The global retinoblastoma outcome study : a prospective, cluster-based analysis of 4064 patients from 149 countries

DATA SHARING : The study data will become available online once all analyses are complete.BACKGROUND : Retinoblastoma is the most common intraocular cancer worldwide. There is some evidence to suggest that major differences exist in treatment outcomes for children with retinoblastoma from different regions, but these differences have not been assessed on a global scale. We aimed to report 3-year outcomes for children with retinoblastoma globally and to investigate factors associated with survival. METHODS : We did a prospective cluster-based analysis of treatment-naive patients with retinoblastoma who were diagnosed between Jan 1, 2017, and Dec 31, 2017, then treated and followed up for 3 years. Patients were recruited from 260 specialised treatment centres worldwide. Data were obtained from participating centres on primary and additional treatments, duration of follow-up, metastasis, eye globe salvage, and survival outcome. We analysed time to death and time to enucleation with Cox regression models. FINDINGS : The cohort included 4064 children from 149 countries. The median age at diagnosis was 23·2 months (IQR 11·0–36·5). Extraocular tumour spread (cT4 of the cTNMH classification) at diagnosis was reported in five (0·8%) of 636 children from high-income countries, 55 (5·4%) of 1027 children from upper-middle-income countries, 342 (19·7%) of 1738 children from lower-middle-income countries, and 196 (42·9%) of 457 children from low-income countries. Enucleation surgery was available for all children and intravenous chemotherapy was available for 4014 (98·8%) of 4064 children. The 3-year survival rate was 99·5% (95% CI 98·8–100·0) for children from high-income countries, 91·2% (89·5–93·0) for children from upper-middle-income countries, 80·3% (78·3–82·3) for children from lower-middle-income countries, and 57·3% (52·1-63·0) for children from low-income countries. On analysis, independent factors for worse survival were residence in low-income countries compared to high-income countries (hazard ratio 16·67; 95% CI 4·76–50·00), cT4 advanced tumour compared to cT1 (8·98; 4·44–18·18), and older age at diagnosis in children up to 3 years (1·38 per year; 1·23–1·56). For children aged 3–7 years, the mortality risk decreased slightly (p=0·0104 for the change in slope). INTERPRETATION : This study, estimated to include approximately half of all new retinoblastoma cases worldwide in 2017, shows profound inequity in survival of children depending on the national income level of their country of residence. In high-income countries, death from retinoblastoma is rare, whereas in low-income countries estimated 3-year survival is just over 50%. Although essential treatments are available in nearly all countries, early diagnosis and treatment in low-income countries are key to improving survival outcomes.The Queen Elizabeth Diamond Jubilee Trust and the Wellcome Trust.https://www.thelancet.com/journals/langlo/homeam2023Paediatrics and Child Healt

Oral versus single intravenous bolus dose antibiotic prophylaxis against postoperative surgical site infection in external dacryocystorhinostomy for primary acquired nasolacrimal duct obstruction – A randomized study

Purpose: To compare the efficacy of a single perioperative bolus dose of intravenous antibiotic versus postoperative oral antibiotic prophylaxis for prevention of surgical site infection (SSI) in external dacryocystorhinostomy (DCR) for primary acquired nasolacrimal duct obstruction (PANDO). Methods: This was a prospective randomized controlled study with a noninferiority design. Patients undergoing external DCR surgery were randomized into two groups A and B. Patients in group A received a single bolus dose of intravenous cefazolin 1 g at surgery, whereas those in group B received oral cephalexin 500 mg postoperatively twice a day for 5 days. Allocation concealment was ensured by sequentially numbered opaque sealed envelopes (SNOSEs). Both groups were advised identical postoperative local wound care regimens. Any clinical evidence of SSI at 4 weeks of follow-up in either group was the main outcome measure. Results: In all, 338 patients randomized into two groups of 169 patients each participated in this study. At follow-up of 4 weeks, only one patient in group B developed postoperative SSI. None in group A developed postoperative SSI. Other potential risk factors for postoperative SSI were also analyzed by univariate and multivariate analyses but none achieved statistical significance in either group. Conclusion: Our results demonstrate that a single bolus dose of perioperative intravenous antibiotic offers adequate prophylaxis against postoperative SSI and compares favorably with the more commonly used oral antibiotic prophylaxis in external DCR for PANDO in our population and our practice scenario

Primary nonendoscopic endonasal versus external dacryocystorhinostomy in nasolacrimal duct obstruction in children

Purpose: The aim is to compare the outcome of nonendoscopic endonasal dacryocystorhinostomy (NEN DCR) with external DCR (EXT-DCR) in the treatment of nasolacrimal duct obstruction (NLDO) in children. Methods: A retrospective, comparative chart analysis of all consecutive children <16 years after EXT-DCR or NEN-DCR between June 2012 and February 2016. Results: Seventy-one children (79 eyes) underwent DCR in the study, of which 37 children (40 eyes) underwent EXT-DCR and 34 (39 eyes) NEN-DCR. Mean age of both groups (8.7 vs. 7.7 years) was comparable. Etiologically, persistent congenital NLDO was the most common indication (50% vs. 72%), followed by acquired and secondary NLDO. Mean duration was shorter for NEN-DCR (47 vs. 37 min; P = 0.0021). Mitomycin C 0.04% was used more often in NEN-DCR (10% vs. 56.41%). Success after primary EXT-DCR was 100% as compared to 75% for primary NEN-DCR at median follow-up of 12 and 16 months respectively. At revision, the main cause of failure was granuloma (60%). After revision, all eyes were symptom-free at a median follow-up of 9.5 months. Conclusion: Primary NEN-DCR has a poorer outcome than EXT-DCR in the treatment of NLDO in children and is more likely to need a revision procedure

Expression of PDK1 in retinoblastoma tissues.

<p>(A) Immunohistochemistry (IHC) showing expression of PDK1 in retinoblastoma specimens. * Indicates vessel lumen. (B) IHC showing poor expression of PDK1 in uninvolved retina and strong expression in RB tumor tissue. Orange curly bracket indicates the uninvolved retina and red arrow denotes the expression of PDK1 in RB tumor region. (C) Relative mRNA expression of PDK1 was compared between retinoblastoma tissues and control retina. C1-C2, control retina; Y79 and Weri-Rb1, retinoblastoma cell lines; P1-P6, retinoblastoma tumor tissues.</p

Effect of DCA on lactate production in RB cells.

<p>Effect of DCA on lactate production in RB cells.</p