Study On Genetic Susceptibility And Clinical Features In Chinese Children With Chronic Pancreatitis

Objectives: More and more children has been diagnosed as chronic pancreatitis(CP)in recent years.Not only was the etiology,but the clinical manifestations of pediatric CP was quite different from those in adult.Especially,impaction of CP on growth and development was very unique in childhood.Up to date,there was few study on pediatric CP in China.Howere,the research by foreign scholars has disclosed that specific gene mutations were found in some pediatric patients with CP.It is necessary to discover clinical features and genetic variations in Chinese children with CP because of the difference in race,geography and culture between foreigners and Chinese.In addition,as a major intervention in CP,endoscopic retrograde cholangiopancreatography(ERCP)was applied in children with CP more and more.Retrospective studies have foucsed on the effect of ERCP on children with congenital choledochal cyst and cholelithiasis.The outcomes of ERCP on pediatric CP still need further study.Methods: 154 children with suspected cholecystopancreatic disease were included.Among them,94 were diagnosed as CP.We did a retrospetive study on clinical featurs.Additionally,genomic DNA extracted from peripheral blood white cells in 56 CP and 13 recurrent acute pancreatitis(RAP)patients whose parents have signed informed consent were obtained.We used Illumina Miseq platform and sequenced exons and flanking sequences of following 11 genes: PRSS1,SPINK1,CFTR,CTRC,PRSS2,CASR,CTSB,KRT8,CLDN2,CPA1 and ATP8B1.Finally,we did analysis of types of operation,findings of ERCP and complications in patients who have received ERCP.Results: Among 94 Chinese childeren with CP,the main etiological factors were idiopathic(61patients)and anomalies in anatomy(25 pati ents).Of the patients,93 had suffered abdominal pain,most of pain attacks(93.3%,28/30)were moderate to severe degree.In the last 6 months,the median of numbers of emergency department visits was 2 times,the median of hospitalizantions was 29 days,the median duration of be absent for working was 30 days and the median of duration of symptoms prior to diagnosis was 6 months.Weight standard score(SDS),BMI SDS and insulin like growth factor 1 SDS in children with CP were lower than normal,but level of 25-hydroxy vitamin D3 had no diffenrence between CP and normal children.Complications of CP observed in our study were steatorrhea,diabetes and pancreatic pseudocyst.Sensibility of magnetic resonance cholangiopancreatography(MRCP)in dectecing CP was 68.25%.After applying NGS among 69 pantients with CP and RAP,there were 45 children harbouring pathological SNVs associated with pancreatitis in the following genes: PRSS1,SPINK1,CFTR,CASR,CTSB,CTRC,KRT8.Mutations in SPINK1 could increase risk of pancreatic intraductal stones(OR=11.07,95% CI=2.29~53.54,P=0.003).Patients with CFTR mutations had a higher level of serum amylase(P<0.05).204 ERCPs were performed on 129 pediatric patients older than 1 years old.Success rate of ERCPs in our center was 99.5%.There were 157 ERCPs on 84 pediatric CP.Common complications of ERCP were hyperamylasemia(58 cases)and post operation pancreatits(35 cases).Howere,5 patients suffered gastrointestinal bleeding,one of them appeared signs of shock and need emergent endoscopic hemostasis.When hyperamylasemia was excluded,the total complication rate was 31.7%.There was a lower risk of post operation pancreatitis in patients who had a second or more ERCPs(OR=0.171,95% CI:0.058~0.506,P=0.001).Conclusions: 1.The common etiological factors in Chinese pediatric choronic pancreatits were idiopathic and anomalies in anatomy.When compared to normal children,CP patients had a lower weight SDS and BMI SDS.Serum amylase and(or)lipase should not be used in CP screening.MRCP had a higher sensitivity in deceting CP.2.Mutaitons in PRSS1? SPINK1 and CFTR were common cause in idiopathic CP.Mutations in SPINK1 could increase risk of pancreatic duct stone.3.There was a high success rate of ERCP on pediatric patient older than 1 year.ERCP was quite fit for CP treatment.After ERCP,a higher complications incidence was observed,especially on pancreatitis.