A 10-year retrospective study on the presentation, treatment, and outcomes of retinoblastoma patients in a Philippine Tertiary Hospital

Objective@#This study reported the demographic profile, clinical presentation, treatment, and outcomes of retinoblastoma (RB) patients seen at Jose R. Reyes Memorial Medical Center (JRRMMC) from January 2011 to December 2020.@*Methods@#This was a single-center, retrospective study. Medical records of patients diagnosed with RB at JRRMMC from January 2011 to December 2020 were reviewed. Descriptive statistics were used to summarize the characteristics of the participants.@*Results@#A total of 31 confirmed RB cases were seen, with almost half residing outside Metro Manila (52%). The median age at diagnosis was 2 years, with a slight male predominance (55%). Majority (81%) of patients had unilateral presentation, with leukocoria as the most common sign (19%) prompting consult. Nearly half (43%) of 37 eyes were diagnosed as Group E using the International Classification of Retinoblastoma (ICRB) system. Majority were in the advanced stage; 57% of eyes underwent enucleation and 29, 3 and 3% of patients required additional treatments such as chemotherapy, laser, and radiotherapy, respectively. RB was confirmed in 20 eyes (54%) through histopathology. Survival outcomes showed that 4 patients (13%) were alive, with either completed or ongoing treatment, and 19 (61%) did not complete prescribed management or were lost to follow-up. There were 8 (26%) known deaths.@*Conclusion@#Majority of cases were unilateral and at an advanced stage needing enucleation which may indicate low levels of awareness and screening efforts. Survival rates are difficult to ascertain due to patients abandoning treatment that may be attributed to limited social service support. The study reflects the 10-year data prior to the establishment of a collaborative, multispecialty RB team in the institution and exposes various areas that need to be addressed to improve clinical outcomes.

The effect of lncRNA ADPGK-AS1 on the proliferation and apoptosis of retinoblastoma cells by targeting miR-200b-5p / 中华肿瘤杂志

Objective: To explore the effect of lncRNA ADPGK-AS1 on the proliferation and apoptosis of retinoblastoma cells and its possible mechanism. Methods: The tumor tissues of 31 patients with retinoblastoma admitted to Henan Provincial Eye Hospital from February to June 2020 and their corresponding normal tissues adjacent to the cancer were collected. The expression levels of lncRNA ADPGK-AS1 and miR-200b-5p in retinoblastoma tissues and normal adjacent tissues were detected by real-time fluorescence quantitative polymerase chain reaction (qRT-PCR). Human retinal epithelial cell ARPE-19, human retinoblastoma cell Y-79 and WERI-Rb-1 were cultured in vitro. The expression levels of lncRNA ADPGK-AS1 and miR-200b-5p were detected by qRT-PCR. Y-79 cells were randomly divided into si-con group, si-lncRNA ADPGK-AS1 group, miR con group, miR-200b-5p group, si-lncRNA ADPGK-AS1+ anti-miR con group, and si-lncRNA ADPGK-AS1+ anti-miR-200b-5p group. The proliferation, cloning and apoptosis of cells in each group were detected by tetramethylazol blue method, plate cloning test and flow cytometry, respectively. The targeting relationship between lncRNA ADPGK-AS1 and miR-200b-5p was detected by double luciferase report test, and the expression level of cleaved-caspase-3 protein was detected by western blot. Results: Compared with the adjacent tissues, the expression of lncRNA ADPGK-AS1 in retinoblastoma tissues was increased (P<0.05), while the expression of miR-200b-5p was decreased (P<0.05). Compared with ARPE-19 cells, the expression of lncRNA ADPGK-AS1 in Y-79 and WERI-Rb-1 cells was increased (P<0.05), while the expression of miR-200b-5p was decreased (P<0.05). Compared with the si-con group, the cell viability of the si-lncRNA ADPGK-AS1 group was reduced (1.06±0.09 vs 0.53±0.05, P<0.05), the number of cell clone formation was reduced (114.00±8.03 vs 57.00±4.13, P<0.05), while the apoptosis rate [(7.93±0.68)% vs (25.43±1.94)%] and the protein level of cleaved-caspase-3 were increased (P<0.05). Compared with the miR-con group, the cell viability of the miR-200b-5p group was decreased (1.05±0.08 vs 0.57±0.05, P<0.05), the number of cell clone formation was decreased (118.00±10.02 vs 64.00±5.13, P<0.05), while the apoptosis rate [(7.89±0.71)% vs (23.15±1.62)%] and the protein level of cleaved-caspase-3 were increased (P<0.05). lncRNA ADPGK-AS1 could target the expression of miR-200b-5p. Compared with the si-lncRNA ADPGK-AS1+ anti-miR-con group, cell viability of the si-lncRNA ADPGK-AS1+ anti-miR-200b-5p group was increased (0.53±0.04 vs 1.25±0.10, P<0.05), and the number of cell clones was increased (54.00±4.39 vs 125.00±10.03, P<0.05), while the rate of apoptosis [(25.38±1.53)% vs (9.76±0.71)%] and the protein level of cleaved-caspase-3 were decreased (P<0.05). Conclusion: Interfering with the expression of lncRNA ADPGK-AS1 could inhibit the proliferation and clone formation and induce apoptosis of retinoblastoma cells by targeting the expression of miR-200b-5p.

