BILIARY TRACT ANOMALIES—The Utilization of Modern Techniques in Differential Diagnosis

The diagnostic aids used in dealing with biliary disease in adults were applied to the study in infants of the principal congenital anomalies of the biliary tract such as choledochal cyst, biliary atresia and biliary stenosis.Choledochal cysts were distinguished from other upper abdominal masses occurring in childhood by the use of intravenous cholecystography.Since the clinical manifestations in infants with biliary atresia or stenosis are almost identical to those associated with the obstructive phase of neonatal hepatitis, the problem of differentiation is difficult. The serial total serum bilirubin curve, a careful analysis of the pigment content of feces and urine and duodenal intubation for bilirubin determinations were found to be useful in making the distinction. Operative cholangiograms were helpful in some cases. Frozen section examinations of liver tissue during operation were of little value except to demonstrate certain unusual cases of intrahepatic biliary atresia. Routine liver function studies, including serum transaminase determination in a limited number of cases, did not help in differentiation.     

Biliary tract anomalies: the utilization of modern techniques in differential diagnosis

The diagnostic aids used in dealing with biliary disease in adults were applied to the study in infants of the principal congenital anomalies of the biliary tract such as choledochal cyst, biliary atresia and biliary stenosis. Choledochal cysts were distinguished from other upper abdominal masses occurring in childhood by the use of intravenous cholecystography. Since the clinical manifestations in infants with biliary atresia or stenosis are almost identical to those associated with the obstructive phase of neonatal hepatitis, the problem of differentiation is difficult. The serial total serum bilirubin curve, a careful analysis of the pigment content of feces and urine and duodenal intubation for bilirubin determinations were found to be useful in making the distinction. Operative cholangiograms were helpful in some cases. Frozen section examinations of liver tissue during operation were of little value except to demonstrate certain unusual cases of intrahepatic biliary atresia. Routine liver function studies, including serum transaminase determination in a limited number of cases, did not help in differentiation.     

Congenital Cystic Malformation of the Bile Ducts: Report of a Case and Review of Related Literature

A 20-year-old woman had a cyst of the proximal part of the common bile duct and a cyst of the left hepatic duct; these lesions were diagnosed preoperatively by intravenous cholangiography and successfully operated upon. At the time of writing, she has been followed up for one year.Congenital defects in the biliary system are rare and, in a review of the literature, only two cases were found similar to this one. It is generally accepted that these lesions are congenital, but the exact pathogenesis is unknown.Alonso-Lej, Rever and Pessagno² reviewed the literature in 1959 and found 403 authentic congenital cysts of the hepatic ducts. The most common congenital defect is a single choledochal cyst of the lower end of the common bile duct. Pain, jaundice and tumour are the main symptoms.Until the advent of intravenous cholangiography, these lesions were seldom recognized preoperatively. Means of operative repair as well as complications and prognosis are reviewed.     

Identification of HSP90 as Potential Biomarker of Biliary Atresia Using Two-Dimensional Electrophoresis and Mass Spectrometry

Biliary atresia (BA) is a devastating cholestatic liver disease targeting infants. Current diagnosis depends on surgical exploration of the biliary tree. The aim of the present study was to identify potential biomarkers for the diagnosis of biliary atresia (BA). Two-dimensional electrophoresis was utilized for the identification of proteins that were differentially expressed in liver biopsies of 20 BA patients and 12 infants with non-BA neonatal cholestasis (NC) as controls. Using mass spectrometry, we identified 15 proteins with expressions significantly altered. Out of the 15 proteins identified, heat shock protein (HSP) 90 was the most significantly altered and was down-regulated in BA samples compared to NC samples using immunoblotting analysis. Our findings suggest that HSP90 might be a potential biomarker for the diagnosis of BA and may be used for monitoring further development and therapy for BA. This study demonstrated that a comprehensive strategy of proteomic identification combined with further validation should be adopted in biomarker discovery.     

