Identification of cerebral response to balloon distention of the bile duct.

AIM: To identify the brain loci that process human biliary sensation. METHODS: In 6 patients (age range: 42-74 years; 4 men), who underwent percutaneous transhepatic biliary drainage (PTBD), the distal biliary tract was stimulated by repeatedly inflating the balloon of the PTBD catheter so that it reached volumes that produced a definite painless sensation. The functional magnetic resonance imaging (fMRI) of the cortical response to biliary sensation was examined. RESULTS: Biliary balloon stimulation elicited activation of the insular cortex, prefrontal cortex, and somatosensory cortex (P < 0.001). CONCLUSION: Biliary balloon stimulation evoked a cerebral cortical response detectable by fMRI.

Efficacy of camostat mesilate against dyspepsia associated with non-alcoholic mild pancreatic disease.

BACKGROUND: The aim of the present study was to examine the potential efficacy of camostat mesilate, a protease inhibitor, against dyspepsia associated with non-alcoholic mild pancreatic disease. METHODS: Patients with upper abdominal pain suggesting pancreatic disease (persistent over hours, pain aggravated by ingestion of food, epigastric pain radiating to the back), without a history of alcohol consumption and who exhibited no abnormalities regarding serum amylase and lipase, ultrasonography, CT and upper gastrointestinal endoscopy, were prescribed 200 mg camostat mesilate three times daily for 2 weeks. The patients were subjected to endoscopic ultrasonography (EUS) while under treatment and were distributed into those who had 4 or more suggestive findings of chronic pancreatitis (suspected pancreatic disease group), 2 or 3 (equivalent group) and those with 1 or no findings (control group). Symptom severity was recorded before and after treatment using a 10-cm visual analog scale (VAS). RESULTS: Among 95 patients, 40 were in the suspected pancreatic disease group, 30 were in the equivalent group and 25 served as controls. A significant intra- and intergroup improvement of symptoms was observed not only in the suspected pancreatic disease group but also in the equivalent group. CONCLUSIONS: Camostat mesilate may serve as a therapeutic agent for patients with dyspepsia associated with mild pancreatic disease, who do not habitually drink alcohol.

Early detection of extrahepatic bile-duct carcinomas in the nonicteric stage by using MRCP followed by EUS.

BACKGROUND: Most extrahepatic bile-duct carcinomas are usually diagnosed when they are already in an advanced stage, which is the main reason for the poor prognosis of this tumor. OBJECTIVE: To examine the usefulness of MRCP followed by EUS in the early diagnosis of extrahepatic bile-duct carcinoma in the nonicteric stage. PATIENTS: This study included patients who were nonicteric, who had abnormal serum concentrations of alkaline phosphatase and gamma glutamyl transpeptidase, and whose common hepatic duct was more than 8 mm in diameter on abdominal US because of unknown reasons. DESIGN: A single-center, prospective study. SETTING: An academic medical center. MAIN OUTCOME MEASUREMENTS: The sensitivity and specificity of MRCP followed by EUS for the early diagnosis of extrahepatic bile duct carcinoma in the nonicteric stage. RESULTS: A total of 142 patients who were nonicteric underwent prospective MRCP, and 26 of them underwent EUS. Ten patients (5 with stricture, 4 with filling defect, and 1 with no stricture or filling defect) had extrahepatic bile-duct carcinoma, including 5 patients with an incidentally diagnosed T1 stage tumor. The sensitivity and specificity of MRCP followed by EUS were 90% and 98%, respectively. LIMITATIONS: A single center and small number of patients. CONCLUSIONS: MRCP followed by EUS was highly sensitive and specific for the early diagnosis of extrahepatic bile-duct carcinoma in the nonicteric stage, including T1 stage tumors. Filling defects, as well as stenosis in the bile duct, are important MRCP findings of T1 stage carcinoma.

Pancreatic-duct-lavage cytology in candidates for surgical resection of branch-duct intraductal papillary mucinous neoplasm of the pancreas: should the International Consensus Guidelines be revised?

BACKGROUND: The International Consensus Guidelines are helpful for the management of branch-duct intraductal papillary mucinous neoplasms (IPMNs), because they allow us to exclude malignancy. However, it is not possible to predict malignancy with certainty, and further preoperative differentiation between benign and malignant IPMNs is required to avoid the false-positive results. OBJECTIVE: To examine the usefulness of pancreatic-duct-lavage cytology by using an originally designed double-lumen catheter for discriminating benign and malignant IPMNs of the branch-duct type in candidates for surgical resection based on the International Consensus Guidelines. PATIENTS: Pancreatic-duct-lavage cytology was investigated in 24 patients with branch-duct IPMNs who underwent surgical resection based on the International Consensus Guidelines, namely, they either had intramural nodules or the ectatic branch duct was >30 mm in diameter. DESIGN: Single-center retrospective study. SETTING: Academic medical center. MAIN OUTCOME MEASUREMENTS: The sensitivity and specificity of pancreatic-duct-lavage cytology for discriminating benign from malignant IPMNs. RESULTS: More than 30 mL of pancreatic-duct-lavage fluid was obtained from each patient, and there were no patients with noninformative results. The sensitivity, specificity, positive predictive value, and negative predictive value of the cytologic diagnosis were 78%, 93%, 88%, and 88%, respectively. LIMITATIONS: Single-center and small number of patients. CONCLUSIONS: Pancreatic-duct-lavage cytology can improve differentiation between benign and malignant IPMNs of the branch-duct type in candidates for surgical resection based on the International Consensus Guidelines.

