagnosis with retinoblastoma could not be made clinically or with the help of imaging studies, such as ultrasonography or computed tomography scanning (CT-scan). The right eye was consequently enucleated for diagnostic and therapeutical purposes. Histopathologic examination confirmed the diagnosis of Coats' disease. Five years later the same boy consulted again with profound visual loss in his only functional left eye. Fundoscopy revealed lesions typical for Coats' disease. Coats' disease can present in very different ways and bilateral disease is possible, even after several years.

Child, Preschool↗
PubMed2001

Genetic profile of 81 retinoblastoma patients from a referral hospital in southern India.

PURPOSE: To determine chromosomal abnormalities and inheritance pattern in patients with retinoblastoma from a referral hospital in southern India. MATERIALS AND METHODS: Eighty-one retinoblastoma patients from 78 families were included in this study. Peripheral venous blood was taken for chromosomal analysis and pedigree was ascertained for segregation analysis. RESULTS: Male to female ratio was 1.7:1, 55.56% were bilateral retinoblastoma, the mean age of onset was 12.37 months in bilateral and 33.07 months in unilateral cases (p=0.048). Majority (90.12%) had sporadic inheritance and 6.17% had autosomal dominant inheritance. In chromosomal abnormalities, 8.33% had 13q14 deletion, three cases had de novo balanced translocations. CONCLUSION: The age of onset of the disease was much earlier in the bilateral cases compared to unilateral cases. Sporadic inheritance was predominant while only a small percentage of patients had autosomal dominant inheritance. The percentage of patients with 13q14 deletion was higher than reported in the literature and three novel chromosomal translocations were observed. This is one of the largest series of cases reported from India.

Adolescent↗
PubMed2005

[Genetic aspects of retinoblastoma].

Retinoblastoma is a genetic expression model of the tumors' suppressor genes. This study explains the most important elements of the genetic mechanisms which govern retinoblastoma's appearance and remission. It also attempts to address questions about the risk of patient's relatives getting retinoblastoma.

Chromosomes, Human, Pair 13↗
PubMed2005

[Analysis of angiogenesis associated factors of retinoblastoma cell line and tumor tissues].

OBJECTIVE: To investigate the factors regulating angiogenesis of retinoblastoma. METHODS: Cultured retinoblastoma cells from HXO-Rb-44 cell lines were inoculated subcutaneously into the leg of nude-mice. Experimental retinoblastoma was studied by immunohistochemistry staining for the expression of angiogenesis factors (VEGF-A, VEGF-C, VEGF-D and bFGF), vascular endothelial cell membrane receptor tyrosine kinases (Flt-1, Flt-4, Flk-1, Tie-2 and FGFR), transcription regulated factor, Hif-1, matrix metalloproteinase (MMP-2, MMP-7 and MMP-9) and tissue inhibitor of metalloproteinase (TIMP-1 and TIMP-2). RESULTS: There were plenty of capillaries and small vessels in the retinoblastoma. Some retinoblastoma cells expressed Hif-1 and most cells expressed VEGF at a high level, especially VEGF-D. Flt-1, Flt-4 and FGFR were found in vascular endothelial cells in the retinoblastoma. Three matrix metalloproteinases were positive and two tissue inhibitors of metalloproteinases were negative in the retinoblastoma. CONCLUSIONS: Down-regulated TIMP and up-regulated MMP and VEGF signal transduction play an important role in the occurrence of angiogenesis in the retinoblastoma. This could be considered as the target of retinoblastoma treatment.

Animals↗
PubMed2005

[Use of ruthenuim 106 in retinoblastoma treatment].

The Charles University Teaching Hospital in Prague - Motol started to treat patients with retinoblastoma by means of brachytherapy after obtaining the permission to use closed source of ionizing radiation in the beginning of the year 2003. The applicator containing ruthenium (106Ru) emitting mostly the beta radiation was chosen. Half-life is 369 days and the nominal activity of the source is 21.1 MBq. The applicator is placed in place for one to several days according to the prominence of the tumor and actual activity of the source. Duration of the application is calculated with a special program. In the year 2003, three patients with retinoblastoma were treated. In one case bilateral involvement was determined, and the brachytherapy was used for treatment of both eyes. The next patient was treated twice; one treatment followed the other with different localization of the applicator because of too large basis of the tumor. In 2003, altogether the brachytherapy was used for treatment of retinoblastoma five times. In all cases, the combined treatment (chemoreduction, teletherapy, transpupillary thermotherapy, or cryotherapy) was performed. One eyeball was enucleated because of severe post-radiation retinopathy, the second one for persisting tractional retinal detachment. In remaining cases no serious complications or progression of the malignancy were observed.

Brachytherapy↗
PubMed2005

Estimating the incidence of retinoblastoma in Texas.

The purpose of this study was to estimate the number of retinoblastoma cases anticipated each year in various urban and rural areas in Texas. We obtained the most recent data on the number of live births in Texas from the Texas Department of Health. Using those data and the retinoblastoma incidence rate of 1 in 15,000 live births, we estimated that 26 cases of the disease will be diagnosed in Texas each year. Nearly half of those cases will occur in infants in rural areas of the state. We compared those values with data from the Texas Cancer Registry. Primary care physicians, particularly in rural areas of Texas, must screen patients for retinoblastoma and consider arrangements for rapid referral when the diagnosis is suspected.

Humans↗
PubMed2005

Cancer stem cell characteristics in retinoblastoma.

PURPOSE: There is increasing evidence that cancer stem cells contribute to tumor progression and chemoresistance in a variety of malignancies, including brain tumors, leukemias, and breast carcinomas. In this study, we tested the hypothesis that retinoblastomas contain subpopulations of cells that exhibit cancer stem cell properties. METHODS: The following sources of retinoblastoma cells and tissues were examined for the presence of stem cell markers by immunocytochemistry: retinoblastoma tumors from mice transgenic for the SV40 T-antigen (driven by the beta-luteinizing hormone promoter), cell pellets of human Y79 and WERI-Rb27 retinoblastoma cell lines, and archival human retinoblastoma pathological specimens. Hoechst dye exclusion, mediated by the stem cell surface marker ABCG2 (ATP-binding cassette transporter, G2 subfamily), was assessed by flow cytometry in mouse tumors and WERI-Rb27 cells. RESULTS: Small numbers of retinoblastoma cells (less than 1%) exhibited immunoreactivity to stem cell markers ABCG2, aldehyde dehydrogenase 1 (ALDH1), MCM2 (minichromosome maintenance marker 2), SCA-1 (Stem cell antigen-1), and p63. Hoechst dye uptake in mouse tumors and WERI-Rb27 cells was enhanced by addition of 50 microM Verapamil, consistent with activity of the calcium-sensitive ABCG2 protein. Flow cytometric analysis confirmed the presence of small subpopulations of cells excluding Hoechst dye in mouse retinoblastoma tumors (0.3%) and WERI-Rb27 cells (0.1%) in a verapamil-sensitive manner. ABCG2 and ALDH1 positive cells were Hoechst-dim, as seen by dual labeling in vitro. CONCLUSIONS: Mouse and human retinoblastoma tumor cells contain a small subpopulation of cells that exhibit a cancer stem cell-like phenotype. Especially significant is the expression of ABCG2 in mouse and human tumor cells, a calcium-sensitive cell surface protein that not only acts to exclude Hoechst dye, but also confers resistance to over 20 different chemotherapeutic agents. These findings point to a heterogeneity in retinoblastoma tumors that may have significant impact on future treatment strategies.

Aldehyde Dehydrogenase↗