视网膜母细胞瘤细胞株SO-Rb50及SO-Rb70对六种抗癌药物敏感性测定

目的 利用体外培养的视网膜母细胞瘤（retinoblastoma,Rb）细胞株筛选对Rb敏感的化疗药物。方法 采用噻唑蓝（3,-4,5 Dimethyliazol tetrazolium bromide,MTT）法对SO-Rb50和SO-Rb70瘤细胞株进行更生霉素、长春新碱、鬼臼噻吩甙、柔红霉素、顺氯氧铂、平阳霉素6种药物体外敏感实验．结果 6种药物作用于SO-Rb5048小时50％抑制浓度（50％ inhibitory concenrtation,IC50）值（μg／ml）分别为0.0004、0.0016、0.0389、0.047、0.29、0.44．72小时分别为0.00025、0.00081、0.0151、0.0192、0.097、0.11,作用于SO-R5048小时IC50值分别为0.00065、0.00149、0.0282、0.043、0.37、0.215,72小时分别为0.00042、0.00082、0.0146、0.0176、0.035、0.084．结论 SO-Rb50和SO-RS70瘤细胞对于上述6种化疗药物均敏感,根据其IC50值．药物敏感性顺序依次为更生霉素、长春新碱、鬼臼噻吩甙、柔红霉素、顺氯氨铂、平阳霉素。     

放射及化学治疗对RB细胞系HXO-Rb44细胞的影响

作者用人视网膜母细胞瘤细胞系HXO-Rb₄₄进行顺铂（DDP）、阿霉素（ADM）和长春新碱（VCR）分别联合放射线对该细胞系杀伤效应的研究。结果提示，这三种药物在低剂量时，都可增强放射线对RB细胞的杀伤作用：高剂量时，则主要表现为两种方法的协同作用。DDP、ADM两种药物，在放射线照射前后运用无明显差别；VCR于照射前运用，效果明显优于照射后运用。DDP和ADM是通过抑制细胞的潜在致死损伤和亚致死损伤的修复，增加放疗效果，VCR只抑制细胞的潜在致死损伤的修复，起放射增敏作用。 （中华眼底病杂志，1995，11：15-18）     

耐长春新碱视网膜母细胞瘤细胞株的建立

目的：研究视网膜母细胞瘤获得性多药耐药现象，探讨其产生机制。方法：利用长春新碱(vincristree，VCR)对人视网膜母细胞瘤细胞系HXO-RB₄₄细胞在体外进行浓度递增法逐步诱导实验，建立一株耐长春新碱视网膜母细胞瘤细胞亚株HXO—RB/VCR。并对其细胞生长，药物含量，药物敏感性与放射性敏感性进行检测。 结果：该耐药细胞株HXO—RB/VCR细胞对长春酰胺、丝裂霉素C、阿霉素、足叶乙甙、顺铂、卡铂等有交叉耐受，对卡氮芥、氟尿嘧啶无明显抗药性，而对氨甲喋呤的敏感性反而增加。对⁶⁰ Coγ射线有轻度耐受性。细胞内药物含量测定显示：耐药细胞内长春新碱浓度明显低于敏感细胞，钙通道阻断剂异博定可使细胞内VCR浓度增加，部分逆转其耐药性。 结论：VCR可诱导视网膜母细胞瘤产生多药耐药和轻度放射耐受，获得性多药耐药作用可被异博定逆转。 （中华眼底病杂志，1997，13：6-9）     

