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Biomedical subjects

J W Gamel

Publications and source records attributed to J W Gamel.

At least 55 records · Page 3Linked to original sources

Clinical parameters predictive of enlargement of melanocytic choroidal lesions.

The authors followed up 197 melanotic choroidal lesions (62 categorised as benign naevi, 76 classified as suspicious naevi, 41 diagnosed as dormant melanomas, and 18 categorised as active melanomas) left untreated after their initial clinical documentation. Thirty-nine of these lesions enlarged during a five-year follow-up interval (cumulative proportion of lesions that enlarged = 26.2% by Kaplan-Meier method). Individual clinical parameters predictive of lesion enlargement (p less than 0.01) included larger size of the lesion, especially lesion thickness, presence of retinal detachment, location of the lesion's posterior margin within 2 disc diameters of the optic disc, presence of symptoms, and presence of orange pigment clumps on the lesion's surface. The best combination of these parameters for prediction of lesion enlargement, as identified by multivariate Cox regression analysis, consisted of thickness of the lesion, retinal detachment, and symptoms. The five-year incidence of lesion enlargement for patients with none of these prognostic parameters was 5.8%, while that for patients with all three unfavourable parameters simultaneously was 90.6%.

Choroid↗

Interval-by-interval Cox model analysis of 3680 cases of intraocular melanoma shows a decline in the prognostic value of size and cell type over time after tumor excision.

In a selected group of 3680 patients treated by ocular excision for uveal melanoma, 1178 deaths were attributed to this tumor during 20 years following ocular excision. Survival time was divided into intervals containing an equal number of deaths, and coefficients of the Cox statistical model were independently derived for each interval. This analysis revealed a statistically significant decline over time in the prognostic value of largest tumor dimension (LTD) and Callender cell type (CT). Mathematical considerations suggest that the prognostic value of parameters derived from other cancers may also decline with time following excision of the primary tumor.

Follow-Up Studies↗

A method for determining the optimum transform for covariates of the Cox model with application to 3680 cases of intraocular melanoma.

For most applications of the Cox Model, a simple exponential relationship is assumed between covariates of this model and relative force of mortality (lambda). A method has been developed to examine this relationship in detail for data sets that contain a sufficient number of deaths. This method was applied to 3680 cases of intraocular melanoma with 1178 deaths over 20 years of follow-up, using largest tumor dimension (LTD) as a predictor of tumor-related death. Results indicated that the transform lambda = exp[beta log LTD] provides a closer approximation to observed mortality for this data set than the more traditional lambda = exp [beta LTD]. Additional applications to mathematically generated data sets revealed a close correspondence between lambda estimated by this method and the lambda programmed into each data set.

Epidemiologic Methods↗

A stable linear algorithm for fitting the lognormal model to survival data.

The lognormal model can be fitted to survival data using a stable linear algorithm. When tested on 800 sets of mathematically generated data, this method proved more stable and efficient than the iterative method of maximum likelihood, which requires initial estimates of model parameters and failed to fit a substantial fraction of data sets. Though maximum likelihood yielded more consistent estimates of proportion cured, mean, and standard deviation of log(survival time), the linear normal algorithm may nevertheless prove useful for these purposes: (i) computing initial estimates of model parameters for the maximum likelihood method; (ii) fitting data sets that cannot be fit by this method; and (iii) deriving the lognormal model directly from cumulative mortality.

Algorithms↗

Prediction of metastasis of uveal melanoma: comparison of morphometric determination of nucleolar size and spectrophotometric determination of DNA.

We studied 95 cases of uveal melanoma using cytomorphometry to measure the standard deviation of nucleolar area (SD-NA) based on 200 cells per tumor and microspectrophotometry to determine the quantity of DNA in the nucleus of 100 cells per tumor. The 95 cases of uveal melanoma, in which the eye was enucleated between 1970 and 1973, were selected from the files of the REgistry of Ophthalmic Pathology. Forty-nine patients survived with a median follow-up of 15 years without evidence of metastasis at the time of the last follow-up, and 46 patients died of metastatic melanoma. Statistical analysis indicated that SD-NA was a better predictor of metastasis than DNA determination in this data set.

