Prognostic factors of intraductal papillary mucinous neoplasm of the bile duct: analysis based on SEER database / 中华肝胆外科杂志

Objective:To explore prognostic factors of intraductal papillary mucinous neoplasm of the bile duct (IPMN-B) patients.Methods:Clinical data on 227 patients with IPMN-B between 2004 and 2015 were retrospectively collected from the surveillance, epidemiology, and end results (SEER) database. There were 126 male and 101 female patients with the age at diagnosis of 69(58, 77) years old. IPMN-B patients were divided into two groups based on whether surgical treatment was performed. There were 129 patients in the surgery group and 98 patients in the non-surgery group. The survival analyses were assessed by Kaplan-Meier analyses and log-rank test was used to compared survival rate. The univariate and multivariate Cox analyses were applied to find independent prognostic factors of the survival in IPMN-B patients.Results:The tumor size of 227 IPMN-B patients from the SEER database was 25(18.5, 45.0) mm. The differences of tumor size, grade of defferentiation, American Joint Committee on Cancer (AJCC) stage, T stage, M stage chemotherapy were statistically significant respectively in surgery group and non-surgery group (all P<0.05). The median overall survival time (OS) of patients with IPMN-B was 14 months and the overall 1-year survival was 53.4%. The median overall survival time of IPMN-B patients in surgery group was 27 months, which was better than 5 months of patients in non-surgery group, and the difference was statistically significant ( P<0.001). Univariate Cox analysis found AJCC stage, T stage, N stage, M stage and surgery were prognostic factors in patients with IPMN-B. Multivariate Cox analysis showed that M1 stage ( HR=2.125, 95% CI: 1.472-3.066, P<0.001) was independent risk factor of prognosis while surgery ( HR=2.983, 95% CI: 2.106-4.224, P<0.001) was independent protective factor of prognosis. Conclusion:The AJCC staging system is an important predictor for evaluating the prognosis of IPMN-B patients. Surgery could significantly improve the prognosis of patients with IPMN-B.

Progress of targeted therapy of intrahepatic cholangiocarcinoma / 中华肝胆外科杂志

The incidence of intrahepatic cholangiocarcinoma (ICC) has been increasing year by year. For most patients, surgical resection is not suitable when they are diagnosed as ICC. Conventional chemotherapy and radiotherapy are not effective for the long-term survival rate of ICC patients and lead to the poor overall prognosis. In recent years, with the deepening understanding about the molecular mechanism of biliary malignant tumors, some key genes and signaling pathways related to the pathogenesis of ICC have been identified, providing new ideas for the targeted therapy. In this paper, major molecular mechanisms and targeted therapies of ICC are reviewed.

Progress of targeted therapy of intrahepatic cholangiocarcinoma / 中华肝胆外科杂志

The incidence of intrahepatic cholangiocarcinoma(ICC)has been increasing year by year.For most patients,surgical resection is not suitable when they are diagnosed as ICC.Conventional chemotherapy and radiotherapy are not effective for the long-term survival rate of ICC patients and lead to the poor overall prognosis.In recent years,with the deepening understanding about the molecular mechanism of biliary malignant tumors,some key genes and signaling pathways related to the pathogenesis of ICC have been identified,providing new ideas for the targeted therapy.In this paper,major molecular mechanisms and targeted therapies of ICC are reviewed.

The Role of Peroral Cholangioscopy in Evaluating Indeterminate Biliary Strictures

Biliary strictures are considered indeterminate when the initial radiologic evaluation and endoscopic retrograde cholangiopancreatography with brush cytology and/or forceps biopsy do not reveal diagnostic findings. Evaluation of these strictures is challenging and often requires a multidisciplinary approach and multiple procedures. Peroral cholangioscopy allows direct visualization of these lesions and targeted tissue acquisition using miniature biopsy forceps. In the past decade, there have been significant improvements in the field of cholangioscopy. These advances have allowed higher-quality image acquisition, easy setup, operation by a single operator, easy maneuverability, and excellent targeted tissue sampling performance. However, the interpretation of cholangioscopic visual findings remains challenging. In this review, we discuss the role of peroral cholangioscopy in the evaluation of indeterminate biliary strictures.

