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1.
Gallbladder carcinoma associated with pancreatobiliary reflux   总被引:1,自引:0,他引:1  
INTRODUCTIONIt is well known that pancreatobiliary reflux is an important risk factor for the carcinogenesis of the biliary system in patients with pancreaticobiliary maljunction(PBM)[1,2],which is a congenital anomaly defined as an abnormal union of the …  相似文献   

2.
AIM: To detect the patients with and without pancreaticobiliary maljunction who had pancreatobiliary reflux with extremely high biliary amylase levels.METHODS: Ninety-six patients, who had diffuse thickness (>3 mm) of the gallbladder wall and were suspected of having a pancreaticobiliary maljunction on ultrasonography, were prospectively subjected to endoscopic retrograde cholangiopancreatography, and bile in the common bile duct was sampled. Among them,patients, who had extremely high biliary amylase levels (>10000 IU/L), underwent cholecystectomy, and the clinicopathological findings of those patients with and without pancreaticobiliary maljunction were examined.RESULTS: Seventeen patients had biliary amylase levels in the common bile duct above 10000 IU/L, including 11 with pancreaticobiliary maljunction and 6 without pancreaticobiliary maljunction. The occurrence of gallbladder carcinoma was 45.5% (5/11) in patients with pancreaticobiliary maljunction, and 50% (3/6) in those without pancreaticobiliary maljunction.CONCLUSION: Pancreatobiliary reflux with extremely high biliary amylase levels and associated gallbladder carcinoma could be identified in patients with and without pancreaticobiliary maljunction, and those patients might be detected by ultrasonography and bile sampling.  相似文献   

3.
OBJECTIVES: Pancreaticobiliary maljunction, an anomalous union of the pancreatic duct with the common bile duct, is a risk factor for biliary carcinoma. We hypothesized that, in patients with pancreaticobiliary maljunction, persistent regurgitation of pancreatic juice into the biliary tract induces oxidative DNA damage. We assessed the expression of an oxidative DNA base-modified product, 8-hydroxy-2'-deoxyguanosine, in gallbladder epithelium. DESIGN: Eleven noncancerous gallbladders from patients with pancreaticobiliary maljunction, 12 gallbladder carcinomas from patients without pancreaticobiliary maljunction and 14 noncancerous gallbladders from patients without pancreaticobiliary maljunction (control) were studied. METHODS: Immunohistochemistry was performed for 4-hydroxy-2-nonenal-modified protein (as a marker for lipid peroxidation), 8-hydroxy-2'-deoxyguanosine and p53 gene product. RESULTS: Stronger cytoplasmic staining of 4-hydroxy-2-nonenal-modified protein was observed in the gallbladder epithelium from patients with pancreaticobiliary maljunction than in epithelium from gallbladder cancer patients or from control subjects with normal gallbladders. Clear, strong nuclear staining of 8-hydroxy-2'-deoxyguanosine was observed in the gallbladder epithelial cells from patients with pancreaticobiliary maljunction. Densitometric quantitation revealed significantly higher expression of 8-hydroxy-2'-deoxyguanosine in gallbladder epithelial cells from patients with pancreaticobiliary maljunction (index 27.3 +/- 3.1) than in cells from patients with gallbladder carcinoma (11.4 +/- 1.5; P < 0.05) or from control subjects with normal gallbladder (6.4 +/- 1.0; P < 0.05). Positivity of p53 was 27% in gallbladder epithelium associated with pancreaticobiliary maljunction, 75% in gallbladder carcinoma epithelium and 0% in control epithelium. CONCLUSIONS: These results suggest that reactive oxygen species are produced in the gallbladder of patients with pancreaticobiliary maljunction and that oxidative DNA injury is related to carcinogenesis in these patients.  相似文献   

