Extrahepatic Bile Duct Carcinoma Research Articles

Decreased expression of focal adhesion kinase is associated with a poor prognosis in extrahepatic bile duct carcinoma

Extrahepatic bile duct (EBD) carcinoma is a relatively rare neoplasm worldwide, and its prognostic outcome remains unfavorable. Therefore, it is necessary to investigate molecular biologic features of EBD carcinomas. Focal adhesion kinase (FAK) plays a pivotal role in cell adhesion, survival, migration, and signal transduction, but FAK expression in EBD carcinomas has not been evaluated. We measured FAK expression in 76 EBD carcinomas using immunohistochemistry and evaluated its correlation with tumor progression, clinicopathologic factors, and patient outcome. FAK was expressed specifically in the cytoplasm of all normal biliary epithelia (100%). Most dysplastic epithelia also showed positive FAK expression except for 2 cases (92%), whereas EBD carcinomas showed positive FAK expression in 53 (77%) of 76 cases (P < .001, versus normal epithelia). FAK expression tended to be gradually reduced along as dysplasia progressed to carcinoma. Although FAK expression had no association with clinicopathologic factors, the positive FAK expression group showed significantly better survival than the negative FAK expression group (P < .05). However, FAK expression was not an independent prognostic factor by multivariate analysis. In conclusion, FAK expression was significantly lower in EBD carcinomas than in normal biliary epithelia and decreased expression of FAK seemed to be indicative of a poor prognosis, suggesting that FAK might play an inhibitory role for tumor progression in EBD carcinomas. It is important to notice the role of FAK in tumor progression when treatments targeting FAK are performed.

Expression of Raf-1 Kinase Inhibitory Protein in Extrahepatic Bile Duct Carcinoma

Background : Raf-1 kinase inhibitory protein (RKIP) recently has been identified as a metastasis suppressor in a variety of human carcinomas. The prognostic significance of RKIP expression in extrahepatic bile duct (EBD) carcinoma has not been studied. The aims of the current study were to evaluate RKIP expression and to determine the prognostic significance of RKIP expression in EBD carcinoma. Methods : Immunohistochemical staining for RKIP was performed for 131 cases of EBD carcinoma. The associations of RKIP expression with clinicopathologic parameters and patient outcomes were examined. Multivariate logistic regression analysis was used to identify independent predictive parameters for lymphovascular invasion and nodal and distant metastases. Results : Loss of RKIP expression was observed in 55.0% (72/131) of cases. EBD carcinoma had significantly lower RKIP immunoreactivity than normal EBD (p < 0.001). Loss of RKIP expression was significantly associated with lymphatic invasion (p = 0.030) and nodal metastasis (p = 0.036), but it was not found to be a significant prognostic predictor for overall, disease-free or distant metastasis-free survival. In addition, loss of RKIP expression was an independent predictor for lymphatic invasion (p = 0.027). Conclusions : These results suggest that RKIP may play a role in the suppression of lymphatic invasion and nodal metastasis in EBD carcinoma.

A standardized technique for safe pancreaticojejunostomy: Pair-Watch suturing technique

To prevent pancreatic leakage after pancreaticojejunostomy, we designed a new standardized technique that we term the "Pair-Watch suturing technique". Before anastomosis, we imagine the faces of a pair of watches on the jejunal hole and pancreatic duct. The first stitch was put between 9 o'clock of the pancreatic side and 3 o'clock of the jejunal side, and a total of 7 stitches were put on the posterior wall, followed by the 5 stitches on the anterior wall. Using this technique, twelve stitches can be sutured on the first layer anastomosis regardless of the caliber of the pancreatic duct. In all cases the amylase activity of the drain were measured. A postoperative pancreatic fistula was diagnosed using postoperative pancreatic fistula grading. From March 2007 to July 2008, 29 consecutive cases underwent pancreaticojejunostomy using this technique. Pathologic examination results showed pancreatic carcinoma (n = 14), intraductal papillary-mucinous neoplasm (n = 10), intraductal papillary-mucinous carcinoma (n = 1), carcinoma of ampulla of Vater (n=1), carcinoma of extrahepatic bile duct (n = 1), metastasis of renal cell carcinoma (n = 1), and duodenal carcinoma (n = 1). Pancreaticojejunal anastomoses using this technique were all watertight during the surgical procedure. The mean diameter of main pancreatic duct was 3.4 mm (range 2-7 mm). Three patients were recognized as having an amylase level greater than 3 times the serum amylase level, but all of them were diagnosed as grade A postoperative pancreatic fistula grading and required no treatment. None of the cases developed complications such as hemorrhage, abdominal abscess, and pulmonary infection. There was no postoperative mortality. Our technique is less complicated than other methods and very secure, providing reliable anastomosis for any size of pancreatic duct.

