口服普萘洛尔治疗婴幼儿血管瘤的临床研究

目的:观察口服普萘洛尔治疗婴幼儿血管瘤的疗效。方法:2009年1月～2011年6月,笔者采用口服普萘洛尔治疗11例婴幼儿血管瘤,2mg/kg/天,分2次口服,3个月为1个疗程。如观察瘤体有复发表现,则重复1个疗程,至患儿1岁停药。结果:口服普萘洛尔后1周,瘤体颜色开始变淡、萎缩变软。治疗3个月后,大部分瘤体明显萎缩。至1岁时,瘤体基本消退,表面遗留毛细血管扩张。部分患儿出现心率减慢和腹泻,均在停药1周后恢复,继续治疗。结论:口服小剂量普萘洛尔治疗婴幼儿血管瘤具有良好疗效。     

婴幼儿血管瘤的普萘洛尔治疗

血管瘤是婴幼儿常见的良性肿瘤之一,发病率为1%～10%,好发于头面部.血管瘤发病率存在明显的性别差异,女性多于男性,比例约3∶ 1～5∶ 1.种族不同,其发病率也稍有差异.高加索人种的发病率高达5%～10%;而在非洲裔的婴幼儿中,发病率约2.8%[1].在早产儿中,低体质量出生是血管瘤发病的危险因素,体质量每减少500g,患血管瘤的风险可增加40%[2].婴幼儿血管瘤具有独特的生命周期,基本分为两个阶段,包括增殖期和消退期.     

普萘洛尔作为严重婴幼儿血管瘤一线治疗的前瞻性研究

目的 前瞻性评价普萘洛尔作为一线方案治疗严重婴幼儿血管瘤的疗效和安全性.方法 2009年3月至2010年2月对78例严重婴幼儿血管瘤患儿口服普萘洛进行治疗,用药剂量为每天2 mg/kg.患儿性别、年龄、肿物部位、并发症以及患儿入选该治疗的指征、不良反应、停药后有无复发等均被详细记录.针对服药后1周、1个月和停药时疗效分别评价.平均随访时间为16.7个月(12.1～23.6个月).结果 初始服药平均年龄为3.7个月(1.1～9.2个月),停止服药的平均年龄为11.2个月(5.2～22.3个月).疗程平均7.6个月(2.1～18.3个月).所有患儿口服普萘洛尔1周后肿物生长有效控制,其中88.5%(69/78)的患儿表现为促进消退.服药1个月和停药时,表现为促进消退的患儿达98.7%(77/78).14例伴发溃疡的血管瘤患儿,溃疡在服药后2个月内均愈合.15.4%(12/78)患儿有轻微不良反应.35.9%(28/78)患儿停药后有复发倾向.结论 普萘洛尔治疗婴幼儿血管瘤疗效明显,不良反应小,可作为严重婴幼儿血管瘤的一线治疗.

Abstract：

Objective To prospectively assess the efficacy and safety of propranolol as a first-line treatment for problematic infantile haemangioma in China. Methods From Mar. 2009 to Feb. 2010, 78 patients with problematic infantile hemangioma were included in the prospective study. The characteristics of the tumor, including sex, age, site, complications, were recorded. The response to treatment at 1 week, at 1 month and at the end of treatment was evaluated. The efficacy of treatment was graded as no response, stabilization, or accelerated regression. The indications for treatment, side effects and relapse after treatment were documented. The mean follow-up period was 16.7 months (range, 12.1-23.6 months). Results Oral therapy was initiated at mean age of 3. 7 months (range, 1.1-9.2 months) as first-line therapy. The mean age at the end of treatment was 11.2 months ( range, 5. 2-22. 3 months) . The treatment was lasted for 7. 6 months (range, 2. 1-18. 3 months). One week after treatment beginning, the hemangioma growth was controlled in all the patients. The accelerated regression was achieved in 88. 5% (69/78) of patients after one week of treatment, and 98.7% (77/78) of patients after 1 month of treatment and at the end of treatment. Ulceration was occurred in 14 cases before treatment, which was healed after treatment for 2 months. Minor side effects were happened in 15.4% ( 12/78) of patients.Rebound growth of lesion was noticed in 35. 9% (28/78 ) of patients. Conclusions Propranolol is effective in the treatment of infantile hemangioma with minor side effect. We suggest it should be used as the first-line treatment.     

