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Biomedical subjects

D H Char

Publications and source records attributed to D H Char.

At least 37 records · Page 2Linked to original sources

Uveal melanoma. Growth rate and prognosis.

OBJECTIVE: To study in vivo tumor growth rates, doubling times, and the association of these parameters with local tumor control and melanoma-related mortality. METHODS: We retrospectively reviewed uveal melanomas with documented growth on serial evaluations before treatment. The tumor dimensions were based on clinical measurements for tumor diameters and quantitative echography to determine tumor thickness. One hundred forty-five patients met study criteria. All tumors were initially measured by the same observer with the same techniques, and, in 133 cases, serial observations and treatment were performed at our institution. RESULTS: Tumor-doubling time estimates were log normally distributed, with a median of 1.4 years. Those 13 patients in whom metastases developed tended to have more rapid tumor growth rates. Iodine 125 brachytherapy failed in 8 patients with more rapidly growing tumors. CONCLUSIONS: Faster growing tumors appear to be more likely to develop early metastases and have failure of local radiation control.

Adult↗

Non-Hodgkin lymphoma and Kaposi sarcoma in an eyelid of a patient with acquired immunodeficiency syndrome. Multiple viruses in pathogenesis.

A 36-year-old patient with acquired immunodeficiency syndrome sought care because of an upper eyelid lesion that dramatically increased in size. The histopathologic examination revealed a high-grade diffuse large cell non-Hodgkin lymphoma in continuity with a Kaposi sarcoma. In situ hybridization revealed Epstein-Barr virus in the large cell lymphoma and Kaposi sarcoma-associated herpesvirus in the Kaposi sarcoma lesion. This collision tumor is an unusual presentation of 2 malignant neoplasms in a patient with acquired immunodeficiency syndrome, with in situ hybridization evidence of Epstein-Barr virus and Kaposi sarcoma-associated herpesvirus in the lesion.

Adult↗

An immunocytochemical study of isolated human retinal Müller cells in culture.

BACKGROUND: We report a modified method for the isolation and propagation of adult human Müller cells in culture. METHODS: The retina of postmortem human eyes was mechanically dissociated and cultured. Using immunocytochemical techniques, these cells were stained with monoclonal antibodies specific for Müller cells, glial fibrillary acidic protein (GFAP), vimentin, glutamine synthetase (GS) and keratin. Transmission electron microscopy (TEM) was also performed. RESULTS: The dissociated and cultured cells expressed vimentin and GS, but not GFAP. At least 85% of these cells stained with a Müller cell-specific monoclonal antibody. Using TEM, flat cells containing 13-nm intermediate filaments and glycogen were identified. CONCLUSION: Human retinal Müller cells can be isolated and propagated in culture. Purified cell cultures are required for controlled studies of the normal physiology and pathologic responses of Müller cells.

Aged↗

Metastatic risk for distinct patterns of postirradiation local recurrence of posterior uveal melanoma.

OBJECTIVE: The purpose of the study is to compare the prognostic significance of horizontal/marginal versus vertical/diffuse patterns of postirradiation local recurrence of posterior uveal melanoma. DESIGN: The study design was a nonrandomized, retrospective clinical study. Semiparametric and nonparametric statistical techniques were used. PARTICIPANTS: Seven hundred sixty-six posterior uveal melanoma patients were studied. INTERVENTION: Either iodine-125 plaque or helium ion radiation therapy was performed. MAIN OUTCOME MEASURES: Local tumor recurrence and systemic metastasis were measured. RESULTS: Local tumor recurrence was detected in 66 (8.6%) of 766 irradiated tumors. The 5-year actuarial rate of local recurrence was 10%. The recurrence pattem was horizontal/marginal in 27 patients (41%) and vertical/diffuse in 39 patients (59%). Systemic metastasis was detected in 5 patients (19%) with horizontal/marginal recurrence and in 19 patients (49%) with vertical/diffuse recurrence. After known metastatic risk factors were controlled, the relative risk for metastasis was 2.2 for horizontal/marginal recurrence and 5.1 for vertical/diffuse recurrence (P = 0.05). The actuarial rate of systemic metastasis was 2.9% per year for all patients, 6.3% per year for patients with horizontal/marginal recurrence, and 15.5% per year for patients with vertical/diffuse recurrence. CONCLUSIONS: Postirradiation local recurrence of posterior uveal melanoma is a risk factor for systemic metastasis. Vertical/diffuse recurrences may be associated more strongly with metastatic disease than horizontal/marginal recurrences.

Adult↗

Orbital metastases: diagnosis and course.