Resected Adenosquamous Carcinoma of the Extrahepatic Bile Duct Concomitant with Cholecystitis

胆嚢炎を合併した肝外胆管原発腺扁平上皮癌の１例を経験したので報告する．症例は79歳の女性で，全身倦怠，黄疸で発症した．造影CT，ERCPで肝外胆管内に乳頭状の腫瘍を認めた．手術直前の造影CTで，胆嚢の腫大と周囲の液体貯留を認めた．肝外胆管癌の診断で膵頭十二指腸切除術を施行した．腫大した胆嚢は炎症所見が強く，周囲の大網内に膿瘍を形成していた．摘出標本で腫瘍は表面乳頭状の有茎性腫瘍で，茎は中部胆管から３管合流部付近にあり腫瘍本体が下部胆管まで充満していた．病理組織学的に，胆管腫瘍は腺扁平上皮癌と診断され，胆嚢は黄色肉芽腫を伴う胆嚢炎であった．有茎性腫瘍により胆嚢管が閉塞し胆嚢炎をきたしたと考えられた．

Expression of the GLUT1 glucose transporter and p53 in carcinomas of the pancreatobiliary tract

Only few studies have evaluated the usefulness of the GLUT1 and p53 status of pancreatobiliary tract carcinomas in revealing tumorigenesis. We studied GLUT1 and p53 immunoexpression in a total of 355 cases of the pancreatobiliary carcinoma to determine the biological significance of GLUT1 and p53 expression. Positive expression of GLUT1 was identified in 38 out of 67 (57.7%) ampulla of Vater (AV) carcinomas, in 27 out of 52 (51.8%) pancreatic (PA) carcinomas, in 38 out of 121 (31.4%) extrahepatic bile duct (EBD) carcinomas, and in 53 out of 115 (46.5%) gallbladder (GB) carcinomas. GLUT1 expression in pancreatobiliary carcinomas showed some positive correlation with histological grade, T stage, N stage, TNM stage, and lymphatic invasion. However, p53 expression showed no correlation with any prognostic factors. In the Kaplan–Meier test, positive GLUT1 expression was a poor prognostic factor in the pancreatobiliary tract cancers; however, only GB cancers were statistically significant ( P=0.002). Our results suggest that GLUT1 expression in the AV, EBD, and GB carcinomas is associated with some prognostic factors, and GLUT1 expression is associated with a worse prognosis in the patients with GB carcinomas.

