Explore the vast range of titles available.

BackgroundRetinoblastoma is the most common intraocular malignancy in childhood. Despite one-third of cases occurring in Africa, little is known of the outcomes on the continent. This study aims to explore survival and globe salvage outcomes and identify their risk factors across a large cohort of patients from the African continent.MethodsA 3-year prospective, observational study was conducted. Kaplan-Meier survival analysis was used to investigate the risk of globe loss and death from retinoblastoma in Africa. Cox regression was used to identify risk factors associated with these outcomes.ResultsA total of 958 patients from 41 African countries and 66 participating centres were enrolled in the study. The survival rate was 78.2% at 1 year and 66.2% at 3 years after diagnosis. Cox regression showed a higher risk of death with the most advanced clinical stage (cT4, HR=6.29 vs cT2, p<0.001). The risk of losing at least one eye after diagnosis was 50% within 4 months and 72.6% within 3 years. Higher risk of enucleation was associated with a higher clinical stage compared with cT1 (cT3, HR=4.11, p=0.001; cT4, HR=3.77, p=0.005).ConclusionNearly one in every four children diagnosed with retinoblastoma in African participating centres succumb to retinoblastoma within 1 year. There is also high morbidity associated with the diagnosis as a large majority of patients require eye removal surgery. The outcome of disease in children with retinoblastoma in Africa is poor compared with other continents and requires prompt intervention by increasing efforts to improve survival and eye salvage outcomes.

Background/aimsEnucleation for retinoblastoma is performed less often in the past decade due to increasingly widespread alternative therapies, but enucleation remains an important option. There is a paucity of reports on the current incidence of metastases and metastatic deaths in unilateral retinoblastoma from US centres.MethodsRetrospective chart review at five tertiary retinoblastoma centres in the USA for unilateral retinoblastoma patients treated with primary enucleation, 2007–2017, with >1 year of follow-up or treatment failure.ResultsAmong 228 patients (228 eyes), there were nine metastases (3.9%) and four deaths (1.7%). The Kaplan-Meier estimate at 5 years for metastasis-free survival was 96% (95% CI, 94% to 99 %), and for overall survival was 98% (95% CI 96% to 100%). All metastases were evident within 12 months. Histopathology revealed higher risk pathology (postlaminar optic nerve and/or massive choroidal invasion) in 62 of 228 eyes (27%). Of these higher risk eyes, 39 received adjuvant chemotherapy. There were four subsequent metastases in this higher risk pathology with adjuvant chemotherapy group, with three deaths. Of the nine overall with metastases, seven (78%) showed higher risk pathology. All metastatic patients were classified as Reese-Ellsworth V and International Classification of Retinoblastoma Groups D or E. Initial metastases presented as orbital invasion in seven of nine cases.ConclusionsPrimary enucleation for unilateral retinoblastoma results in a low rate of metastatic death, but is still associated with a 3.9% chance of metastases within a year of enucleation. Most but not all patients who developed metastases had higher risk histopathological findings.

To report on the influence of ophthalmic artery chemosurgery (OAC) on enucleation rates, ocular and patient survival from metastasis and impact on practice patterns at Memorial Sloan Kettering for children with advanced intraocular unilateral retinoblastoma. Single-center retrospective review of all unilateral retinoblastoma patients with advanced intraocular retinoblastoma treated at MSKCC between our introduction of OAC (May 2006) and December 2014. End points were ocular survival, patient survival from metastases and enucleation rates. 156 eyes of 156 retinoblastoma patients were included. Primary enucleation rates have progressively decreased from a rate of >95% before OAC to 66.7% in the first year of OAC use to the present rate of 7.4%. The percent of patients receiving OAC has progressively increased from 33.3% in 2006 to 92.6% in 2014. Overall, ocular survival was significantly better in eyes treated with OAC in the years 2010-2014 compared to 2006-2009 (p = 0.023, 92.7% vs 68.0% ocular survival at 48 months). There have been no metastatic deaths in the OAC group but two patients treated with primary enucleation have died of metastatic disease. OAC was introduced in 2006 and its impact on patient management is profound. Enucleation rates have decreased from over 95% to less than 10%. Our ocular survival rate has also significantly and progressively improved since May 2006. Despite treating more advanced eyes rather then enucleating them patient survival has not been compromised (there have been no metastatic deaths in the OAC group). In our institution, enucleation is no longer the most common treatment for advanced unilateral retinoblastoma.

