不同质量浓度5-氟尿嘧啶联合曲安奈德治疗瘢痕疙瘩的多中心前瞻性随机对照临床研究

A multicenter prospective randomized controlled clinical study of 5-fluorouracil in different mass concentrations combined with triamcinolone in the treatment of keloids

目的评价不同质量浓度的5-氟尿嘧啶联合曲安奈德治疗瘢痕疙瘩的临床效果。方法2018年3月—2019年3月,将福建医科大学附属协和医院整形外科接诊的29例患者31个瘢痕疙瘩、平潭综合实验区医院皮肤科接诊的11例患者20个瘢痕疙瘩、福州市仓山迪娅医疗美容门诊部接诊的9例患者9个瘢痕疙瘩纳入此前瞻性随机对照研究,其中男27例、女22例,年龄(30±9)岁。将瘢痕疙瘩按随机数字表法分为低质量浓度组(19个瘢痕疙瘩,17例患者)、中质量浓度组(21个瘢痕疙瘩,19例患者)、高质量浓度组(20个瘢痕疙瘩,17例患者),分别采用质量浓度为0.5、5.0、12.5 mg/mL的5-氟尿嘧啶联合曲安奈德注射治疗,每4周注射1次,共3次。首次治疗前及末次治疗后3个月,采用温哥华瘢痕量表(VSS)评价瘢痕疙瘩外观、采用视觉模拟评分法(VAS)评定瘢痕疙瘩疼痛和瘙痒程度,并计算治疗前后的评分差值。末次治疗后6个月,采用疗效满意度评价量表行患者疗效满意度评分。记录治疗期间不良反应。末次治疗后1年随访,统计瘢痕疙瘩复发率。对数据行χ^(2)检验、单因素方差分析、配对样本t检验、LSD-t检验、Wilcoxon秩和检验、Kruskal-Wallis秩和检验、Fisher确切概率法检验。结果首次治疗前,3组瘢痕疙瘩外观VSS评分相近(F=0.039,P>0.05);末次治疗后3个月,低质量浓度组瘢痕疙瘩外观VSS评分明显高于中质量浓度组及高质量浓度组(t=2.267、4.086,P<0.05或P<0.01)。末次治疗后3个月,低质量浓度组、中质量浓度组、高质量浓度组瘢痕疙瘩外观VSS评分均较首次治疗前明显降低(t=18.222、44.272、22.523,P<0.01)。低质量浓度组瘢痕疙瘩治疗前后外观VSS评分差值明显低于中质量浓度组与高质量浓度组(t=-4.096、-6.357,P<0.01),中质量浓度组瘢痕疙瘩治疗前后外观VSS评分差值明显低于高质量浓度组(t=-2.368,P<0.05)。首次治疗前,3组瘢痕疙瘩疼痛和瘙痒VAS评分相近(χ^(2)=0.149,P>0.05);末次治疗后3个月,低质量浓度组瘢痕疙瘩疼痛和瘙痒VAS评分明显高于中质量浓度组及高质量浓度组(Z=2.191、4.386,P<0.05或P<0.01),中质量浓度组瘢痕疙瘩疼痛和瘙痒VAS评分明显高于高质量浓度组(Z=2.276,P<0.05)。末次治疗后3个月,中质量浓度组和高质量浓度组瘢痕疙瘩疼痛和瘙痒VAS评分均较首次治疗前明显降低(Z=-3.904、-3.844,P<0.01)。低质量浓度组瘢痕疙瘩治疗前后疼痛和瘙痒VAS评分差值明显低于中质量浓度组与高质量浓度组(Z=-4.265、-6.104,P<0.01)。末次治疗后6个月,高质量浓度组瘢痕疙瘩对应患者疗效满意度评分为(88±8)分,明显高于中质量浓度组的(76±8)分和低质量浓度组的(60±8)分(t=-3.820、-6.675,P<0.01),中质量浓度组瘢痕疙瘩对应患者疗效满意度评分明显高于低质量浓度组(t=-2.984,P<0.05)。3组瘢痕疙瘩治疗期间仅疼痛差异明显(P<0.01)。末次治疗后1年随访,高质量浓度组瘢痕疙瘩复发率明显低于低质量浓度组(χ^(2)=8.313,P<0.01),中质量浓度组瘢痕疙瘩复发率与低质量浓度组、高质量浓度组相近(χ^(2)=3.536、0.577,P>0.05)。结论高质量浓度的5-氟尿嘧啶联合曲安奈德治疗瘢痕疙瘩后,症状改善明显,患者治疗满意度增加,无明显不良反应且疗效持久,较中、低质量浓度的5-氟尿嘧啶整体效果好,值得临床推广。