视网膜母细胞瘤患者全身化学药物治疗联合眼部治疗的临床疗效观察

目的：观察视网膜母细胞瘤（RB）患者全身化学药物治疗（化疗） 联合眼部治疗的 临床效果。 方法：回顾分析37例56只眼行全身化疗联合眼部治疗的RB患 者的生存率、眼球保留 率以及病情得到良好控制的情况。病情得到良好控制的标准为：（1）眼部肿瘤缩小乃至消 失，肿瘤病灶呈软乳酪样改变或出现钙化和瘢痕化；（2）眼球摘除者未出现眼眶肿瘤复发 ；（3）临床检查未见肿瘤转移。所有患者均至少有一只肿瘤眼分期为Ⅲb期或以上并接受化 疗。根据肿瘤对化疗的反应情况，一般接受6轮全身化疗，每轮化疗间隔3~4周。化疗药物组 成为：长春新碱、环磷酰胺、依托泊甙(VP16)、卡铂。另外,根据情况分别联合激光光凝、 冷冻、经瞳孔温热疗法（TTT）、钌¹⁰⁶放射敷贴器局部放射治疗以及眼球摘除等眼部 治疗。 治疗和观察时间2~59个月，平均观察时间为35个月。 结果：除1例双眼发 病患者眼球摘除手术 后失访外，观察期内30例患者存活，占83.3%；6例患者死亡，占16.6%。30例存活患者的45 只肿瘤眼中，肿瘤分期为I-Ⅱ期(早期)、Ⅲ-Ⅳ期(中期)和Ⅴ期(晚期)者眼球保存率分 别为100%（10只眼）、7 0.0%（10只眼）和14.3%（21只眼），随访期内病情均得到良好控制。6例死亡患者均为肿瘤 分期Ⅳ期 以上，最终死于肿瘤脑转移。 结论：全身化疗联合多种眼部治疗可以有效地治疗RB。     

放射及化学治疗对RB细胞系HXO－Rb_（44）细胞的影响

作者用人视网膜母细胞瘤细胞系ＨＸＯ－Ｒｂ４４进行顺铂（ＤＤＰ）、阿霉素（ＡＤＭ）和长春新碱（ＶＣＲ）分别联合放射线对该细胞系杀伤效应的研究。结果提示，这三种药物在低剂量时，都可增强放射线对ＲＢ细胞的杀伤作用；高剂量时，则主要表现为两种方法的协同作用。ＤＤＰ、ＡＤＭ两种药物，在放射线照射前后运用无明显差别；ＶＣＲ于照射前运用，效果明显优于照射后运用。ＤＤＰ和ＡＤＭ是通过抑制细胞的潜在致死损伤和亚致死损伤的修复，增加放疗效果，ＶＣＲ只抑制细胞的潜在致死损伤的修复，起放射增敏作用。     

人胚胎和兔结膜成纤维细胞对抗肿瘤药物敏感性的比较

比较了体外培养条件下人胚胎和兔结膜成纤维细胞对5种抗肿瘤药的敏感性。结果表明长春新碱和阿霉素在0.001~10mg/L、5-FU在1~1000mg/L、顺铂在0.01~10mg/L的浓度范围内时，人胚胎结膜成纤维细胞对这几种药物的敏感性显著低于兔结膜成纤维细胞（P＜0.01）；两种细胞对VP-16的敏感性差别不明显（P＞0.05）.提示在进行眼内增殖性疾病防治药物的体外筛选时，用人结膜成纤维细胞较好；将动物实验结果用于临床时，要考虑种属之间的药物敏感性差异。 （中华眼底病杂志，1994，10：223-225）     

视网膜母细胞瘤化疗减瘤后长期的视力结果

目的：评价化疗减瘤后长期的视力结果。 设计：评价40个儿童中54例成功进行化疗减瘤的视网膜母细胞瘤的患眼。治疗包括静脉使用卡铂，磷酸鬼臼毒苷，硫酸长春新碱及局部治疗，不包括放疗或手术治疗。所有患者随访5年以上，使用单变量或多变量回归模型对患者及肿瘤数据进行分析，分析其对结果（最终视力达到或好于20／40及达到或好于20／200）的作用。     

