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N Bornfeld

Publications and source records attributed to N Bornfeld.

At least 19 recordsLinked to original sources
PubMed2000

The prognostic value of cyclin D1, p53, and MDM2 protein expression in uveal melanoma.

Malignant uveal melanoma is the commonest primary intraocular tumour in adults. It metastasizes frequently and 50% of patients die within 10 years of diagnosis. The expression of cyclin D1, p53, and MDM2 in uveal melanoma and their relationship to metastasis-free 5-year survival was determined, in order to investigate whether these proteins help to distinguish those patients with a favourable prognosis from those with a poorer one. Ninety-six eyes enucleated for uveal melanomas were immunohistochemically analysed for the protein expression of cyclin D1 and related cell-cycle markers, p53 and MDM2. The evaluation of the specimens was undertaken by two independent pathologists without knowledge of the outcome. Statistical analysis of clinical, morphological, and immunohistological features was performed. A 'favourable outcome' was defined as survival of at least 5 years after diagnosis, without metastases (n=57). An 'unfavourable outcome' was defined as death from metastases within the first 5 years after diagnosis of uveal melanoma (n=39). Cyclin D1 positivity (>15% positive tumour cells) as well as p53 positivity (>15% positive tumour cells) was associated with an unfavourable outcome (for cyclin D1: odds ratio=4. 2, 95% confidence interval 1.5-11.8, p=0.006; for p53: odds ratio=3. 2, 95% confidence interval 1.1-9.3, p=0.03). In addition, cyclin D1 positivity was associated with the presence of extraocular extension of the tumour (p=0.01), with the mixed or epithelioid cell type (p=0. 02), and with the tumour cell MIB-1 positivity (p=0.0001). MDM2 immunoreactivity of the tumour cells showed a potential correlation with clinical outcome (odds ratio=2.1, 95% confidence interval 0.8-5. 8, p=0.13). Multiple logistic regression models showed that cyclin D1 positivity is an independent prognostic factor after control for other prognostic markers. The expression of cyclin D1 in uveal melanoma is associated with a more aggressive course and histologically unfavourable disease. This could serve as a further independent prognostic factor in uveal melanoma.

Adolescent↗
PubMed2000

[Current therapy aspects of intraocular tumors].

The most frequent primary intraocular malignancies are uveal melanoma in adults and retinoblastoma in children. Genetic findings in uveal melanoma now allow a better risk-prediction with regard to metastatic disease. New treatment modalities like endo-resection, trans-scleral resection, proton beam irradiation and trans-pupillary thermotherapy are now being established in clinical routine. Management of retinoblastoma has changed during the last years considerably. In hereditary retinoblastoma external beam radiotherapy (EBR) results in a sixfold increased risk for the development of secondary, non ocular malignant tumors in these patients. New treatment regimens based on systemic chemotherapy were developed to replace EBR. In combination with chemotherapy there has been a continuing trend toward more conservative focal treatment for retinoblastoma. Indications and first results of these new treatment modalities are presented.

Adult↗
PubMed2000

[Adhesive properties of basal membranes of Bruch's membrane. Immunohistochemical studies of age-dependent changes in adhesive molecules and lipid deposits].

BACKGROUND: In addition to deposition of debris between the plasma and basal membrane of the RPE, different types of early and late AMD-like drusen, choroidal neovascularization and pigment epithelial detachments are characterized by splitting of Bruch's membrane between the basement membrane of the RPE and the inner collagenous layer. Because these layers are normally attached by adhesion molecules, the possible age-related regression of these adhesion molecules in this structure was examined. METHODS: The presence of the adhesion molecules laminin, fibronectin, collagen IV and of lipid deposits was examined in 44 macular specimen (age 4-88 years). RESULTS: Age-related regression of the adhesion molecules laminin, fibronectin and collagen IV was observed in the basement membrane of the RPE and the endothelium cells of the choriocapillaris. This effect correlated with an increase in lipid deposits. CONCLUSION: The regression of adhesion molecules, especially in the basement membrane of the RPE in association with increased lipid deposits in Bruch's membrane, may explain the development of a "cleavage edge" for the splitting of Bruch's membrane between the basement membrane of the RPE and the inner collagenous layer.

