BACKGROUND: Intraductal papillary neoplasm of the bile duct (IPNB) is a recently defined entity and its clinical characteristics and classifications have yet to be established. We aimed to clarify the clinical features of IPNB and determine the optimal morphological classification criteria. METHODS: From 2003 to 2016, 112 patients with IPNB who underwent surgery were included in the analysis. After pathologic reexamination by a specialized biliary-pancreas pathologist, previously suggested morphological and anatomical classifications were compared using the clinicopathologic characteristics of IPNB. RESULTS: In terms of histologic subtypes, most patients had the intestinal type (n = 53; 48.6%) or pancreatobiliary type (n = 33; 30.3%). The simple “modified anatomical classification” showed that extrahepatic IPNB comprised more of the intestinal type and tended to be removed by bile duct resection or pancreatoduodenectomy. Intrahepatic IPNB had an equally high proportion of intestinal and pancreatobiliary types and tended to be removed by hepatobiliary resection. Morphologic classifications and histologic subtypes had no effect on survival, whereas a positive resection margin (75.9% vs. 25.7%; P = 0.004) and lymph node metastasis (75.3% vs. 30.0%; P = 0.091) were associated with a poor five-year overall survival rate. In the multivariate analysis, a positive resection margin and perineural invasion were important risk factors for survival. CONCLUSION: IPNB showed better long-term outcomes after optimal surgical resection. The “modified anatomical classification” is simple and intuitive and can help to select a treatment strategy and establish the proper scope of the operation.
Bile Duct Neoplasms ; Bile Ducts* ; Bile Ducts, Extrahepatic ; Bile Ducts, Intrahepatic ; Bile* ; Cholangiocarcinoma ; Classification* ; Humans ; Lymph Nodes ; Multivariate Analysis ; Neoplasm Metastasis ; Pancreaticoduodenectomy ; Risk Factors ; Survival Rate

The effects of cholic acid and eight related cholanic acid analogs on bile flow and biliary excretion of bile salts and cholesterol were studied in rabbits. Bile acids were infused intravenously in anesthetized rabbits. In all except hyodeoxycholic or lithocholic acid treated animals increases in bile flow were recorded within 10 minutes during infusion of bile acid-The increase in bile f1ow associated with an increase in bile salt level in bile after cholic acid infusion was observed, however, there were little changes in biliary, cholesterol levels. Bile salt level in bile was not associated with bile flow after chenodeoxycholic acid infusion but the cholesterol level in bile was significantly increased. Ursodeoxycholic acid similarly increased cholesterol but to a lesser extent. Keto-forms of chenodeoxycholic acid were without action. These results indicate that both cholic and chenodeoxycholic acids have the capacity to alter specific biliary excretion of bile components, the former on bile salts and the latter on cholesterol-a precursor of bile acids in bile.
Animal ; Bile/analysis ; Bile/secretion* ; Bile Acids and Salts/administration & dosage ; Bile Acids and Salts/metabolism ; Bile Acids and Salts/pharmacology* ; Bilirubin/analysis ; Cholesterol/analysis ; Cholesterol/metabolism* ; Cholic Acids/analogs & derivatives ; Cholic Acids/analysis ; Female ; Liver/metabolism ; Male ; Rabbits

PURPOSE: There are several reports that intraoperative transfusion may be a prognostic factor in periampullary cancer, but it is not conclusive. The purpose of this study is to clarify the prognostic significance of a transfusion following a pancreatoduodenectomy for periampullary cancers. METHODS: We analyzed 357 periampullary cancers from 1985 to 1997 (ampullary cancer: 130 cases; distal bile duct cancer: 141 cases; and pancreatic head cancer: 86 cases). Analytic variables for possible prognostic factors were various clinicopathologic factors combined with the presence of the perioperative transfusion. RESULTS: Of the overall 357 patients, 215 (60%) have received an intraoperative transfusion. The 5-year survival rate of the 130 ampullary cancer patients was 59%, and 76 cases (58%) underwent an intra operative transfusion. The 5-year survival rate of patients without intraoperative transfusion was 79% whereas that of patients with a transfusion was 47% (p=0.029). Following multivariate analysis, an intraoperative transfusion was an independent prognostic factor in ampullary cancer (relative risk: 2.174). In common bile duct cancer, the overall 5-year survival rate was 33%, and the 5-year survival rates of patients with (N=87) or without (N=54) a transfusion were 25% and 38% respectively, which showed a marginal statistical significance (p=0.0717). In pancreatic head cancer, the overall 5-year survival rate was 16% and there was no survival difference between transfused (N=52) and untransfused (N=34) patients. CONCLUSION: In the present study, intraoperative transfusion was an independent significant prognostic factor in ampullary cancer. Careful dissection to minimize intraoperative bleeding is mandatory in pancreatoduodenectomy for ampullary cancer.
Bile Duct Neoplasms ; Common Bile Duct ; Head and Neck Neoplasms ; Hemorrhage ; Humans ; Multivariate Analysis ; Pancreaticoduodenectomy* ; Survival Rate

