Retinoblastoma is the most common intraocular malignancy in childhood. Diagnosis is currently made by ophthalmologists under general anesthesia as it is the gold standard for intraocular assessment. However, evaluations for extraocular disease are also necessary. Treatment strategies vary according to the disease status. If a single eye is involved, the treatment goal is oriented to the removal of the tumor and prevention of relapse. In bilateral retinoblastoma, the main treatment goal is to save monocular vision and save life. This article will explore the available treatment options for retinoblastoma including enucleation, radiotherapy, local therapy, intravenous chemotherapy, intra-arterial injection and intra-vitreal injections. There were recent advances in our understanding on the genetic pathophysiology of the retinoblastoma protein gene in tumorigenesis, which may help developing future treatment. Early detection of retinoblastoma is important for prolonging survival and improving quality of life.
Anesthesia, General ; Carcinogenesis ; Diagnosis ; Drug Therapy ; Injections, Intra-Arterial ; Quality of Life ; Radiotherapy ; Recurrence ; Retinoblastoma Protein ; Retinoblastoma ; Stem Cell Transplantation ; Vision, Monocular

BACKGROUND: By estimating the survival rates and exploring prognostic factors in pediatric patients with relapsed or progressed solid tumors, our purpose was to generate background data for future studies. METHODS: We reviewed the medical records of 258 patients with solid tumors who experienced relapse/progression and received subsequent salvage treatment between 1996 and 2016. RESULTS: A total of 60 patients remained progression-free during first-line salvage treatment, while the remaining 198 patients experienced relapse/progression again; 149 underwent second-line salvage treatment. A total of 76 patients underwent high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT), and 44 patients received allogeneic SCT. The 10-year progression-free survival (PFS) and overall survival (OS) from relapse/progression were 18.4% ± 2.7% and 24.5% ± 3.0%, respectively. Survival rates were relatively higher in patients with anaplastic ependymoma, initially non-high-risk neuroblastoma, osteosarcoma, Wilms tumor and retinoblastoma. A multivariate analysis showed that relapse/progression during initial treatment, metastatic relapse/progression, and impossible debulking surgery were independent poor prognostic factors for both PFS and OS. Patients who exhibited a complete response or partial response during conventional salvage treatment showed significantly higher survival after SCT than those with stable disease or progressive disease (10-year OS: 54.8% ± 7.0% vs. 7.0% ± 3.5%, P < 0.001). CONCLUSION: The prognosis of relapsed/progressed pediatric solid tumors still remains unsatisfactory. New, effective treatment strategies are needed to overcome limitations of current approaches. Hopefully, the background data generated herein will be used in future clinical trials involving patients with relapsed/progressed solid tumors.
Adolescent* ; Child* ; Disease-Free Survival ; Drug Therapy ; Ependymoma ; Humans ; Medical Records ; Multivariate Analysis ; Neuroblastoma ; Osteosarcoma ; Prognosis ; Recurrence ; Retinoblastoma ; Salvage Therapy ; Stem Cell Transplantation ; Survival Rate ; Wilms Tumor

PURPOSE: To evaluate the long-term visual outcomes and complications of cataract surgery in eyes previously treated for retinoblastoma. METHODS: We reviewed the medical records of patients who underwent cataract extraction and intraocular lens implantation at Seoul National University Children's Hospital for a secondary cataract that developed after retinoblastoma treatment. RESULTS: During the period between 1990 and 2014, 208 eyes of 147 patients received eye-salvaging treatment (radiotherapy, chemotherapy, and local therapy) for retinoblastoma at Seoul National University Children's Hospital. Among these eyes, a secondary cataract was detected in 17 eyes of 14 patients, and five eyes of five patients underwent cataract surgery. The median age of cataract formation was 97 months (range, 38 to 153 months). The medial interval between the diagnosis of retinoblastoma and cataract formation was 79 months (range, 29 to 140 months). All patients received posterior chamber intraocular lens insertion after irrigation and aspiration of the lens through a scleral tunnel incision. Anterior vitrectomy and posterior capsulotomy were performed in two eyes and a laser capsulotomy was subsequently performed in one eye. No intraoperative and postoperative complications occurred. The median follow-up after surgery was 36 months (range, 14 to 47 months). The final best corrected visual acuities were improved in all five eyes. No intraocular tumor recurrences or metastases occurred. CONCLUSIONS: After retinoblastoma regression, cataract extraction in our series was not associated with tumor recurrence or metastasis. Visual improvement was noted in every patient.
Capsule Opacification ; Cataract Extraction ; Cataract* ; Diagnosis ; Drug Therapy ; Follow-Up Studies ; Humans ; Lens Implantation, Intraocular ; Lenses, Intraocular ; Medical Records ; Neoplasm Metastasis ; Posterior Capsulotomy ; Postoperative Complications ; Radiotherapy ; Recurrence ; Retinoblastoma* ; Seoul ; Visual Acuity ; Vitrectomy