Adolescent↗
PubMed2000

Determination of surgeon's absorbed dose in iodine 125 and ruthenium 106 ophthalmic plaque surgery.

OBJECTIVE: Validation of dosimetry and exposition time to an ophthalmic surgeon during radioactive plaque operations. DESIGN: Experimental study in which videotaped operations and dosimetric measurements were used to model dosimetry. METHODS: We used thermoluminescence detectors for high sensitivity readings in radiation fields. Typical intersurgical mobility was videotaped and distances to the plaque was evaluated. MAIN OUTCOME MEASURE: Estimated radiation received by surgeons. RESULTS: All simulated plaque operations have a maximum dose rate of 6 mGy per minute (value in the inner eyeball). Mean dose rate is 2 mGy per minute (average of approximately all measurements). The surgeon's fingers receive a dose from 2 to 6 mSv from plaque operation. CONCLUSIONS: Results suggest that radioactive plaque operations are safe for the surgeon but that the time for plaque handling should be minimized. A surgeon should not exceed 100 to 200 operations per year.

Brachytherapy↗
PubMed2000

Telomerase expression in uveal melanoma.

BACKGROUND/AIMS: Accumulating evidence indicates that telomerase activity is repressed in normal human somatic cells but reactivated in cancers and immortal cells, suggesting that activation of telomerase activity has a role in carcinogenesis and immortalisation. To date, telomerase in uveal melanoma and, whether, it may have a role in the development or progression of these tumours has not been described. The expression patterns and the activity of telomerase were investigated in 14 uveal melanoma and these results were correlated with histological and immunohistological features of these tumours. METHODS: A modified PCR based telomeric repeat amplification protocol (TRAP) assay was used to demonstrate telomerase activity in 14 uveal melanomas. In addition, in situ hybridisation was used to demonstrate the expression pattern of the telomerase RNA component (hTR) at the single cell level in eight of these globes. RESULTS: The TRAP assay revealed moderate telomerase activity in all uveal melanomas examined. In situ hybridisation visualised a moderate to high upregulation of hTR in the melanoma cells but not in the admixed reactive cells. There was no correlation among tumour location, cell type, or growth fraction and the amount of telomerase activity. In addition, the cells of the germinative zone of the lens demonstrated a strong hTR expression. CONCLUSION: Telomerase activity is upregulated in uveal melanomas. The expression of hTR was located to the tumour cells and not the reactive tumour infiltrating cells. Strong telomerase expression was also demonstrated in cells of the germinative zone of the lens.

Adult↗
PubMed2000

Expression of the cell adhesion molecules ICAM-1, VCAM-1 and NCAM in uveal melanoma: a clinicopathological study.

To investigate the relationship between the expression of the cell adhesion molecules intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and neural cell adhesion molecule (NCAM) in uveal melanoma and the metastatic spread in the first 5 years after diagnosis, we performed a hospital-based case-control study with human tissue from 90 patients who underwent enucleation for primary uveal melanoma (iris melanoma excluded). Thirty-five patients developed metastasis within the first 5 years, and 55 patients lived metastasis-free for at least 5 years after enucleation. The paraffin-embedded and formalin-fixed globes were studied by immunohistochemistry with monoclonal antibodies for ICAM-1, VCAM-1 and NCAM. A strong ICAM-1 positivity (more than 75% of the tumor cells stained positive) was detected in 73 tumors (81%). The expression of 75% or less ICAM-1 positive cells in tumors was strongly associated with the development of metastases (odds ratio: 7.5, p = 0.001). Multiple logistic regression models showed that ICAM-1 is an independent risk factor for metastasis even after control for important prognostic markers like extraocular growth, ciliary body involvement, scleral infiltration and cell type. VCAM-1 was expressed in 24 out of 88 tumors (27.3%) and NCAM only in 14 out of 87 tumors (16%). Only spindle cells stained positive with anti-NCAM. NCAM and VCAM-1 expression was not related to metastasis. Our results show that the loss of ICAM-1 expression is associated with an increased risk of metastasis within the first 5 years after diagnosis.

Adult↗
PubMed1999

[Retinal capillary angioma. Clinical and molecular genetic studies].

