SEARCH · Search PubMed
Results for “Retinal Neoplasms”
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
An aggressive bone marrow evaluation including immunocytology with GD2 for advanced retinoblastoma.
There is general agreement that bone marrow (BM) examination for staging in patients with retinoblastoma should be limited to cases with advanced disease. However, there are limited data about the yield of sampling multiple sites with aspirations and biopsies and immunocytology. Our policy for BM examination included: 2 aspirates and 2 biopsies at the posterior iliac crest scheduled only for cases with postlaminar optic nerve extension (n=56), scleral invasion (n=10) or orbital (n=5) or metastatic disease at diagnosis (n=7) or at extraocular relapse (n=18). Immunocytology with the antibodies 3A7 or 3F8 for the ganglioside GD2 was performed. From 1/1994 to 3/2005, 277 newly diagnosed patients and 5 at extraocular relapse were included. BM invasion was not found in any of the 66 patients enucleated with disease confined to the globe, but was found in 11/27 of those with overt extraocular disease. There were 2/11 cases with at least 1 negative aspirate with positive biopsy and/or immunocytology for GD2. GD2 positivity was found in 9/9 cases. A more aggressive BM evaluation has a low yield in enucleated patients with high-risk features but disease limited to the globe. However, in cases with overt extraocular dissemination, the use of BM biopsy and immunocytology for GD2 allowed for the detection of cases that would have been missed by aspirations alone. GD2 was intensively expressed and it may also be used to monitor disease response and the presence of minimal residual disease.
Relationship between histopathological features of chemotherapy treated retinoblastoma and P-glycoprotein expression.
BACKGROUND: P-glycoprotein (P-gp) has been identified as a possible mediator of chemoresistance in retinoblastoma. The aim of this study was to determine the expression of P-gp in retinoblastoma treated with chemotherapy prior to enucleation. METHODS: Seventeen enucleated specimens of retinoblastoma from 16 patients were studied. Nine had been treated with chemotherapy alone, and eight had been treated with chemotherapy and other forms of local treatment. Tumour differentiation as well as choroidal and optic nerve invasion were assessed. P-gp immunohistochemical staining was performed and evaluated as negative, low or high. RESULTS: Histopathological assessment of the cases showed that 14 of 17 eyes (82.3%) had viable retinoblastoma cells. Nine retinoblastomas were considered regressed with a well-differentiated component, five regressed retinoblastomas had viable cells with poor differentiation and three retinoblastomas had regressed leaving no viable cells. Sixteen of 17 retinoblastomas were P-gp positive. In the one case with optic nerve invasion and the three cases with massive choroidal invasion, P-gp expression was found in invading retinoblastoma cells. CONCLUSION: Almost all retinoblastomas expressed P-gp. High levels of P-gp expression might play a role in chemotherapy resistance of retinoblastoma or, conversely, chemotherapy might induce P-gp expression. These results might have an impact on management of bilateral retinoblastoma.
Racemose haemangioma of the retina; two additional cases, including one with defects of the visual fields as a complication of arteriography.
Explore the source record for details and available documents.
A multicentre report from the Mexican Retinoblastoma Group.
BACKGROUND: Retinoblastoma (RB) is a relatively uncommon tumour in childhood. The incidence of retinoblastoma in Mexico is probably higher than the incidence reported worldwide, however there is not enough information about the characteristics of this illness in Mexico. This report aims to present the results of a multicentre clinical survey of RB in Mexico. METHODS: A retrospective study was carried out on all RB cases treated in 16 institutions during the last six years. The variables analysed were age at diagnosis, sex, affected eyes, treatment modalities, and pathological staging. Overall survival was obtained. RESULTS: The authors analysed 500 cases; age range was 0-182 months. There were 364 unilateral cases (72.8%). Enucleation was performed in 84.9% of the patients. The St Jude's staging was: 7.4% stage I, 52.8% stage II, 18.0% stage III, 11.4% stage IV, 7.2% not evaluated, and 3.2% missing data. Chemotherapy was used in 74.4% of the patients. Disease free survival was 89% at 73 months follow up. CONCLUSIONS: The paper presents a great number of cases and pioneers multicentre studies in paediatric ophthalmology and oncology in this country. Given the great number of patients in advanced stages and the variability on treatment schemes, it is evident that it is mandatory to work in a cooperative group and develop a national early detection programme as well as a treatment protocol which include all specialists involved in the care of patients with RB.