Early cancer in congenital choledochal cyst

We report a case of 35-yr-old woman with early cancer in congenital choledochal cyst. She had a five-year history of intermittent right upper abdominal pain and intermittent jaundice. In this period she had a few abdominal ultrasonographies, but the cholelithiasis had not been found. Now, she was admitted to our hospital because she felt right upper abdominal pain with slight jaundice and subfebrile temperature four weeks ago. Abdominal ultrasonography showed enormous dilatation of the common bile duct, which was suspected as choledochal cyst. Computed tomography and endoscopic retrograde cholangiopancreatography revealed cystic dilatation of extrahepatic bile duct. An anomalous pancreaticobiliary junction was not found. The patient with congenital choledochal cyst was operated on. The excision of choledochal cyst was done with hepaticojejunostomy Roux-en-Y. There were no lymph nodes metastases. On the central part of choledochal cysts mucosa, it was shown a white plain area of thickness 0.3 cm and 0.8 cm in diameter. Histologically it was well-differentiated tubular adenocarcinoma, which was limited to the mucosa and which did not penetrate to other parts of the bile duct wall. From our knowledge, only small number cases of early cholangiocarcinoma in choledochal cyst were until now reported. Nearly eight years after the operation the patient feels very well, and has optimal working ability (Karnofsky 100%).     

Screening of newborn infants for cholestatic hepatobiliary disease with tandem mass spectrometry

ObjectiveTo assess the feasibility of screening for cholestatic hepatobiliary disease and extrahepatic biliary atresia by using tandem mass spectrometry to measure conjugated bile acids in dried blood spots obtained from newborn infants at 7-10 days of age for the Guthrie test.SettingThree tertiary referral clinics and regional neonatal screening laboratories.DesignUnused blood spots from the Guthrie test were retrieved for infants presenting with cholestatic hepatobiliary disease and from the two cards stored on either side of each card from an index child. Concentrations of conjugated bile acids measured by tandem mass spectrometry in the two groups were compared.Results218 children with cholestatic hepatobiliary disease were eligible for inclusion in the study. Two children without a final diagnosis and five who presented at <14 days of age were excluded. Usable blood spots were obtained from 177 index children and 708 comparison children. Mean concentrations of all four bile acid species were significantly raised in children with cholestatic hepatobiliary disease and extrahepatic biliary atresia compared with the unaffected children (P<0.0001). Of 177 children with cholestatic hepatobiliary disease, 104 (59%) had a total bile acid concentration >33 μmol/l (97.5th centile value for comparison group). Of the 61 with extrahepatic biliary atresia, 47 (77%) had total bile acid concentrations >33 μmol/l. Taurotrihydroxycholanoate and total bile acid concentrations were the best predictors of both conditions. For all cholestatic hepatobiliary disease, a cut off level of total bile acid concentration of 30 μmol/l gave a sensitivity of 62% and a specificity of 96%, while the corresponding values for extrahepatic biliary atresia were 79% and 96%.ConclusionMost children who present with extrahepatic biliary atresia and other forms of cholestatic hepatobiliary disease have significantly raised concentrations of conjugated bile acids as measured by tandem mass spectrometry at the time when samples are taken for the Guthrie test. Unfortunately the separation between the concentrations in these infants and those in the general population is not sufficient to make mass screening for cholestatic hepatobiliary disease a feasible option with this method alone.

Key messages

• The prognosis of cholestatic hepatobiliary disease in infancy, in particular biliary atresia, is improved by early detection
• Infants destined to present with cholestatic jaundice in the first few months of life have raised concentrations of bile acids in the blood spots obtained at 7-10 days for current neonatal screening programmes
• Tandem mass spectrometry can be used to detect this marker of neonatal cholestasis
• Unfortunately there is too much overlap between bile acid concentrations in infants with cholestasis and those in control infants for this to be used as a single screening test for cholestatic hepatobiliary disease in general and biliary atresia
• Tandem mass spectrometry is a powerful tool for neonatal screening but every potential application must be carefully assessed

     

L'Anastomose cavo-pulmonaire dans les malformations tricuspidiennes: Evolution de 10 cas opérés

Certain congenital malformations affecting the rightsided cavities of the heart and accompanied by a diminished pulmonary blood flow can be improved by an end-to-side anastomosis between the right pulmonary artery and the superior vena cava. Nine out of the 10 patients who underwent the operation survived. The results have been very impressive in six patients with tricuspid atresia who were critically ill. The anoxemic episodes ceased completely and cyanosis has disappeared. Three cases of Ebstein''s anomaly have also been improved. This clinical study has given us the opportunity to review the physiological consequences of the anastomosis, its complications and its surgical indications. We believe that this type of shunt is especially indicated in cases of tricuspid atresia, in which only a palliative form of surgery can be performed.     

