先天性胆总管囊肿的特点及危险因素

Clinical characteristics and risk factors of congenital choledochal cysts

目的探讨先天性胆总管囊肿的临床特点及危险因素。方法本研究为回顾性研究。研究对象为广东省妇幼保健院2013年1月至2018年8月收治的胎儿期确诊先天性胆总管囊肿,于生后手术治疗,临床资料完整的52例患儿。根据孕期囊肿增大的程度,分为进展型组(≥15 mm,22例)和稳定型组(<15 mm,30例)。分析2组患儿产前产后超声、MRI的特点。比较2组术前、术后的临床表现、生化检查结果,术中囊液淀粉酶水平、胆道造影和探查、肝脏活检,以及术后随访等资料。采用t(或t')或χ^2检验,以及Pearson相关分析等统计学方法分析数据。结果(1)52例患儿手术年龄为46(7~822)d。囊肿均在孕19~21周首次发现。>34孕周产前检查时,进展型组囊肿最大径明显大于稳定型组[孕31~34、>34周和术前,2组分别为(31.1±8.4)与(23.1±6.6)mm,t=3.911;(36.1±6.8)与(27.1±7.3)mm,t=4.557;(51.8±18.0)与(34.0±15.6)mm,t=3.809;P值均<0.01]。(2)进展型组产前MRI显示囊肿形态不规则,逐步增大,肝总管及肝内胆管可见,至产后逐渐明显扩张,胆总管远端呈逐渐变窄的圆锥样改变,胆总管末端逐渐闭塞,产后囊肿内可见沉淀物形成。稳定型组产前MRI显示囊肿形态不规则,其中5例可见肝总管及肝内胆管扩张,产后扩张加重,胆总管远端无圆锥样改变,产后囊肿内偶有沉淀物形成,胆总管末端可见。(3)25例开腹手术治疗的先天性胆总管囊肿患儿中,7例囊液淀粉酶高于正常水平,其中4例为正常值上限的2~5倍(进展型组1例,稳定型组3例);另3例均为稳定型组患儿,其囊液淀粉酶水平是正常值上限的10倍以上。进展型组术前直接胆红素水平高于稳定型组[18.40(2.50~113.30)与8.70(0.00~16.80)μmol/L,u=2.400,P<0.05]。(4)52例患儿中,Ⅰ型囊肿37例(71.1%),Ⅳ型14例(26.9%),Ⅴ型1例(2.0%)。所有病例术后均定期随访半年至1年,肝功能和胆红素可降至正常水平,患儿生长发育情况与同龄儿童相当。(5)52例患儿中的46例(88.5%)有不同程度的肝纤维化及炎症。进展型组手术年龄较大的患儿,肝纤维化及炎症程度较重。稳定型组手术干预时间对肝脏纤维化及炎症程度无显著影响。进展型组肝纤维化及炎症较稳定型组更严重(肝纤维化分级:χ^2=14.260,P=0.006;炎症活动程度分级:χ^2=9.904,P=0.019)。结论孕期首次检查时肝门部囊肿较大(≥30 mm)或者随孕期明显增大(≥15 mm),是先天性胆总管囊肿的危险因素,应警惕早期胆总管末端狭窄或闭塞,生后需密切追踪随访。对于产后合并大便颜色变浅、黄疸及肝功能损害的患儿建议生后早期(1~2月)外科干预,一般不超过3个月,以解除胰胆管合流解剖异常及肝脏病理状态,同时排除囊肿型胆道闭锁可能。

Objective To investigate the clinical characteristics and risk factors of congenital choledochal cysts(CCC).Methods This retrospective study recruited 52 cases who were antenatally diagnosed with CCC and underwent surgical treatment after birth in Guangdong Women and Children Hospital from January 2013 to August 2018,with complete clinical data.According to the enlargement of cysts during pregnancy,they were divided into two groups:progressive group(≥15 mm,22)and stable group(<15 mm,30).Antenatal and postpartum ultrasound and MRI features of the two groups were analyzed.Clinical manifestations and biochemical examination results before and after operation were compared between the two groups.Other data,including amylase level in cyst fluid during operation,cholangiography findings,liver biopsy results,and post-operation follow-up,were also analyzed.Chi-square test,t(t')test,and Pearson correlations tests were performed for data analysis.Results(1)The average age of the 52 patients at operation was 46(7-822)d.The cysts of all cases were first detected during 19-21 weeks of gestation.The maximum diameter of the cyst in the progressive group was larger than that in the stable group after 34 weeks of pregnancy[31-34 weeks:(31.1±8.4)vs(23.1±6.6)mm,t=3.911;>34 weeks:(36.1±6.8)vs(27.1±7.3)mm,t=4.557;pre-operation:(51.8±18.0)vs(34.0±15.6)mm,t=3.809;all P<0.01].(2)In the progressive group,the cysts were irregular in shape and enlarged after birth.The common hepatic duct and intrahepatic bile duct were dilated and gradually distended after birth,while the distal end of the common bile duct was narrowed,thus to form a cone-like duct.Deposits could be seen inside the cysts after delivery.Irregular cysts were also presented in the stable group,and five of them had dilatation of common hepatic duct and intrahepatic bile duct after birth.However,no cone-like formation was seen,the distal end of the common bile duct was visible,and deposits in cysts were occasionally found.(3)Twenty-five patients underwent laparotomy,and seven of them showed increased amylase level in cyst fluid including four with 2-5 times above the upper limit of normal value(one in the progressive group and three in the stable group).The other three cases were all in the stable group and their amylase levels in cyst fluid were more than ten times of the upper limit.The level of direct bilirubin in the progressive group was higher than that in the stable group before the operation[18.40(2.50-113.30)vs 8.70(0.00-16.80)μmol/L,u=2.400,P<0.05].(4)Among the 52 cases,patients with typeⅠ,ⅣandⅤcyst accounted for 71.1%(37/52),26.9%(14/52)and 2.0%(1/52),respectively.All cases were followed up regularly six months to one year after the operation.Liver function and bilirubin became normal and the growth and development of the babies were similar to those of the same age.(5)Different degrees of liver fibrosis and inflammation were shown in 46(88.5%)cases and more severe in older babies among those who underwent surgery in the progressive group.The time at operation was not associated with the severity of liver fibrosis and inflammation in the stable group.Hepatic fibrosis and inflammation were more serious in the progressive group than in the stable group(fibrosis grading:χ^2=14.260,P=0.006;inflammatory activity grading:χ^2=9.904,P=0.019).Conclusions Larger diameter(≥30 mm)in the initial prenatal examination or a significant increase in cystic diameter(≥15 mm)during pregnancy are risk factors for early stenosis or occlusion in the distal end of common bile duct requiring close follow-up after birth.When jaundice or abnormal liver function occur and stool color becomes light,early surgical treatment(one to two months after birth,generally within three months)for CCC is recommended to rule out the anomalous union of the pancreaticobiliary duct and hepatic disorders,as well as the cystic biliary atresia.