4.
BACKGROUND: Anomalous pancreaticobiliary ductal junction, a rare congenital anomaly, is associated with various biliary and pancreatic diseases. The aim of this study was to determine the frequency of anomalous pancreaticobiliary ductal junction in Chinese patients with gallbladder cancer. METHODS: One thousand eight hundred seventy-six patients underwent ERCP between April 2000 and September 2001 with biliary and pancreatic duct opacification in 1082. Among the latter patients, those with proven gallbladder carcinoma were identified. Anomalous pancreaticobiliary ductal junction was defined as a common channel greater than 15 mm in length or a contractile segment totally distal to the union of the biliary and pancreatic ducts. When the common bile duct appeared to join the main pancreatic duct, the anomalous pancreaticobiliary ductal junction was denoted as B-P subtype; if the main pancreatic duct appeared to join the common bile duct, it was denoted P-B subtype. RESULTS: Fifty-four patients had gallbladder carcinoma, 7 of whom (3 men, 4 women) had anomalous pancreaticobiliary ductal junction (P-B subtype 6, B-P subtype 1). The mean (SD) length of the common channel was 21.0 mm (11.2 mm) with a range of 12 to 45 mm. One patient had early cystic dilation of bile duct. Three other patients had anomalous pancreaticobiliary ductal junction; 1 had an associated choledochal cyst and 2 a normal biliary tree. The overall frequency of anomalous pancreaticobiliary ductal junction was 0.9% (10/1082 cases). The frequency of anomalous pancreaticobiliary ductal junction was significantly higher in patients with gallbladder carcinoma (p < 0.001; OR, 50.7; 95% CI [12.7, 202.3]). CONCLUSIONS: Anomalous pancreaticobiliary ductal junction is strongly associated with gallbladder cancer among Chinese patients.  相似文献   

5.
We report a rare case of metachronous double cancer of the biliary tract. At age 59 years, a man had undergone a cholecystectomy and resection of the liver bed for gallbladder cancer pathologically diagnosed as papillary adenocarcinoma, in 1997. Four years later, he was admitted to our hospital with jaundice. At first, we suspected lymph node metastasis of the gallbladder cancer along the common bile duct. But abdominal computed tomography demonstrated circular wall thickness of the common bile duct, so primary bile duct cancer was strongly suspected. Thus, extended right hepatectomy and pancreaticoduodenectomy were performed after right portal vein embolization. The pathological diagnosis of the resected specimen was well-differentiated tubular adenocarcinoma, and this case was clarified to be metachronous double cancer. A review of the literature regarding double cancer of the biliary tract is presented following this case report. We showed that half of 30 cases of double cancer of the biliary tract were not associated with pancreaticobiliary maljunction, including all 6 metachronous cases.  相似文献   

6.
A 58-year-old man on abdominal ultrasonography and CT had an irregularly elevated lesion at the neck of the gallbladder and a cyst of approximately 6.5 cm in diameter at the pancreatic tail. Percutaneous transhepatic cholangiography revealed a 2-cm shadow defect at the neck of the gallbladder and an irregular, translucent 30 x 12 mm lesion in the intrapancreatic bile duct. Total pancreatectomy and extended cholecystectomy with regional lymph node dissection was performed. An anomalous arrangement of the pancreaticobiliary ductal system (AAPBD) was demonstrated by postoperative contrast radiography of resected specimen. The lesions of the gallbladder and common bile duct were papillary adenocarcinoma. In addition, papillary adenocarcinoma was limited almost entirely to the mucosal layer of the main pancreatic duct and its branches, from the junction of the common bile duct and pancreatic duct to the pancreatic tail. The three tumors were not continuous. The cyst at the pancreatic tail was a pseudocyst. This case represents synchronous cancer of the gallbladder, common bile duct, and pancreas associated with AAPBD.  相似文献   

7.
BACKGROUND/AIMS: The incidence of biliary tract cancer development is high among patients with pancreaticobiliary maljunction. However, there have been no reports published evaluating the incidence of development of biliary tract cancers in pancreaticobiliary maljunction based on the morphology of the common channel at the junction of the bile and pancreatic ducts. We evaluated between types of common channel and development of biliary tract cancers in pancreaticobiliary maljunction. METHODOLOGY: During the last 21 years, we have experienced 78 patients with pancreaticobiliary maljunction. Of those patients, 44 adult patients, whose morphologic types of common channel were identified by cholangiography, were enrolled in this study. The dilatation patterns of the common channel were classified into 3 types: A type (moderately dilated type), B type (markedly dilated type), and C type (non-dilated type). Evaluated items included the length and dilation patterns of the common channel, incidence of development of biliary tract cancers and proliferative activity in the biliary tract epithelium. RESULTS: Seventeen patients had a common channel shorter than 20 mm, while 27 had a common channel of 20 mm or longer. Eleven patients with a common channel of 20 mm or longer had development of bile tract cancers. The dilation patterns of the common channel were classified as A (11 patients), B (16 patients) and C type (17 patients). Amylase levels in the biliary tract were higher in patients with A and B type than in patients with the C type. Development of gallbladder cancer was observed in 6 patients with A, 2 patients with B and one patient with C, while development of bile duct cancer was observed in 2 patients with C and one patient with B. The PCNAL.I. of the biliary epithelium was higher in patients with A, B and C type in descending order. CONCLUSIONS: The incidence of development of biliary tract cancer was higher in patients with common channel of 20 mm or longer. The proliferative activity in the biliary epithelium was accelerated in patients with A type, together with a high incidence of development of gallbladder cancer.  相似文献   

