Pancreatobiliary reflux in individuals with a normal pancreaticobiliary junction: a prospective multicenter study

Background

Pancreatobiliary reflux (PBR) can occur in individuals without pancreaticobiliary maljunction. The aim of this study was to elucidate the incidence of PBR in individuals with a normal pancreaticobiliary junction and its impact on the biliary tree.

Methods

Data were prospectively collected from 15 centers on 420 patients with a morphologically normal pancreaticobiliary junction who had undergone bile sampling and measurement of the biliary amylase level. We investigated the incidence and predictive factors for high biliary amylase levels (HBAL), as well as the relationship of HBAL with biliary malignancy.

Results

Twenty-three patients (5.5 %) showed HBAL (≥10,000 IU/L). Univariate analysis showed that risk factors for the elevation of biliary amylase levels were the existence of a relatively long common channel (≥5 mm), acute pancreatitis, and papillitis. Multivariate analysis revealed that only the existence of a relatively long common channel was a significant factor for PBR. Biliary amylase levels in patients with a relatively long common channel were significantly higher than in patients without a long common channel (12,333 vs. 2,070 IU/L, P = 0.001). The incidence of HBAL (P < 0.001), as well as the overall biliary amylase levels (P = 0.007) were significantly higher in patients with gallbladder cancer than in those without gallbladder cancer.

Conclusions

The PBR was frequently observed in individuals with a relatively long common channel. Patients showing HBAL with normal pancreaticobiliary junction are at high risk for gallbladder cancer.     

Gallbladder carcinoma associated with pancreatobiliary reflux

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.     

Gallbladder carcinoma associated with pancreatobiliary reflux

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 …     

Amylase levels in bile in patients with a morphologically normal pancreaticobiliary ductal arrangement

Background We investigated the presence of occult pancreaticobiliary reflux in patients with a morphologically normal pancreaticobiliary ductal arrangement by measuring biliary amylase levels and compared histopathological findings of the gallbladder between groups with high and low biliary amylase levels. Methods In 178 patients with a normal pancreaticobiliary ductal arrangement who had undergone endoscopic retrograde cholangiopancreatography (ERCP), we sampled bile from the bile duct and measured amylase levels. Then we compared clinical features and histological findings of the gallbladder between high (HALG) and low amylase level groups (LALG). Results A high biliary amylase level was observed in 25.8% (46/178) of the patients. The prevalence of a high biliary amylase level was high in patients with gallbladder carcinoma (40%) and in those with choledocholithiasis (28.4%). The level of amylase in bile was high in patients with gallbladder carcinoma, adenomyomatosis of the gallbladder, and chronic cholecystitis. A strong correlation between the levels of amylase and lipase in bile and the dominance of amylase of pancreatic origin in bile were confirmed by isozyme analysis. Thickening of the gallbladder mucosa was a significant manifestation in HALG. Histological examination of the gallbladder mucosa showed that incidences of metaplastic change and atypical epithelium and Ki67-LI in were higher in HALG than in LALG. Conclusions Occult pancreaticobiliary reflux is observed in a considerable number of ERCP candidates. Those who show an extremely high biliary amylase level, at least, may be at high risk for biliary malignancies.     

Surgical treatment for non-dilated biliary tract with pancreaticobiliary maljunction should include excision of the extrahepatic bile duct

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.     

Occult pancreatobiliary reflux and gallbladder carcinoma]

A total of 108 patients with a normal pancreaticobiliary junction who had gallbladder wall thickness as shown by ultrasonography or computed tomography underwent secretin injection magnetic resonance cholangiopancreatography. Based on the changes in the diameter of the biliary system after secretin injection, patients were categorized into the intensified group (n = 19) or the non-intensified group (n = 89). The mean (+/- SD) biliary amylase level in the bile duct was 41674 (+/- 59779) IU/L in the intensified group, which was significantly higher than that in the non-intensified group (210 (+/- 418)) IU/L (p < 0.0001). There were four patients with carcinoma of the gallbladder in the intensified group and their biliary amylase level in the bile duct was 90783 (+/- 82528) IU/L. Pancreatobiliary reflux similar to that seen in patients with pancreaticobiliary maljunction can occur in persons with a normal pancreaticobiliary junction and this may be associated with carcinoma of the gallbladder. Secretin injection magnetic resonance cholangiopancreatography proved useful to identify such persons.     