普萘洛尔治疗增生期婴幼儿血管瘤的临床研究

目的：通过对普萘洛尔治疗婴幼儿血管瘤的临床研究,评估其治疗效果和安全性。方法：将我科从2009年9月至2010年8月收集的41例血管瘤患儿根据其家属的意见分为治疗组和观察组,其中治疗组20例,接受口服普萘洛尔治疗;观察组21例,接受门诊随访观察,比较两组的血管瘤变化情况,并检测治疗组服药前后患儿的心率、血糖、肝功能、肾功能、甲状腺功能等变化情况。结果：经过2个月的观察或治疗,治疗组显效9例,有效11例,无效0例;观察组显效0例,有效8例,无效13例。治疗组和观察组疗效有显著性差异,同时治疗组患儿治疗前与治疗后1h心率有所变化,其他如血糖和肝功能、肾功能及血FT3、FT4、sTSH等变化无明显统计学意义。结论：普萘洛尔在治疗婴幼儿血管瘤的过程中可抑制血管瘤的生长,部分患儿效果显著;治疗过程中不良反应少,安全性较高。     

小剂量普萘洛尔治疗婴幼儿血管瘤的临床观察

目的：探讨小剂量普萘洛尔治疗婴幼儿血管瘤的疗效及安全性。方法：收集增生期婴幼儿血管瘤23例（男6例,女17例）,口服普萘洛尔0.5～0.75 mg/（kg.d）,疗程1～9个月,并进行疗效评定和安全性评价。结果：疗效评定：优6例（26.1%）,良9例（39.1%）,中等8例（34.8%）;不良反应包括：心率轻度减慢8例（34.78%）,睡眠障碍2例（8.7%）,腹泻1例（4.3%）。不良反应轻,均1周内自行消失;安全性评定：15例为安全,8例为比较安全。结论：小剂量普萘洛尔治疗婴幼儿血管瘤,疗效良好,不良反应轻,安全性较好。     

普萘洛尔治疗婴幼儿血管瘤的临床研究进展

血管瘤多发生于婴幼儿期,是起源于血管内皮细胞的一种良性肿瘤,发生率为5%～10%[1].婴幼儿血管瘤(infantile hemangioma, IH)多具有自限性,有85%～90%的患儿在7～10岁时自然消退,但一些血管瘤因其显著生长或影响机体功能而须及时干预治疗[2].目前的治疗方法有药物、手术、激光、冷冻等.2008年,Léauté-Labrèze等[3] 偶然发现并提出普萘洛尔可作为一种新的药物治疗方法.随后,多国专家学者进行了一系列临床研究和科学分析,相继报道了普萘洛尔治疗IH的良好疗效及其安全性,并建议将其作为治疗IH的一线药物.笔者就近年来普萘洛尔治疗IH的临床研究现状进行综述.     

口服普萘洛尔治疗严重婴幼儿血管瘤的临床观察

目的:评估普萘洛尔治疗严重婴幼儿血管瘤的临床疗效和安全性。方法:2010年9月～2012年9月,笔者科室对34例严重婴幼儿血管瘤患儿进行口服普萘洛治疗,服药剂量为第1天1.0mg/kg,第2天1.5mg/kg,第3天2mg/kg,12h 1次、分2次服用。服药后1周、1个月和停药时进行疗效评价,并进行随访。结果:所有患儿在口服普萘洛尔1周后瘤体得到控制,服药1月和停药时,97.1%(33/34)的患儿表现为促进消退。3例伴发溃疡的血管瘤患儿,溃疡在服药后1个月内均愈合。8.8%(3/34)患儿有腹泻、食欲减退的不良反应。26.5%(9/34)患儿停药后有复发倾向。结论:普萘洛尔治疗婴幼儿血管瘤疗效明显,不良反应小,可作为严重婴幼儿血管瘤的治疗方法之一。     