8.
It is widely known that pancreaticobiliary maljunction (PBM), an anomalous arrangement of the pancreaticobiliary ductal system, is frequently associated with biliary tract cancer in patients with or without bile duct dilatation. In 1985, we surveyed patients with PBM who had been operated on at 133 Japanese institutions. A close relationship was shown between biliary tract carcinogenesis and PBM, according to the type of maljunction and age distribution: PBM patients with cystic dilatation had a high risk of bile duct cancer, even in those who were young (aged less than 20 years); the incidence of gallbladder cancer increased markedly in PBM patients over 40 years old with cystic dilatation, while it gradually increased with age in the PBM patients without cystic dilatation. Therefore, we recommend surgical treatment for patients with PBM even if they have no symptoms.  相似文献   

9.
Kamisawa T  Okamoto A 《Digestion》2006,73(4):228-236
The sphincter of Oddi is located at the distal end of the pancreatic and bile ducts and regulates the outflow of bile and pancreatic juice. A common channel can be so long that the junction of the pancreatic and bile ducts is located outside of the duodenal wall, as occurs in pancreaticobiliary maljunction; in such cases, the action of the sphincter does not functionally affect the junction. Thus, biliopancreatic and pancreatobiliary refluxes occur, resulting in various pathological conditions in the biliary tract and in the pancreas. Biliopancreatic reflux could be confirmed by operative or postoperative T tube cholangiography, computed tomography combined with drip infusion cholangiography, histological detection of gallbladder cancer cells in the main pancreatic duct, and reflux of bile on the cut surface of the pancreas. Pancreatobiliary reflux could be diagnosed on the basis of an elevated amylase level in the bile, secretin-stimulated dynamic magnetic resonance cholangiopancreatography, and pancreatography via the minor duodenal papilla. Recently, it has become obvious that these refluxes can occur in individuals without pancreaticobiliary maljunction. Biliopancreatic reflux is related to the occurrence of acute pancreatitis, and pancreatobiliary reflux might be related to biliary carcinogenesis even in some individuals without pancreaticobiliary maljunction. Since few systemic studies exists with respect to diagnostic imaging techniques and clinical relevance of these refluxes in individuals with a normal pancreaticobiliary junction, further prospective clinical studies including appropriate management should be performed.  相似文献   

10.
BACKGROUND/AIMS: Pancreaticobiliary maljunction (PBM) and pancreas divisum (PD) are congenital anomalies that develop in the embryo at an early stage. They are possibly the result of bile and pancreatic duct misarrangement. We investigated the configuration of the pancreatic duct in patients with PBM and its clinical implications. METHODOLOGY: In 84 PBM patients, the configuration of the pancreatic duct and the presence of biliary cancer were documented. Patency of Santorini's duct was determined fluoroscopically or by dye-injection endoscopic retrograde pancreatography. Bile amylase levels were measured in 10 patients. RESULTS: Incomplete PD was detected in 8 (9.5%) of the 84 PBM patients. All of the 8 patients had a patent Santorini's duct, and only 1 patient had gallbladder cancer. The frequency of associated gallbladder cancer and the bile amylase level were significantly lower in PBM patients with a patent Santorini's duct than in PBM patients with a nonpatent Santorini's duct. CONCLUSIONS: PBM is sometimes associated with incomplete PD. In PBM patients with an incomplete PD, the incidence of cancer of the biliary tract may be lower, since pancreatic juice reflux into the bile duct might be reduced by the flow of pancreatic juice into the duodenum through Santorini's duct.  相似文献   

