目的:观察视网膜激光光凝术(laser photocoagulation,LP)及玻璃体腔注射雷珠单抗(intravitreal ranibizumab,IVR)对病变位于II区的阈值前病变1型早产儿视网膜病变(retinopathy of prematurity,ROP)的疗效。方法:收集2015年10月至2019年12月厦门市儿童医院收治的病变位于II区的阈值前病变1型44例(81眼)。根据手术方式分为LP组、IVR组。观察各组术后病变消退、视网膜血管化情况、全身及眼部并发症,分析不同手术方式的效果。结果:LP组20例(37只眼)行视网膜激光光凝治疗,术后未出现复发,首次治愈率100%;术后(3.42±1.57)周病情控制,术后(9.84±4.75)周可观察到周边视网膜血管化。IVR组24例(44只眼)注射雷珠单抗,39只眼行单次手术后病情控制,首次治愈率88.6%,5眼术后病情未控制。术后(2.95±2.58)周病情控制,术后(14.19±4.95)周可观察到周边视网膜血管化。两组手术方式首次治愈率、视网膜血管化时间差异有统计学意义(P<0.05)。结论:视网膜LP及IVR治疗病变位于II区的阈值前病变1型均有较好疗效,IVR复发率较高,手术方式的选择需慎重。
Objective: To observe the efficacy of laser photocoagulation (LP) and intravitreal ranibizumab (IVR) injection in the treatment of type 1 prethreshold retinopathy of prematurity (ROP) with lesions located in zone II. Methods:Forty-four patients (81 eyes) with type 1 prethreshold retinopathy of prematurity with lesions located in zone II staying in our hospital from October 2015 to December 2019 were collected and divided into LP group and IVR group according to the operation method. Through observation of the postoperative disease involution, retinal vascularization, systemic and ocular complications in each group, the effects of different surgical methods were analyzed. Results: In LP group, 20 patients (37 eyes) underwent retinal laser photocoagulation treatment, with no recurrence occurred after the operation; the cure rate after the first operation was 100%; the disease was controlled at (3.42±1.57) weeks after the operation; and peripheral retinal vascularization was observed at (9.84±4.75) weeks after the operation. In IVR group, 24 patients (44 eyes) were injected with ranibizumab; 39 eyes were under control after a single operation; the cure rate after the first operation was 88.6%; and 5 eyes were not under control after surgery. The disease was controlled for an average of (2.95±2.58) weeks after operation; peripheral retinal vascularization was observed at (14.19±4.95) weeks after operation; there were statistically significant differences in the cure rate after the first operation and retinal vascularization time between the two groups. Conclusion:Retinal laser photocoagulation and IVR have good effects in the treatment of type 1 prethreshold retinopathy of prematurity with lesions located in zone II. However, the recurrence rate using IVR is relatively high. Therefore,the surgical method needs to be cautious and still requires clinical observation.
目的:玻璃膜疣主要成分胆固醇对人视网膜色素上皮细胞ARPE-19中细胞膜钙ATP酶1(plasma membrane Ca2+ ATPase 1,PMCA1)、L型电压依赖性钙离子通道(L-type voltage-dependent calcium channel,LVDCC)和细胞膜钠钙交换蛋白1(sodium calcium exchange protein 1,NCX1)表达的影响。方法:体外培养ARPE-19细胞,将细胞分为对照组和胆固醇处理组(2.5 mg/mL),取样时间为0、6、12、24、48、72 h。通过实时定量PCR检测PMCA1、LVDCC和NCX1 mRNA的表达水平,用蛋白质印迹法检测蛋白质的表达水平。结果:主要负责细胞内钙离子外排的PMCA1的mRNA和蛋白表达水平在胆固醇处理下出现下调。在胆固醇处理下,钙流入通道LVDCC和钙稳态调控蛋白NCX1的mRNA和蛋白表达明显增多,并且呈现时间依赖性,都是在24 h或48 h表达最多后出现回落。其中LVDCC表达上调倍数较大。结论:玻璃膜疣主要成分胆固醇可以影响人视网膜色素上皮细胞中钙转运通道蛋白的表达,PMCA1的表达受到胆固醇抑制, LVDCC和NCX1的表达受到胆固醇处理上调。这可能会影响细胞内钙离子外排,引起钙离子内流,是否能进一步导致细胞内钙超载而引起细胞凋亡,值得探讨。
