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1.
Neuroradiology ; 61(9): 1083-1091, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31332478

RESUMO

PURPOSE: Purposes are (1) to measure main radiation parameters and (2) to propose a method to estimate the absorbed doses of internal organs starting from DAP values. Measuring the exposition of internal organs by repeated irradiations on an anthropomorphic phantom with the same settings used in vivo, we could establish correlations between (1) DAP and the dose recorded by a dosimeter placed along the X-ray beam entrance pathway; (2) the dose recorded by the same dosimeter and the absorbed dose in internal organs. METHODS: Forty-four consecutive patients (16 males, 28 females) (mean age 35.4 months) treated at our institution with IAC (216 procedures: 196 via the ICA and 20 into branches of the ECA) were included in this prospective study. IAC was divided into 5 phases. Fluoroscopic time, DAP, and ESD were measured. RESULTS: The mean DAP was 595 ± 445 cGy cm2 and the mean fluoroscopic time was 540 ± 403 s. ESD was on average 9.59 mGy (range 0.8-165 mGy). The absorbed dose was lower than 12.1 mGy in the left retina (the more exposed organ) in 75% of single treatments and lower than 25 mGy in 95% of treatments. In the cases of 3 and 6 sessions, the left retina of 75% of patients absorbed respectively less than 36.3 and 72.7 mGy, whereas the left retina of 95% of patients received less than 75.2 and 150.4 mGy. Other organs were less exposed. CONCLUSION: This paper describes a method of absorbed dose estimation providing ranges used clinically in a single practice and the basis for further prospective studies.


Assuntos
Antineoplásicos/administração & dosagem , Fluoroscopia , Doses de Radiação , Neoplasias da Retina/diagnóstico por imagem , Retinoblastoma/diagnóstico por imagem , Adolescente , Angiografia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Infusões Intra-Arteriais , Masculino , Imagens de Fantasmas , Estudos Prospectivos , Radiometria , Neoplasias da Retina/tratamento farmacológico , Retinoblastoma/tratamento farmacológico
2.
Oncol Rep ; 42(3): 1214-1224, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31322174

RESUMO

Tetramethylpyrazine (TMP; an extract of the Chinese herbal medicine, Chuanxiong) has been shown to exert remarkable antiretinoblastoma (RB) effects. Based on our previous study, the target gene was found to be C­X­C chemokine receptor type 4 (CXCR4). CXCR4 is a prognostic marker in various types of cancer, but the exact mechanisms underlying the regulation of CXCR4 expression by TMP in WERI­Rb1 cells have yet to be fully elucidated. In the present study, it was revealed that TMP significantly downregulated CXCR4 expression and inhibited CXCR4 promoter activity in WERI­Rb1 cells, indicating that TMP inhibits CXCR4 expression in WERI­Rb1 cells through transcriptional regulatory mechanisms. Among the numerous transcription factors involved in CXCR4 function, including Yin Yang 1 (YY1), nuclear respiratory factor­1 (Nrf­1), Krüppel­like Factor 2 (KLF2), specificity protein 1 (SP1), and nuclear factor­κB subunit 1 (NF­κB1), only TMP led to a significant downregulation of Nrf­1 expression. Chromatin immunoprecipitation assays further indicated that Nrf­1 directly binds to the promoter region of CXCR4, and silencing Nrf­1 via siRNA transfection notably inhibited CXCR4 expression in WERI­Rb1 cells. In addition, the expression levels of both Nrf­1 and CXCR4 increased concomitantly with WERI­Rb1 cell density. Furthermore, the downregulation of Nrf­1 and CXCR4 expression in RB by TMP was confirmed in vivo. Taken together, the results of the present study have uncovered a novel mechanism in which CXCR4 expression is regulated by Nrf­1 in WERI­Rb1 cells, thereby identifying novel potential targets for the treatment of RB, and providing evidence for the clinical application of TMP in adjuvant retinoblastoma therapy.


