Efficacy And Safety Of Rapamycin In The Treatment Of Complicated Low-flow Vascular Malformations In Children

Objective: Study the efficacy and safety of Rapamycin in the treatment of complicated low-flow vascular malformation in children,in order to guide clinical medication.Methods: From July 2018 to December 2019,11 children with complex and difficult low flow vascular malformations were enrolled from Pediatric Surgery of the First Affiliated Hospital of Gannan Medical College.All the patients were confirmed by color Doppler,MRI,histopathological examination and had previously received sclerotherapy and / or surgery and other traditional treatment methods were ineffective.The age was no more than 13 years old,and 11 of them met the enrollment criteria Rapamycin treatment(also known as sirolimus)was followed up for 1 year.The maximum diameter,coagulation parameters,pain score,quality of life score,clinical manifestations and adverse reactions of all children before and after 1 month,3 months and 6 months after medication were monitored.Results: 1.Changes in lesion size: the largest diameter(LD)(11.38±8.863)cm in 11 patients before oral Rapamycin treatment,and the LD(12.48±8.989)cm,(11.36±9.451)cm,and(9.50±9.645)cm after 1,3 and 6 months of treatment,respectively.T =1.723 and P=0.116 > 0.05 were compared with LD of the lesion 1 month after treatment,showing no statistical difference.Before treatment,LD was compared with 3 and 6 months after treatment(t=2.285,p=0.045)and(t=3.340,p=0.007),respectively.All p values were < 0.05,showing statistical differences.Results of the correlation analysis between LD and age: |r|=0.085,p=0.803 > 0.05.2.Before and after treatment with pain situation changed: 11 cases of oral Rapamycin therapy before pain coefficient of 0.49 ±0.226;1,3,6 months after treatment pain coefficient were(0.27±0.110)、(0.17±0.119)、(0.14±0.092),before treatment and 1,3 and 6 months after treatment comparison results are respectively(t=3.695,p=0.004),(t=4.311,p=0.002),(t=4.983,p=0.001),p values < 0.05,statistically significant.3.Changes in quality of life assessment before and after treatment for 6 months.Quality of life was assessed in 9 out of 11 children(≥2 years old).Quality of life was assessed in 9 out of 11 children(≥2 years old).The total score before oral Rapamycin treatment was(49.11±8.964)points,and the total score after 6 months of treatment was(31.00±8.631)points.The comparison before and after treatment t=6.746,p=0.000 < 0.05 showed statistical differences.Among them,the improvement in physiological function and school performance was outstanding.Activity or function improved in all patients,pain decreased,bleeding or errhysis,or infection was reduced or stopped.4.Changes in coagulation parameters of children before and after treatment: according to the study,4 of the 11 children with complicated low-flow vascular malformations were found to contain venous components,accompanied by abnormal coagulation function,showing high d-dimer and/or normal-low fibrinogen levels.The d-dimer of all children was reduced after treatment for 1-3 months,and the low fibrinogen significantly recovered after 6 months of evaluation.4 patients with abnormal coagulation showed significant improvement in coagulation after oral treatment with Rapamycin.5.Adverse reactions:take Rapamycin orally therapy for a year,the adverse reactions are fever in 2 cases(18.2%,3#,6#),mucosal inflammation such as oral cavity ulcer,2 cases(18.2%,2#,8#),flu-like symptoms,3 cases(27.3%,3#,4#,6#),gastrointestinal reaction in 2 cases(18.2%,3#,6#),fatigue in 2 cases(18.2%,8#,10#),skin rash in 1 case(9.1%,2#),baby teeth growth retardation in 1 case(9.1%,4#),mild thrombocytosis in 1 case(9.1%,2#),mild abnormal liver function in 1 case(9.1%,1#),etc.Most of the symptoms were mild and did not stop medication or other special treatment.Conclusion: 1.Oral Rapamycin is effective in the treatment of complex low flow vascular malformation in children.2.Children generally tolerate the standard dose of Rapamycin,with mild adverse reactions and high safety.3.Children with complex vascular malformation are younger and may be affected by long-term illness and medical treatment experience in psychological cognition,and their quality of life assessment is significantly reduced.After receiving Rapamycin treatment,they can significantly improve,especially in terms of physiological function and school performance.