Significance of mucin expression in pancreatobiliary neoplasms

Mucins are high molecular weight glycoproteins that play important roles in carcinogenesis and tumor invasion. We have described, for the first time, that pancreatic ductal adenocarcinomas (PDACs) with an aggressive behavior and a poor outcome expressed MUC1 (pan-epithelial membrane-associated mucin) but did not express MUC2 (intestinal-type secreted mucin), whereas intraductal papillary mucinous neoplasms (IPMNs) with indolent behavior and a favorable outcome did not express MUC1 but did express MUC2. These expression profiles of MUC1 and MUC2 related to the prognoses of the patients were also observed in biliary neoplasms such as intrahepatic cholangiocarcinoma (ICC)-mass-forming type (MF), mucin-producing bile duct tumor (MPBT), and extrahepatic bile duct carcinoma (EHBDC). We also found recently that high expression of MUC4 (tracheobronchial membrane-associated mucin) in PDACs, ICCs-MF, and EHBDCs was a new independent poor prognostic factor, although MUC4 was not expressed in normal pancreatobiliary tissue. High de novo expression of MUC5AC (gastric-type secreted mucin) was observed in many types of pancreatobiliary neoplasms, including all grades of pancreatic intraepithelial neoplasia (PanIN) and biliary intraepithelial neoplasia (BilIN), and all types of IPMNs and MPBTs, as well as PDACs and ICCs-MF, although MUC5AC was not expressed in normal pancreatobiliary tissue. The combined status of MUC1, MUC2, MUC4, and MUC5AC expression may be useful for the early detection of pancreatobiliary neoplasms and evaluation of their malignancy. In regard to the mechanism of mucin expression, we have recently reported that MUC1, MUC2, MUC4, and MUC5AC gene expression is regulated by epigenetics (DNA methylation and histone H3 lysine 9 modification) in cancer cell lines, including PDAC cells. Translational research of mucin gene expression mechanisms, including epigenetics, in pancreatobiliary neoplasms may give us new tools for the early and accurate detection of these neoplasms.

Prognostic significance of fascin expression in extrahepatic bile duct carcinomas

Extrahepatic bile duct (EBD) carcinoma is an aggressive cancer with a poor prognosis. Fascin is an actin-bundling protein with roles in forming cell protrusions and mesenchymal and neuronal cell motility. Many human neoplasms up-regulate fascin. High fascin expression is thought to be a poor prognostic factor in some cancers; however, few data are available for the role of fascin in EBD carcinoma. We investigated fascin immunoreactivity in EBD carcinoma and tested it for correlations between fascin expression and clinicopathological parameters. Conventional tissue sections of 114 cases of EBD carcinomas were immunohistochemically analyzed for fascin expression. Fascin expression was tested by cytoplasmic staining. Negative, weak positive, and strong positive fascin staining was observed in 49 (43.0%), 32 (28.1%), and 33 cases (28.9%), respectively. Fascin expression in EBD carcinomas was significantly correlated with histological grade ( P<0.0001), primary tumor (T) ( P=0.002), TNM stage ( P=0.036), lymphatic invasion ( P=0.048), venous invasion ( P=0.024), and adjacent organ invasion ( P<0.0001). High fascin expression was a significant poor prognostic factor ( P=0.0001) in EBD carcinoma. High fascin expression ( P=0.004) and TNM stage ( P=0.001) in EBD carcinoma were independent adverse prognostic factors. High fascin expression is significantly correlated with aggressive tumor phenotype in EBD carcinoma and is an independent poor prognostic factor in EBD carcinoma.

Impact of residual in situ carcinoma on postoperative survival in 125 patients with extrahepatic bile duct carcinoma

The aim of this study was to determine the impact of the presence of carcinoma in situ at the bile duct stump on postoperative survival in patients who underwent resection of extrahepatic bile duct carcinoma. The patients with resected extrahepatic bile duct carcinoma were divided into three groups according to resected margin status: no evidence of residual carcinoma (Negative group, n = 96); carcinoma in situ at the bile duct stump (CIS group, n = 10); and invasive carcinoma at any surgical margin (Invasive group, n = 19). Cause-specific survival for these groups was compared statistically. Surgical margin status was identified as a prognostic factor on univariate analysis (p = 0.005) and was an independent prognostic factor on multivariate analysis (p = 0.018). The CIS group displayed significantly better survival than the Invasive group (p = 0.006), and the survival was comparable to that for the Negative group (p = 0.533). Two of three patients in the CIS group with local recurrence died >5 years after surgical resection. Patients with positive ductal margins of carcinoma in situ of the extrahepatic bile duct do not appear to show different survival after resection compared to patients with negative margins, but remnant carcinoma in situ is likely to develop late local recurrence.