Diagnosis of mild chronic pancreatitis (Cambridge classification): comparative study using secretin injection-magnetic resonance cholangiopancreatography and endoscopic retrograde pancreatography.

AIM: To investigate the usefulness of secretin injection-MRCP for the diagnosis of mild chronic pancreatitis. METHODS: Sixteen patients having mild chronic pancreatitis according to the Cambridge classification and 12 control subjects with no abnormal findings on the pancreatogram were examined for the diagnostic accuracy of secretin injection-MRCP regarding abnormal branch pancreatic ducts associated with mild chronic pancreatitis (Cambridge Classification), using endoscopic retrograde cholangiopancreatography (ERCP) for comparison. RESULTS: The sensitivity and specificity for abnormal branch pancreatic ducts determined by two reviewers were respectively 55%-63% and 75%-83% in the head, 57%-64% and 82%-83% in the body, and 44%-44% and 72%-76% in the tail of the pancreas. The sensitivity and specificity for mild chronic pancreatitis were 56%-63% and 92%-92%, respectively. Interobserver agreement (kappa statistics) concerning the diagnosis of an abnormal branch pancreatic duct and of mild chronic pancreatitis was good to excellent. CONCLUSION: Secretin injection-MRCP might be useful for the diagnosis of mild chronic pancreatitis.

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.

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 19,900 IU/L and that of the gallbladder was 127,000 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.

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.

Precancerous mucosal changes in the gallbladder of patients with occult pancreatobiliary reflux.

BACKGROUND: Pancreatobiliary reflux can occur even if the pancreaticobiliary junction is normal (occult pancreatobiliary reflux), and it may be associated with gallbladder carcinoma. The aim of the present study was to examine precancerous mucosal changes in the gallbladder from patients with occult pancreatobiliary reflux. METHODS: The mucosa of the gallbladder from 13 patients who underwent cholecystectomy was examined histopathologically. These patients had an anatomically normal pancreatobiliary junction and a biliary amylase concentration greater than 10,000 IU/L. The gallbladder of patients without carcinoma was further examined by using immunohistochemical techniques to detect Ki-67, and the results were compared with those from control patients. RESULTS: Of the 13 patients, 5 (38%) had gallbladder carcinoma and 8 (62%) did not. Of the 8 patients without carcinoma, 4 (50%) had dysplasia accompanied by hyperplasia, and 2 (25%) had hyperplasia alone of the gallbladder mucosa. The Ki-67 labeling index was significantly higher in hyperplastic and dysplastic mucosa than in control gallbladder mucosa (p < 0.0004). CONCLUSIONS: Occult pancreatobiliary reflux could be associated with precancerous mucosal changes in the gallbladder, such as hyperplasia and dysplasia with increased cellular proliferation, and could be a possible risk factor for gallbladder carcinoma.

[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.

Persistence of the left part of the ventral pancreas may cause congenital biliary dilatation.

INTRODUCTION: Congenital biliary dilatation (CBD) is a congenital anomaly by which pancreaticobiliary maljunction (PBMJ) is accompanied in most patients. The etiology of these conditions is unknown. AIMS To clarify the pattern of fusion between the ventral and dorsal parts of the pancreas. METHODOLOGY: We examined the pancreases from five patients who had PBMJ with or without CBD and five control subjects, and we detected pancreatic polypeptide (PP) immunohistochemically. RESULTS: In cases of CBD, the pancreatic head was huge, while the uncinate process was undetectable. The dorsal portion of the head was formed by the ventral pancreas macroscopically. It was divided into PP-rich and PP-poor portions immunohistochemically. In cases of PBMJ without CBD, the uncinate process was relatively small. The PP-rich portion (ventral pancreas) was situated obliquely dorsal to the PP-poor portion (dorsal pancreas). CONCLUSIONS: In case of CBD, the PP-rich and PP-poor portions of the ventral pancreas may be derived from the right and left parts of the ventral primordia, respectively. CBD may occur when the remnant of the left part of the ventral primordium prevents normal recanalization of the common bile duct, resulting in dilatation of the duct. In cases of PBMJ without CBD, PBMJ without CBD may be caused by abnormal fusion between the ventral and dorsal primordia.

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.