目的：分析46例双眼视网膜母细胞瘤(retinoblastoma，RB)的临床特点及治疗效果。方法：回顾性分析2008年12月至2019年12月重庆市陆军军医大学陆军特色医学中心收治的46例接受静脉化疗联合经瞳孔温热疗法(transpupillary thermotherapy，TTT)或眼摘治疗的双眼RB住院患儿的临床资料，对患儿的保眼率、摘眼率、视力情况及化疗不良反应进行评估。结果：46例患儿中，男27例，女19例，初诊年龄为(13.21±11.13)个月。单纯化疗10例，化疗+TTT治疗11例，化疗+TTT+眼摘治疗17例，化疗+冷凝治疗2例，化疗+冷凝+眼摘治疗6例。46例92眼总保眼率73.1%(57/78)，残留视力眼占64.1%(50/78)，各期保眼率：A、B期均100.0%，C期86.7%，D期94.1%，E期35.7%。手术摘除24眼，总摘眼率26.1%(24/92)，E期手术摘除21眼，占E期患眼60.0%(21/35)。平均化疗(4.1±1.9)次，化疗的骨髓抑制主要表现为白细胞减少、血小板减少及血红蛋白减少。46例患儿随访时间(35.4±23.8)个月，死亡7例，总病死率15.2%(7/46)；存活39例，总存活率为84.8%(39/46)，5年累积生存率为80.2%。结论：静脉化疗联合局部治疗总体疗效较好，在双眼RB患儿治疗中占据重要地位。化疗具有骨髓抑制作用，停止化疗后骨髓抑制逐渐恢复。
Objective: To analyze the clinical characteristics and therapeutic effect of 46 patients with bilateral retinoblastoma(RB). Methods: The clinical data of 46 patients with bilateral retinoblastoma who received intravenous chemotherapy combined with transpupillary thermotherapy (TTT) or enucleation from December 2008 to December 2019 in our department were analyzed retrospectively. The eye salvage rate, enucleation rate, visual acuity, and chemotherapy side effects were evaluated. Results: The 46 enrolled patients were 27 males and 19 females, at an average age of (13.21±11.13) months at the first visit. Among them, 10 received chemotherapy, 11 received chemotherapy combined with TTT, 17 received chemotherapy combined with TTT and enucleation,and 2 received chemotherapy combined with freezing, 6 received chemotherapy combined with freezing and enucleation. After treatment, 58 eyes were salvaged, with a total salvage rate of 73.1% (57/78), and the eyes that preserved vision account for 64.1% (50/78). The eye salvage rate in each stage were 100.0% for stage A and B, 86.7% for stage C, and 94.1% for stage D, 35.7% for stage E. Twenty-four eyes were enucleated, with a total enucleation rate of 26.1% (24/92), and among 35 eyes at stage E, 21 eyes were enucleated, accounting for 60.0%(21/35). The average time of chemotherapy was 4.1±1.9 and the myelosuppressive effects of chemotherapy include leucopenia, thrombocytopenia and hemoglobinopenia. During the mean follow-up time of (35.4±23.8) months, 7 (15.2%) patients died, and 39 (84.8%) cases survived. The 5-year cumulative survival rate was 80.2%. Conclusion: Intravenous chemotherapy combined with local treatment has a good overall effect and plays an important role in the treatment of bilateral retinoblastoma. Intravenous chemotherapy leads to myelosuppression, and the myelosuppression gradually recovered after stopping intravenous chemotherapy.
