脉络膜黑色素瘤多中心随机对照研究22年回顾

脉络膜黑色素瘤是成年人最常见的眼内原发性恶性肿瘤,对于眼球摘除及其他一系列保留眼球的治疗方法的效果始终存在争议.1986年"眼黑色素瘤合作研究(COMS)"在美国和加拿大43家临床中心开展,两大著名的试验研究包括眼球摘除前放射治疗和单纯眼球摘除治疗大脉络膜黑色素瘤的对照试验,以及125I敷贴放射治疗和眼球摘除术治疗中等体积脉络膜黑色素瘤的对照研究.这两项研究规模宏大,研究内容丰富,二十多年来所得出的成果对脉络膜黑色素瘤的诊治有重要的指导意义.     

脉络膜黑色素瘤的临床、组织病理学特点及研究进展

脉络膜黑色素瘤是成人最常见的原发性的眼内恶性肿瘤 ,严重威胁成人的生命 ,尽管诊断正确率较高 ,但其病因、发病机制、自然病程尚不清楚 ,目前除眼球摘除外治疗方式多样 ,但临床医生对不同病人治疗方案的选择无统一标准。本文对脉络膜黑色素瘤的流行病学、生物学特性、诊断、治疗、预后等进行综述     

-70℃反复冻融对人眼脉络膜黑色素瘤细胞OCM-1杀伤作用的体外研究

脉络膜黑色素瘤是成年人最常见的眼内原发性恶性肿瘤。放射治疗、激光光凝、肿瘤手术切除等是现代治疗脉络膜黑色素瘤的常用方法。近年来，现代冷冻治疗技术因其治疗范围广、安全有效及微创等特点，在恶性肿瘤治疗中显示了令人鼓舞的应用价值。在眼部肿瘤治疗中，冷冻治疗常用于视网膜母细胞瘤、血管瘤等，在脉络膜黑色素瘤的治疗中则较少应用。我们通过体外实验观察反复冻融对人眼脉络膜黑色素瘤细胞系OCM-1的杀伤作用及细胞形态学的变化，以期更好的认识和理解眼部肿瘤的冷冻治疗。     

脉络膜黑色素瘤的临床、组织病理学特点及研究进展

脉络膜黑色素瘤是成人最常见的原发性的眼内恶性肿瘤，严重威胁成人的生命，尽管诊断正确率较高，但其病因、发病机制、自然病程尚不清楚，目前除眼球摘除外治疗方式多样，但临床医生对不同病人治疗方案的选择无统一标准。本文对脉络膜黑色素瘤的流行病学、生物学特性、诊断、治疗、预后等进行综述。     

内切除法治疗后部葡萄膜黑色素瘤

葡萄膜黑色素瘤是眼内恶性肿瘤中最常见的原发性肿瘤。长期以来,睫状体和脉络膜黑色素瘤的最佳治疗方法一直是一个有争议的问题,各种各样的治疗方法的适应证也在持续不断地修改;多年来,眼球摘除术被认为是治疗后部葡萄膜黑色素瘤的唯一的适当的方法。在１９７９年,Ｚ...     

光动力学疗法在眼科的应用

光动力学疗法９Ｐｈｏｔｏｄｙｎａｍｉｃ ｔｈｅｒａｐｙ,ＰＤＴ）是用光化学方法治疗病变的一种方法,近年在眼科用来治疗脉络膜恶性黑色素瘤、脉络膜新生血管等病变。由于其具有较高的特异性,能有效地治疗病变地周围正常组织损伤极小,故受到广泛的研究。     

葡萄膜黑色素瘤的放射敷贴治疗现状

葡萄膜黑色素瘤是成人最常见的原发眼内恶性肿瘤[1] ,可发生于虹膜、睫状体及脉络膜 ,多数葡萄膜黑色素瘤位于后部葡萄膜[2 ] 。放射敷贴疗法是一种近距离放射治疗 ,是多年来治疗葡萄膜黑色素瘤最常用的方法之一[3] 。早在 1930年 ,Ｍｏｏｒｅ[4 ] 曾用镭针治疗脉络膜黑色素瘤。 196 6年Ｓｔａｌｌａｒｄ[5] 首先报道使用60 Ｃｏ放射敷贴器治疗脉络膜黑色素瘤。自 2 0世纪 70年代至今 ,12 5Ｉ、10 6Ｒｕ、192 Ｉｒ及10 3Ｐａ相继用于放射敷贴法治疗葡萄膜黑色素瘤。一、用于放射敷贴治疗的放射性元素的物理特点用于放射敷贴治疗的放射性元素…     

