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Background: Trophoblast cell surface antigen 2 (TROP2) was found to be associated with tumor progression and poor prognosis in a variety of epithelial carcinomas. The aim of the study was to investigate TROP2 expression and its prognostic impact in hilar cholangiocarcinoma., Methods: Immunohistochemistry and quantitative real-time PCR were used to determine TROP2 expression in surgical specimens from 70 hilar cholangiocarcinoma patients receiving radical resection. The relationship between TROP2 expression and microvessel density was investigated and standard statistical analysis was used to evaluate TROP2 prognosis significance in hilar cholangiocarcinoma., Results: High TROP2 expression by immunohistochemistry was found in 43 (61.4 %) of the 70 tumor specimens. Quantitative real-time PCR confirmed that TROP2 level in tumor was significantly higher than in non-tumoral biliary tissues (P = 0.001). Significant correlations were found between TROP2 expression and histological differentiation (P = 0.016) and tumor T stage (P = 0.031) in hilar cholangiocarcinoma. TROP2 expression correlated with microvessel density in hilar cholangiocarcinoma (P = 0.026). High TROP2 expression patients had a significantly poorer overall survival rate than those with low TROP2 expression (30 vs. 68.5 %, P = 0.001), and multivariate Cox regression analysis indicated TROP2 as an independent prognostic factor for hilar cholangiocarcinoma (P = 0.004)., Conclusion: TROP2 expression correlates with microvessel density significantly and is an independent prognostic factor in human hilar cholangiocarcinoma.

Background and Aims: Intrahepatic cholangiocarcinomas (ICCs) are usually adenocarcinomas with fibrotic and hypovascular stroma. Intrahepatic cholangiocarcinomas in cirrhosis and precirrhotic liver (ICC-cirrhosis) are increasingly being diagnosed, and can display hypervascular enhancement resembling a hepatocellular carcinoma on dynamic imaging., Methods: In this study using ICC-cirrhosis (71 cases), ICC with non-specific reactive changes (ICC-reactive) (72 cases) and the cholangiocarcinoma component of combined hepatocellular cholangiocarcinoma (HCC-ICC) (30 cases), we tried to compare the tumour vasculature., Results: It was found that ICC-cirrhosis and the cholangiocarcinoma component of HCC-ICC showed a higher density of arteries and microvessels (1.59 ± 0.58/mm(2) (mean ± SD) and 140 ± 43/mm(2) in ICC-cirrhosis and 1.74 ± 0.67/mm(2) and 131 ± 46/mm(2) in the cholangiocarcinoma component of HCC-ICC) than in ICC-reactive (1.26 ± 0.61/mm(2) and 103 ± 45/mm(2) ). Dynamic computed tomography (CT) and magnetic resonance imaging (MRI) showed that a majority of ICC-cirrhosis displayed strong hypervascular enhancement, whereas one-third of ICC-reactive each showed strong, weak and no or minimal enhancement respectively. The increased vascular density was positively correlated with enhanced arterial phase of dynamic CT and MRI., Conclusion: The density of arteries and microvessels of ICC-cirrhosis was higher than that in ICC-reactive and comparable to that in the cholangiocarcinoma component of HCC-ICC, and the higher density of arteries and microvessels in ICC may be responsible for the hypervascular enhancement of ICC-cirrhosis., (© 2012 John Wiley & Sons A/S.)

Contrast-enhanced ultrasound (CEUS) has long been present in important guidelines and recommendations for the diagnostic work-up of focal liver lesions in patients with cirrhosis. These guidelines have included the guidelines of the American Association for the Study of Liver Diseases (AASLD) 2005, the Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma, the recommendations of the Japanese Society of Hepatology, and the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) guidelines 2004, 2008 and 2012 (in preparation). Recently, the AASLD removed CEUS from their guidelines in part because of the perceived possibility of false-positive hepatocellular carcinoma (HCC) diagnosis in patients with intrahepatic cholangiocarcinoma (ICC), and in part because CEUS is not available in the USA. This latter factor means that published results are not entirely applicable to a North American population. The present manuscript discusses the diagnostic algorithm of hepatocellular carcinoma and provides information on the differential diagnosis between HCC and ICC., (© Georg Thieme Verlag KG Stuttgart · New York.)

Contrast-enhanced ultrasound (CEUS) is a well established diagnostic imaging technique for a variety of indications and applications. One of the most important applications is in the liver where it is frequently a first-line technique for the detection and diagnosis (characterization) of focal liver lesions (FLLs). In this setting the accurate differentiation of benign lesions from malignant lesions is critical to ensure that the patient undergoes the appropriate therapeutic option. In this article the role of CEUS in the characterization of FLLs is described on the basis of recently published guidelines, in particular in terms of the enhancement patterns of the most common FLLs, e. g. hemangioma, focal nodular hyperplasia, hepatocellular adenoma and their differentiation from malignant lesions., (© Georg Thieme Verlag KG Stuttgart · New York.)

Multicenter trials to assess contrast-enhanced ultrasound (CEUS) for the imaging of focal liver lesions (FLLs) have included more than 1000 patients. This article reviews the published literature pertaining to these trials to determine the role of CEUS in the characterization of FLL., (© Georg Thieme Verlag KG Stuttgart · New York.)

A 78-year-old man who had hepatitis C was examined by computed tomography(CT)because of prostate cancer, and was found to have a liver tumor 8. 0 cm in size at S4/S8. The view of the liver tumor was enhanced by CTHA image and washed out by CTAP image. It was suspected to have invaded the RHV and MHV. The pathological examination of the liver biopsy sample revealed cholangiocellular carcinoma or cholangiolocellular carcinoma. Hepatic arterial infusion chemotherapy with gemcitabine and cisplatin was performed. The size of the tumor reduced to 6. 0 cm and the invasion to the RHV was no longer evident. Hepatic resection for the middle two segments was performed after 3 months of chemotherapy. After a histological examination of the resected specimen, the patient was given the final diagnosis of cholangiolocellular carcinoma. Over 50% of the tumor was estimated as necrosis by chemotherapy, indicating that the gemcitabine and cisplatin regimen was remarkably effective. The patient is alive with no evidence of recurrence.

Backgrounds: Portal vein embolization (PVE) has been widely applied before extended hepatectomy; however, its clinical utility for patients with biliary cancer has not been fully addressed., Methods: Between 1991 and 2010, 494 patients with cholangiocarcinoma (n = 353) or gallbladder cancer (n = 141) underwent PVE before extended hepatectomy. PVE was performed by a transhepatic ipsilateral approach using fibrin glue or absolute ethanol with steel coils. Surgical outcomes of this cohort were retrospectively reviewed., Results: PVE-related complications requiring interventions were found in 3 (0.6%) of the 494 patients; no patient died of these complications. Among the 494 patients, 122 (24.7%) did not undergo subsequent hepatectomy. The unresectability rate was significantly higher in patients with gallbladder cancer than in those with cholangiocarcinoma [43.2% (61/141) and 17.3% (61/353), respectively, p < 0.001]. The remaining 372 patients underwent hepatectomy, and 24 (6.5%) died of postoperative complications [13 of 80 (16.3%) with gallbladder cancer vs. 11 of 292 (3.8%) with cholangiocarcinoma, p < 0.05]. The overall survival for patients with cholangiocarcinoma was significantly better than that for patients with gallbladder cancer, where the 5-year survival rate was 39 and 23%, respectively (p < 0.001). Thirty-six patients with cholangiocarcinoma and 10 patients with gallbladder cancer survived more than 5 years after extended surgery., Conclusion: PVE can be performed safely in patients with cholestatic liver, and it has a potential benefit for patients with advanced biliary cancer who are to undergo extended, difficult hepatectomy., (Copyright © 2012 S. Karger AG, Basel.)

