(1/324) Ultrasonic characterisation of malignant melanoma of choroid.
An in-vitro study of wave spectral analysis in 8 enucleated eyes was conducted in order to differentiate histological subtypes of malignant melanoma. To obtain the backscattering coefficient for the tissues, we used a broadband focussed transducer with a frequency range of 7-12 MHz and a centre frequency of 10 MHz. Experimental measurement of backscattering coefficient and attenuation coefficient at various frequencies was done by substitution techniques. The backscattering coefficient, scatterer size, and root mean square velocity fluctuation were derived by the numerical method, while the attenuation coefficient at 1 MHz was derived from attenuation coefficient at different frequencies. This study revealed that backscattering coefficient and attenuation coefficient, over a frequency range of 7-12 MHz, show an increase in the spindle cell type compared to the mixed cell type of malignant melanoma. Particularly, the scatterer size was significantly higher in the spindle cell group (p = 0.013) in contrast to the mixed cell type. Spindle cells have uniform and compact histological pattern which contributes to an increase in scatterer size and root mean square velocity fluctuation. The ultrasonically obtained parameters have been shown to have a good correlation with the histology of malignant melanoma. (+info)
(2/324) Radioactive phosphorus uptake testing of choroidal lesions. A report of two false-negative tests.
Two false-negative results from 32P testing for histologically verified malignant melanomas of the choroid are reported. In the first case, a haemorrhagic choroidal detachment caused an increase in probe; additionally, the tumour was necrotic. Both factors are likely to have contributed to the false-negative result. A satisfactory explanation for the false-negative result in the second case was not determined, although it may have accurately reflected a period of minimal tumour activity, inasmuch as repeat 32P testing was strongly positive eight months later, when unequivocal evidence of tumour growth was present. An alternative explanation is that the orally administered 32P was incompletely absorbed. Since 32P testing is frequently accompanied by significant manipulation both in the manoeuvre associated with tumour localization and in that associated with the actual radioactive counting, it would seem desirable to perform indicated enucleation immediately after completion of the 32P testing. While the properly performed 32P test remains a valuable diagnostic test for helping to establish the presence or absence of malignancies of the posterior globe, it is important to guard against the tendency to underestimate careful clinical evaluation. (+info)
(3/324) Combination chemotherapy for choroidal melanoma: ex vivo sensitivity to treosulfan with gemcitabine or cytosine arabinoside.
Treatment of choroidal melanoma by chemotherapy is usually unsuccessful, with response rates of less than 1% reported for dacarbazine (DTIC)-containing regimens which show 20% or more response rates in skin melanoma. Recently, we reported the activity of several cytotoxic agents against primary choroidal melanoma in an ATP-based tumour chemosensitivity assay (ATP-TCA). In this study, we have used the same method to examine the sensitivity of choroidal melanoma to combinations suggested by our earlier study. Tumour material from 36 enucleated eyes was tested against a battery of single agents and combinations which showed some activity in the previous study. The combination of treosulfan with gemcitabine or cytosine arabinoside showed consistent activity in 70% and 86% of cases, respectively. Paclitaxel was also active, particularly in combination with treosulfan (47%) or mitoxantrone (33%). Addition of paclitaxel to the combination of treosulfan + cytosine analogue added little increased sensitivity. For treosulfan + cytosine arabinoside, further sequence and timing experiments showed that simultaneous administration gave the greatest suppression, with minor loss of inhibition if the cytosine analogue was given 24 h after the treosulfan. Administration of cytosine analogue 24 h before treosulfan produced considerably less inhibition at any concentration. While we have so far been unable to study metastatic tumour from choroidal melanoma patients, the combination of treosulfan with gemcitabine or cytosine arabinoside shows activity ex vivo against primary tumour tissue. Clinical trials are in progress. (+info)
(4/324) Differential expression of the retinoblastoma gene family members in choroidal melanoma: prognostic significance.
We evaluated 55 samples of choroidal melanoma managed by enucleation. Knowing that the immunohistochemical expression of the retinoblastoma gene family members Rb/p105, p107, and pRb2/p130 was inversely correlated with the degree of malignancy in at least some histological types, we investigated the expression of these three proteins in choroidal melanoma. We focused on the relationship between patient survival and the immunohistochemical detection of the retinoblastoma proteins. No correlation with clinical outcome was found for Rb/p105 and p107. However, we found pRb2/p130 to be an independent prognostic factor correlating positively or directly with patient survival times and indirectly or inversely with the degree of malignancy. Demonstration of the prognostic value of the immunohistochemical expression of pRb2/p130 is of significance, even if additional studies are required to confirm these data and to compare the prognostic value of pRb2/p130 immunodetection to that of other recently proposed markers, such as p53. (+info)
(5/324) Alpha/beta- and gamma/delta TCR(+) lymphocyte infiltration in necrotising choroidal melanomas.