Perfil Clínico-Epidemiológico e Sobrevida dos Casos de Retinoblastoma em um Hospital Referência em Oncologia do Estado de Goiás / Clinical-Epidemiological Profile and Survival of the Cases of Retinoblastoma in a Reference Hospital in Oncology in the State of Goiás / Perfil Clínico-Epidemiológico y Sobrevida de los Casos de Retinoblastoma en un Hospital de Referencia en Oncología del Estado de Goiás

Introdução: O retinoblastoma é a malignidade primária intraocular mais comum na infância, é raro e corresponde de 2% a 4% dos tumores malignos pediátricos. Objetivo: Descrever o perfil clínico-epidemiológico e a sobrevida dos casos de retinoblastoma em um hospital de referência em oncologia do Estado de Goiás, entre 2008 a 2014. Método: Estudo observacional analítico do tipo transversal, construído com base na análise de prontuários de pacientes diagnosticados com retinoblastoma entre 2008 e 2014. Realizaram-se análises por estatística descritiva e teste de associação qui-quadrado. Adotou-se o nível de significância de 5%. A sobrevida foi avaliada por meio do método de Kaplan-Meier. Resultados: Foram atendidos 55 pacientes com retinoblastoma, permitindo identificar o predomínio do sexo feminino (54,5%); na faixa etária de 1 a 4 anos (27,3%); com etnia parda (50,9%). As características clínicas mais prevalentes foram: acometimento intraocular (74,5%); unilateral (65,5%); sem histórico familiar (56,4%); e com sinal clínico de leucocoria (80%). A maioria não apresentou metástases ao diagnóstico (87,3%), sendo o principal tratamento a enucleação unilateral (72,7%). Verificou-se associação quanto à evolução clínica do paciente em relação à localização extraocular (p = 0,001), presença de metástase (p = 0,001) e estádio IV de Chantada et al. (p = 0,001). Pacientes classificados como E foram submetidos a maior número de enucleações (olho direito ­ p = 0,05 e olho esquerdo ­ p = 0,001). A sobrevida global em cinco anos foi de 72,7%. Conclusão: Tais achados são relevantes para o planejamento de ações de prevenção, pois o diagnóstico precoce é um dos principais aliados na determinação da cura e na preservação da visão.

Introduction: Retinoblastoma is the most common intraocular primary malignancy in childhood, it is rare and accounts for 2% to 4% of pediatric malignant tumors. Objective: To describe the clinical-epidemiological profile and survival of cases of retinoblastoma in a reference hospital in oncology in the state of Goiás, between 2008 and 2014. Method: Crosssectional analytical observational study built from the analysis of medical records of patients diagnosed with retinoblastoma between 2008 and 2014. Analyzes were performed using descriptive statistics and chi-square association test. A significance level of 5% was adopted. Survival was assessed using the Kaplan-Meier method. Results: 55 patients with retinoblastoma were treated, with predominance of females (54.5%), in the age group of 1 to 4 years (27.3%) and of brown ethnicity (50.9%). The most prevalent clinical characteristics were intraocular involvement (74.5%), unilateral (65.5%), with no family history (56.4%) and with clinical signs of leukocoria (80%). Most of them did not present metastases at diagnosis (87.3%), the main treatment being unilateral enucleation (72.7%). Association between the clinical evolution of the patient and extraocular location (p = 0.001) was found, presence of metastasis (p = 0.001), and stage IV classified by Chantada et al. (p = 0.001). Patients classified as E were submitted to higher volume of enucleation (right eye ­ p = 0.05 and left eye ­ p = 0.001). The 5-year overall survival was 72.7%. Conclusion: These findings are relevant for planning preventive actions, as early diagnosis is one of the main allies in determining the cure and preserving vision