AIMTo develop a method for separating the major bile acids by capillary zone electrophoresis (CZE).

METHODSThe effect of different separations, such as the compose, pH and the concentration of buffer, on the electro-osmotic flow (EOF), the migration time and resolution of 8 bile acids in this system were studied. The general trends in migration time could be correlated to the pH and concentration of the buffer. The effect of organic reagent on EOF and migration time were also investigated. By addition of methanol, the EOF went smaller than before, and better resolution was achieved. The experimental results showed that optimum separation was achieved under the following condition: buffer composition of 126 mmol.L-1 disodium tetraborate, 43 mmol.L-1 disodium hydrogenphosphate, 18% methanol; temperature 30 degrees C; voltage 30 kV; total length of capillary 570 mm and 500 mm from injection end; ultraviolet detection at 200 nm; pressure injection 5 kPa for 8 s.

RESULTSEight kinds of bile acid had been separated by CZE with only one injection. The method was used to analyse the contents of bile acids from different kinds of bear biles, the recovery was 89%-107%.

CONCLUSIONThis method is simple and rapid, and can be used to determine the content of bile acids in bear biles. The calibration curve showed good linearity for eight bile acids in the concentration range of 4-60 mg.mL-1 (gamma > 0.9954). The total time for seperation and determination was within 25 min.

Animals ; Bile ; chemistry ; Bile Acids and Salts ; analysis ; isolation & purification ; Electrophoresis, Capillary ; methods ; Materia Medica ; chemistry ; Ursidae

PURPOSE: T category of the eighth edition of the American Joint Committee on Cancer (AJCC) staging system for distal bile duct carcinoma (DBDC) was changed to include tumor invasion depth measurement, while the N category adopted a 3-tier classification system based on the number of metastatic nodes. MATERIALS AND METHODS: To validate cancer staging, a total of 200 surgically resected DBDCs were staged and compared according to the seventh and eighth editions. RESULTS: T categories included T1 (n=37, 18.5%), T2 (n=114, 57.0%), and T3 (n=49, 24.5%). N categories included N0 (n=133, 66.5%), N1 (n=50, 25.0%), and N2 (n=17, 8.5%). Stage groupings included I (n=33, 16.5%), II (n=150, 75.0%), and III (n=17, 8.5%). The overall 5-year survival rates (5-YSRs) of T1, T2, and T3 were 59.3%, 42.4%, and 12.2%, respectively. T category could discriminate patient survival by both pairwise (T1 and T2, p=0.011; T2 and T3, p < 0.001) and overall (p < 0.001) comparisons. The overall 5-YSRs of N0, N1, and N2 were 47.3%, 17.0%, and 14.7%, respectively. N category could partly discriminate patient survival by both pairwise (N0 and N1, p < 0.001; N1 and N2, p=0.579) and overall (p < 0.001) comparisons. The overall 5-YSRs of stages I, II, and III were 59.0%, 35.4%, and 14.7%, respectively. Stages could distinguish patient survival by both pairwise (I and II, p=0.002; II and III, p=0.015) and overall (p < 0.001) comparisons. On multivariate analyses, T and N categories (p=0.014 and p=0.029) and pancreatic invasion (p=0.006) remained significant prognostic factors. CONCLUSION: The T andNcategories of the eighth edition AJCC staging system for DBDC accurately predict patient prognosis.
Bile Ducts* ; Bile* ; Cholangiocarcinoma ; Classification ; Humans ; Joints* ; Multivariate Analysis ; Neoplasm Staging* ; Prognosis ; Survival Rate