眼科手术或联合系统化学疗法治疗视网膜母细胞瘤的短期观察

观察视网膜母细胞瘤（RB）患者全身化学药物治疗联合局部治疗的临床效果。方法回顾分析2006年8月至2007年9月本院收治的68例84只眼行全身化疗联合局部治疗并随访3个月以上的RB患儿的临床资料。所有患儿均进行眼部超声（B型超声或彩色多普勒超声）、影像学（CT/MRI）以及眼底照相检查（RetCam婴幼儿眼底照相机）,确诊为RB的患儿共66例82只眼,双眼16例,单眼50例;男性36例,女性30例。按照国际眼内视网膜母细胞瘤分期（IIRC）系统分期,A期选择局部治疗（包括激光光凝和冷冻疗法）,B、C、D、E期在系统化疗（CCTV方案,环孢霉素、卡铂、替尼泊苷、长春新碱）的基础上,联合手术（包括局部治疗、眼球摘除和眶内容剜出）治疗。随访时间6~13个月,平均8.6个月。结果 按IIRC分期,A期5只眼,B期6只眼,C期5只眼,D期15只眼,E期51只眼（包括球外转移的）;治疗结束后22只眼得以保存,其中,A~E期分别为5、6、5、4、2只眼,分别占同期治疗眼的100%、100%、100%、26.7%、3.9%;死亡5例,均为E期患者,占总人数的7.6%。结论 眼科手术或联合系统化学治疗RB是有效的,其疗效与患者肿瘤的临床分期有关,A、B、C期患者治疗效果较好,D、E期次之。     

视网膜母细胞瘤的临床表现和诊断

视网膜母细胞瘤（RB）是一种好发于3 岁以下儿童的高度恶性眼内肿瘤,其临床表现因就诊时疾病所处的阶段不同而不同。可表现为视网膜感觉层内的透明或半透明病灶； 朦胧可见视网膜血管的白色混浊团块；继发视网膜脱离的视网膜下黄白色肿物等。任何大小的RB均可表现为白瞳症。最常见的假性RB包括永存增生性原始玻璃体、Coats病和眼弓蛔虫病。对可疑RB患儿的正确诊断过程，应包括详细的病史采集、体格检查、 外眼检查、裂隙灯生物显微镜检查、结合巩膜压迫法的双目间接检眼镜检查等。B型超声 和CT检查可显示眼内肿瘤并检测出肿块内可能存在的钙化；MRI通常不能检测出钙化，但对评估视神经、眼眶和脑内是否有转移极具价值；光相干断层扫描可用于对化学药物治疗不敏 感的囊性RB检查以及评估随访患者的黄斑解剖结构。外周血和肿瘤组织的DNA检测分析有助于鉴定患者是否存在种质(germline)突变。对具有13号染色体长臂缺失综合征或其他面部畸形特征的儿童,染色体组型分析有可能早期检测出RB.（中华眼底病杂志，2004，20：67-132）     

化学减容术联合局部疗法治疗眼内晚期视网膜母细胞瘤的近期疗效观察

目的:察化学减容术联合眼肿瘤局部加强治疗方法治疗晚期眼内 视网膜母细胞瘤 的疗效。 方法:对9例13只视网膜母细胞瘤（RB）患眼采用化学减容术联 合眼肿瘤局部冷冻和(或)经瞳孔温 热 疗法（TTT）进行治疗，并对其临床随访资料进行回顾性分析。化学减容术采用长春新碱， 卡铂和依托箔苷（VEC）方案。平均随访时间15.3个月。 结果：所有13只患 眼均对化学减容术显 示出良好初始反应。经第一疗程化疗后，肿瘤基底最大直径平均缩小37.2%；肿瘤厚度平均 缩小46.7%。6只眼视网膜下积液部分或完全吸收，10只眼视网 膜下肿瘤种植明显减少、消失或钙化，11只眼玻璃体内肿瘤种植明显减少、消失或钙化。治疗期间及治疗后随访期间共有8只眼出现了肿瘤和(或)肿瘤 种植的复发和(或)新发，经补充冷冻和(或)TTT治疗后，最终2只眼（2/13）摘除，11只眼 得以保留，其中8只眼恢复或保持较好有用视力。9例患者均未发生白血病、肝肾功能及听力 损害等严重化学治疗毒性反应。 结论：对高度进展的晚期RB，化学减容术在治疗初期显示了良好的初始反 应。化学减容术联合眼肿瘤局部加强疗法近期内可有效控制视网膜肿瘤、视网膜下种植及 玻璃体内种植； 远期疗效有待继续观察。     

