Peripheral Intrahepatic Cholangiocarcinoma Research Articles

Implication of Lymph Node Metastasis Detected on 18F-FDG PET/CT for Surgical Planning in Patients With Peripheral Intrahepatic Cholangiocarcinoma

Intrahepatic cholangiocarcinoma (ICC) is the second most common primary hepatic malignancy after hepatocellular carcinoma. ICC can be divided into 2 types according to their location: peripheral and hilar types. Intense F-FDG uptake on PET was reported in peripheral ICC. However, the usefulness of PET/CT in detecting tumors and predicting prognosis in peripheral ICC has not been fully evaluated. In this study, we evaluated the clinical role of F-FDG PET/CT to predict the recurrence after the curative resection in patients with surgically indicated peripheral ICC. Eighteen patients with ICC underwent preoperative CT and F-FDG PET/CT scans. SUVmax of tumor, tumor to normal liver SUV ratio (TNR), lymph node status evaluated by F-FDG PET/CT, tumor and lymph node size measured by CT, vascular invasion confirmed by pathology, and satellite nodules found on CT were compared between 1-year recurrence group and recurrence-free group by chi-square test. Of total 23 measurable lymph nodes, 4 nodes were positive and other 19 nodes were negative or equivocal on CT. Among those 23 nodes, 9 nodes were positive and other 14 nodes were negative on F-FDG PET/CT. The sensitivity and specificity of CT were 20.0% and 86.4%, and those of F-FDG PET/CT were 80.0% and 92.3%. In the comparison between 1-year recurrent and nonrecurrent groups, lymph node metastasis detected on F-FDG PET/CT had statistically positive correlation with the 1-year recurrence after surgical resection (P = 0.02). Other factors showed no statistically significant difference between the groups. We found that lymph node metastasis detected on F-FDG PET/CT correlated positively with 1-year recurrence after surgical resection in patients with peripheral ICC.

What are the precursor and early lesions of peripheral intrahepatic cholangiocarcinoma?

Cholangiocarcinoma (CC) is divided into distal, perihilar, and intrahepatic CCs (ICCS), and are further subdivided into large bile duct ICC and peripheral ICC. In distal and perihilar CC and large duct ICC, biliary intraepithelial neoplasm (BilIN) and intraductal papillary neoplasm (IPN) have been proposed as precursor lesions. Peripheral ICC, bile duct adenoma (BDA), biliary adenofibroma (BAF), and von Meyenburg complexes (VMCs) are reportedly followed by development of ICCs. Herein, we surveyed these candidate precursor lesions in the background liver of 37 cases of peripheral ICC and controls (perihilar CC, 34 cases; hepatocellular carcinoma, 34 cases and combined hepatocellular cholangiocarcinoma, 25 cases). In the background liver of peripheral ICC, BDA and BAF were not found, but there were not infrequently foci of BDA-like lesions and atypical bile duct lesions involving small bile ducts (32.4% and 10.8%, resp.). VMCs were equally found in peripheral CCs and also control CCs. In conclusion, BDA, BAF, and VMCs are a possible precursor lesion of a minority of peripheral CCs, and BDA-like lesions and atypical bile duct lesions involving small bile ducts may also be related to the development of peripheral ICC. Further pathologic studies on these lesions are warranted for analysis of development of peripheral ICCs.

Prediction of the Postoperative Prognosis of Intrahepatic Cholangiocarcinoma (ICC): Importance of Preoperatively-Determined Anatomic Invasion Level and Number of Tumors

Preoperative prediction of the prognosis of patients with intrahepatic cholangiocarcinoma (ICC) following surgical treatment remains quite difficult and controversial. We attempted to identify the preoperative and postoperative predictors of the overall survival rates inpatients with ICC in order to clarify the appropriate indications for surgical resection of ICC. We retrospectively investigated the clinicopathological features of ICC and outcome of surgical resection in 111 consecutive patients who underwent surgical treatment at our hospital between 1980 and March 2012. Both preoperative factors and operatively confirmed factors were evaluated as potential risk factors for determination of the post-surgical prognosis. Curative resection (R0) was performed in 72 patients (64.9 %). The 1- and 3-year overall survival rates were 85.0 and 59.7 % in the R0 group. Two preoperative factors [hilar invasion as recognized by computed tomography(HR 3.16, P = 0.020) and multiple intrahepatic tumors (HR 7.09, P = 0.0002)] and two operatively confirmed factors [multiple intrahepatic tumors (HR 9.17,P = 0.0009) and lymph node metastasis as confirmed by final histology (HR 6.41, P = 0.003)] were identified as significant risk factors adversely influencing the overall survival rate after surgery. Furthermore, solitary, small(\5 cm) and peripheral ICCs were associated with a very low probability of lymph node metastasis. Preoperatively diagnosed hilar invasion,multiple intrahepatic tumors and histologically confirmed lymph node metastasis were the main determinants of an adverse postoperative prognosis in patients with ICC.Lymph node dissection could be omitted for patients with solitary, small and peripheral ICCs.

