化疗缩小双侧视网膜母细胞瘤

目的：评价应用化疗和局部治疗双侧视网膜母细胞瘤的方法。     

全身化疗联合局部化疗治疗视网膜母细胞瘤眼眶侵犯

目的 探讨全身化疗联合局部化疗对视网膜母细胞瘤(Rb)眼眶侵犯患者的临床效果.方法 从2009年2月到2011年1月,中山大学中山眼科中心诊断的17例17只眼影像学显示明显Rb眼眶侵犯患者,接受CEV方案(卡铂、依托泊甙和长春新碱)全身化疗联合卡铂眶周注射治疗.其中12例(原发眼眶侵犯9例,继发眼眶侵犯3例)诊断后立即联合化疗;其余5例(原发眼眶视神经侵犯)先行眼球摘除术再用联合化疗.结果 所有患者对术前化疗有明显反应.9例原发眼眶侵犯的患者中,8例在联合化疗后3个疗程行眼球摘除术,7例术后病理回报肿瘤坏死或限于球内,1例回报视神经断端肿瘤浸润;另1例仅联合化疗后6个月复发视神经侵犯,行眼球摘除术病理显示视神经断端肿瘤浸润.3例继发眼眶侵犯的患者对联合化疗有完全反应.随访时间平均12.5个月(7～23个月).7例因中枢神经系统转移死亡.13个月的生存率为48.5％.结论 采用全身化疗联合眼局部化疗对眼眶视网膜母细胞瘤是有效的,有可能替代眶内容剜除术和眼外放疗.     

视网膜母细胞瘤化疗进展

视网膜母细胞瘤是婴幼儿的一种先天性眼内恶性肿瘤,其治疗手段有化疗、眼球摘除术、外放疗、光凝治疗、冷冻治疗、内放射敷贴术.近年来化疗作为一种很有前途的疗法而受到重视.在视网膜母细胞瘤的眼内阶段,人们通过化疗来缩小肿瘤体积,以便于进一步进行局部治疗,化疗亦能预防眼内肿瘤转移及预防三侧性视网膜母细胞瘤.但单用化疗不能治愈视网膜母细胞瘤.化疗具有副作用,主要为骨髓抑制.     

足叶乙甙眼局部化疗治疗视网膜母细胞瘤的实验研究

目的 为避免大剂量、多周期全身化疗治疗RB所带来的严重副作用，应用眼结膜下注射足叶乙甙治疗RB裸鼠，评价该药物眼局部用药对RB的疗效及对眼局部毒副作用。方法 20只RB裸鼠分4组(G1～G4)，每组5只，全身用药组(G1)腹腔内注药足叶乙甙150ug及环孢霉索A(CSA)1．0mg。G2～G4组结膜下注射不同剂量的足叶乙甙，浓度分别为50、75、150ug，每周2次。共3周。每天裂隙灯观察前房肿瘤情况并作照相。第6周取眼球作病理切片和图像处理。结果 1．G1：前房RB肿瘤未见控制。病理检查RB细胞广泛侵犯前房、晶体前后部位。G2前房肿瘤继续增大，与G1相比无差异。G3前房肿瘤生长延缓。瘤体控制率为20％。G4前房肿瘤生长明显控制。肿瘤控制率为40％，肿瘤治愈率为20％。病理检查肿瘤细胞数量明显少于全身用药组。2．眼局部注射部位结膜及巩膜大体和病理检查未见异常。3．图像分析G1～G4组肿瘤面积(mm^2)分别为：0．659、0．634、0．515、0．235，肿瘤抑瘤率分别为7．18％、10．70％、27．43％、66．90％。统计学分析显示，G2、G3肿瘤面积大小和抑瘤率与G1之间无显著性差异。G4肿瘤面积及抑瘤率与G1统计学有显著性差异。结论 1．结膜下局部注射足叶乙甙对眼内RB肿瘤有明显疗效。治疗效果与药物剂量呈相关关系。2．结膜下注射足叶乙甙(150ug)对控制和杀灭RB肿瘤细胞比全身化疗用药方法更有效。眼局部化疗用药剂量较全身用药量明显降低。该方法对眼结膜、巩膜组织无明显刺激作用，是一种安全而有效的化疗用药方法。     