口服普萘洛尔治疗婴幼儿血管瘤的临床效果观察

目的:评价普萘洛尔治疗婴幼儿血管瘤的疗效。方法:按照严格的纳入、排除标准,成功筛选30例血管瘤患儿作为口服普萘洛尔的治疗对象,年龄为28天～10月,平均年龄4.8月。<3个月患儿,剂量1.5mg.kg-1.d-1;>3个月患儿,剂量2.5mg.kg-1.d-1,每天分2次服用。一般住院治疗5～7天,复查心电图、三大常规、肝肾功能、血糖、血脂及电解质等。如无异常予以出院带药。嘱患者出院后继续服药,用药前3个月,每2周复诊1次;3个月后每月复诊一次。结果:按四级评分法对药物疗效进行评估。治疗30例患儿,其中I级疗效有2例(差);Ⅱ级4例(中);Ⅲ级14例(好);Ⅳ级10例(优)。结论:口服普萘洛尔治疗婴幼儿血管瘤效果明显,副作用小,用药安全范围广,今后在临床上有望推广应用。     

口服普萘洛尔治疗婴幼儿体表血管瘤临床观察

目的:探讨口服普萘洛尔治疗婴幼儿血管瘤的临床疗效、安全性及方法。方法:共收治56例体表血管瘤患儿,完善检查后口服普萘洛尔治疗,初始剂量为0.5mg/kg/d,分2次餐后服用,若患儿无不良反应,则每日增加0.2mg/kg至总量1.5mg/kg/d,维持治疗4个月后每日减少0.2mg/kg至停药,治疗结束半年后参照Achauer标准进行疗效评定。结果:其中1例服药不到1个月因出现疲劳、乏力,家属放弃治疗,2例服药3个月后瘤体基本消退而停药,其余53例均维持服药4个月,治疗结束时,大部分血管瘤明显缩小,颜色变淡,甚至消退,停药6个月后评定疗效:Ⅰ级2例(含复发1例),Ⅱ级6例(含复发5例),Ⅲ级17例,Ⅳ级31例,停药后复发6例。结论:口服普萘洛尔是治疗婴幼儿血管瘤有效方法之一,其疗效及安全性可能与剂量及用药方式有关。     

普萘洛尔凝胶治疗婴幼儿血管瘤的疗效观察

目的 评价普奈洛尔凝胶外涂治疗婴幼儿血管瘤的临床疗效与安全性.方法 2010年10月至2011年9月,采用外涂普萘洛尔凝胶的方法治疗51例血管瘤患儿,动态观察患儿血管瘤大小、质地、颜色、瘤体血流峰值、阻力系数等变化及不良反应.结果 按照Achauer疗效评定法,51例患儿疗效评定Ⅰ级4例(7.84％),Ⅱ级18例(35.29％),Ⅲ级22例(43.14％),Ⅳ级7例(13.73％,P＜0.05).彩色超声多普勒血流仪检查示血管瘤血流峰值减少、阻力系数增加(P＜0.05).浅表型血管瘤疗效优于深部型及混合型血管瘤(P＜0.05),而不同部位的血管瘤疗效之间比较差异无统计学意义(P＞0.05).结论 外涂普萘洛尔凝胶治疗婴幼儿浅表型血管瘤治疗效果满意,无明显不良反应.     

大剂量普萘洛尔治疗严重婴幼儿血管瘤的初步临床观察

目的 初步探讨口服大剂量普萘洛尔治疗严重婴幼儿血管瘤的临床疗效和安全性.方法 2010年4月至2011年2月为56例严重的婴幼儿血管瘤患儿行口服普萘洛尔治疗,治疗前行全面的临床评估、心电图、血常规、肝功能、心肌酶和肌钙蛋白检查,治疗时口服普萘洛尔剂量逐渐增加,前3 d的剂量分别为每天1 ms/kg、1.5 mg/kg、2 mg/kg,每天按12 h 1次,分2次,喂奶后半小时服用,住院6 d,患儿无异常表现后出院;出院后每周复测心率,每个月复诊,6个月为1个治疗疗程,治疗结束时逐渐减量后停药.结果 56例患儿在服药后第2～4天就可观察到血管瘤的颜色改变.治疗后1个月复诊时观察血管瘤明显改善,瘤体体积不同程度变小、质地变软,伴有溃疡的患儿除1例溃疡扩大外其余均愈合.56例中10例血管瘤完全消退,46例明显改善;1例治疗3个月后血管瘤消退停止;3例出现不良反应:1例在治疗1个月后出现肝功能轻度异常,1例治疗过程中CKMB升高,给予继续观察,1例CK-MB、LDH、ALT、GGT持续升高,给予停药.结论 大剂量口服普萘洛尔治疗严重的婴幼儿血管瘤显效快,疗效明显,患儿耐受性好,不良反应少,可显著缩短血管瘤的病程,可能成为治疗严重婴幼儿血管瘤的首选方法.