Treatment outcomes and prognostic factors of intrahepatic cholangiocarcinoma

The aim of the present study was to determine the treatment outcome and prognostic factors for survival in patients with peripheral intrahepatic cholangiocarcinoma (ICC). A retrospective chart review was performed for patients diagnosed with ICC between 2000 and 2009 at a single institution. We identified a total of 105 patients with ICC. Among them, 63.8% were older than 60 years of age, 50.5% were male and 88.6% were Caucasian. By preoperative imaging approximately half of the patients (50.5%) were surgical candidates and underwent resection. The other half of the patients (49.5%) were unresectable. The unresectable group received chemoradiotherapy (53%) and transarterial chemoembolization (7.7%) as palliative treatments while 23.0% of the patients (12/52) received best supportive care alone. The median survival rates were 16.1 months (13.1–19.2) for the entire cohort, 27.6 months (17.7–37.6) for curative resection, 12.9 months (6.5–19.2) for palliative chemoradiotherapy and 4.9 months (0.4–9.6) for best supportive care (P<0.001). Independent predictors on multivariate analysis were advanced stage at diagnosis and treatment received. In those patients who underwent resection, advanced AJCC stage and presence of microvascular invasion were also independent predictors of poor survival. We concluded that surgery offers the most beneficial curative option and outcome, emphasizing the importance of resectability as a major prognostic factor. The present study also revealed that use of chemoradiotherapy in the adjuvant setting failed to improve survival but its palliative use in those patients with unresectable ICC offered a modest survival advantage over best supportive care. The overriding factors influencing outcome were stage and the presence of microvascular invasion on pathology.

Peripheral intrahepatic cholangiocarcinoma occurring in patients without cirrhosis or chronic bile duct diseases

Peripheral intrahepatic cholangiocarcinoma (ICC) occurring mainly in the absence of cirrhosis represents an increasing subgroup of primary liver tumors in Western countries. Histopathologic changes in the non-neoplastic liver in this context are not well characterized. We assessed the clinical characteristics and histopathologic changes in the distant nontumoral liver of 57 consecutive White patients (34 men, mean age 59 years) referred to one medical and one surgical liver institution over a 16-year period who developed a peripheral ICC in the absence of cirrhosis or bile duct disease. High alcohol consumption was observed in 11 patients (20%), 38 patients (66%) had a BMI of 25 kg/m or more, 22 patients (40%) had diabetes, two patients had hepatitis B virus infection, two others had hepatitis C virus infection, three patients had genetic hemochromatosis, and two patients had cutaneous porphyria tarda. The distant nontumoral liver was normal in 10 patients (18%). The two main histopathologic changes observed were macrovesicular steatosis (>10% of hepatocytes) in 38 patients (66%), including 11 patients (19%) with steatohepatitis, and moderate or intense hepatocyte iron overload in 22 patients (38%). This study shows a high prevalence of macrovesicular steatosis associated or not with steatohepatitis and iron overload in patients who develop peripheral ICC in the absence of cirrhosis or bile duct disease.

Diagnosis of peripheral intrahepatic cholangiocarcinoma using color Doppler ultrasound

Objective To investigate the diagnostic value of color Doppler ultrasound for peripheral intrahepatic cholangiocarcinoma (ICC).Methods Ninety- five patients with ICC which were confirmed histopathologically were retrospectively studied.The features on color Doppler ultrasound were analyzed.Results There were 102 tumors which ranged from 20 mm× 20 mm to 130 mm× 100 mm in size.On gray-scale ultrasonic imaging,a large proportion of the tumors presented with inhomogeneous echo (n=75,73.5％), indefinite boundaries (n =70, 68.6％),and irregular shape (n=55,53.9％).On color Doppler ultrasonic imaging,most tumors had flow signals (75,73.5％) mainly in the shape of areatus,short- line and color-dot.Most flow signals had a resistant index greater than 0.6.Of the 102 tumors,thirty-seven (36.3％) were observed to produce streak hyperecho,twentynine (28.4％) slight attenuation in the rear and 22 (21.6％) unbilical depression.The coincidence rate with ultrasound was 84.2％ (80/95). Conclusions The features of peripheral intrahepatic cholangiocarcinoma on color Doppler ultrasound are characteristic.To be able to appreciate these features is helpful to improve on the accuracy rate of ultrasound. Key words: Intrahcpatic cholangiocarcinoma; Color Doppler ultrasound; Diagnosis