Introducción: El retinoblastoma es la neoplasia maligna primaria intraocular más frecuente en la infancia, es raro y corresponde del 2% al 4% de los tumores malignos pediátricos. Objetivo: Describir el perfil clínicoepidemiológico y la sobrevida de los casos de retinoblastoma en un hospital de referencia en oncología en el Estado de Goiás, entre 2008 y 2014. Método: Estudio observacional analítico transversal, construido a partir del análisis de las historias clínicas de los pacientes diagnosticados con retinoblastoma entre 2008 y 2014. Los análisis se realizaron mediante estadística descriptiva y prueba de asociación ji cuadrada. Se adoptó un nivel de significancia del 5%. La sobrevida se evaluó mediante el método de Kaplan-Meier. Resultados: Fueron tratados 55 pacientes con retinoblastoma, lo que permitió identificar un predominio femenino (54,5%); en el grupo de edad de 1 a 4 años (27,3%); con etnia parda (50,9%). Las características clínicas más prevalentes fueron: afectación intraocular (74,5%); unilateral (65,5%); y sin antecedentes familiares (56,4%) y con signos clínicos de leucocoria (80%). La mayoría no presentaba metástasis al diagnóstico (87,3%); siendo el principal tratamiento la enucleación unilateral (72,7%). Hubo asociación entre la evolución clínica del paciente y la localización extraocular (p = 0,001), presencia de metástasis (p = 0,001) y estadio IV de Chantada et al. (p = 0,001). Los pacientes clasificados como E tenían más ojos enucleados (ojo derecho ­ p = 0,05 y ojo izquierdo ­ p = 0,001). La sobrevida global a los 5 años fue del 72,7%. Conclusión: Estos hallazgos son relevantes para la planificación de acciones preventivas, ya que el diagnóstico precoz es uno de los principales aliados para determinar la cura y preservar la visión.

Ocular cysticercosis in pediatric patient / Cisticercose ocular em paciente pediátrico

ABSTRACT Ocular cysticercosis is a parasitic infection caused by Taenia solium. Its early diagnosis and treatment decreases the possibility of visual morbidity. It can either compromise the anterior chamber or the posterior segment, which translates into an very variable and interspecific presentation that changes depending on the site of the infection. It is important to report this case due to its low presentation rate and the fact that a high suspicion index is required to make an assertive and timely diagnosis. This is especially important in geographical areas that are endemic to this parasite due to the direct relationship between an early diagnosis and treatment and better visual outcomes. In this case report, we will discuss the multidisciplinary interventions of a pediatric patient in a high complexity hospital.

RESUMO A cisticercose ocular é uma infecção parasitária causada pela Taenia solium. O diagnóstico e tratamento precoces diminuem a possibilidade de morbidade visual. Ela pode comprometer a câmara anterior ou o segmento posterior, o que se traduz em uma apresentação muito variável e interespecífica, que muda dependendo do local da infecção. É importante relatar esse caso devido à sua baixa taxa de apresentação e ao fato de que é necessário um alto índice de suspeita para fazer um diagnóstico assertivo e oportuno. Isso é especialmente importante em áreas geográficas endêmicas para esse parasita, devido à relação direta entre diagnóstico e tratamento precoces e melhores resultados visuais. Neste relato de caso, discutiremos as intervenções multidisciplinares de um paciente pediátrico em um hospital de alta complexidade.

Enucleated pseudoretinoblastoma: A six-year review from a Philippine Center

Objectives@#To evaluate the prevalence, etiologies, demographics, and clinical presentation of enucleated pseudoretinoblastoma. @*Methods@#This retrospective study reviewed ocular pathology records of enucleated globes with clinically diagnosed or suspected retinoblastoma submitted to a public university ocular pathology laboratory from 2013 to 2018. Hematoxylin-eosin-stained sections of pseudoretinoblastoma cases were reevaluated, and additional clinical data were taken from hospital charts.@*Results@#Of the 211 enucleated eyes with clinically diagnosed or suspected retinoblastoma, 202 (95.7%) had histologically confirmed retinoblastoma, while 9 (4.3%) had pseudoretinoblastoma. The most common ocular conditions mimicking retinoblastoma were retinal dysplasia (2 eyes) and persistent fetal vasculature (2 eyes). The pseudoretinoblastoma group consisted of 4 females and 5 males, and enucleated were 6 right eyes and 3 left eyes. The mean age at the time of enucleation was 3.65 years, and the mean symptom duration was 17.36 months. Leukocoria, which was noted in 4 patients, was the most frequent initial symptom. No significant difference between the pseudoretinoblastoma group and the retinoblastoma group were found in terms of sex, laterality of the enucleated eye, age at the time of enucleation, and symptom duration.@*Conclusion@#In this retrospective review, the prevalence of pseudoretinoblastoma in enucleated globes clinically suspected or diagnosed with retinoblastoma was 4.3%. Persistent fetal vasculature and retinal dysplasia were the most common pseudoretinoblastomas. Clinicians should perform a thorough clinical evaluation and judiciously utilize the available diagnostic means to differentiate retinoblastoma from pseudoretinoblastoma.