Abstract：

Objective To investigate the clinical results of the treatment of severe infantile hemangioma with high-dose propranolol in Chinese. Methods 56 cases with severe infantile hemangioma were treated with propranolol. Clinical evaluation, electrocardiography, and experimental examination of liver function and heart function were performed before treatment. The daily dose of propranolol was increased from 1 mg/kg at the first day to 1. 5 mg/kg at the second day, and to 2 mg/kg at the third day.The propranolol was given twice a day. The treatment was lasted for six months. The patients were visited every month. Results The lesion color was changed after 2-4 days of treatment in all the cases. All the lesions were dramatically improved after one month of treatment. The ulceration were healed, except one case. Until now, complete regression was achieved in 10 cases and marked improvement in 46 cases. Side effects were happened in 3 cases, including one case of abnormal liver function, one case of CK-MB increase and one case of continuous increase of CK-MB, LDH, ALT, GGT. Conclusions High-dose Propranolol is very effective in the treatment of infantile hemangioma with minor side effects and short disease period. It might be used as the first-line treatment for infantile hemangioma.     

口服普萘洛尔治疗眶周部增生期婴幼儿血管瘤

目的 探讨口服普萘洛尔治疗眶周部增生期婴幼儿血管瘤的疗效及安全性.方法 2009年9月至2010年10月,临床治疗12例眶周部增牛期婴幼儿血管瘤患儿,女9例,男3例,年龄1.5～8.5个月,平均3.3个月,采用口服普萘洛尔治疗.服药剂量每日2 mg/kg,分3次给药,治疗时间为4～41周(平均16周),依据服药前后瘤体大小、颜色变化进行疗效评价,通过服药疗程及期间出现的并发症情况进行安全性评估.结果 12例患儿中,9例服药后瘤体明显消退;2例瘤体生长明显受抑制;1例服药后,因药物不良反应而终止治疗.服药期间,除少数患儿出现轻度的心率、血压暂时性降低及胃返流外,未出现其他较为严重的并发症.结论 口服普萘洛尔治疗眶周部增生期婴幼儿血管瘤安全有效,随着临床研究的不断深入,有望成为非手术治疗婴幼儿血管瘤的重要方法之一.

Abstract：

Objective To observe the efficacy and safety of oral propranolol in the treatment of periorbital proliferating phase infantile hemangioma. Methods A retrospective review of patient medical records was performed. 12 patients (9 female, 3 male; 1.5-8.5 months, average 3.3 months) with periorbital proliferating phase infantile hemangioma underwent oral propranolol therapy. The dosage was slowly increased to 2 mg/kg daily in divided doses for a mean duration of 16 weeks ( range 4 weeks41 weeks). Therapeutic outcomes and safety were established by evaluating colour, size of lesion, duration of treatment and side-effects of treatment before and after treatment. Results Of these, 9 had a signification reduction in colour and size of the lesions, 2 had no further growth. 1 is stopped therapy due to hypotension after drug administration. 11 other patients, although mild adverse effects were noted, no symptoms were severe enough to discontinue treatment. Conclusions Propranolol appears to be a safe and effective treatment in the management of periorbital proliferating phase infantile hemangioma.     

普萘洛尔对血管瘤内皮细胞的抑制作用

目的:探讨不同浓度普萘洛尔在不同时间段内对血管瘤内皮细胞的抑制作用。方法:收集手术切除的新鲜婴幼儿血管瘤标本,采用组织块法培养内皮细胞,免疫荧光法对培养的细胞进行鉴定;通过绘制生长曲线和流式细胞仪检测普萘洛尔(propranolol)对血管瘤内皮细胞增殖影响。结果:伴随普诺洛尔浓度增大(0μg/ml,20μg/ml,40μg/ml,60μg/ml,80μg/ml,100μg/ml,120μg/ml)及作用时间的增加(24h,48h,72h)对血管瘤内皮细胞的抑制作用明显增强;流式细胞仪测定不同浓度普萘洛尔作用不同时段后血管瘤内皮细胞凋亡明显。结论:普萘洛尔能抑制血管瘤内皮细胞的增殖并促进其凋亡,抑制血管瘤的生长。     