S100P immunostaining identifies a subset of peripheral‐type intrahepatic cholangiocarcinomas with morphological and molecular features similar to those of perihilar and extrahepatic cholangiocarcinomas

S100P is a calcium-binding protein that is frequently expressed in pancreatic adenocarcinoma and perihilar cholangiocarcinoma. The aim of this study was to investigate the pathological significance of the expression of S100P in peripheral intrahepatic cholangiocarcinoma (ICC). Immunohistochemical staining was used to investigate S100P expression in 112 cases of peripheral ICC. The results were compared with those for perihilar and extrahepatic cholangiocarcinomas. Patients with S100P-positive peripheral ICC were more likely to have elevated serum levels of carcinoembryonic antigen (CEA) and CA19-9 than those with S100P-negative peripheral ICCs. All cases of peripheral ICC associated with intrahepatic lithiasis and all cases with intraductal/periductal growth patterns were positive for S100P. S100P-positive peripheral ICCs were highly associated with 'bile duct' morphology rather than cholangiolar differentiation. Nearly all cases of perihilar and extrahepatic cholangiocarcinoma were positive for S100P. Similarly to perihilar and extrahepatic cholangiocarcinomas, S100P-positive peripheral ICCs showed more frequent expression of CEA and MUC2, and were more likely to be N-cadherin-negative, than S100P-negative cases. Notably, K-RAS mutations were only detected in S100P-positive peripheral ICCs, with a frequency similar to that in perihilar and extrahepatic cholangiocarcinomas. Patients with S100P-positive peripheral ICC were more likely to have poor prognoses than those with S100P-negative tumours. S100P immunostaining identifies a subset of peripheral ICC that probably originates from larger bile ducts. This subset of peripheral ICCs shares common morphological and molecular features with perihilar and extrahepatic cholangiocarcinomas.

P-0144 Adjuvant Therapy and Prognostic Factors for Biliary Tract Cancer Intrahepatic Cholangiocarcinoma: Single-Center Experience

ABSTRACT Introduction Biliary tract cancers (BTCs) encompass both cholangiocarcinoma (CC), arising in the intrahepatic, or distal biliary tree, ampulla of Vater and gallbladder carcinoma (GBC). The prognosis is poor for the majority of these patients (pts).The treatment outcome and prognostic factors for survival in patients with peripheral intrahepatic cholangiocarcinoma (ICC) are poorly defined. Given the rarity of BTC compared with other solid tumours, there have been few large studies looking at long-term outcomes. Methods 43pts with a diagnosis of no metastatic BTC were followed from diagnosis to death between Jan 2000 and Mar 2011. We calculated survival rates and prognostic factors for global survival and disease free survival. Results A total of 43 patients were identified with no metastatic BTCs. The median age was 65 years (29–82 years); 25/43 pts (58%) males, performance status of 0 in 33/43 (76%); PS1 in 8/43 (19%) and PS2 in 2/43 (5%) pts. A histological diagnosis of adenocarcinoma was confirmed in 100%. Localization of CC: 26% (11/43) intrahepatic, 9% (4/43) distal choledochal tract, 42% (18/43) gallbladder and 10/43 (23%) ampulla of Vater. Surgical resection was performed in all patients. After resection 12% (5/43) had positive margins, 42% (18/43) had positive nodes, 15/43 (35%) perineural invasion, and 3/43 (7%) had vascular infiltration. The pathologic stage was T1-T2 in 19/43 (44%) and T3-T4 in 24/43 (56%). Adjuvant chemoradiotherapy had 31/43 (72%), preferred with gemcitabine and a median number of cycles 6. Grade 3 or 4 toxicities rarely occurred. During median follow-up of 6.6 years tumor recurrence or metastatic disease occurred in 63% with median survival global were 2 years and 1.5 years for disease free survival. For stage T, the median survival global rates were 58 months (95% CI 44.6-71.3) for T1-T2 and 35 months (95% CI 23.3-46.8) for T3-T4 (p=0.015) and for median recidive-free survival were 23 months (95% CI 11.8-34) for T1-T2 and 14 months (95% CI 6.5-21) for T3-T4 (p=0.05). For N stage, the median survival global were 58 months (95% CI 50.5-65.4) for negative nodes and 26 months (95% CI 3.7-48.2) for positive nodes (p=0.003) and for median recidive-free survival were 55 months (95% CI 31.7-57.5) for negative nodes and 10 months (95% CI 6.8-13) for positive nodes (p=0.006). The vascular infiltration was significance statics for median recidive-free survival was 10 months (95% CI 2-15) for positive vascular infiltration and 23 months (95% CI 14.5-31.4) for negative vascular infiltration (p=0.006) but no for SG. Further, only stage T, N and vascular infiltration were independent predictors of survival. Conclusion This represents a biliary cancer cohort with survival benchmarks obtained in the modern era of multidisciplinary care. Surgical resection and adjuvant chemotherapy offers the optimal treatment outcome in patients with ICC. From our results depth of tumor invasion (T), the presence the lymph node metastases (N) and vascular infiltration are the strongest predictors of relapse and survival.