脉络膜黑色素瘤治疗进展

脉络膜黑色素瘤是成人最常见的原发性眼内恶性肿瘤,白种人发病率是黄种人的3倍,是黑种人的8倍,无色素性脉络膜黑色素瘤占约1/3[1]。为了研究脉络膜黑色素瘤的自然病程及治疗方法等,美国于1986年成立了多中心协作眼黑色素瘤研究项目(Collaborative Ocular Melanoma Study Group,COMS),将黑色素瘤按照直径分为3类:大肿瘤(高度>5mm,基底直径>16mm),中等大小(高度在3～5mm,基底直径10～16mm),小肿瘤(高度<3mm,基底直径<10mm)[2]。在近几十年,研究者进行了大量工作,试图寻求除眼球摘除术外理想的治疗方案,目前脉络膜黑色素瘤的治疗方法已有新…     

脉络膜黑色素瘤的研究进展

脉络膜黑色素瘤(choroidal melanoma,CM)是葡萄膜恶性肿瘤中的最多的一种,也是成年人较常见的眼内恶性肿瘤,其患病率在我国居眼内恶性肿瘤的第二位,仅次于视网膜母细胞瘤.本文就近年来脉络膜黑色素瘤的病理特征、发病机制、影像检查及治疗研究进展予以综述.     

光动力学疗法在眼科的应用

光动力学疗法（Ｐｈｏｔｏｄｙｎａｍｉｃｔｈｅｒａｐｙ，ＰＤＴ）是用光化学方法治疗病变的一种方法，近年在眼科用来治疗脉络膜恶性黑色素瘤、脉络膜新生血管等病变。由于其具有较高的特异性，能有效地治疗病变而对周围正常组织损伤极小，故受到广泛的研究。     

脉络膜黑色素瘤的治疗进展

脉络膜黑色素瘤（choroidal melanoma,CM）是成年人眼球最常见的眼内恶性肿瘤。CM恶性程度高、发生转移早、预后差,早期诊断及选择合理治疗方式对改善患者的预后至关重要。近年来,眼球摘除术作为治疗CM的传统方法已受到挑战。针对不同部位和大小的肿瘤及患者具体情况采取不同的疗法或联合治疗已成为CM的治疗原则。本文就CM的治疗进展进行综述,为降低转移率和死亡率提供相关依据。     

Clinical treatment options for early-stage and advanced conjunctival melanoma

Conjunctival melanoma (CM) is an ocular malignant tumor arising from the bulbar and palpebral conjunctiva and from the caruncle. The treatment of early-stage CM is wide local excision, followed by cryotherapy to the margins and adjuvant therapy postoperatively. Advanced CM has a poor prognosis, and there is no consensus on its management. With the development of precision medicine, the identification of genetic alterations assumes great importance. The genetic characteristics of CM, such as BRAF, NRAS, and NF1 mutations, may provide potential therapeutic targets. For locally advanced tumors and metastatic disease, targeted therapy such as BRAF inhibitors and MEK inhibitors in vitro show therapeutic benefit. Some individual case reports indicate their potential effectiveness in advanced CM. In addition, immune checkpoint inhibitors, such as programmed cell death-1 and cytotoxic T lymphocyte antigen-4 inhibitors, have been successfully used for advanced cutaneous melanoma and may be effective in CM. Limited clinical case reports found immune checkpoint inhibitors effective in advanced CM. More clinical studies are needed.     

