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D H Char

Publications and source records attributed to D H Char.

At least 55 records · Page 3Linked to original sources

Lacrimal gland lymphoma: a cytomorphologic and immunophenotypic study.

The cytomorphology of lacrimal gland lymphoma has not been specifically described. Herein we present six cases of histologically proven lacrimal gland lymphoma which we analyzed using fine-needle aspiration cytology, cell suspension immunophenotype analysis, and immunoglobulin gene rearrangement studies. Fine-needle aspiration cytology revealed atypical populations of cells comprised of either monomorphic small round lymphocytes with or without plasmacytoid features (4 cases), a mixed population of small and large irregular lymphocytes (1 case), or a population of large irregular lymphocytes (1 case). The initial cytologic diagnosis was malignant lymphoma in all six cases. Cell suspension immunophenotype analysis demonstrated that the lesions were composed predominantly of B-cells that expressed monotypic surface immunoglobulin. Three cases demonstrated an immunoglobulin heavy chain gene rearrangement. The atypical cytologic features and the abnormal immunophenotype were consistently predictive of malignant lymphoma. Given that these lesions are small and biopsy material is often limited, fine-needle aspiration offers the advantage of providing tissue that is ideal for cytologic and cell suspension immunophenotype evaluation, obviating the need to provide surgical biopsy material for this purpose. We conclude that fine-needle aspiration can identify malignant lymphoid lesions of the lacrimal gland and may serve as a valuable adjunct in the assessment of these lesions. Additional study is warranted to determine whether fine-needle aspiration can reliably distinguish between benign and malignant lymphoid proliferations of the lacrimal gland.

Aged↗

Efficacy of unanesthetized spiral computed tomography scanning in initial evaluation of childhood leukocoria.

PURPOSE: To evaluate the use of spiral/helical computed tomography (CT) in the preoperative evaluation of pediatric leukocoria. METHODS: A total of 34 patient charts and imaging studies were reviewed from a consecutive series of children referred with the diagnosis of presumed retinoblastoma. Of these patients, 31 had a confirmed diagnosis of retinoblastoma. Three patients had simulating lesions, including one patient with persistent hyperplastic primary vitreous and two with Coats disease. RESULTS: In all patients, a diagnosis of intraocular retinoblastoma could be established or excluded at the same clinical level by spiral CT as by conventional CT. Spiral CT of the eye, orbit, and midline structures was performed without a requirement for patient anesthesia. This technique resulted in a reduced volume of contrast material required for evaluation of the central nervous system and a small decrease in total radiation exposure. There was an attendant reduction in the amount of monitoring equipment required and the necessity for attending anesthesia staff. CONCLUSIONS: The primary advantage of spiral CT is reduced anesthesia risk in small children. In addition, this technique provides necessary clinical information with a reduction in image acquisition time, monitoring equipment, and monitoring staff.

Anesthesia↗

Accuracy of presumed uveal melanoma diagnosis before alternative therapy.

AIMS/BACKGROUND: This study was performed to ascertain the diagnostic accuracy rate of non-invasive tests in patients with presumed uveal melanomas scheduled to be treated with either irradiation or cyclochoroidectomy. METHODS: One hundred consecutive patients who had non-invasive tests followed by fine needle aspiration biopsy (FNAB) as prior alternative treatment were analysed retrospectively. RESULTS: In 86 cases the diagnosis of uveal melanoma was confirmed on FNAB. In five cases false negative results were obtained. In nine patients a diagnosis other than a uveal melanoma was made on the basis of cytopathology. No significant morbidity and no evidence of tumour spread occurred. CONCLUSION: In presumed uveal melanomas eligible for treatment with alternative therapies, the diagnostic accuracy of non-invasive tests is not as good as with larger tumours that require enucleation. Fine needle aspiration biopsy data resulted in correct management of 9% of cases that were thought to have uveal melanomas on non-invasive tests, but had other lesions on cytopathological evaluation.

Biopsy, Needle↗

Comparative analysis of proliferating cell nuclear antigen, bromodeoxyuridine, and mitotic index in uveal melanoma.

