Study of the Malformation of Ductal Plate of the Liver in Meckel Syndrome and Review of Other Syndromes Presenting with This Anomaly

Meckel syndrome (MIM 249.000) is an autosomal recessive disorder with a variable spectrum of anomalies. Since the first reports of this syndrome, very broad diagnostic criteria have been proposed, but the process of defining them continues. It is probable that at least two of three manifestations, including cystic kidney dysplasia, occipital encephalocele or other anomaly of the central nervous system, and postaxial polydactyly occur in most cases. Arrest of the development of intrahepatic bile ducts at the stage of the bilaminar plate formation or ductal plate malformation is considered of high diagnostic value in Meckel syndrome, but there is no complete agreement in the literature about its occurrence. The aims of this investigation were to study the prevalence and morphologic patterns of ductal plate malformation of the liver in Meckel syndrome by evaluating the dilatation of primitive biliary structures and the increase in connective tissue of the portal tract. Archival data files from four German centers (Berlin, Freiburg, Heidelberg, Mainz) were reviewed. Liver sections of 30 well-studied fetuses with Meckel syndrome were immunostained with antibodies against cytokeratins (intermediate filaments of the cytoskeleton) and factor VIII (an endothelial cell marker) and were evaluated both qualitatively and quantitatively. Cystic kidney dysplasia, occipital encephalocele, and postaxial polydactyly were found in 100%, 90%, and 83.3% of the fetuses, respectively. Ductal plate malformation of the liver was a constant anomaly in Meckel syndrome, seen as frequently as renal lesions. We observed essentially two kinds of hepatic lesions: 23 cases showed mainly a cystic dilatation of primitive biliary structures with little portal fibrosis, while 7 cases showed mainly rings of interrupted curved lumina around a central fibrovascular axis and pronounced portal fibrosis. In these seven cases an abnormal pattern of the portal vein, with many small and closely spaced branches of the portal vein (the so-called pollard willow pattern), was also seen. With respect to other fetal developmental anomalies, no difference between the two types of lesions was found. We also provide a potentially useful comprehensive review of other genetic syndromes in which ductal plate malformations may occur. Received May 14, 1999; accepted October 11, 1999.     

Successful liver transplantation in a child with Caroli's disease

Abstract:  CD is a rare autosomal recessive disease, characterized by multifocal cystic dilatation of intrahepatic bile ducts. The course of the disease is characterized by intrahepatic cholelithiasis, recurrent episodes of cholangitis, because of cholelithiasis, hepatic abscesses often ending in death caused by uncontrolled infection. Other conditions such as choledochal cyst and renal cystic disease are frequently associated, and patients have a higher risk for the development of cholangiocarcinoma. Endoscopic drainage of the bile duct is palliative and ineffective. OLT appears to be the treatment of choice. In monolobar cases partial liver resection has been shown to be a curative therapeutic option. We report on the course of disease in a Turkish girl who was diagnosed with CD in the neonatal period. At the age of 8.2 yr, she received OLT and is in good health 57 months post-transplantation.     

Fibropolycystic liver disease in children

Fibropolycystic liver diseases are a group of associated congenital disorders that present most often in childhood. These disorders include congenital hepatic fibrosis, biliary hamartomas, autosomal dominant polycystic liver disease, choledochal cysts and Caroli disease. We present a discussion and illustrations of the embryology, genetics, anatomy, pathology, imaging approach and key imaging features that distinguish fibropolycystic liver disease in children. The pathogenesis of these disorders is believed to be abnormal development of the embryonic ductal plates, which ultimately form the liver and biliary systems. An understanding of the abnormal embryogenesis helps to explain the characteristic imaging features of these disorders.     

Central diabetes insipidus associated with Caroli syndrome

Caroli disease is a rare congenital malformation characterized by cystic dilatations of large bile ducts. There are two forms of Caroli disease. Simple form entails the bile duct dilatation or ectasia. Complex form is copresence of hepatic fibrosis and portal hypertension. Here is presented a case of central diabetes insipidus (CDI) associated with Caroli disease.     