Multidrug resistant proteins: P-glycoprotein and lung resistance protein expression in retinoblastoma.
BACKGROUND/AIM: Retinoblastoma is the commonest primary intraocular tumour in children. Chemotherapy now plays a big part in the treatment of these tumours. There is not much information about the role of the multidrug resistance proteins (MDR)-P-glycoprotein (P-gp) and vault protein lung resistance protein (LRP)-in retinoblastoma. The authors investigated the expression of P-gp and LRP in retinoblastoma and correlated them clinicopathologically. METHODS: Among 60 retinoblastomas, 40 tumours were not subjected to preoperative or postoperative chemotherapy and 20 tumours were subjected to postoperative chemotherapy. In this cohort 27 tumours had no invasion and 33 tumours had invasion of choroid, optic nerve, and orbit. P-gp and LRP expression were studied by immunohistochemistry. Immunoanalysis was done semiquantitatively. RESULTS: Among the 60 tumours P-gp was expressed in 23 (38%) tumours and LRP was expressed in 35 (58%). P-gp was expressed in 11/27 (40%) tumours with no invasion and in 12/33 (36%) tumours with invasion. LRP was expressed in 15/27 (55%) tumours with no invasion and in 20/33 (60%) tumours with invasion. Both P-gp and LRP were negative in three tumours with invasion, which had later developed bone marrow metastasis. There was no correlation between P-gp and LRP expression with invasion, differentiation and laterality of the tumours and response to treatment. CONCLUSION: Retinoblastoma expresses P-gp and LRP intrinsically before chemotherapy and none of these proteins predicted the response to chemotherapy. Thus, further studies are needed to understand the significance of the expression of the P-gp and LRP proteins in retinoblastoma.
P-glycoprotein expression in retinoblastoma.
Explore the source record for details and available documents.
Vitreous relapse following primary chemotherapy for retinoblastoma: is adjuvant diode laser a risk factor?
AIMS: To evaluate rates of vitreous relapse among retinoblastoma patients treated with primary chemotherapy and assess diode laser as a potential risk factor for relapse. METHODS: Retrospective review of all patients treated with primary chemotherapy at a large ocular oncology centre. Eyes that developed vitreous relapse were coded with regard to Reese-Ellsworth Group, laterality, time to relapse, type of relapse (vitreous base or non-vitreous base relapse), treatments used (including adjuvant diode laser), and ocular preservation. Individual tumour foci treated with laser hyperthermia were also coded for laser parameters including power settings, number of treatments, and concomitant administration of systemic chemotherapy (chemothermotherapy). RESULTS: 15 of 106 eyes (14.15%) developed vitreous relapse over a 6 year period. Mean time to relapse was 7.2 months after chemotherapy was completed. Five cases (33%) were of the vitreous base variety. Ocular salvage was attempted in 11 cases using a variety of methods; one patient was lost to follow up. Six of the remaining 10 eyes (60%) were salvaged. Eight of 38 eyes (21%) treated with systemic chemotherapy and laser hyperthermia developed vitreous relapse compared with seven of 68 eyes (10%) treated with primary chemotherapy alone (p<0.005). Laser settings, number of hyperthermia treatments, and the concomitant use of systemic chemotherapy (chemothermotherapy) were not associated with higher rates of vitreous relapse. CONCLUSION: Nearly one in seven eyes with retinoblastoma treated with primary chemotherapy may develop vitreous relapse. The administration of diode laser hyperthermia appears to increase this risk. Despite additional therapy a number of these eyes succumb to enucleation.
Expression patterns of cyclin D1 and related proteins regulating G1-S phase transition in uveal melanoma and retinoblastoma.