SU-FF-T-47: Automated Planning Volume Definition for HDR Brachytherapy: Application to Intraluminal Treatment of the Bile Duct

Purpose: Although surgery remains the treatment of choice, patients with carcinoma of the extrahepatic bile duct who are not candidates for surgical resection(∼75%) are treated palliatively with radiation therapy and/or chemotherapy. Intraluminal LDR or HDR brachytherapy has the well‐documented advantage of delivering a large target dose, while significantly sparing surrounding healthy tissues. Typically, treatment planning is performed with respect to source‐guide catheter(s) inserted along the biliary canal under fluoroscopic guidance. The prescription hull refers to a volume at a distance of 0.5–1.0 cm from catheter(s). Because of the irregular shape of the source guides, manual contouring of the prescription hull is time consuming and subject to errors. We describe, and illustrate with actual treatment plans, an automatic algorithm to outline the planning volume. Methods and Materials: The contouring of a single catheter can be considered as the trajectory generated by a moving ball. The path of the ball forms a guide curve, which is given by the digitized‐coordinates of the source‐guide catheter. Given a radius r that defines the thickness of the PTV, our volume‐definition algorithm applies curve fitting via Ferguson spline interpolation, followed by circle generation and sphere generation. For multiple catheters, the algorithm is more complex, requiring curve fitting, warping, slicing, and linking to obtain the resulting tumor shape. Results: For the biliary intraluminal case, the algorithm takes only seconds to generate a 3D‐planning volume. Applying it to complex hypothetical cases reveals that it handles irregular tumor volumes and shapes well, and returns a 3D‐planning volume within 1 CPU‐minute. Conclusion: The automatic volume‐definition algorithm works reliably and quickly, and results in plans that are demonstratively superior to those obtained by manual planning. Furthermore, the planning volume is a necessary input to computer‐based plan optimization. The volume‐definition algorithm improves the treatment dosimetric conformity, a factor that may contribute to improved clinical outcome.

Expression and Significance of Angiopoietin-1, 2 and Tie-2 Receptor in Human Extrahepatic Bile Duct Carcinoma: Correlation with Clinicopathological Factors

Title Expression and Significance of Angiopoietin-1, 2 and Tie-2 Receptor in Human Extrahepatic Bile Duct Carcinoma: Correlation with Clinicopathological Factors Author(s) Mihara, Yumi; Nakayama, Toshiyuki; Nanashima, Atsushi; Kuroki, Tamotsu; Onizuka, Shinya; Ito, Masahiro; Naruke, Yuki; Hayashi, Tomayoshi; Sanefuji, Hayato; Sekine, Ichiro Citation Acta medica Nagasakiensia, 53(4), pp.89-95 ; 2009

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

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. To examine the usefulness of MRCP followed by EUS in the early diagnosis of extrahepatic bile-duct carcinoma in the nonicteric stage. 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. A single-center, prospective study. An academic medical center. The sensitivity and specificity of MRCP followed by EUS for the early diagnosis of extrahepatic bile duct carcinoma in the nonicteric stage. 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. A single center and small number of patients. 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.

A novel approach for treatment of unresectable extrahepatic bile duct carcinoma: design of radioactive stents and an experimental trial in healthy pigs