Classification of hilar cholangiocarcinoma:a comparison study between three-dimensional ultrasonography and magnetic resonance cholangiopancreatography / 中华超声影像学杂志

Objective To investigate the accuracy and availability of three‐dimensional ultrasonography ( 3DUS ) in the Bismuth‐Corlette classification of hilar cholangiocarcinoma ( HCCA ) . Methods Forty‐eight patients who underwent surgery and obtained pathologic diagnosis of HCCA were retrospectively analyzed . All patients underwent 3DUS and magnetic resonance cholangiopancreatography (MRCP) before surgery . With surgical outcomes as the gold standard ,the diagnostic efficacy of two examinations in classification of HCCA were compared . Results Forty‐eight cases of HCCA were divided into 5 types according to surgical results ,including type Ⅰ (8 cases) ,type Ⅱ(13 cases) ,Ⅲa(8 cases) ,Ⅲb (11 cases) and type Ⅳ(8 cases) respectively . Among them ,39 cases accepted radical resection and the rest of 9 cases received palliative resection . The accuracy of the Bismuth classification confirmed by 3DUS was 85 .4% (41/48) . The percentage of underestimated and overestimated classification confirmed by 3DUS were 10 .4% (5/48) and 4 .2% (2/48) respectively . The accuracy of the classification confirmed by MRCP was 87 .4% (42/48) .Both of the percentage of underestimated and overestimated classification confirmed by MRCP were samely 6 .3% (3/48) .The difference between the 3DUS and MRCP was not statistically significant(χ2 =0 .597 ,P=0 .440) . Both the percentage of underestimated and overestimated classification between 3DUS and MRCP were samely not statistically significant ( P =0 .714 , P =1 .000 ,respectively) . Conclusions As a new diagnostic technique ,3DUS was feasible and had significant value in evaluating HCCA classification comparable to MRCP .

Imaging features of intraductal papillary neoplasm of the bile duct / 中华放射学杂志

Objective To investigate the CT and MRI features of intraductal papillary neoplasm of the bile duct (IPNB).Methods Thirty eight patients with IPNB finally diagnosed by puncture biopsy or surgery were enrolled in this study.All the CT or MRI data were investigated retrospectively.Twenty one patients underwent CT examinations,17 patients underwent MRI examinations.The features of IPNB including the distribution features of the nodules or masses,CT and MRI features of cholangiectasis,mucus were analyzed.The accuracy differences of CT and MRI for the preoperatively diagnosing mucus and tumor growing along mucous were compared by nonparametric test.Results The lesions (including 5 patients with solitary lesions and 19 patients with multiple lesions) were located in intrahepatic bile duct in 24 patients,3 patients occurred simultaneously in intrahepatic and portal bile duct,2 lesions occurred in portal bile duct,8 lesions occurred in common bile duct,the lesions of 1 patient occurred simultaneously in common bile duct,cystic duct and gallbladder.Seventeen and 11 patients appeared nodules locating in dilated bile duct on CT and MRI,respectively.Four and 5 patients appeared cystic lesions with multiple nodules of the liver on CT and MRI,respectively.Higher contrast enhancement on CT and MRI in arterial phase than that in portal vein and equilibrium phase were observed in 18 and 12 patients,respectively.Excluding the patients undergoing puncture,CT was better than MRI in evaluating whether the mucus was present,with the accuracies of 30.0％ (6/20) and 6.3％ (1/16) for CT and M RI,respectively (Z =2.58,P ＜ 0.05).CT was worse than MRI in preoperatively evaluating the features of tumor growing along mucous,with the accuracies of 77.8％ (14/18) and 92.6％ (13/14) for CT and MRI,respectively (Z =4.23,P ＜ 0.01).Conclusion IPNB had the features of growing along mucous of the bile duct,nodule or mass in dilated bile duct and other features,CT and MRI are important in diagnosing the IPNB.