Intravitreous chemotherapy as adjuvant rteatment for vitreous seeding in retinoblastoma: A Philippine tertiary hospital experience

Background@#Intravitreal chemotherapy has been an effective addition in treating vitreous seeding in retinoblastoma. However, it was only in 2020 that it was used in the Philippines. There is no literature on its use in multiple Filipino retinoblastoma patients. @*Objectives@#To describe the clinical course of the four patients who are the first to undergo intravitreal chemotherapy for vitreous seeding of retinoblastoma in the Philippine tertiary hospital.@*Methods@#A case series of four eyes of four patients with retinoblastoma who underwent intravitreous injection of melphalan and topotecan for vitreous seeding at the Department of Ophthalmology and Visual Sciences of a Philippine tertiary hospital. @*Results@#Two eyes, with International Intraocular Retinoblastoma Classification (IIRC) Group C with vitreous seeding, responded well to intravitreous melphalan and topotecan. One eye had recurrent vitreous seeding despite 10 intravitreal injections. One eye with IIRC Group E, did not respond to intravitreous chemotherapy and was eventually enucleated. This is the first case series on the local use of intravitreous chemotherapy in the country for vitreous seeding in retinoblastoma. The control of 50% achieved in this case series is lower than in other series due to longer treatment interval from poor follow-up and the presence of advanced disease.@*Conclusion@#The use of intravitreous melphalan and topotecan can be an effective adjuvant for systemic chemotherapy in controlling vitreous seeding in eyes with IIRC Group C. It is not effective in controlling IIRC Group E disease.

Capacity to treat retinoblastoma in the Philippines

Objective@#This study determined the capacity to treat retinoblastoma (RB) in the Philippines.@*Method@#This was a cross-sectional study which included all Department of Health (DOH) hospitals and all government and private tertiary hospitals in the Philippines. An online modified questionnaire taken from the St. Jude Children’s Research Hospital study on RB assessment was emailed to 143 hospitals in all 17 regions. Primary outcome measures were human resources capacity, treatment capacity and education and network capacity. Availability, frequency and confidence of use were assessed for treatment capacity. An asset-based tier classification of hospitals was created based on the human resources capacity and treatment capacity.@*Results@#This assessment survey had a 49% response rate. There were 3 regions that had zero correspondence. A general ophthalmologist, a subspecialized ophthalmologist, and a general pathologist were the most available physicians in the management of RB. Almost all respondents had the necessary diagnostic technology in their hospitals, but frequency and confidence of use were low. A quarter of the respondents (23%) used a standardized treatment protocol, while only 26% had established a referral network in their area. Tier classification was able to differentiate capacities for particular resources only. Only 23% of the participating hospitals have the capacity to treat RB through its trained human resources, available diagnostic and treatment technology, and education and network programs. Distribution of hospitals identified as tier I, II and III were 18%, 8%, and 41%, respectively.@*Conclusion@#Capacity to treat RB in the Philippines is evident only in a few hospitals, majority of which are located in the National Capital Region. However, tier 3 hospitals were identified in 10 other regions, making accessibility to RB care possible to patients in the provinces. Although human resource and technology are made available, utilization of these resources is low in many hospitals for the management of RB. Clinical practice guidelines for RB is still lacking. Connecting the different tiers in each region as a form of referral network can improve capacity and management of RB.

Treatment outcomes of retinoblastoma patients at a Tertiary Government Hospital in the Philippines

Objective@#This study determined the treatment outcomes of patients with retinoblastoma seen at a Philippine tertiary government hospital from January 2000 to January 2020.@*Method@#This is a cohort study. Medical records of patients with histopathologic-proven retinoblastoma were reviewed and pertinent information on clinical profile and presentation, treatment and outcomes were recorded.@*Results@#This study included 118 patients (146 eyes) with mean age at symptom onset of 7.4 + 6.6 months and mean age at consult of 11.5 + 13.7 months. There were 69 (47%) eyes with International Classification of Retinoblastoma (ICRB) stage E. The most common primary treatment was enucleation (n=137, 94%). The most common high-risk histopathologic feature was involvement of the optic nerve at the cut-end section (n=27, 34%). Only 14 patients (11%) completed treatment with median follow-up of 30.5 months (range 4- 122). @*Conclusion@#The rate of overall survival of patients with retinoblastoma is low in this study, similar to other developing countries. This can be due to higher proportion of patients with advanced stage at presentation and lower percentage of treatment completion. Early diagnosis and treatment may lead to better survival rate, visual outcome and quality of life. Due to limited data on follow-up, globe preservation could not be determined.

Sociodemographic, clinical, epidemiological and care aspects of children and adolescents treated for retinoblastoma in Brazil: a cross-sectional study / Aspectos sociodemográficos, clínicos, epidemiológicos e assistenciais de crianças e adolescentes atendidos por retinoblastoma no Brasil: estudo transversal

Introduction: Retinoblastoma greatly impacts the affected children and adolescents and their families. Epidemiological approaches to this form of cancer in Brazil are scarce, and this gap motivated this study. Objectives:This study aimed to describe the sociodemographic, clinical, epidemiological, and care characteristics of children and adolescents treated for retinoblastoma in Brazil and analyze whether there is any association between them. Methods: It is a cross-sectional, descriptive-analytical study, carried out with accompanying family members of children and adolescents treated for retinoblastoma in Brazil, sampled by snowball sampling, via a web survey, based on a semi-structured questionnaire elaborated by the authors, shared on social media. Results: The children and adolescents were represented by 129 accompanying family members from the five largest regions of Brazil. Low education level, housewifery, and low family income were associated with exclusive care provided by the Unified Health System, while low family income was associated with the use of ocular prosthesis post retinoblastoma. Conclusion: The identified odds ratio indicated the importance of family members' sociodemographic aspects for the clinical, epidemiological and care outcomes of the children and adolescents treated. Public healthcare services were the most used for oncology care, which endorses the relevance of the Unified Health System for children, adolescents, and their family members who have been impacted by retinoblastoma in the country (AU)