PURPOSE: Recent production of a monoclonal antibody, PC10, against proliferating cell nuclear antigen (PCNA) makes it possible to evaluate cell cycling in formalin-fixed tissues. In this study, the authors quantitatively evaluated the relationship between PCNA expression and two other measures of cell cycling, bromodeoxyuridine labeling index (BrdU LI) and mitotic index (MI), in archival uveal melanomas. The authors also examined the relative prognostic importance of each measure. METHODS: Serial sections from 35 formalin-fixed, paraffin-embedded uveal melanomas were immunostained with PC10 and BrdU antibody using a standard avidin-biotin-peroxidase method. A quantitative scoring system was used to evaluate the fraction of cells that were positive for PCNA, BrdU, and mitotic figures in the regions of high cycling. The LIs of the different markers were compared, and their prognostic importance was evaluated. RESULTS: The median PCNA LI was 3.05% compared to the median BrdU LI of 0.94% and the median MI of 0.034%. The PCNA LI was more variable in replicate sections than either the MI or the BrdU LI. The correlation between PCNA LI and BrdU LI was 0.58, between PCNA LI and MI it was 0.46, and between BrdU LI and MI it was 0.81. The relative risk of tumor-related mortality per doubling of BrdU LI was 2.35, and of MI it was 2.34. Although these were significant, PCNA LI of 1.08 was not. CONCLUSIONS: Proliferating cell nuclear antigen immunostaining did not demonstrate a strong relationship with either BrdU LI or MI. Unlike MI and BrdU LI, PCNA LI was not correlated with tumor-related mortality. Caution is warranted in the interpretation of PCNA immunostaining in uveal melanomas.

Adult↗

Cell cycling and prognosis in uveal melanoma.

Uveal melanoma cell cycling, quantified by bromodeoxyuridine (BrdUrd)-labeling index and mitotic index, is predictive of tumor-related mortality. Serial sections from 36 formalin-fixed melanoma specimens were labeled with BrdUrd and stained with hematoxylin and eosin. All tumors were assessed for the area of highest cell cycling activity and counts for mitotic figures and BrdUrd labeling were performed in these areas in a masked manner. The BrdUrd labeling index and mitotic index were calculated and analyzed in relation to tumor-related mortality and histopathological criteria (largest tumor diameter, cell type, extra-scleral extension, ocular location). Cox multivariate analysis estimated an increased relative risk of tumor-related mortality of 2. 32 (95% confidence interval, 1.22-4.41) per doubling of BrdUrd labeling index and 2.41 (95% confidence interval, 1.29-4.49) per doubling mitotic index. Larger tumors, nonspindle cell tumors, and anterior-located tumors tended to have higher cycling rates.

Adult↗

Comparative genomic hybridization in the detection of DNA copy number abnormalities in uveal melanoma.

Genomic instability appears to play an important role in the development, growth, invasiveness, and eventual metastasis of the neoplastic cell. We have used a powerful new technique, comparative genomic hybridization, to evaluate genetic alterations in 10 fresh frozen uveal melanomas. Comparative genomic hybridization utilizes dual fluorescence in situ hybridization to characterize chromosome deletions and duplications, allowing for simultaneous evaluation of the entire human genome. Several consistent chromosomal abnormalities were detected. This study confirmed previous findings obtained using standard cytogenetic techniques but demonstrated an increased incidence in abnormalities of chromosomes 3 and 8; there was loss of chromosome 3 and duplication of 8q. In addition, we identified, although less frequently, other recurrent abnormal regions including alterations on chromosomes 6p, 7q, 9p, and 13q.

Chromosome Aberrations↗

Anterior segment complications after helium ion radiation therapy for uveal melanoma. Radiation cataract.