Patients diagnosed with extrahepatic bile duct carcinoma (EBDC) have a poor prognosis. The purpose of these studies was to design radioactive stents for EBDC and to evaluate the feasibility and safety of the stents in healthy pigs. Plastic stents with inserted iodine-125 seeds were designed and tested in 11 healthy pigs. The pigs were divided into 4 groups on the basis of radiation doses. The stents with estimated radiation dose at a 5-mm radial distance from the axis of the seeds of 30 Gy, 60 Gy, and 90 Gy were implanted in the common bile duct (CBD) in groups A, B, and C (n = 3 in each group), with the control group (n = 2) being implanted with the stents containing nonradioactive seeds. Histologic evaluation was performed under a light microscope. The procedures were successfully performed on all pigs. Severe hyperplasia of the mucosa was seen in the control group. In the experimental groups, obvious mucosal necrosis near the radioactive seeds was observed but without perforation of the CBD wall. In lower-dose groups (30 Gy), mild hyperplasia of mucosal glands with fibrosis under the necrosis layer was seen. However, after the increase of the dose, mucosal glands were disappearing without a visible mucosal layer. The radioactive stents are safe at each dose in healthy pigs. Moreover, our observations indicate the feasibility to design specific radioactive stents according to the size, shape, and position of EBDC in future clinical applications.

Expression of syndecan-1 and E-cadherin is inversely correlated with poor patient's prognosis and recurrent status of extrahepatic bile duct carcinoma

Extrahepatic bile duct carcinoma is one of the most extremely aggressive cancers with poor prognosis after curative resection. Syndecan-1 and E-cadherin are transmembrane glycoproteins, and have important roles in cell-cell adhesion and tumor progression. In this study, we examined 84 surgically resected cases of extrahepatic bile duct adenocarcinoma to clarify clinicopathological significance of syndecan-1/E-cadherin expression. Reduced expressions of syndecan-1 and Ecadherin were found in 69.0% (58/84) and 46.4% (39/84) of the bile duct carcinomas. Reduced syndecan-1 expression was correlated with lymphatic/venous/nervous invasion (P < 0.0001), and was associated with short overall survival (P = 0.0002). Reduced E-cadherin expression was correlated with lymphatic and nervous invasion (P = 0.008, P < 0.0001, respectively), and was associated with short overall survival (P = 0.0038). The results indicated that reduced syndecan-1/E-cadherin expression may be good indicators of recurrence and prognosis in extrahepatic bile duct carcinoma.

Small Cell Carcinoma of Extahepatic Bile Duct Presenting with Hemobilia

We report a case of small cell carcinoma of extrahepatic bile duct presenting with jaundice and hemobilia. A 59-year-old woman was admitted due to right upper quadrant pain and jaundice. An abdominal computed tomography revealed a 2 cm sized mass in the extrahepatic bile duct. Endoscopic retrograde cholangiopancreatography revealed bloody discharge coming out of the papillary orifice in endoscopic view and a dilated extrahepatic bile duct with multiple irregular filling defects in cholangiogram. A coronal T2-weighted image revealed a hyperintense mass at extrahepatic bile duct. Laparotomy was performed, and pathologic examination of resected specimen showed tumor cells having round to oval nuclei with coarsely granular chromatin and scanty cytoplasm, which were immunoreactive for synaptophysin and chromogranin A, compatible with the diagnosis of small cell carcinoma. The small cell carcinoma of bile duct, despite its rarity, should be considered in differential diagnosis of the causes for obstructive jaundice and hemobilia.

Clinical and pathological features of primary carcinoma of the cystic duct

According to Farrar's criteria, a tumor restricted to the cystic duct is defined as cystic duct carcinoma, but this definition excludes advanced carcinoma originating from the cystic duct. For the purpose of this study, primary cystic duct carcinoma was defined as a tumor originating from the cystic duct. We investigated the clinicopathological features of 15 cystic duct carcinomas, including 13 that did not fit Farrar's criteria, and compared them with those of 52 cases of gallbladder carcinoma and 161 cases of extrahepatic bile duct carcinoma. The incidence of primary cystic duct carcinoma was 6.6% among all malignant biliary tumors. The main symptom was jaundice in 67% of cases. The operative procedures employed ranged from cholecystectomy to hepatopancreatoduodenectomy. The cases of cystic duct carcinoma and bile duct carcinoma showed a high frequency of perineural infiltration. The overall 5-year survival rate of the 15 patients was 40%. Patients with advanced cystic duct carcinoma show a high frequency of jaundice and perineural infiltration. Our data suggest that cystic duct carcinoma may be considered a distinct subgroup of gallbladder carcinoma. Radical surgery is necessary for potentially curative resection in patients with advanced cystic duct carcinoma.

