Yoshihiro Kubokawa

Management of branch duct-type intraductal papillary mucinous tumor of the pancreas based on magnetic resonance imaging

Background: We assessed the usefulness of magnetic resonance imaging (MRI) in identifying nonmalignant intraductal papillary mucinous tumors (IPMTs) of the pancreas.Methods: Thirty-three patients with branch duct-type IPMT diagnosed by endoscopic retrograde cholangiopancreatography were prospectively examined with magnetic resonance cholangiopancreatography followed by dynamic gadolinium-enhanced MRI examinations, and patients with no findings suggestive of malignancy, including a solid mass, mural nodules, a main pancreatic duct wider than 5 mm in diameter, and stenosis of the main pancreatic duct, were prospectively followed up with sequential MRI examinations once or twice a year.Results: Twenty-six (79%) patients showed no findings suggestive of malignancy in the initial MRI examination. The diameter (mean ± standard error) of the main pancreatic duct was 3.9 ± 0.7 mm and that of the ectatic branch pancreatic duct was 36.0 ± 9.1 mm. Twenty-three patients were prospectively followed for more than 36 months and 22 of them showed no findings suggestive of malignancy during follow-up periods ranging from 39 to 77 months (mean = 55 months).Conclusion: MRI was useful to identify nonmalignant IPMTs of the branch duct type, and close follow-up observation with serial MRI examinations may be appropriate in the management of such patients.

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.

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.

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.

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 and Associated Mucosal Changes of the Gallbladder

Occult Pancreatobiliary Reflux and Associated Mucosal Changes of the Gallbladder Jin Kan Sai, Masafumi Suyama, Yoshihiro Kubokawa, Hiroyuki Tadokoro, Nobuhiro Sato Purpose: To investigate pancreatobiliary reflux in individuals with a normal pancreatobiliary junction and assoicated mucosal changes of the gallbladder. Methods: A total of 108 patients, who had diffuse thickness of the gallbladder wall detected by ultrasonography and normal pancreatobiliary junction on ERCP, were examined for their pathological findings and biliary amylase levels. Results: Nine patients showed biliary amylase levels more than 10,000 IU/L, in whom 4 patients had carcinoma, 2 patients had dysplasia, and 2 patients had hyperplasia of the gallbladder. In contrast, none of the patients with biliary amylase levels less than 1,000 IU/L, had dysplasia nor hyperplasia of the gallblader. Conclustion: Pancreatobiliary reflux can occur in patients with a normal pancreatobiliary junction and induce cancerous and pre-cancerous lesion of the gallbladder.