11.
BACKGROUND/AIMS: The authors evaluated the surgical treatment for non-dilated biliary tract with pancreaticobiliary maljunction. METHODOLOGY: Sixty-nine patients with pancreaticobiliary maljunction were divided into 61 patients with the dilated biliary tract and 8 with the non-dilated biliary tract. The levels of amylase activity in the bile in the gallbladder and the bile duct, the incidence and severity of postoperative cholangitis, and cell proliferating activity of the biliary tract epithelium, examined the proliferating cell nuclear antigen labeling index (PCNALI), were examined. RESULTS: Of the 61 dilated type patients, 12 were of Ia, 1 was of Ib, 22 were of Ic, 25 were of IV-A, and 1 was of IV-B according to Todani's classification. Cancer was detected in 7 dilated type patients and in 3 non-dilated type patients. A high level of amylase activity was measured in the bile juice in both the gallbladder and bile duct in all of the patients with pancreaticobiliary maljunction. PCNALI of the biliary tract epithelium of the patients without cancer (dilated type: bile duct 11.4%, gallbladder 12.7%; non-dilated type: bile duct 5.9%, gallbladder 13.8%) was higher than that of the patients without pancreaticobiliary maljunction (bile duct 1.5%, gallbladder 1.4%). CONCLUSIONS: In a non-dilated type, as well as in a dilated type, a high level of amylase activity and increase of cell proliferative activity of the biliary tract epithelium were observed. Therefore, these results suggest that the extrahepatic bile duct should be prophylactically removed in patients with non-dilated type as well as in those with dilated type pancreaticobiliary maljunction.  相似文献   

12.
We report the case of a 46-year-old woman who presented with chronic intermittent abdominal pain without jaundice; abdominal ultrasonography showed thickening of the gallbladder wall and dilatation of the bile duct. Endoscopic retrograde cholangiopancreaticography showed pancreatobiliary maljunction with proximal common bile duct dilatation. Pancreatobiliary maljunction was diagnosed. A computed tomography scan of the abdomen showed suspected gallbladder cancer and distal common bile duct obstruction. A pancreatic head mass was incidentally found intraoperative. Radical cholecystectomy with pancreatoduodenectomy was performed. The pathological report showed gallbladder cancer that was synchronous with pancreatic head cancer. In the pancreatobiliary maljunction with pancreatobiliary reflux condition, double primary cancer of the pancreatobiliary system should be awared.  相似文献   

13.
BACKGROUND/AIMS: Pancreaticobiliary maljunction is a rare anomaly, but causes various pathological conditions in the biliary tract and the pancreas. This study aims at clarifying the features of pancreatitis associated with pancreaticobiliary maljunction. METHODOLOGY: A total of 100 patients with pancreaticobiliary maljunction were reviewed. Clinical findings and cholangiopancreatographic results in patients with acute or chronic pancreatitis associated with pancreaticobiliary maljunction were analyzed. RESULTS: Of 100 patients, 14 had pancreatic disorders: acute pancreatitis (n = 3), chronic pancreatitis (n = 5), hyperamylasemia (n = 4), and pancreatic carcinoma (n = 2). The acute pancreatitis was mild (n = 3) and relapsing (n = 2). In patients with chronic pancreatitis, pancreatic stones (n = 2) and radiolucent protein plugs (n = 2) were detected only in the dilated common channel or in the main pancreatic duct near the common channel. Two patients received cyst-duodenostomy in the infant developed chronic pancreatitis 11 and 27 years later. CONCLUSIONS: Acute or chronic pancreatitis was sometimes associated with pancreaticobiliary maljunction. These pancreatitis cases showed different clinical and pancreatographic findings from others. These differences might be due to the peculiar mechanism that they were induced by bile reflux into the pancreatic duct via the anomalous connection.  相似文献   