The impact of old age on surgical outcomes after pancreaticoduodenectomy for distal bile duct cancer

BACKGROUNDS/AIMS: To compare surgical results and survival of two groups of patients, age > or =70 vs. age <70, who underwent pancreaticoduodenectomy and to identify the safety of this procedure for elderly patients for the treatment of distal common bile duct (CBD) cancer. METHODS: Between January 2003 and December 2009, 55 patients who underwent pancreaticoduodenectomy for the treatment of distal CBD cancer at Keimyung University Dong San Medical Center were enrolled in our study. RESULTS: Of 55 patients, 28 were male and 27 female. Nineteen were over 70 years old (older group) and 36 were below 70 years (younger group). The mean ages of the two groups of patients were 73.5 years and 60.5 years respectively. Although patients of the older group had significantly more comorbid diseases, perioperative results including operation time, amount of intraoperative bleeding, duration of postoperative hospital stay and postoperative complications were not significantly different. A higher level (more than 5 mg/dl) of preoperative initial bilirubin showed significant correlations with operative morbidity by univariate analysis, and age was not an independent risk factor of operative morbidity. Overall 5 year survival of older and younger groups were 45.9% and 39.5% respectively (p=0.671) and disease-free 5-year survival were 31.7% and 31.1%, respectively (p=0.942). CONCLUSIONS: Surgical outcomes of elderly patients were similar to those of younger patients, despite a higher incidence of comorbid disease. This results shows that pancreaticoduodenectomy can be applied safely to elderly patients.

Influence of cholangiocardnoma cells on endothelial cells in a co-culture system / 中华消化外科杂志

Objective To study the influence of cholangiocarcinoma cells on endothelial cells in a co-culture system. Methods A co-culture system of eholangioeareinoma cell line QBC939> and endothelial cells was established in vitro (co-culture group). Endothelial cells were cultured individually during the same time (control group). The mixed supematant of cholangiecareinoma cells and endothelial cells was in the mixed group. Light microscopy and transmission electron micrescopy were used to observe the morphology of the endothelial cells. Changes in expression of ppI25FAK, MMP-2, MMP-9 and uPA of the endothelial cells were detected by mmunofluorescence, and the activities of MMP-2 and MMP-9 were detected by gelatin zymography. All the data were analyzed by paired t test. Results The intercellular space between endothelial cells in co-cuhure group was wider than in the control group. The expression of pp125FAK, MMP-2, MMP-9 and uPA was 394 ±51,455±82, 377±48,422±55 in control group, and was 1096±128,931±72,815±76,801±56 in the eo-euhure group. The difference between the 2 groups had statistical significance (t = 6.53,4.32, 3.61,3.45, P < 0. 05). The values of gray-scale scanning of MMP-2 and MMP-9 in the mixed group were 240.2±15.2 and 2.4±0.8, respectively. The values of gray-scale scanning of MMP-2 and MMP-9 in the co-culture group were significantly increased, they were 687.4 ± 43.6 and 150.9 ± 13.2, respectively (t = 4.89, 5.43, P < 0.05). Conclusions The intercellular space between endothelial ceils and the expression of the proteolytie enzymes are increased after co-culturing endothelial cells with eholangiocarcinoma cells. Proteolytie enzymes may be involved in the process of degradation of subendothelial matrix, and promotes the metastasis of cholangiocarcinoma.

MRI findings of intraductal papillary neoplasm of intrahepatic bile duets / 中华放射学杂志

Seven cases exhibited segmental bile duct dilation with filling defects. One case only showed dilatation of lobar bile ducts. Conclusion MRI features of IPNB are helpful for distinguishing IPNB from other hepatic lesions.

Study of inhibition of GABA on proliferation of cholangiocarcinoma cell line QBC939 and its mechanism / 中华肝胆外科杂志

Objective To explore the effect of gamma-aminobutyric acid (GABA) on the growth, apoptosis and telomerase activity of Cholangiocarcinoma cell line QBC939. Methods Cholangiocarcinoma cell line QBC939 was cultured by routine method, and then treated with different concentrations of GABA (1-1000 μmmol/L). The proliferation, apoptosis and cell cycle of QBC939 cells was investigated by MTT, Flow cytometry and transmission electron microscopy. The telomer-ase activity of QBC939 cells was examined by modified PCR-ELISA assay. Radioimmunoassay was used to measure the intracellular cyclic adenosine monophosphate(cAMP) content. Results The dif-ferent concentrations of GABA inhibited the growth of QBC939 cells and promoted the apoptosis. The apop-totic rate of QBC939 cells was increased from 4. 8% to 28. 03%, which had significant difference (P<0.05). It had no effect for distribution of cell cycle. Cell nuclear condensation and apoptotic bodies were seen by transmission electron microscopy. Telomerase activity was inhibited by GABA(0. 82±0. 048 vs 0.56±0. 054, P<0.05). The content of intracellular cAMP was increased with the increase of GABA concentration in a dose-dependent manner [(0. 59±0. 049) nmol/L vs (0. 82±0. 033)nmol/L, P<0. 05]. Conclusion GABA can inhibit the proliferation of QBC939 cells by promoting apoptosis and inhibiting telomerase activi-ty, which may be mediated by the information transmission of post-receptor.