Cholangiocarcinoma (CCA) is a highly metastatic tumor linked to liver fluke infection and consumption of nitrosamine-contaminated foods and is a major health problem especially in South-Eastern Asia. In search for a suitable chemopreventive agents, we investigated the effect of curcumin, a traditional anti-inflammatory agent derived from turmeric (Curcuma longa), on CCA development in an animal model by infection with the liver fluke Opisthorchis viverrini and administration of N-nitrosodimethylamine and fed with curcumin-supplemented diet. The effect of curcumin-supplemented diet on histopathological changes and survival were assessed in relation to NF-κB activation, and the expression of NF-κB-related gene products involved in inflammation, DNA damage, apoptosis, cell proliferation, angiogenesis and metastasis. Our results showed that dietary administration of this nutraceutical significantly reduced the incidence of CCA and increased the survival of animals. This correlated with the suppression of the activation of transcription factors including NF-κB, AP-1 and STAT-3, and reduction in the expression of proinflammatory proteins such as COX-2 and iNOS. The formation of iNOS-dependent DNA lesions (8-nitroguanine and 8-oxo-7,8-dihydro-2'-deoxyguanosine) was inhibited. Curcumin suppressed the expression of proteins related to cell survival (bcl-2 and bcl-xL), proliferation (cyclin D1 and c-myc), tumor invasion (MMP-9 and ICAM-1) and angiogenesis (VEGF), and microvessel density. Induction of apoptotic events as indicated by caspase activation and PARP cleavage was also noted. Our results suggest that curcumin exhibits an anticarcinogenic potential via suppression of various events involved in multiple steps of carcinogenesis, which is accounted for by its ability to suppress proinflammatory pathways., (Copyright © 2010 UICC.)

Hepatocellular carcinoma (HCC) has a poor prognosis when diagnosed in advanced stages. Patients with cirrhosis of any etiology are a clear risk group. Thus, to improve prognosis, these patients should be included in surveillance programs to detect HCC in the early phases. Ultrasonographic examination is recommended for this purpose. The imaging techniques currently available for characterization of focal liver lesions are dynamic ultrasound, magnetic resonance imaging (MRI) and computed tomography (CT). MRI and CT are also suitable to determine tumoral extension. This article reviews the role of imaging techniques in the diagnosis and study of extension of HCC and in assessment of tumoral response after treatment, according to tumoral stage at diagnosis and the clinical status of the patient., (Copyright © 2010 Elsevier España, S.L. All rights reserved.)

Aim: Cholangiolocellular carcinoma (CoCC) is currently considered to originate from hepatic progenitor cells. The purpose of this study was to evaluate the imaging features of cholangiolocellular carcinoma of the liver., Materials and Methods: Five cases of surgically resected cases of CoCC from 4 institutions were retrospectively evaluated. All of the five patients underwent contrast-enhanced dynamic CT. MRI and angio-CT including CT during arterioportography (CTAP) and CT during hepatic arteriography were performed in 3 and 2 patients, respectively. Histological evaluation was also performed and was correlated with radiographic findings., Results: On dynamic CT or MRI, the lesions presented hypervascular tumors with delayed washout in 2 cases and in the other 3 cases, the lesions showed peripheral enhancement with concentric delayed filling. On CTAP, the continued existence of portal veins or tiny spots of portal flow was identified in the tumors. Fibrous capsule or tumor necrosis was not observed., Conclusion: CoCC tumors have the dual imaging characteristics of hepatocellular carcinoma and cholangiocarcinoma. The absence of a fibrous capsule, the absence of tumor necrosis, peripheral location within the liver, and the presence of portal venous penetration within the tumor also appear to be characteristic features., (Copyright 2009 Elsevier Ireland Ltd. All rights reserved.)

Unlabelled: The aim of this study was to describe the imaging features by contrast-enhanced ultrasound (CEUS) of intrahepatic cholangiocarcinoma (ICC) in cirrhosis patients. We registered the CEUS images of cirrhosis patients with histologically confirmed ICC. In all cases magnetic resonance imaging (MRI) was done to confirm the diagnosis and/or staging purposes. A total of 21 patients met all the criteria to be included in the study. The median nodule size was 32 mm. All nodules showed contrast enhancement at arterial phase; in 10 cases it was homogeneous and in 11 cases peripheral (rim-like). All nodules displayed washout during the venous phases; it appeared during the first 60 seconds in 10 nodules, between 60-120 seconds in five cases, and in six cases after 2 minutes. Ten nodules (five larger than 2 cm) displayed homogeneous contrast uptake followed by washout and they correspond to the specific pattern of hepatocellular carcinoma according to the American Association for the Study of Liver Diseases criteria. However, none of these lesions displayed washout on MRI., Conclusion: CEUS should not be used as the sole imaging technique for conclusive hepatocellular carcinoma diagnosis and if the MRI does not display the diagnostic vascular pattern, a confirmatory biopsy is mandatory.

Aim: Evaluation of high resolution linear ultrasound and intra-operative linear contrast enhanced ultrasound (CEUS) and its benefit for the detection and characterization of tumor lesions., Material and Methods: Twenty patients were investigated preoperatively regarding tumor detection using CT (n = 8) or MRI (n = 12) and image fusion (VNav) (n = 3). All patients had surgery for their hepatic tumor (hepatocellular carcinoma (HCC), cholangiocellular carcinoma (CCC), metastasis, and adenoma). Ultrasound was performed intra-operatively first with B-scan using a convex probe. Than multifrequency linear transmitters (6-9 MHz, 6-15 MHz, LOGIQ E9, GE) were applied for B-scan, coulor coded Doppler sonography (CCDS) and Power Doppler followed by dynamic CEUS with Contrast Harmonic Imaging (CHI) after bolus injection of a maximum of 15 mL SonoVue®., Results: In 9 cases with the use of intra-operative CEUS additional tumor lesions (diameter 4-15 mm) could be detected and were histologically confirmed after surgical resection (7 cases) or intra-operative biopsy (2 cases). Using intraoperative CEUS 64 tumor lesions could be detected compared to 51 tumor lesions detected by preoperative CT or MRI (p < 0.05). Using the 6-15 MHz multifrequency linear transducer with CHI, arterial perfusion of adenomas, neuroendocrine metastases and HCC lesions was detectable. In 3 cases a resection was not achievable. Two of these cases were treated with radio frequency ablation (RFA). The other case had no curable option due to multifocal tumor manifestation., Conclusion: The intra-operative use of high-resolution linear transducer techniques with CEUS offers new diagnostic perspectives for an effective liver surgery.