儿童肾囊性疾病的诊治

Potter分型将儿童肾囊性疾病分为4型:常染色体隐性遗传性多囊性肾病、多囊性肾发育不良、常染色体显性遗传性多囊性肾病、梗阻性囊性发育不良肾.此外,单纯性肾囊肿、发生在肾肿瘤及其他伴囊性肾病的综合征也可引起肾脏呈囊性改变.这类病由于其发病机制和病理基础不同,临床诊断及治疗方案选择亦不同,要正确诊断这类疾病,需要仔细分类并查明病因.该文就儿童常见的肾囊性疾病进行综述.     

儿童Caroli's综合征

目的：Caroli's综合征是一种罕见的常染色体隐性遗传病。该文报道1例儿童Caroli's综合征合并髓质海绵肾病例。此病例为幼年男性患儿,以发现肝脾大入院,无发热、腹痛、黄疸等症状,影像学检查显示典型肝内胆管囊性扩张及脾大,伴有髓质海绵肾及双肾弥漫钙质沉积。结合此病例,介绍了Caroli's综合征的临床特点、诊断和治疗方面的最新进展。［中国当代儿科杂志,2009,11（1）：10-14］     

Morphometric Studies of Cystic and Tubulointerstitial Kidney Diseases with Hepatic Fibrosis in Children

Portal tract fibrosis with biliary ductular enlargement or proliferation occurs in a number of genetic diseases that have cystic or tubulointerstitial renal lesions. These include some with renal cystic disease such as autosomal recessive diseases (e.g., infantile polycystic disease, juvenile polycystic disease, and Meckel's syndrome), autosomal dominant diseases (e.g., adult polycystic disease), and, rarely, tuberose sclerosis and dominant glomerulocystic disease. Portal tract fibrosis with biliary enlargement and proliferation occurs also with tubulointerstitial kidney diseases. These probably include at least three disorders in the category nephronophthisis-congenital hepatic fibrosis (one autosomal recessive disease and two either autosomal or X-linked recessive diseases) plus Jeune's syndrome (the tubulointerstitial diseases Fanconi's familial nephronophthisis and anti-tubular membrane antibody disease do not regularly cause hepatic fibrosis). Morphometric data on ratios of bile ductules to connective tissue in hepatic portal tracts show high values for infantile polycystic disease (mean, 0.616) compared to lower values for juvenile polycystic disease (mean, 0.286). That the cystic renal lesions of the first two diseases differ in type and time course is known. Similar data on ratios of glomeruli plus tubules to connective tissue in renal cortices and of tubules to connective tissue in outer medullary zones of kidneys, respectively, are as follows: for Fanconi's nephronophthisis, 0.445 and 0.197; for anti-tubular basement membrane antibody disease, 0.585 and 0.164; and for the three types of nephronophthisis-congenital hepatic fibrosis studied, 0.668 and 0.446, 1.39 and 0.921, and 1.18 and 0.12. These data support clinical impressions that the category nephrophthisis-congenital hepatic fibrosis includes more than one disease entity.     

Morphometric studies of cystic and tubulointerstitial kidney diseases with hepatic fibrosis in children

Portal tract fibrosis with biliary ductular enlargement or proliferation occurs in a number of genetic diseases that have cystic or tubulointerstitial renal lesions. These include some with renal cystic disease such as autosomal recessive diseases (e.g., infantile polycystic disease, juvenile polycystic disease, and Meckel's syndrome), autosomal dominant diseases (e.g., adult polycystic disease) and, rarely, tuberose sclerosis and dominant glomerulocystic disease. Portal tract fibrosis with biliary enlargement and proliferation occurs also with tubulointerstitial kidney diseases. These probably include at least three disorders in the category nephronophthisis-congenital hepatic fibrosis (one autosomal recessive disease and two either autosomal or X-linked recessive diseases) plus Jeune's syndrome (the tubulointerstitial diseases Fanconi's familial nephronophthisis and anti-tubular membrane antibody disease do not regularly cause hepatic fibrosis). Morphometric data on ratios of bile ductules to connective tissue in hepatic portal tracts show high values for infantile polycystic disease (mean, 0.616) compared to lower values for juvenile polycystic disease (mean, 0.286). That the cystic renal lesions of the first two diseases differ in type and time course is known. Similar data on ratios of glomeruli plus tubules to connective tissue in renal cortices and of tubules to connective tissue in outer medullary zones of kidneys, respectively, are as follows: for Fanconi's nephronophthisis, 0.445 and 0.197; for anti-tubular basement membrane antibody disease, 0.585 and 0.164; and for the three types of nephronophthisis-congenital hepatic fibrosis studied, 0.668 and 0.446, 1.39 and 0.921, and 1.18 and 0.12. These data support clinical impressions that the category nephrophthisis-congenital hepatic fibrosis includes more than one disease entity.     