Cell Nucleolus↗

Death from uveal melanoma. Number of epithelioid cells and inverse SD of nucleolar area as prognostic factors.

Criteria for the Callender classification of uveal melanoma are subjective and lead to variations among observers of the same tumor. Two other measures for cell type-the number of epithelioid cells per high-power field (Epi/HPF) and the inverse SD of nucleolar area (ISDNA)-were evaluated as prognostic factors for survival following enucleation for uveal melanoma in 232 patients. Variables significantly related to the number of Epi/HPF were related to ISDNA. Larger, more anteriorly located tumors had a high number of Epi/HPF and a low ISDNA. The two measures were also correlated. Using Kaplan-Meier survival analysis, both measures were related to tumor deaths. Worse prognosis was associated with a higher number of Epi/HPF and a lower ISDNA. Considered together in Cox' proportional hazards analysis, both measures independently predicted outcome. Separately, each measure predicted uveal melanoma-related deaths, in combination with largest tumor dimension, invasion of tumor to the line of transection, and location of the anterior tumor margin. Although ISDNA is the more objective measure of cell type, its practicality compared with other measures of cell type must also be considered.

Adult↗

Post-irradiation regression of choroidal melanomas as a risk factor for death from metastatic disease.

To determine the prognostic value of the regression rate of choroidal melanomas after cobalt-60 plaque radiotherapy, the authors performed a multivariate analysis on 159 patients treated with a cobalt plaque during the interval from 1976 through 1980. Thirty-three of the 159 patients had died as of the survey date; 29 of metastatic melanoma and 4 of other causes. Multivariate Cox proportional hazards modeling identified a two-term regression incorporating maximal basal tumor diameter at treatment and tumor thickness at 12 months posttreatment as the best model (P less than 0.005 for both parameters) for predicting length of tumor-free survival. These results are consistent with the hypothesis that rapid regression of a choroidal melanoma after cobalt-60 plaque radiotherapy is an unfavorable prognostic sign for prolonged metastasis-free survival.

Brachytherapy↗

Suicide enzyme inhibition as a chemotherapeutic strategy for controlling metastases derived from intraocular melanomas.

The anti-metastatic effect of two chemotherapeutic agents was analyzed in a murine melanoma model. Difluoromethylornithine (DFMO), a specific irreversible inhibitor of ornithine decarboxylase, was administered as a 2% aqueous solution in the drinking water. A second drug, dacarbazine (DTIC) was administered intravenously in single bolus injections. Each drug produced significant anti-metastatic effects that were manifested by a reduction in the number of pulmonary metastases and in the prolongation of host survival times. Maximal chemotherapy was achieved when both drugs were combined. The specificity, low toxicity, ease of administration, infrequent side effects, and therapeutic effectiveness of DFMO make it an attractive candidate for clinical use in human subjects being treated for uveal melanoma. The effectiveness of DTIC against blood-borne melanoma cells suggests that this drug may prove useful as a prophylactic adjunct in patients undergoing enucleation of a melanoma-containing eye.

Animals↗

Statistical methods for the practical clinical application of morphometric measurements.

Four statistical methods are presented to determine the practical clinical value of measurements made from malignant tumors and to translate these measurements into a prediction of survival for each patient: the Cox statistical model, which must be derived from a data base of cases with known outcome; the null-rank test, a modified rank-sum test that provides an overall measure of the effectiveness of the Cox model; the predicted survival curve, an estimate of survival derived for each new patient from measurements of the primary tumor; and the standard error of measurement, an empirical method for estimating the variability introduced into predicted survival by errors in measurement. The value of these statistical methods was demonstrated by application to 200 cases of human intraocular melanoma, with the two predictive morphometric measurements used being the standard deviation of nucleolar area (SDNA) and the largest tumor dimension (LTD) derived from a single histologic slide of each tumor. Sufficient references and mathematical details are provided to allow anyone with moderate skills as a computer programmer to construct or obtain all of the relevant algorithms.