BACKGROUND/AIMS: A checkpoint mechanism in late G1, whose regulation via loss of retinoblastoma protein (pRB) or p16, or overexpression of cyclin D1 or cyclin dependent kinase 4 (CDK4), has been proposed to constitute a common pathway to malignancy. The aims of this study were (a) to compare markers of cell cycle G1-S phase transition in an intraocular tumour with known pRB deficiency (retinoblastoma) and compare it with one with an apparently functional pRB (uveal melanoma); (b) to determine if one of these markers may have a role in the pathogenesis of uveal melanoma; and (c) to determine if there is a difference in cell cycle marker expression following treatment of uveal melanoma and retinoblastoma. METHODS: 90 eyes were enucleated from 89 patients for retinoblastoma (n = 24) or for choroidal or ciliary body melanoma (n = 66). Conventional paraffin sections were assessed for cell type and degree of differentiation. Additional slides were investigated applying standard immunohistochemical methods with antibodies specific for cyclin D1 protein, pRB, p53, p21, p16, BCL-2, and MIB-1. RESULTS: Cyclin D1 protein and pRB were negative in retinoblastoma using the applied antibodies. In contrast, cyclin D1 protein expression was observed in 65% of uveal melanomas; a positive correlation between cyclin D1 cell positivity and tumour cell type, location, growth fraction, as well as with pRB positivity was observed. p53, p21, and p16 could be demonstrated in both tumours. An inverse relation between p53 and p21 expression was demonstrated in most choroidal melanomas and in some retinoblastomas. Apart from a decrease in the growth fractions of the tumours as determined by MIB-1, a significant difference in the expression of G1-S phase transition markers in vital areas of uveal melanoma and retinoblastoma following treatment with radiotherapy and/or chemotherapy was not observed. CONCLUSION: Retinoblastomas and uveal melanomas, two tumours of differing pRB status, differ also in their immunohistochemical pattern for markers of the G1-S phase transition of the cell cycle. The results of the present study support the concept of (a) an autoregulatory loop between pRB and cyclin D1 in tumours with a functional pRB and the disruption of this loop in the presence of pRB mutation, as well as (b) a checkpoint mechanism in late G1, whose regulation via loss of p16 or pRB, or overexpression of cyclin D1 constitutes a common pathway to malignancy. Further, the results raise the possibility of cyclin D1 overexpression having a role in the pathogenesis of uveal melanoma.
Eye cancer incidence in Singapore.
AIM: To describe the epidemiological characteristics of patients with primary intraocular, conjunctival, and orbital cancers seen in Singapore from 1968 to 1995. METHODS: Epidemiological data of all cancers diagnosed in Singapore are collected by the Singapore Cancer Registry. The data of all cases of Singapore residents with eye cancers (ICD-9, site 190) were retrieved for analysis. This includes intraocular, conjunctival, and orbital cancers but excludes cancer of the eyelids. RESULTS: There were 125 patients of which 67 (53.6%) were male and 58 (46.4%) were female. The average annual age standardised incidences for male and female Singapore residents were 1.89 and 1.81 per million respectively. The most common cancer was retinoblastoma (53.6%), followed by malignant melanoma (19.2%) and squamous cell carcinoma (11.2%). The most common cancer among patients younger than 15 years was retinoblastoma (95.7%) and that for those 15 years and older was malignant melanoma (42.6%). The most common subsite was the retina (53.6%), followed by conjunctiva (12.8%), orbit (8.8%), and lacrimal gland (6.4%). CONCLUSION: The annual age standardised incidence have been stable for the 28 years studied. Retinoblastoma is much more common than melanoma in Singapore. These expanded epidemiological characteristics serve to provide ophthalmologists and epidemiologists with a foundation to monitor future disease patterns in Singapore and provide a basis for comparison with other selected populations elsewhere.
When to look for Von Hippel-Lindau disease in gastroenteropancreatic neuroendocrine tumors?