国产125I巩膜敷贴器治疗兔眼脉络膜黑色素瘤的有效性及安全性研究

背景 脉络膜黑色素瘤(CM)是成人眼内常见的原发性恶性肿瘤,巩膜表面敷贴放射治疗(EPRT)是一种近距离放射疗法,是多年来治疗CM最常用的方法之一.但该治疗方法的研究与应用目前在国内报道较少,大多数的CM患者需行眼球摘除术. 目的 通过观察兔CM模型眼、正常兔眼经敷贴放射后的反应以及兔全身免疫状态,评价国产125I巩膜敷贴器的有效性及安全性.方法 新西兰大白兔40只,按随机数字表法分成5个组,每组8只兔8只眼(均取右眼).其中放射治疗组1及模型对照组用于评价国产125I巩膜敷贴器的有效性;放射治疗组2、伪放射对照组、正常对照组用于评价国产125I巩膜敷贴器的生物安全性.有效性研究:利用B16F10鼠皮肤黑色素瘤细胞株植入兔眼制作动物模型,造模3周后放射治疗组1模型兔眼放置国产125I巩膜敷贴器进行放射治疗,肿瘤局部照射总剂量为100 Gy,模型对照组不进行治疗.每日间接检眼镜检查,每周行眼底照相、B型超声、彩色超声多普勒检查.安全性研究:放射治疗组2正常兔眼放置巩膜敷贴器,伪放射对照组正常兔眼植入不带放射粒子的敷贴器外壳,正常对照组不作任何干预.放射治疗组2、伪放射对照组于放置敷贴器前及敷贴器取出后3、7、15、30 d抽取外周血,用流式细胞术检测外周血CD4+、CD8+T细胞数量.于放射治疗组1、模型对照组肿瘤种植后6周,放射治疗组2、伪放射对照组、正常对照组观察30 d后耳缘静脉空气栓塞法处死实验兔,对实验眼进行常规组织病理学检查. 结果 放射治疗组1、模型对照组间放置敷贴器前肿瘤的平均高度差异无统计学意义(P=0.550).放置敷贴器1周后,放射治疗组1肿瘤高度明显小于模型对照组,差异有统计学意义(P=0.001);放射治疗组1放置敷贴器2周后肿瘤高度较敷贴前明显缩小,差异有统计学意义(P=0.007).常规组织病理学检查发现,与模型对照组比较,放射治疗组1虽然仍有肿瘤细胞残存,但肿瘤内部血管明显减少且管径较细,肿瘤细胞排列紊乱,部分细胞空泡样变性,色素外露,大量纤维结缔组织增生.安全性研究中,放射治疗组2、伪放射对照组在各时间点CD4+、CD8+、CD4+/CD8+T细胞流式细胞术结果比较,差异均无统计学意义(F分组=0.770、8.110、2.230;P=0.380、0.060、0.140;F时间 =0.770、3.220、4.230;P=0.550、0.170、0.004).放射治疗组2、伪放射对照组表现为角膜、结膜上皮下、巩膜表面慢性炎性细胞浸润,未见巩膜坏死、机化等表现. 结论 国产125I巩膜敷贴器对兔眼CM的疗效确切,对眼部其他组织以及兔全身免疫状态的影响较小.     

Use of interferon alpha 2b to manage conjunctival primary acquired melanosis and conjunctival melanoma

Primary acquired melanosis (PAM) is acquired conjunctival pigmentation that can give rise to conjunctival melanoma (CM), a malignant tumor of the bulbar and palpebral conjunctiva or the caruncle. Surgical excision is the treatment of choice for this neoplasm. Topical chemotherapy is also used for patients with PAM with atypia or CM and, in patients with recurrent or extensive disease, this may be an important option. Of the several chemotherapeutic drugs used, topical interferon alpha 2b (IFN-α2b) has become popular because of its low toxicity. Clinical evidence from case reports and case series supports the efficacy of IFN-α2b as the preferred adjuvant treatment for PAM and CM. In addition, topical IFN-α2b has been successfully applied to melanocytic tumors refractory to other treatments, such as cryotherapy and topical mitomycin C. In patients with locally advanced CM, the combination of IFN-α2b and systemic immunotherapy may serve as an alternative to exenteration. Given the low frequency of CM, long-term multicenter studies are needed to demonstrate the efficacy of IFN-α2b for preventing local recurrence and distant metastasis.     

组织因子在脉络膜黑色素瘤中的表达及意义

目的探讨组织因子（TF）在脉络膜黑色素瘤（CM）细胞株及人CM组织中的表达,为CM的治疗提供新的思路和方法。方法体外培养人CM细胞株（OCM-1）,应用免疫组织化学染色法观察TF在OCM-1中的表达。对人CM眼球标本行免疫组织化学染色检测TF在CM组织中的表达。结果OCM-1细胞中TF蛋白主要表达在细胞质,阳性细胞率为（85．33±5．47）％。CM组织中TF蛋白主要表达在细胞质,少部分表达于CM细胞膜及CM组织内血管内皮细胞的细胞质。CM组织切片中,TF表达阳性细胞率为（41．60±14．17）％,正常人眼脉络膜组织中TF表达阳性细胞率为（5．65±4．26）％,差异有统计学意义（t=5．433,P〈0．01）。CM组织切片阳性细胞积分光密度（IOD）值为33853．67±16445．30,正常人眼脉络膜组织切片平均IOD值为426．43±316．62,差异有统计学意义（t=4．460,P〈0．01）。结论TF在OCM-1细胞及CM组织中呈特异性表达,可作为CM的一个特异性免疫治疗靶点,为CM的治疗提供了新的思路。     