Liver-intestine cadherin (LI-cadherin) represents a novel type of cadherin within the cadherin superfamily that comprises seven cadherin repeats and a short cytoplasmic domain. In this study, we first examined LI-cadherin expression immunohistochemically in 34 specimens of human intrahepatic cholangiocarcinoma (ICC). LI-cadherin expression was positive (defined as positivity in > or = 10% of cells) in 18 of the ICCs (52.9%). LI-cadherin negativity was significantly correlated with tumor dedifferentiation (P=0.026) and vascular invasion (P=0.015). The cumulative survival rate of patients with LI-cadherin-negative ICC was significantly shorter than that of patients with LI-cadherin-positive ICC (P=0.021). Multivariate analysis identified the extent of LI-cadherin staining as an independent prognostic factor for ICC survival (P=0.027). Next, to elucidate the mechanism of loss of LI-cadherin-mediated aggressiveness in ICC, we knocked down LI-cadherin expression in an ICC cell line using small interfering RNA (siRNA) technology, and screened for genes that were expressed differentially between these cells and ICC cells transfected with scrambled siRNA using microarray analysis with real-time polymerase chain reaction confirmation. Among 21 identified genes, we focused on metal-responsive transcription factor-1 (MTF-1), whose target genes might contribute to tumor aggressiveness. Expression of placental growth factor (PlGF), one of the MTF-1 target genes, was up-regulated in the ICC cells transfected with LI-cadherin siRNA. Likewise, PlGF expression was up-regulated in LI-cadherin-negative ICC specimens. There was a significant inverse relationship between these expressions (P=0.033). Furthermore, the microvessel density of LI-cadherin-negative ICC specimens was higher than that of LI-cadherin-positive specimens. These findings suggest that loss of LI-cadherin in ICC is associated with tumor dedifferentiation and vascular invasion, and thus poor prognosis. Loss of LI-cadherin results in up-regulation of MTF-1 and PlGF, thereby regulating angiogenesis in ICC.

Background: The present study aimed to elucidate the relationship between microvessel count (MVC) according to CD34 expression and prognosis in intrahepatic cholangiocarcinoma (ICC) patients who underwent hepatectomy based on our preliminary study., Methods: Relationships between MVC and clinicopathological factors were examined in 37 ICC patients. CD34 expression was analyzed using immunohistochemical methods., Results: Median MVC for ICC patients was 140/mm(2), which was applied as a cutoff value. Lower MVC was significantly associated with larger tumor size, periductal infiltrating type, and advanced Japanese tumor-node-metastasis stage (p < 0.05). Univariate survival analysis identified higher carcinoembryonic antigen level, periductal infiltrating type, poor histological differentiation, and lower MVC as significantly associated with lower 5-year survival rates. The 5-year survival rate in the higher-MVC group was significantly greater than that in the lower-MVC group (44% vs. 7%, p = 0.048). According to Cox multivariate survival analysis, only periductal infiltrating type on macroscopic examination was identified as a significant independent risk factor for poor survival after hepatectomy (risk ratio 4.8; p = 0.006), not MVC (1.1; p = 0.82)., Conclusion: Tumor MVC might offer a useful prognostic marker of ICC patient survival after hepatectomy and further investigation in a larger series is warranted.

Background/aims: Hepatic cholangiocarcinomas are tumors with poor prognosis and with increasing incidence worldwide. The aim of the study was to compare morphological features and protein profiles of hilar and peripheral cholangiocarcinomas., Methods: Clinicopathological data were collected from 111 cholangiocarcinomas (59 peripheral and 52 hilar). Protein expression, assessed on tissue samples using tissue microarray and protein array technologies, was compared between both types of tumors and with extrahepatic cholangiocarcinoma and hepatocholangiocarcinoma., Results: Hilar cholangiocarcinomas were smaller in size (mean: 2.7 vs. 8 cm, p<0.001), were more often well differentiated adenocarcinomas (65% vs. 36% well differentiated, p<0.01) and carried out stronger perineural invasion (83% vs. 42%, p<0.001) than peripheral cholangiocarcinomas. Regarding protein expression, hilar cholangiocarcinomas more often expressed MUC5AC (62% vs. 22%, p<0.0001), Akt2 (54% vs. 27%, p<0.001), CK8 (98% vs. 81%, p<0.005) and annexin II (92% vs. 66%, p<0.001). Interestingly, VEGF A expression was more frequently encountered in peripheral cholangiocarcinoma (69% vs. 25%, p<0.0001) and correlated with increased vascular density. Using protein array antibody, we identified filamin A as significantly overexpressed (>2-fold) in peripheral cholangiocarcinomas., Conclusions: Our results show that hilar and peripheral cholangiocarcinomas display specific protein profiles, especially regarding VEGF expression. This suggests a potential benefit for anti-angiogenic therapies in peripheral hepatic CCs.

Aims: To assess the relationship between arterial blood supply and the progression of intrahepatic cholangiocarcinoma (ICC)., Methods and Results: The intratumoral arterial vessel density (AVD) was assessed in 76 cases of mass-forming type of ICC using anti-h-caldesmon antibody, a marker of smooth muscle cells, and AVD compared with pathological findings. AVD was directly correlated with the presence of intratumoral portal tracts (P < 0.0001) and inversely correlated with the grade of tumour necrosis (P = 0.0013). AVD was inversely correlated with vascular invasion and lymph node metastasis (P = 0.0159 and P = 0.0023, respectively). The hilar type of ICC had lower AVD regardless of tumour size, whereas the peripheral type with high AVD showed branching ductular formation composed of cuboidal cells with mild nuclear atypia. AVD was found to be an independent prognostic factor on multivariate survival analysis (P = 0.0013)., Conclusions: This study demonstrates that intratumoral arterial vessels reflect engulfed portal tracts in ICC and decreased arterial vessels indicate aggressive tumour behaviour. Our results could contribute to clinical tumour staging and more effective therapy.

Accurate diagnosis of local invasion of hilar cholangiocarcinomas is challenging due to their small size and the anatomic complexity of the hepatic hilar region. On the other hand, the correct diagnosis of local invasion is essential for assuring the possibility of curative surgery. The purpose of this study was to evaluate the feasibility of four-channel multidetector-row computed tomography (MDCT) in the assessment of vascular and bile duct involvement, by which we could obtain useful information for the surgical management of hilar cholangiocarcinoma. The subjects were 18 patients for whom the extent of tumor invasion was surgically and pathologically confirmed. All patients underwent preoperative multiphasic CT scanning by MDCT. Arterial and portal dominant phases were acquired using a detector configuration of 1.25 mm X 4 mm, and both axial and multiplanar reconstructed images were interpreted. Longitudinal extension was evaluated up to second-order branches. Vascular invasion is considered to be the degree of tumor contiguity to the hepatic arteries and portal vein and was graded by CT. The longitudinal extension was correctly diagnosed in 14 patients (77.8%). Hepatic artery invasion was correctly diagnosed in 17 patients with sensitivity of 100% and specificity of 90%, respectively. Portal vein invasion was correctly diagnosed in 47 of 51 branches with sensitivity and specificity of 92.3% and 90.2%, respectively. Multiplanar reconstructed images contributed to the correct diagnosis for both vascular encasement and longitudinal tumor extension. In conclusion, MDCT is useful in preoperative evaluation of hilar cholangiocarcinoma, especially when combined with multiplanar reconstructed images.