Assuntos
Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Fator 1 Nuclear Respiratório/metabolismo , Pirazinas/farmacologia , Receptores CXCR4/genética , Neoplasias da Retina/patologia , Retinoblastoma/patologia , Transcrição Genética/efeitos dos fármacos , Animais , Apoptose , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Proliferação de Células , Feminino , Humanos , Camundongos , Camundongos Nus , Fator 1 Nuclear Respiratório/genética , Receptores CXCR4/metabolismo , Neoplasias da Retina/tratamento farmacológico , Neoplasias da Retina/genética , Retinoblastoma/tratamento farmacológico , Retinoblastoma/genética , Células Tumorais Cultivadas , Vasodilatadores/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
3.
BMC Cancer ; 19(1): 693, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31307410

RESUMO

BACKGROUND: To evaluate the safety and efficacy of intra-arterial chemotherapy (IAC) for the primary or secondary treatment of infants diagnosed with advanced retinoblastoma before 3 months of age. METHODS: This single-center retrospective study included 39 infants (42 eyes) aged ≤3 months who were diagnosed with unilateral or bilateral advanced intraocular retinoblastoma (group D and E eyes) and received IAC as primary or secondary treatment between June 2012 and February 2017. Based on each patient's therapeutic history and response to chemotherapeutic drugs, melphalan, topotecan, and/or carboplatin were used for IAC. The main outcomes included the technical success rate for IAC, survival rates, and adverse events. RESULTS: In total, 29 and 13 eyes received IAC as primary and secondary treatments, respectively. Catheterization was successful in 136 of 137 procedures. All eyes in the secondary IAC group had previously received intravenous chemotherapy. The mean number of IAC sessions for each eye was 3 (range, 2-6). The 2-year ocular survival rates were 80.7% (95% confidence interval [CI], 58.9-91.7) in the primary IAC group and 91.7% (95% CI, 53.9-98.8) in the secondary IAC group. During the follow-up period, 1 patient with unilateral disease (group E) developed extraocular disease and died. The 2-year recurrence-free survival rates in the primary and secondary IAC groups were 71.9% (95% CI, 49.4-85.7) and 75.0% (95% CI, 40.8-91.2), respectively. During each catheterization procedure, the main complications included eyelid erythema (2.4%), fundus hemorrhage (11.9%), myelosuppression (7.7%), transient vomiting and hair loss (2.6%), and transient pancytopenia (2.6%). Prolonged complications included phthisis bulbi (19.0%), vision loss (19.0%), poor vision (9.5%), and cataract (2.4%). There was no case of stroke, neurological impairment, secondary malignant tumor, or metastasis. CONCLUSIONS: Our findings suggest that IAC, whether primary or secondary, is effective and fairly safe for the management of advanced retinoblastoma in infants aged < 3 months. However, adverse events related to intra-arterial injection and the visual outcomes cannot be neglected and require further investigation.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Carboplatina/uso terapêutico , Etoposídeo/uso terapêutico , Infusões Intra-Arteriais/efeitos adversos , Neoplasias da Retina/tratamento farmacológico , Retinoblastoma/tratamento farmacológico , Vincristina/uso terapêutico , Antineoplásicos Fitogênicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/efeitos adversos , Cateterismo/efeitos adversos , Pré-Escolar , Etoposídeo/efeitos adversos , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Neoplasias da Retina/mortalidade , Retinoblastoma/mortalidade , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Vincristina/efeitos adversos
4.
J Neurointerv Surg ; 11(12): 1273-1276, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31197028