Objective To evaluate the clinical effects of 5-fluorouracil in different mass concentrations combined with triamcinolone in the treatment of keloids.Methods From March 2018 to March 2019,29 patients with 31 keloids receipted in the Department of Plastic Surgery of Fujian Medical University Union Hospital,11 patients with 20 keloids receipted in the Department of Dermatology of Pingtan Comprehensive Experimental Area Hospital,and 9 patients with 9 keloids receipted in the Fuzhou Heisey-Dea Aesthetic Clinic were included in this prospectively randomized control study,with 27 males and 22 females,aged(30±9)years.According to the random number table,the keloids were divided into low mass concentration group(19 keloids,17 patients),medium mass concentration group(21 keloids,19 patients),and high mass concentration group(20 keloids,17 patients).Then 5-fluorouracil at mass concentrations of 0.5,5.0,and 12.5 mg/mL combined with triamcinolone acetonide were injected respectively,once every 4 weeks,for a total of 3 times.Before the first treatment and in 3 months after the last treatment,the appearance of keloids was evaluated by Vancouver Scar Scale(VSS)and pain and pruritus of keloids were evaluated by Visual Analogue Scale(VAS).Then the score differences before and after the treatment were calculated.In 6 months after the last treatment,the patients'efficacy satisfaction was evaluated by efficacy satisfaction rating scale.Adverse reactions during the treatment were recorded.In the follow-up of one year after the last treatment,the recurrence rates of keloids were counted.Data were statistically analyzed with chi-square test,one-way analysis of variance,paired sample t test,least significant difference t test,Wilcoxon rank sum test,Kruskal-Wallis rank sum test,or Fisher′s exact probability test.Results Before the first treatment,the appearance VSS scores of appearance of keloids in the three groups were similar(F=0.039,P>0.05).In 3 months after the last treatment,the appearance VSS scores of keloids in low mass concentration group were significantly higher than those in medium mass concentration group and high mass concentration group(t=2.267,4.086,P<0.05 or P<0.01).In 3 months after the last treatment,the appearance VSS scores of keloids in low mass concentration group,medium mass concentration group,and high mass concentration group were significantly decreased compared with those before the first treatment(t=18.222,44.272,22.523,P<0.01).The differences of appearance VSS scores of keloids in low mass concentration group before and after treatment were significantly lower than those in medium mass concentration group and high mass concentration group(t=-4.096,-6.357,P<0.01),and the differences of appearance VSS scores of keloids in medium mass concentration group before and after treatment were significantly lower than those in high mass concentration group(t=-2.368,P<0.05).Before the first treatment,the pain and pruritus VAS scores of keloids in the three groups were similar(χ^(2)=0.149,P>0.05).In 3 months after the last treatment,the pain and pruritus VAS scores of keloids in low mass concentration group were significantly higher than those in medium mass concentration group and high mass concentration group(Z=2.191,4.386,P<0.05 or P<0.01),and the pain and pruritus VAS scores of keloids in medium mass concentration group were significantly higher than those in high mass concentration group(Z=2.276,P<0.05).In 3 months after the last treatment,the pain and pruritus VAS scores of keloids in medium mass concentration group and high mass concentration group were significantly decreased compared with those before the first treatment(Z=-3.904,-3.844,P<0.01).The differences of pain and pruritus VAS scores of keloids in low mass concentration group before and after treatment were significantly lower than those in medium mass concentration group and high mass concentration group(Z=-4.265,-6.104,P<0.01).In 6 months after the last treatment,the efficacy satisfaction scores of the corresponding patients of keloids were(88±8)points in high mass concentration group,which were significantly higher than(76±8)points in medium mass concentration group and(60±8)points in low mass concentration group(t=-3.820,-6.675,P<0.01),and the efficacy satisfaction scores of the corresponding patients of keloids in medium mass concentration group were significantly higher than those in high mass concentration group(t=-2.984,P<0.05).There was only statistically significant difference in pain within the 3 groups(P<0.01).In the follow-up of one year after the last treatment,the recurrence rate of keloids in high mass concentration group was significantly lower than that in low mass concentration group(χ^(2)=8.313,P<0.01),and the recurrence rate of keloids in medium mass concentration group was similar to the recurrence rates in low mass concentration group and high mass concentration group(P>0.05).Conclusions After treating keloids with high mass concentration of 5-fluorouracil combined with triamcinolone acetonide,the symptoms were significantly improved,the efficacy satisfaction of patients was increased,with no obvious adverse reactions but long lasting efficacy.Their overall effects are better than treatment using medium and low mass concentrations of 5-fluorouracil,which is worthy of clinical promotion.