Aim: Common enhancement pattern of intrahepatic cholangiocarcinoma (ICC) on computed tomography (CT) is that of hypovascular enhancement; however, in some cases, tumor shows identical enhancement in the arterial phase to that in hepatocellular carcinoma. To identify the specific characteristics of different enhancement patterns, we examined the relationship between CT enhancement pattern and clinicopathological features or postoperative prognosis., Method: Subjects were 43 consecutive ICC patients who had undergone hepatectomy. Enhancement patterns were divided into two types: hypovascular or delayed enhancement (Type A), and early enhancement in the arterial phase (Type B)., Results: Type A enhancement was observed in 23 patients and Type B in 20. Accompanying chronic viral hepatitis was significantly more frequent in Type B than Type A. Well-differentiated adenocarcinoma was significantly more frequent in Type B than Type A. Multiple tumors were significantly more frequent in Type A than Type B. Japanese TNM stage I and II was more frequent in patients with Type B than those with Type A. Disease-free or overall survival was significantly better in patients with Type B than those with Type A., Conclusion: Early enhancement in the arterial phase might be a useful indicator of lower malignant potential and better survival in ICC patients., ((c) 2008 Wiley-Liss, Inc.)

Intrahepatic cholangiocarcinoma account for 13% of annual cancer-related deaths worldwide and for 3% in the USA. Patient with unresectable disease can benefit from palliative therapies such as systemic chemotherapy. However, the only curative treatment for intrahepatic cholangiocarcinoma is complete surgical resection with histologically negative resection margins.

Objective: To evaluate the effects of selective hepatic vascular exclusion (SHVE) on prevention of serious hemorrhage and air embolism during hepatectomy and on the liver function after operation., Methods: From January 2004 to March 2007, 29 huge hepatic tumors were resected in our department. Both SHVE and Pringle maneuver were used to control the blood loss during hepatectomy. They were divided into two groups: SHVE group (15 cases) and Pringle group (14 cases). Data regarding the intraoperative and postoperative courses of the patients were analyzed., Results: There was no significant difference between the two groups regarding the age, sex, tumor size, cirrhosis, HbsAg positive rate and operating time (P > 0.05). Intraoperative blood loss was reduced significantly in the SHVE group (P < 0.05). The serum prealbumin levels on the postoperative day 1, 3 and 7 in SHVE group were significantly higher than those in the Pringle group (P < 0.05). The serum ALT value in SHVE group was significantly lower than that in the Pringle group on postoperative day 1, 3 and 7. The mean drainage volume in SHVE group was significantly less than that in the Pringle group on postoperative day 1 and 2. Liver failure occurred in two cases of the Pringle group, while no one in the SHVE group. Rupture of hepatic vein with massive blood loss occurred in 3 cases and air embolism in one case of the Pringle group, but did not occur in any case of the SHVE group., Conclusion: When the selective exclusion of hepatic outflow and inflow is applied in hepatectomy, the resection rate of huge hepatic tumors and operative tolerance of hepatectomy are improved. It is a safe and rational operation type, and provides an optimal choice for hepatectomy.

Purpose: To retrospectively evaluate the performance of breath-hold contrast-enhanced 3D dynamic parallel gradient echo MRI (pMRT) for the characterization of focal liver lesions (standard of reference: histology) and for the analysis of hepatic vasculature (standard of reference: contrast-enhanced 64-detector row computed tomography; MSCT) in a single MRI session., Materials and Method: Two blinded readers independently analyzed preoperative pMRT data sets (1.5T-MRT) of 45 patients (23 men, 22 women; 28 - 77 years, average age, 48 years) with a total of 68 focal liver lesions with regard to image quality of hepatic arteries, portal and hepatic veins, presence of variant anatomy of the hepatic vasculature, as well as presence of portal vein thrombosis and hemodynamically significant arterial stenosis. In addition, both readers were asked to identify and characterize focal liver lesions. Imaging parameters of pMRT were: TR/TE/matrix/slice thickness/acquisition time: 3.1 ms/ 1.4 ms/ 384 x 224 / 4 mm/ 15 - 17 s. MSCT was performed with a pitch of 1.2, an effective slice thickness of 1 mm and a matrix of 512 x 512., Results: Based on histology, the 68 liver lesions were found to be 42 hepatocellular carcinomas (HCC), 20 metastases, 3 cholangiocellular carcinomas (CCC) as well as 1 dysplastic nodule, 1 focal nodular hyperplasia (FNH) and 1 atypical hemangioma. Overall, the diagnostic accuracy was high for both readers (91 - 100 %) in the characterization of these focal liver lesions with an excellent interobserver agreement (kappa-values of 0.89 [metastases], 0.97 [HCC] and 1 [CCC]). On average, the image quality of all vessels under consideration was rated good or excellent in 89 % (reader 1) and 90 % (reader 2). Anatomical variants of the hepatic arteries, hepatic veins and portal vein as well as thrombosis of the portal vein were reliably detected by pMRT. Significant arterial stenosis was found with a sensitivity between 86 % and 100 % and an excellent interobserver agreement (kappa = 0.85)., Conclusions: Diagnostic image quality remains good or excellent in most cases when the data acquisition time is accelerated by means of parallel imaging in dynamic MRI. It allows reliable detection and characterization of focal liver lesions as well as the depiction of hepatic vascular variants, portal vein thrombosis, and arterial stenosis. Introducing pMRT in routine liver MRI may be another step towards a simplified diagnostic work-up prior to liver surgery.

Background/aims: In advanced cancers of hepatobiliary and pancreatic lesions, major vascular resection and reconstruction are necessary to accomplish curative resection, which may provide better patient outcomes., Methodology: Surgical records, morbidity and mortality, and prognosis were examined in patients with combined vascular resection. Thirty-six patients underwent 18 hepatectomies and 18 pancreatectomies., Results: In 18 patients who underwent hepatic resection, the resected vessels were the portal vein (PV) in 10, vena cava or hepatic vein in 9 and right hepatic artery (RHA) in 3. An artificial graft was used in 2 to replace the vena cava. Vascular bypass was performed in 5 patients. Morbidity was due to biliary stricture in 1 patient and adult respiratory distress syndrome in another who died during hospital stay. Fourteen (82%) had cancer recurrence, of whom 12 died of cancer, one died of other disease, and 2 survived cancer-free. The 5-year survival was 28%. In 18 patients who underwent pancreatectomy, resected vessels were PV in 18 and RHA in 1. An artificial graft was used in 3 and vascular passive bypass was performed in 6. One patient died of sepsis after total pancreatectomy during hospital stay. Eleven (64%) had cancer recurrence, of whom 11 died of cancer, 2 died of other disease, and 4 survived cancer-free. The 3-year survival was 27%., Conclusions: Complete surgical resection (R0) combined with main vascular resection could be safely performed in many patients with disease of the hepatobiliary and pancreas, which achieved longer survival in some patients even in the advanced stage.

The clinical application of portal vein embolization (PVE) has contributed to improving the postoperative outcome of hilar cholangiocarcinoma. The enlarged nonembolized lobe after PVE protects the patient from postoperative hepatic failure, due to the increased functional reserve, and shortens the hospital stay. Although numerous reports have shown beneficial effects of PVE on postoperative outcome after extended hepatectomy, no randomized controlled study has been performed so far. It is urgent to establish a "gold standard" of PVE, because the indications, approach to the portal vein, types of embolic materials, and methods used to evaluate the function of the future liver remnant are variable among institutions. The indications and procedures of PVE for hilar cholangiocarcinoma may be different from those for hepatocellular carcinoma or colorectal metastasis, because, in many patients with hilar cholangiocarcinoma, biliary cancer is associated with biliary obstruction and cholangitis. This review article summarizes the contribution of PVE to the outcome of postoperative management in patients with hilar cholangiocarcinoma needing extended hepatectomy. We also describe our PVE procedure, which has been established from our experience of more than 240 cases of biliary cancer. Furthermore, the drawbacks of PVE, which may reduce the pool of candidates for surgery, are also discussed.