Surgical alternatives in the treatment of hepatic hydatidosis]

Echinococcosis is an endemic zoonosis in the south of Chile, so we have the opportunity to treat many patients especially the liver location which is the most common situation of this disease. Hepatic hydatid cyst presents its own morbidity and mortality due its complications and associated with surgical procedures. Morbidity has rates between 11 and 86% and is related with previous surgical interventions, cysts complications, the necessity of perform additional procedures during surgery and the treatment of other disease locations. Mortality by otherwise has rates below 5%. But both, morbidity and mortality persist high in spite of technological advances and therapeutical improvement. The surgical treatment of hepatic hydatidosis can be divided in four phases: surgical area isolation, cysts evacuation, treatment of cyst complications (biliary tract rupture, hepatothoracic transit, etc.), and residual cavity treatment. For each one exist different alternatives. On the other hand, hydatid cyst surgery can be classified in conservative and resective procedures. In the first group we consider marsupialization, cystostomy, Knowsly or Posadas operation and cystojejunostomy. In the resective group we include pericystectomy, partial or subtotal cystectomy and the different types of hepatectomies. Finally, some other surgical procedures are under evaluation. These include the laparoscopic approach of liver echinoccosis with few studies in the field, but with hopeful results.     

VISUALIZATION OF THE BILIARY TRACT—Preoperative,Operative and Postoperative Radiologic Investigation

Modern operative treatment of diseases of the bile passages requires the use of x-ray visualization of the biliary tract before, after and during operation. Nearly every surgeon uses x-ray study of the biliary tract before operation and it is widespread practice to carry out such study after operations in which a tube has been placed in the bile passages. However, there is a remarkable aversion to operative cholangiography.The usual reasons for avoiding operative cholangiography are unfamiliarity, inertia, concern over complications of the technique, and the feeling that it is unnecessary or wasteful of surgeon''s time and patient''s money. Yet the results of operative cholangiograms compare favorably with those obtained with the more customary x-ray studies of the bile ducts carried out after operation, at a time when the information gained is much less valuable in avoiding additional operations and in contributing to a smooth and rapid convalescence.     

麻醉诱导期预保温措施对胆道闭锁患儿术中体温的影响

目的:探讨麻醉诱导期预保温措施对胆道闭锁患儿手术中体温的影响。方法:将我院2012年4月~2014年8月收治入院需要行肝门空肠吻合重建肝外胆道术的100例胆道闭锁患儿,按电脑随机法分为对照组和治疗组,每组各50例,对照组患儿麻醉诱导期采用普通盖被覆盖保温0.5 h,试验组患儿麻醉诱导期采用充气保温毯进行预保温0.5h,手术中观察并记录两组患儿的基本情况和术中体温变化。结果:两组患儿入室体温、入室室温、麻醉时室温、手术时间、出血量及输液总量比较差异均无统计学意义(P0.05)。治疗组术中发生低体温的概率为36.2%,明显低于对照组的63.8%。对照组术中患儿体温变化较大,体温下降较明显(P0.05),而治疗组体温变化相对稳定(P0.05)。结论:麻醉诱导期应用充气保温毯预保温有利于胆道闭锁患儿行肝门空肠吻合术时保持相对稳定体温,是预防胆道闭锁患儿术中发生低体温的有效方法。     

Factors Interfering with Delineation on MRCP of Pancreaticobiliary Maljunction in Paediatric Patients

BackgroundThe aim of this study was to assess factors for delineating the pancreaticobiliary junction in the presence of pediatric congenital choledochal cysts (CCC) using Magnetic resonance cholangiopancreatography (MRCP).MethodsRetrospective review of medical records for 48 patients with CCC was conducted, including demographics, biliary amylase and MRCP findings if available. With univariate and multivariate logistic regression, we measured significant factors affecting pancreaticobiliary maljunction(PBM) diagnoses by MRCP.ResultsOf the subjects enrolled with CCC. Twenty-eight cases had PBM according to MRCP. Univariate analysis confirmed that age, cyst diameter > 30 mm and cysts that descended to the introitus pelvis affected junctional delineation and detection of PBM (P<0.05). Stepwise logistic regression analysis confirmed large cysts in the introitus pelvis predicted pancreaticobiliary junctional delineation in MRCP and these data agreed with the literature. A correlation between cyst diameter and the length of the common channel was found as was cyst diameter and biliary amylase although there were no significant differences between them.ConclusionsAge, cyst diameter >30 mm and descending cysts into the introitus pelvis affected junctional delineation of the pancreatic and bile duct in PBM with MRCP. Large cyst descension into the introitus pelvis was an independent factors affecting PBM detection.     

