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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.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.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 (P0.001), 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.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.

Recently, the clinical application of diffusion-weighted magnetic resonance imaging (DWI) has been expanding to abdominal organs. However, only a few studies on gallbladder diseases have been published. The aim of this study was to evaluate the usefulness and limitations of high b-value DWI for gallbladder diseases. A total of 153 patients (mean age 60 ± 15 years, 78 males) who had undergone DWI for evaluating gallbladder wall thickening or polypoid lesions were included in this study. Of these 153 patients, 36 had gallbladder cancer and 117 had benign gallbladder diseases (67 chronic cholecystitis, 44 adenomyomatosis, four cholesterol polyp, one gallbladder adenoma, and one xanthogranulomatous cholecystitis). We evaluated the positive signal rate with DWI and the apparent diffusion coefficient (ADC) value of each disease. The positive signal rate with DWI was significantly higher in gallbladder cancer (78 %) than in benign gallbladder diseases (22 %) (p

This study assessed the mechanism of fistula formation in intraductal papillary mucinous neoplasm (IPMN) of the pancreas.A total of 274 patients with IPMN who had been diagnosed by endoscopic retrograde cholangiopancreatography and endoscopic ultrasonography (EUS) at our center were enrolled. The patients with IPMN which had fistula formation into other organs were investigated retrospectively as to (1) clinical prevalence and the organs penetrated by IPMN, (2) analysis of the mechanism of fistula formation by immunohistopathological study, (3) efficacy of EUS in progression assessment, and (4) prognosis.Among the subjects, fistula formation into other organs was observed in 18 patients (6.6%) and into 28 organs. There were 7 patients (39%) in whom multiple organs were penetrated. Of 16 patients who had undergone investigation of the expression of mucin markers, 94% had an intestinal-type tumor. Of 9 patients who had undergone surgery or autopsy, 67% showed mechanical penetration without invasion around the fistula. Only papillary protrusions were seen by EUS in 4 of these patients with noninvasive papillary adenocarcinoma showing mechanical penetration. All 5 patients who had pancreatic parenchymal invasion showed a mass with a mixed-echo pattern in addition to papillary protrusions shown by EUS, corresponding to colloid carcinoma.There were 2 processes in the development of fistulas in IPMN. Of those patients showing fistula formation, 94% had intestinal-type IPMN, and 67% showed mechanical penetration. Delineation of a mass with the mixed-echo pattern suggested an invasive penetration due to colloid carcinoma.

The diagnostic efficacy of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) cytology may vary greatly depending on the treatment of the samples obtained and the level of proficiency of the cytopathologist or cytoscreener. We prospectively evaluated the diagnostic efficacy of the cell block (CB) method and that of smear cytology using tissue samples obtained in the same needle pass at EUS-FNA in 33 patients with pancreatic tumors, abdominal tumors or swollen lymph nodes. An average of 3.1 passes were applied during the procedure without affirmation by rapid cytology. About half of the material obtained by each single pass was subjected to smear cytology, while the other half was evaluated by the CB method. Four to 12 glass slides were prepared for both Papanicolaou stain and Giemsa stain. The CB sections were prepared using the sodium alginate method and subjected to HE, PAS-AB and immunohistochemical stains. Two pathologists independently made cytological and histological diagnoses. The final diagnosis was based on integration of cytohistological findings, diagnostic imaging, and clinical course. The diagnostic accuracy of the CB method and that of smear cytology were 93.9 and 60.6%, respectively (p = 0.003), and their respective sensitivities were 92.0 and 60.0% (p = 0.02). It was easier to make a definite diagnosis of not only malignancies but also benign conditions by the CB method than by the smear method. The CB method with immunostaining showed a higher diagnostic yield than smear cytology in patients who had undergone EUS-FNA without rapid on-site cytology.

Prior Billroth II gastrectomy is an important factor presenting difficulties in endoscopic retrograde cholangiopancreatography (ERCP) administration. We retrospectively evaluated the usefulness and safety of therapeutic ERCP using an anterior oblique-viewing endoscope for bile duct stones in patients with prior Billroth II gastrectomy.Forty-three patients with bile duct stones after Billroth II gastrectomy who underwent ERCP from January 1998 to February 2008 were enrolled in this study. We used anterior oblique-viewing endoscopes for all procedures. Endoscopic sphincterotomy was performed using a needle knife guided by a biliary stent. A total of 808 patients without gastrectomy who had undergone ERCP for bile duct stones in the same period were reviewed as controls.The success rate of access to the papilla of Vater was 88.4%, and the average time required for such access was 13 min. In cases of successful access, selective cannulation of the bile duct and complete stone removal were achieved in 94.7% and 94.6% of patients, respectively. The incidence of complications was 4.7%. As for the success rate of selective cannulation, complete stone removal ratio, and the incidence of complications, there were no significant differences compared with the control group.Use of an anterior oblique-viewing endoscope enables good success rates in selective cannulation and complete stone removal to be achieved in patients with prior Billroth II gastrectomy. The safety of therapeutic ERCP for removal of bile duct stones in those patients is comparable to that in patients with normal anatomy.