OBJECTIVE: To delineate the factors in the development of visually significant cataract after helium ion irradiation of eyes with uveal melanomas. DESIGN: Retrospective analysis with multivariate analysis using life tables and Cox proportional hazard models in addition to other nonparametric techniques. PATIENTS: All patients with a noncataractous other eye and adequate dosimetry data who were treated with helium ion irradiation. RESULTS: Significant cataracts (grade 3+ or 4+ on a 0 to 4+ scale) developed in 129 patients (44%). The risk of cataract development peaked at 3 years (25% per person-year) and then declined to a sustained level of 7% to 9% per year after 7 years. In multivariate analysis, the percentage of lens included in the treatment port was the predominant predictive correlate with time to significant cataract (relative risk of 2.97 for a 25% increase in the percentage of lens in the treatment port). Patient age, preexisting cortical opacity, and ultrasound tumor height were also significant; ciliary body involvement and tumor dose had smaller effects. Kaplan-Meier analysis demonstrated an increased rate of cataractogenesis with each increment of the percentage of lens in the treatment port; when more than half of the lens was in the beam, the risk of cataract exceeded 90% within 7 years. CONCLUSIONS: Cataract development after helium ion irradiation is a function of the amount of the lens in the beam. Unlike neovascular glaucoma that develops mainly in the first few years after treatment, cataract continues to develop during the entire length of follow-up.

Adult↗

Helium-ion-induced human cataractogenesis.

Retrospective and ongoing analyses of clinical records from 347 primary intraocular melanoma patients treated with helium ions at LBL will allow examination of the exposure-response data for human cataract; which is a complication of the therapy from incidental exposure of the lens. Direct particle beam traversal of at least a portion of the lens usually is unavoidable in treatment of posterior intraocular tumors. The precise treatment planned for each patient permits quantitative assessment of the lenticular dose and its radiation quality. We are reporting our preliminary results on the development of helium-ion-induced lens opacifications and cataracts in 54 of these patients who had 10% or less of their lens in the treatment field. We believe these studies will be relevant to estimating the human risk for cataract in space flight.

Adult↗

Natural history of indeterminate pigmented choroidal tumors.

PURPOSE: The purpose of this study is to delineate the natural history of indeterminate pigmented choroidal lesions and identify parameters from the initial visit that correlate with lesion enlargement. METHODS: The authors retrospectively reviewed the records of all patients with indeterminate pigmented choroidal lesions seen in consultation at the Ocular Oncology Unit at the University of California, San Francisco, after 1975. Clinical examination, fundus photography, fluorescein angiography, and ultrasound data were examined. Investigators masked to outcome coded sequential parameters of each of these modalities. Data were analyzed using both univariate and multivariate censored data techniques. RESULTS: Of 293 lesions, 98 grew. The 5-year actuarial rate of growth was 36%. Greater tumor thickness, presence of symptoms, orange pigment, internal quiet zone on B-scan, and hot spots on fluorescein angiography all were significant predictors of tumor enlargement (relative risk of detectable tumor growth, > 1.8). Risk scores were calculated, and subsets with higher probability of future growth were identified. In five of the patients with growing lesions, metastatic disease developed after a median posttreatment follow-up period of 51 months. CONCLUSION: Most small indeterminate pigmented lesions can be followed safely by serial observation and ancillary testing. The authors identified models based on data from the initial visit that can be used as an adjunct to planning tumor management.

Adult↗

31P magnetic resonance spectroscopy after combined hyperthermia and radiation.

Mechanisms of uveal melanoma response to therapy are poorly understood. There are a paucity of changes that have been detected immediately after tumor treatment to differentiate successful from ineffective therapy. In this study we used in vivo 31P magnetic resonance spectroscopy (MRS) to assess intra-tumor treatment alterations. The metabolic consequences of effective and ineffective levels of solitary hyperthermia and combined hyperthermia-radiation were investigated. We have previously noted a characteristic 31P MRS pattern with successful hyperthermia in this intraocular melanoma model. The metabolic response after effective or ineffective combined radiation/hyperthermia therapy was indistinguishable from solitary radiation therapy and opposite to that with successful hyperthermia therapy. In contrast to solitary hyperthermia therapy, early changes in 31P spectral ratios following radiation or combined hyperthermia/radiation therapy of uveal melanoma were not predictive of treatment response. Twenty-four to 48 hours after effective or ineffective radiation or combined treatment the Pi/beta-NTP ratio decreased significantly (delta Pi/beta-NTP = -0.433 +/- 0.08 and -0.478 +/- .13 and .10 +/- 0.2, respectively). There was over a 2.0 thermal enhancement of radiation with heat. The increased tumor cell death after combined therapy was reflected by a two-fold larger decrease in beta-NTP signal-to-noise (S/N).