PURPOSE: Surgery remains the only curative option for patients with extrahepatic bile duct cancer (EHBD Ca). But, long-term survival is typically not good because of the advanced stage of disease at the time of diagnosis and frequent disease recurrence after surgical resection. The purpose of this study was to evaluate factors that influence survival and recurrence after surgical resection of EHBD Ca. METHODS: A retrospective analysis of 113 patients who had received surgical resection for EHBD Ca between 2004 and 2009 was done. We investigated histopathological features, and survival and recurrence rates, and evaluated prognostic factors affecting survival and disease recurrence after surgical resection. RESULTS: Overall survival rates for 1, 3 and 5 years were 73.2%, 42.8%, and 36.0% respectively. In univariate analysis, prognostic factors influencing survival were histologic differentiation, T stage, lymph node (LN) metastasis, TNM stage, perineural invasion (PNI), lymphovascular invasion (LVI) and resection margin state. Among them, LN metastasis, PNI and resection margin state were found to be independent prognostic factors for overall survival in multivariate analysis. Recurrence occurred in 44 patients (48.9%) and disease-free survival rates were 50.6% at 1 year and 38.3% at 3 year. Univariate analysis revealed that histologic differentiation, T stage, LN metastasis, TNM stage, PNI and LVI were significantly associated with recurrence. In multivariate analysis, only LN metastasis was found to be a significant independent predictor of recurrence. CONCLUSION: LN metastasis, PNI and positive resection margin were significant prognostic factors affecting survival. LN metastasis was found to be a significant independent predictor of recurrence in surgical resection of EHBD Ca.
Bile ; Bile Duct Neoplasms ; Bile Ducts ; Bile Ducts, Extrahepatic ; Disease-Free Survival ; Humans ; Lymph Nodes ; Multivariate Analysis ; Neoplasm Metastasis ; Recurrence ; Retrospective Studies ; Survival Rate

Animals ; Bile Duct Neoplasms ; chemistry ; Bile Ducts, Intrahepatic ; Cholangiocarcinoma ; chemistry ; Cricetinae ; Epidermal Growth Factor ; analysis ; Immunohistochemistry ; Receptor, Epidermal Growth Factor ; analysis ; Transforming Growth Factor alpha ; analysis

PURPOSE: To evaluate the results of postoperative radiotherapy in patients with extra-hepatic bile duct cancer (EHBDC) and identify the prognostic factors for local control and survival. MATERIALS AND METHODS: Between January 2001 and December 2010, we retrospectively reviewed the cases of 70 patients with EHBDC who had undergone curative resection and received postoperative radiotherapy. The median radiation dose was 50.4 Gy (range, 41.4 to 54 Gy). The resection margin status was R0 in 30 patients (42.9%), R1 in 25 patients (35.7%), and R2 in 15 patients (21.4%). RESULTS: The 5-year rates of overall survival (OS), event-free survival (EFS), and locoregional control (LRC) for all patients were 42.9%, 38.3%, and 61.2%, respectively. The major pattern of failure was distant relapses (33 patients, 47.1%). A multivariate analysis showed that the postradiotherapy CA19-9 level, radiation dose (> or =50 Gy), R2 resection margins, perineural invasion, and T stage were the significant prognostic factors for OS, EFS, and LRC. OS was not significantly different between the patients receiving R0 and R1 resections, but was significantly lower among those receiving R2 resection (54.6%, 56.1%, and 7.1% for R0, R1, and R2 resections, respectively). CONCLUSION: In patients with EHBDC who had undergone curative resection, a postoperative radiotherapy dose less than 50 Gy was suboptimal for OS and LRC. Higher radiation doses may be needed to obtain better LRC. Further investigation of novel therapy or palliative treatment should be considered for patients receiving R2 resection.
Bile Duct Neoplasms* ; Bile Ducts* ; Bile* ; Disease-Free Survival ; Humans ; Multivariate Analysis ; Palliative Care ; Radiotherapy Dosage ; Radiotherapy* ; Radiotherapy, Adjuvant ; Recurrence ; Retrospective Studies