Effect of Pre-operative Biliary Drainage on Surgical Outcomes after Pancreaticoduodenectomy in Patients with Common Bile Duct Cancer

INTRODUCTION: Biliary drainage is tried before surgery because it is thought that obstructive jaundice is associated with post-operative mortality and morbidity. However, there are no confirmed criteria about the optimal operation time after drainage. We attempted to determine the appropriate pre-operative bilirubin level after drainage which should be achieved before pancreaticoduodenectomy is done for extrahepatic bile duct cancer. METHODS: We reviewed 100 patients (69 males and 31 females with a mean age of 61.3 +/- 9.4 years) who underwent pancreaticoduodenectomy after a pre-operative biliary drainage procedure for distal common bile duct cancer by one surgeon at the Asan Medical Center in Seoul Korea between 1994 and 2005. RESULTS: We compared the group with pre-operative bilirubin levels or = 5.0 mg/dl (N = 86). In the bilirubin or = 5.0 group (p = 0.032). CONCLUSION: The pre-operative bilirubin or = 5.0 groups had a clear difference in postoperative morbidity. Therefore, we suggest waiting until the pre-operative bilirubin level decreases to <5.0 mg/dl after biliary drainage.

Surgical treatment and prognostic analysis of hilar cholangiocarcinoma: a report of 41 cases / 中华肝胆外科杂志

Objective To explore surgical strategy for patients with hilar cholangiocarcinoma (HCC) and study prognostic factors after curative treatment. Methods We retrospectively reviewed medical records of 41 patients with HCC surgically treated in our department during the 9-year period from January 1999 to February 2007. Clinicopathological factors were evaluated for their association with post-operational survival by univariate and multivariate analysis using Cox proportional hazard model. Results All the 41 patients underwent laparotomy following preoperative assessment of extent of disease and 21 patients (resectability rate 51.2%) ultimately underwent resection with curative in-tent. In the resection group, R0 radical resection was possible in 11 patients, while R1 resection in 6and R2 in 4. Different types of hepatectomy were combined to accomplish resection. Meanwhile, por-tal vein wedge resection or reconstruction was needed in two patients. The 1-, 3-and 5-year survival rates were 41.5%, 14.6% and 4.9% in the overall group and 71.3%, 28.6%, 9.5% in the resection group, respectively. In R0-resection, Rl-resection and R2 resection group, the 1-,3-and 5-year sur-vival rates were 81.8% ,45.5% ,18.2% ;66.7% ,16.7% ,0 and 50% ,0,0, respectively. Survival rates after resection were significantly higher than those after palliative drainage and exploratory laparotomy (P<0. 001). Higher survival rates were seen in R0-resected patients when compared with Rl-or R2-resected patients (P<0.001). Multivariate analysis revealed that tumor-free margins, pTNM stage and combined hepatectomy were independent prognostic factors affecting survival. Conclusion Only surgery can provide chance to achieve the possibility of cure and long-term survival. Tumor-free margins, pTNM stage and combined hepatectomy are the most important prognostic factors affecting the survival.

Differentiation Between Mass-forming Type Peripheral Cholangiocarcinoma and Hepatic Abscesses: Application of Artificial Neural Networks to CT Images

PURPOSE: To determine which CT findings are useful for differentiating cholangiocarcinomas (CC) from hepatic abscesses and also to determine whether artificial neural networks (ANNs) improve radiologists' performance. MATERIALS AND METHODS: CT findings of 51 patients with mass-forming type CC and 70 patients with hepatic abscesses were analyzed with morphologic, enhancing and other ancillary findings by three radiologists with differing levels of expertise independently. ANNs were constructed using statistically significant CT findings derived from the analyses. The performances of the ANNs and the radiologists were evaluated using receiver operating characteristic analysis. RESULTS: CT findings of rim-like enhancement, lymphadenopathy, capsular retraction, focal bile duct dilatation and a solid component were significant features of CC (p< 0.05). Findings of a clustered sign, multilayered enhancement, sharp margin, round shape, and air-biliary gram were significant features of hepatic abscesses. The ANNs showed better performance (AZ=0.9673, 98.0%, 97.1%, and 97.5%, respectively) than the resident (AZ=0.898, 78.4%, 81.4%, 80.2%) (p<0.05) in differentiating between the two diseases: (AZ, sensitivities, specificities, and overall accuracies). However, there were no significant differences in the diagnostic performance of the ANNs and the two board-certified radiologists. CONCLUSION: Several CT findings are useful in differentiating CC from hepatic abscesses and ANNs may improve the performance of a radiologist with little experience.