Treatment of metastatic retinoblastoma

PURPOSE: The risk for death in patients with retinoblastoma is increased in those who present with metastatic disease, and the role of intensive chemotherapy and autologous hematopoietic stem cell rescue in these patients remains unclear. DESIGN: Nonrandomized interventional case series. PARTICIPANTS: Four consecutive patients with metastatic retinoblastoma. METHODS: We treated four patients with retinoblastoma metastatic to the bone and bone marrow with intensive chemotherapy, consolidation with megatherapy, and autologous hematopoietic stem cell rescue. Chemotherapy included courses of carboplatin and etoposide alternating with cyclophosphamide, etoposide, and either carboplatin or cisplatin. Radiation therapy was delivered to areas of bone metastases. MAIN OUTCOME MEASURES: Patient survival. RESULTS: All patients completed and responded to the scheduled therapy; complete response of the bone marrow disease was documented after two courses of chemotherapy in all cases. Two patients are long-term survivors. CONCLUSIONS: The treatment described has been successful in obtaining disease-free survival in patients with metastatic retinoblastoma.     

Anecortave acetate as single and adjuvant therapy in the treatment of retinal tumors of LH(BETA)T(AG) mice

PURPOSE: To evaluate the tumor control efficacy of the antiangiogenic agent anecortave acetate as single and combined therapy, in retinal tumor reduction using the LH(BETA)T(AG) mouse model of retinoblastoma. METHODS: Group A: Ten-week-old, LH(BETA)T(AG) mice received a single subconjunctival injection of anecortave acetate (1200, 600, 300, and 150 microg) delivered to right eyes only. Group B: Ten-week-old, LH(BETA)T(AG) mice received a single subconjunctival injection of anecortave acetate (600, 300, and 150 microg) delivered to right eyes only, either during a cycle of carboplatin (six subconjunctival deliveries) or after the completed cycle. Carboplatin was delivered at the subtherapeutic concentration of 62.5 microg. All animals were euthanatized at 16 weeks of age, and the eyes were examined histopathologically. RESULTS: A statistically significant reduction in tumor burden was detected after a single periocular injection of anecortave acetate. The reduction of tumor burden followed a U-shaped dose-response curve. Tumor burden was significantly decreased when anecortave acetate and carboplatin were combined. However, varying doses and delivery schedule of these agents had significant impact on the effectiveness of the combined treatment. The most effective scheme was delivering a low dose (150-300 microg) of anecortave acetate after a complete cycle of carboplatin. Histopathological evaluation showed no signs of retinal toxicity to anecortave acetate delivery alone or in combination with carboplatin. CONCLUSIONS: Anecortave acetate, as monotherapy or as adjuvant therapy, significantly controlled tumor burden in a murine model of retinoblastoma. Moreover, adjuvant therapy enabled the use of typically subtherapeutic carboplatin doses without decreasing efficacy of the therapy.     

Diode laser thermotherapy and chemothermotherapy in the treatment of retinoblastoma

