婴儿多发型和弥漫型肝血管瘤临床特征比较与新亚型探索

Comparison of clinical features between multifocal versus diffuse hepatic hemangiomas and identification of new subtype in infants

目的尝试对肝血管瘤进行进一步分类,以探讨多发型和弥漫型肝血管瘤间是否存在连续性。方法对2000年1月至2020年1月在复旦大学附属儿科医院确诊的43例多发型或弥漫型肝血管瘤患儿的临床资料进行回顾性分析。依据影像学特征将患儿分为多发型组(34例)及弥漫型组(9例),再依据病灶数是否可数将多发型组分为可计数(multifocal-type with countable lesions,MC)组(6例)和难以计数(multifocal-type with uncountable lesions,MU)组(28例),比较各组间临床特征差异。结果MC组、MU组及弥漫型组皮肤血管瘤伴发率分别为66.7%(4/6)、50.0%(14/28)和44.4%(4/9),肝肿大发生率分别为0、46.4%(13/28)和100%(9/9),心力衰竭发生率分别为0、28.6%(8/28)和44.4%(4/9),呼吸困难发生率分别为0、25.0%(7/28)和66.7%(6/9),甲状腺功能减退发生率分别为0、21.4%(6/28)和77.8%(7/9)。其中,弥漫型组肝肿大、呼吸困难、甲状腺功能减退发生率较MC组和MU组均明显升高,组间比较,差异均有统计学意义(P<0.001、=0.017、0.006和P=0.004、0.032、0.004)。而MU组较MC组肝肿大发生率明显增高,组间比较,差异有统计学意义(P=0.040)。多发型组34例中,有16例(47.1%)仅观察随访,18例(52.9%)采用药物或药物联合介入治疗。其中,MC组6例(100%)均仅观察随访;MU组28例中,10例(35.7%)仅观察随访,18例(64.3%)患儿采用药物或药物联合介入治疗。弥漫型组9例(100%)均采用药物治疗,其中3例(33.3%)联合介入治疗。弥漫型组药物或药物联合介入治疗率较多发性组、MU组和MC组均显著增高,差异均具有统计学意义(P=0.027、0.038和<0.001);MU组与MC组药物或药物联合介入治疗率比较,差异亦有统计学意义(P=0.006)。所有患儿随访6个月以上,其中多发性组患儿均存活且病情好转;弥漫型组患儿死亡2例(22.2%),均采用药物联合肝动静脉瘘栓塞术治疗,均因并发严重心力衰竭死亡。MC组、MU组和弥漫型组分别有5例(83.3%)、14例(50.0%)和3例(33.3%)患儿病变完全消退,三组消退率逐渐降低。结论多发型肝血管瘤中部分病例CT或MRI横断面上病灶数量过多以至于难以准确计数,其临床特征与弥漫型肝血管瘤相似,提示其可能是多发性病变和弥漫型病变的中间连续体,需加以区分以得到及时治疗。

Objective To further classify liver hemangiomas to examine whether or not a continuum existed between multifocal versus diffuse liver hemangioma.Methods Between January 2000 and January 2020,a total of 43 children with a diagnosis of multifocal or diffuse hepatic hemangioma at Children's Hospital of Fudan University were analyzed retrospectively.They were divided into multifocal-type(n=34)and diffuse-type(n=9)groups according to radiological features.And multifocal-type group was further divided into countable(MC)(n=6)or uncountable(MU)(n=28)subgroups according to whether lesions were countable or not.Clinical features between each group were compared.Results For MC,MU and diffuse-type groups,the incidence of cutaneous hemangioma was 66.7%(4/6),50.0%(14/28)and 44.4%(4/9);the incidence of hepatomegaly 0,46.4%(13/28)and 100%(9/9);the incidence of heart failure 0,28.6%(8/28)and 44.4%(4/9);the incidence of dyspnea 0,25.0%(7/28)and 66.7%(6/9);the incidence of hypothyroidism 0,21.4%(6/28)and 77.8%(7/9).The incidence of hepatomegaly,dyspnea and hypothyroidism was higher in diffuse-type group with statistical significance than that in MC group(P<0.001;P=0.017;P=0.006)and that in MU group(P=0.004;P=0.032;P=0.004).And the incidence of hepatomegaly was higher in MU group than that in MC group(P=0.040).Among 34 cases in multifocal-type group,16 cases(47.1%)were observed and 18 cases(52.9%)received medical treatment or medical treatment plus interventional measures.Particularly,6 cases(100%)in MC group were observed;10/28 cases(35.7%)in MU group were observed and 18 cases(64.3%)received medical treatment or medical treatment plus interventional measures.Nine cases(100%)in diffuse-type group received medical treatment and 3 cases(33.3%)received medical treatment plus interventional measures.The proportion of children receiving medical treatment or medical treatment plus interventional measures in diffuse-type group was higher than those in MC/MU/multifocal-type group with statistical significance(P=0.027;P=0.038;P<0.001).And the proportion of those receiving medical treatment or medical treatment plus interventional measures was also higher in MU group than that in MC group with statistical significance(P=0.006).During a follow-up period of over 6 months,all children in multifocal-type group finally survived with stable conditions.However,2 cases(22.2%)in diffuse-type group died of severe heart failure after medical treatment plus hepatic arteriovenous fistula embolization.In contrast,the rate of complete remission was 83.3%(5/6)in MC group,50.0%(14/28)in MU group and 33.3%(3/9)in diffuse-type group.It decreased gradually.Conclusions MU group is a subgroup of multifocal hepatic hemangioma with too-numerous-to-count lesions on transverse sections of CT/MRI.With similar clinical features to diffuse hepatic hemangioma,there may be a continuum between multifocal and diffuse hepatic hemangiomas.Timely treatment is needed.