Objective: To study the effects of cholesterol, the main component of drusen, on the expression plasma membrane Ca2+ ATPase 1 (PMCA1), L-type voltage-dependent calcium channel (LVDCC) and cell membrane sodium calcium exchange protein 1 (NCX1) of ARPE-19 cells. Methods: The ARPE-19 cell line was cultured in vitro, and the cells were divided into a control group and a cholesterol treatment group (2.5 mg/mL). The treatment time was 0, 6, 12, 24, 48, 72 hours. Real-time quantitative PCR was used to detect the expression of PMCA1, LVDCC and NCX1 at the mRNA level, and western blot was used to detect the expression at the protein level. Results: The mRNA and protein expression levels of PMCA1 which mainly responsible for the efflux of intracellular calcium ions, was down regulated under cholesterol treatment. Meanwhile, the expression of the mRNA and protein of the calcium inflow channel LVDCC and calcium stability regulatory protein NCX1 were significantly increased, and the time-dependency was present, which was up expressed to 24 or 48 h and then fell back. Among them, the LVDCC expression had a large number of times. Conclusion: Cholesterol, the main component of drusen, can affect the expression of calcium channels in human retinal pigment epithelial cells. The expression of PMCA1 was suppressed by cholesterol, and expression of LVDCC and NCX1 were up-regulated with cholesterol treatment, which may affect intracellular calcium efflux then cause calcium influx. Whether it can further cause intracellular calcium overload and cell death is worth exploring.
近5年来眼睑皮脂腺癌研究取得一系列成果。临床研究方面,明确了眼睑皮脂腺癌冰冻切缘控制显微手术的意义,提出了患者预后指标;在基础研究方面,描述了基因突变谱,揭示了3种相互独立的发病模式,以及提出了免疫及靶向治疗相关研究;我国眼肿瘤工作者也在眼睑皮脂腺癌研究方面树立了国际地位。本文对近5年国内外眼睑皮脂腺癌相关研究方面的主要成果进行总结分析,并展望治疗前景,为临床提供有益参考。
In recent 5 years, a series of studies have been made in the mechanism of onset of eyelid sebaceous carcinoma worldwide. In clinical research, the prognosis has made in predicting progression of patients with eyelid sebaceous carcinoma, and the significancy of frozen margin control in microsurgery was clarified. In field of basic research,from elucidation of mutational landscape to revelation of three independent pathogenesis patterns, from researches on immunotherapy to targeted therapy, efforts have been made to reveal the pathological mechanism to both aspect of its morbidity and development. This paper summarizes, analyzes and reviews the main achievements in recent 5 years on eyelid sebaceous carcinoma.
眼睑皮脂腺癌是起源于眼睑部位皮脂腺体的恶性上皮性肿瘤,易复发、转移,主要治疗方式仍以手术切除为主,但患者整体预后并不理想,早期正确诊断和靶向治疗是改善患者预后和改进治疗的关键。眼睑皮脂腺癌临床表现复杂,早期容易误诊或漏诊进而延误治疗,病理检查是其诊断的金标准。此外,目前关于眼睑皮脂腺癌发病机制未完全阐明,癌发生发展的分子生物学过程尚未明确。因此,多方面了解眼睑皮脂腺癌发病机制为靶向治疗提供理论基础是十分必要的。本文主要从眼睑皮脂腺癌发病机制包括遗传因素、表观遗传、外源病毒感染、免疫逃逸、端粒酶学说等方面对眼睑皮脂腺癌作一综述。
Eyelid sebaceous gland carcinoma is a malignant epithelial tumor originating from eyelid sebaceous glands, which is prone to relapse and metastasis. The treatment mainly depends on surgical excision, but the overall prognosis of patients is not ideal. Early diagnosis and targeted therapy are the keys to improve the prognosis of patients.Due to its complex clinical manifestations, early misdiagnosis or missed diagnosis is easy to delay treatment, and pathological examination is still the gold standard for its diagnosis. In addition, the pathogenesis of eyelid sebaceous gland carcinoma is still unclear, and the molecular biological process of the occurrence and development is less understood. Therefore, it is very necessary to understand the pathogenesis of eyelid sebaceous gland carcinoma in various aspects to provide a theoretical basis for targeted therapy. In this paper, the pathogenesis of eyelid sebaceous gland carcinoma was reviewed from the aspects of gene , epigenetic, viral infection, immune escape, , telomerase theory and so on.