AIM: To detect specific tumour infiltrating T cells (TIL) carrying antigen specific MHC-I restricted receptor genes on necrotising and non-necrotising malignant melanomas and to correlate the findings with clinical data. METHODS: alpha/beta- and gamma/delta- TIL were determined by immunohistochemical staining in melanomas of patients with known follow up of more than 10 years. An antigen retrieval method was used to determine variable genes delta1 and gamma1 on TCR(+) cells by an anti-TCR Vdelta1 and anti-CrgammaM1, and of Valpha and Vbeta TCR(+) by an anti-pan-TCR(+) alpha/beta antibody. RESULTS: Intratumoral TIL were present in 86 of 113 (76.1%) necrotising melanomas (NMM) v 21 of 100 (21%) in non-necrotising melanomas (MM); of these, Valpha/beta- TCR(+) cells were present in 52 of 74 (70.3%) TIL harbouring NMM v four of 21 (19%) MM; Vgamma1 in 29 of 74 (39.2%) NMM v two of 21 (10%) MM; and Vdelta1 in 39 of 74 (52.7%) NMM v three of 21 (14%) MM. Extratumoral lymphocytic infiltration was seen in 86 (76.1%) NMM including Valpha/beta TCR(+) cells in 10 (11.6%) cases, v five (5%) MM cases with no Valpha/beta TCR(+) cells detected. Vgamma1 and Vdelta1 TCR(+) cells were not found in extratumoral infiltrates. CONCLUSIONS: In NMM, the median survival was 69.3 (range 6-237) months, 19 of 74 patients (25.7%) survived 5 years, and mortality was associated with advanced stage (p<0.001), patient age (p<0.023), and extent of necrosis (p<0.048). Survival was increased with evidence of Vgamma1 and Vdelta1 TCR(+) cells (p<0.026). (+info)
(6/324) Microvascular density in predicting survival of patients with choroidal and ciliary body melanoma.
PURPOSE: Although malignant uveal melanoma disseminates predominantly hematogenously because of the absence of intraocular lymphatics, consensus about prognostic impact of microvascular density (MVD) has not been reached. This study was undertaken to investigate whether MVD, microvascular patterns, or both determine prognosis of uveal melanoma. METHODS: A population-based retrospective cohort study of melanoma-specific and all-cause mortality of 167 consecutive patients who had an eye enucleated because of choroidal or ciliary body melanoma from 1972 through 1981 was conducted. MVD was determined by counting tumor vessels in a masked fashion from areas of highest vessel density after immunostaining for CD34 epitope, factor VIII-related antigen (FVIII-RAg), and alpha-smooth muscle actin (SMA). Kaplan-Meier and Cox regression analyses of survival were performed. The association between MVD and tumor size and location, cell type, and microvascular patterns was assessed. RESULTS: MVD could be determined from 134 of 167 melanomas (80%). Based on globally highest count obtained with antibodies to CD34, MVD ranged from 5 to 121 vessels/0.313 mm2 (median, 40) and its association with presence of microvascular loops and networks (P = 0.0006), epithelioid cells (P = 0.028), and largest basal tumor diameter (P = 0.0029) was statistically significant. The 10-year melanoma-specific mortality increased with MVD (0.09, 0.29, 0.59, and 0.64, according to quartiles; P < 0.0001), as did all-cause mortality (P = 0.0022). Equivalent results were obtained with immunostaining for FVIII-RAg, whereas MVD obtained with antibodies to SMA was not associated with prognosis. Cox regression showed a hazard ratio of 2.45 (95% CI, 1.43-4.18) for presence of epithelioid cells, 1.11 (95% CI, 1.03-1.20) for largest basal diameter, 1.23 (95% CI, 1.06-1.43) for square root-transformed MVD, and 1.51 (95% CI, 1.09-2.10) for presence of loops and networks, all of which independently contributed to prognosis. CONCLUSIONS: The findings support the theory that both MVD and microvascular patterns contribute independently to prognosis in uveal melanoma in addition to cell type and size of the tumor. (+info)
(7/324) Ocular arterial blood flow of choroidal melanoma eyes before and after stereotactic radiotherapy using Leksell gamma knife: 2 year follow up.
AIMS: To evaluate the effect of high dose stereotactic radiotherapy on the ocular blood flow of patients with uveal melanoma. METHODS: Colour Doppler imaging (CDI) was used to measure blood flow velocity and vascular resistance in the ophthalmic, short posterior, and central retinal arteries of nine patients suffering from uveal melanoma. The measurements were taken before, 6 months, 1 year, and 2 years after stereotactic radiotherapy. Irradiation was performed with the Leksell gamma knife with the 59 (41-66.5) Gy total marginal dose divided in two equal fractions. CDI results were compared with age and sex matched healthy control eyes. RESULTS: At each time of measurement, blood flow velocity in the central retinal artery of the affected eyes was significantly reduced whereas vascular resistance was only increased at the 2 year follow up. Blood flow velocity and vascular resistance in the short posterior arteries of melanoma eyes were also only significantly altered at the 2 year follow up. Blood flow velocity and vascular resistance in the ophthalmic artery of melanoma eyes were not changed at all follow ups. CONCLUSIONS: In the melanoma eyes, blood flow velocity in the central retinal artery is reduced. High dose stereotactic radiotherapy with the Leksell gamma knife and a 59 (41-66.5) Gy total marginal dose in two fractions leads to a significant reduction of blood flow and a significant increase in resistance variables in the small ocular arteries within 2 years. (+info)
(8/324) Transpupillary thermotherapy as primary treatment for small choroidal melanomas.
PURPOSE: To report short-term follow-up of eyes containing small choroidal melanomas that were treated with transpupillary thermotherapy (TTT). METHODS: Twenty eyes with suspected small choroidal melanomas were treated with TTT using infrared light delivered from the diode laser. RESULTS: The age of patients ranged from 26 to 82 years. In 14, there was documented growth of the melanoma prior to TTT. Tumor thicknesses ranged from less than 1 to 3.2 mm. Seven tumors were treated more than once. Follow-up ranged from 6 months to more than 3 years. Following treatment, tumor thicknesses decreased in all cases, usually within 2 months. Progressive atrophy of tumor mass and loss of pigmentation within the tumor continued beyond 1 year of follow-up in some eyes. Complications included field defects, vascular changes, and macular abnormalities. CONCLUSIONS: Transpupillary thermotherapy of small choroidal melanomas is usually followed by early tumor shrinkage but is complicated by dense scotomas, nerve fiber bundle defects, and occasionally macular abnormalities. Short-term follow-up suggests that TTT may arrest growth of selected small melanomas. (+info)