Background: Maspin, a member of the serpin family, is a suppressor of tumor growth, an inhibitor of angiogenesis and an inducer of apoptosis. Maspin induces apoptosis by increasing Bax, a member of the Bcl-2 family of apoptosis-regulating proteins. In this exploratory study, we investigated the associated expression of Maspin and Bax proteins as a potential prognostic factor in intrahepatic cholangiocarcinoma (IHCCA)., Methods: Twenty-two paraffin-embedded samples were analyzed by immunohistochemical methods using Maspin, Bax and CD34 antibodies. Maspin was scored semiquantitatively (HSCORE). Apoptosis was assessed using an antibody against cleaved caspase-3., Results: The strong relationship observed between the expression of Maspin and Bax, indicates that Bax is likely to be the key effector of Maspin-mediated induction of apoptosis as indicated by the activation of cleaved caspase-3. We categorized Maspin HSCORE by calculating the optimal cutpoint. A Maspin HSCORE above the cutpoint was inversely related with tumor dimension, depth of tumor and vascular invasion. Uni/multivariate analysis suggests that a Maspin HSCORE below the cutpoint significantly worsens the patients' prognosis. Tumors with Maspin HSCORE below the cutpoint had a shorter survival (11+/-5 months) than did patients with Maspin HSCORE above the cutpoint (27+/-4 months), whereas Kaplan-Meier analysis and logrank test showed no significant difference in overall survival between the patients., Conclusion: The associated expression of Maspin and Bax might delay tumor progression in IHCCA. Maspin above the cutpoint might counteract tumor development by increasing cell apoptosis, and by decreasing tumor mass and cell invasion. The combined expression of Maspin and Bax appears to influence the susceptibility of tumor cholangiocytes to apoptosis and thus may be involved in delaying IHCCA progression.

Angiogenesis in cholangiocellular carcinoma (CCC) has rarely been investigated. The aim of this study was to determine the angiogenesis status of CCC and assess its relationship with angiogenic factors and clinicopathological characteristics. We examined 33 surgically resected CCC specimens. Tumor angiogenesis was assessed by microvessel density (MVD) using the anti-CD34 antibody, and the expression of VEGF, Ang-1, Ang-2, and TSP-1 was determined by immunohistochemistry. The mean (+/- SD) MVD was 87.2+/-52.6/mm2 (range, 0-229/mm2). A total of 75.6% cases were positive for VEGF expression, 36% for Ang-1, 57.6% for Ang-2 and 45.5% for TSP-1. VEGF and Ang-2 expression was associated with a significantly higher level of MVD (p=0.004 and 0.015, respectively). TSP-1 expression was associated with a significantly lower level of MVD (p=0.005) and a higher level of intrahepatic metastasis (46.7% vs. 5.6%, p=0.012). There was no significant correlation between VEGF, Ang-1, Ang-2, and TSP-1 expression and tumor size, capsule formation, infiltration of capsule, portal vein invasion, intrahepatic metastasis or CCC differentiation. There was no significant correlation between MVD levels, VEGF, Ang-1, Ang-2, and TSP-1 expression and postoperative survival. A considerable degree of angiogenesis, comparable to that of other solid tumors, was observed in CCC. VEGF and Ang-2 might play a proangiogenic role, and TSP-1 may play an inhibitory role in CCC. Although TSP-1 may increase intrahepatic CCC metastases, neither MVD levels nor the expression of VEGF, Ang-1, or Ang-2 was associated with clinicopathological factors and prognosis.

Objective: To assess clinical benefit of portal vein embolization (PVE) before extended, complex hepatectomy for biliary cancer., Summary Background Data: Many investigators have addressed clinical utility of PVE before simple hepatectomy for metastatic liver cancer or hepatocellular carcinoma, but few have reported PVE before hepatectomy for biliary cancer due to the limited number of surgical cases., Methods: This study involved 240 consecutive patients with biliary cancer (150 cholangiocarcinomas and 90 gallbladder cancers) who underwent PVE before an extended hepatectomy (right or left trisectionectomy or right hepatectomy). All PVEs were performed by the "ipsilateral approach" 2 to 3 weeks before surgery. Hepatic volume and function changes after PVE were analyzed, and the outcome also was reviewed., Results: There were no procedure-related complications requiring blood transfusion or interventions. Of the 240 patients, 47 (19.6%) did not undergo subsequent hepatectomy. The incidence of unresectability was higher in gallbladder cancer than in cholangiocarcinoma (32.2% versus 12.0%, P < 0.005). The remaining 193 patients (132 cholangiocarcinomas and 61 gallbladder cancers) underwent hepatectomy with resection of the caudate lobe and extrahepatic bile duct (n = 187), pancreatoduodenectomy (n = 42), and/or portal vein resection (n = 63). Seventeen (8.8%) patients died of postoperative complications: mortality was higher in gallbladder cancer than in cholangiocarcinoma (18.0% versus 4.5%, P < 0.05); and it was also higher in patients whose indocyanine green clearance (KICG) of the future liver remnant after PVE was <0.05 than those whose index was >or=0.05 (28.6% versus 5.5%, P < 0.001). The 3- and 5-year survival after hepatectomy was 41.7% and 26.8% in cholangiocarcinoma and 25.3% and 17.1% in gallbladder cancer, respectively (P = 0.011). In 136 other patients with cholangiocarcinoma who underwent a less than 50% resection of the liver without PVE, a mortality of 3.7% and a 5-year survival of 27.6% were observed, which was similar to the 132 patients with cholangiocarcinoma who underwent extended hepatectomy after PVE., Conclusions: PVE has the potential benefit for patients with advanced biliary cancer who are to undergo extended, complex hepatectomy. Along with the use of PVE, further improvements in surgical techniques and refinements in perioperative management are necessary to make difficult hepatobiliary resections safer.

Background: The remnant left liver after right hepatectomy tends to rotate spontaneously into the right subphrenic space. This rotation might induce venous outflow impairment. The aim of this study was to assess immediate venous outflow in the left hepatic vein by intraoperative Doppler ultrasound (US) according to the position of the remnant liver., Methods: From August 2003 to February 2004, assessment of left hepatic venous outflow was systematically performed in 44 consecutive right hepatic resections by Doppler US in spontaneous and anatomical positions. The anatomical position was defined as the position in which the falciform ligament was in its strict median position., Results: The placement of the left liver from the spontaneous position to the anatomical position resulted in a significant increase in left hepatic venous outflow (20.1 +/- 5.7 versus 8.5 +/- 4.4 cm/s; P < 0.0001). In the spontaneous position, the decrease in left hepatic venous outflow persisted even without division of the left triangular ligament (10.2 +/- 5.4 versus 21.7 +/- 5.3 cm/s in the anatomical position) or removal of the middle hepatic vein (8.4 +/- 3.4 versus 21.3 +/- 5.8 cm/s)., Conclusion: : Results of this study strongly suggest that after right hepatectomy the remnant left liver should always be fixed in the anatomical position., (Copyright (c) 2005 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)