患者女,因左眼睑反复红肿3个月余就诊。眼眶CT检查:左眶前部可见边界清楚的低密度软组织影,病变向眶外上方延伸,通过位于蝶骨大翼与蝶骨嵴交汇处侵蚀性骨孔与颅内病变沟通。颅内可见额叶、颞叶散在分布的团块状高密度病灶。眼眶MRI检查:边界清楚的异常信号病灶从左上睑延伸至眶上方和眶外上方,呈囊性改变。颅内病变呈混杂信号,散在分布于颞叶和额叶。临床诊断为左眼眶、颅沟通性病变。于全身麻醉下行左眼眶病变切除术,术后病理诊断为眼眶棘球蚴囊肿(包虫病)。发生于眶、颅的沟通性包虫病少有报道,本病例提示对于眶、颅沟通性包虫病需要根据病变的性质、位置采取个性化治疗原则,术前影像学检查的判断分析是辅助治疗的重要手段。
A young female patient complained of recurrent redness and swelling of the right eyelid for more than 3 months.Orbital CT examination showed that low density soft tissue density shadow with clear boundary can be seen in the anterior part of the left orbit. The lesion extended to the upper part of the orbit and communicated with the intracranial lesion through the erosive foramen at the intersection of the great wing of the sphenoid bone and the sphenoid ridge. There were massive high-density lesions in the frontal and temporal lobes. MRI examination of orbit showed that the left upper eyelid extended to the upper orbit and the upper extraorbital region. There were cystic signal of the orbit lesion and mixed signals of intracranial scattering in temporal and frontal lobes. The clinical diagnosis was left orbital cranial communicating lesion. The patient underwent orbital tumor resection under general anesthesia and was diagnosed as echinococcosis by postoperative pathology. This case suggests that for orbital cranial communicating echinococcosis, individualized treatment should be adopted according to the nature and location of the lesions, in which imaging examination are important.
Merkel细胞癌(Merkel cell carcinoma,MCC)是一种少见的高度恶性的皮肤原发性神经内分泌癌,发生于眼睑的MCC更加罕见。本文对2例眼睑MCC患者的临床病史和治疗过程进行回顾和总结。1例初发患者经手术彻底切除,效果良好,随访7年,未再复发;1例患者在外院切除术后2个月,于眼睑原位复发,再次行手术彻底切除,2个月后同侧腮腺淋巴结及颈前淋巴结扩散,目前仍在肿瘤科进一步放化疗中。复习相关文献并结合本组病例提示,MCC诊断主要依靠病理检查,彻底切除病灶并结合术后放化疗是其治疗的主要手段,免疫治疗是目前新的发展趋势。
The Merkel cell carcinoma (MCC) is a rare highly malignant primary neuroendocrine carcinoma of the skin,especially in the eyelids. In this report, the clinical history and treatment course of 2 patients with MCC of the eyelid were reviewed and summarized. Patient 1 with primary MCC of eyelid was treated with complete surgical excision, with good results. Follow-up for 7 years had shown no recurrence. Patient 2 with the eyelid relapse in situ two months after resection in another hospital, was treated with complete surgical excision again, but the tumor metastasized to the ipsilateral lymphonodi parotidici and cervical lymph nodes two months after the surgery. The patient is now going through radiotherapy and chemotherapy in oncology department. According to the review of literatures, the diagnosis was based on the pathologic evidence. Complete removal of lesion combined with postoperative radiotherapy and chemotherapy is a major means of treatment for MCC. Immunotherapy will play a more important role in the future.
眼眶泪腺淋巴上皮癌是一种非常少见的恶性肿瘤。本例为一位46岁女性患者,表现为左眼睑红肿、眼球突出和视力下降,临床和影像学表现类似于泪腺炎型假瘤。手术完整切除后送检病理检查,其特征是未分化的癌巢之间有大量分化成熟的淋巴细胞、浆细胞浸润,确诊为淋巴上皮癌。术后行化学治疗和局部放射治疗,随访6.5年无复发。眼眶泪腺淋巴上皮癌的临床表现容易与泪腺炎型假瘤相混淆,应该进行病理学检查以明确其恶性表型,完整切除后辅助放化学治疗有较好的效果。
Lymphoepithelial carcinoma of the orbital lacrimal gland is a rare carcinoma. A 46-year-old female patient presented with red and swollen left eyelid, proptosis and blurred vision. The clinical and imaging manifestations were similar to inflammatory pseudotumor. Pathological examination was performed after complete resection.Pathological features showed undifferentiated carcinoma nests surrounded by obvious infiltration of non-neoplastic lymphocytes and plasma cells, which was consistent with the diagnosis of lymphoepithelial carcinoma.Chemotherapy and local radiotherapy were performed after the resection. The case did not relapse after 5 years of follow-up. The clinical manifestations of orbital lacrimal lymphoepithelial carcinoma were easily confused with inflammatory pseudotumor. Pathological examination should be performed to clarify its malignant phenotype.Adjuvant radiotherapy and chemotherapy after complete resection had a good effect.