PURPOSE: To report the clinical characteristics of retinoblastoma patients whose diagnosis was difficult due to atypical ocular manifestations. METHODS: Among retinoblastoma patients who were diagnosed and treated from January 1999 to December 2014 at Seoul National University Children's Hospital, 6 patients whose diagnosis was difficult were retrospectively reviewed. Factors including age, sex, family history, initial findings, time to final diagnosis, histopathologic examination, additional treatment, and survival rate were evaluated. RESULTS: Among 6 patients, 5 were male, and the mean age at the initial visit was 32.9 ± 19.1 months. None of the patients had family history, and all presented with unilateral lesion at the initial visit. The initial diagnoses were Coats' disease and uveitis in 2 patients, respectively, and persistent hyperplastic primary vitreous and traumatic hyphema in 1 patient, respectively. During an intensive short-term follow-up of 8.3 ± 5.3 weeks, 2 patients showed malignant cells after external subretinal fluid drainage procedure, and 4 patients demonstrated increasing ocular size or calcification in imaging. These patients received enucleation under suspicion of malignancy and were finally diagnosed with retinoblastoma after histopathologic examination. There were 2 patients with optic nerve involvement, and 3 patients underwent additional systemic chemotherapy. Five patients were followed-up for 7.6 ± 6.3 years after enucleation, and the mean age at final follow-up was 10.6 ± 7.4 years. CONCLUSIONS: Retinoblastoma is one of the diseases in which early diagnosis and treatment are important. However, some cases are difficult to diagnose, even for experienced clinicians. If there are no typical manifestations such as mass or calcification and early findings show retinal detachment, glaucoma, pseudohypopyon, or hyphema, intensive short-term follow-up to exclude retinoblastoma is needed.
Diagnosis* ; Drainage ; Drug Therapy ; Early Diagnosis ; Follow-Up Studies ; Glaucoma ; Humans ; Hyphema ; Male ; Optic Nerve ; Persistent Hyperplastic Primary Vitreous ; Retinal Detachment ; Retinoblastoma* ; Retrospective Studies ; Seoul ; Subretinal Fluid ; Survival Rate ; Uveitis

Retinoblastoma is a rare disease, but most common tumor which arises in eye. It can affect one or both eyes, and the main pathophysiology is explained by the "Two-hit theory" - the germline mutation of the RB1 gene. Most common clinical symptoms are leuocoria, strabismus, poor visual tracking, glaucoma, and orbital cellulitis. Diagnosis is made by ophthalmologist through fundoscopic examination; Examination under General Anesthesia (EUA) is recommended until the age 3. Orbital CT and MRI can detect the tumor invasion on optic nerve, central nervous system. CSF studies, examination of bone is helpful if the distant metastasis is suspected. Biopsy is rarely done unless in the case of enucleation. Enucleated eye should be explored for the invasion to the optic nerve, choroid, anterior chamber, iris and pupil. Treatment strategies can be different according to the disease status. If the single eye is involved, the treatment goal will be the removal of tumor and prevention of relapse. Local therapies include cryotherapy, laser photocoagulation, thermotherapy can be the choice, and if the tumor is too large for the local therapy, enucleation should be concerned. Nowadays, chemo-reduction combined with local therapy, intra-arterial and intravitreous chemotherapeutic agent injections are studied to avoid enucleation. In bilateral retinoblastoma, multidisciplinary treatments include chemoreduction, external beam radiotherapy, local therapy and other experimental therapies are needed: like intra-arterial injection, intra-vitreal injection, and high-dose chemotherapy with autologous stem cell transplantation. Early detection of retinoblastoma is important to save the vision and eyeball.
Anesthesia, General ; Anterior Chamber ; Biopsy ; Central Nervous System ; Choroid ; Cryotherapy ; Diagnosis ; Drug Therapy ; Eye Enucleation ; Germ-Line Mutation ; Glaucoma ; Hyperthermia, Induced ; Injections, Intra-Arterial ; Intravitreal Injections ; Iris ; Light Coagulation ; Magnetic Resonance Imaging ; Neoplasm Metastasis ; Optic Nerve ; Orbit ; Orbital Cellulitis ; Pupil ; Radiotherapy ; Rare Diseases ; Recurrence ; Retinoblastoma ; Stem Cell Transplantation ; Strabismus ; Therapies, Investigational