RESUMO

BACKGROUND: Intra-arterial chemotherapy has an increasingly prominent role in the management of retinoblastoma. One concern regarding this technique is procedural radiation exposure. OBJECTIVES: To examine the effects of our institution's procedural technique on fluoroscopy parameters for patients undergoing intra-arterial chemotherapy infusions for intraocular retinoblastoma. Secondary goals included describing the effect of anatomical variations of the carotid siphon and ophthalmic artery on radiation dose. METHODS: A retrospective review of pediatric patients with retinoblastoma referred to interventional neuroradiology for chemosurgery was performed. Techniques were classified as: A (1.2 Fr or 1.5 Fr microcatheter with continuous verapamil flush, advanced without guide through a 2 Fr sheath) or B (1.5 Fr or 1.7 Fr microcatheter advanced within a 4 Fr base catheter, through a 4 Fr sheath). Statistical analysis was performed to determine if there was a significant difference in fluoroscopy parameters based on technique or due to anatomical variation. RESULTS: 26 patients were treated with 94 intra-arterial chemotherapy infusions. 34 procedures were performed using technique A and 60 using technique B. Mean fluoroscopy time (4.75 min), fluoroscopy dose (23.3 mGy), and dose-area product (DAP; 85.2 µGy.m2) for technique A were significantly lower (p value <0.05) than for technique B, 14.0 min., 191 mGy, and 586 µGy.cm2, respectively. CONCLUSIONS: Microcatheter-only technique with continuous verapamil infusion resulted in decreased fluoroscopy times, DAP, and radiation doses at our institution for the treatment of intraocular retinoblastoma. Furthermore, our fluoroscopy times using this technique are the lowest reported in the current literature. Additionally, our anatomical analysis has demonstrated a positive correlation between increasing vessel tortuosity and fluoroscopy times.


Assuntos
Infusões Intra-Arteriais/métodos , Doses de Radiação , Neoplasias da Retina/tratamento farmacológico , Neoplasias da Retina/radioterapia , Retinoblastoma/tratamento farmacológico , Retinoblastoma/radioterapia , Pré-Escolar , Feminino , Fluoroscopia/métodos , Humanos , Lactente , Masculino , Artéria Oftálmica/diagnóstico por imagem , Exposição à Radiação/análise , Estudos Retrospectivos , Fatores de Tempo
5.
J Neurointerv Surg ; 11(12): 1266-1272, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31103993

RESUMO

BACKGROUND AND PURPOSE: Intra-arterial chemotherapy for retinoblastoma has been adopted as a first-line treatment option by numerous tertiary centers. The effect of intra-arterial chemotherapy on future rates of metastatic disease as well as on globe salvage in advanced eyes remains relatively unknown. METHODS: A search of PubMED, MEDLINE, EMBASE, and Web of Science electronic databases was conducted from inception until January 2019 for studies with a minimum of 10 patients reporting outcomes and complications following intra-arterial chemotherapy for retinoblastoma. RESULTS: A total of 20 studies met the inclusion criteria for analysis, comprising 873 patients and 1467 eyes. Only one study was comparative; there was substantial heterogeneity in reported outcomes and several overlapping patient cohorts that were published. Across all studies, 174 of 1467 eyes were enucleated (11.8%). Metastatic disease occurred in 8 of 513 patients (1.6%). Globe salvage was achieved in 318 of 906 (35.6%) cases of advanced retinoblastoma. The most common ocular complication was retinal detachment, occurring in 23% of eyes, and the most common systemic complications were transient fever and nausea/vomiting. CONCLUSIONS: There is a paucity of higher-level evidence with adequate follow-up surrounding the long-term safety of intra-arterial chemotherapy and effect on metastasis in retinoblastoma. Studies to date have been limited by short-term follow-up. Longitudinal prospective studies could provide greater insight into the ability of intra-arterial chemotherapy to reduce the risk of retinoblastoma metastasis.


Assuntos
Antineoplásicos/administração & dosagem , Infusões Intra-Arteriais/métodos , Neoplasias da Retina/tratamento farmacológico , Retinoblastoma/tratamento farmacológico , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Melfalan/administração & dosagem , Estudos Prospectivos , Neoplasias da Retina/diagnóstico , Retinoblastoma/diagnóstico , Estudos Retrospectivos , Terapia de Salvação/métodos
6.
Indian J Ophthalmol ; 67(6): 740-754, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31124482