Von Hippel-Lindau (VHL) disease is a progressive autosomal dominant multisystem disorder that is associated with a germ line mutation of the VHL gene on the short arm of chromosome 3. A variety of benign and malignant diseases, including eye and CNS hemangioblastomas, renal cell carcinoma and pheochromocytoma are the major components. Gastroenteropancreatic neuroendocrine tumors are also listed among the typical complications, although these occur seldom. Virtually all such tumors are pancreatic islet cell tumors. VHL-associated islet cell tumors are mostly hormone-inactive. They can be detected during screening investigations according to the multidisciplinary disorder or by workup of space-occupying lesions. There are no specific predictors for malignancy in VHL-associated islet cell neoplasias, but tumors smaller than 3 cm in diameter are believed to be always benign. Gadolinium-enhanced MRI is currently the imaging method of choice, but contrast-enhanced CT is also a diagnostic option. The spectrum of manifestations is illustrated by selected cases.
[A new case, the first, of Hippel-Lindau disease; historical note].
Explore the source record for details and available documents.
[Cavernous angioma of the retina].
Explore the source record for details and available documents.
[Microangioma with degeneration of the retina; possible mono-symptomatic from of the Hippel-Lindau disease].
Explore the source record for details and available documents.
Expression of the lipogenic enzyme fatty acid synthase (FAS) in retinoblastoma and its correlation with tumor aggressiveness.
PURPOSE: Fatty acid synthase (FAS) performs the anabolic conversion of dietary carbohydrate or protein to fatty acids. Many common human cancers express high levels of FAS, and its differential expression between normal and neoplastic tissues has led to the consideration of FAS as a target for anticancer therapy. To investigate the potential of targeting FAS in the treatment of retinoblastoma, we first determined whether FAS was activated in this human tumor. Moreover, correlation of FAS expression with tumor aggressiveness was determined. METHODS: FAS reactivity was evaluated by immunohistochemistry in 66 retinoblastoma specimens from 65 patients. Degree of tumor differentiation, choroid invasion, optic nerve infiltration, mitotic rate, and necrosis extension were estimated. FAS expression was correlated with all these tumor characteristics by means of parametric and nonparametric statistical analyses. RESULTS: Eighty-two percent of tumors were FAS positive. Stronger FAS expression correlated with more advanced choroid (P < 0.001) and optic nerve (P = 0.016) invasion, high mitotic index (P < 0.001), and less differentiated histology (P = 0.047). Correlation with extension of necrosis was not statistically significant. Unaffected retina was negative. CONCLUSIONS: The data suggest that expression of FAS and fatty acid synthesis support an essential functional aspect of retinoblastoma cells, perhaps cell growth or survival. FAS activation may serve as a novel target for systemic and local antineoplastic therapy and, because it increases with tumor aggressiveness, its inhibition could represent an alternative treatment strategy in advanced and resistant retinoblastomas.
Vitamin D analogues increase p53, p21, and apoptosis in a xenograft model of human retinoblastoma.
PURPOSE: To study the antineoplastic effect of vitamin D analogues in a xenograft model of human retinoblastoma. METHODS: Athymic mice were injected subcutaneously with Y79 cells and treated 5 days a week with either mineral oil (control group) or the vitamin D analogues calcitriol or 1,25-dihydroxy-16-ene-23-yne vitamin D(3) (16,23-D(3)). BrdU was injected 1 hour before death. Animals were killed after 1, 2, 3, or 5 weeks. Paraffin-embedded sections of the tumors were studied for cell proliferation by monitoring for BrdU incorporation and cell death by terminal transferase dUTP-nick end labeling (TUNEL), 3'-overhang ligation, and histology. Sections of the tumors were immunostained for p53 and p21. RESULTS: There was no significant difference in incorporation of BrdU among the three groups, suggesting that cell proliferation is unaffected by vitamin D analogues. TUNEL was increased in tumors treated with vitamin D analogues compared with the control group. This increase was statistically significant for calcitriol in the time frame examined, but not statistically significant for 16,23-D(3). Alternatively, the ratio of proliferation to cell death was significantly different for both calcitriol and 16,23-D(3) compared with control tumors after 3 weeks of treatment. Dying cells contained DNA strand breaks with overhanging nucleotides and nuclear changes characteristic of apoptosis. There was an increase in staining for p53 and p21 in areas associated with cell death in specimens treated with vitamin D analogues. CONCLUSIONS: Vitamin D analogues appear to attenuate retinoblastoma tumor growth in athymic mice by increasing apoptosis. Cell death is associated with the upregulation of both p53 and p21.