BACKGROUNDThe use of post-enucleation adjuvant therapy to decrease the extraocular relapse rate is frequently considered, but there is much controversy about the indications for adjuvant therapy. The aim of this retrospective study was to observe the treatment and prognosis for different degrees of invasion of eye tissue in retinoblastoma (RB) and identify the indications for post-enucleation adjuvant therapy.

METHODSWe recruited 537 children who had been diagnosed with unilateral RB and had received enucleation from January 2006 to December 2012 in our hospital, and divided them into three groups according to their number of histopathologic risk factors: 0 factor, 1 factor, or ≥2 factors. Histopathologic high-risk factors included invasion of the optic nerve posterior to the ethmoid plate (including optic nerve stumps) and extensive invasions of the choroid, sclera, anterior chamber, iris, and ciliary body. Treatment was delivered accordingly, and the prognosis of different degrees of histopathologic invasion was observed. The subjects were followed up for 6 months to 7 years (average follow-up time: 35 months). Statistical analysis was analyzed using χ(2) test. P < 0.05 was considered significant.

RESULTSOf the 537 RB patients who received enucleation, 25 died (overall survival: 95.3%). Of the 369 (68.7%) with no histopathologic risk factors, 1 died of recurrence, with a mortality rate of 0.3%, whereas of the 168 (31.3%) with histopathologic risk factors, 26 had recurrences and 24 died (mortality rate: 14.3%; P = 0.000). Of the 93 patients (17.3%), each of whom had a single risk factor, nine had recurrences, 16 died (8.6%). Of the 75 patients (14%) with two or more high-risk factors, 16 died (21.3%). These differences were statistically significant between the three (P = 0.000).

CONCLUSIONChemotherapy is recommended for patients with histopathologic risk factors, especially those with two or more histopathologic risk factors.

Antineoplastic Agents ; therapeutic use ; Child ; Child, Preschool ; Humans ; Infant ; Infant, Newborn ; Prognosis ; Retinoblastoma ; drug therapy ; pathology ; Risk Factors

Brugada syndrome is a rare channelopathy associated with the SCN5A gene that causes fatal ventricular arrhythmias. This case of Brugada syndrome, in which ventricular tachycardia (VT) was provoked by high fever, is the first report in a Korean child. The boy had retinoblastoma of his left eye diagnosed at 16 months of age. After chemotherapy, he contracted a catheter-related infection with a high fever up to 41degrees C leading to monomorphic VT. This was characterized as having right bundle branch block morphology, superior axis deviation, and a heart rate of 212/min. Direct current cardioversion recovered the VT to sinus rhythm after a lack of response to amiodarone and lidocaine. A second attack of VT that was not controlled by cardioversion, however, responded to lidocaine. The baseline electrocardiogram showed a long PR interval and QRS duration, and the patient's grandfather had a history of Brugada syndrome. A mutation in SCN5A was identified in this patient, his father, and his grandfather. The patient was treated with quinidine and followed up for 1 year.
Amiodarone ; Arrhythmias, Cardiac ; Axis, Cervical Vertebra ; Brugada Syndrome* ; Bundle-Branch Block ; Catheter-Related Infections ; Channelopathies ; Child ; Drug Therapy ; Electric Countershock ; Electrocardiography ; Fathers ; Fever ; Heart Rate ; Humans ; Lidocaine ; Male ; Quinidine ; Retinoblastoma ; Tachycardia, Ventricular*