视网膜母细胞瘤治疗后的眼内手术

目的：分析对治疗后的视网膜母细胞瘤进行眼内手术的结果，并且对眼部及全身结果进行评估。设计：回顾性非比较性病例研究。患者：在视网膜母细胞瘤治疗后进行眼内手术的连续45例患者。主要结果测评：（1）视网膜母细胞瘤的复发，（2）需行眼球摘除术，（3）全身转移。当不存在上述评测结果，总结果判定为满意，而当存在1项或更多结果，则判定为不满意。结果：34例患者（76％）仅接受了白内障手术，单纯巩膜扣带术，或经睫状体平坦部玻璃体切割术1种手术，而11例（24％）患者接受了2种或更多的联合手术。总计16例患者（36％）获得的最终视力好于20／200。不满意的结果包括有14例（31％）视网膜母细胞瘤复发，16例（36％）眼球摘除术，3例（7％）全身转移。5例（20％）接受白内障手术，5例（63％）接受巩膜扣带术和9例（75％）接受经睫状体平坦部玻璃体切割术。在视网膜母细胞瘤的治疗结束与眼内手术的时间间隔在结果满意的患者中为26个月，而在结果不满意的患者中为6个月。结论：在某些特定的临床情况下，对治疗后的视网膜母细胞瘤患者进行眼内手术有充分理由。在大多数病例中，白内障手术是安全和有效的。然而，巩膜扣带术和经睫状体平坦部玻璃体切割术可能伴有视网膜母细胞瘤复发、眼球摘除术和全身转移的高风险性，因此有理由采用谨慎的方法。     

化疗联合放疗治疗进展期眼内视网膜母细胞瘤的结果

目的：判断化疗联合全眼放疗治疗双侧性ＲｅｅｓｅＥｌｌｓｗｏｒｔｈＶ级视网膜母细胞瘤的视力和解剖学结果及存活率。地点：一所视网膜母细胞瘤的全国转诊中心（英国，伦敦）患者：自１９８９年３月１日～１９９５年４月３０日就诊并接受治疗的１４例双侧性Ｒｅｅｓｅ－ＬｌｌｓｗｏｒｔｈＶ级视网膜母细胞瘤的患者。介入方式：用化学疗法（碳化铂，鬼臼乙叉甙和长春新碱）和全眼放疗（４０～４４ＧＹ，２０～２２等分子数）。复习     

视网膜母细胞瘤化疗耐药的研究进展

视网膜母细胞瘤(retinoblastoma,RB)是儿童最常见的眼内恶性肿瘤,化疗是目前治疗RB最常用的方法,包括静脉化疗、动脉化疗和玻璃体腔化疗。然而,RB的化疗耐药时有发生,是导致RB患者保眼治疗失败的主要原因。因此,探索RB化疗耐药的发生发展机制、寻找RB治疗新策略及药物联合治疗的新方法具有重要临床意义。本文综述了RB细胞可通过ATP结合盒式蛋白(ABC转运蛋白)、非编码RNA、表观遗传学修饰、自噬、上皮-间充质转化、细胞外基质改变等多种途径获得化疗耐药性,并对其潜在的治疗靶点或药物进行总结,以期为RB化疗耐药性的进一步研究提供参考。     

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     

高危视网膜母细胞瘤患者的术后辅助化疗

目的探讨术后辅助化疗对高危视网膜母细胞瘤（Rb）患者生存及预后的影响。方法收集1997～2004年于中山眼科中心诊治的268例Rb患者资料,随访了135例,其中男80例,女55例;单眼107例,双眼28例。分析患者的一般状况、病理结果、治疗情况、生存率等。用SPSS13.0软件包进行统计学分析。结果135例患者中经治疗但未行化疗75例,曾行化疗51例,未行治疗9例;存活111例（其中1例双眼患者的未摘除眼肿瘤仍有进展）,死亡24例,主要死亡原因为肿瘤颅内蔓延。51例化疗患者中存活46例,死亡5例。未经化疗的患者总体生存率略低于经过化疗的患者,两者间无统计学差异（P=0.369）。眼外期患者中化疗组生存率明显高于未经化疗组,两者间有统计学差异（P=0.000）。未行化疗的患者与经过化疗的患者Ⅰ期义眼座植入后暴露率无统计学差异（P=0.815）。结论术后辅助化疗对有复发和转移高危因素的视网膜母细胞瘤患者可提高其生存和预后,多数患者可耐受化疗的副作用,建议对此类患者术后辅以化疗。     