AIMS: Three issues were investigated in adult outpatients with orbital metastases. One, how accurate are current diagnostic methods? Two, what is the survival associated with orbital metastases? Three, did any clinical factors correlate with prognosis in this patient cohort? METHODS: Retrospective analysis of patients with orbital metastases managed in an ocular oncology unit. RESULTS: 11 of 31 (35%) patients had no known primary malignancy at the time of orbital diagnosis. In eight of 31 (26%) computed tomography and/or magnetic resonance imaging data did not yield the diagnosis of metastases. In 15 of 17 (88%) cases a fine needle aspiration biopsy was diagnostic. Several types of therapy were used. The median survival was 1.3 years. CONCLUSION: Orbital metastases, even with newer diagnostic techniques can be difficult to diagnose. Management was based on location and extent of both orbital and systemic disease as well as vision. In most cases, orbital symptoms were palliated; however, survival was dismal. No clinical factor correlated with prognosis.

Adult↗

Long-term follow-up after uveal melanoma charged particle therapy.

PURPOSE: To examine the results of helium ion irradiation in 218 uveal melanoma patients treated more than 10 years ago. METHODS: Retrospective review of 218 eyes treated with helium ion radiation for uveal melanoma between 1978 and 1984. Several parametric and non-parametric statistical analysis techniques were used. RESULTS: In 218 eyes treated with helium ion radiation for uveal melanoma, the mean dimension for largest basal diameter was 11.9 mm (range 5 mm to 24 mm). The mean tumor thickness was 6.7 mm (range 1.3 mm to 14.2 mm). Following helium ion radiation 208 (95.4%) of 218 eyes had local tumor control. At 10 years after radiation 46 (22.4%) of 218 eyes were enucleated; the majority (37 of 46) of enucleations were due to anterior ocular segment complications. At 10 years after radiation 102 (46.8%) of the 218 patients were dead; half had non-tumor related deaths and 51 died from metastatic melanoma. Best corrected visual acuity after radiation was > or = 20/40 in 21 of 93 eyes of patients that were alive and retained their eyes 10 or more years after treatment. In patients with tumors that were less than 6 mm in height and more than 3 mm away from the nerve or the fovea, 13 of 18 (72%) retained > or = 20/40. In contrast, only 11% of the patients with either thicker tumors or those close to the nerve or fovea retained that level of acuity. The actuarial enucleation rate at 5 years was 17.2% (2.7% S.E.) and at 10 years this was 22.4% (3.1% S.E). The recurrence tumor control rate at both 5 and 10 years was 5.3% (S.E 1.7%). CONCLUSIONS: Helium ion radiation of uveal melanoma is associated with good local tumor control and reasonable retention of the treated eye 10 years after treatment. In tumors that are less than 6 mm in thickness and greater than 3 mm from the optic nerve and fovea, many retain excellent vision. Approximately one-half of the deaths 10 years after treatment were due to non-tumor-related causes.

Adult↗

Benign mixed tumor (pleomorphic adenoma) of the lacrimal gland in a 6-year-old boy.

PURPOSE: To report a 6-year-old boy who had benign mixed tumor (pleomorphic adenoma) of the lacrimal gland. METHODS: A 6-year-old boy was referred for evaluation of a lacrimal fossa mass. We performed a lateral orbitotomy and excised the mass. RESULTS: Histopathologic evaluation of the excised orbital mass disclosed a benign mixed tumor (pleomorphic adenoma) of the lacrimal gland. CONCLUSION: Benign mixed tumors (pleomorphic adenomas) of the lacrimal gland are rare in children. However, they must be considered in the differential diagnosis of pediatric orbital masses because of the prognostic importance of removing a pleomorphic adenoma with the capsule intact.

Adenoma, Pleomorphic↗

Irradiated uveal melanomas: cytopathologic correlation with prognosis.

PURPOSE: We analyzed the additional prognostic information from cytopathologic data obtained at the time of uveal melanoma irradiation. METHODS: Fine-needle aspiration biopsies (FNABs) were performed and reviewed in a masked manner. These data and standard prognostic variables were correlated with survival and local tumor recurrence using Kaplan-Meier and Cox model statistical techniques. RESULTS: Cytopathologic assessment of cell type added to prognostic accuracy. In 116 patients, the percentage of epithelioid cells on FNAB and ciliary body involvement were most strongly correlated with melanoma-related mortality. CONCLUSIONS: FNAB data improved our prognostic accuracy in irradiated uveal melanoma patients.

Biopsy, Needle↗

p53 gene and cell cycling in uveal melanoma.