抑癌基因PTEN在脉络膜黑色素瘤中的表达

目的 通过对脉络膜黑色素瘤（choroidal melanoma,CM）以及不同组织病理分类的CM中抑癌基因PTEN表达的观察,探讨CM中PTEN的表达与CM预后的关系.方法 取已经病理学证实的54例CM患者石蜡包埋的组织进行切片.采用免疫组织化学法检测抑癌基因PTEN在CM和正常眼脉络膜组织中的表达,并且观察不同的组织病理分型、不同最大基底直径、不同年龄、不同位置的CM中抑癌基因PTEN的表达.结果 CM和正常眼脉络膜组织中PTEN的表达率差异有显著性（P＜0.01）;不同的组织病理分型表达率差异有显著性（P＜0.01）;不同最大基底直径、不同年龄、不同位置的CM中抑癌基因PTEN的表达率差异无显著性（P＞0.05）.结论 CM可表达抑癌基因PTEN,表达的强弱与其病理分型有密切关系,但与患者的发病年龄、肿瘤的位置和肿瘤的最大基底直径无明显相关关系.     

Mortality after uveal and conjunctival melanoma: which tumour is more deadly?

Purpose: We aimed to model and compare mortality rates for uveal melanoma (UM) and conjunctival melanoma (CM) by adjusting for differences in tumour size and local recurrence. Methods: Population‐based mortality data for 240 and 85 patients with primary UM and CM and 91 and 23 patients with disseminated UM and CM, respectively, were compared with cumulative incidence analysis. Cox proportional hazards multivariate regression with time‐dependent variables was used to adjust for differences in tumour diameter, thickness and recurrence rates. Results: The 10‐year cumulative incidences of metastatic death from UM and CM were 39% (95% confidence interval [CI] 33–45) and 32% (95% CI 21–44), respectively. After adjusting for tumour size, risk of death from CM was higher than from UM (hazard ratio [HR] 1.9; p = 0.039). Additional adjustment for more frequent local recurrence of CM diminished the difference (HR 1.5; p = 0.25). Survival periods after systemic metastasis of UM and CM were comparable (median 8 months). Conclusions: Clinical observations show longer survival after primary CM than after primary UM. This reflects the smaller average size of CM. However, a primary CM of a given size is more deadly than a UM of equivalent size because primary CM tends to recur after treatment and, possibly, because additional lymphatic dissemination occurs with CM.     

Treatment of metastatic uveal melanoma: Review and recommendations

This article reviews the published clinical responses of metastatic uveal melanoma and metastatic cutaneous melanoma with visceral involvement to current therapeutic protocols. Despite isolated patient responses to systemic treatment, no effective treatment currently exists for metastatic uveal melanoma. However, several new approaches involving interferons and interleukin and combination chemotherapy have shown some activity against metastatic cutaneous melanoma. The effectiveness against metastatic uveal melanomas has not been determined. A new approach to intrahepatic administration of chemotherapy also warrants further evaluation because of the high incidence of hepatic involvement with metastatic uveal melanoma. When an effective systemic treatment is found, early administration as an adjuvant to primary treatment may provide the best strategy for control of systemic spread.     

New treatment modalities for uveal melanoma

The management of uveal melanoma has evolved tremendously for the past century, and more recently there is a trend toward more focal conservative treatment. Enucleation is still performed for large uveal melanoma when there is no hope for useful vision with conservative treatment. Plaque radiotherapy is particularly recommended for medium- or small-sized uveal melanoma. Special custom-designed plaque radiotherapy can be used for iris, ciliary body, or juxtapapillary choroidal melanoma. Charged-particle irradiation constitutes an alternative treatment modality for posterior uveal melanoma. However, charged-particle therapy is limited by the availability of appropriate therapeutic facilities. Local tumor resection using lamellar sclerouvectomy is mainly suitable for selected iris, ciliary body, or anterior choroidal tumors with smaller basal dimension and greater thickness. Ablative laser photocoagulation is indicated for very selected cases of small posterior choroidal uveal melanoma. Combined plaque radiotherapy with indirect ophthalmoscope laser therapy appears to be a more effective local tumor treatment plan than plaque radiotherapy alone. Transpupillary thermotherapy is the newest modality used as primary treatment or as complementary method to brachytherapy for treatment of selected choroidal melanomas. Hyperthermia with infrared irradiation below photocoagulation level produces tumor necrosis with few ocular complications. Based on the published ophthalmic literature, it seems that enucleation carries the same survival prognosis as each of the conservative treatment modalities.