Whether or not prophylactic excision of the extrahepatic bile duct is appropriate for patients with pancreaticobiliary maljunction without bile duct dilatation

BACKGROUND/AIMS: The standard treatment for patients with a pancreaticobiliary maljunction (PBM) without bile duct dilatation remains controversial. METHODOLOGY: We followed up 29 patients with such PBM who mainly underwent a cholecystectomy alone. The ages of the patients ranged from 3 to 76 years (average age 47.3 years) and the ratio of males to females was 8 vs. 21. When the diameter of the common bile duct was less than 10mm, such bile ducts were diagnosed to have no dilatation. The main clinical indications for surgery were cholecystolithiasis in 15 patients, choledocholithiasis in 3, cholecystocholedocholithiasis in 2, gallbladder polyp in 2, adenomyomatosis in 2, cholecystitis in 2, and protein plug in 1. RESULTS: The amylase levels of gallbladder bile in 20 patients ranged from 115 to 460,200 IU/mL (a mean of 191,698 IU/mL). One patient died of gastric cancer 182 months after surgery and two patients died of other diseases 153, 171 months after surgeries, respectively. The remaining 26 patients have all been doing well for 36 months to 326 months after surgery (a median follow-up period, 160.5 months). The 10- and 15-year survival rates were 100% and 89.7%. CONCLUSIONS: In conclusion, a prophylactic resection of the extrahepatic bile duct and biliary diversion could be unnecessary for patients with PBM without bile duct dilatation.     

A case of gallbladder carcinoma associated with pancreatobiliary reflux in the absence of a pancreaticobiliary maljunction： A hint for early diagnosis of gallbladder carcinoma

A 62-year-old man with progressive thickening of the gallbladder wall visited our outpatient clinic. The biliary amylase level in the common bile duct was 19900 IU/L and that of the gallbladder was 127000 IU/L, although endoscopic retrograde cholangiopancreatography revealed no pancreaticobiliary maljunction. Histology demonstrated a moderately differentiated adenocarcinoma of the gallbladder. Pancreatobiliary reflux and associated gallbladder carcinoma were confirmed in the present case, in the absence of a pancreaticobiliary maljunction. Earlier detection of the pancreatobiliary reflux and progressive thickening of the gallbladder wall might have led to an earlier resection of the gallbladder and improved this patient's poor prognosis.     

Assessment of occult pancreatobiliary reflux in patients with pancreaticobiliary disease by ERCP

Background The aim of this study was to evaluate the degree of occult pancreatobiliary reflux by measuring the biliary amylase levels in the common bile duct (CBDA) and gallbladder (GBA) at endoscopic retrograde cholangiopancreatography (ERCP).Methods Eligible patients included 86 consecutive cases of pancreaticobiliary disease with prospective implementation of bile collection during an ERCP procedure. Patients with pancreatobiliary maljunction (PBM) were excluded. Nineteen cases of eligible patients had simultaneous collection of gallbladder bile. Bile was further collected by cholecystectomy in 8 cases.Results Twenty-two cases (26%) revealed a CBDA level higher than serum amylase (high bile amylase level, HBA group) and 64 cases exhibited a CBDA level lower than serum (LBA group). The mean values of CBDA in the HBA and LBA groups were 5502IU/l and 29IU/l, respectively. The rate of HBA was significantly higher in patients who were elderly, had a dilated common bile duct, and those with choledocholithiasis (P < 0.05). Three cases (16%) showed a CBDA greater than twice the GBA. Eleven cases (58%) exhibited a GBA higher than the CBDA. The values of GBA obtained during ERCP and cholecystectomy were consistent.Conclusions These findings suggest that even non-PBM cases can exhibit occult pancreatobiliary reflux, which can thereby cause biliary disease.     