INTRODUCTION: The use of transpupillary thermotherapy alone or associated with systemic chemotherapy is a therapeutic modality of ocular retinoblastoma that allows ocular preservation without external beam irradiation of the eye. We present our experience with thermotherapy in the treatment of selected cases of retinoblastoma. MATERIAL AND METHODS: This paper reports a retrospective case series of patients treated for retinoblastoma by thermotherapy or chemothermotherapy (carboplatin IV followed by thermotherapy) in a single institution from October 1994 to December 2000. Data collected include general characteristics of the treated children, tumor characteristics, and the results of the treatments on local tumor control. Transpupillar thermotherapy was delivered with a diode laser through an operating microscope. Each tumor was treated separately and laser intensity, spot size, and duration were adapted to the size of the tumor and the clinical response. Chemothermotherapy consisted in thermotherapy delivered shortly after an intravenous injection of carboplatin (560 mg/m(2)) at day 1, followed by thermotherapy alone at day 8 if the lesion was 6mm or more in diameter. This cycle was administered every 28 days. The choice between thermotherapy and chemothermotherapy depended on the initial size of the lesions. Thermotherapy was used when the lesion measured 3mm or less. Lesions measuring more than 15 mm, or associated with substantial vitreous seeding, retinal detachment, or optic nerve head involvement are not suitable for these techniques. RESULTS: During the study period, 239 children were treated in our institution and 109 of them (147 eyes, 372 tumors) could be treated conservatively without external beam radiation. The median tumor diameter at the moment of thermotherapy or chemothermotherapy was 2mm (range, 0.2-15.0mm). One hundred and ninety-four tumors were treated by chemothermotherapy and 18 by thermotherapy alone. In 75% of the cases, the treatment was administered after two courses of chemotherapy (etoposide and carboplatin). After a mean follow-up of 55 months (range, 16-89 months), tumor control was obtained in 87.1% of lesions after chemothermotherapy and 77.8% after thermotherapy. Salvage enucleation was necessary for seven lesions (seven eyes) but none in the cases where thermotherapy was used alone. No severe systemic side effects were noted. DISCUSSION: Diode laser delivers hyperthermia on the tumor bed and its use alone or in association with systemic administration of carboplatin makes it possible to preserve the eye without external beam irradiation, with few side effects and less cumulative doses of chemotherapy. CONCLUSION: Thermotherapy and chemothermotherapy provide excellent local tumor control and eye preservation in selected cases of retinoblastoma.     

Ischemic necrosis and atrophy of the optic nerve after periocular carboplatin injection for intraocular retinoblastoma

PURPOSE: To report four cases of optic nerve neuropathy in three children treated with periocular carboplatin injections for unilateral or bilateral intraocular retinoblastoma. DESIGN: Retrospective, observational case series. METHODS: Setting: University-based Ophthalmology Practice. Study population: Four eyes of three children with retinoblastoma enucleated after nonsuccessful multimodality treatment including periocular carboplatin injections. Observation procedures: The enucleated eyes were routinely processed and evaluated by light microscopy. A retrospective chart review of all four cases was performed. RESULTS: Three enucleated eyes (Reese-Ellsworth groups III and VB) were obtained from two children with bilateral multifocal retinoblastoma, and one eye (Reese-Ellsworth group IIB) was harvested from a child with unilateral retinoblastoma. All affected eyes underwent three to seven periocular carboplatin injections before enucleation. Additional treatment modalities included systemic chemotherapy, transpupillary thermotherapy, transscleral cryotherapy, and external beam radiotherapy. Histopathologic evaluation of the enucleated eyes revealed focal areas of ischemic necrosis or atrophy of the optic nerve along with dystrophic calcification and mild inflammation in the surrounding fibrovascular adipose tissue. CONCLUSIONS: Periocular injections of carboplatin may be a useful treatment approach in the management of patients with advanced intraocular retinoblastoma and may minimize systemic side-effects. However, ophthalmologists and pediatric oncologists should be aware of potential marked local complications with periocular carboplatin delivery, including ischemic optic neuropathy. Modifying the injection site/location (for example, subtenon space) or adding other delivery routes adjuncts (for example, fibrin sealant) deserves further study.     

Expression of multidrug resistance proteins in retinoblastoma

AIM: To elucidate the mechanism of multidrug resistance in retinoblastoma, and to acquire more insights into in vivo drug resistance. METHODS: Three anticancer drug resistant Y79 human RB cells were generated against vincristine, etoposide or carboplatin, which are used for conventional chemotherapy in RB. Primary cultures from enucleated eyes after chemotherapy (PCNC) were also prepared. Their chemosensitivity to chemotherapeutic agents (vincristine, etoposide and carboplatin) were measured using MTT assay. Western blot analysis was performed to evaluate the expression of p53, Bcl-2 and various multidrug resistant proteins in retinoblastoma cells. RESULTS: Following exposure to chemotherapeutic drugs, PCNC showed less sensitivity to drugs. No significant changes observed in the p53 expression, whereas Bcl-2 expression was found to be increased in the drug resistant cells as well as in PCNC. Increased expression of P-glycoprotein (P-gp) was observed in drug resistant Y79 cells; however there was no significant change in the expression of P-gp found between primary cultures of primarily enucleated eyes and PCNC. Multidrug resistance protein 1 (Mrp-1) expression was found to be elevated in the drug resistant Y79 cells as well as in PCNC. No significant change in the expression of lung resistance associated protein (Lrp) was observed in the drug resistant Y79 cells as well as in PCNC. CONCLUSION: Our results suggest that multidrug resistant proteins are intrinsically present in retinoblastoma which causes treatment failure in managing retinoblastoma with chemotherapy.     