Aim: High levels of serum sialyl Lewis(a) (sLea) are frequently found in cholangiocarcinoma (CCA) patients and have been suggested to be a serum marker for CCA. However, the significance of this antigen in CCA is unknown. In this study, the clinical significance of sLea expression in CCA tissues and the possible role of sLea in vascular invasion in vitro were elucidated., Methods: Expression of sLea in tumor tissues of 77 patients with mass-forming CCA and 33 with periductal infiltrating CCA was determined using immunohistochemistry. The in vitro assays on adhesion and transmigration of CCA cells to human umbilical vein endothelial cells were compared between CCA cell lines with and without sLea expression., Results: sLea was aberrantly expressed in 60% of CCA tumor tissues. A significant relationship was found between the frequency of sLea expression and the mass-forming type CCA (P = 0.041), well differentiated histological grading (P = 0.029), and vascular invasion (P = 0.030). Patients with positive sLea expression had a significantly poorer prognosis (21.28 wk, 95% CI = 16.75-25.81 wk) than those negative for sLea (37.30 wk, 95% CI = 27.03-47.57 wk) (P<0.001). Multivariate analysis with adjustment for all covariates showed that patients positive for sLea possessed a 2.3-fold higher risk of death than patients negative for sLea (P<0.001). The role of sLea in vascular invasion was demonstrated using in vitro adhesion and transmigration assays. KKU-M213, a human CCA cell-line with a high expression of sLea, adhered and transmigrated to IL-1beta-activated endothelial cells of the human umbilical vein more than KKU-100, the line without sLea expression (P<0.001). These processes were significantly diminished when the antibodies specific to either sLea or E-selectin were added to the assays (P<0.001)., Conclusion: This study demonstrates the clinical significance of sLea expression in vascular invasion, and an unfavorable outcome in CCA. The role of sLea in vascular invasion which may lead to poor prognosis is supported by the in vitro adhesion and transmigration studies.

A 45-years-old patient with recurrent intrahepatic cholangiocarcinoma 3 years after resection is described. 2 sessions of percutaneous radiofrequency ablation (RFA) were performed and complete destruction of the tumor was achieved. The patient was followed-up for 15 months by means of power-Doppler, CT and tumor markers. No local or heterotopic recurrences were observed. The case demonstrates the possibilities of RFA in the management of postoperative recurrences of intrahepatic cholangiocarcinoma and confirms the significance of the method in the complex approach to the liver tumors.

Background/aims: To understand the three-dimensional relationship between the liver vasculature and tumor by intraoperative sonography, some training is inevitable. Three-dimensional ultrasound has been evaluated in various fields, but not yet in intraoperative sonography., Methodology: Extracorporeal 3-D ultrasonography was performed in 32 patients. Of these, 20 underwent intraoperative 3-D ultrasonography. Using these images, we evaluated whether or not the portal vein, hepatic vein and its branches were discernible., Results: Satisfactory images were obtained in all 32 patients by extracorporeal methods and in 15 by intraoperative 3-D ultrasonography. The number of visualized veins, including the right portal vein, its anterior branch, posterior branch, anterior superior branch, anterior inferior branch and right hepatic vein, was 32, 32, 23, 28, 22, and 30 by extracorporeal 3-D ultrasonography, and 15, 14, 10, 8, 5, and 12 by intraoperative 3-D ultrasonography. The relationships between the intrahepatic artery, portal vein, and hepatic vein were more clearly visualized by intraoperative 3-D sonography., Conclusions: Intraoperative 3-D ultrasonography clearly showed small branches of the liver vasculature and their 3-D relation, which may be helpful for liver surgery. However, this method requires further improvement.

Background: We determined the radiologic characteristics of intrahepatic cholangicarcinoma (ICC) on single-level dynamic computed tomography during hepatic arteriography (CTHA) and assessed the hemodynamics of the tumor., Methods: Eleven patients with pathologically confirmed ICC underwent single-level dynamic CTHA. After placing the catheter tip in the proper hepatic artery and running a 30-s continuous scan, scanning was performed every 15 or 30 s for 120 s. The change of contrast-enhancement pattern of the ICCs were interpreted retrospectively., Results: The pattern of enhancement was classified into two types: vascular and hypovascular. In the vascular type, the contrast enhancement gradually spread from each intratum oral artery and became mottled. It changed from a mottled and hypoattenuated pattern to an even and hyperattenuated appearance in comparison with the adjacent liver approximately 120 s after the injection of contrast agent. In the hypovascular type, the tumor was barely enhanced and remained hypoattenuated compared with the adjacent liver at 120 s after the beginning of the injection. The 11 ICCs were classified into eight vascular types and three hypovascular types. Intratumoral arteries were visualized in nine tumors: eight vascular types and one hypovascular type., Conclusion: The contrast-enhancement pattern of ICC on single-level dynamic CTHA is related to the intratumoral artery.

Background: The aim of this study was to clarify prognostic factors and recurrence patterns in patients with node-negative intrahepatic cholangiocarcinoma (IHCC)., Methods: A retrospective study was performed to review prognostic factors and recurrence patterns (1) in 22 patients with node-negative IHCC after curative hepatic resection and (2) in 49 patients who underwent resection and lymph node dissection for IHCC. In addition to determining the clinicopathologic factors, the investigators also performed immunohistochemical examination of microvessel counts using antihuman CD-31 and antibody., Results: The significant poor prognostic factors in node-negative IHCC were the presence of intrahepatic metastasis, portal vein invasion of cancer cells, and high microvessel counts. After multivariate analysis was conducted, the independent poor prognostic factors were the presence of intrahepatic metastases and high microvessel counts. Of 9 patients who had postoperative recurrence of their disease, intrahepatic recurrence was observed in 7 (78 %)., Conclusions: The factors linked to poor prognosis in IHCC were tumor angiogenesis and the presence of intrahepatic metastasis. Because intrahepatic recurrence was common, regional and adjuvant chemotherapy to the liver may improve the outcome of patients with these risk factors and node-negative IHCC.

Multiplanar volume rendering and maximum intensity projection of multislice computed tomography data allow for robust evaluation of the hepatic parenchyma, with early detection of neovascularity and tumor stain, and enable better assessment of the tumor burden compared with routine axial images. Lesion characterization can also potentially improve. This is in addition to accurate delineation of the hepatic vascular anatomy, which allows for segmental localization and assists in surgical and nonsurgical planning.