Does endoscopic sphincterotomy cause prolonged pancreatobiliary reflux?

OBJECTIVE: Endoscopic sphincterotomy (ES) reduces sphincter function, which may allow reflux of pancreatic juice and intestinal contents into the common bile duct. The reflux, if present, may cause development of biliary tract carcinomas, as may anomalous pancreaticobiliary junction. We prospectively investigated pancreatobiliary and duodenobiliary reflux after ES. METHODS: In 15 patients with choledocholithiasis, ductal bile was sampled for amylase concentration and bacterial culture during endoscopic retrograde cholangiopancreatography, before and at 7 days to 5 yr after ES. To provide comparative data, ductal bile was sampled in 11 patients with gallbladder cholesterol polyps or anomalous pancreaticobiliary junction who did not undergo ES. RESULTS: Amylase concentration of ductal bile in patients with choledocholithiasis before ES was not different from that in patients with gallbladder polyps. Its concentration was increased 7 days after ES compared with that before ES, reaching the level of that in patients with anomalous pancreaticobiliary junction. Thereafter, amylase concentration gradually decreased, returning to that before ES by 1 yr. After ES, bactobilia occurred in 60-80% of patients, although none developed acute cholangitis. CONCLUSIONS: Although ES causes transient pancreatobiliary reflux, the reflux is abolished by 1 yr after ES. ES is unlikely to increase the risk for development of biliary tract carcinoma as long as cholangitis or bile duct stones do not recur.     

Occult pancreatobiliary reflux in patients with a normal pancreaticobiliary junction

BACKGROUND: The aim of this study was to investigate pancreatobiliary reflux in individuals with a normal pancreaticobiliary junction. METHODS: Seventy-four patients with a normal pancreaticobiliary junction, as determined by ERCP, underwent secretin injection MRCP before cholecystectomy. Based on changes in the diameter of the biliary system after secretin injection, patients were categorized into enhanced or nonenhanced groups. RESULTS: Biliary amylase was measured in the 4 patients allocated to the enhanced group and 60 in the nonenhanced group. The mean (SD) biliary amylase level in the gallbladder was 123,723 (115,125) IU/L in the enhanced group and 238 (507) IU/L in the nonenhanced group (p < 0.0001). The mean (SD) biliary amylase level in gallbladders with carcinoma (n = 7) was 68,281 (106,500) IU/L, which was significantly higher than that in gallbladders without carcinoma (p < 0.01). CONCLUSION: Pancreatobiliary reflux similar to that seen in patients with pancreaticobiliary maljunction can occur in individuals with a normal pancreaticobiliary junction and may be associated with carcinoma of the gallbladder. Secretin injection MRCP is useful for identifying these individuals.     

Increased lysophosphatidylcholine and pancreatic enzyme content in bile of patients with anomalous pancreaticobiliary ductal junction