The Prevention of Residual Biliary Calculi

Residual calculi following cholecystectomy may be expected in approximately seven percent of cases. The vast majority of these are overlooked during operation; truly re-formed stones are rare.Calculi are missed during cholecystectomy because of failure to explore the common bile duct. This is due to (1) the presence of silent choledochal stones, and (2) reliance on negative cystic duct cholangiograms in the presence of indications for common duct exploration.Overlooking of silent stones during cholecystectomy may be prevented by routine operative cholangiography. Ideally, false-negative cystic duct cholangiograms should be eliminated by the use of fluoroscopic cholangiography.Retained calculi following duct exploration may be prevented by (a) routine biliary endoscopy and (b) completion fluoroscopic cholangiography.Re-formation of ductal calculi can probably be prevented by appropriate biliary drainage procedures performed during the initial choledochotomy. Selection of patients for primary biliary decompression remains an experimental problem.     

A New Clarification Method to Visualize Biliary Degeneration During Liver Metamorphosis in Sea Lamprey (Petromyzon marinus)

Biliary atresia is a rare disease of infancy, with an estimated 1 in 15,000 frequency in the southeast United States, but more common in East Asian countries, with a reported frequency of 1 in 5,000 in Taiwan. Although much is known about the management of biliary atresia, its pathogenesis is still elusive. The sea lamprey (Petromyzon marinus) provides a unique opportunity to examine the mechanism and progression of biliary degeneration. Sea lamprey develop through three distinct life stages: larval, parasitic, and adult. During the transition from larvae to parasitic juvenile, sea lamprey undergo metamorphosis with dramatic reorganization and remodeling in external morphology and internal organs. In the liver, the entire biliary system is lost, including the gall bladder and the biliary tree. A newly-developed method called “CLARITY” was modified to clarify the entire liver and the junction with the intestine in metamorphic sea lamprey. The process of biliary degeneration was visualized and discerned during sea lamprey metamorphosis by using laser scanning confocal microscopy. This method provides a powerful tool to study biliary atresia in a unique animal model.     

Isolation of Neonatal Extrahepatic Cholangiocytes

The intra and extrahepatic bile ducts of the liver are developmentally distinct, and may be differentially affected by certain diseases. However, differences between intra and extrahepatic cholangiocytes, and between neonatal and adult cells, are not well understood.Methods for the isolation of cholangiocytes from intrahepatic bile ducts are well established^1-4. Isolation of extrahepatic ductal cells, especially from the neonate, has not yet been described, although this would be of great benefit in understanding the differences between distinct cholangiocyte populations and in studying diseases such as biliary atresia that appear to target the extrahepatic ducts. Described here is an optimized technique to isolate both neonatal and adult mouse extrahepatic bile duct cells. This technique yields a pure cell population with minimal contamination from mesenchymal cells like fibroblasts.This method is based on the removal of the extrahepatic ducts and gallbladder, followed by meticulous dissection and scraping to remove fat and fibroblast layers. Structures are embedded in thick layers of collagen and cultured for approximately 3 weeks to allow outgrowth of cholangiocytes in monolayers, which can then be trypsinized and re plated for experimental use.     

Interleukin-33 overexpression is associated with gamma-glutamyl transferase in biliary atresia

Interleukin-33 (IL-33) plays a crucial role in inflammation. However, it is not clear whether IL-33 levels are of clinical significance for patients with biliary atresia (BA). The purpose of this study was to determine correlations between serum IL-33 levels and the clinicopathologic features of BA. Serum samples were collected from 18 BA infants, 12 nonicteric choledochal cyst (CC) infants with normal liver function, and 10 healthy controls (HCs). Serum IL-33 levels were measured with an enzyme-linked immunosorbent assay (ELISA). Routine liver function tests were performed on the serum samples. qRT-PCR and Western blot analysis were used to detect IL-33 expression in BA liver biopsy tissues. Hepatic lobule localization of IL-33 expression in the hepatic lobule was conducted by immunohistochemistry (IHC). IL-33 levels in serum collected from BA infants were significantly elevated in comparison with CC and HC patients. Furthermore, the elevated serum levels of IL-33 in BA infants were correlated with gamma-glutamyl transferase (GGT) levels. The expression of IL-33 mRNA and protein levels were up-regulated in BA liver biopsy tissues in comparison with CC patients. IHC analysis revealed increased positive immunostaining for IL-33 in BA liver tissues as compared to that in CC tissues. These results suggest that IL-33 may play an important role in the pathogenesis of BA. In addition, the correlation of serum IL-33 levels with GGT levels may provide a novel marker for the diagnosis of BA.     