The latest findings of our laboratory showed that Angelica sinensis polysaccharide (ASP) showed a definite effect in regulating the aging of hematopoietic stem cells. Leukemia is a type of malignant hematopoietic tumor in hematopoietic stem cells. There have been no relevant reports about ASP's effect in regulating the aging of leukemia cells. In this study, human acute myeloid leukemia (AML) KG1alpha cell lines in logarithmic growth phase were taken as the study object, and were divided into the ASP group, the cytarabine (Ara-C) group, the ASP + Ara-C group and the control group. The groups were respectively treated with different concentration of ASP, Ara-C and ASP + Ara-C for different periods, with the aim to study the effect of ASP combined with Ara-C in regulating the aging of human acute myeloid leukemia KG1alpha cell lines and its relevant mechanism. The results showed that ASP, Ara-C and ASP + Ara-C could obviously inhibit KG1alpha cell proliferation in vitro, block the cells in G0/G1 phase. The cells showed the aging morphological feature. The percentage of positive stained aging cells was dramatically increased, and could significantly up-regulate the expression of aging-related proteins P16 and RB, which were more obvious in the ASP + Ara-C group. In conclusion, the aging mechanism of KG1alpha cell induced by ASP and Ara-C may be related to the regulation of the expression of aging-related proteins, suggesting that the combined administration of ASP and anticancer drugs plays a better role in the treatment of leukemia .
Aging ; drug effects ; genetics ; metabolism ; Angelica sinensis ; chemistry ; Cell Cycle ; drug effects ; Cell Proliferation ; drug effects ; Cyclin-Dependent Kinase Inhibitor p16 ; genetics ; metabolism ; Humans ; Leukemia ; drug therapy ; genetics ; metabolism ; physiopathology ; Polysaccharides ; pharmacology ; Retinoblastoma Protein ; genetics ; metabolism ; Tumor Cells, Cultured

PURPOSE: Retinoblastoma (RB) is the most common primary malignant intraocular tumor in children. Although systemic chemotherapy has been the primary treatment, intra-arterial chemotherapy (IAC) represents a new treatment option. Here, we performed alternate systemic chemotherapy and IAC and retrospectively reviewed the efficacy and safety of this approach. METHODS: Patients diagnosed with intraocular RB between January 2000 and December 2011 at Severance Children's Hospital, Yonsei University, were reviewed. Before February 2010, the primary treatment for RB was chemotherapy (non-IAC/CTX). Since February 2010, the primary treatment for RB has been IAC (IAC/CTX). External beam radiotherapy or high-dose chemotherapy were used as "last resort" treatments just prior to enucleation at the time of progression or recurrence during primary treatment. Enucleation-free survival (EFS) and progression-free survival were assessed. RESULTS: We examined 19 patients (median age, 11.9 months; range, 1.4 to 75.6 months) with a sum of 25 eyes, of which, 60.0% were at advanced Reese Ellsworth (RE) stages. The enucleation rate was 33.3% at early RE stages and 81.8% at advanced RE stages (P=0.028). At 36 months, EFS was significantly higher in the IAC/CTX group than in the non-IAC/CTX group (100% vs. 40.0%, P=0.016). All 5 patients treated with IAC achieved eye preservation, although most patients were at advanced RE stages (IV-V). CONCLUSION: Despite the limitation of a small sample size, our work shows that an alternative combined approach using IAC and CTX may be safe and effective for eye preservation in advanced RB.
Child ; Disease-Free Survival ; Drug Therapy, Combination ; Eye ; Eye Enucleation ; Humans ; Infusions, Intra-Arterial ; Recurrence ; Retinoblastoma ; Retrospective Studies ; Sample Size

Adaptor Proteins, Signal Transducing ; analysis ; Apoptosis ; drug effects ; Female ; Humans ; Inhibitor of Apoptosis Proteins ; analysis ; Male ; Neoplasm Proteins ; analysis ; PTEN Phosphohydrolase ; analysis ; Retinal Neoplasms ; drug therapy ; Retinoblastoma ; drug therapy ; Topoisomerase I Inhibitors ; pharmacology ; Topotecan ; pharmacology