目的:采用角膜激光共焦显微镜观察研究颗粒状角膜营养不良家系患者的角膜状况。方法:采用角膜激光共焦显微镜对4例(6只眼)颗粒状角膜营养不良患者的角膜进行扫描检测,对比裂隙灯及普通显微镜观察分析检查情况。结果:颗粒状角膜营养不良患者的病变角膜裂隙灯下呈现面包屑样的灰白色混浊,在苏木精-伊红(hematoxylin-eosin,HE)染色中呈现出伊红染的颗粒,沉积于基质板层之间,在共焦显微镜下则为中高反光的团块,相互融合,并取代了基质细胞。结论:颗粒状角膜营养不良患者角膜病变从裂隙灯到普通HE染色下的显微镜,乃至高倍的共焦显微镜观察到的沉积物,分布情况相吻合,印证角膜病变发展的状况,有利于了解该病变的发展情况。
Objective: To observe and study the corneal in patients of family with granular corneal dystrophy by confocal laser scanning microscopy. Methods: The corneas of 4 patients (6 eyes) with granular corneal dystrophy were scanned by laser confocal microscopy, and the results were compared with those observed by slit lamp and ordinary microscope. Results: The image were gray and white bread-crumb-like opacity under the slit-lamp of cornea in patients of family with granular corneal dystrophy, were eosin-stained granules deposited between stroma layers in hematoxylin-eosin (HE) stain under the microscopy, were high reflective masses under the confocal laser scanning microscopy, which fused with each other. Conclusion: The image of the corneal in patients of family with granular corneal dystrophy were clearer and clearer by from Slit Lamp and microscopy to the confocal laser scanning microscopy. The distribution of sediments was consistent with each other. It can be a good understanding of the development of the disease.
目的:探讨血管生成拟态(vasculogenic mimicry,VM)与翼状胬肉初发型及复发型的相关性。方法:采用血小板-内皮细胞黏附分子/过碘酸雪夫(platelet endothelial cell adhesion molecule-1/periodic acid-schiff,CD31/PAS)免疫组织化学双重染色法检测139例翼状胬肉组织(初发型105例;复发型34例)和10例正常结膜中VM的表达,分析VM与初发型及复发型翼状胬肉的相关性及其与患者性别、年龄等因素的关系。原代培养人翼状胬肉成纤维细胞(human pterygium fibroblasts,HPFs),免疫细胞化学染色法鉴定,利用三维培养及PAS染色观察初发型和复发型HPFs构成VM管腔个数的差异。结果:10例正常结膜均未见VM结构,初发型翼状胬肉VM阳性率43.81%,复发型翼状胬肉VM阳性率82.35%,差异具有统计学意义(P<0.001)。相关性分析显示VM与复发型翼状胬肉呈显著正相关(r=0.332)。不同性别、年龄及病程的翼状胬肉患者VM的表达差异均无统计学意义(均P>0.05)。原代培养的HPFs Vimentin表达阳性,符合成纤维细胞特性。细胞三维培养及PAS染色结果提示HPFs具有构建体外VM模型的能力,且复发型HPFs构成的VM管腔数明显高于初发型,差异具有统计学意义(P<0.01)。结论:翼状胬肉组织中存在VM结构,可作为其血供途径之一。VM与翼状胬肉的复发具有密切关系。
Objective: The purpose of this study was to investigate the correlation of vasculogenic mimicry in the primary and recurrent pterygium. Methods: Platelet endothelial cell adhesion molecule-1/periodic acid-schiff (CD31/PAS)immunohistochemical double staining method was adopted to detect the expression of VM in 139 cases of pterygium (105 cases of primary pterygium and 34 cases of recurrent pterygium)and 10 cases of normal conjunctival tissues. The correlation between VM and primary pterygium, recurrent pterygium and the factors such as gender and age of patients were analyzed. Human pterygium fibroblasts (HPFs) were primary cultured and identified by immunocytochemical staining. The differences in the number of VM channels between primary HPFs and recurrent HPFs were observed by three-dimensional culture and PAS staining. Results: There was no VM structure in 10 normal conjunctiva and the positive rate of VM was 43.81% in primary pterygium and 82.35% in recurrent pterygium with a significantly difference (P<0.001). Correlation analysis showed a significant positive correlation between VM and recurrent pterygium (r=0.332). There was no significant difference in the expression of VM in pterygium patients with different sex, age and course (all P>0.05). Vimentin was positive in the primary cultured cells, which was consistent with the characteristics of fibroblasts. The results of three-dimensional culture and PAS staining indicated that HPFs had the ability to construct VM model in vitro, and the number of VM channels constituted by recurrent HPFs was significantly higher than that by primary HPFs, the difference was statistically significant (P<0.01). Conclusion: VM exists in pterygium tissues, and it can be used as one of the blood supply routes, which is closely related to the recurrence of pterygium.