RESUMO

Intra-arterial chemotherapy (IAC), also known as superselective ophthalmic artery chemotherapy or chemosurgery, is currently widely accepted as one of the primary treatment modalities for intraocular retinoblastoma worldwide. Following the introduction of the technique in 1998, IAC has evolved over the past decades to be safer and more effective. Accumulated evidence shows that IAC is more effective in providing eye salvage in group D and E retinoblastoma as compared to conventional systemic intravenous chemotherapy (IVC). In contrast to IVC, IAC has the added benefits of reduced overall treatment duration and minimal systemic toxicity. This review provides a comprehensive update on the history, technique, indications, contraindications, and outcome of IAC. We have also identified the strengths, weaknesses, opportunities and threats (SWOT analysis) of the technique in this review.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias da Retina/tratamento farmacológico , Retinoblastoma/tratamento farmacológico , Humanos , Injeções Intra-Arteriais , Artéria Oftálmica
7.
JAMA Ophthalmol ; 137(7): 834-837, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31046111

RESUMO

Importance: Bilateral diffuse uveal melanocytic proliferation is a rare sign of several systemic malignant neoplasms. Observations: A patient presenting with uveal melanocytic proliferation underwent a detailed physical examination and extensive imaging. No systemic malignant neoplasm was found. Chorioretinal biopsy was performed, and its immunohistochemical results revealed the presence of primary vitreoretinal lymphoma. Conclusions and Relevance: This patient's results suggest that diffuse uveal melanocytic proliferation may be associated not just with systemic malignant disease, but also with primary intraocular tumors, in this case a primary vitreoretinal lymphoma.


Assuntos
Proliferação de Células , Linfoma Difuso de Grandes Células B/patologia , Melanócitos/patologia , Síndromes Paraneoplásicas Oculares/patologia , Neoplasias da Retina/patologia , Úvea/patologia , Corpo Vítreo/patologia , Antimetabólitos Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/metabolismo , Feminino , Angiofluoresceinografia , Humanos , Infusões Intravenosas , Injeções Intravítreas , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/metabolismo , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Proteínas de Neoplasias/metabolismo , Síndromes Paraneoplásicas Oculares/tratamento farmacológico , Síndromes Paraneoplásicas Oculares/metabolismo , Neoplasias da Retina/tratamento farmacológico , Neoplasias da Retina/metabolismo , Tomografia de Coerência Óptica , Acuidade Visual/fisiologia , Corpo Vítreo/efeitos dos fármacos , Corpo Vítreo/metabolismo
8.
Invest Ophthalmol Vis Sci ; 60(5): 1696-1705, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-31009525

RESUMO

Purpose: The goal of this work was to design and assess the ability of unmodified and surface-modified poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) to enhance cell association, provide efficacy in retinoblastoma cells, and overcome current administration challenges, including hydrolysis and precipitation, of intravitreal administration. Methods: A single emulsion method was used to encapsulate Coumarin 6, to enable NP visualization via fluorescence microscopy. Melphalan NPs were synthesized using an adapted double-emulsion method to reduce melphalan loss during fabrication. Melphalan loading and release were quantified against a free melphalan standard. The cellular association and internalization of unmodified and surface-modified NPs were determined using flow cytometry, and the efficacy of melphalan NPs was quantified in retinoblastoma cells. Results: The highest cell association was observed with TET1 and MPG-NPs after 24 hours administration; however, a significant fraction of NPs were associated with the cell surface, instead of undergoing internalization. MPG-NPs fabricated with the low saturation process were most efficacious, while all surface-modified NPs improved efficacy relative to unmodified NPs when formulated using the highly saturated process. Similar effects were observed as a function of NP dose, with TET1 and MPG-NPs particularly efficacious. Conclusions: Surface-modified NPs achieved enhanced association and efficacy in retinoblastoma cells relative to unmodified NPs, with MPG and surface-modified NPs exhibiting the strongest efficacy relative to other NP groups. In future work we seek to assess the ability of these NPs to improve transport in the vitreous, where we expect a more dramatic impact on efficacy as a function of surface modification.


