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J L Hungerford

Publications and source records attributed to J L Hungerford.

At least 37 records · Page 2Linked to original sources
PubMed1999

Ring melanoma--a rare cause of refractory glaucoma.

BACKGROUND: Ring melanoma of the ciliary body and iris is extremely rare and often has adverse histology. This tumour may cause raised intraocular pressure. METHODS: A review of four cases of ring melanomas with insidious presentations seen in the ocular oncology service over a 12 month period. RESULTS: All four patients presented with unilateral anterior segment abnormalities and refractory glaucoma. The misdiagnoses of the causes of the glaucoma included angle recession from previous blunt trauma (patient 1); iridocorneal endothelial (ICE) syndrome supported by endothelial specular microscopy (patients 2 and 3); and melanocytoma on ciliary body biopsy (patient 4). Two patients were treated by several cyclodiode ciliary body ablation treatments and the other two underwent trabeculectomies and Molteno tubes. Two of the four patients have since died from their disease. CONCLUSION: The ophthalmologist should re-evaluate the diagnosis in patients with anterior segment abnormalities and refractory ipsilateral glaucoma. Endothelial specular microscopy and biopsy of the suspicious lesion may give misleading reassurance. The potential presence of an anterior uveal melanoma must always be considered.

Adult↗
PubMed1999

Modelling uveal melanoma.

BACKGROUND/AIM: There has been no consistent pattern reported on how mortality for uveal melanoma varies with age. This information can be useful to model the complexity of the disease. The authors have examined ocular cancer trends, as an indirect measure for uveal melanoma mortality, to see how rates vary with age and to compare the results with their other studies on predicting metastatic disease. METHODS: Age specific mortality was examined for England and Wales, the USA, and Canada. A log-log model was fitted to the data. The slopes of the log-log plots were used as measure of disease complexity and compared with the results of previous work on predicting metastatic disease. RESULTS: The log-log model provided a good fit for the US and Canadian data, but the observed rates deviated for England and Wales among people over the age of 65 years. The log-log model for mortality data suggests that the underlying process depends upon four rate limiting steps, while a similar model for the incidence data suggests between three and four rate limiting steps. Further analysis of previous data on predicting metastatic disease on the basis of tumour size and blood vessel density would indicate a single rate limiting step between developing the primary tumour and developing metastatic disease. CONCLUSIONS: There is significant underreporting or underdiagnosis of ocular melanoma for England and Wales in those over the age of 65 years. In those under the age of 65, a model is presented for ocular melanoma oncogenesis requiring three rate limiting steps to develop the primary tumour and a fourth rate limiting step to develop metastatic disease. The three steps in the generation of the primary tumour involve two key processes-namely, growth and angiogenesis within the primary tumour. The step from development of the primary to development of metastatic disease is likely to involve a single rate limiting process.

Adult↗
PubMed1998

Treatment of retinoblastoma vitreous base seeding.

OBJECTIVE: The purpose of the study is to describe results of a new treatment for retinoblastoma vitreous base seeding. DESIGN: The study design was a retrospective review of patients treated at an ocular oncology referral center. PARTICIPANTS: Five eyes of five patients with vitreous base seeding that occurred after previous external beam radiation therapy were treated between October 1987 and December 1994. INTERVENTION: A customized plaque made from iridium-192/platinum wire was placed to deliver 4000 cGy to the tumor apex along its entire length and systemic chemotherapy (consisting of carboplatin, vincristine, and etoposide) was given. MAIN OUTCOME MEASURES: Eye preservation and tumor control were measured. RESULTS: Vitreous base seeding was controlled completely and the eye preserved in four of the five treated eyes with an average follow-up of 26.2 months. CONCLUSIONS: The combination of a customized iridium-192 plaque and systemic chemotherapy is an effective means of treating vitreous base seeding of retinoblastoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Proton beam therapy for posterior pole circumscribed choroidal haemangioma.

BACKGROUND: Macular and juxtapapillary circumscribed choroidal haemangiomas (CCH) have always posed a diagnostic and therapeutic challenge. Proton beam therapy has been advocated by Zografos and associates as optimal for treating these tumours in this critical region as charged particles have a highly localised and uniform dose distribution. PATIENTS: We present 3 cases of CCH treated with proton beam therapy. Two patients developed radiation optic neuropathy and maculopathy, and one had a persistent exudative macular detachment following treatment. CONCLUSION: Our experience with proton therapy of these tumours has been disappointing in preventing radiation optic neuropathy and maculopathy and offers little advantage over external irradiation. The majority of our patients with this condition are now treated with low-dose lens-sparing external beam radiotherapy or brachytherapy, which has encouraging visual results and is a far more cost-effective option.

Adult↗
PubMed1998

Predictive power of screening tests for metastasis in uveal melanoma.