The management of choledochal cysts in the newborn

Choledochal cysts are now being diagnosed before birth on routine maternal sonography (US). There is no report in the literature outlining the management of newborns with choledochal cysts, many of whom are asymptomatic. Our study details the diagnosis, treatment and outcome of six such children, four girls and two boys. Five had antenatal US revealing cystic abdominal masses. One had intermittent vomiting and US suggested a choledochal cyst. Four of six had normal serum bilirubin levels; two had elevations. In five babies the choledochal cyst was correctly diagnosed from the preoperative studies; in one the preoperative diagnosis was an ovarian cyst. The children underwent an operation at an average of 6 weeks of age (range 5 days to 17 weeks). At exploration, cholangiography showed Alonso-Lej type I cysts in all cases. Treatment consisted of resection of the cyst with Roux-en-Y choledochojejunostomy in five and with a valved jejunal choledochoduodenal conduit in one. In no case was the dissection of the choledochal cyst off the portal vein and hepatic artery difficult. There were no intra- or early postoperative complications. Mean hospital stay was 8 days (range 5 to 9 days). Presently, all 6 patients have normal bilirubin levels at an average length of follow-up of 35 months (range 16 to 70 months) after operation. We conclude that operative treatment of choledochal cysts in early infancy, even in asymptomatic children, is safe and effective and may prevent serious complications later in life.     

Synchronous Todani types I and III choledochal cysts in a 10-month-old-infant: type IVb

A 10-month-old, previously healthy boy presented with one week of mild jaundice, light-colored stools and irritability. Abdominal sonography showed a large type I choledochal cyst and a separate, distinct cystic mass at the head of the pancreas. Magnetic resonance cholangiopancreatography was performed to evaluate the relationship of the two lesions. A type I choledochal cyst was confirmed, and a coexisting type III choledochocele was identified as the second cystic structure in conjunction with pancreaticobiliary malunion. The infant had complete resection of the type I choledochal cyst with Roux-en-Y hepaticojejunostomy, and anterior duodenotomy with marsupialization of the choledochocele. After five years of follow-up, the child is thriving and has had no recurrence of his symptoms. An exhaustive review of the literature identifies only one previous case of synchronous types I and III choledochal cysts, and this association is not clearly defined among the traditional classifications of type IV multiple choledochal cysts. Because operative management of a type III cyst requires the addition of a transduodenal approach, we encourage accurate reporting of mixed type choledochal cysts for the benefit of surgical planning, epidemiologic tracking and outcomes.     

A case of cystic biliary atresia with an antenatally detected cyst: the possibility of changing from a correctable type with a cystic lesion (I cyst) to an uncorrectable one (IIId)

This report presents the case of a 6-day-old male with cystic biliary atresia (CBA), and the cyst was detected antenatally. Antenatal ultrasonography suggested the possibility of CBA or a choledochal cyst at 16 weeks’ gestation. However, the cyst disappeared during the later gestational period. The cyst was detected again by preoperative imaging. Surgical cholangiography at 30 days of age confirmed CBA, but the common hepatic duct (CHD) was extremely narrow. The histopathological findings revealed the partial obstruction of CHD. These findings suggest that correctable CBA (I cyst) may change into uncorrectable CBA (IIId).     

Antenatal diagnosis of choledochal cyst: the first four cases

Four infants in whom choledochal cyst was diagnosed by maternal ultrasound examinations are reviewed. The infants, from different institutions, represent a spectrum with regard to clinical presentation and subsequent course. They show that choledochal cyst can develop at different stages of gestation and is often not associated with biliary obstruction or biliary atresia. Definitive surgery can be safely performed in the neonatal period and is the treatment of choice. Follow-up data indicate that despite marked differences in the initial severity of their hepatic parenchymal disease, all four infants have done well in their early years, with essentially normal liver function. These unique patients provide insights into the possible etiology and pathophysiology of choledochal cyst and suggest guidlines for future evaluation and management of such infants.     