Assuntos
Antineoplásicos Alquilantes/administração & dosagem , Sistemas de Liberação de Medicamentos , Melfalan/administração & dosagem , Nanopartículas/química , Neoplasias da Retina/tratamento farmacológico , Retinoblastoma/tratamento farmacológico , Cumarínicos/química , Citometria de Fluxo , Humanos , Injeções Intravítreas , Microscopia Eletrônica de Varredura , Tamanho da Partícula , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Tiazóis/química , Células Tumorais Cultivadas
9.
Ophthalmic Surg Lasers Imaging Retina ; 50(4): 248-252, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30998248

RESUMO

A 35-month-old boy was diagnosed with retinoblastoma and underwent combination intra-arterial (IAC) and intravitreal chemotherapy. His course was complicated by anaphylactic reaction to IAC, yet he continued to improve with sustained intravitreal therapy. Eight months into treatment, the affected eye developed exudative retinal detachment, which resolved with sub-Tenon's steroid administration. As the management of retinoblastoma evolves, treaters need to be aware of potential complications of therapy. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:248-252.].


Assuntos
Melfalan/efeitos adversos , Descolamento Retiniano/induzido quimicamente , Neoplasias da Retina/tratamento farmacológico , Retinoblastoma/tratamento farmacológico , Topotecan/efeitos adversos , Antineoplásicos Alquilantes/administração & dosagem , Antineoplásicos Alquilantes/efeitos adversos , Pré-Escolar , Quimioterapia Combinada , Angiofluoresceinografia/métodos , Seguimentos , Fundo de Olho , Humanos , Injeções Intraoculares , Injeções Intravítreas , Macula Lutea/diagnóstico por imagem , Masculino , Melfalan/administração & dosagem , Descolamento Retiniano/diagnóstico , Descolamento Retiniano/tratamento farmacológico , Neoplasias da Retina/diagnóstico , Retinoblastoma/diagnóstico , Inibidores da Topoisomerase I/administração & dosagem , Inibidores da Topoisomerase I/efeitos adversos , Topotecan/administração & dosagem , Triancinolona Acetonida/administração & dosagem , Ultrassonografia
10.
Interv Neuroradiol ; 25(5): 556-561, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30931673

RESUMO

OBJECTIVE: Intra-arterial chemotherapy (IAC) is now the first line treatment for selected patients with retinoblastoma (Rb). Typically, IAC is infused following the selective catheterization of the ophthalmic artery (OA) on the affected side. However, in some patients, the OA alone may not provide vascular supply to the tumor, whereas in other instances the efficacy of IAC could be compromised due to the presence of prominent collateral vessels from the external carotid artery (ECA). We report our experience with catheterizing vessels other than the OA for IAC treatment for Rb. METHODS: After institutional review board approval, a retrospective analysis was conducted of electronic medical records and imaging of our Rb population. RESULTS: We identified 13 patients who received IAC for Rb treatment. Of these, five patients required alternative methods of chemotherapy delivery other than through the OA, totaling 17 treatments. Two patients needed balloon-assisted occlusion of the ECA, two patients required selective catheterization of the middle meningeal artery, and one patient had no internal carotid artery supply to the choroidal blush, thus the superficial temporal artery provided access for IAC. Total globe salvage rate was 76% and 80% with the alternative route subset. CONCLUSIONS: Alternatives to the OA may be necessary to deliver IAC for selected cases of Rb. These routes can be safe and effective. However, thorough understanding of the orbital blood supply is essential. Whether these alternative IAC methods result in similar outcomes to OA infusions has not been established.


Assuntos
Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Neoplasias da Retina/tratamento farmacológico , Retinoblastoma/tratamento farmacológico , Antineoplásicos/efeitos adversos , Oclusão com Balão , Artéria Carótida Externa , Cateterismo , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Infusões Intra-Arteriais , Masculino , Artérias Meníngeas , Artéria Oftálmica , Órbita/irrigação sanguínea , Estudos Retrospectivos , Resultado do Tratamento
13.
Invest Ophthalmol Vis Sci ; 60(4): 954-964, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30882851