Diagnosis of choledochal cysts in children with special reference to ultrasonographic examination]

Early diagnosis of the choledochal cysts in childhood, especially obstructing bile outflow to the duodenum, is an important clinical problem; often leading to serious complications--if not treated. Authors treated 5 children with choledochal cysts. Three out of them have been treated surgically. Ultrasound examination is sufficient to diagnose the disease, if the cyst is connected with intrahepatic bile ducts. If such a case is not possible to be imaged, cholescintigraphy and thin-needle biopsy with contrast filling are necessary to confirm the diagnosis.     

Genetic variability of interleukin4 gene in Taiwanese children with biliary atresia

Biliary atresia (BA) is a neonatal cholangiopathy of unknown etiology that leads to biliary cirrhosis and is the most common cause of liver transplantation in children. A still undetermined hepatobiliary viral infection may elicit an uncontrollable autoimmune response against the biliary epithelial cells in genetically predisposed children and culminates in atresia of the biliary trees. Interleukin 4 (IL4) is crucial for the differentiation of naive T helper cells into the T helper 2 effector cells that promote humoral immunity. This study aims to investigate whether polymorphisms of the IL4 gene are associated with susceptibility to BA. Genomic DNA was extracted from whole blood samples of 53 Taiwanese children with BA and 904 ethnically-matched healthy controls. The IL4 -590 C/T, -33 C/T, and 8375 A/G polymorphisms were genotyped using the Pre-Developed TaqMan Allelic Discrimination Assay in a real-time polymerase chain reaction system. No significant difference between children with BA and healthy controls were found when comparing genotype, allele, carrier, and haplotype frequencies of these IL4 gene variants. These results suggest that the tested polymorphisms of IL4 gene are unlikely to contribute significantly to BA susceptibility in Taiwanese children.     

Practical management of congenital choanal atresia

Prevailing theories on the causation of choanal atresia are presented, with emphasis on some of the embryologic and anatomic abnormalities that are consistently found. The teleologic significance of nose breathing has been emphasized. This neonatal characteristic leads to a tongue-palate seal that can be rapidly fatal. Treatment of these patients has been divided into two phases. Phase I deals with immediate establishment of an airway, and phase II deals with the definitive surgical management in these patients. Our preference is for the transpalatine approach. Representative cases highlight our technique. A wire-reinforced double-barreled Elastomer stent has been developed and is described. Successful use in five patients is reported.     

EMERGENCY OPERATIONS IN THE NEWBORN

With the present-day development and understanding of anesthetic methods, fluid and electrolyte therapy, antibiotic medications and pediatric care, many congenital anomalies once uniformly fatal are now being successfully treated by emergency operations in the neonatal period. The eight most common of these which demand emergency operation in the immediate postnatal period are esophageal atresia and tracheoesophageal fistula, diaphragmatic hernia with dislocation of the abdominal viscera into the chest, malrotation of the intestine with obstruction, intestinal atresia, meconium ileus, imperforate anus, omphalocele and myelomeningocele.Although infants born with any of these serious problems often are born prematurely and often have more than one congenital anomaly, survival rates in the surgical treatment of these conditions are steadily improving. Early diagnosis and prompt treatment are the most important factors in the continued improvement of these survival rates.     

Has prenatal ultrasonic diagnosis modified the prognosis of intestinal atresia? Results of a multicenter study

A multicentric investigation concerning intestinal atresia diagnosed in french university hospitals from 1979 to 1983, has been done. Out of 96 exploitable cases coming from 8 centers, 28 correspond to intestinal atresias which had subject to prenatal echographic diagnosis: that is 29%. 15 of the 96 atresias were affected with trisomy. 21 which had not been recognised in utero. Concerning the isolated duodenal atresia, not accompanied by any other malformation, the post surgical evolution has been appreciated during the 12 months following the surgical operation. There was no statistically significant difference, in favour of the group of children whose malformation has been recognised in utero, concerning the number of post surgical complications. This result, apparently deceitful, can be explained by the early management of these malformations in specialised centers which have participated in this study.