Introdução: O retinoblastoma impacta sobremaneira as crianças, adolescentes e familiares acometidos. Abordagens epidemiológicas sobre tal câncer no Brasil são escassas, lacuna esta que motivou este trabalho. Objetivos: Os objetivos desse estudo foram descrever as características sociodemográficas, clínicas, epidemiológicas e assistenciais de crianças e adolescentes atendidos por retinoblastoma no Brasil e analisar se existe associação entre tais características. Métodos: Tratou-se de um estudo transversal, descritivo-analítico, realizado com acompanhantes familiares de crianças e adolescentes atendidos por retinoblastoma no Brasil, amostrados por snowball sampling, via web survey, a partir de um roteiro autoral semiestruturado, compartilhado em mídias sociais. Os dados foram analisados por meio de estatística descritiva e inferencial, com o auxílio do software Statistical Package for the Social Sciences. Resultados: As crianças e os adolescentes foram retratados por 129 acompanhantes familiares das cinco grandes regiões brasileiras. A escolaridade baixa, a ocupação do lar e a baixa renda familiar dos respondentes associaram-se ao atendimento exclusivo pelo Sistema Único de Saúde, sendo que a baixa renda familiar também associou-se ao uso de prótese ocular pós retinoblastoma. Conclusões: As razões de chances identificadas sinalizaram para a importância dos aspectos sociodemográficos dos familiares para os desfechos clínicos-epidemiológicos-assistenciais das crianças e dos adolescentes atendidos. Os serviços públicos foram os mais utilizados para a assistência oncológica, o que endossa a relevância do Sistema Único de Saúde para as crianças, adolescentes e familiares impactados pelo retinoblastoma no país (AU)

Sociodemographic, clinical, epidemiological and care aspects of children and adolescents treated for retinoblastoma in Brazil: a cross-sectional study / Aspectos sociodemográficos, clínicos, epidemiológicos e assistenciais de crianças e adolescentes atendidos por retinoblastoma no Brasil: estudo transversal

ABSTRACT: Introduction: Retinoblastoma greatly impacts the affected children and adolescents and their families. Epidemiological approaches to this form of cancer in Brazil are scarce, and this gap motivated this study. Objectives:This study aimed to describe the sociodemographic, clinical, epidemiological, and care characteristics of children and adolescents treated for retinoblastoma in Brazil and analyze whether there is any association between them. Methods: It is a cross-sectional, descriptive-analytical study, carried out with accompanying family members of children and adolescents treated for retinoblastoma in Brazil, sampled by snowball sampling, via a web survey, based on a semi-structured questionnaire elaborated by the authors, shared on social media. Results: The children and adolescents were represented by 129 accompanying family members from the five largest regions of Brazil. Low education level, housewifery, and low family income were associated with exclusive care provided by the Unified Health System, while low family income was associated with the use of ocular prosthesis post retinoblastoma. Conclusion: The identified odds ratio indicated the importance of family members' sociodemographic aspects for the clinical, epidemiological and care outcomes of the children and adolescents treated. Public healthcare services were the most used for oncology care, which endorses the relevance of the Unified Health System for children, adolescents, and their family members who have been impacted by retinoblastoma in the country. (AU)

RESUMO: Introdução: O retinoblastoma impacta sobremaneira as crianças, adolescentes e familiares acometidos. Abordagens epidemiológicas sobre tal câncer no Brasil são escassas, lacuna esta que motivou este trabalho. Objetivos: Os objetivos desse estudo foram descrever as características sociodemográficas, clínicas, epidemiológicas e assistenciais de crianças e adolescentes atendidos por retinoblastoma no Brasil e analisar se existe associação entre tais características. Métodos: Tratou-se de um estudo transversal, descritivo-analítico, realizado com acompanhantes familiares de crianças e adolescentes atendidos por retinoblastoma no Brasil, amostrados por snowball sampling, via web survey, a partir de um roteiro autoral semiestruturado, compartilhado em mídias sociais. Os dados foram analisados por meio de estatística descritiva e inferencial, com o auxílio do software Statistical Package for the Social Sciences. Resultados: As crianças e os adolescentes foram retratados por 129 acompanhantes familiares das cinco grandes regiões brasileiras. A escolaridade baixa, a ocupação do lar e a baixa renda familiar dos respondentes associaram-se ao atendimento exclusivo pelo Sistema Único de Saúde, sendo que a baixa renda familiar também associou-se ao uso de prótese ocular pós retinoblastoma. Conclusões: As razões de chances identificadas sinalizaram para a importância dos aspectos sociodemográficos dos familiares para os desfechos clínicos-epidemiológicos-assistenciais das crianças e dos adolescentes atendidos. Os serviços públicos foram os mais utilizados para a assistência oncológica, o que endossa a relevância do Sistema Único de Saúde para as crianças, adolescentes e familiares impactados pelo retinoblastoma no país. (AU)