In 2006, the Japan Pancreas Society revised the diagnostic criteria for autoimmune pancreatitis (AIP) so as to more clearly define its morphological, pathological, and immunological features, as follows: (1) diffuse or segmental narrowing of the main pancreatic duct with an irregular wall and diffuse or localized enlargement of the pancreas recognized by imaging studies; (2) high serum gamma globulin, IgG, or IgG4 levels, or the presence of autoantibodies; and (3) marked interlobular fibrosis and prominent infiltration of lymphocytes and plasma cells in the periductal area, occasionally with lymphoid follicles in the pancreas. Establishing a diagnosis of AIP has become easier with knowledge of its immunological abnormalities, including serum IgG4 levels. However, the localized form of AIP sometimes mimics pancreatic cancer. The rate of focal mass formation in patients with AIP is reportedly 24%-43%; however, there have been few reports on the histological findings of localized AIP, in contrast to mass-forming pancreatitis (MFP). Our review of patients who had undergone resection due to a preoperative diagnosis of MFP with possible cancer revealed 72% to be patients with localized AIP. For the discrimination of these conditions, it is important to recognize the characteristic ultrasonographic findings of AIP, i.e., (1) diffuse or localized enlargement and hypoechogenicity of the pancreas; (2) rarity of calcification, cystic lesions, and peripancreatic fluid collection; (3) thickened layer structure of the bile duct wall; (4) iso/hypervascularity in the swollen portion of the pancreas; (5) attenuation of pancreatic swelling and bile duct wall thickening after steroid therapy; and (6) multiple hypoechoic masses in various organs, including the pancreas. Contrast-enhanced endoscopic ultrasonography is potentially a useful tool in the differential diagnosis and for assessment of the efficacy of steroid therapy by enabling evaluation of the vascularity of the lesions. Along with the presence of IgG4-positive plasma cells, verification of obliterative phlebitis is highly specific for the histological diagnosis of AIP.

Cystic duct cancer fulfilling Farrar's criteria is relatively rare, but tumors whose origin is estimated to be in the cystic duct exist. The clinical features of such "broadly defined" cystic duct cancer have not been clarified.The endoscopic retrograde cholangiography (ERC) findings, intraductal ultrasonography (IDUS) findings, histological findings, and prognoses of 11 cases of cystic duct cancers resected at our institution (group C) were retrospectively analyzed. As a control group, 55 cases of middle or lower bile duct cancer (group B) were used (in 20 of the 55 cases of group B, tumors extended to the cystic duct intraluminally (group B-C (+)).(1) ERC findings of group C as compared with those of group B-C (+) were as follows: (a) unilateral bile duct narrowing (spoon-like appearance): 55% versus 5% (P0.01); (b) bilateral bile duct narrowing (apple-core-like appearance): 27% versus 95% (P0.001). (2) IDUS was unable to visualize the cysticocholedochal junction (negative "confluence sign") more often in group C (67%) than in group B-C (+) (13%) (P0.01). (3) Histologically, tumors extended to the gallbladder and the bile duct in 36% and 91% of the cases in group C, respectively. (4) The median survival time of the two groups was 21 and 28 months, respectively.Cystic duct cancers frequently extended to the bile duct. The spoon-like appearance by ERC and the negative confluence sign by IDUS were characteristic findings.

To elucidate the correlation of autoimmune pancreatitis (AIP) and mass-forming pancreatitis, in which a localized mass is formed in the pancreas.Nine cases of mass-forming pancreatitis were divided into two groups, one consisting of cases that met the histological diagnostic criteria for AIP by the Japan Pancreas Society (JPS) and the other consisting of cases which did not. Histological findings, immunohistological findings, and pancreatograms were compared between these groups.Six cases met the histological criteria of JPS (group A) and the other three did not (group B). In the mass-forming portion in group A, the wall of the pancreatic duct showed marked thickening. However, the epithelium was well preserved, and dilatation of the branch ducts or protein plugs were rarely observed. All cases showed marked obliterative phlebitis. The IgG4 labeling index (LI) was 25% or more in all but one case. In the portion other than the mass, the lobular structure was well preserved and the IgG4 LI was less than 10%. The pancreatogram showed localized stenosis or obstruction at the site of the mass associated with a normal-appearing main pancreatic duct in the remaining portion. In group B, histological findings typical of chronic pancreatitis with dilated branch ducts and protein plugs were observed. Obliterative phlebitis was not confirmed. The IgG4 LI in the mass-forming portion was low (2.3%-11.1%).There exists a subgroup of AIP showing localized mass formation and stenosis or obstruction of the main pancreatic duct with prominent obliterative phlebitis associated with a normal ductal segment.