Genetic Alteration of Keap1 Confers Constitutive Nrf2 Activation and Resistance to Chemotherapy in Gallbladder Cancer

Biliary tract cancer (BTC) is a highly malignant tumor, and identification of effective therapeutic targets to improve prognosis is urgently required. Oncogenic activation of survival genes is important for cancer cells to overcome oxidative stresses induced by their microenvironments that include chronic inflammation or exposure to anticancer drugs. We attempted to examine whether deregulation of Nrf2, a master transcriptional factor of various cytoprotective genes against oxidative stress, plays a role in the carcinogenesis of BTC. We screened genetic alteration of Keap1, a negative regulator of Nrf2, in BTC including tumors originated from gallbladder and extra- and intrahepatic bile ducts. Functional analysis of cancer-related mutant Keap1 in Nrf2 repression and the association between Nrf2 activation and resistance to 5-fluorouracil (5-FU) were investigated. Recurrent (in 1/11 cell lines and 6/53 primary tumors) Keap1 gene alterations were observed in BTC and were especially frequent (4/13, 30.7%) in gallbladder cancer (GBC). These alterations led to a considerable loss of Nrf2 repression activity, caused constitutive activation of Nrf2, and promoted cell proliferation. Down-regulation of Nrf2 activity by either Keap1 complementation or Nrf2 short interference RNA increased sensitivity to 5-FU in Keap1-altered BTC cells. Keap1 mutation occurs frequently in GBC. Aberrant Nrf2 activation provoked by Keap1 alteration is one of the molecular mechanisms for chemotherapeutic resistance in GBC and will be a novel therapeutic target as an enhancer of sensitivity to 5-FU-based regimens.

Carcinoma of Extrahepatic Bile Ducts and Gallbladder Metastatic to the Ovary: A Report of 16 Cases

Information on ovarian metastasis of carcinoma of the extrahepatic bile ducts and gallbladder is limited. Sixteen examples are reported; 3 primary tumors were hilar cholangiocarcinomas, 5 common bile duct carcinomas, and 8 gallbladder carcinomas. The patients ranged from 21 to 87 years (mean, 59 years); 7 presented to gynecologists with nonspecific pelvic symptoms similar to primary ovarian neoplasms. The primary tumor was identified before the detection of the ovarian lesions in 5 cases, was simultaneously detected with the ovarian metastases in 9, and was diagnosed postoperatively in 2. All but one case had bilateral ovarian involvement. The thirty-one ovarian lesions included twenty-nine grossly abnormal ovaries that were enlarged (range, 3.0-16.5 cm, mean, 9.4 cm) and 2 ovaries with only microscopic involvement. The sectioned surface was solid in 9, solid-cystic in 15, and multicystic in 5. Microscopically, ovarian surface implants were seen in 66%, multinodular growth in 58%, and infiltrative stromal invasion in 81%. Mucinous epithelial differentiation was seen in 81%, sometimes with foci of benign-like or borderline-like epithelium simulating primary ovarian mucinous neoplasia. Cystadenoma and cystadenofibroma of nonmucinous type was even mimicked strikingly in some cases because of flattening of epithelium lining glands and cysts. Signet ring cells were present in sufficient quantity for a diagnosis of Krukenberg tumor in four tumors. Colloid-type carcinoma was observed at least focally in 3 tumors. Nonmucinous carcinomatous components included adenocarcinoma with high-grade endometrioid-like morphology in 2 cases, papillary adenocarcinoma simulating mixed müllerian epithelial adenocarcinoma in 1, and undifferentiated carcinoma in 2. Immunohistochemical studies in 8 cases showed a positive reaction for cytokeratin 7 in all and for cytokeratin 20 in 4 cases. The high rate of bilaterality, surface involvement, multinodular growth, and heterogeneity of patterns were the most helpful features for indicating a metastatic nature, with signet ring cells also being helpful in the minority of cases in which they were present. Although the diagnosis of a metastatic tumor to the ovary is possible in most of the cases based on standard diagnostic criteria, problems in the differential diagnosis may be posed by morphologic patterns that overlap strikingly with primary ovarian neoplasms, benign, borderline, and malignant, as discussed herein.