目的：分析各种病因摘除眼球的患儿中视网膜母细胞瘤(retinoblastoma，RB)的误诊率，并总结其临床和病理特点。方法：回顾性分析2003年以来在中山眼科中心因临床诊断为RB并接受眼球摘除的患者563例(577眼)，比较术前临床诊断和术后病理诊断，从中筛选出误诊病例，分析这些病例的临床和病理特点，包括患者年龄、性别、治疗过程、临床影像学、肿瘤病理分期、病理诊断以及分化程度。结果：共发现误诊病例22例(22眼)，误诊率3.91%，所有误诊病例均为单眼摘除患者。常见的临床误诊类型为：与Coats病相混淆12例(12眼)，与眼内炎症反应混淆5例(5眼)，以及与眼内其他肿瘤混淆5例(5眼)。所有患者中，>4岁者55例，其中误诊12例，误诊率21.82%。结论：与RB相关的临床误诊并不罕见，其中最常见的误诊病因是Coats病，>4岁患者是误诊的主要人群。
Objective: To investigate the misdiagnosis rate in enucleated eyes for retinoblastoma (RB), analyze the clinicopathological features and summarize differential diagnosis. Methods: Retrospective analysis was performed on 563 cases (577 eye) undergoing eyeball enucleation in Zhongshan Ophthalmic Center Sun Yat-sen University since 2003. Misdiagnosed cases were screened out by comparing the preoperative clinical diagnosis and postoperative pathological diagnosis. The clinical and pathological features of those misdiagnosed caseswere summarized, including age, gender, therapeutic process, imagological examination, pathological stage and pathological diagnosis. Results: Twenty-two cases had been misdiagnosed, which account for 3.91% of 563 enucleated eyeball cases. All of misdiagnosed cases had underwent monocular eyeball enucleation. Diseases that were easily misdiagnosed with RB were Coats disease (12/22), endophthalmitis (5/22) and other intraocular tumor (5/22). Among all patients, 55 patients were older than 4 years old, of which 12 cases were misdiagnosed,with a misdiagnosis rate of 21.82%. Conclusion: It is not unusual for clinical misdiagnosis of RB. Coats disease is the most frequent cause of RB misdiagnosis. Misdiagnosis rates is higher in patients over 4 years old.
目的：应用生物信息学方法分析视网膜母细胞瘤(retinoblastoma，RB)基因表达谱芯片，从转录水平探讨RB与正常视网膜组织的差异表达基因(differentially expressed genes，DEGs)的功能及相互作用。方法：通过公共基因表达数据库(gene expression omnibus，GEO)数据库中选取GSE97508和GSE110811两个芯片数据，共有34个RB组织和6个正常视网膜组织。利用GEO2R工具对和Draw Venn Diagrams软件，筛选出正常视网膜组织与RB组织间的DEGs。通过在线STRING检索工具(search tool for the retrieval of interacting genes，STRING)，对DEGs进行基因本体注释(gene ontology，GO)、KEGG富集通路分析、蛋白互作(protein-protein interaction，PPI)K分析。结果：在2个芯片中发现视网膜母细胞瘤共有20个DEGs，包括3个上调DEGs和17个下调DEGs，GO本体注释结果显示表达上调DEGs所富集的功能主要在细胞分裂、染色体浓缩、核分裂和DNA构象改变。下调DEGs主要富集在光传导、视觉感知、光感受器细胞修复、感光细胞内外节和调节视紫红质介导的信号通路等。KEGG通路显示上调DEGs没有显著的信号通路，下调DEGs参与光传导信号通路，其中包括CNGA1，CNGB1，RHO，SAG四个基因，通过PPI网络提示这4个基因相互联系，并发现与其他节点连接最紧密核心基因RHO。结论：利用生物信息学方法能有效对RB基因芯片数据进行挖掘，为进一步研究RB发生发展机制及寻找潜在的药物治疗靶点提供参考。
Objective: To find differentially expressed genes between retinoblastoma and normal retinal tissues by bioinformatics analysis, and to investigate their molecular function and interactions in the transcriptional level.Methods: The gene expression profile datasets GSE97508 and GSE110811, including 34 retinoblastoma (RB) tissues and 6 normal retinal tissues, were downloaded from gene expression omnibus (GEO). Differentially expressed genes (DEGs) between normal retinal tissues and RB tissues were identified by GEO2R tool and the Draw Venn Diagrams software. The gene ontology (GO) analysis, KEGG pathway and protein-protein interaction (PPI) were analyzed by STRING. Results: In two microarrays of retinoblastoma we found total 20 DEGs were identified, including 3 up-regulated and 17 down-regulated genes. The GO ontology annotation results showed that the enrichment functions of up-regulated genes were mainly in cell division, chromosome enrichment, nuclear division, and DNA conformation change. Down-regulated genes were mainly concentrated in light conduction,visual perception, photoreceptor cell repair, photoreceptor cell inner and outer segment, and regulation of rhodopsin mediated signaling pathway. The KEGG pathway showed that there was no significant signal pathway in which up-regulated genes up-regulated DEGs, and down-regulated genes were involved in the phototransduction signaling pathway, including four genes of CNGA1, CNGB1, RHO and SAG. PPI network suggested that these four genes were interlinked, and RHO was found to be the most closely connected core gene with other nodes.Conclusion: Bioinformatics can be used effectively to analyze RB microarray data to provide theoretical reference for further exploration of tumorigenesis mechanism and help search for potential drug therapeutic targets.