Caroli disease, bilateral diffuse cystic renal dysplasia, situs inversus, postaxial polydactyly, and preauricular fistulas: a ciliopathy caused by a homozygous NPHP3 mutation

We report the rare association of Caroli disease (intrahepatic bile duct ectasia associated with congenital hepatic fibrosis), bilateral cystic renal dysplasia, situs inversus, postaxial polydactyly, and preauricular fistulas in a female child. She presented with end-stage renal disease at the age of 1 month, followed by a rapidly progressing hepatic fibrosis and dilatation of the intrahepatic bile ducts, leading to secondary biliary cirrhosis and portal hypertension. Combined liver–kidney transplantation was performed at the age of 4 years, with excellent outcome. DNA analysis showed a NPHP3 (coding nephrocystin-3) homozygote mutation, confirming that this malformation complex is a ciliopathy. Conclusion: This rare association required an exceptional therapeutic approach: combined simultaneous orthotopic liver and kidney transplantation in a situs inversus recipient. The long-term follow-up was excellent with a very good evolution of the renal and hepatic grafts and normalization of growth and weight. This malformation complex has an autosomal recessive inheritance with a 25% recurrence risk in each pregnancy.     

SKELETAL ABNORMALITIES IN MECKEL SYNDROME

Meckel syndrome is an autosomal recessive condition with a wide phenotypic variation. The most consistent features are cystic kidneys and intrahepatic bile duct anomalies, frequently accompanied by central nervous system (CNS) malformations and polydactyly. Approximately one sixth of all cases also show skeletal anomalies. We present two cases, siblings born to a consanguineous couple, in whom there was a striking curvature and shortening of the long bones in addition to cystic kidneys, CNS abnormalities, and polydactyly. Histological examination of the long bones in the second affected sibling showed mid-diaphysial ectopic cartilaginous growth plates differentiating the long bone changes from other skeletal dysplasias with similar radiological features.     

Non-correctable biliary atresia with large extrahepatic cyst: a report of two cases.

Biliary atresia constitutes a serious problem in early infancy, due to the concomitant cholestasis. The conventional classification falls into 3 main types: type I, atresia of the common bile duct; type II, atresia of the hepatic duct; and type III, atresia of the porta hepatis. We report 2 unusual cases of biliary atresia type III with a cystic structure that could be mistaken for correctable biliary atresia or choledochal cyst.     

先天性胆管扩张症合并肝内胆管扩张及复杂胆道畸形的诊断与治疗对策

目的研究先天性胆管扩张症合并肝内胆管扩张及复杂胆道畸形的特殊检查方法及其临床意义，探讨在标准术式即囊肿切除胆道重建的基础上对肝内胆管扩张及可能存在的复杂胆道畸形处理的方法。方法对于合并肝内胆管扩张患儿，以术中胆管造影、胆道镜观察等仔细进行术中检查，了解肝总管、胆囊管、左右肝管、肝内胆管扩张及狭窄情况，以及胰胆管共同通道的病理变化，同时仔细检查有无复杂胆道畸形的存在并予以手术处理。结果全组57例，33．3％合并肝内胆管扩张，其中10例为肝内胆管囊样扩张，其汇入肝总管的开口呈瓣膜状、隔膜状或细短管状狭窄。9例为自肝门向肝内胆管起始端逐渐变细的锥形扩张，无明显狭窄。2例合并迷走胆管，3例为左右肝管分别汇入扩张的胆总管囊肿。结论对合并肝内胆管扩张者进行相应的特殊检查具有重要的临床意义，可以指导在标准根治术，即囊肿切除胆道重建的基础上对近端肝内胆管狭窄矫治、可能存在的迷走胆管、复杂胆道畸形及远端胰胆管共同通道病变的处理。     

Caroli syndrome

We describe a case of Caroli syndrome (Caroli's disease and congenital hepatic fibrosis) in a 10-year-old boy with bilobar involvement and numerous renal cysts. Liver transplantation offers the only hope for such patients. Accepted: 17 May 1999     

