VEC方案联合激光治疗RB眼内期患儿的效果与安全性

目的：评价VEC方案联合激光治疗不同年龄视网膜母细胞瘤(RB)眼内期患儿的效果与安全性。

方法：选择我院2016-01/2018-03 RB眼内期患儿63例作为研究对象,根据年龄分为≤1岁组23例36眼,>1岁组40例66眼,均给予VEC方案联合激光治疗,参照国际抗癌联盟制定的疗效标准评价疗效。治疗前、6个疗程结束后采用间接检眼镜与超声下测量肿瘤及肿瘤基底厚度与直径,记录治疗期间毒副反应。

结果：≤1岁组缓解率为75.0%,>1岁组缓解率为92.4%(P<0.05)。≤1岁组进展5眼,>1岁组进展1眼均行眼球摘除,其余患眼治疗后肿瘤厚度与基底直径明显小于治疗前(P<0.05)。>1岁组治疗后肿瘤厚度与基底直径均比≤1岁组小(P<0.05)。两组患儿均有轻度恶心呕吐等消化道症状及脱发,≤1岁组各有1例轻度骨髓抑制和肝功能损害,>1岁组有2例轻度骨髓抑制,1例轻度肝功能损害。

结论：VEC方案联合激光治疗RB眼内期患儿安全可行,>1岁患儿疗效优于≤1岁患儿。     

Establishment of a formal program for retinoblastoma: Feasibility of clinical coordination across borders and impact on outcome

Retinoblastoma is an ocular tumor that occurs in young children, in either heritable or sporadic manner. The relative rarity of retinoblastoma, and the need for expensive equipment, anesthesia, and pediatric ophthalmologic expertise, are barriers for effective treatment in developing countries. Also, with an average age‐adjusted incidence of two to five cases per million children, patient number limits development of local expertise in countries with small populations. Lebanon is a small country with a population of approximately 4.5 million. In 2012, a comprehensive retinoblastoma program was formalized at the Children's Cancer Institute (CCI) at the American University of Beirut Medical Center, and resources were allocated for efficient interdisciplinary coordination to attract patients from neighboring countries such as Syria and Iraq, where such specialized therapy is also lacking. Through this program, care was coordinated across hospitals and borders such that patients would receive scheduled chemotherapy at their institution, and monthly retinal examinations and focal laser therapy at the CCI in Lebanon. Our results show the feasibility of successful collaboration across borders, with excellent patient and physician adherence to treatment plans. This was accompanied by an increase in patient referrals, which enables continued expertise development. However, the majority of patients presented with advanced intraocular disease, necessitating enucleation in 90% of eyes in unilateral cases, and more than 50% of eyes in bilateral cases. Future efforts need to focus on expanding the program that reaches to additional hospitals in both countries, and promoting early diagnosis, for further improvement of globe salvage rates.     

视网膜母细胞瘤化疗减容加局部治疗瘤体后的临床消退类型分析

目的：探讨视网膜母细胞瘤化疗减容加局部治疗后瘤体的消退类型及预后。方法回顾性病例研究。63例（93眼）视网膜母细胞瘤患者在经过化疗减容加局部治疗后的消退类型进行回顾性分析。结果138个视网膜母细胞瘤体消退类型分为五型：0型（n=3），1型（n=19），2型（n=6），3型（n=35），4型（n=75）。肿瘤初始厚度小于或等于3mm的消退类型多为4型（84.21%），初始厚度在3~8mm的肿瘤多为3型（34.43%）和4型（40.98%），初始厚度大于8mm的肿瘤多为1型（35.00%）和3型（50.00%）。在黄斑区的瘤体中常见3型（45.10％）和4型（33.33％）消退类型，在黄斑区-赤道部和赤道部-锯齿缘区的瘤体中常见4型消退类型（54.35％，80.48％）。138个瘤体中其中有14个（10.14%）瘤体复发，其中有2个为0型瘤体，3个为1型瘤体，1个为2型瘤体，8个为3型瘤体。结论化疗减容加局部治疗后4型及3型消退类型最常见。多数小的瘤体转为萎缩瘢痕，中间大小的瘤体多转为萎缩瘢痕或部分钙化残留，大的瘤体多转为完全或部分钙化残留。3型消退类型的瘤体可能易复发。     

