Two cases of chronic pancreatitis associated with anomalous pancreaticobiliary ductal union and SPINK1 mutation / 소아과

Chronic pancreatitis is a progressive inflammatory disease resulting from repeated episodes of acute pancreatitis that impair exocrine function and eventually produce endocrine insufficiency. Some causes of chronic pancreatitis appear to be associated with alterations in the serine-protease inhibitor, Kazal type 1 (SPINK1), cationic trypsinogen (PRSS1), and cystic fibrosis-transmembrane conductance regulator (CFTR) genes, or with structural disorders in the pancreaticobiliary ductal system, such as pancreatic divisum or anomalous pancreaticobiliary ductal union (APBDU). However, it is unusual to observe both genetic alteration and structural anomaly. Here, we report 2 cases with both APBDU and a mutation in the SPINK1 genes, and we discuss the implications of these findings in clinical practice.

Endoscopic Treatment of a Pediatric Patient with Acute Pancreatitis Caused by Anomalous Union of Pancreaticobiliary Duct Combined with Incomplete Pancreatic Divisum / 대한소화기학회지

The most common causes of acute pancreatitis are microlithiasis and alcohol. In pediatrics, anomalies in pancreaticobiliary system should be considered as possible causes. Among many anomalies, pancreas divisum associated with anomalous pancreaticobiliary ductal union (APBDU) is very rare. APBDU is associated with acute pancreatitis, choledochal cyst, and gallbladder cancer. Pancreas divisum is also a well known cause of acute recurrent pancreatitis. In adult cases with such conditions, the role of endoscopic management including sphincterotomy or stenting through the Santorini duct is well documented. However, it is still controversial to perform endoscopic retrograde cholangiopancreatography in pediatrics. Herein, we experienced a case of 4 year 7 month old female patient suffered from recurrent attacks of acute pancreatitis, which were caused by APBDU and incomplete pancreas divisum. She was treated by endoscopic sphincteretomy of both openings to the Santorini's and Wirsung's ducts. Thus, we report this interesting case with literature review.

Effect of anomalous pancreaticobiliary ductal union on the injuries of pancreas / 中华胰腺病杂志

Objective To investigate the effect of anomalous pancreaticobiliary ductal union on the injuries of pancreas.Methods 10 health cats were treated by a 4～6 cm incision in biliary and pancreatic duct adjacent to duodenum, and interrupted suture was made to induce the model of anomalous pancreaticobiliary ductal union.The pancreatic tissues were harvested during model induction and 6 months after model induction,and histopathological changes were evaluated by electron microscopic examination and the level of maleic dialdehyde (MDA) were determined.Results Seven out of 10 cats survived surgery and remained alive for 6 months.6 months later,the pancreas appeared to be in the color of dark red and hyperemia,edema was present.Dilated pancreatic duct could be found in three of them.Light microscopic examination suggested there was inflammatory cell infiltration in the pancreas in 3 cats;mesenchymal vascular proliferation and white cell adhesion was present in the pancreas in 4 cats.Electron microscopic examination suggested rough endoplasmic reticulum expanding in the shape of pool,swelling mitochondria disaggregated and increased in number,Golgi complex became well developed.The preoperative level of MDA in pancreatic tissue was (1.23±0.7 ) nmol/mg prot,which increased to (2.90±1.9 ) nmol/mg prot 6 months later with statistically significant difference (F=4.80,P=0.0215 ).Conclusions This animal model demonstrated that anomalous pancreaticobiliary ductal union may cause injury to the pancreas,and antioxidant treatment may alleviate this injury.

The relation between acute biliary pancreatitis and anomalous pancreaticobiliary ductal union / 中华胰腺病杂志

Objective To investigate the relationship between acute biliary pancreatitis (ABP) and anomalous pancreaticobiliary duetal union (APBDU). Methods 131 patients with ABP were enrolled to test the serum total bilirubin (TB), alanine amintransferase (ALT), aspartate amintransferase (AST), alkaline phosphates (ALP), γ-glutamyl transferase (γ-GT). All the patients received medical treatment, and then these tests were performed again. Thereafter, all the patients underwent selective surgery and intra-operative cholangiography was performed to observe the pancreaticobiliary duetal union. Results 27 patients (20.6%) with APBDU were found in 131 patients. Among them, 8 cases (29.6%) was B-P subtype (TypeⅠ), 16 cases (59.3%) was P-B subtype (TypeⅡ) , and the remaining 3 cases was mixed subtype (TypeⅢ). A significant decrease of ALT, AST, ALP, γ-GT after non-surgical treatment in both group of APBDU and NAPBDU was noted (P＜0.05). The serum levels of ALT, AST,γ-GT in APBDU patients were (71.81± 23.19) U/L, (47.85±27.87) U/L, (52.86±31.49) U/L, respectively; and in NAPBDU patients were (51.96±15.40) U/L, (40.77±16.58) U/L, (34.86±26.47) U/L. The difference was statistically significant (P＜0.05). Condusions APBDU is an important etiology of ABP.