RESUMO

Purpose: To use our intra-arterial chemotherapy (IAC) rabbit model to assess the impact of IAC procedure, drug, dose, and choice of technique on ocular structure and function, to study the nature and etiology of IAC toxicity, and to compare to observations in patients. Methods: Rabbits received IAC melphalan (0.4-0.8 mg/kg), carboplatin (25-50 mg), or saline, either by direct ophthalmic artery cannulation, or with a technique emulating nonocclusion. Ocular structure/function were assessed with examination, electroretinography (ERG), fundus photography, fluorescein angiography, optical coherence tomography (OCT), and OCT angiography, prior to and 5 to 6 weeks after IAC. Blood counts were obtained weekly. We reviewed our last 50 IAC treatments in patients for evidence of ocular or systemic complications. Results: No toxicity was seen in the saline control group. With standard (0.4 mg/kg) melphalan, no vascular/microvascular abnormalities were seen with either technique. However, severe microvascular pruning and arteriolar occlusions were seen occasionally at 0.8 mg/kg doses. ERG reductions were dose-dependent. Histology showed melphalan dose-dependent degeneration in all retinal layers, restricted geographically to areas of greatest vascular density. Carboplatin caused massive edema of ocular/periocular structures. IAC patients experienced occasional periocular swelling/rash, and only rarely experienced retinopathy or vascular events/hemorrhage in eyes treated multiple times with triple (melphalan/carboplatin/topotecan) therapy. Transient neutropenia occurred after 46% of IAC procedures, generally after triple therapy. Conclusions: IAC toxicity appears to be related to the specific drug being used and is dose-dependent, rather than related to the IAC procedure itself or the specific technique selected. These rabbit findings are corroborated by our clinical findings in patients.


Assuntos
Antineoplásicos Alquilantes/toxicidade , Antineoplásicos/toxicidade , Carboplatina/toxicidade , Infusões Intra-Arteriais/métodos , Melfalan/toxicidade , Doenças Retinianas/induzido quimicamente , Vasos Retinianos/efeitos dos fármacos , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos Alquilantes/administração & dosagem , Carboplatina/administração & dosagem , Relação Dose-Resposta a Droga , Eletrorretinografia , Feminino , Angiofluoresceinografia , Humanos , Lactente , Masculino , Melfalan/administração & dosagem , Modelos Animais , Artéria Oftálmica/efeitos dos fármacos , Coelhos , Retina/fisiopatologia , Doenças Retinianas/fisiopatologia , Neoplasias da Retina/tratamento farmacológico , Vasos Retinianos/fisiopatologia , Retinoblastoma/tratamento farmacológico , Estudos Retrospectivos , Tomografia de Coerência Óptica
15.
Asia Pac J Ophthalmol (Phila) ; 8(3): 211-217, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30714357

RESUMO

PURPOSE: To study the safety and efficacy of intra-arterial chemotherapy (IAC) as a treatment for intraocular retinoblastoma in Thailand. DESIGN: Retrospective, interventional case series. METHODS: In this study, IAC was performed as primary or secondary treatment for patients with intraocular retinoblastoma using melphalan with or without additional topotecan or carboplatin. Survival rate, globe salvage rate, and treatment complications were recorded and analyzed. RESULTS: Of 27 eyes of 26 patients with retinoblastoma, 7 (26%) had IAC as primary treatment and 20 (74%) had IAC as secondary treatment. The eyes were classified by International Classification of Retinoblastoma (ICRB) as group B (n = 3, 11%), group C (n = 1, 4%), group D (n = 12, 44%), and group E (n = 11, 41%). Catheterization was successful in 75 (94%) of 80 sessions. The median number of IAC sessions was 3 (range, 1-7). At a mean follow-up of 32 months (range, 3-95 months), the overall globe salvage rate was 52%, with 100% in groups B and C, 75% in group D, and 9% in group E. Complications of IAC included occlusive vasculopathy (n = 4, 15%), vitreous hemorrhage (n = 3, 11%), retinal artery precipitation (n = 2, 7%), strabismus (n = 2, 7%), and transient ischemic attack (n = 1, 4%). The overall survival rate was 96% (n = 25). CONCLUSIONS: Our experience suggests that IAC is a safe and effective treatment for patients with ICRB group B, C, D, and some group E retinoblastoma. Careful patient selection and experienced surgeons are critical for achieving the best treatment outcome.