PURPOSE: Uveal melanoma undergoes haematogenous dissemination, particularly to the liver. It is routine practice to screen for metastatic disease. The purpose of this study was to evaluate such screening tests and to determine their value in detecting metastatic disease at presentation. METHODS: In this study of a series of 245 patients with uveal melanoma of whom 55 (22%) died, the sensitivity, specificity, positive and negative predictive powers and likelihood ratio of the blood tests, chest radiographs and liver ultrasound investigations performed at diagnosis were determined. RESULTS: All the screening investigations were found to have a low yield, but the most sensitive were those for gamma-glutamyl transpeptidase (gamma GT; sensitivity 21%) and alkaline phosphatase (sensitivity 25%), with gamma GT being more specific (specificity 92%). No blood test had a positive predictive power greater than 50%. The chest radiograph and liver ultrasonography were both 100% specific but had sensitivities of 2% and 14% respectively. CONCLUSIONS: Only the chest radiograph and liver ultrasonography had positive predictive powers greater than 50% and these tests had very poor sensitivity. We conclude that there is no good test available for screening for metastatic uveal melanoma.

Biomarkers, Tumor↗
PubMed1998

The prognostic significance of c-myc oncogene expression in uveal melanoma.

The role of the c-myc oncogene has been little investigated in uveal melanoma. In this study an analysis of c-myc oncoprotein expression was undertaken using flow cytometry in 71 patients with posterior uveal melanoma. Nuclear c-myc oncoprotein was detected in all of the tumours, and survival analysis revealed a significant association between high oncoprotein positivity and improved survival (log rank test: chi2 = 6.47, P = 0.01). Multifactorial analysis using Cox's proportional hazards model revealed nuclear c-myc oncoprotein to be an independent prognostic marker more accurate than other clinicopathological parameters (log rank test: chi2 = 6.61, P = 0.01). However, this result of high oncoprotein expression correlating with improved outcome is surprising and in contrast to our previous studies using the same method on cutaneous melanoma, where high levels of nuclear c-myc expression have been found to correlate with poor outcome both in primary and secondary disease. This study suggests that the pattern of oncogene expression in uveal melanoma is distinct from cutaneous melanoma and that the underlying biology of these tumours is different.

Adolescent↗
PubMed1997

Topical mitomycin C for the treatment of conjunctival and corneal epithelial dysplasia and neoplasia.

PURPOSE: To evaluate the efficacy of topical mitomycin C in treating conjunctival and corneal epithelial dysplasia and neoplasia. METHODS: Seven eyes of seven patients with conjunctival and corneal epithelial dysplasia and neoplasia were treated with one drop of topical mitomycin C 0.04% four times a day for 7 days in alternate weeks. The patients' charts were reviewed retrospectively. Patients with either multiple recurrences or extensive ocular surface involvement were treated. In all eyes, the diagnosis of epithelial dysplasia or neoplasia was confirmed by histopathology before the onset of therapy. Patients were examined at least every 14 days during treatment and examined at intervals after completion of treatment. RESULTS: With topical mitomycin C, six eyes of seven patients had complete clinical regression of their conjunctival and corneal epithelial dysplasia and neoplasia. One eye of one patient had partial clinical regression of conjunctival and corneal epithelial dysplasia. Follow-up after completion of topical mitomycin C therapy and excision of residual disease ranged from 2 to 16 months (mean, 9 months; SD, 4.3 months) and was without clinical sign of recurrence. Topical mitomycin C therapy was associated with transitory ocular discomfort, conjunctival injection, tearing, photophobia, and punctate epithelial keratopathy. CONCLUSION: In this small series of eyes, topical mitomycin C was effective as a treatment for conjunctival and corneal epithelial dysplasia and neoplasia.

Adult↗
PubMed1997

Choroidal hemangiomas: visual and anatomic results of treatment by photocoagulation or radiation therapy.

PURPOSE: Choroidal hemangioma is a benign hamartoma that causes accumulation of subretinal fluid and resultant visual loss. Although photocoagulation can result in resolution of subretinal fluid, some have found that recurrence is common and final visual acuity often is poor. The purpose of this study is to evaluate the visual and anatomic results of radiation therapy and photocoagulation in treating patients with visual loss from choroidal hemangiomas. METHODS: A retrospective review was performed of patients with circumscribed choroidal hemangiomas (CCH) or diffuse choroidal hemangiomas (DCH) treated for visual loss caused by accumulation of subretinal fluid. Of 23 patients with CCH, 13 were treated by photocoagulation, 8 by plaque brachytherapy, and 2 by lens-sparing external beam radiation therapy (LSRT). All five patients with DCH were treated by LSRT. RESULTS: Of patients with CCH treated by brachytherapy, six (75%) of eight had visual acuity of 6/12 or better at 1 year and 8 (100%) of 8 had no subretinal fluid. Of patients with CCH treated by photocoagulation, 5 (38%) of 13 had visual acuity of 6/12 or better at 1 year and 6 (46%) of 13 had no subretinal fluid. Of patients with CCH treated by LSRT, none of two had visual acuity of 6/12 or better at 1 year and one of two had no subretinal fluid. Of the five patients with DCH treated by LSRT, all had complete resolution of subretinal fluid. Two had marked visual improvement and in the other three, vision was stabilized. CONCLUSIONS: Plaque brachytherapy is an effective alternative to photocoagulation for treatment of subretinal fluid caused by CCH. Lens-sparing external beam radiation therapy is effective treatment in patients with DCH.