Clinical presentation, treatment, and outcomes of retinoblastoma in India: A literature review

Background@#India has the highest incidence of retinoblastoma globally and is one of the six Asian countries identified to contribute 43% to the global retinoblastoma cases. Data on clinical presentation, treatment, and outcomes were reviewed which can serve as basis in the creation of clinical guidelines, policies and programs, and resource allocation in the diagnosis and management of retinoblastoma in India. @*Methodology@#Articles on retinoblastoma in India gathered from different databases were reviewed for clinical features, treatment, and outcomes. @*Result@#Fourteen articles with 3,666 patients involving around 4,945 eyes seen from 1983-2017 were reviewed. The median age at consult ranged from 14-48 months. The median delay of consult ranged from 2-9 months. Majority of the patients were males (59%) and unilateral disease was present in 63%. Family history was reported in 4%. Retinoblastoma was intraocular in at least 75% of eyes. Systemic chemotherapy was the most used treatment option given to >2,042 eyes. Enucleation was done in >1,695 eyes. The mean follow-up period ranged from 4-50 months. Three hundred fifty six (356) patients were lost to follow-up. The functional vision was retained in 134 eyes. The globe salvage rate for Group A was 100%, 94-100% for Group B, and 50-100% in Group C. The highest globe salvage rate for Group D eyes was 85% and 58% for group E. The overall survival rate was 75% (2,233 patients).@*Conclusion@#Common among the articles was the relatively high proportion of extraocular disease attributed to delay in consult attributed to financial factors and lack of knowledge on the disease.

Health care timeline for patients with retinoblastoma seen in Southern Philippines Medical Center: Policy notes

@#Retinoblastoma (RB), the most common intraocular malignancy in infants and young children,1 2 may lead to the loss of one or two eyes, central nervous system involvement, or even death, if treatment is delayed.3 However, if RB is diagnosed and treated early, patients with the malignancy have a survival rate of almost 100%.4 Delay in diagnosis of RB affects treatment outcomes and prognosis of patients with the disease. With the significant number of RB referrals that result in delays in receiving specialized care in low- and middle-income countries (LMICs)5—where most cases occur—global disparities in the outcomes of RB are evident, such that children with RB in LMICs often have poor prognosis.6 Difficulty of caregivers and primary health care providers in recognizing the earliest presenting signs of RB also contributes to the delay and can increase the risk of local tumor invasion.7 At present, the Department of Health (DOH) has included in its Philippine Cancer Control Program the Cancer in Children Awareness Month, as one of its health advocacies aimed to increase the public’s knowledge and understanding of childhood cancer.8 In September 2021, the first ever DOH-WHO Cancer Control Stakeholders Virtual Summit was held, with special focus given on childhood cancer.9 The DOH program has given emphasis on eight childhood cancers, including RB, that are common in Filipino children.10 In 2011, the Southern Philippines Medical Center (SPMC) and the National University Hospital in Singapore, in collaboration with the Dana Farber Children’s Hospital Cancer Center in Boston and St. Jude Children’s Research Hospital in Memphis, joined together to establish the RB Early Detection Campaign Program. This collaborative project started to educate the public on the early signs of RB, established a referral system across Davao City and other regions in Mindanao (Tagum City, General Santos City, Zamboanga City, and Cagayan de Oro City), and developed a multidisciplinary RB management team at SPMC.11 With the opening of a dedicated RB center at SPMC in 2012 as part of the program, the hospital’s RB census increased, and the majority of the cases detected were still at the early (intraocular) stage.12 However, despite the stringent implementation of the program in SPMC, the time interval between onset of symptoms and initiation of therapy among patients with RB has remained protracted.13 The aim of this article is to recommend health care policies based on the results of a study on the clinical profile and health care timeline of patients seen in a tertiary hospital in Davao City.

Health care timeline for patients with retinoblastoma seen in Southern Philippines Medical Center: Brief report

@#Any health care delay in the management of patients with retinoblastoma increases the risk of tumor invasion and permanent loss of vision in the affected eye.1 2 Factors that affect the speed of medical management, such as low physician density, few ophthalmology specialists, and limited third-level referral centers in a locality have been linked to poor health outcomes among patients with retinoblastoma.3 4 5 6 7 A two-month lag between the onset of symptoms and treatment of retinoblastoma has been associated with poor prognosis (i.e., tumor invasion and metastasis),8 9 while a six-month delay in diagnosis has been associated with high mortality rates.