UNLABELLED: Capillary retinal angiomas are rare vascular tumors that frequently occur in von Hippel-Lindau syndrome (vHL) but may also be sporadic. In all patients presenting with this tumor a thorough search for other vHL-associated lesions must be performed. After identification of the vHL gene on the short arm of chromosome 3 (3p25-26), the diagnosis is supported by molecular genetic analysis. PATIENTS: In 20 patients with retinal angioma a clinical search for other manifestations of vHL was performed. In 5 patients only one angioma was present. In all patients molecular genetic tests for a mutation of the vHL gene were performed by SSCP and direct sequencing. RESULTS: In 16 (80%) patients vHl was present, and in 15 it could be diagnosed by clinical findings or a positive family history. Organ lesions in vHL patients were CNS hemangioblastoma in 10 (63%), pancreatic cysts in 7 (43%) and renal cysts in 7 (43%) patients. In two patients (13%) renal carcinoma could be detected; in one patient a pheochromocytoma was present. A mutation could be detected in all 15 patients with clinically confirmed vHL. In three patients a new mutation of vHL disease was diagnosed genetically. In one of these patients a single retinal angioma was the only sign of vHL. CONCLUSION: In patients presenting with capillary retinal angioma a careful search for other vHL lesions has to be performed. A mutation of the vHL gene can be detected in the majority of patients; thus, molecular genetic testing is a powerful tool for diagnosis and detection of asymptomatic gene-carriers.

Adolescent↗
PubMed1999

Choroidal metastasis in men with metastatic breast cancer.

PURPOSE: To report two cases of choroidal metastasis in metastatic breast cancer in men. METHOD: Case reports of a 50-year-old man with an 8-year history of breast cancer who was initially examined with a solitary amelanotic choroidal tumor and a 62-year-old man with an 8-month history of breast cancer who was initially examined with numerous unilateral amelanotic choroidal tumors. RESULTS: Ophthalmoscopic and echographic characteristics of the choroidal tumors were typical for breast cancer metastasis. Systemic screening disclosed advanced metastatic disease in both patients. Choroidal metastasis could be effectively treated by external beam irradiation. CONCLUSIONS: Although breast cancer is a rare condition in men, it should be considered as a possible primary cancer in cases of choroidal metastasis.

Bone Neoplasms↗
PubMed1999

Radiotherapy of unilateral choroidal metastasis: unilateral irradiation or bilateral irradiation for sterilization of suspected contralateral disease?

Radiotherapy is the highly effective standard in the treatment of choroidal metastasis. Visual acuity can be stabilized or increased in about 70-80% of eyes treated, thus prevailing the quality of life in these worse prognostic patients. In about 30-40% bilateral macroscopic disease is found at diagnosis. The best treatment for unilateral metastasis remains controversial: unilateral or bilateral irradiation for sterilization of suspected contralateral metastasis or unilateral irradiation without irradiation of the contralateral choroidea. In the analysis of a prospective study (ARO 95-08) 35 out of 50 patients with choroidal metastasis had unilateral disease and received unilateral irradiation with a lateral field using 6 MeV-photons (40 Gy in 20 fractions) without sparing the contralateral choroidea. Therefore the posterior contralateral choroidea received 50-70% of the total dose (20-28 Gy) for suspected micrometastasis. None of these patients developed contralateral choroidal metastasis during the median follow up time of 11.5 months. A unilateral field with 40 Gy for unilateral choroidal metastasis without sparing the contralateral choroidea seems to be effective in destroying contralateral micrometastasis with a lower risk of late side effects compared with bilateral fields.

Adult↗
PubMed1999

Uveal melanoma: correlation of histopathologic and radiologic findings by using thin-section MR imaging with a surface coil.