目的:分析发生于眶骨的占位性病变的CT表现及其与组织病理学之间的关系。方法:回顾性收集15例经临床表现、影像学特征、病理证实为发生于眶骨占位病变患者的临床资料,分析其CT检查、组织病理学切片及其他临床表现。结果:在15例患者中,经病理诊断为骨瘤的患者有4例,骨内血管瘤3例,骨样骨瘤和骨化性纤维瘤各2例,嗜酸性肉芽肿3例,尤文肉瘤1例。骨瘤由成熟板层骨构成,对应在CT上呈现为高密度的骨样结节状隆起;骨内血管瘤病理主要表现为骨小梁间的畸形血管,在CT上表现为典型的“栅栏状”“蜂窝状”特征;骨样骨瘤以骨样组织和结缔组织为主,在CT上为类圆形的高密度影,中央为典型的低密度“瘤巢“影,外周为增生的骨密度影;骨化性纤维瘤由增生的纤维组织及骨样组织构成,CT表现为肿瘤表面常有骨壳包绕,病变多呈圆形或椭圆形;嗜酸性肉芽肿主要由大量朗格汉斯细胞组成,对应CT上的软组织肿块影,可伴溶骨性破坏;尤文肉瘤以低分化的小圆细胞为主,CT表现为虫蚀样骨质破坏,破坏的骨组织间有软组织病变。结论:发生于眶骨的各类病变有其特有的病理组成,不同的病理组成在CT上表现出相应的影像特征。
Objective: To analyze computed tomography (CT) manifestations of space-occupying lesions of the orbital bone and their relationship with histopathology. Methods: The clinical data of 15 patients with orbital bone occupying lesions confirmed by clinical manifestations , imaging features and pathological symptoms features were retrospectively collected, and their CT examination, histopathological sections and other clinical manifestations were analyzed. Results: Among the 15 patients, 4 cases were pathologically diagnosed with osteoma, 3 cases of intraosseous hemangioma, 2 cases of osteoid osteoma and 2 cases of ossifying fibroma, 3 cases of eosinophilic granuloma and 1 case of Ewing’s sarcoma. Osteoma was composed of mature lamellar bones, which corresponded to a high-density osteoid nodular protuberance on CT. The pathological features of intraosseous hemangioma were mainly malformed blood vessels between bone trabeculae and typical “fence” and “honeycomb” features on CT. Osteoid osteoma was mainly composed of bone-like tissue and connective tissue, mainly showing round high-density shadow, typical low-density “tumor nest” shadow in the center, and hypertrophic bone density shadow in the periphery. Ossifying fibroma was composed of proliferative fibrous tissue and bone-like tissue. CT showed that the surface of the tumor was often surrounded by bone shell, and the lesions were mostly round or oval. Eosinophilic granuloma was mainly composed of a large number of Langerhans cells, which corresponded to the soft tissue mass on CT and could be accompanied by osteolytic destruction. Ewing’s sarcoma was mainly composed of poorly differentiated small round cells, and CT manifestations were worm-eaten bone destruction with soft tissue lesions between destroyed bone tissues. Conclusion: Various lesions occurring in the orbital bone have their own special pathological composition. Different pathological components show corresponding imaging features on CT.