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.

Congenital anophthalmia and microphthalmia: epidemiology and orbitofacial rehabilitation.

OBJECTIVE: To describe the prevalence of congenital anophthalmia and microphthalmia in Hospital Universitario La Paz, and to identify associated risk factors and evaluate cosmetic results in treated and nontreated patients. METHODS: A retrospective, descriptive, cross-sectional study of patients treated with orbital expanding techniques (cases) and nontreated patients (controls) was carried out as a comparative case series study. A total of 36 patients with unilateral or bilateral anophthalmia or microphthalmia as main diagnosis were included; 52 epidemiological and management variables for each patient were analyzed. The study evaluated orbital growth and facial symmetry. RESULTS: The overall cosmetic result in the study's group of patients was satisfactory: 66.7% showed good or very good orbital growth, and 75% showed good or very good facial symmetry. Controls had better cosmetic outcome but showed more cataracts (P = 0.05), inferior colobomas (P = 0.026), and family history (P = 0.056) than the cases. Controls also showed significantly better orbital growth (P = 0.042) and facial symmetry (P = 0.014) than the cases. CONCLUSION: This study suggests that the mere presence of a globe (controls) still provides better orbitofacial development than the artificial stimulation (cases) currently available for patients with congenital anophthalmia and microphthalmia, who receive internal and external orbital rehabilitation.

[Orbital rhabdomyosarcoma: difficulties with European treatment protocol]. / Rabdomiosarcoma orbitario: dificultades con el protocolo de tratamiento Europeo.

UNLABELLED: PURPOSE, MATERIAL AND METHODS: To present the experience in management of orbital rhabdomiosarcoma over 21 years in our centre. Review of the 12 cases of paediatric rhabdomiosarcoma and results of treatment in terms of mortality and morbidity comparing our results with other studies. RESULTS/CONCLUSION: Management of orbital rhabdomyosarcoma following the European Protocol leads to poor results compared with the American protocol. Early radiotherapy and complete tumoral excision could play a role in management of this tumour

[Interferon alpha and infantile orbital hemangioma]. / Interferón-alfa y hemangiomas orbitarios infantiles.

OBJECTIVE: To determine the efficacy and safety of interferon alpha therapy for the treatment of infantile periorbital hemangiomas associated with visual impairment. METHODS: Retrospective study of 4 patients diagnosed of orbital hemangioma during infancy. All of them were treated with interferon alpha 2b at doses of 3 million U/m2, administered once daily by subcutaneous injection, at least during 3.5 months. The lesions were compared through clinical evaluation and diagnostic imaging (echography, CT and MRI) before, during and after treatment, estimating the percentage of lesion reduction in relation to the initial size. RESULTS: In 3 cases, a 95% volume reduction was detected, and greater than 50% in the other one. Spastic diplegia was detected in a child during treatment, but resolved without persistent neurological deficits when discontinued. Alterations in plasmatic lipid profile were detected in one patient. CONCLUSION: Interferon alpha can be a valuable treatment for periorbital hemangiomas of infancy; even though, adverse effects can be clinically significant.

Interferón-alfa y hemangiomas orbitarios infantiles / Interferon alpha and infantile orbital hemangioma

Objetivo: Estudiar la eficacia y seguridad de la terapia con interferón-alfa en el tratamiento de los hemangiomas infantiles con afectación orbitopalpebral y compromiso visual. Métodos: Estudio retrospectivo de 4 pacientes, diagnosticados de hemangioma orbitario en la infancia. Se administró interferón-alfa 2b a la dosis de 3 millones U/m2 de superficie corporal, en inyección subcutánea diaria, durante un período de tiempo mínimo de 3,5 meses. Se compararon las lesiones a través de la exploración clínica y por métodos de imagen (ecografía, TAC, RNM) antes, durante y después del tratamiento, estimándose el porcentaje de reducción de la lesión con respecto al tamaño inicial de la misma. Resultados: En 3 casos se produjo una reducción del 95 por ciento de la lesión y en el restante ésta fue de más del 50 por ciento. En un caso se detectó diplejia espástica durante el tratamiento que, al suspenderlo, revirtió sin dejar secuelas neurológicas permanentes. En un caso detectamos alteraciones en el perfil lipídico con elevación de las cifras de colesterol y, principalmente, de los triglicéridos. Conclusiones: El interferón alfa puede constituir una alternativa terapéutica eficaz para el tratamiento de los hemangiomas infantiles con participación orbitopalpebral y, compromiso visual, aunque los efectos secundarios pueden ser importantes (AU)