A Case of Choledochal Cyst (Type IVa) and Anomalous Pancreaticobiliary Ductal Union Combined with Pancreatic Duct Stone / 대한소화기내시경학회지

Pancreatic duct stones are commonly associated with recurrent pancreatitis. They are believed to develop as a result of the calcification of an intraductal protein plug. A choledochal cyst is a relatively rare anomaly usually presenting with abdominal pain, jaundice and palpable mass. APBDU (anomalous pancreaticobiliary ductal union) is frequently associated with various pancreatobiliary diseases, including choledochal cyst, biliary tumor, pancreatitis and pancreas divisum. We report a 48-year-old woman who presented with right upper quadrant pain with a pancreatic duct stone, a choledochal cyst and APBDU. She underwent endoscopic pancreatic sphincterotomy, a surgical choledochal cyst excision and Roux-en-Y choledochojejunostomy.

The Usefulness of Magnetic Resonance Cholangio-Pancreatography in the Diagnosis of Choledochal Cyst

PURPOSE: Choledochal cysts are cystic or diffuse dilatation of any portion of the biliary tree. An anomalous pancreaticobiliary ductal union (APBDU) is one of the commonly accepted causes of a cholodochal cyst. The ability of MRCP to demonstrate an APBDU has not been established in children and appears to have limited value in demonstrating an associated APBDU. We investigate the usefulness, and application, of MRCP in delineating the cyst type and an APBDU in patients with choledochal cysts, and compared it with operative cholangiography. METHODS: Ten children with choledochal cyst, who had both MRCP and cholangiography, as preoperative diagnostic modalities, at the Division of Pediatric Surgery, Keimyung University, Dongsan Medical Center, between March 1999 and August 2002, were selected for this study. We analyzed and compared their MRCP images with those of the intraoperative cholangiographies, with regard to the type of cyst, size and association of an APBDU. RESULTS: The types of the choledochal cyst, based on the MRCP, were two Ia, three Ic, and five IVa, whereas those based on the operative cholangiographies were one Ic and nine IVa. A common channel was demonstrated by MRCP and operative cholangiography in four (40%) and six (60%) of the ten patients, respectively. Each diagnostic modality correlated with the size (Pearson correlation, P<0.01) and the length of the cyst, but an APBDU on both modalities did not reach statistical significance, even though the common channel was not identified in a large cyst on MRCP. CONCLUSION: MRCP is a noninvasive and safe diagnostic modality for the delineation an APBDU in children with choledochal cysts. However, it has limited value for demonstrating an APBDU in children with a large cyst due to overlapping with the pancreaticobiliary ductal system. Operative cholangiography seems to be more valuable than MRCP in patients with large choledochal cysts.

A Study for Mechanism of Biliary Ductal Injury in Patients with Anomalous Pancreaticobiliary Ductal Union: A Study for Mechanism of Biliary Injury in APBDU / 한국간담췌외과학회지

PURPOSE: It has been known that clinical features of anomalous pancreaticobiliary ductal union (APBDU) are thought to result from cholestasis and regurgitation of pancreatic juice. The purpose of our study is to clarify the relationship of clinicopathological factors and to get information on mechanism of biliary ductal injury in APBDU. METHODS: A total of 23 patients who underwent operation for APBDU from March 1995 to March 2003 were examined. The results of patients were analyzed for their relevance to the clinicopathological factors such as age, sex, age at onset, size of cyst, grade of inflammation, type of APBDU, level of pancreatic enzymes sampled from biliary ductal system, and Ki67 labeling index. RESULTS: Level of amylase in biliary ductal system was decreased with age, especially after 20 years. The grade of hyperplasia in gallbladder was increased with level of amylase in gallbladder. The grade of inflammation in gallbladder was increased with age, but inflammation of gallbladder decreased with the level of amylase in gallbladder, and the size of cyst was increased with grade of inflammation and age. CONCLUSION: Level of amylase in the bile of biliary ductal system was decreased with age, especially after 20 years, which suggests that reflux of pancreatic amylase is closely related with onset of symptom in adult with APBDU. As far as mechanism of biliary ductal injury in APBDU is concerned, inflammation of biliary ductal system is increased with age and size of cyst. And hyperplasia of gallbladder is increased with the degree of regurgitation of pancreatic juice.