Aim: To evaluate the characterization of liver hemangiomas and malignant tumors using power Doppler sonography before and after intravenous injection of a sonocontrast agent., Methods: Forty-five patients with 57 liver tumors (22 hemangiomas, 24 metastases, 10 hepatocellular carcinomas (HCC) and one cholangiocellular carcinoma) were examined prospectively. The distribution (peripheral, central, mosaic) and extent (none, minimal, moderate and strong) of intratumoral flow pattern in each sonographic examination was subjectively classified., Results: The administration of the sonocontrast agent by bolus injection caused enhancement to gradually increase up to 2 min and lasted for 4-5 min. After injection of contrast agent, flow signals appeared or increased in 34 tumors. No signal enhancement was observed in 18 hemangiomas, four metastases and one HCC. The sensitivity and specificity of intratumoral vascularity for the detection of malignant liver tumors was 37.1 and 90.9% for unenhanced power Doppler sonography, and 85.7 and 81.8% for contrast-enhanced power Doppler sonography, respectively., Conclusion: Contrast-enhanced power Doppler sonography is superior to unenhanced power Doppler sonography in the demonstration of malignant tumor vascularity, and is helpful in differentiating between hemangiomas and malignant liver tumors. A specific flow pattern within the tumor is not established in primary and metastatic malignant tumors with contrast-enhanced power Doppler sonography., (Copyright 2003 Blackwell Publishing Asia Pty Ltd)

A 70-year-old man presented with a mass-forming perihilar cholangiocarcinoma in his left liver, and both the portal trunk and proper hepatic artery were involved by the tumor. We performed a hepato-ligamento-pancreatoduodenectomy (HLPD), including an extended left lobectomy with a caudate lobectomy, and the external iliac vein graft was harvested for portal vein reconstruction while the right middle colic artery was anastomosed to the right posterior hepatic artery. Vascular involvement (portal vein and hepatic artery) and peripancreatic lymph node metastases were proven histologically. Although the liver abscess and pancreatic fistula both occurred postoperatively, the patient is now healthy and still alive 3 years 9 months after surgery without recurrence. We consider that the absence of para-aortic lymph node metastases and hepatic invasion which is not involved beyond the second order of the hepatic ducts in the future remnant liver might therefore have contributed to the satisfactory outcome after performing HLPD in this case.

Arterial chemoinfusion therapy through an implanted port system was performed for patients with unresectable intrahepatic cholangiocarcinoma (ICC). Eleven patients with unresectable ICC were studied. Seven patients had stage-IV disease, two had stage-III disease, and two had stage-II disease. The mean tumor size was 7.0+/-2.6 cm (range 3.8-13.5 cm). A catheter and port system was percutaneously implanted, and anticancer drugs featuring fluorouracil were administered via the infusion system every 1-2 weeks on the outpatient basis in all patients except 2. Arterial chemoinfusion therapy was repeated 12-84 times per patient (mean 51 times). Partial and minor responses were achieved in sevenents (64%). Disease was stable in two patients (18%), and progressed in the other two patients (18%). Tumor growth was controlled during a mean period of 14.5 months in seven responders and two patients with stable disease. The survival rates were 91% at 1 year, 51% at 2 years, 20% at 3 years, and 10% at 4 years, respectively. The mean survival period was 26 months. Toxicity such as cholangitis and pancytopenia was found in three patients (27%). This treatment seems to improve the prognosis of patients with unresectable ICC and deserves further studies.

Thymidine phosphorylase (TP), an important regulator of angiogenesis, is correlated with progression, metastasis, and prognosis in various types of tumor. In contrast, both positive and negative effects of thrombospondin-1 (TSP-1) on angiogenesis have been reported. In the present study, we examined the expression of TP and TSP-1 in carcinoma cells in 67 primary intrahepatic cholangiocarcinomas (ICCs) immunohistochemically and its correlation with angiogenesis, clinicopathological features, and prognosis. Twenty-six (38.8%) cases were classified as exhibiting positive TP expression. TP expression showed a significant correlation with vascular invasion, lymphatic permeation, perineural invasion, and lymph node metastasis. Thirty-four (50.7%) cases were classified as exhibiting positive TSP-1 expression. TSP-1 expression was significantly correlated with only lymphatic permeation. The microvessel count in positive TP expression cases was significantly higher than that in negative cases. In contrast, the microvessel count in negative TSP-1 expression cases was significantly higher than that in positive cases. Survival in patients who were positive for both TP and TSP-1 expression was significantly poor. Our results suggest that the increased TP expression and decreased TSP-1 expression contribute to angiogenesis, but that the role of angiogenesis in ICC is not closely related to tumor aggressiveness. The TP and TSP-1 expression in ICC may enhance tumor aggressiveness.

Background: The objective of this study was to analyze the clinicopathologic variables and the postoperative outcome in patients with mass-forming intrahepatic cholangiocarcinoma (ICC) to identify important factors for predicting postresection prognosis. Although it has been reported that mass-forming ICC has a different etiology and biologic features compared with hepatocellular carcinoma (HCC), patients with ICC have been dealt with clinicopathologically in the same manner as patients with HCC., Methods: Sixty patients who underwent hepatectomy for mass-forming ICC with curative intent between 1981 and 1999 were studied. Fourteen preoperative clinical and diagnostic parameters and 12 postoperative surgicopathologic parameters were analyzed., Results: The rate of operative mortality in this patient cohort was 5%, and the overall 1-year, 3-year, and 5-year survival rates were 68%, 35%, and 29%, respectively, with a median survival of 19.6 months. A multivariate analysis revealed that independent negative prognostic factors were 1) hepatic regional lymph node metastasis, 2) multiple tumor presentation, 3) symptomatic tumor, and 4) the presence of vascular invasion. Using these factors, a new staging system was devised: Stage I disease was defined as a solitary tumor without vascular invasion, Stage II disease was defined as a solitary tumor with vascular invasion, Stage IIIA disease was defined as multiple tumors with or without vascular invasion, Stage IIIB disease was defined as any tumor with regional lymph node metastasis, and Stage IV disease was defined as any tumor with distant metastases. The Kaplan-Meier estimated 3-year survival rate and the median survival for each subgroup were 74% for patients with Stage I disease (median survival is the time when the cumulative survival rate of some patients' group declined to 50%; thus, the median survival could not be calculated in patients with Stage I disease because survival was 74% at the latest follow-up), 48% and 26.2 months for patients with Stage II disease, 18% and 16.8 months for patients with Stage IIIA disease, and 7% and 11.2 months for patients with Stage IIIB disease, respectively (P < 0.0001). None of the patients met the criteria for Stage IV disease., Conclusions: The current results support the use of a new staging system for patients with ICC that is simple and predicts well the differences in survival after patients undergo hepatic resection., (Copyright 2001 American Cancer Society.)

Background: The purpose of our study was to evaluate the imaging features and patterns of contrast enhancement in peripheral cholangiocarcinomas with computed tomography (CT) and correlate these features with histologic findings when available., Methods: We reviewed the CT scans of 24 patients with 25 peripheral cholangiocarcinomas proved by orthotopic liver transplantation (n = 1), liver resection (n = 7), percutaneous needle biopsy (n = 10), and fine needle aspiration biopsy (n = 6). Incremental dynamic nonhelical CT was performed in four cases and helical CT in 21 cases. Portal venous phase images were obtained in all 25 cases. Fourteen patients underwent helical CT during arterial and portal phases. Delayed images were obtained in 20 patients., Results: The size of the tumors ranged from 1.2 to 17 cm. Bile duct dilatation was present in 13 patients (52%), and regional lymph node enlargement was observed in six patients (24%). Retraction of the liver capsule was present in nine patients (36%). In eight patients (32%), satellite nodules were also detected. All tumors were globally hypodense during the portal phase. In 14 patients (70%), delayed images disclosed hyperattenuating tumors. Rimlike contrast enhancement was the most frequent pattern observed in either arterial (57% of patients) or portal (60% of patients) phase imaging. Portal venous encasement was seen in 10 patients (40%)., Conclusion: In the proper clinical setting, detection of a hypodense hepatic lesion with peripheral enhancement, biliary dilatation, and contrast enhancement on delayed images are highly suggestive of peripheral intrahepatic cholangiocarcinoma.