Adolescent↗
PubMed1997

The RB1 gene mutation in a child with ectopic intracranial retinoblastoma.

The RB1 gene mutation was investigated in a child with ectopic intracranial retinoblastoma using DNA obtained from both the pineal and retinal tumours of the patient. A nonsense mutation in exon 17 (codon 556) of the RB1 gene was found to be present homozygously in both the retinal and the pineal tumours. The same mutation was present heterozygously in the DNA from the constitutional cells of the patient, proving it to be of germline origin. The initial mutation was shown to have occurred in the paternally derived RB1 allele. The mutation is in an area of the gene that encodes the protein-binding region known as the 'pocket' region and has been detected in other cases of retinoblastoma.

Brain Neoplasms↗
PubMed1997

The ex vivo chemosensitivity profile of choroidal melanoma.

Uveal melanoma has a high mortality rate and responds poorly to existing chemotherapy. We have therefore examined the sensitivity of uveal melanoma to cytotoxic agents using an ex vivo chemosensitivity assay to determine whether some agents which have not been used for this tumor might have activity. An ATP-based tumor chemosensitivity assay (ATP-TCA) was used to determine the effect of nine cytotoxic drugs at multiple dilutions in 28 primary uveal melanoma specimens. Evaluable assay results from up to 16 tumors with each drug showed variable sensitivity to alkylating agents (three of nine with mitomycin C, one of 15 with cisplatin and seven of 15 with treosulfan), cytosine arabinoside (seven of 16), paclitaxel (one of five) and doxorubicin (two of 16). No tumors were sensitive to temozolomide, or 5-fluorouracil, and only one of 14 to vincristine. The combination of treosulfan with cytosine arabinoside resulted in enhanced tumor cell inhibition in three of five tumors tested. Combinations containing paclitaxel combined with doxorubicin or cisplatin showed some activity, but none achieved 100% inhibition and the results were similar to those obtained with paclitaxel alone. Uveal melanoma shows considerable heterogeneity of sensitivity to cytotoxic drugs, with considerable resistance to most agents, matching clinical experience. The results suggest that cytosine arabinoside or gemcitabine plus treosulfan may be an active combination. Clinical trials will commence shortly. The use of the ATP-TCA provides a method of testing multiple agents and combinations in a way which would be otherwise impossible in rare tumors such as uveal melanoma.

Antineoplastic Agents↗
PubMed1997

Reassessment of the PAS patterns in uveal melanoma.

BACKGROUND: Previous work has highlighted the prognostic importance of patterns of periodic acid Schiff (PAS) staining (the Folberg patterns) in uveal melanoma. These patterns have been ascribed to blood vessels but the patterns are different from those seen with other staining techniques for blood vessels. It has recently been shown that microvessel density is the dominant prognostic factor in uveal melanoma. This study reinvestigates the nature and significance of the PAS patterns. METHODS: The PAS patterns were compared with the patterns seen with conventional connective tissue stains and with the patterns seen in sections stained for the presence of blood vessels (by immunohistochemistry for factor VIII related antigen). The PAS patterns were determined on a panel of 117 cases of uveal melanoma. The prognostic significance of each of these patterns was determined and, as more than one pattern can exist in a tumour, principal components analysis was performed to determine the number of underlying factors. RESULTS: Comparison of the PAS patterns with other stains demonstrates that they are based on connective tissue including fibrovascular tissue. Five of the nine PAS patterns carried prognostic significance on univariate analysis. Principal components analysis suggested that these patterns represented three underlying factors, which were tentatively identified as representing disordered growth (factor 1), emergence of rapidly growing subclones (factor 2), and section orientation (factor 3). CONCLUSIONS: The PAS patterns are based on fibrovascular tissue and can be ascribed to three underlying factors. The first two of these factors carried prognostic significance and the first (disordered growth) retained independent prognostic significance in a multivariate Cox model which included microvessel density and tumour size.