Assuntos
Carboplatina/administração & dosagem , Melfalan/administração & dosagem , Retina/diagnóstico por imagem , Neoplasias da Retina/tratamento farmacológico , Retinoblastoma/tratamento farmacológico , Centros de Atenção Terciária , Topotecan/administração & dosagem , Adolescente , Adulto , Cateterismo Periférico , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Angiofluoresceinografia , Seguimentos , Fundo de Olho , Humanos , Incidência , Infusões Intra-Arteriais , Masculino , Pessoa de Meia-Idade , Oftalmoscopia , Neoplasias da Retina/diagnóstico , Neoplasias da Retina/epidemiologia , Retinoblastoma/diagnóstico , Retinoblastoma/epidemiologia , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Tailândia/epidemiologia , Fatores de Tempo , Ultrassonografia , Adulto Jovem
16.
BMC Ophthalmol ; 19(1): 61, 2019 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-30808420

RESUMO

BACKGROUND: To evaluate the efficacy, complications, and clinical characteristics, including the ocular toxicity, of intravitreal melphalan(IVM) treatment for vitreous seeding in Chinese retinoblastoma patients. METHODS: This was a retrospective, non-comparative analysis including 30 consecutive eyes of 23 patients with viable persistent or recurrent vitreous seeding following retinoblastoma treatment. All of the eyes received IVM injections (20-33 µg). Vitreous seeding control, determination of the ocular toxicity, and the clinical characteristics of intravitreal melphalan treatments were observed. RESULTS: The mean patient age at the time of the injection was 28 months (median = 22 months, range = 12-50 months). In total, 80 injections were administered in 30 eyes, the overall enucleation-free survival rate was 83.3% (25/30). The complications included retinal pigment epithelium (RPE) and choroidal atrophy (19/30, 63.3%), pupillary synechiae (13/30, 43.3%), iris atrophy (12/30, 40%), retinal vascular occlusion (12/30, 40.0%), optic atrophy (6/30, 20%), vitreous hemorrhage (3/30, 10%), persistent hypotonia and phthisis bulbi (4/30 13.3%), and cataracts (8/30, 26.6%). Twelve eyes demonstrated grade 3 or greater IVM-associated retinal or anterior segment toxicity post injection. Mean dosage given showed significant difference between the groups. There were no significant differences in the retinal toxicity grades regarding the seed classification or seed regression patterns. CONCLUSIONS: Intravitreal melphalan is an effective treatment for refractory vitreous seeding from retinoblastoma, but exhibits both anterior and posterior segment toxicity in Chinese patients.


Assuntos
Antineoplásicos Alquilantes/efeitos adversos , Melfalan/efeitos adversos , Neoplasias da Retina/tratamento farmacológico , Retinoblastoma/tratamento farmacológico , Antineoplásicos Alquilantes/uso terapêutico , Pré-Escolar , Feminino , Humanos , Lactente , Injeções Intravítreas , Masculino , Melfalan/uso terapêutico , Inoculação de Neoplasia , Estudos Retrospectivos , Corpo Vítreo/efeitos dos fármacos
17.
PLoS One ; 14(1): e0210647, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30650131