ABSTRACT Background Retinoblastoma (Rb) is a rare intraocular malignancy that originates in the retina of children under 5 years of age. Approximately one‐third of children diagnosed with retinoblastoma are associated with germline mutations in one of the RB1 alleles. In this study, we aim to identify RB1 mutations in retinoblastoma patients using Sanger sequencing in combination with multiplex ligation‐dependent probe amplification (MLPA). Method The genomic DNA of 167 Rb patients was isolated from peripheral blood and their clinical information was extracted from medical records. The mutations in the RB1 gene were identified through PCR sequencing. Negative results from the PCR sequencing were further analyzed using MLPA reactions. Results RB1 mutations were identified in 56 of the 167 (33.5%) patients. The common mutation types were frameshift mutations (n = 19), followed by nonsense (n = 20), splicing (n = 8), missense (n = 5), and whole exon deletion (n = 2). The overall survival rate was 98.2%, with an average follow‐up duration of 59 months. Moreover, germline RB1 mutation's correlation with enucleation rates is less pronounced in unilateral cases (12.1%) compared to bilateral cases (65.5%). A total of 13 novel mutations have been identified, of which four are specifically associated with enucleation. Conclusion This study provides a comprehensive analysis of RB1 germline mutations in a group of cases with Rb, leading to the identification of 13 novel mutations in Rb patients at a referral center in Iran. We expect that our findings will yield valuable insights to inform the management and genetic counseling of Rb patients, as well as their relatives who are at a higher risk. A comprehensive outline of the study, detailing the process from DNA extraction to the evaluation of RB1 mutations in relation to clinical features and patient outcomes.

Cell free DNA ( cf DNA) and circulating tumor cell free DNA ( ct DNA) from blood (plasma) are increasingly being used in oncology for diagnosis, monitoring response, identifying cancer causing mutations and detecting recurrences. Circulating tumor RB1 DNA (ctDNA) is found in the blood (plasma) of retinoblastoma patients at diagnosis before instituting treatment (naïve). We investigated ctDNA in naïve unilateral patients before enucleation and during enucleation (6 patients/ 8 mutations with specimens collected 5–40 minutes from severing the optic nerve) In our cohort, following transection the optic nerve, ctDNA RB1 VAF was measurably lower than pre-enucleation levels within five minutes, 50% less within 15 minutes and 90% less by 40 minutes.

Purpose To analyze the safety and efficacy of Pars Plana Vitrectomy (PPV) as a treatment for retinoblastoma patients and to evaluate the feasibility. Methods and patients We collected 342 eyes who had PPV after systemic chemotherapy in our retrospective study, then analyze the 5-year overall survival and 5-year event-free survival rate, recurrence rate, and metastasis rate. The above data were used to evaluate the feasibility of PPV in the treatment of retinoblastoma. Results The mean value of follow-up time was 62.9 months from PPV. Of all 342 eyes, 18% eyes underwent enucleation of the eyeball. Excluding Non-PPV related deaths eyes, the 5-year overall survival rates and event-free survival were 95% and 80%; the tumor recurrence rate and metastasis rate were approximately 26% and 1.2%, respectively; the mortality was 3.9%. And the incidence of high-risk pathological factors of enucleated eyes after PPV was 32%. Conclusion Our results suggest that Pars Plana Vitrectomy as a new approach to preserve the eyeball of RB children is feasible, especially for those patients who cannot be completely controlled by systemic chemotherapy or the tumors with vitreous seeds. Although the outcomes in our study are very optimistic, we also recommend an experienced eye surgeon to perform the operation and strictly control the indications for PPV surgery. And enough systemic chemotherapy is very important before and after surgery. Level of evidence Treatment study (Retrospective comparative study), III.

Report on the 7-year experience with bilateral ophthalmic artery chemosurgery (OAC-Tandem therapy) for bilateral retinoblastoma. Retrospective, single institution study. 120 eyes of 60 children with bilateral retinoblastoma treated since March 2008. Retrospective review of all children treated at Memorial Sloan Kettering with bilateral ophthalmic artery chemosurgery (Melphalan, Carboplatin, Topotecan, Methotrexate) delivered in the same initial session to both naïve and previously treated eyes. Ocular survival, metastatic disease, patient survival from metastases, second cancers, systemic adverse effects, need for transfusion of blood products, electroretinogram before and after treatment. 116 eyes were salvaged (4 eyes were enucleated: 3 because of progressive disease, 1 family choice). Kaplan Meier ocular survival was 99.2% at one year, 96.9% at 2 and 3 years and 94.9% for years 4 through 7. There were no cases of metastatic disease or metastatic deaths with a mean follow-up of 3.01 years. Two children developed second cancers (both pineoblastoma) and one of them died. Transfusion of blood products was required in 3 cases (4 transfusions), 1.9%. Two children developed fever/neutropenia requiring hospitalization (0.95%). ERGs were improved in 21.6% and unchanged after treatment in 52.5% of cases (increase or decrease of less than 25μV). Bilateral ophthalmic artery chemosurgery is a safe and effective technique for managing bilateral retinoblastoma-even when eyes are advanced bilaterally, and if both eyes have progressed after systemic chemotherapy. Ocular survival was excellent (94.9% at 8 years), there were no cases of of metastatic disease and no deaths from metastatic disease, but children remain at risk for second cancers. In 21.6% of cases ERG function improved. Despite using chemotherapy in both eyes in the same session, systemic toxicity was low.