Biometry↗

A clinically useful method for combining gross and microscopic measurements to select high-risk patients after enucleation for ciliochoroidal melanoma.

An objective and reproducible method was devised for estimating the malignant potential of ciliochoroidal melanomas after enucleation. This method requires only a single, routine microslide from which nucleolar area and largest tumor dimension are measured. Previous studies have shown these measurements to be reproducible and highly correlated with mortality. To demonstrate a practical method for clinical application of these measurements, a Cox statistical model was derived from 200 cases supplied by the Armed Forces Institute of Pathology. The resulting model, when applied to 340 cases with known outcome from two independent laboratories, allowed subdivision of patients into groups that suffered a six-fold difference in mortality. These results suggest that a central registry, by applying this method to histologic slides from around the world, could provide information useful for the clinical management of patients enucleated for ciliochoroidal melanoma.

Actuarial Analysis↗

Blastomycosis of the eyelid.

An 84-year-old man had a verrucous lesion of the left lower eyelid that caused progressive ectropion. Cultures of the lesion taken at the time of surgical excision demonstrated Blastomyces dermatitidis. Histologically, the excised tissue demonstrated pseudoepitheliomatous hyperplasia, a characteristic change of cutaneous blastomycosis.

Aged↗

Enucleation vs cobalt plaque radiotherapy for malignant melanomas of the choroid and ciliary body.

Clinical risk factors were assessed prospectively in a nonrandomized concurrent observational study of 237 patients with posterior uveal malignant melanoma. One hundred forty of these patients were treated with enucleation, and 97 underwent cobalt plaque radiotherapy. Tumor size and location of the anterior tumor margin proved to be the most significant clinical risk factors for death from metastatic melanoma. When Cox proportional hazards modeling was used to adjust for recognized intergroup differences in risk factors, the effect of therapy (enucleation vs cobalt plaque radiotherapy) on survival time was not statistically significant. We discuss the implications of this study for a randomized clinical trial of enucleation vs cobalt plaque therapy or comparable forms of irradiation.

Adult↗

Regression of posterior uveal malignant melanomas after cobalt plaque radiotherapy.

We reviewed the records of 17 patients with posterior uveal malignant melanoma who had been followed for at least 3 months prior to cobalt plaque radiotherapy and whose tumor had been documented to enlarge in thickness during that interval. We evaluated the relationship between the rates of pretreatment tumor enlargement and post-treatment tumor shrinkage using linear regression analysis. We found that the rate of postirradiation tumor shrinkage correlated strongly with the rate of preirradiation tumor enlargement regardless of whether the pretreatment rate of growth was slow, intermediate or rapid. We speculate that the more rapidly regressing tumors were more mitotically active than their more slowly regressing counterparts. If true, the survival rate of patients whose posterior uveal malignant melanomas regress rapidly following radiation therapy may prove to be worse than that of patients whose tumors regress slowly.

Brachytherapy↗

Fine-needle aspirates of uveal melanomas and prognosis.

The computer-assisted measurement of the standard deviation of the nucleolar area from pathologic slides of uveal melanomas correlates strongly with prognosis, but the eye must be removed and examined histologically. Because it is possible to perform fine-needle aspiration biopsies of intraocular tumors, we designed a study to determine if a fine-needle aspiration biopsy sample yields the same prognostic information as the enucleation specimen. In comparing the standard deviation of the nucleolar area measured from a fine-needle aspiration biopsy sample obtained from 53 freshly enucleated eyes with the standard deviation of the nucleolar area measured from the matched enucleation specimen, we found only a modest correlation (r = 0.57) between the two measurements. A t-test of matched pairs indicated a significant difference between the two measurements (P less than .01). The fine-needle aspiration biopsy technique does not yield the same prognostic information as the larger enucleation specimen because fine-needle aspiration biopsy material may not be representative of the tumor.

Biopsy, Needle↗

Ocular melanoma.

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Cobalt Radioisotopes↗