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A J Foss

Publications and source records attributed to A J Foss.

At least 19 recordsLinked to original sources
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

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

Trends in eye cancer mortality among adults in the USA and England and Wales.

Trends in eye cancer mortality are presented for the USA and England and Wales during the period 1955-89. Mortality rates have fallen by 58% in the USA during this period. The fall in mortality is paralleled by an equal fall in incidence rates in the USA. In England and Wales, mortality rates and incidence rates have remained relatively constant during the last three decades. The explanation for these differences between the USA and England and Wales is unknown.

Age Factors↗
PubMed1996

A comparison of slit-lamp supported versus hand-held biometry.

Biometry allows determination of the final refractive outcome following cataract extraction with intraocular lens implantation. We compared the accuracy of axial length measurement performed with the slit-lamp supported biometry probe versus a hand-held technique. The two methods of biometry were performed on 32 patients undergoing endocapsular cataract extraction with lens implantation. One of the methods was selected at random in order to predict implant power for a desired refractive outcome using the SRK-T formula. There was no difference in 'within-subject' variance of axial length measurement between the two methods (t = 1.74, p = 0.091), and there was no difference in refractive outcome when the power calculations for the two techniques were compared (t = 0.12, p = 0.906). The hand-held technique provides a useful alternative method of biometry in 'difficult' patients.

Biometry↗
PubMed1996

The immunoalkaline phosphatase technique in immunohistochemistry: the effect of permanganate-oxalate melanin bleaching upon four final reaction products.

Melanin bleaching prior to the application of primary antibody can alter the immunoreactivity of a number of antigens. The effect of melanin bleaching subsequent to antigen visualisation by four different chromogens used with an immunoalkaline phosphatase technique was investigated. Vector black was the only final reaction product that withstood exposure to the permanganate-oxalate sequence for a time sufficient to bleach melanin.

Choroid Neoplasms↗
PubMed1995

Estrogen and progesterone receptor analysis in ocular melanomas.

BACKGROUND: It has been suggested that pregnancy may promote metastases in melanoma and that the contraceptive pill may be an etiologic factor. The purpose of this study is to determine if uveal or conjunctival melanomas express estrogen or progesterone receptors. METHODS: Twenty-seven choroidal and five conjunctival melanomas were investigated. Immunohistochemistry was performed using the antibodies ER-D5, which recognizes heat-shock protein 27 (formerly called the estrogen receptor-associated cytoplasmic antigen); ER-1D5, which recognizes the estrogen receptor; and PgR, which recognizes the progesterone receptor. RESULTS: Most of the conjunctival and uveal melanomas stained strongly for heat-shock protein 27 but none of the tumors showed positive nuclear staining for either the estrogen or the progesterone receptor. CONCLUSIONS: No evidence was found for either estrogen receptor or progesterone receptor expression in choroidal or conjunctival melanomas. Based on the literature, there is little evidence for these hormones having a role in the development or progression of these tumors.

Adult↗
PubMed1995

The detection of melanoma cells in peripheral blood by reverse transcription-polymerase chain reaction.

Both cutaneous and uveal melanoma undergo haematogenous dissemination. Detection of tyrosinase mRNA by reverse transcription-polymerase chain reaction (RT-PCR) has been described as an extremely sensitive way of detecting circulating viable melanoma cells in the peripheral venous blood, and this technique may be of value in the early detection of dissemination. Also, it has been suggested that surgical manipulation of the eye, such as occurs during enucleation, can provoke uveal melanoma dissemination. The purpose of this study was to evaluate whether tyrosinase mRNA is detectable in the peripheral blood of patients with uveal and cutaneous melanoma and in patients with uveal melanoma undergoing surgical procedures on the eye harbouring the tumour. Venous blood samples from 36 patients diagnosed as having active uveal melanoma and from six patients with advanced metastatic cutaneous melanoma were analysed. In addition, blood samples were spiked with known numbers of cells from three cell lines and four primary uveal melanoma cultures. The reported sensitivity of the technique was confirmed, with an ability to detect down to one cell per ml of blood. All 51 blood samples from the 36 patients with uveal melanoma were negative, and this included 20 perioperative blood samples. The test was also negative for the six patients with advanced cutaneous melanoma. There were two positives among 31 control samples analysed. This study demonstrates that there are far fewer circulating viable melanocytes than has been previously supposed in patients with melanoma and that the RT-PCR is of no clinical value in detecting metastatic melanoma disease. There was no evidence for surgery causing a bolus of melanoma cells to enter the peripheral circulation.

Base Sequence↗
PubMed1995

Is the first day postoperative review necessary after cataract extraction?