Extrahepatic bile duct carcinoma with extensive intraepithelial spread: a clinicopathological study of 21 cases

Extrahepatic bile duct carcinoma occasionally presents with intraepithelial spread for a considerable area around the main tumor. In this study, we compared clinicopathological features of extrahepatic bile duct carcinoma with and without extensive intraepithelial spread (≥20 mm from the main tumor). Out of 117 cases of extrahepatic bile duct carcinoma, 21 (18%) were found to have extensive intraepithelial spread. Those cases were pathologically characterized by a papillary or nodular main tumor, a more differentiated histological grade, less deep invasion, and infrequent portal vein or hepatic invasion in comparison with cases without intraepithelial spread. Areas of intraepithelial spread histologically consisted of low-papillary growth (17 cases, 81%) and completely flat growth (4 cases, 19%) of carcinoma cells. The former histology corresponded to a macroscopic granular mucosa, whereas the latter growth was hardly detected by gross examination. Immunohistochemically, in 16 of 21 cases (76%), at least one of p53, CEA, and MUC1 was expressed in both the main tumor and the spreading area. Interestingly, patients with intraepithelial spread had a better postoperative prognosis than those without intraepithelial spread (P=0.009). However, three patients had anastomotic recurrence 54–130 months after surgery. In conclusion, intraepithelial-spreading bile duct carcinoma is characterized by papillary or nodular main lesions, a more differentiated histological grade, and less invasiveness. The presence of intraepithelial spread was not an indicator of a poor prognosis, but carcinoma in situ at the bile duct stump could cause late anastomotic recurrence after surgery.

Biliary Malignancy

To assess the diagnostic value of arterial, pancreatic, and hepatic phase imaging with multidetector-row computed tomography of a bile duct malignancy. Our institutional review board approved this retrospective study and waived the requirement for informed consent. Forty-two patients with surgically proven hilar or extrahepatic cholangiocarcinoma, who underwent preoperative imaging with triple-phasic multidetector-row computed tomography, were included in this study. Images obtained during each phase were reviewed by 2 independent observers who assessed the tumor conspicuity and the biliary extent of the tumor and vascular invasion by the tumor. For quantitative analysis, another radiologist measured the tumor attenuation, the normal liver parenchyma, the aorta, and the main portal vein on each phase image. The degree of tumor conspicuity was higher in the pancreatic and hepatic phases than in the arterial phase (P < 0.01); however, there was no statistical difference in tumor conspicuity between the pancreatic and hepatic phases (P > 0.05). The mean tumor attenuation was greater in the hepatic phase at 114.2 +/- 24.6 Hounsfield units versus 72.9 +/- 18.3 Hounsfield units in the arterial phase (P < 0.001). The images obtained in the hepatic phases were significantly superior to those obtained in the arterial phase for predicting the tumor involvement into the secondary biliary confluence (P < 0.05). In predicting for the vascular involvement by the tumors, there was no significant difference among the 3 enhancement phases (P > 0.05). Routine acquisition of arterial phase images is not necessary for successful detection and evaluation of the extent of hilar or extrahepatic bile duct carcinoma.

Intraluminal Implantation of Radioactive Stents for Treatment of Unresectable Pancreatic Cancer, Extrahepatic Bile Duct Carcinoma and Ampullary Carcinoma: A Pilot Trial

Intraluminal Implantation of Radioactive Stents for Treatment of Unresectable Pancreatic Cancer, Extrahepatic Bile Duct Carcinoma and Ampullary Carcinoma: A Pilot Trial