Bile cystadenocarcinoma:MRI findings with pathologic correlation / 中华放射学杂志

Objective To describe the MRI features and pathologic findings of biliary cystadenocarcinoma(BCAC)and to assess the diagnostic value of MRI in those tumors.Methods Five cases of BCAC were collected.All cases were proved by pathology.Non-enhanced and multiphase-enhanced MRI were performed in all cases.MRCP were performed in two cases.The MRI features of the five cases were reviewed retrospectively and correlated with pathologic findings.Results Histological evidence demonstrated five cases of BCAC.Four cases were solitary,whereas the other case was multifocal.All cases were solid and cystic lesions.Two cases were unilocular,whereas the other three cases were multilocular. Multiple mural nodules and irregular thickening cystic walls were presented in all cases.The cystic parts of the lesions were homogeneous in signal intensity and showed no enhancement after contrast administration in the five BCAC.Septa were present in three BCAC with multilocular cyst.On MRCP the bile duct dilatation was found in two BCAC.Conclusion MRI can reveal the characteristic findings of BCAC and accurate preoperative diagnosis can be made.

Determination of N-acetylglucosaminyltransferase Ⅲ, Ⅳ and Ⅴ activity in extrahepatic cholangiocarcinoma / 中国普通外科杂志

Objective To study the activity of N acetylglucosaminyltransferase Ⅲ, Ⅳ and V in extrahepatic cholangiocarcinoma and its significance.Methods The activities of N acetylglucosaminyltransferase(GnT) Ⅲ, Ⅳ and Ⅴ in extrahepatic bile duct carcinoma (EBDC) of 15 cases were determined by reverse phase HPLC (high performance liquid chromatography), and results were compared with benign biliary diseases in 15 cases. Results Compared with normal control, that the specific activities of GnT Ⅲ and GnT Ⅴ increased by 3 3 and 13 5 fold respectively in all of the EBDC samples(all P

Intrahepatic cholangiocarcinoma presenting as liver Abscess: Report of Two Cases

Intrahepatic cholangiocarcinoma is the second most common primary malignant hepatic neoplasm. We describe twocases of intrahepatic cholangiocarcinoma which initially presented as liver abscess both clinically andradiologically. Mucin-hypersecretion from the tumor cells and extensive necrosis or secondary bacterial infectionwas responsible for the radiologic appearance of a liver abscess.

Cholangiocarcinoma Arising in Choledocal Cyst / 대한소화기내시경학회지

Choledochal cyst is a relatively rare disease entity considered to be a congenital cyatic dilatation of the common bile duct. Since occurrence of malignant tumor in choledochal cyet was first reported by Irwin and Morrison in 1944, approximately 100 more cases of malignant tumors arising in congenital choledocal cyst have been reported in the world, and the risk of malignant tumor related to choledochal cyst have been reported 2.4-14%. Recently, we experienced a case of adenocarcinoma arising in choledochal cyst in 39 year-old woman who was diagnosed by ERCP and cholangioscopy with forceps biopsy, and was treated with en bloc resection of the choledochal cyst along with the pancreatic head and duodenum.

Cholangiocarcinoma Arising in Choledocal Cyst / 대한소화기내시경학회지

Choledochal cyst is a relatively rare disease entity considered to be a congenital cyatic dilatation of the common bile duct. Since occurrence of malignant tumor in choledochal cyet was first reported by Irwin and Morrison in 1944, approximately 100 more cases of malignant tumors arising in congenital choledocal cyst have been reported in the world, and the risk of malignant tumor related to choledochal cyst have been reported 2.4-14%. Recently, we experienced a case of adenocarcinoma arising in choledochal cyst in 39 year-old woman who was diagnosed by ERCP and cholangioscopy with forceps biopsy, and was treated with en bloc resection of the choledochal cyst along with the pancreatic head and duodenum.