PURPOSE: Choledochal cysts are rare congenital or acquired cystic dilatations of the intra- or extra-hepatic bile ducts. The mechanism of carcinogenesis in choledochal cyst has not been clearly elucidated, although stasis of bile and reflux of pancreatic juice appear to be important factors. The aim of this study was to identify the clinical risk factors predicting development of biliary tract cancers in patients with choledochal cyst. METHODS: The study subjects included 170 consecutive patients who underwent surgery for choledochal cysts at Seoul National University Hospital between December 1980 and May 2008. We analyzed the demographic characteristics, clinical symptoms, laboratory findings, type of choledochal cysts, pathologic characteristics, and long-term outcomes of the patients with associated biliary tract cancers. RESULTS: Out Of 170 patients with choledochal cysts, combined biliary tract cancers ware identified in 29 patients, which included extrahepatic bile duct (n=15; 51.7%), gallbladder (n=12; 41.4%), and ampulla of Vater cancers (n=2; 6.9%). There were no significant differences in gender, clinical symptoms (abdominal pain, jaundice, and abdominal masses), laboratory findings (leukocytosis, hyperbilirubinemia, and increased alkaline phosphatase), and Todani classification of choledochal cysts between the two groups with or without combined biliary tract cancer. Multivariate analysis revealed that age > or =41 years and pancreatico-choledochal type APBDU were associated with the development of biliary tract cancers in patients with choledochal cysts. CONCLUSION: Age > or =41 years and pancreatico-choledochal type APBDU were associated with the development of biliary tract cancers in patients with choledochal cysts. Therefore, the possibility of associated biliary tract cancers should be considered when planning surgical management for patients with these risk factors.
Ampulla of Vater ; Bile ; Bile Ducts ; Bile Ducts, Extrahepatic ; Biliary Tract ; Biliary Tract Neoplasms ; Choledochal Cyst ; Dilatation ; Gallbladder ; Humans ; Hyperbilirubinemia ; Jaundice ; Multivariate Analysis ; Pancreatic Juice ; Risk Factors

PURPOSE: Choledochal cysts are rare congenital or acquired cystic dilatations of the intra- or extra-hepatic bile ducts. The mechanism of carcinogenesis in choledochal cyst has not been clearly elucidated, although stasis of bile and reflux of pancreatic juice appear to be important factors. The aim of this study was to identify the clinical risk factors predicting development of biliary tract cancers in patients with choledochal cyst. METHODS: The study subjects included 170 consecutive patients who underwent surgery for choledochal cysts at Seoul National University Hospital between December 1980 and May 2008. We analyzed the demographic characteristics, clinical symptoms, laboratory findings, type of choledochal cysts, pathologic characteristics, and long-term outcomes of the patients with associated biliary tract cancers. RESULTS: Out Of 170 patients with choledochal cysts, combined biliary tract cancers ware identified in 29 patients, which included extrahepatic bile duct (n=15; 51.7%), gallbladder (n=12; 41.4%), and ampulla of Vater cancers (n=2; 6.9%). There were no significant differences in gender, clinical symptoms (abdominal pain, jaundice, and abdominal masses), laboratory findings (leukocytosis, hyperbilirubinemia, and increased alkaline phosphatase), and Todani classification of choledochal cysts between the two groups with or without combined biliary tract cancer. Multivariate analysis revealed that age > or =41 years and pancreatico-choledochal type APBDU were associated with the development of biliary tract cancers in patients with choledochal cysts. CONCLUSION: Age > or =41 years and pancreatico-choledochal type APBDU were associated with the development of biliary tract cancers in patients with choledochal cysts. Therefore, the possibility of associated biliary tract cancers should be considered when planning surgical management for patients with these risk factors.
Ampulla of Vater ; Bile ; Bile Ducts ; Bile Ducts, Extrahepatic ; Biliary Tract ; Biliary Tract Neoplasms ; Choledochal Cyst ; Dilatation ; Gallbladder ; Humans ; Hyperbilirubinemia ; Jaundice ; Multivariate Analysis ; Pancreatic Juice ; Risk Factors