Background/AimsTo report the long-term outcomes of enucleation and insertion of porous polyethylene (PP) orbital implant according to the evolving surgical techniques and implant in patients with paediatric retinoblastoma .MethodsPatients with paediatric retinoblastoma who underwent enucleation and PP implant insertion from December 1998 to December 2014 were retrospectively reviewed and divided into four groups: group A, classic enucleation +PP implant; group B, enucleation +PP implant +anterior closure of the posterior Tenon’s (ACPT) capsule; group C, enucleation +PP implant +free orbital fat graft +ACPT and group D, enucleation +smooth surface tunnel PP implant +ACPT. Survival analysis of implant exposure and eyelid malpositions was performed.ResultsOne hundred and ninety-eight eyes of 196 patients were included. The median follow-up period was 13.0 years (range, 5.0–21.1). A 20 mm implant was inserted for 149 eyes (75.3%). The 10-year exposure-free survival probabilities were 44.6% in group A, 96.4% in group B, 97.4% in group C and 97.7% in group D. ACPT was associated with significant reduction in implant exposure (p<0.001). The most common eyelid malposition was upper eyelid ptosis (24.2%). The eyelid malposition-free survival probability did not differ among the four groups. However, the insertion of a 20 mm implant was associated with significant reduction in upper eyelid ptosis and lower eyelid entropion (p=0.004 and 0.038, respectively).ConclusionsThe long-term postenucleation implant exposure was rare after PP implant insertion and ACPT, even with a 20 mm-diameter implant. A larger implant can be beneficial in long-term prevention of eyelid malposition.

Background Retinoblastoma (RB) is an intraocular malignant tumor detected in early childhood with variable global impact. Histopathological classification of the tumor in enucleated globes with RB is the key for the decision of adjuvant chemotherapy use. We aim to validate the use of adjuvant chemotherapy in cases with combined pre-laminar/intralaminar optic nerve (ON) invasion and focal choroidal invasion according to the American Joint Committee on Cancer (AJCC) 8th classification. Methods This is a retrospective study conducted at King Abdulaziz University Hospital (KAUH) and King Khalid Eye Specialist Hospital (KKESH) in Riyadh, Saudi Arabia of all RB cases who underwent enucleation over 22 years (2000 to 2021). The histopathological findings were reviewed to identify the enucleated globes classified as pT2a tumors, as an inclusion criterion. Basic demographic and clinical data were collected via chart review Simple descriptive and basic statistical analysis of the data was used where applicable. Results Thirty-one patients who had an enucleated globe with RB that fit into the above classification were included. Sixteen were males and 15 were females. The median age was 14 months (IQR = 14 months). Most of the patients (93.5%) had no family history of RB. The commonest presentation was leukocoria in 87.1% followed by squint in 32.3%. Fourteen patients (45.2%) were treated by enucleation alone while 17 patients (54.8%) received adjuvant chemotherapy. Out of these, 7 patients had unilateral RB and the remaining 10 patients had bilateral RB. None of our patients developed recurrence or metastatic disease irrespective of the indication for adjuvant chemotherapy use after a maximum period of follow up reaching 17.84 years and a median of 10.6 years (IQR = 5.92). Conclusions In patients with 8th AJCC histopathological classification of pT2a, chemotherapy following enucleation might not be justified. The outcome in our untreated group of patients did not differ from the treated group with the absence of metastasis after a relatively long period of follow up with a median exceeding 10 years in both groups. Therefore, the risk and benefit of post enucleation adjuvant chemotherapy in the treatment of unilateral RB should be carefully decided and discussed with the primary caregivers taking into consideration the most recent evidence and recommendations in the literature.

Retinoblastoma (RB) is a well-vascularized tumor dependent on angiogenesis. The present study aimed to explore whether microRNA (miR)-182 regulates cell viability, invasion and angiogenesis in RB via the phosphatidylinositol-3-OH kinase (PI3K)/protein kinase B (AKT) signaling pathway and by targeting cell adhesion molecule 2 (CADM2). The expression levels of miR-182 and CADM2 were initially detected in RB tissues from patients with RB who underwent ophthalmectomy, and normal retinal tissues collected from other trauma patients who underwent eye enucleation. To determine whether CADM2 was targeted by miR-182, a dual luciferase reporter assay was conducted. Subsequently, Y79 and WERI-Rb-1 RB cells were transfected with a miR-182 mimic or miR-182 inhibitor, or small interfering RNA against CADM2, in order to investigate the effects of miR-182 on viability and invasion, which were detected using MTT and Transwell assays, respectively. In addition, to determine whether the regulatory mechanism underlying the effects of miR-182 was associated with the PI3K/AKT signaling pathway, the expression levels of associated genes were detected by reverse transcription-quantitative polymerase chain reaction and western blot analysis. A xenograft tumor model in nude mice was also established, in order to evaluate the effects of miR-182 on tumor growth and angiogenesis. The results indicated that miR-182 expression was increased and CADM2 expression was reduced in RB tissues; CADM2 was confirmed to be targeted and negatively regulated by miR-182. When the expression of miR-182 was downregulated, cell viability, invasion, tumor volume and angiogenesis were significantly decreased. Furthermore, the expression levels of PI3K/AKT signaling pathway-associated genes were increased in response to miR-182 overexpression or CADM2 silencing. Taken together, these results suggested that inhibition of miR-182 may suppress cell viability, invasion and angiogenesis in RB through inactivation of the PI3K/AKT pathway and CADM2 upregulation. This mechanism may reveal a novel potential therapeutic target.