A Peculiar Type of Anomalous Pancreaticobiliary Ductal Union / 대한소화기내시경학회지

Anomalous pancreaticobiliary ductal union (APBDU) is an uncommon anomaly, defined as the junction between the common bile duct and the pancreatic duct outside the duodenal wall and beyond the influence of the sphincter of Oddi. This anomaly, which has been recognized frequently since the introduction of ERCP, is believed to be associated with biliary tract lesions such as congenital biliary dilatation, biliary tract carcinoma, and pancreatic lesions such as pancreatitis new paragraph. A 28-year-old male was admitted due to sudden abdominal pain and vomiting. An ERCP revealed a peculiar type of APBDU; the duct of Wirsung and CBD fused and formed a long common channel before entering the major papilla, and the duct of Santorini connected to the duct of Wirsung is patent. So, when contrast dye was inserted into the minor papilla, both the CBD and the duct of Wirsung were made visible. This case of the peculiar type of APBDU which showed characteristic ERCP findings are herein reported.

An Experimental Animal Model of Anomalous Pancreaticobiliary Duct Union

It is generally believed that the anomalous pancreaticobiliary duct union (APBDU) might be involved in the formation of choledochal cyst and malignancies of hepatopancreaticobiliary system. The purpose of this study is to make an animal model of APBDU similar to that of human. One to two-month-old Mongrel dogs (n=12) were divided into two groups; the control group (n=2) in which sham operation was performed, and the experimental group (n=10) in which the end of distal common bile duct (CBD) was anastomosed to the side of dorsal pancreatic duct to produce APBDU. Serum was obtained for chemical analysis at the 10th postoperative day. The dogs were sacrificed at the 5th week (n=3), the 6th week (n=3), the 7th week (n=2), the 8th week (n=2) and the 6th month (n=2) after the operative intervention. At the day when the experimental animals were sacrificed, operative cholangiogram was taken, and bile juice was obtained for chemical analysis and bacterial culture. The en-bloc specimens of hepatopancreaticobiliary system were obtained for microscopic examination. Serum and bile juice amylase levels were elevated in the experimental group (n=10), but not in the control group (n=2). On operative cholangiogram, there was no evidence of bile duct dilatation in control group (n=2). On the other hand, bile duct in the experimental group was markedly dilated without any evidence of stenosis in all (n=10). Histologic examination of the hepatopancreaticobiliary system in the experimental group resembled the findings of choledochal cyst in human. The APBDU of this animal model can produce bile duct dilatation by pancreaticobiliary reflux. We think that this animal model can be potentially promising for the research about the APBDU associated hepatopancreaticobiliary diseases.

Choledochal Cyst in Childhood

BACKGROUND: Choledochal cysts are not so rare in far east Asian countries as in western countries and are found mainly in children. Reflux of pancreatic juice to the bile duct through anomalous pancreaticobiliary ductal union (APBDU) is considered to be an important etiologic factor. METHOD: To study the clinical characteristics of choledochal cysts in children and the significance of APBDU in this disease, we reviewed 80 choledochal cyst cases. APBDU is defined as a long common channel (>1.5 cm). RESULTS: Ages ranged from 19 days to 13 years, and the male to female ratio was 1 to 4 which revealed a predominance among females. The symptoms, in order of frequency, were abdominal pain (63%), jaundice (48%), and abdominal mass (26%); classic triads were present in 3 cases (4%). The diagnosis was made mainly with ultrasonography. Todani type I (88%) and IV (11%) were the two most common types of cysts. An operative cholangiography was performed in 80 cases, among which an analysis of the status of the pancreaticobiliary ductal union was possible in 21 cases. A long common channel (>1.5 cm) was found in all 21 cases, 16 cases being of the P- type and 5 cases of the B- type. A cyst excision and hepaticojejunostomy was performed in 79 cases of type I and type IV cysts, and a liver biopsy only was performed in one case of a type V cyst. A common bile duct stone was associated with one case and cholangitis was associated with two cases as postoperative complications. One patient expired due to heart disease. Seventy-ine patients were followed up for a mean period of 7.2 years after the operation. Seventy-ight patients are healthy now, and liver function tests have returned to normal level. One Carolie's disease patient has been followed up outpatiently without bad liver function. An intraoperative liver biopsy was performed in 73 cases. The results were normal in 3 cases; cholestasis was noted in 2 cases, inflammation in 26, fibrosis in 38, and cirrhosis in 4. CONCLUSIONS: APBDU seems to play an important role in the pathogenesis of choledochal cysts, especially type I and type IV cysts. Excision of the cyst is the procedure of choice for treatment because it eliminates the APBDU and prevents both hepatic cirrhosis and the potential for developing a malignancy.