Mechanism of retinoblastoma tumor cell death after focal chemotherapy, radiation, and vascular targeting therapy in a mouse model

PURPOSE: To evaluate the mechanism and timing of retinal tumor cell death in the LH(BETA)T(AG) mouse model of retinoblastoma after treatment with vascular targeting therapies and conventional therapies (focal chemotherapy and radiation). METHODS: For vascular targeting therapy, 12- or 16-week-old mice were treated with a single subconjunctival injection of either anecortave acetate (300 microg) or combretastatin A4 (1.5 mg). Eyes were analyzed at 1 day and 1 week after treatment. Tumor cell death was evaluated using TUNEL assays or immunofluorescence analysis of activated caspase 3 to detect apoptosis. Histopathologic analysis was performed to identify areas of necrosis. For conventional therapy, LH(BETA)T(AG) mice were treated with six serial subconjunctival injections of focally delivered carboplatin chemotherapy (100 microg/delivery) or hyperfractionated external beam radiotherapy (EBRT; 15 Gy total dose). Cell death was analyzed by TUNEL assay. RESULTS: The highest levels of apoptotic cell death were seen 1 day after treatment in all treatment groups compared with vehicle controls. At 1 week after treatment, apoptotic cell death remained significantly elevated in the EBRT and carboplatin groups, but not after vessel targeting therapy. No significant necrosis was detected by histology in tumors of treated or of control eyes. CONCLUSIONS: Conventional therapies (focal carboplatin chemotherapy and EBRT) and vascular targeting agents significantly increase cell death through apoptosis, while not having a significant effect on necrosis in this murine model of retinoblastoma. These studies will aid in the optimization of delivery schemes of combined treatment modalities.     

Intraocular carboplatin concentrations following intravenous administration for human intraocular retinoblastoma

Previous studies of the penetration of carboplatin into the vitreous have depended on unaffected animals or on animal models for other cancers. The objective of this study was to determine the intraocular levels of carboplatin following intravenous administration of carboplatin in the treatment of human intraocular retinoblastoma. Eight patients with bilateral intraocular retinoblastoma were treated in a consistent fashion with intravenous carboplatin. One additional patient was similarly treated, but enucleated one month later. Samples were taken from those nine eyes after enucleation one to two hours after the administration of 18.7 mg/kg (560 mg/m 2 for patients more than 12 kg) of intravenous carboplatin, and carboplatin concentrations in the aqueous and vitreous were then measured by atomic absorption spectrometry. The mean concentration measured in the aqueous was 5.13 µg/ml and in the vitreous 4.05 µg/ml, and vitreal concentrations were an average of 80% of aqueous concentrations. In one patient, a vitreous concentration of carboplatin was detected after an interval of one month that was 10% of the levels found in the samples enucleated one hour post-administration. These concentrations are much higher than previous animal studies would predict, and are similar to levels measured in unaffected animals when the drug is given after the use of cryotherapy. The concentration also approaches levels previously shown to be toxic to the retina. This elevation in carboplatin concentration may be due to disruption of the blood-vitreous barrier by active tumor.     

