Biomedical subjects

Bertil E Damato

Publications and source records attributed to Bertil E Damato.

11 recordsLinked to original sources

PubMed2006

On the use of multi-objective evolutionary algorithms for survival analysis.

This paper proposes and evaluates a multi-objective evolutionary algorithm for survival analysis. One aim of survival analysis is the extraction of models from data that approximate lifetime/failure time distributions. These models can be used to estimate the time that an event takes to happen to an object. To use of multi-objective evolutionary algorithms for survival analysis has several advantages. They can cope with feature interactions, noisy data, and are capable of optimising several objectives. This is important, as model extraction is a multi-objective problem. It has at least two objectives, which are the extraction of accurate and simple models. Accurate models are required to achieve good predictions. Simple models are important to prevent overfitting, improve the transparency of the models, and to save computational resources. Although there is a plethora of evolutionary approaches to extract models for classification and regression, the presented approach is one of the first applied to survival analysis. The approach is evaluated on several artificial datasets and one medical dataset. It is shown that the approach is capable of producing accurate models, even for problems that violate some of the assumptions made by classical approaches.

Algorithms↗

PubMed2006

Transretinal choroidal tumor biopsy with a 25-gauge vitrector.

OBJECTIVE: To describe and evaluate transretinal biopsy of choroidal tumors using 25-gauge vitrectomy instrumentation. DESIGN: Retrospective, consecutive, noncomparative case series. PARTICIPANTS: Fourteen patients undergoing choroidal tumor biopsy at an ocular oncology center. METHODS: The biopsies were performed under local or general anesthesia, alone or in combination with ruthenium plaque or tantalum marker insertion. Immunohistochemistry was performed on all samples, and some melanomas were also analyzed cytogenetically. RESULTS: Surgery was uneventful in all cases. A positive tissue diagnosis was made in 13 of 14 patients, albeit at the second attempt in 1 patient. The only failure occurred because the tumor was calcified. CONCLUSION: Transretinal choroidal biopsy with 25-gauge instrumentation yields a larger sample than fine-needle aspiration biopsy, usually producing sufficient tissue for cytogenetic studies. We did not identify safety concerns in this series of patients. Insufficient samples can occur in some patients, and further studies are needed to understand the reason for such failure.

Adenocarcinoma↗

PubMed2006

Presymptomatic diagnosis of bronchogenic carcinoma associated with bilateral diffuse uveal melanocytic proliferation.

A 62-year-old man presented with bilateral diffuse uveal melanocytic proliferations (BDUMP) and painful flexor contractures of the fingers of both hands. All these features were considered paraneoplastic but extensive and repeated investigations revealed no underlying malignancy. Oral steroids and orbital radiotherapy were ineffective. The diagnosis was confirmed by trans-scleral biopsy of the right choroid. Rapidly progressive cataracts were treated by phacoemulsification. Severe exudative retinal detachment with rubeosis and neovascular glaucoma in the left eye were treated successfully by partial choroidectomy. Fifteen months after presentation, investigations detected a 22 mm, poorly differentiated adenocarcinoma, which was resected without complication. The ocular tumours in both eyes regressed, without improvement in vision of Light Perception, and the palmar fasciitis also improved. The patient remained free of tumour recurrence until sudden death from myocardial infarction five years after he first presented.

Carcinoma, Bronchogenic↗

PubMed2004

Modelling survival after treatment of intraocular melanoma using artificial neural networks and Bayes theorem.

This paper describes the development of an artificial intelligence (AI) system for survival prediction from intraocular melanoma. The system used artificial neural networks (ANNs) with five input parameters: coronal and sagittal tumour location, anterior tumour margin, largest basal tumour diameter and the cell type. After excluding records with missing data, 2331 patients were included in the study. These were split randomly into training and test sets. Date censorship was applied to the records to deal with patients who were lost to follow-up and patients who died from general causes. Bayes theorem was then applied to the ANN output to construct survival probability curves. A validation set with 34 patients unseen to both training and test sets was used to compare the AI system with Cox's regression (CR) and Kaplan-Meier (KM) analyses. Results showed large differences in the mean 5 year survival probability figures when the number of records with matching characteristics was small. However, as the number of matches increased to > 100 the system tended to agree with CR and KM. The validation set was also used to compare the system with a clinical expert in predicting time to metastatic death. The rms error was 3.7 years for the system and 4.3 years for the clinical expert for 15 years survival. For < 10 years survival, these figures were 2.7 and 4.2, respectively. We concluded that the AI system can match if not better the clinical expert's prediction. There were significant differences with CR and KM analyses when the number of records was small, but it was not known which model is more accurate.