Aspects épidemiologiques, cliniques, thérapeutiques et évolutifs du rétinoblastome, à l'hôpital ophtalmologique Saint André de Tinré / NA

Introduction : Le rétinoblastome est une tumeur intra oculaire embryonnaire hautement maligne de l'enfant. Il met le plus souvent en jeu le pronostic visuel et fonctionnel en absence de prise en charge précoce. Méthode : Il s'agissait d'une étude ambidirectionnelle, réalisée sur une période de 30 mois à l'Hôpital Saint André de Tinré. Elle a concerné tous les enfants suivis dans cet hôpital pour le rétinoblastome. Résultats : La fréquence du rétinoblastome était de 0,73% (41/5592 patients). L''âge moyen des enfants était de 35,60 ± 15,70 mois. Une prédominance était observée à 51,22% avec un sex-ratio de 0,95. Les principaux signes cliniques étaient repésentés par l'exophtalmie à 46,34% et la leucocorie à 39,02%. La notion de consanguinité était retrouvée dans 7,32% des cas. Selon la classification internationale, les groupes D et E étaient les plus représentés dans 36,59% chacun. Le traitement a consisté en une énucléation pour 26 yeux (soit 63,43%) parmi lesquels 36,59% ont reçu une chimiothérapie néoadjuvante et 2,44% une chimiothérapie adjuvante. L'évolution a été marquée par la survenue de la guérison chez 3 patients (soit 7,32%) et la récidive chez 2 patients (4,88%) avec 78,05% des patients qui étaient perdus de vue. Conclusion : L'amélioration de la prise en charge du rétinoblastome nécessite une sensibilisation de la population sur ses signes d'appels mais aussi le renforcement de la relation médecin et parents de ces enfants pour une bonne adhérence thérapeutique.

Introduction: Retinoblastoma is a highly malignant intraocular embryonic tumor in children. It more often brings into play the visual and functional prognosis in the absence of early treatment. Method: This was an ambidirectional study, carried out over a period of 30 months at Saint André Hospital in Tinré. It concerned all the children followed in this hospital for retinoblastoma. Results: The frequency of retinoblastoma was 0.73% (41/5592 patients). The average age of the children was 35.60 ± 15.70 months. A predominance was observed at 51.22% with a sex ratio of 0.95. The main clinical signs were represented by exophthalmos at 46.34% and leukocoria at 39.02%. The notion of consanguinity was found in 7.32% of cases. According to the international classification, groups D and E were the most represented in 36.59% each. The treatment consisted of enucleation for 26 eyes (63.43%) of which 36.59% received neoadjuvant chemotherapy and 2.44% adjuvant chemotherapy. The course was marked by the onset of healing in 3 patients (7.32%) and recurrence in 2 patients (4.88%) with 78.05% of the patients who were lost to follow-up. Conclusion: Improving the management of retinoblastoma requires raising public awareness of its warning signs but also strengthening the relationship between the doctor and the parents of these children for good therapeutic adherence

Experiencia de la implementación de la cirugía láser en los pacientes pediátricos diagnósticados con retinoblastoma en Hospital Nacional de Niños Benjamin Bloom desde Enero 2012 hasta Diciembre 2017 / Experience of the implementation of laser surgery in pediatric patients diagnosed with retinoblastoma at the Benjamin Bloom National Children's Hospital from January 2012 to December 2017

Este fue un estudio de tipo serie de casos de pacientes pediátricos que fueron diagnosticados con retinoblastoma e intervenidos con terapia láser. Se realizó la revisión de 32 expedientes clínicos de los cuales 11 pacientes se les intervino con la modalidad laser teniendo la característica común de ser pacientes con retinoblastoma bilateral, la edad media de diagnóstico fue 1 año 1 mes, con mayor predominio en sexo masculino provenientes de zona geográfica rural.

microRNA-144 functions as a diagnostic and prognostic marker for retinoblastoma

OBJECTIVES: Retinoblastoma (RB) is a highly malignant eye tumor with a low survival rate and a high metastatic rate. The current work was designed to investigate the potential roles of microRNA-144 (miR-144) in the diagnosis and prognosis of RB. METHODS: miR-144 expression levels in RB tissues and adjacent normal tissues, as well as serum samples from RB patients and healthy controls were measured. The association between miR-144 expression levels and clinical features were analyzed. Moreover, diagnostic and prognostic values of miR-144 in RB were verified by receiver operating characteristic analysis and Kaplan-Meier survival assays. RESULTS: The expression level of miR-144 was markedly decreased in tumor tissues of RB patients, and the expression level of miR-144 was positively associated with tumor size and metastasis in RB patients. Moreover, miR-144 can distinguish tumor tissues from normal tissues with high specificity and sensitivity, and RB patients with lower miR-144 expression have shorter overall and disease-free survival rates than those with higher miR-144 expression. Alternatively, miR-144 also decreased in the serum of RB patients in comparison with healthy subjects, and miR-144 expression levels in the tissue samples and serum were positively correlated. Furthermore, miR-144 levels in the serum of RB patients sensitively distinguished RB patients from healthy controls. CONCLUSIONS: miR-144 expression was downregulated in serum and tissue samples of RB patients and may function as a diagnostic and prognostic marker for RB.