PURPOSE: To evaluate whether the different signal intensities at magnetic resonance (MR) imaging of melanoma are associated with a higher content of melanin. MATERIALS AND METHODS: In a prospective study, MR imaging and ophthalmoscopic examination findings in 42 patients (19 women, 23 men; age range, 30-87 years) with uveal melanoma were compared with histopathologic examination findings obtained after enucleation. MR imaging was performed with 2-mm sections by using a 5-cm surface coil. T1- and T2-weighted images were obtained before and after contrast material administration. RESULTS: In 33 (79%) of the patients, there was homogeneous tumor pigmentation, whereas in nine (21%) patients, there was inhomogeneous bipartite tumor pigmentation. Compared with the histopathologic data, the results of qualitative evaluation were accurate in 29 (58%) of 50 and in 26 (53%) of 49 tumorous areas on T1- and T2-weighted images, respectively. Quantitative evaluation yielded better results, especially at T1-weighted imaging; an 86% correlation was found. Because of methodological reasons, only the superficial pigmentation of inhomogeneous tumors could be evaluated with ophthalmoscopy. CONCLUSION: Thin-section MR imaging of the eye enables an accurate prediction of melanomatous pigmentation with quantitative evaluation of plain T1-weighted images and is superior to ophthalmoscopy in cases of inhomogeneous pigmentation.

Adult↗
PubMed1999

[Retinoblastoma].

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Adolescent↗
PubMed1998

Clinicopathologic features of retinoblastoma after primary chemoreduction.

BACKGROUND: Primary chemotherapy is a new treatment approach in retinoblastoma, aiming to avoid radiogenic adverse effects, such as second tumor-associated mortality, as observed following external beam irradiation. OBJECTIVE: To describe the clinical and histopathologic regression pattern after primary chemotherapy in retinoblastoma. METHODS: Five patients with sporadic bilateral retinoblastoma underwent planned enucleation of their functionally blind eye after 2, 3 (in 2 patients), 4, and 6 courses of primary chemotherapy with carboplatin, etoposide, cyclophosphamide, and vincristine. The eyes were examined histopathologically, using light microscopy and immunohistochemical analysis with proliferation markers. RESULTS: One patient had a type 1 (cottage cheese) regression and 4 patients had either a type 2 (fish flesh) or a type 3 (combined) regression pattern. Histopathologic examination revealed a complete tumor necrosis in 1 patient with type 1 regression after 3 courses of chemotherapy and in 1 patient with type 3 regression after 4 courses of chemotherapy. The remaining 3 patients with type 2 or type 3 regression had histologically still active proliferative tumor cells after 2, 3, and 6 courses of chemotherapy. CONCLUSION: This article correlates histopathologically the clinically described efficacy of primary chemotherapy in the treatment of retinoblastoma, underlining, however, the necessity of careful observation and the use of ancillary treatment whenever there is no complete tumor regression.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Rubeosis iridis after vitrectomy for diabetic retinopathy.

BACKGROUND: Iris rubeosis and neovascular glaucoma (NVG) are serious complications of vitrectomy for proliferative diabetic retinopathy. The present study analyzes incidence and risk factors of these complications. METHODS: Preoperative and postoperative iris rubeosis were compared in 389 diabetic eyes after vitrectomy. Minimum follow-up was 6 months (median 26 months). Risk factors were studied using multivariate logistic regression analysis. RESULTS: Following vitrectomy, in 8.5% of the eyes stromal iris rubeosis developed de novo; NVG occurred in 5%. Significant risk factors for postoperative rubeosis were preexisting iris neovascularizations and postoperative retinal detachment. Six months after surgery, regression of preexisting iris rubeosis was observed in 57% of the eyes. In eyes without preoperative iris rubeosis, progression was found in 13% of cases 6 months postoperatively. CONCLUSION: With current surgical techniques iris rubeosis is more commonly regressive than progressive after vitreous surgery in diabetic eyes.

Adult↗
PubMed1998

Ruthenium-106 brachytherapy for peripheral retinal capillary hemangioma.