Bayes Theorem↗

PubMed2004

Systemic remission of non-Hodgkin's lymphoma after intralesional interferon alpha-2b to bilateral conjunctival lymphomas.

PURPOSE: To report the beneficial systemic effect of a 5-week course of intralesional interferon alpha-2b (IFN-A) injections to bilateral conjunctival lymphomas in a patient with relapsing non-Hodgkin's lymphoma. DESIGN: Interventional case report. METHODS: A patient in relapse with non-Hodgkin's lymphoma who declined further systemic therapy received 1.5-million IU IFN-A injected intralesionally to each of two conjunctival lymphomas to reduce ocular discomfort. This dose was repeated 10 times over 5 weeks. RESULTS: Conjunctival, postauricular, and facial lesions clinically resolved within 3 months of the start of treatment. Inguinal lymph nodes reduced in size, and the patient reported increased well-being and less fatigue. Side effects included injection discomfort and mild flulike symptoms, which were well tolerated. The improvement lasted 6 months from the first IFN-A injection. CONCLUSIONS: Intralesional treatment of conjunctival lymphomas with IFN-A induced disappearance of the tumors and also had a beneficial systemic effect.

Aged↗

PubMed2004

Histopathology of eyes enucleated after endoresection of choroidal melanoma.

PURPOSE: To demonstrate the histopathologic features of eyes enucleated after endoresection for choroidal melanoma to assess the complications of this treatment and to determine indications for further treatment after endoresection in the setting of possible tumor recurrence. DESIGN: Retrospective, observational case series. PARTICIPANTS: Sixty-one consecutive patients who had undergone endoresection for uveal melanoma. METHODS: Eyes that had undergone enucleation after endoresection were identified, and their charts and histologic characteristics were reviewed. Pertinent features were described. One patient was excluded because enucleation was performed as a primary treatment when endoresection was abandoned at the time of his initial treatment. MAIN OUTCOME MEASURES: The outcome measures included: reasons for enucleation; tumor recurrence; and location, clinical, and histologic characteristics of each recurrence. RESULTS: Twelve eyes were identified that had undergone enucleation after endoresection. The reasons for enucleation were: (1) local tumor recurrence detected by ophthalmoscopy (2 patients) or echography (1 patient); (2) opaque media preventing adequate ophthalmoscopy (4 patients); (3) blind and painful eye of uncertain cause (1 patient); and (4) a combination of blind eye and limited fundus view (4 patients), which was the result of untreatable retinal detachment (3 patients) and endophthalmitis (1 patient). Eight of 12 patients had recurrent choroidal melanoma. Recurrences were all located adjacent to the resection site, although in 1 patient there was extensive diffuse recurrence throughout the eye. The recurrence was visible clinically in 3 patients and obscured because of opaque media (2 patients), a combination of inadequate echography and retinal detachment (1 patient), retinal detachment (1 patient), and endophthalmitis (1 patient). CONCLUSIONS: Recurrent disease occurred at the site of the primary tumor with no seeding except in 1 patient, whose marginal recurrence was not immediately detected and treated because of opaque media. As with other treatments conserving the eye, enucleation should be performed if adequate ocular examination is not possible, and follow-up should be lifelong.

Adult↗

PubMed2004

BRAF mutations are detectable in conjunctival but not uveal melanomas.

Activating mutations in exon 15 of BRAF have been detected in a high proportion of cutaneous melanomas. To determine whether such mutations are a feature of conjunctival or uveal melanomas, we screened DNA from these tumours. Twenty-one conjunctival and 88 uveal tumours were included in the study. Mutation analysis of BRAF exons 11 and 15 was undertaken using a combination of conformationally sensitive gel electrophoresis and direct sequencing. Mutations in exon 15 were detected in three of the conjunctival tumours (two V599E and one E585 K). None of the uveal tumours possessed a BRAF mutation in either exon 15 or 11. We conclude that uveal melanomas arise independently of oncogenic BRAF mutations, but the development of a proportion of conjunctival tumours involves mutation of this gene.

Adult↗

PubMed2003

Consecutive choroidal melanoma in the same eye of a patient.

PURPOSE: To report the occurrence of two entirely separate choroidal melanomas in the same eye of one patient. DESIGN: Observational case report. METHODS: Retrospective case report from one clinical practice. Two choroidal melanomas were observed to develop in the same eye of one patient. RESULTS: An inferonasal choroidal melanoma was diagnosed in the left eye of a 30-year-old woman in 1990. This was successfully treated with proton beam radiotherapy. In 1996, a superotemporal choroidal tumor in the same eye was observed to grow rapidly and it was treated with a ruthenium plaque in 1996. There was a history of cutaneous malignant melanoma. CONCLUSIONS: It is extremely rare for two choroidal melanomas to develop in one eye, and there may be a genetic predisposition.