Purpose: The objective of this study was to determine the usefulness, safety and acceptance of a new technique of percutaneous implantation of port-catheter-systems (PIPS) for locoregional intraarterial chemotherapy of the liver., Material and Methods: In 50 patients with malignant hepatic disease, 52 percutaneously implantable port-catheter systems were implanted for intraarterial chemotherapy of the liver as an interventional radiological technique. A commercially available angiographic catheter was placed in the hepatic artery under fluoroscopic control via a transfemoral approach and connected to a Port-A-Cath situated in the groin. This procedure was done on an outpatient basis; no medical treatment was administered., Results: Percutaneous placement of the port-catheter system was successful in all cases, also in those with a hepatomesenteric trunk. No peri- and post-interventional complications occurred. The median patency was 312 days (13-547 days). The catheter-related complication rate was 12%. The function could be restored by replacement or an interventional procedure in all but one case (2%). Infection and leakage did not occur. The system had been withdrawn without complications in 7/52 cases for a variety of reasons (e.g. hemihepatectomy, desire of the patient or clinician, dissection after intervention, replacement)., Conclusion: Percutaneous placement of a port-catheter system is a safe and easy alternative to the surgical placement of port systems for hepatic intraarterial chemotherapy. Long-term complication rates are comparable. The option of easy withdrawal and interventional correction of dysfunction as well as lower costs are additional advantages.

Purpose: To define the hemodynamic features of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma by using quadruple phase helical computed tomography (CT) and determine the value of this information in characterizing tumors., Materials and Methods: Helical CT of the liver was performed in 45 patients with newly diagnosed HCC or peripheral cholangiocarcinoma. Scans were obtained before and 25 seconds, 70 seconds, and 2-6 minutes after the start of the contrast material injection. The intensity and spatial distribution of contrast material uptake were evaluated during all phases. Time-attenuation curves were established for each lesion. Relative attenuation and lesion conspicuity were assessed. A diagnostic confidence level was assigned to each lesion., Results: In the majority of HCC lesions, a single, early peak of enhancement followed by a continuous decrease in tumor attenuation over time was seen. The greatest tumor conspicuity occurred during the delayed phase. In cholangiocarcinoma, tumor attenuation increased during the delayed phase. In the majority of lesions, the greatest tumor conspicuity was seen during the portal venous phase. In both tumor types, the diagnostic confidence level improved when the delayed phase was used., Conclusion: The variation over time in the intensity of contrast enhancement in HCC and cholangiocarcinoma differs sufficiently to make this a useful diagnostic criterion. The delayed phase is particularly important because it amplifies this difference.

Purpose: The aim of this study was to evaluate whether intravenous injection of an ultrasound contrast agent aids in the visualization of focal liver lesions on power Doppler images., Methods: Fifty patients with focal liver lesions were studied by B-mode and power Doppler sonography before and after intravenous injection of the contrast agent Levovist (galactose-based microbubbles; 10 ml of a concentration of 300 mg/ml). Thirty-two patients had malignant liver lesions (19 metastases, 12 hepatocellular carcinomas, 1 cholangiocellular carcinoma), while 18 had benign lesions (12 hemangiomas, 2 focal nodular hyperplasias, 4 others)., Results: After contrast medium injection, the number of lesions with no intralesional flow dropped from 18 to 9. Flow signal intensity was rated subjectively as marked on contrast-enhanced images in 17 patients; only 4 patients had marked flow on precontrast images. On precontrast studies, central flow in 10 lesions and peripheral flow in 29 lesions could be observed. After enhancement, the numbers increased to 18 and 34 lesions, respectively., Conclusions: On power Doppler images, a greater number of intratumoral vessels are seen in focal liver lesions after contrast medium administration.

Two rare cases of small intrahepatic cholangiocarcinoma with marked hypervascularity are reported. Dynamic computed tomographic and magnetic resonance images of the two cases revealed strong enhancement of the whole tumor on the early phase and prolonged enhancement on the late and delayed phases. In both cases, the tumors turned out to be well-differentiated tubular cholangiocarcinoma that contained a large number of tumor cells and few interstitial fibrous tissues. These results suggest that some intrahepatic cholangiocarcinoma should be differentiated from other hypervascular hepatic tumors, especially hepatocellular carcinoma, and that prolonged enhancement of the tumor on late and delayed phases of dynamic images could be of diagnostic value.

Cholangiocarcinoma (CCC) is relatively hypovascular, in contrast to hepatocellular carcinoma (HCC), which is often highly vascular. We investigated if the diminished vascularity of CCC is related to altered expression of thrombospondin-1 (TSP-1), an antiangiogenic factor, and/or vascular endothelial growth factor (VEGF), a potent angiogenic factor, comparing the relationships with those of high- and low-vascular HCC. We also investigated the relationship between the mutation of the p53 gene and TSP-1 expression or VEGF expression. Northern blot analysis and immunohistochemical staining were performed on surgically resected human CCC and HCC. The ratios of TSP-1 mRNA level in cancer cells versus adjacent noncancerous cells (T/N ratios) were significantly higher in CCC (n = 11) than in HCC with high vascularity (n = 15). In contrast, T/N ratios of VEGF mRNA level in CCC (n = 11) were comparable with those in HCC with low vascularity (n = 5). In CCC, the cancer cells and fibroblasts were positively stained with anti-TSP-1 antibody. We observed that T/N ratios of VEGF mRNA level, but not those of the TSP-1 mRNA level, were significantly correlated with vascularity in HCC. The relative increase in TSP-1 and the relative decrease in VEGF in tumors compared with normal tissue may underlie the limited angiogenesis of CCC. The p53 gene did not affect the expression of TSP-1 in CCC or VEGF in HCC.

Objective: This study was conducted to determine whether an immediate change occurs in the blood flow distribution in hepatic segments after segmental portal vein embolization., Conclusion: We found an immediate change in the distribution of blood flow in the liver after embolization; with portal vein embolization, we found an immediate increase in the hepatic artery blood flow in the affected segments.

The aim of this study was to evaluate the correlation of development of the collateral circulation to the liver during hepatic arterial infusion chemotherapy (HAIC) with the presence of hepatic tumours adjacent to the hepatic surface, and with pretreatment occlusion of aberrant hepatic arteries. In 102 patients with unresectable malignant hepatic tumours treated with HAIC using an implantable port system, development of collaterals to the liver was assessed with CT arteriography using the implantable port and pre- and postoperative angiography. Aberrant hepatic arteries, if present, were occluded prior to treatment for hepatic arterial redistribution. Collaterals to the liver were seen in 29 patients, who had 35 areas with collateral perfusion: 22 areas were in the right posterosuperior area, 6 in the left peripheral area and 7 in the right or left lobar area. Collaterals were revealed more frequently in patients with hepatic tumours adjacent to the hepatic surface than in those without hepatic tumours in peripheral areas in the liver (p < 0.0001). In addition, collaterals developed more frequently in patients with an aberrant hepatic arterial anatomy compared with those with conventional anatomy (p = 0.0007). Our results indicated that patients with hepatic tumours adjacent to the hepatic surface and with pretreatment occlusion of aberrant hepatic arteries had the potential to develop collaterals to the liver during HAIC.