超选眼动脉介入灌注美法仑联合卡铂治疗晚期视网膜母细胞瘤

目的　探讨超选眼动脉介入灌注美法仑联合卡铂治疗眼内晚期视网膜母细胞瘤的临床效果,以期改善患儿预后。方法　选取经全身化疗失败的眼内晚期视网膜母细胞瘤患儿４９例（６７眼）,行眼动脉灌注化疗,化疗采用卡铂联合美法仑方案,每４周１次,每次化疗结束后对患儿的一般情况及不良反应进行观察,每次治疗后４周通过超声检查和眼底检查对瘤体大小和消退情况进行评价。结果　所有患儿均股动脉穿刺插管和眼动脉插管治疗成功。患儿在进行介入治疗后,６７眼中２０眼瘤体完全消失,在局部形成钙化灶或者瘢痕,无复发及转移;２７眼瘤体缩小;其余２０眼中１０眼肿瘤复发,２例（３眼）为术后３个月复查时发现肿瘤复发,放弃治疗死亡;２例（２眼）于术后６个月发现肿瘤侵犯视神经并伴颅内转移死亡;其余５眼肿瘤复发,５眼玻璃体内广泛种植,３眼视网膜下种植,２眼玻璃体出血,均行眼球摘除。治疗后瘤体最大径以及厚度均较治疗前明显缩小,与治疗前相比差异有统计学意义（Ｐ＜０．０５）,其中最大径≤３ｍｍ的瘤体在治疗１～２次后仅能看到钙化灶以及瘢痕;最大径＞３ｍｍ的瘤体经过多次治疗也发生不同程度缩小。部分患儿在术后出现了一过性的眼周和全身不适,但未造成严重不良后果。结论　超选眼动脉介入灌注美法仑联合卡铂治疗眼内晚期视网膜母细胞瘤可以取得一定的效果,且治疗较为安全。临床医师应不断提高介入技术,为患儿提供更好的服务。     

In vitro and in vivo evaluation of carboplatin delivery to the eye using hydrogel-iontophoresis

PURPOSE: To investigate in vitro and in vivo hydrogel-iontophoresis delivery of carboplatin to the eye. METHODS: Iontophoresis was applied on agar gels resembling the eye using different current intensities and durations. Transscleral iontophoresis was performed on healthy rabbits, applying 0, 1, and 3 mA current for 10 min. RESULTS: Similar drug concentrations were obtained in all experimental groups, in in vitro and in vivo studies, regardless of the iontophoretic current applied. A 20-mm penetration depth was found for carboplatin at the agar model. High drug levels were found at the sclera and retina, while lower levels were found at ocular fluids. CONCLUSION: Carboplatin-iontophoretic application at the above conditions does not have an obvious advantage over passive penetration due to high diffusion properties and insufficient molecular charge. Passive carboplatin diffusion from loaded hydrogels inserted in the lower cul-de-sac should be further investigated as a potential clinical treatment for intraocular retinoblastoma.     

Role of chemotherapy alone or in combination with hyperthermia in the primary treatment of intraocular retinoblastoma: preliminary results

BACKGROUND—The efficacy of the etoposide-carboplatin combination in extraocular retinoblastoma is well known. This drug combination is therefore used in intraocular retinoblastoma, as primary reduction chemotherapy, before local treatment. The use of carboplatin in combination with diode laser hyperthermia as local treatment (thermochemotherapy) has been recently described as a conservative approach avoiding external beam radiotherapy in posterior pole tumours.
METHODS—All patients were reviewed, who were treated for retinoblastoma at the Institut Curie between June 1994 and October 1995, in whom treatment included either reduction chemotherapy or thermochemotherapy or both modalities successively. 23 patients presenting with unilateral (three) or bilateral (20) intraocular retinoblastoma received neoadjuvant chemotherapy consisting of two courses of etoposide 150 mg/m²/day and carboplatin 200 mg/m²/day for 3 days. 15 patients (17 eyes), eight of whom had already received neoadjuvant chemotherapy, were treated by thermochemotherapy.
RESULTS—Neoadjuvant chemotherapy: overall, seven eyes in seven patients could be treated conservatively, avoiding external beam irradiation, with a median follow up of 14 months. Thermochemotherapy: external beam irradiation was avoided for 14 of the 17 eyes treated.
CONCLUSION—Integration of neoadjuvant chemotherapy and combined treatment with carboplatin and diode laser, into the therapeutic armamentarium for retinoblastoma allows use of more aggressive treatments such as enucleation and external beam radiation.

Keywords: retinoblastoma; chemotherapy; thermochemotherapy