PURPOSE: To determine whether alterations of p53, a tumor suppressor gene, were present in uveal melanoma, and to characterize further the nature of those changes. METHODS: Immunohistochemical analysis with a monoclonal antibody was used to determine whether alterations of p53 were present in 35 enucleated archival uveal melanomas. Further characterization was done by comparing the p53 gene and cell cycling status by using bromodeoxyuridine staining. The alterations in p53 were characterized using polymerase chain reaction single-strand conformational polymorphism analysis and sequencing. RESULTS: Four of 35 uveal melanomas showed low levels (0.5% to 5.0%) of positive immunostaining for altered p53 in tumor cell nuclei using monoclonal antibody DO-7. These four tumors had the three highest and the 14th highest bromodeoxyuridine labeling indices, ranging from 1.3% to 7.0%. Polymerase chain reaction single-strand conformational polymorphism analysis of p53 exons 5 to 8 was performed on three p53-positive and six p53-negative tumors, and no altered motility shifts were detected. Sequencing of one of the positive staining specimens confirmed no mutations in exons 5 through 8 in the p53 gene. Double immunohistochemical labeling for both bromodeoxyuridine and p53 in one tumor showed that most of p53-positive cells were in S phase. CONCLUSIONS: Mutation of p53 is an uncommon event in uveal melanomas. Nuclear accumulation of p53 protein was found in three of the four tumors with the highest levels of cell cycling.

Adult↗

Iris melanomas. Diagnostic problems.

PURPOSE: To illustrate some management problems with pigmented iris tumors. METHODS: This is a retrospective analysis of 234 iris tumors managed by one of the authors. Five patients were selected whose clinical course and pathologic data illustrate diagnostic problems that can occur with these tumors. RESULTS: In the patients described, diagnostic problems were noted. In two patients, glaucoma specialists were unable to correctly diagnose an iris melanoma before filtration. One patient had a 3-clock-hour iris biopsy that was not diagnostic for malignancy, yet the enucleated eye showed melanoma. One patient with a clinically stable iris tumor had a mixed-cell melanoma. CONCLUSIONS: Most iris-pigmented tumors have a benign disease course. In some case, despite little clinical evidence of disease activity or progression, a melanoma, often with epithelioid cells, may be present and neither a fine-needle nor an open biopsy is always diagnostic.

Adult↗

Comparative genomic hybridization analysis of archival formalin-fixed paraffin-embedded uveal melanomas.

Comparative genomic hybridization (CGH) was used to analyze seven autologous uveal melanomas with both formalin-fixed, paraffin-embedded and fresh-frozen specimens. In addition, DNA from two archival formalin-fixed tumors more than 45 years old were also analyzed. The most frequent genetic changes were loss of chromosome 3; increase in copy number of 6p and loss of 6q; and increase in copy number of 8q. A comparison of CGH data from the fresh-frozen tumors and their autologous formalin-fixed tumors revealed a correlation coefficient of 0.83. Comparative genomic hybridization (CGH) analysis of 45-year-old specimens identified genetic changes similar to those found in more recent tumors including loss of chromosome 3 and increase in copy numbers of 6p and 8q. The results indicate that there is a good agreement between data obtained from formalin-fixed and fresh-frozen specimens using CGH. Furthermore, the results demonstrate the applicability of this technique in analyzing archival formalin-fixed tumors that were previously not accessible to cytogenetic analysis.

Analysis of Variance↗

Long term visual outcome of radiated uveal melanomas in eyes eligible for randomisation to enucleation versus brachytherapy.

AIMS: To determine the long term visual outcome of patients who were eligible for randomisation to enucleation versus brachytherapy in a US collaborative ocular melanoma study (COMS) but were treated with either helium ion or 125I radioactive plaque therapy. METHOD: A retrospective analysis was performed of 426 ciliochoroidal melanomas that met COMS inclusion criteria for randomisation to enucleation versus radioactive plaque but were treated with either helium ions or 125I brachytherapy. RESULTS: At 3 years 36.0% of eyes had 6/12 or better visual acuity. The length of visual retention was most dependent on tumour thickness, tumour location with respect to the optic nerve, fovea, or ciliary body, and patient age. In addition to these factors, the retention of 6/12 visual acuity and the time to 6/120 visual acuity were dependent on the preoperative visual acuity. The risk of visual loss was greatest immediately after treatment and decreased with time. The 5 year actuarial metastatic rate was approximately 13%. Patients at the greatest risk of post-radiation visual loss had significantly greater risk of tumour related mortality. CONCLUSIONS: Some patients who would have been eligible for randomisation to either enucleation or radioactive plaque therapy can be irradiated with retention of excellent vision.

Adult↗

Late effects of radiation on the eye and ocular adnexa.

A clinically useful classification system is suggested that can be used in prospective trials to evaluate the effects of radiation on the visual system. We review radiation-induced pathophysiological and clinical changes of the various ocular structures as well as dose-response data and management of ocular complications. The rationale for the classification scheme chosen is also discussed.

Cataract↗