不消退型先天性血管瘤与婴幼儿血管瘤的病理比较

目的 比较研究不消退型先天性血管瘤(noninvoluting congenital hemangioma,NICH)与婴幼儿血管瘤(infantile hemangioma,IH)的病理特征,检测葡萄糖转运蛋白-1(Glut-1)的表达,探讨NICH的病理结构与病程发展的关系.方法 2005年1月至2010年8月,收集13例NICH,13例增殖期IH和13例消退期IH临床标本,采用HE染色和免疫组化染色方法,比较NICH、增殖期IH和消退期IH的病理结构以及Glut-1的表达.结果 HE染色显示,NICH瘤体呈规则的小叶结构,小叶被丰富的纤维组织包绕,小叶内微血管管径较大,小叶内血管壁完整,内皮细胞罕有增殖和凋亡.IH病变呈现从增殖到消退改变,微血管管径较小,血管壁不完整,周细胞扁平,血管内皮细胞和间质细胞可见增殖和凋亡.NICH中不表达Glut-1,增殖期IH肿瘤内皮细胞中Glut-1表达阳性,消退期IH中Glut-1表达阴性或弱阳性.结论 NICH是一种具有低增殖性的血管瘤,病理结构稳定,与增生期IH血管内皮细胞的增殖性具有明显的不同;Glut-1可以作为鉴别NICH和增殖期IH的可靠抗原标记.

Abstract：

Objective To distinguish noninvoluting congenital hemangioma (NICH) and infantile hemangioma ( IH ) by comparing the pathological structure and marker antigen expression. Methods From Jan. 2005 to Aug. 2010,39 paraffin-embedded samples, including 13 cases of NICH, 13 cases of proliferating IH and 13 cases of involuting IH, were collected from operation. Hematoxylin-eosin staining was used to observe the pathological structure. Immunohistochemical analysis was also performed to investigate the expression of Glut-1. Results The lobules of capillaries were well-defined in NICH. The lobules were surrounded by abundant fibrous tissue. The capillaries were often large and integrity in NICH.There were few mitosis and apoptosis in endothelial cells and stromal cells in NICH. While in IH, the pathologic findings were totally different. Immunochemistry revealed that the Glut-1 was expressed in endothelial cells of IH, but not in NICH. Conclusions NICH has a steady histologic structure and low proliferation, while the endothelial cells in proliferative IH has a high proliferation. Glut-1 can be used as the reliable marker antigen for differential diagnosis of NICH and proliferative infantile hemangiomas.     

Effect of propranolol vs prednisolone vs propranolol with prednisolone in the management of infantile hemangioma: A randomized controlled study

Aims and Objectives

The purpose of this study was to compare the efficacy of orally administered propranolol versus prednisolone versus both in the treatment of potentially disfiguring or functionally threatening infantile hemangiomas.

Material and Methods

A prospective study of 30 patients aged 1 week–8 months was randomized into three equal groups. These were as follows: A, propranolol (2–3 mg/kg/d); B, prednisolone (1–4 mg/kg/d); and C, receiving both for a minimum duration of 3 months. Dimensions, color, consistency, ultrasonography, photographic documentation based on Visual Analogue Scale (VAS) were recorded before and periodically after starting treatment. A minimum 75% improvement was considered as success with no regrowth up to 1 month of stopping treatment.

Results

Mean initial response time (days) in A (4.1 ± 3.3 SD) and C (4.7 ± 3.4SD) was significantly lower than B (9.78 ± 7.8SD) (p < 0.047). Significant change in consistency was noted very early in A (24 hours) compared to B and C (8 days). VAS results are as follows: (a) color fading—significant reduction in A within 48 hours compared to B and C (p = 0.025), (b) flattening—more significant and earlier in A and C than B (p < 0.05), and (c) mean reduction in size: significant in A and C at 3 months (p = 0.005, p = 0.005), 6 months (p = 0.005, p = 0.008), 12 months (p = 0.005, p = 0.008), and 18 months (p = 0.02, p = 0.04), whereas in B, it was seen only at 6 months (p = 0.008).

Conclusions

Propranolol had a consistent, rapid therapeutic effect compared to prednisolone. A combination of the two had a comparable but not higher efficacy than propranolol alone. Prednisolone was associated with a higher number of complications, thereby decreasing patient compliance.