腹腔镜下手术治疗先天性胆总管囊肿198例分析

目的探讨腹腔镜下手术治疗先天性胆总管囊肿的中短期效果,总结临床体会。方法回顾性分析2006年10月至2014年4月我们收治的198例腹腔镜下胆总管囊肿患儿临床资料。其中男性53例,女性144例;年龄1个月至13岁,平均年龄38.2个月。临床特征:102例为间歇性右上腹痛,25例黄疸,7例排陶土便,13例存在腹部包块,45例有肝功能损害,31例血淀粉酶升高。均予囊肿切除、肝管-空肠Roux-en-Y吻合术。总结分析术中、术后及随访情况。结果 198例患儿囊肿直径1~20 cm,平均4.26 cm,其中囊状扩张186例,梭型扩张12例。Todari's分型Ⅰ型191例,Ⅳ型7例。198例中,19例中转开腹手术,其中9例炎症粘连剧烈,4例肝总管细小,2例囊肿突入十二指肠,2例囊肿巨大术野暴露不清楚,1例腹腔镜下无法确认肝管,1例见右副肝管。其余179例顺利完成腹腔镜下胆总管囊肿切除、肝管-空肠Roux-en-Y吻合胆道重建术。手术时间130~480 min,平均255 min。术后6例出现胆漏,3例出现吻合口狭窄,其中5例再次行开腹手术。1例出现输入袢粘连绞窄坏死,重新行Roux-en-Y吻合。1例出现粘连性肠梗阻,经保守治疗好转。其余病例随访3个月至8年,无并发症,肝功能均正常。结论腹腔镜下手术治疗先天性胆总管囊肿具有切口小、暴露清晰、恢复快等优点,但对术者要求较高,术中操作困难时及时中转开腹手术,可降低手术风险,减少并发症的发生。     

Ectopic pancreas associated with choledochal cyst and multiseptate gallbladder.

Congenital choledochal cyst is a rarely seen malformation of childhood, particularly when associated with multiseptate gallbladder or ectopic pancreas. The current case represents a 15-day-old boy with jaundice. Ultrasonography suggested a cystic lesion, probably of the common bile duct. The patient underwent a total excision of type I choledochal cyst and gallbladder with Roux-en-Y anastomosis, and a wedge biopsy from the liver. Gross examination revealed multiple septa dividing the gallbladder into multiple compartments. The outer and inner surfaces of the choledochal cyst were unremarkable. Microscopically, the cyst wall was composed of dense fibrous tissue with a single layer of cubic to columnar cells constituting the overlying epithelium. Serial sections incidentally revealed ectopic pancreatic tissue lying along the cyst wall characterized by acini, islets, and ductal structures with endocrine cells reactive for chromogranin A. Septa dividing the gallbladder were composed of fibrotic stalks containing smooth muscle fibers. Areas of papillary hyperplasia and intestinal metaplasia of gallbladder epithelium were also noted. The liver biopsy specimen demonstrated the presence of intrahepatic bile ducts, subsequently confirmed by cytokeratin 7. To our knowledge, this case represents the 1st one associated with these 3 entities and only the 2nd choledochal cyst with ectopic pancreatic tissue in its wall.     

经腹腔镜手术治疗3个月内婴儿先天性胆总管囊肿

目的探讨经腹腔镜行囊肿切除、肝管空肠Roux-en-Y吻合治疗3个月以内先天性胆总管囊肿的可行性和治疗效果。方法本院2011年7月至2015年7月经腹腔镜手术治疗的3个月以内先天性胆总管囊肿患儿41例,其中男13例,女28例,均为囊肿型;手术年龄8~89 d,平均(50.2±23)d,体重2.7~6.47 kg,平均(4.47±1.01)kg。33例合并黄疸,8例大便颜色变浅,7例出现白陶土样便;31例术前检查转氨酶升高。全部病例均采用经腹腔镜完整囊肿切除,肝管空肠Roux-en-Y吻合术。结果 40例患儿成功完成手术,手术时间117~296 min,平均(186±42)min,出血量5 mL;1例损伤门静脉,中转开腹,出血50 mL;术后无一例发生肠瘘、胆瘘和胰瘘;随访5~53个月,无胆管狭窄、胆管炎、粘连性肠梗阻等发生。结论 3个月以内婴儿胆总管囊肿容易发生肝功能损害、肝脏纤维化,应尽早手术治疗。经腹腔镜手术治疗先天性胆总管囊肿安全有效。