RESUMO

IMPORTANCE: Predictions of visual outcomes are useful in clinical and family decisions regarding treatment for retinoblastoma. Very little has been published on the association of post-treatment visual acuity with pre-treatment electroretinography (ERG), which can be performed on infants too young to reliably quantify visual acuity. OBJECTIVE: To report associations of pre-treatment ERG with post-treatment visual acuity in eyes with advanced retinoblastoma treated with ophthalmic artery chemosurgery (OAC). DESIGN: Retrospective case-control study of eyes treated from 2006 through 2017, with mean follow-up of 51 months (range 2.3-150 months). SETTING: Single large academic center. PARTICIPANTS: Group D and E eyes treated with OAC at Memorial Sloan Kettering Cancer Center with recorded visual acuity and ERG (30Hz flicker). MAIN OUTCOME AND MEASURE: Snellen visual acuity (uncorrected) compared to initial 30Hz flicker ERG. RESULTS: This study included 157 Group D and E eyes. Results of the Jonckheere-Terpstra test for trend were statistically significant and indicated that eyes with lower pre-treatment ERG readings tended to have more visual impairment post-treatment. Among eyes with initial ERG 75+ µV, 11 of 32 eyes (34%) had visual acuity 20/40 or better. Among eyes with ERG 0 µV, 44 of 46 (96%) had visual acuity of 20/200 or worse. CONCLUSIONS AND RELEVANCE: Eyes with advanced intraocular retinoblastoma treated with OAC can achieve excellent visual acuity, but poor ERG at initial visit is associated with poor visual acuity after treatment in the majority of eyes. Expectations regarding visual potential may influence decisions about treatment.


Assuntos
Eletrorretinografia/métodos , Neoplasias da Retina/diagnóstico por imagem , Neoplasias da Retina/cirurgia , Retinoblastoma/diagnóstico por imagem , Retinoblastoma/cirurgia , Carboplatina/uso terapêutico , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Melfalan/uso terapêutico , Neoplasias da Retina/tratamento farmacológico , Retinoblastoma/tratamento farmacológico , Estudos Retrospectivos , Topotecan/uso terapêutico , Acuidade Visual/fisiologia
18.
Curr Top Med Chem ; 19(17): 1535-1544, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30659544

RESUMO

Retinoblastoma is the intraocular malignancy that occurs during early childhood. The current standard of care includes chemotherapy followed by focal consolidative therapies, and enucleation. Unfortunately, these are associated with many side and late effects. New drugs and/or drug combinations need to be developed for safe and effective treatment. This compelling need stimulated efforts to explore drug repurposing for retinoblastoma. While conventional drug development is a lengthy and expensive process, drug repurposing is a faster, alternate approach, where an existing drug, not meant for treating cancer, can be repurposed to treat retinoblastoma. The present article reviews various attempts to test drugs approved for different purposes such as calcium channels blockers, non-steroidal antiinflammatory drugs, cardenolides, antidiabetic, antibiotics and antimalarial for treating retinoblastoma. It also discusses other promising candidates that could be explored for repurposing for retinoblastoma.


Assuntos
Antineoplásicos/uso terapêutico , Reposicionamento de Medicamentos , Neoplasias da Retina/tratamento farmacológico , Retinoblastoma/tratamento farmacológico , Antibacterianos/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Antimaláricos/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Cardenolídeos/uso terapêutico , Humanos , Hipoglicemiantes/uso terapêutico
19.
Interv Neuroradiol ; 25(3): 335-337, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30486724

RESUMO

We report the intentional occlusion of the middle meningeal artery arising from the lacrimal artery, a novel technique to improve drug delivery in a 14-month-old boy with a history of right sporadic unilateral cavitary retinoblastoma group D. The patient was referred to our institution for intra-arterial chemotherapy after two systemic chemotherapy treatments. The digital subtraction angiography showed a large middle meningeal artery arising from the right lacrimal artery and decrease choroidal enhancement thus decreased flow to the tumor. The ophthalmological examination after the first intra-arterial chemotherapy observed no tumor regression. Assuming a vascular steal, in the second intra-arterial chemotherapy session, the origin of the middle meningeal artery was occluded. Following this treatment, a significant response was observed at ophthalmological follow up. In the presented case, the efficacy of intra-arterial chemotherapy was improved after occlusion of a meningeal branch arising from the lacrimal artery, which was responsible for the vascular steal.


Assuntos
Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Infusões Intra-Arteriais/métodos , Artérias Meníngeas/cirurgia , Neoplasias da Retina/tratamento farmacológico , Retinoblastoma/tratamento farmacológico , Angiografia Digital , Humanos , Lactente , Imagem por Ressonância Magnética Intervencionista , Masculino , Resultado do Tratamento
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