A high incidence of inflammation and carcinoma of the biliary tract in patients with anomalous pancreaticobiliary ductal junction has been well documented. The change in biliary phospholipids as a result of the reflux of pancreatic juice into the biliary tract through anomalous pancreaticobiliary ductal junction may be responsible for it. We developed a new method of analysis of phospholipid classes using aminopropyl Bond Elut cartridge for extraction and high-performance liquid chromatography for separation. Satisfactory recovery was achieved (i.e., more than 95% for both phosphatidylcholine and lysophosphatidylcholine). With this method, the bile of 11 patients with anomalous pancreaticobiliary ductal junction was examined. The concentration and proportion of lysophosphatidylcholine in bile were much higher in the presence of anomalous pancreaticobiliary ductal junction than in controls (3.44 +/- 1.50 mmol/L vs. 0.52 +/- 0.25 mmol/L, 60.0% +/- 31.0% vs. 2.3% +/- 1.4% in gallbladder bile; p less than 0.001). In contrast, the concentration of phosphatidylcholine and the sum of phosphatidylcholine and lysophosphatidylcholine in gallbladder bile significantly decreased (p less than 0.001), but in hepatic bile they did not. An inverse correlation was found between the proportion of lysophosphatidylcholine and phospholipid concentration in gallbladder bile. Phospholipase A2 and amylase activities in bile were markedly high. Increased total fatty acid concentration and proportion of unsaturated fatty acid in bile were found. Total bile acid concentration in gallbladder bile was significantly lower than in controls. These results suggest that a considerable amount of lysophosphatidylcholine, which is known to have a cytotoxic effect, isp reduced by phospholipase A2 in refluxing pancreatic juice, and an increased concentration of lysophosphatidylcholine gives rise to cell damage causing mucosal hyperplasia and metaplasia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Role of endoscopic ultrasonography in diseases of the extrahepatic biliary system

Endoscopic ultrasonography (EUS) is one of the most recent advances in gastrointestinal endoscopy. Available EUS devices include echoendoscopes, such as radial scanning and linear array echoendoscopes, and catheter ultrasound probes. Endoscopic ultrasonography has various applications, such as staging of gastrointestinal malignancy, evaluation of submucosal tumors, and has grown to be an important modality in evaluating the pancreaticobiliary system. With regard to the biliary system, EUS is useful for the detection and staging of ampullary tumors, detection of microlithiasis and choledocholithiasis and evaluation of benign and malignant bile-duct strictures. Endoscopic ultrasonography may be used as an adjunct to transabdominal ultrasound for the detection and characterization of gallbladder polyps. In addition, EUS is helpful in the staging of gallbladder cancer as well as in diagnosing anomalous pancreaticobiliary junction with its associated pancreatobiliary diseases. The present paper reviews the current applications of EUS for imaging and intervention in diseases of the extrahepatic biliary system.     

Periampullary diverticula cause pancreatobiliary reflux

BACKGROUND: Periampullary diverticula are associated with dysfunction of the sphincter of Oddi. Papillary dysfunction may allow reflux of pancreatic juice as well as intestinal contents into the common bile duct. We prospectively investigated pancreatobiliary reflux in patients with and without periampullary diverticula. METHODS: The ductal bile was sampled for amylase concentration during endoscopic retrograde cholangiopancreatography in 47 patients with choledocholithiasis (n = 29; with (n = 14) or without (n = 15) periampullary diverticula) or gallbladder cholesterol polyps (n = 18; with (n = 6) or without (n = 12) diverticula). RESULTS: The amylase concentration within the ductal bile was significantly higher in choledocholithiasis patients with periampullary diverticula (1621 +/- 587 IU/l) than in those without diverticula (1155 +/- 418 IU/l). The amylase concentration tended to be higher in gallbladder polyp patients with diverticula (1087 +/- 275 IU/l) than in those without diverticula (833 +/- 272 IU/l). Irrespective of the presence or absence of diverticula, patients with bile duct stones had significantly higher amylase concentrations than those with gallbladder polyps. CONCLUSIONS: Periampullary diverticula cause pancreatobiliary reflux. Further investigation is required to determine the clinical implication of pancreatobiliary reflux.     

Association of anomalous pancreaticobiliary ductal junction with gallbladder carcinoma in Chinese patients: an ERCP study

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.     

Anomalous pancreaticobiliary ductal junction without bile duct dilatation in gallbladder cancer

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.     

Relationship between types of common channel and development of biliary tract cancer in pancreaticobiliary maljunction

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.     