Clinicopathological Study of Resected Gallbladders and Bile Ducts with Anomalous Pancreaticobiliary Ductal Union (APBDU)

BACKGROUND : Anomalous pancreaticobiliary ductal union (APBDU) is a congenital defect defined as a union of the pancreatic and the biliary ducts located outside the duodenal wall. Accordingly, this anomalous connection between the choledochus and the pancreatic duct is considered to be a factor in the development of biliary tract diseases such as choledochal cysts, pancreatitis, cholangitis, gallbladder cancer, and bile duct cancer. Our purpose is to analyze combined disease, especially biliary neoplasm, and to evaluate biliary tract microscopic changes in the biliary tract. METHODS : To study the clinical characteristics of APBDU, we reviewed 21 APBDU cases which were treated from June 1994 to January 1998. We studied the associated diseases, the surgical treatment, histological findings and the PCNA expression. We also analyzed the gallbladder epithelium in 10 control patients without APBDU. RESULTS : Among the 21 cases, 12 cases were accompanied by a choledochal cyst. A gallbladder carci noma occurred in 5 cases. Of the 13 operations, 4 involved a cholecystectomy only, and 9 involved a cholecystectomy, bile duct resection and hepaticojejunostomy. The histologic findings were reviewed in 13 cases. Bile duct metaplasia was found in 8 of the 9 cases with a bile duct resection, and gallbladder metaplasia was found in 8 of the 12 cases whereas metaplasia was detected in 1 of the 10 control patients. The PCNA expression was significantly high in APBDU group. CONCLUSIONS : The patients with APBDU showed a high incidence of gallbladder carcinoma and meta plasia in the epithelium of the gallbladder and the bile duct. This metaplasia in the gallbladder and the bile duct was thought to be related to the cancerous change.

A Case of Choledochal Cyst with Anomalous Pancreaticobiliary Ductal Union

Choledochal cysts are congenital or acquired lesions of the biliary tree with a cystic dilatation of the bile duct. We experienced a choledochal cyst accompanying acute pancreatitis caused by anomalous pancreaticobiliary ductal union (APBDU) in a 2 year old boy. The choledochal cyst associated with APBDU is rarely encountered in the clinical field, and thus we report this case with the presentation of abdominal ultrasonogram, computed tomogram, and intraoperative cholangiogram. A brief review of choledochal cyst associated with APBDU is also presented.

Biliary Malignancy associated with Anomalous Pancreaticobiliary Ductal Union / 한국간담췌외과학회지

BACKGROUND/AIMS: Anomalous connection between the choledochus and the pancreatic duct is considered to be a factor in the development of carcinoma of the biliary tract. There is especially a malignant potential for gallbladder cancer without dilatation of bile duct. We intend to find the clinical significance of anomalous pancreaticobiliary ductal union (APBDU) and biliary malignancy, and the correlation between type of APBDU and that of biliary malignancy (gallbladder of bile duct). Our purpose is to certificate the propriety of prophylactic cholecystectomy and to recall operation. METHOD AND RESULTS: We reviewed 880 ERCP cases from September 1994 through February 1996. There were fifteen cases of APBDU and six cases of biliary tumor associated with APBDU. They consisted of three gallbladder cancer with all P-C type union, two bile duct cancer with C-P type union and one villous adenoma in dilated bile duct. In one reoperation case in which cystojejunostomy had already been performed, there was no evidence of malignancy, but one was inoperable due to multiple liver metastasis. CONCLUSION: The patients with APBDU showed an increase of gallbladder cancer occurrence and furthermore those with the C-P type of APBDU, not associated with bile duct dilatation had a higher occurrence. And therefore were censidered preventive cholecystectomy and in operation to divide the biliary duct and pancreatic duct. Preoperative CA 19-9 test is helpful in finding the hidden cancer and is a guide to preventive operation in APBDU patients and to post-operative follow-up.

Clinical Significance of Anomalous Pancreaticobiliary Ductal Union Diagnosed by Endoscopic Retrograde Cholangiopancreatography / 대한소화기내시경학회지

To evaluate the clinical significance of anomalous pancreaticobiliary ductal union(PBDU), we analysed 11 cases(0.19%) of anomalous PBDU among 5675 cases performed ERCP from Jan. 1973 to Aug. 1992. According to the classification of Kimura et al., 4 cases were type 1(P-C union) and 7 cases type 2(C-P union). The length of common channel ranged from 1.5 cm to 3.1 cm(mean 1.9 cm). The common associated disease were choledochal cyst(7 cases), carcinoma of the gallbladder(5 cases) and biliary stone(3 cases). Four cases of carcinoma of the gallbladder were type 1. The incidence of anomalous PBDU was significantly higher in cases with carcinoma of the gallbladder(5 cases among 49 cases) than in case without carcinoma of the gallbladder(6 cases among 5626 cases). And the incidence of gallbladder carcinoma(45%) among the 11 cases of anomalous PBDU was significantly higher than that(0.78%) among those who did not have anomalous PBDU. In conclusion, the common associated diseases with the anomalous PBDU were choledochal cyst, carcinoma of the gallbladder and stone, and the anomalous PBDU may be risk factor in the development of carcinoma of the gllbladder.