Biomarkers, Tumor↗
PubMed1997

Predictive factors for the development of rubeosis following proton beam radiotherapy for uveal melanoma.

AIMS/BACKGROUND: Proton beam radiotherapy can effectively treat primary uveal melanomas of any size. Some patients, however, develop adverse late effects following treatment and the purpose of this study was to determine which factors give rise to a poor local outcome. METHODS: The hospital records from a first cohort of 127 patients treated by protons from 1989 to 1992 were reviewed retrospectively. The presence of rubeosis was selected as a measure of significant ocular damage. Split file analysis was performed with 73 cases forming a test group with the remaining 54 cases acting as a validation group. RESULTS: Large tumour size and the presence of retinal detachment were significant, independent risk factors for developing rubeosis for both the test and validation groups. These factors also predicted subsequent enucleation for uncontrolled ocular pain. Patients with tumours too large to plaque and with an associated retinal detachment had a 90% chance of developing rubeosis within 4 years of proton beam radiotherapy. CONCLUSIONS: Patients with a uveal melanoma too large for plaque therapy and an associated retinal detachment run a very high risk of developing rubeosis after proton beam radiotherapy and one third of individuals developing rubeosis required enucleation for pain even if local tumour control was satisfactory.

Adult↗
PubMed1996

Microvessel count predicts survival in uveal melanoma.

Microvessel density has become established as an important prognostic indicator for many tumor types. This study investigates the microvessel density as a prognostic factor for survival in patients with uveal melanoma, which is the commonest intraocular tumor and has a clear tendency for metastatic spread to the liver. Factor VIII-related antigen was identified immunohistochemically in bleached sections from 123 tumors. Maximum blood vessel density in an area of 0.25 mm2 was recorded, along with other accepted prognostic information. Microvessel density was the single most important prognostic factor on univariate testing, and in a Cox proportional hazard model, tumor size was the only other variable to be entered. No other accepted prognostic factor entered the model. We conclude that microvessel density is an important prognostic factor for survival in patients with uveal melanoma and allows the identification of high-risk patients for whom adjuvant therapy should be considered.

Biomarkers, Tumor↗
PubMed1996

Results of combined chemotherapy and radiotherapy for advanced intraocular retinoblastoma.

OBJECTIVE: To determine the visual anatomical results and survival after combined chemotherapy and whole eye radiotherapy for patients with bilateral Reese-Ellsworth group V retinoblastoma. SETTING: A national referral center for retinoblastoma. PATIENTS: Fourteen patients with bilateral Reese-Ellsworth group V retinoblastoma seen between March 1, 1989, and April 30, 1995, were treated. INTERVENTIONS: Patients were treated with chemotherapy (using carboplatin, etoposide, and vincristine) and whole eye radiotherapy (40-44 Gy in 20-22 equivalent fractions). A medical record review was performed to determine outcomes. MAIN OUTCOME MEASURES: Survival, eye preservation rate, and visual acuity. RESULTS: Two patients died, 1 from a primitive neuroectodermal tumor and the other from the meningeal spread of retinoblastoma. Four eyes were enucleated primarily because of severe disease at presentation. Of the remaining 20 eyes, 6 required enucleation. The disease recurred in 4 of those patients, and neovascular glaucoma developed in 2 patients. Of the 12 surviving children, 5 have a visual acuity better than l/60 in at least 1 eye. CONCLUSION: Although most of the treated group V eyes could be salvaged with chemotherapy plus radiotherapy, the resultant visual acuity was often poor.

Antineoplastic Agents, Phytogenic↗
PubMed1996

The role of cytology in the diagnosis of periocular basal cell carcinomas.

The accurate diagnosis of eyelid tumors such as basal cell carcinoma (BCC) requires histological confirmation, usually obtained by biopsy. Cytology provides a rapid alternative that can yield a diagnosis during the initial outpatient appointment. The accuracy of this technique has been reported to be very good but its sensitivity in the diagnosis of periocular lesions is unknown. In order to assess the accuracy of cytology in eyelid lesions suspected clinically to be BCCs, the cytological and histopathological diagnoses were compared retrospectively in 20 lesions from 17 consecutive patients who underwent cytology followed by excision biopsy. The sensitivity of cytology for the diagnosis of BCC was 92% compared with 88% for the diagnosis of malignant tumor. The predictive accuracy was 75% for either diagnosis. This was compared with a second group of 26 clinical BCCs from 22 consecutive patients who had incisional biopsy and histological examination followed by excision with histological confirmation, in which case the sensitivity was 100% and accuracy 96%. It was concluded that cytology was sufficiently accurate to plan excision and reconstructive surgery, when a confirmatory tissue diagnosis can be made, but not sufficiently sensitive for conservative regimens such as radiotherapy because of the small risk of false negative diagnoses.

Biopsy↗