14.
While gallbladder carcinoma is occasionally associated with pancreaticobiliary maljunction, spontaneous necrosis of carcinoma is extremely rare. We herein present a case of spontaneous necrosis of gallbladder carcinoma associated with direct invasion of viable cancer cell nests to the muscularis propria and subserosal layer located beneath the primary nodules. A 65-year-old Japanese man was admitted to a local hospital, complaining of repeated discomfort in the right hypochondrium. Ultrasonography and computed tomography scanning revealed cholecystitis associated with gallstones. Cholecystectomy was performed, and operative cholangiography demonstrated pancreaticobiliary maljunction. The resected gallbladder showed multiple mixed stones filled with necrotic debris and bile sludge. Scrutiny of the mucosal surface revealed multiple small necrotic nodules in the fundus, which were histologically confirmed to be necrotic remnants of a cancerous glandular structure. Small nests of papillary adenocarcinoma were found beneath the nodules in the muscularis propria and in the venous structure located in the connective tissues next to the divided margin of the gallbladder bed. Resection of S4a and S5 of the liver and resection of the extrahepatic bile duct was then performed to remove the remaining cancerous tissues and/or micrometastasis in the liver and bile duct. The biliary tree was reconstructed with a hepaticoduodenostomy. No cancer nests or any precancerous lesions were found in the additionally resected specimens. This case indicates a unique morphological feature of gallbladder carcinoma associated with pancreaticobiliary maljunction, which provides some insight into the pathogenesis of spontaneous necrosis of gallbladder carcinoma.  相似文献   

15.
We report a case of double cancer of the gallbladder and the common bile duct associated with anomalous junction of the pancreaticobiliary ductal system, and review the literature of similar case reports. A 66-year-old woman was admitted to an associated hospital complaining of upper abdominal pain, and was diagnosed as having pancreatitis. Abdominal imaging revealed an irregularly protruding mass at the body of the gallbladder and an intraluminal protrusion at the lower third of the common bile duct. Endoscopic retrograde cholangiopancreatography also revealed anomalous junction of the pancreaticobiliary ductal system with congenital biliary dilatation of 14 mm in the largest diameter. She underwent surgical resection of the gallbladder, the extrahepatic bile duct and the gallbladder bed of the liver with a dissection of the regional lymph nodes for double cancer of the gallbladder and the bile duct associated with anomalous junction of the pancreaticobiliary ductal system. She is still alive 33 months after surgery without any signs of recurrence. There were 12 patients (including our case) reported in the literature who had double cancer of the gallbladder and the extrahepatic bile duct associated with anomalous junction of the pancreaticobiliary ductal system. Only 33% of these 12 patients had jaundice. Tumors of the 12 patients were commonly early-stage cancer both in the gallbladder (36%) and in the extrahepatic bile duct (73%). Therefore, we concluded that precise preoperative imaging of the total biliary tract should be required in order to detect early-stage cancer in patients with anomalous junction of the pancreaticobiliary ductal system before planning surgical procedures, and consideration should be given to the possibility of multiple occurrences of biliary tract cancers.  相似文献   

16.
BACKGROUND/AIMS: Anomalous pancreaticobiliary junction is a rare anomaly but is a risk factor for primary carcinoma of the gallbladder. To define the relationship between anomalous pancreaticobiliary junction, especially if it is not associated with common bile duct dilatation, and gallbladder carcinoma, we retrospectively reviewed data of 126 patients with gallbladder carcinoma. METHODOLOGY: All these patients had undergone direct cholangiography either by endoscopic retrograde cholangiopancreaticography or percutaneous transhepatic cholangiography. RESULTS: Among 126 patients with gallbladder cancer, 23 patients (18.3%) exhibited anomalous pancreaticobiliary junction. Patients with anomalous pancreaticobiliary junction were younger (mean age: 54 +/- 9.1 years) than patients without anomalous pancreaticobiliary junction (mean age: 65 +/- 9.7 years). The incidence of gallstones in patients with anomalous pancreaticobiliary junction (17%) was significantly lower than in those without this anomaly (64%) (P < 0.01). Among the 23 patients with anomalous pancreaticobiliary junction, 12 patients (52%) had no bile duct dilatation and, 11 patients (48%) had bile duct dilatation in the form of fusiform or cylindrical dilatation. However, no cases with severe cystic dilatation were found. Patients of anomalous pancreaticobiliary junction without common bile duct dilatation had more advanced disease and poor prognosis than those with common bile duct dilatation. CONCLUSIONS: The present study revealed that gallbladder cancer in the patients of anomalous pancreaticobiliary junction without common bile duct dilatation was diagnosed at advanced stage and the prognosis was very poor. Therefore, if a minor abnormality is detected in the wall of acalculous gallbladder on ultrasonography, direct cholangiography should be done to exclude this anomaly.  相似文献   