Le rétinoblastome : les avancées récentes

Retinoblastoma is the most common intraocular malignancy of infancy with an incidence of 1/15,000 to 1/20,000 births. Sixty percent of retinoblastomas are unilateral, with a median age at diagnosis of two years, and in most cases are not hereditary. Retinoblastoma is bilateral in 40% of cases, with an earlier median age at diagnosis of one year. All bilateral and multifocal unilateral forms are hereditary and are part of a genetic cancer predisposition syndrome. All children with a bilateral or familial form, and 10 to 15% of children with an unilateral form, constitutionally carry an RB1 gene mutation. The two most frequent symptoms revealing retinoblastoma are leukocoria and strabismus. Diagnosis is made by fundoscopy, with ultrasound and magnetic resonance imaging (MRI) contributing both to diagnosis and assessment of the extension of the disease. Treatment of patients with retinoblastoma must take into account the various aspects of the disease (unilateral/bilateral, size, localization…), the risk to vision and the possible hereditary nature of the disease. The main prognostic aspects are still premature detection and adapted coverage by a multi-disciplinary specialized team. Enucleation is still often necessary in unilateral disease; the decision for adjuvant treatment is taken according to the histological risk factors. The most important recent therapeutic advances concern the conservative treatment which is proposed for at least one of the two eyes in most bilateral cases: laser alone or in combination with chemotherapy, cryotherapy or brachytherapy. Recently, the development of new conservative techniques of treatment, such as intra-arterial selective chemotherapy perfusion, aims at preserving visual function in these children and decreasing the number of enucleations and the need for external beam radiotherapy. The vital prognosis related to retinoblatoma is now excellent in industrialized countries, but long-term survival is still related to the development of secondary tumors, mainly secondary sarcoma. Retinoblastoma requires multi-disciplinary care as well as a long term specialized follow-up. Early counseling of patients and their family concerning the risk of transmission of the disease and the risk of development of secondary tumors is necessary.     

Time to diagnosis of retinoblastoma in Latin America: A systematic review

Retinoblastoma (RB) is the most common intraocular tumor of childhood. In low income countries, Time to diagnosis (TTD: interval between first symptom and diagnosis) has been associated with extraocular disease, metastasis and mortality. However, the relationship between TTD and prognosis is complex and not simply a linear correlation, particularly if TTD is <6?months. This systematic review aims to identify studies reporting TTD of retinoblastoma in Latin America, highlighting factors affecting TTD, alongside proposals and initiatives to obtain shorter intervals. The review also aims to discuss the methodology linked to cancer pathways studies. The study respected PRISMA recommendations, was registered on Prospero, an international database for systematic review registries under number CRD42017076777. MEDLINE/PUBMED, LILACS and SCIELO databases were searched. Studies from Latin America and the Caribbean, published between 1997 and 2017, reporting TTD and age at diagnosis of patients with retinoblastoma were selected. Nine studies were selected, concerning 1560 patients from Argentina, Brazil, Chile, Honduras, Mexico and Peru. The median TTD ranged from 3 to 5?months and the median age at diagnosis ranged from 16.5 to 22.2?months. A prolonged TTD was observed and was associated to damaging results on retinoblastoma outcomes, particularly increasing extraocular disease, and mortality rates. Methodological heterogeneity was observed and reiterates the importance of standardization of TTD studies, allowing more reliable comparisons and greater knowledge about retinoblastoma pathways before diagnosis. Reports on successful initiatives against delayed diagnosis were scarce, emphasizing a need for further studies.     

Detection and reporting of RB1 promoter hypermethylation in diagnostic screening

Background: RB1 gene screening aids clinical management and genetic counselling in retinoblastoma families. Here we present epigenetic changes identified during routine molecular RB1 screening of tumor and blood samples. Complications in interpreting RB1 methylation are discussed.

Materials and Methods: Screening for RB1 promoter hypermethylation was carried out by Methylation Specific PCR (MS-PCR) after bisulphite modification of DNA. The cohort consisted of 315 tumors, and 204 blood samples, from 497 retinoblastoma patients (22 patients had both blood and tumor screened).

Results: 11.4% of retinoblastoma tumors had promoter hypermethylation. It was not routinely detected in blood samples, or in tumors with two other oncogenic RB1 changes. One blood sample had promoter hypermethylation due to an X;13 translocation. One tumor had low level methylation as well as two other oncogenic changes. Histopathological analysis of a small subset of age-matched tumors was similar regardless of promoter hypermethylation status.

Conclusions: Promoter hypermethylation was detected in 11.4% of the retinoblastoma tumors and should be tested for in routine RB1 screening programmes. Constitutional samples are not expected to display RB1 hypermethylation. In a small proportion of cases it may not be possible to use this somatic change in patient management.     

A new rosette in retinoblastoma

Retinoblastoma, the most common primary malignant intraocular tumor of childhood is a great success story in pediatric and ocular oncology. Pathology of retinoblastoma is important to guide the treatment modalities. Differentiated retinoblastoma is commonly seen in younger age group. Since a hundred years, we have been observing two typical true rosettes in retinoblastoma in the form of Flexner-Wintersteiner (FW) and Homer Wright (HW) rosettes and in many occasions pseudorosettes have been documented. In the present case report, a third new type of rosette was identified in a differentiated retinoblastoma which had an unusual anterior segment involvement.