Animals↗

High intensity 125-iodine (125I) plaque treatment of uveal melanoma.

PURPOSE: Episcleral 125I plaque therapy of uveal melanoma is an important treatment modality to control tumor, salvage the globe, and potentially preserve vision. We retrospectively analyzed our experience in 239 patients to assess treatment outcome with this technique. METHODS AND MATERIALS: Between 1983 and 1990, 239 uveal melanoma patients were treated with 125I plaques at the University of California, San Francisco. High intensity 125I seeds in the range of 3-20 mCi were used to give a minimum tumor dose of 70 Gy in 4 days. Initial mean tumor size was 10.9 mm x 9.2 mm x 5.5 mm with a range in tumor diameter from 4 to 18 mm and tumor height from 1.9 to 11.1 mm. Best corrected pre-treatment visual acuity was 20/200 or better in 92% of patients. RESULTS: Local tumor control was maintained in 91.7% of patients with a mean follow-up of 35.9 months; 19 patients had local tumor progression; mean time to progression was 27.3 mo (1.8 to 60.1 mo). Actuarial local control is 82% at 5 years. Multivariate analysis demonstrates significant correlation of local failure with larger maximum tumor diameter (p = 0.0008), closer proximity to the fovea (p = 0.0001), lower radiation dose (p = 0.0437), and smaller ultrasound height (p = 0.0034). The actuarial incidence of distant metastases is 12% at 5 years with multivariate analysis showing significant correlation only with maximum tumor diameter (p = 0.0064). Visual outcome is 20/200 or better in 58% of patients. CONCLUSION: While the tumor control rates appear favorable, ocular morbidity is significant. A current randomized trial comparing 125I plaque with Helium ion therapy is in progress with specific comparison of tumor control, survival, and visual outcome.

Adult↗

Management of orbital tumors.

Orbital tumors are uncommon. In children, both malignant and benign causes of orbital proptosis necessitate urgent assessment; in many cases, emergent intervention is necessary to avoid blindness. In adults, proptosis is most commonly associated with thyroid orbitopathy. Orbital tumors in adults rarely are characterized by the explosive growth and damage that can occur with childhood lesions. In both age-groups, the evolution of better scanning modalities, such as magnetic resonance imaging with fat saturation and gadolinium enhancement, has improved diagnostic accuracy, especially in patients with loss of vision. In more than 95% of cases, noninvasive techniques yield a correct diagnosis. In patients who require nonsurgical intervention, especially if the diagnosis is uncertain, fine-needle aspiration biopsy has an accuracy that exceeds 95%. Combined-modality therapy has improved the control of and decreased the morbidity associated with several orbital tumors. Surgical advances, such as the ancillary use of the CO2 laser, have enhanced the management of some orbital tumors.

Adolescent↗

Helium ions versus iodine 125 brachytherapy in the management of uveal melanoma. A prospective, randomized, dynamically balanced trial.

PURPOSE: Optimal radiation therapy for uveal melanoma is uncertain, and the relative efficacies of radioactive plaques and charged particles are unclear. METHODS: The authors prospectively studied helium-ion irradiation and iodine 125 (125I) brachytherapy in a randomized, dynamically balanced trial. Of the 184 patients who met the eligibility criteria, 86 were treated with helium ions and 98 with 125I brachytherapy. RESULTS: No patients with uveal melanoma had a history of systemic malignancy. Tumors were less than 15 mm in maximum diameter and less than 10 mm in thickness. A minimum tumor dose of 70 GyE was delivered to the tumor apex. There was a significantly higher local recurrence rate after 125I brachytherapy than after helium-ion irradiation. Enucleations occurred more frequently after brachytherapy (relative risk = 1.99; 95% confidence interval, 0.78-5.78). More anterior segment complications occurred after helium-ion irradiation. To date, there has been no measurable impact on survival. CONCLUSIONS: Most uveal melanomas can be managed with radiation with retention of the eye. There was better tumor control with helium-ion irradiation; however, there were more anterior segment complications.