A 74-year-old woman, who had suffered from acute cholangitis, was referred to our department for further evaluation of the biliary tree. A diagnosis of choledochocele was made by endoscopic ultrasonography and endoscopic retrograde cholangiopancreatography. A small flat elevation with cholesterolosis was observed in the lower bile duct, and circumferential wall thickening was apparent in some parts of the upper and middle bile duct by intraductal ultrasonography and peroral cholangioscopy. With the diagnosis of choledochocele associated with superficial spreading cancer and cholesterolosis of the bile duct, pylorus-preserving pancreaticoduodenectomy was carried out. Microscopically, the tumor had spread extensively from the lower to the upper bile duct. Its invasion was limited to the mucosa for the most part, with microinvasion of the subserosa in the upper bile duct. In the lower bile duct, foamy cells were located beneath the neoplastic epithelium of the elevation. The number of cases of choledochocele associated with biliary cancer is becoming higher than previously reported. This anomaly may play some role in the development of biliary malignancy. Histological examination seems to be mandatory before making a diagnosis of cholesterolosis of the bile duct, since this condition may occasionally accompany cancer.

We aimed to clarify the clinical characteristics of choledochocele and to evaluate the possibility of choledochocele as a risk factor for biliary malignancies.The clinical feature, the configuration of the pancreatobiliary ductal system, coexistent pancreatobiliary lesions, and amylase level in bile in 21 patients with choledochocele were reviewed. The correlation between the configuration, comorbid diseases, and amylase level in the bile was investigated.There was a female predominance, and 57% of the patients showed abdominal pain. Quite a few patients showed elevation of the levels of hepatobiliary enzymes. The configuration of the pancreatobiliary ductal system and choledochocele was classified into two categories: type I, where the choledochocele and pancreatic duct were visualized independently or simultaneously (90.5%); and type II, where the pancreatic duct was visualized after filling of the choledochocele (9.5%). Among coexistent bilio-pancreatic diseases, biliary stone diseases were the most frequent. Biliary malignancy was seen in 3 patients (14.3%). The amylase level in the bile was high in 50% (4/8) of the patients examined. The rate of abnormal elevation of amylase level in the bile in the two types of pancreatobiliary ductal system and choledochocele was 3/7 and 1/1, respectively.The prevalence of organic abnormal arrangement of the pancreatobiliary ductal system in which the choledochocele serves as a common channel is low. However, there are patients with suspected functional abnormal arrangement of the pancreatobiliary ductal system, who may possibly be a high-risk group for biliary malignancy.

We herein report a case of abnormal arrangement of the pancreato-biliary ductal system (AAPB) followed by advanced gallbladder cancer 9 years after the initial endoscopic retrograde cholangiopancreatography (ERCP) diagnosis and almost 3 years after follow-up ultrasonography (US). A 65-year-old woman was referred to our department from a private clinic because of difficulty in controlling her diabetes mellitus. The patient had no complaints, and physical examination revealed no jaundice in her skin or conjunctiva. ERCP demonstrated the presence of AAPB (bile duct-main type) without congenital dilatation of the bile duct or irregularity in the gallbladder wall. She did not wish to undergo cholecystectomy. Follow-up transabdominal US revealed no change in the gallbladder. Two years and 9 months after this US examination, she developed advanced gallbladder cancer involving the liver and bile duct, with paraaortic lymph node metastases confirmed by US, computed tomography, and ERCP. This case re-emphasizes the necessity for patients with AAPB to undergo intensive follow-up examinations or cholecystectomy when the diagnosis of AAPB has been established.

Although many cases of solid cystic tumor of the pancreas (SCT) have been reported, its nature and histogenesis remain controversial. We herein report six cases of SCT, including three cases of noncystic type. A review of 22 cases of noncystic type SCT, including our 3 cases, was carried out to compare their features with those of 173 cases of classic SCT reported in Japan. Noncystic type SCTs tend to occur in male patients and are smaller in size and less frequently symptomatic, although they show histological characteristics similar to those of classic SCTs. The developmental process might be a cause of cyst formation. The accumulation and analysis of many, at present, "atypical" cases for clarification of its nature, will, it is hoped, lead to a new nomenclature for this condition that adequately describes its biological origin.