The pathways of cell cycle regulation in retinoblastoma / As vias de regulação do ciclo celular em retinoblastoma

Retinoblastoma is a childhood ocular tumor often caused by the biallelic inactivation of the RB1 gene affecting children up to 5 years of age. A retinoblastoma protein (pRB), encoded by the tumor suppressor gene RB1, is responsible for the regular progression of the G1 phase to the phase S of the cell cycle. This protein forms a complex with the transcriptional factor E2F causing the cell cycle to remain in the G0/G1 stage. With a phosphorylation of cyclin-dependent kinases (CDK), the phosphorylation of the RB protein is activated and the complex formed with E2F is disrupted, with the advancement of the cell cycle to an S phase and cell proliferation. All the control of cell proliferation is regulated not only by the complex formed by RB and E2F proteins, but also by other proteins that participate in and/or interfere in this cell division control mechanism, such as mdm2, mdm4 and p21 proteins.

O retinoblastoma é um tumor ocular infantil ocasionado, frequentemente, pela inativação bialélica do gene RB1 acometendo crianças até os 5 anos de idade. A proteína retinoblastoma (pRB), codificada pelo gene supressor tumoral RB1, é responsável por regular a progressão da fase G1 para a fase S do ciclo celular. Essa proteína forma um complexo com o fator transcricional E2F fazendo com que o ciclo celular permaneça no estágio G0/G1. Com a fosforilação de quinases dependentes de ciclinas, a fosforilação da proteína RB é ativada e o complexo formado com o E2F é desfeito, havendo o avanço do ciclo celular para a fase S e a proliferação celular. Todo esse controle da proliferação celular é regulado não só pelo complexo formado pela proteína RB e E2F, mas também por outras proteínas que participam e/ou interferem neste mecanismo de controle da divisão celular, como, por exemplo, as proteínas mdm2, mdm4, p21

The Amazon Ocular Oncology Center: The first three years / Centro de Oncologia Ocular do Amazonas: primeiros três anos

ABSTRACT Purpose: To evaluate the first three years of The Amazon Ocular Oncology Center, the first ocular cancer center in the North of Brazil. Methods: Here, we report patient information including patients' age, gender, diagnosis, treatment, and city of origin. Results: Two hundred and twenty-one patients were included on this study: 160 (72%) patients came from the city of Manaus, 52 (24%) from other cities in Amazonas, and 9 (4%) from other states. Of the 221 patients, 150 (68%) were afflicted with benign lesions and the remaining 71 (32%) had malignant lesions. Benign diagnosis included pterygium, chalazium, conjunctival nevus, and papilloma, cataract, and retinal detachment. Of the malignant cases, squamous cell carcinoma (SCC) of the conjunctiva was the most frequent with 43 cases (60%). Other diagnoses included choroidal melanoma (8 cases, 11%), retinoblastoma (7 cases, 9%), lymphomas (5 cases, 7%), basal cell carcinomas of the eyelid (4 cases, 5%), conjunctival melanoma (2 cases, 2%), and Kaposi sarcomas (1 case, 1%). Of the 43 patients with SCC, the mean age was 62 years old, and 30 (69%) were male; 29 patients (67%) were treated with an excisional biopsy, and 14 (33%) were treated with neoadjuvant topic chemotherapy, followed by surgery.

RESUMO Objetivo: Reportar sobre os primeiros três anos do Centro de Oncologia Ocular do Amazonas, primeiro centro de oncologia ocular na região Norte do Brasil. Métodos: Relatamos informações de diagnóstico, idade, sexo, tratamento e cidade de origem dos pacientes atendidos nos 3 primeiros anos. Resultados: Identificamos 221 pacientes, dos quais 160 (72%) eram da cidade de Manaus, 52 (24%) de outras cidades do Amazonas e 9 (4%) de outros estados. Dos 221 casos, 150 (68%) eram lesões benignas e 71 (32%) malignas. Lesões benignas incluíram pterígio, calázio, nevus e papiloma de conjuntiva, catarata e descolamento de retina. Das lesões malignas a mais comum foi o carcinoma escamoso de conjuntiva com 43 casos (60%). Outros diagnósticos incluíram melanoma de coróide (8 casos, 11%), retinoblastoma (7 casos, 9%), linfomas (5 casos, 7%), carcinoma da pálpebra (4 casos, 5%), melanoma da conjunctiva (2 casos, 2%) e sarcoma de Kaposi (1 caso, 1%). Dentre os CEC de conjuntiva, a idade media foi de 62 anos e 30 pacientes (69%) eram do sexo masculino. Vinte e nove casos (67%) foram tratados com biópsia excisional e 14 (33%) com quimioterapia tópica neoadjuvante seguida de cirurgia.