Adult↗

[Cytokines in uveal melanoma. Original title: uveal melanoma cytokines].

Cytokines may be important in both the pathophysiology an ocular morbidity associated with treated and untreated uveal melanomas. In this study we used message amplification phenotyping to identify cytokines present in uveal melanoma samples. A number of cytokines were noted that have been associated with tumor progression, neovascularization, and inflammation in other malignancies. Interferongamma was commonly found in spindle cell tumors. Only one of 16 tumors had detectable levels of TNF-alpha and this occurred in one of two patients who developed metastatic disease.

Cytokines↗

Orbital pseudotumor. Fine-needle aspiration biopsy and response to therapy.

PURPOSE: To determine the diagnostic accuracy of fine-needle aspiration biopsy and study the natural history and therapeutic response of a group of patients with orbital pseudotumor. METHODS: Retrospective review of patients seen by one ocular oncologist for diagnosis and management of presumed orbital pseudotumor. RESULTS: Thirty-eight patients had fine-needle aspiration biopsy under computed tomographic (CT) guidance. No false-positive results were observed. In 10% of fine-needle aspiration biopsies, negative results were observed. In all patients in this series, lymphomas could be differentiated from pseudotumors. Flow cytometry or Southern blot analysis could be performed on these cytopathologic specimens and was useful in selected cases. Eighty-one patients were followed after various forms of treatment. Essentially complete remissions were observed in 49 of 81 patients. High-dose oral corticosteroids were effective in approximately 31% of patients. A poor steroid response was observed in patients with mass lesions and those with fibrotic disease. Surgical resection was effective in 76% of patients; most of these had relatively discrete mass lesions. Radiation was effective in approximately 64% of patients. Radiation was more effective in nonfibrotic lesions and in patients with erythema. This type of treatment was less effective in fibrotic lesions and in patients who had a longer interval between diagnosis and therapy. CONCLUSIONS: Fine-needle aspiration biopsy is useful in evaluating patients with presumed orbital pseudotumor. There is a high success rate in many patients with orbital pseudotumor, although patients with diffuse fibrotic disease have a poor prognosis.

Adolescent↗

Alteration of human conjunctival epithelial proliferation.

We used in vitro bromodeoxyuridine to analyze the labeling indexes of conjunctival cells in several external eye diseases. Patients with superior limbic keratoconjunctivitis, squamous cell carcinoma of the conjunctiva, drug-induced pseudopemphigoid, and Stevens-Johnson syndrome had increased conjunctival DNA synthesis.

Bromodeoxyuridine↗

Radiation therapy of acquired immunodeficiency syndrome-related Kaposi's sarcoma of the eyelids and conjunctiva.

We retrospectively studied 42 men with acquired immunodeficiency syndrome-related Kaposi's sarcoma of the conjunctiva or eyelids who were treated with radiation. Forty-nine sites were treated, 35 (71%) of which involved the eyelids, 12 (24%) the conjunctiva, and two (4%) both the eyelids and conjunctiva. Group 1 consisted of 31 sites treated with a single dose of 800 cGy and group 2 consisted of 18 sites treated with a multiple-fraction regimen and total doses between 1500 and 3600 cGy. The response and recurrence rates in the two groups were similar. One patient from group 2 died within 1 month of treatment and was not included in the analysis. The lesions improved in all cases. A complete response was obtained in 10 (32%) of the 31 lesions in group 1, compared with four (22%) of 18 lesions in group 2. A partial response was obtained in 21 (68%) of 31 lesions in group 1, compared with 13 (72%) of 18 lesions in group 2. Expected minor reactions in the treatment field, primarily loss of cilia, were comparable in the two groups. No serious complications were noted. Recurrence occurred in seven (22%) of the 31 sites in group 1 (six patients) and seven (39%) of the 18 sites in group 2 (six patients). The results suggest that a single treatment of 800 cGy is a safe and effective palliative therapy for ophthalmic acquired immunodeficiency syndrome-related Kaposi's sarcoma.

Acquired Immunodeficiency Syndrome↗