Risk factor for extrahepatic bile duct cancer in patients with anomalous pancreaticobiliary ductal union

BACKGROUND/AIMS: Anomalous connection between the choledochus and pancreatic duct is considered to be a factor in the development of biliary tract diseases such as choledochal cyst, pancreatitis, cholangitis, gallbladder cancer, and bile duct cancer. Our purpose was analysis of combined disease, especially biliary neoplasm and evaluated microscopic changes of extrahepatic bile ducts. METHODOLOGY: To study the clinical characteristics of anomalous pancreaticobiliary ductal union (APBDU), we reviewed 14 APBDU cases from June 1994 to June 1998. We studied the associated disease, surgical treatment, and the histological findings of the extrahepatic bile ducts. RESULTS: Gallbladder cancer was identified in 5 out of 14 patients with APBDU. The incidences of metaplasia of gallbladder and bile duct with APBDU were higher than that of control gallbladder epithelium. The proliferating cell nuclear antigen-labeling index of the gallbladder in patients with APBDU was significantly higher than that in the control group. CONCLUSIONS: The patients with APBDU showed high incidence of gallbladder carcinoma and metaplasia in epithelium of gallbladder and bile duct. As this metaplasia in the gallbladder and bile duct is thought of as a precancerous condition, it is important to remove the place that causes bile stasis and to stop backflow of pancreatic juice into the bile duct in managing patients with this anomaly. In other words, prophylactic cholecystectomy and reconstruction of the biliary tract are both necessary.     

Severe dysplasia of the gallbladder associated with occult pancreatobiliary reflux

Pancreatobiliary reflux usually occurs in patients with pancreaticobiliary maljunction and can be associated with the occurrence of gallbladder carcinoma. We present the case of a patient with pancreatobiliary reflux despite having a normal pancreatobiliary junction (occult pancreatobiliary reflux; OPBR), in whom the resected gallbladder presented severe dysplasia. The patient, a 61-year-old woman, showed thickness of the gallbladder wall, detected by ultrasonography and computed temography (CT). Her biliary amylase level in the common bile duct was 103 000 IU/l, and in the gallbladder it was 153 500 IU/l, although endoscopic retrograde cholangiopancreatography revealed a normal pancreaticobiliary junction. Immunohistochemical staining showed many p53-positive nuclei in the dysplastic lesion, and about 50% of the dysplastic cells exhibited diffuse nuclear staining for Ki-67. In the present patient, early diagnosis of occult pancreatobiliary reflux led to early detection of a precancerous lesion of the gallbladder mucosa.     

Different Expression of S100A8 in Malignant and Benign Gallbladder Diseases

Background

Proteomic analysis is a powerful tool for complete establishment of protein expression. Comparative proteomic analysis of human bile from malignant and benign gallbladder diseases may be helpful in research into gallbladder cancer.

Aims

Our objective was to establish biliary protein content for gallbladder cancer, gallbladder adenoma, and chronic calculous cholecystitis for comparative proteomic analysis.

Methods

Bile samples were collected from patients with gallbladder cancer, gallbladder adenoma, and chronic calculous cholecystitis. Peptides of biliary proteins were separated by two-dimensional liquid chromatography then identified by tandem mass spectrometry.

Results

Up to 544, 221, and 495 unique proteins were identified in bile samples from gallbladder cancer, gallbladder adenoma, and chronic calculous cholecystitis. Forty-three, 16, and 28 proteins with more than one unique peptide, respectively, were identified in the three groups. Among these, 30 proteins including S100A8 were overexpressed in gallbladder cancer, compared with benign gallbladder diseases. We also confirmed, by immunohistochemical analysis, that S100A8 is more abundant in tumor-infiltrating immune cells in cancerous tissue.

Conclusions

Compared with benign gallbladder diseases, consistently elevated S100A8 levels in malignant gallbladder bile and tissue indicate that gallbladder cancer is an inflammation-associated cancer. S100A8 may be a biomarker for gallbladder cancer.