Adult↗

PubMed2003

Contribution of germline mutations in BRCA2, P16(INK4A), P14(ARF) and P15 to uveal melanoma.

PURPOSE: Reports suggest that a subset of uveal melanoma is familial. The association of uveal melanoma with breast and ovarian cancer and the increased risk in BRCA2-linked families implicates germline BRCA2 mutations as the cause of a subset of uveal melanomas. Similarly, the association between cutaneous and uveal melanomas in some families, coupled with the high frequency of somatic deletions of the INK4A-ARF locus in uveal melanomas, strongly suggests that mutations in P16(INK4A) and P15 account for a proportion of uveal melanomas. METHODS: To examine this proposition, a systematically ascertained series of 385 patients with uveal melanoma were screened for germline mutations in BRCA2, P16(INK4A), P14(ARF), and P15. RESULTS: One patient was found to harbor a Gly35Ala substitution in exon 1alpha of P16(INK4A), which has previously been reported to be pathogenic. No mutations were detected in P14(ARF) or P15. None of the patients harbored germline nucleotide changes that lead to truncation or that create or disrupt consensus splice sites of BRCA2 or missense variants with clear pathogenic potential. CONCLUSIONS: These findings suggest that less than 2% of cases of uveal melanoma can be ascribed to germline mutations in BRCA2, P16(INK4A), P14(ARF), or P15. It is likely that mutations in other genes contribute to an inherited predisposition to uveal melanoma.

Adult↗

PubMed2003

Monosomy 3 in uveal melanoma: correlation with clinical and histologic predictors of survival.

PURPOSE: To correlate monosomy 3 in uveal melanoma with clinical and histologic prognostic variables and death caused by metastatic disease. METHODS: Loss of heterozygosity (LOH) on chromosome 3 was investigated by PCR-based microsatellite analysis in 105 tumors and related to large basal tumor diameter (LBD), ciliary body (CB) involvement, tumor cell type, periodic acid-Schiff (PAS)-positive loops, and death related to metastatic disease. A model relating monosomy 3 to these was created with forward-stepwise logistic regression and used to derive a prognostic index. RESULTS: Monosomy 3 occurred in 54 (51%) tumors and regional chromosome 3 LOH in another six (6%) tumors. Monosomy 3 was associated with epithelioid cells (chi(2) test, P < 0.001), PAS-positive loops (chi(2), P = 0.001), LBD (Mann-Whitney test, P = 0.002), CB involvement (chi(2) test, P = 0.008), and metastasis-related death (log rank analysis, P = 0.0003). The regression coefficients indicated that epithelioid histology was 15 times as influential with each millimeter of increase in LBD. A prognostic score was derived: one point for each LBD category (<7.4, 7.5-12.4, 12.5-17.4, and >17.4 mm) and three points for epithelioid histology. The prevalence of monosomy 3 increased with score, from 0% in 18 tumors scoring less than 4 to 95% in 21 tumors scoring 7. CONCLUSIONS: Monosomy 3 correlates with survival but can be predicted only in patients with large epithelioid tumors. The absence of monosomy 3 is predictable only in patients who have small, spindle-cell tumors. In most patients, prediction of monosomy 3 according to tumor size and histology is unreliable.

Adult↗

PubMed2002

Noncontiguous tumor recurrence of posterior uveal melanoma after transscleral local resection.

OBJECTIVE: To describe the clinical and histopathologic features of noncontiguous tumor recurrence after transscleral local resection of posterior uveal melanoma. METHODS: Chart review was performed to identify patients with noncontiguous tumor recurrences from a series of 494 consecutive patients treated with transscleral local resection for uveal melanoma. The clinical and histopathologic features of noncontiguous tumor recurrences were studied. RESULTS: Nine cases were identified, for an estimated incidence of 1.8%. The average diameter of the primary tumors was 16.1 mm (range, 9-22 mm) and the average thickness was 9.8 mm (range, 6-14 mm). Noncontiguous tumor recurrences were solitary in 7 cases and multiple in 2 cases, with an average diameter of 5.8 mm (range, 3.0-9.5 mm). Eight of the 9 patients developed tumor recurrences at multiple intraocular sites. With a mean follow-up of 82.1 months (range, 22-171 months), 7 patients had a final visual acuity of counting fingers or worse, and there were 3 deaths from metastatic disease. CONCLUSIONS: Noncontiguous tumor recurrence after local resection appears to be related to intraocular dissemination from the primary tumor, either through the natural course of the disease or secondary to surgical manipulation. Eyes with large primary uveal melanomas developing noncontiguous tumor recurrence have a high risk of developing tumor spread to multiple intraocular sites, and aggressive treatment is warranted.

Adult↗