17.
A 46-yr-old woman was admitted to our hospital with mild epigastric pain. Ultrasonography and computed tomography revealed an extremely thickened gallbladder wall. Endoscopic retrograde cholangiopancreatography demonstrated that the main pancreatic duct joined the nondilated common bile duct at the outer point of the duodenal wall (P-C type of pancreaticobiliary maljunction), and the cystic duct joined the common channel directly. The intraoperative amylase levels of the bile juices both in the common bile duct and the cystic duct were high. A cholecystectomy was performed. The wall of the gallbladder was markedly thick, yellowish, elastic, and soft. Histologically, Rokitansky-Aschoff sinus proliferation, hypertrophy of smooth muscles, and fibrosis were seen. The diagnosis was a generalized type of adenomyomatosis. The pathogenesis of the adenomyomatosis was believed to result from chronic stimulation as a result of pancreatic juice reflux. The etiology of this unusual type of junction was considered to be the result of the combination of pancreaticobiliary maljunction and an anomaly of lower junction of the cystic duct.  相似文献   

18.
A rare case of pancreaticobiliary maljunction (PBM) without dilatation of the biliary tract (DBT) associated with gallbladder carcinoma is described herein. A 62‐year‐old European woman with a long history of right upper abdominal pain was diagnosed as having PBM without DBT by endoscopic retrograde cholangiopancreatography and other examinations. Excision of the gallbladder and biliary duct with a Roux‐en‐Y hepaticojejunostomy was performed, and subsequent pathological examination of the surgical specimen showed a well differentiated adenocarcinoma of the gallbladder. She had no clinical symptoms for 58 months postoperatively. PBM allows reflux of pancreatic juice into the biliary tract. Recent findings support the idea that epithelial hyperplasia plays an important role in gallbladder carcinogenesis with PBM, and also support the concept that gene mutations are involved in the carcinogenesis of biliary epithelium in patients with PBM. For these reasons, we advocate that resection of the extrahepatic biliary tract in PBM patients without bile duct dilatation, rather than cholecystectomy alone, is the treatment of choice for preventing bile duct carcinoma.  相似文献   

19.
The common bile duct and the main pancreatic duct open into the duodenum, where they frequently form a common channel. The sphincter of Oddi is located at the distal end of the pancreatic and bile ducts; it regulates the outflow of bile and pancreatic juice. In patients with a pancreaticobiliary maljunction, the action of the sphincter does not functionally affect the junction. Therefore, in these patients, two-way regurgitation (pancreatobiliary and biliopancreatic reflux) occurs. This results in various pathological conditions of the biliary tract and the pancreas. Biliopancreatic reflux could be confirmed by: operative or postoperative T-tube cholangiography; CT combined with drip infusion cholangiography; histological detection of gallbladder cancer cells in the main pancreatic duct; and reflux of bile on the cut surface of the pancreas. Biliopancreatic reflux occurs frequently in patients with a long common channel. Although the true prevalence, degree, and pathophysiology of biliopancreatic reflux remain unclear, biliopancreatic reflux is related to the occurrence of acute pancreatitis. Obstruction of a long common channel easily causes bile flow into the pancreas. Even if no obstruction is present, biliopancreatic reflux can still result in acute pancreatitis in some cases.  相似文献   

20.
BACKGROUND/AIMS: The objective of this study was to evaluate the clinicopathological features of patients with pancreaticobiliary maljunction, which was detected by intraoperative cholangiography in laparoscopic cholecystectomy. METHODOLOGY: Among 78 patients who underwent intraoperative cholangiography in laparoscopic cholecystectomy, 8 patients had the radiological findings of pancreaticobiliary maljunction. The clinicopathological factors were analyzed in them. RESULTS: They consisted of 2 males and 6 females with a mean age of 57.8 years (range: 36-76 years). Preoperatively, 7 patients were diagnosed as cholelithiasis and one was diagnosed as polypoid lesions of the gallbladder. None of them had dilated choledochus. All of them underwent cholecystectomy alone extrahepatic bile duct resection was omitted, and was performed. Histopathologic examinations of the resected gallbladder revealed epithelial hyperplasia in one patient, in whom amylase level of the gallbladder bile was also highly elevated. Postoperatively, none of them had acute pancreatitis, cholangitis, or biliary cancer. CONCLUSIONS: Further prolonged careful follow-up is warranted in our series of patients.  相似文献   

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