视网膜母细胞瘤的化学治疗及耐药性研究进展

视网膜母细胞瘤（RB）是婴幼儿常见的眼内恶性肿瘤,其治疗手段包括化学治疗、眼球摘除、外放射治疗、冷冻治疗及经瞳孔温热疗法。近年来,化学治疗作为一种常见且有效的治疗方法日益受到重视。国内外的研究包括化学治疗药物的机制、化学治疗方案的研究、化学治疗后耐药性的研究等,均取得了一定的进展。其中化学疗法药物的多药耐药性与多种机制有关,p-糖蛋白、多药耐药相关蛋白、拓扑异构酶、谷胱甘肽-s-转移酶以及多种细胞凋亡相关蛋白等都与化学治疗耐药性有关,就其研究进展进行综述。     

Pathologic comparisons of enucleated eyes with retinoblastoma after superselective ophthalmic arterial chemotherapy with or without intravenous chemotherapy

AIM: To describe and compare pathologic findings in eyes enucleated after superselective ophthalmic arterial chemotherapy (SOAC) or SOAC with intravenous chemotherapy (IVC) for retinoblastoma. METHODS: Medical records between January 1st, 2014 and June 31st, 2017 were retrospectively analyzed, and pathologic findings were recorded. This study included 36 eyes from 22 (61.1%) male and 14 (38.9%) female patients. Nineteen of 36 (52.8%) eyes received SOAC (mean=3, range=1-7) as primary treatment, and 17 of 36 (47.2%) eyes received SOAC (mean=3.7, range=1-10) after IVC (mean=6.1, range=2-11). Tumor extension including choroidal invasion (n=9, 25%), optic nerve invasion (n=5, 13.9%) and anterior segment invasion (n=5, 13.9%) were recorded. RESULTS: Histopathologic evidence of ischemic damage in the retina and choroid was found in 28 (77.8%) eyes. Thrombosed blood vessels were identified in 9 (25%) eyes, including orbital artery in the retrobulbar orbit (n=1), intrascleral vessels (n=4), and chorioretinal vessels (n=6). Fibrotic changes were found in extraocular muscles (n=5, 13.9%) and optic nerve (n=5, 13.9%). Varying degrees of scleral degeneration were found in all eyes. In statistical analysis, there was no significant difference in clinical and pathologic changes between SOAC group and SOAC with IVC group except for optic nerve invasion (P=0.047). CONCLUSION: SOAC for retinoblastoma can result in ocular toxicity, and SOAC with IVC did not increase the toxicity but reduced the incidence of optic nerve invasion.     

儿童视网膜母细胞瘤的化学疗法

视网膜母细胞瘤是婴幼儿的一种先天性眼内恶性肿瘤,现阶段已有的治疗手段包括化疗（局部＋全身）、外照射、温热治疗、冷冻治疗、内放射敷贴术、光凝治疗、眼球摘除等。本文主要对视网膜母细胞瘤的化疗进展予以阐述。视网膜母细胞瘤化疗分为全身化疗和局部化疗两个阶段,全身化疗对于早期视母具有较好的疗效,但对晚期阶段效果欠佳,而合并局部化疗（眼内注射＋介入化疗）可有效帮助晚期视母患者获得更好的预后。     

经眼动脉介入化学疗法治疗视网膜母细胞瘤的研究进展

经眼动脉介入化学药物治疗（intra-arterial chemotherapy,IAC）是通过介入的方法从眼动脉向患眼注射化学治疗（化疗）药物,对视网膜母细胞瘤（retinoblastoma,RB）进行局部化疗的一种治疗方法。目前IAC治疗RB的常用药物有美法仑、拓扑替康和卡铂。经眼动脉注射化疗药物,可在局部形成高浓度药物作用,有效杀伤肿瘤细胞,同时可显著降低静脉化疗全身并发症的发生率。应用IAC治疗RB国际分期中B、C、D期及部分E期患者,可有效提高保眼率。IAC的主要并发症包括眼睑、结膜水肿,眼睑下垂,眼球运动障碍,玻璃体出血,视网膜、脉络膜缺血和一过性骨髓抑制等。目前,IAC技术已在国际上广泛开展,本文主要对其临床应用研究进行综述。     