Histopathological features and P-glycoprotein expression in retinoblastoma.
PURPOSE: To investigate the expression of P-glycoprotein (P-gp) in retinoblastoma specimens enucleated as a primary treatment or after conservative treatment and to correlate this expression with histopathological tumor features. METHODS: Retrospective analysis was performed on retinoblastoma specimens obtained consecutively between 1993 and 2003 by enucleation either as primary treatment (group I) or after the failure of conservative treatment (group II). Sections from the formalin-fixed, paraffin-embedded specimens were stained with hematoxylin and eosin. Group I tumor differentiation was classified according to the percentage of Flexner-Wintersteiner rosettes. Group II tumors, categorized as viable-appearing, regressed with a well-differentiated component (WDC), and regressed. Other features, such as choroidal and optic nerve invasion, were evaluated. P-gp expression was graded semiquantitatively as negative, low, or high. Variables were statistically analyzed by chi(2) and Student's t-tests. RESULTS: Histopathological assessment of group I revealed 65% moderately differentiated tumors, 30% well differentiated, and 5% poorly differentiated. Fifteen percent had optic nerve tumor invasion only, 20% choroidal invasion only, and 55% both choroidal and optic nerve invasion. Group II had 62.5% well-differentiated, regressed tumors; 25% had regressed tumors replaced by glial scarring; and 12.5% had tumors containing viable, poorly differentiated cells. Approximately 18% had choroidal tumor invasion only, 6.3% optic nerve tumor invasion only, and 6.3% simultaneous optic nerve and choroidal invasion. P-gp expression was observed in 60% of group I and 66.6% of group II. All P-gp-positive cases in group II had a high expression. P-gp was also expressed by 81.2% of well-differentiated tumors. CONCLUSIONS: P-gp was expressed more frequently by well-differentiated retinoblastomas, especially those treated by chemotherapy before enucleation. This finding could be related to treatment failure.
Response of retinoblastoma with vitreous tumor seeding to adenovirus-mediated delivery of thymidine kinase followed by ganciclovir.
PURPOSE: To evaluate the feasibility and safety of adenovirus-mediated gene therapy as a treatment for tumor seeds in the vitreous of children with retinoblastoma. PATIENTS AND METHODS: An Institutional Biosafety Committee-, Institutional Review Board-, Recombinant DNA Advisory Committee-, and US Food and Drug Administration-approved phase I study used intrapatient dose escalation of adenoviral vector containing a herpes simplex thymidine kinase gene (AdV-TK) followed by systemic administration of ganciclovir to treat bilateral retinoblastoma with vitreous tumor seeding refractory to standard therapies. Vitreous tumor seeds were treated by intravitreous injection of AdV-TK adjacent to disease sites. Each injection was followed by ganciclovir delivered intravenously every 12 hours for 7 days. RESULTS: Eight patients with vitreous tumor seeds were enrolled. One patient who was treated with 10(8) viral particles (vp) had resolution of the tumor seeds around the injection site. The seven patients who were treated with doses > or = 10(10) vp had resolution of their vitreous tumor seeds documented by fundoscopy. Toxicity included mild inflammation at 10(10) vp and moderate inflammation, corneal edema, and increased intraocular pressure at 10(11) vp. One patient was free of active vitreous tumor seeds 38 months after therapy. There has been no evidence of extraocular spread of tumor along the needle tract in any patient. CONCLUSION: AdV-TK followed by ganciclovir can be administered safely to children with retinoblastoma. Suicide gene therapy may contribute to the treatment of children with retinoblastoma tumor seeds in the vitreous, a resistant complication of retinoblastoma.