OBJECTIVE: This study aimed to evaluate the efficacy and safety of ruthenium-106 brachytherapy of large peripheral retinal capillary hemangiomas. DESIGN: A retrospective case series. PARTICIPANTS: In 25 eyes of 24 patients, peripheral capillary retinal hemangiomas were treated. INTERVENTION: Brachytherapy using 106-ruthenium/106-rhodium plaques was performed. MAIN OUTCOME MEASURES: Eyes were reviewed for hemangioma regression after brachytherapy, occurrence of retinal detachment, requirement of additional vitreoretinal surgery, final visual outcome, and final retinal status. RESULTS: Preoperative mean visual acuity of all eyes treated was 20/60, mean hemangioma diameter was 3.8 mm, corresponding to approximately 2 disc diameters. In 14 eyes, the retina was attached before surgery, 8 eyes showed an exudative detachment, and 3 eyes showed a traction detachment. Fifteen patients had definite von Hippel-Lindau syndrome. Twenty-three of 25 hemangiomas could be destroyed by single brachytherapy. In 16 eyes, a favorable outcome could be achieved. In nine eyes, outcome was unfavorable, characterized by a severe drop in visual acuity, a persisting exudative retinal detachment, or a recurrent traction detachment. In one eye requiring repeated brachytherapy, irradiation retinopathy occurred. Hemangiomas up to a size of approximately 5.0 mm without preoperative exudative detachment could be treated safely by brachytherapy, whereas a larger hemangioma size or a pre-existing exudative retinal detachment predisposed to an unfavorable outcome. CONCLUSION: Solitary peripheral retinal hemangioma can be ablated effectively by ruthenium-106 brachytherapy. A favorable outcome can be expected if the hemangioma diameter is 5.0 mm or smaller and if there is no preoperative exudative retinal detachment.

Adolescent↗
PubMed1998

Lymphoproliferative lesions of the ocular adnexa. Analysis of 112 cases.

OBJECTIVE: Lymphoproliferative lesions of the ocular adnexa were analyzed to examine (1) the suitability of the Revised European-American Lymphoma (REAL) classification for the subtyping of the lymphomas in these sites; (2) the predictive value of the REAL classification for the evolution of these tumors; and (3) the frequency and prognostic impact of tumor type, location, proliferation rate (Ki-67 index), p53, CD5 positivity and the presence of monoclonality within these tumors. DESIGN: Retrospective review. METHODS: The clinical, histomorphologic, immunohistochemical, and molecular biologic (polymerase chain reaction [PCR]) features of lymphoid proliferations of the ocular adnexa were studied. STUDY MATERIALS: The ocular adnexal lymphoproliferative lesions were located as follows: orbit in 52 patients (46%), conjunctiva in 32 patients (29%), eyelid in 23 patients (21%), and caruncle in 5 patients (4%). RESULTS: Reactive lymphoid hyperplasia was diagnosed in 12 cases and lymphoma in 99 cases; 1 case remained indeterminate. The five main subtypes of lymphoma according to the REAL classification were extranodal marginal-zone B-cell lymphoma (64%), follicle center lymphoma (10%), diffuse large cell B-cell lymphoma (9%), plasmacytoma (6%), and lymphoplasmocytic lymphoma (5%). Age, gender, and anatomic localization of the lymphomas did not have prognostic significance during a follow-up period of 6 months to 16.5 years (mean, 3.3 years). Extent of disease at time of presentation was the most important clinical prognostic factor: advanced disease correlated with increased risk ratios of having persistent disease at the final follow-up and with lymphoma-related death (P < 0.001). Histomorphologic features and immunohistochemical markers positively correlating with disseminated disease at presentation, stage at final follow-up, and occurrence of lymphoma-related death included cytologic atypia (P < 0.001), MIB-1 proliferation rate (P < 0.001), and tumor cell p53 positivity (P < 0.001). The MIB-1 proliferation rates greater than 20% in extranodal marginal-zone B-cell lymphoma corresponded to at least stage II lymphoma (P < 0.05). CONCLUSION: The REAL classification is suitable for the subdivision of the ocular adnexal lymphomas. The MIB-1 proliferation rate and p53 positivity may aid the prediction of disease stage and disease progression, whereas PCR can support the diagnosis and reduce the number of histologically indeterminate lesions.

Adolescent↗
PubMed1998

[Appearance of choroidal melanoma on high resolution MRI using 1.5T with a dedicated surface coil in 200 consecutive patients].

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 T1-WI were moderately or markedly hyperintense compared to the vitreous in 29.3% and moderately or markedly hypointense in the T2-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 homogeneous high signal in the T1-WI and low signals in the T2-WI. For further differentiation, morphological criteria (e.g. shape, size, and position) were used, which are also discussed.

Choroid Neoplasms↗