Genetic analysis in retinoblastoma and peripheral blood correlation.

OBJECTIVE: To determine the importance of intratumoral genetic analysis in the diagnosis of germ-line mutations in patients with retinoblastoma. To underline the importance of performing these genetic tests in every case of retinoblastoma. METHOD: Intratumoral genetic analysis of RB1 mutation was performed on 17 enucleated eyes that were non-responsive to conservative treatment. Patients had no family history of retinoblastoma, and lesions were always single. The identified mutations were then also studied in peripheral blood analysis. RESULTS: There were 12 (70.6%) cases with positive results in intratumoral analysis. In 8 cases (47.1%) mutation of both RB1 alelli were detected, and in 4 (23.5%) cases only one allele was found mutated. In 5 patients (29.4%) no mutation was identified. In the first hit, mutations comprised 7 frameshift or nonsense and 2 splice, whereas in the second hit, one splice mutation, 2 nonsense and 8 loss of heterozygosity were identified. Among 6 patients where intratumoral analysis detected a single mutation associated with a loss of heterozygosity, the peripheral blood analysis was able to detect the same mutation in 3 cases (50%). CONCLUSIONS: Intratumoral genetic analysis of sporadic retinoblastoma can detect germ-line mutations. These patients are at higher risk of bilateralization and development of second tumors or trilateral retinoblastoma. Genetic screening is recommended in every patient diagnosed with retinoblastoma.

[Genetic analysis results of patients with a retinoblastoma refractory to systemic chemotherapy]. / Resultados del analisis genético de los pacientes con retinoblastoma resistente a quimioterapia sistémica.

OBJECTIVE: To analyze the genetic alterations identified in the RB1 gene in retinoblastoma patients who do not respond to systemic chemotherapy. METHODS: A genetic analysis was performed on 115 patients with retinoblastoma, 40 of whom had received systemic chemotherapy, and 29 of them had bilateral disease. Descriptive and retrospective study. Non-responders were considered as patients who are finally enucleated. RESULTS: Patients with deletion type mutations are those with less preservation of the eyeball (Pearson Chi-square, P=.055). Patients with an impaired nonsense-frameshift type are more likely to preserve the eyeball. Of the 3 patients who had undergone bilateral enucleation, 2 of them had deletions and one missense alteration. Survival analysis (Kaplan-Meier curve) shows that patients with deletion type mutations are more resistance to chemotherapy, are suffering higher rates of enucleation, and for a shorter period of time (log rank [Mantel-Cox] with a significance level of P=.053), which are also associated with increased rate of being bilateral. CONCLUSIONS: Patients with a genotype show increased resistance to chemotherapy should be evaluated more closely and treated with various therapeutic weapons early. Patients that have deletions in the RB1 gene are at increased risk of chemoresistance. It is likely that other genetic alterations other than RB1 gene may be related to tumor aggressiveness and treatment resistance.

[Trilateral retinoblastoma. Correlation between the genetic anomalies of the RB1 gene and the presence of pineal gland cysts]. / Retinoblastoma trilateral. Correlación de las alteraciones genéticas del gen RB1 y la presencia de quistes de la glándula pineal.

OBJETIVE: To determine the correlation between the presence of genetic anomalies identified in the RB1 gene and the development of trilateral retinoblastoma. METHOD: No patients with primitive neuroectodermal tumour (PNET) were identified out of a total of 206 patients, but there were 17 cases of pineal cysts, of which 11 had a genetic study. RESULTS: Of the 11 patients who had a genetic study performed, the anomaly in the germinal line was identified in 8 cases, which was equivalent to 100% of the bilateral retinoblastomas, and 25% of the unilateral ones. It is more common to find a germinal mutation in patients with bilateral disease (P=.024). There are no significant differences in the type of anomaly identified, although the nonsense-frameshift type is more frequent in cases with bilateral involvement. Identification of the genetic anomaly is more frequent in patients who have pineal cysts (Fisher test; P=.490). Nine of the 17 patients received systemic chemotherapy (52.29% of the cases), which could be able to prevent the development of PNET. Although a certain trend was observed in all the mentioned parameters, there was a relationship between, the presence of pineal cysts and bilateral disease (Pearson Chi X2: P=.191), a known family history (Fisher test; P=.114) and age of early diagnosis (Fisher test; P=.114). There were no significant differences in the mutation type identified. CONCLUSIONS: Considering pineal cysts as a pre-malignant form of pinealoblastoma, we found a relationship between the germinal line mutation of the RB1 gene and the cases with bilateral or unilateral retinoblastoma.

[Nosocomial outbreak of epidemic keratoconjunctivitis in a neonatal intensive care unit]. / Brote nosocomial de queratoconjuntivitis epidémica en una unidad de cuidados intensivos neonatal.

OBJECTIVE: To describe an epidemic nosocomial outbreak of keratoconjunctivitis affecting at least 43 people in a Neonatal Intensive Care Unit in Madrid, between May and October 2002, perform epidemiologic research and determine preventive measures to prevent new outbreaks. METHODS: Description of the outbreak, clinical case definition, microbiologic and epidemiologic research through the use of questionnaires. Analysis of the incidence of subepithelial infiltrates 1 year after infection and the use of topical corticosteroid therapy. RESULTS: The epidemic began in the Neonatal Service, with a pair of twins being found as the initial focus. Dissemination occurred to about 24 workers of the unit, and 19 workers from other services. The microbiologic diagnosis confirmed adenovirus in 10 conjunctival smears and one serologically, with the remainder obeying clinical and epidemiological criteria of such infection. Infected patients using topical corticosteroids had a higher incidence of infiltrates 12 months later than those not using such agents (p=0.003 in Fisher test). CONCLUSIONS: Epidemic keratoconjunctivitis occurs frequently, is highly contagious and has possible long-term sequelae, necessitating the use of preventive measures to avoid spread and new outbreaks.

[Photic maculopathy and iris damage in a psychotic patient]. / Maculopatía solar y lesiones del iris autoinducidas en paciente psicótico.

CASE REPORT: A 37-year-old psychotic patient inflicted injuries to his skin and eyes in the context of an interpretational delirium with aesthetic content. He used magnifying glasses to concentrate sunlight and suffered burns to his arms and face. In the eyes, these resulted in massive iridial atrophy with loss of the sphincteric function, photic maculopathy and peripheral retinal coagulation. The macular lesion resolved spontaneously although he did not recover visual acuity. DISCUSSION: This is the first reported case of ocular self-injury secondary to sunlight. It is also the first case reporting retinal photo-coagulative lesions secondary to sunlight.