BACKGROUND: In current ophthalmic practice day-case surgery cataract patients are conventionally discharged and then reviewed the following morning thus limiting the advantages of what 'true' day-case surgery strives to achieve. The aim of this study was to see if there was a difference in outcome between 'true' day-case cataract surgery and non-day-care surgery. METHODS: A total of 387 consecutive cataract operations were followed, comprising 122 local anaesthetic day-cases, 149 local anaesthetic non-day-cases, 63 general anaesthetic non-day-cases, and 53 general anaesthetic day-cases. RESULTS: Although not randomised the groups were comparable with respect to age, operator grade, sex, presence of diabetes, anaesthetic type, pre and postoperative visual acuities, and time to first planned outpatient visit. There were 10 early postoperative complications in the day-case group (5.71% of total) and 14 in the non-day-case group (6.6% of total), the commonest complications in both groups were raised intraocular pressure, corneal oedema, and wound leaks. One patient in each group had an early complication that necessitated attending the casualty department. The visual outcomes in both groups were comparable. CONCLUSIONS: These findings suggest that there were no preventable complications within the constraints of the number of operations studied and that no additional risk is attached to 'true' day-case surgery relative to non-day-case surgery.

Aged↗
PubMed1995

Immunohistochemical techniques: the effect of melanin bleaching.

This study addresses two questions: i) which antigens can withstand bleaching by 2.5 g/L of potassium permanganate followed by 10 g/L of oxalate, before immunohistochemical staining; and ii) are any other steps in the immunohistochemical staining technique resistant to bleaching? A panel of 10 antigens was stained immunohistochemically and the results compared with staining performed with a bleaching step interpolated at different steps in the procedures. Four antigens (HMB-45, S-100, factor VIII-related antigen and collagen type IV) were unaffected by bleaching; two antigens (CD-20 and CD-45) had their staining enhanced by bleaching; one had the staining reduced (hsp27); and in three it was abolished (CD-45Ro, CD-31 and Ulex/anti-ulex antibody) by bleaching. Two antibodies (UCHL-1 and L-26) showed evidence for altered specificity following bleaching. None of the steps after application of the primary antibody was resistant to bleaching. Three chromagens used for peroxidase demonstration-amino ethyl-carbazole, diaminobenzidine and chloro-naphthol-were also found to be sensitive to bleaching. While some antigens were resistant to the effects of bleaching, some were not, and no other step in the immunohistochemical procedure could withstand bleaching.

Antigens, Neoplasm↗
PubMed1994

Are most intraocular "leiomyomas" really melanocytic lesions?

BACKGROUND: Intraocular smooth muscle tumors have long been a subject of controversy. The advent of immunohistochemistry with antibodies against HMB-45, S-100, smooth muscle actin, desmin, and vimentin has helped greatly in the distinction between smooth muscle tumors and melanocytic lesions. METHODS: Twenty-seven archival tissue blocks from patients who had had intraocular leiomyomas or leiomyosarcomas diagnosed were located and fresh sections cut and stained for the above markers. The cases constituted 24 iris lesions and 3 ciliary body lesions. RESULTS: All 24 iris tumors were reclassified as iris melanocytic lesions. Two of the three ciliary body leiomyomas retained their classification, and the third was reclassified as a spindle B-cell melanoma. CONCLUSION: The authors suggest that intraocular leiomyomas are much rarer than previously suggested and that many of the cases previously reported in the literature are open to question.

Actins↗
PubMed1994

Uveal melanoma: is solar ultraviolet radiation a risk factor?

Age-standardized mortality rates for cancers of the eye among adults in England and Wales are compared with those for cutaneous malignant melanoma. While cutaneous malignant melanoma rates have increased three-fold since 1950-54, rates for cancers of the eye have remained relatively constant over the same period. Collectively, the inconclusive findings of case-control studies for an association between exposure to ultraviolet radiation and uveal melanoma, the lack of supporting dosimetry data, together with the lack of an upward trend in mortality rates for cancers of the eye, suggests that exposure to ultraviolet radiation may not be a major factor in the etiology of uveal melanoma.

Adult↗
PubMed1994

Current indications for scleral contact lenses.

Scleral contact lenses have been largely superseded by corneal contact lenses, but they still retain a role as a treatment of choice for a small group of patients who have tried other types of contact lens wear without success and who are not good candidates for surgery. We performed a cross sectional survey of 44 patients attending clinics at Moorfields Eye Hospital who were successful long-term scleral contact lens wearers and reviewed their indications. Twenty-one patients had been fit to improve visual acuity, 20 for therapeutic indications, and three for cosmetic reasons. Scleral lenses were most useful were with patients with ocular surface disorders, such as Stevens-Johnson syndrome, and for visual rehabilitation of patients with grossly irregular corneal topography. All patients were benefiting from scleral contact lens wear, and none had serious complications as a result of the scleral lens wear. We conclude that all ophthalmic departments should have access to these lenses.

Adolescent↗
PubMed1993

Anterior hyaloidal fibrovascular proliferation after extracapsular cataract extraction in diabetic eyes.

Four patients with proliferative diabetic retinopathy developed anterior hyaloidal fibrovascular proliferation after extracapsular cataract extraction and posterior chamber lens implantation. This complication of cataract extraction has been described after vitrectomy in diabetic eyes. Risk factors for this entity after extracapsular cataract extraction include proliferative diabetic retinopathy, iris neovascularization, and anterior ischemic retina. Anterior hyaloidal fibrovascular proliferation was observed an average of 12 months postoperatively and affected vision in one of four patients. No progression was seen within an average of six months of follow-up, and no complications such as traction retinal detachment and vitreous hemorrhage developed.

Aged↗