Necrotic intraocular retinoblastoma associated with orbital cellulitis

Orbital cellulitis associated with retinoblastoma is uncommon and is characterized by noninfectious inflammation of the periorbital structures. The underlying mechanism is thought to be necrosis of the intraocular tumor, leading to intraocular and periorbital inflammation. We report 2 retinoblastoma patients who presented with an orbital cellulitis-like picture and discuss clinical characteristics, histopathologic features, and treatment.     

Use of intra-arterial chemotherapy for retinoblastoma:results of a survey

AIM: To obtain baseline knowledge about the current use of intra-arterial chemotherapy (SSOAIC) in centers worldwide.METHODS:A survey including questions about the use of SSOAIC was emailed to retinoblastoma experts.RESULTS:Seventy-nine (response rate 69.9%) doctors from 63 centers in 35 countries responded. Thirty-one centers from 19 countries use SSOAIC. Twelve performed more than 50 procedures. Melphalan is the most commonly used drug but 15 centers use more than one drug. First line therapy for advanced unilateral disease is the most common use of SSOAIC (74.2%). Centers with larger experience (>50 applications) were less likely using melphalan alone (P=0.06) and significantly more likely using SSOAIC in more situations such as second line in preference to radiotherapy P=0.05. Nineteen (61.2%) stated that SSOAIC improved their results and 21 (77.8%) reported less toxicity compared to other treatments. Three centers reported that SSOAIC did not improve their results. There were regional variations in the use of SSOAIC which is used more frequently as secondary treatment in Europe compared to the USA and Japan. Ten centers identified cost is the major limiting factor for SSOAIC.CONCLUSION:SSOAIC is used in an increasing number of centers worldwide with regional variations. Centers with more experience in SSOAIC use it in more situations including other drugs than melphalan. The majority of the centers using this technique reported improved results and few complications.     

Intra-arterial chemotherapy for retinoblastoma: First Indian report

Aim:

To describe treatment outcomes and complications of selective intra-arterial chemotherapy (IAC) for retinoblastoma (RB) in Indian eyes.

Materials and Methods:

Single center, retrospective interventional case series of 6 eyes with RB who underwent IAC using Melphalan (3 mg/5 mg/7.5 mg) and topetecan (1 mg) (n = 4) or melphalan (3 mg/5 mg/7.5 mg) alone (n = 2) between December 2013 and June 2014. In all, 17 IAC procedures were performed using selective ophthalmic artery cannulation. Treatment outcomes were evaluated in terms of tumor control, vitreous and subretinal seeds control and globe salvage rates.

Results:

IAC was employed as primary (n = 1) or secondary (n = 5) modality of treatment. Each eye received mean 3 IAC sessions (median: 3; range: 1-4 sessions). Eyes were classified according to international classification of RB as Group B (n = 1), C (n = 1), D (n = 2) and E (n = 2). Following IAC, complete regression of the main tumor was seen in 3 cases (50%), partial regression in 2 (33%), while 1 case (15%) showed no response. Of 4 eyes with subretinal seeds, 1 (25%) eye had complete regression while 3 (75%) eyes had partial regression. Of 5 eyes with vitreous seeds, 2 (40%) eyes had complete regression while 3 (60%) eyes had a partial response. Globe salvage was achieved in 5 of 6 eyes (83%). Diffuse choroidal atrophy and vitreous hemorrhage were observed in 1 (17%) eye, each. No hematologic toxicity or cerebro-vascular events were observed. Mean follow-up period was 5.5 months (median: 6 months, range: 1-6 months).

Conclusion:

IAC is an effective therapy for globe preservation in eyes with RB. Larger studies with longer follow-up are required to validate these results.