Dynamic enhancing vascular pattern of intrahepatic peripheral cholangiocarcinoma on contrast-enhanced ultrasound: the influence of chronic hepatitis and cirrhosis

To analyse the dynamic enhancing features by real-time contrast-enhanced ultrasound (CEUS) of intrahepatic peripheral cholangiocarcinoma (ICC) in patients with chronic hepatitis and cirrhosis. CEUS was performed by using contrast pulse sequencing (CPS) imaging with mechanical index of <0.2 after injection of 2.4 mL of contrast agent. CEUS images of histologically confirmed ICC in 54 patents (15 patents with chronic hepatitis B, 16 patents with cirrhosis, and 23 patents with normal underlying liver) were analyzed. Heterogeneous hyperenhancement was more frequently identified in ICC with chronic hepatitis (9 of 15, 60.0%, p = 0.000) and cirrhosis (8 of 16, 50.0%, p = 0.010) than in patients with normal liver (6 of 23, 26.1%) during arterial phase. The majority of ICC in patients with normal liver displayed peripheral hyperenhancement (13 of 23, 56.5%), than in patients with chronic hepatitis (4 of 15, 26.7%, p = 0.000) and cirrhosis (5 of 16, 31.3%, p = 0.001). Intense contrast uptake during the arterial phase (heterogeneous hyperenhancement or global hyperenhancement) followed by washout in venous phases was more frequently displayed in ICC patients with chronic hepatitis (11 of 15, 73.3%, p = 0.000) and in patients with cirrhosis (11 of 16, 68.8%, p = 0.000) than in ICC patients with normal underlying liver (8 of 23, 34.8%). The enhancing vascular pattern of ICC on CEUS in patients with chronic hepatitis and cirrhosis is different from that in ICC without underlying liver disease. The enhancing vascular pattern is indistinguishable from HCC on CEUS in most ICC patients with chronic hepatitis or cirrhosis.

Value of contrast‐enhanced sonography in the diagnosis of peripheral intrahepatic cholangiocarcinoma

To illustrate contrast-enhanced harmonic ultrasonography (CEUS) findings of peripheral intrahepatic cholangiocarcinoma (PICC) and to assess the usefulness of CEUS in the diagnosis of this disease. This study is a retrospective analysis of 46 patients (20 men, 26 women) with PICC who underwent both preoperative CEUS and pathologic examination. Sonographic examinations were performed with sonographic instruments equipped with low mechanical index contrast imaging software. The contrast agent SonoVue was used. The wash-in and wash-out features of the lesions were documented and the enhancement patterns were analyzed by visual inspection of the real-time cine loops. During the hepatic arterial phase of CEUS, the majority of PICC lesions (43/46, 93.5%) showed hypervascularity compared with the liver parenchyma, whereas three lesions (3/46, 6.5%) showed hypovascularity. In the portal phases, all lesions were either isoechoic or hypoechoic, while they were all hypoechoic in the late phase. Of all the hypervascular lesions, 48.8% (21/43) showed diffuse enhancement and 51.2% (22/43) showed rim-like or thick, rim-like enhancement. In 62.8% (27/43) of cases, progressive dendritic and centripetal fill-in of the contrast agent was observed. There were 83.7% (36/43) of hypervascular nodules showing heterogeneous enhancement during peak contrast enhancement of the lesions. CEUS provided clearer visualization of lesion margins than did conventional sonography. CEUS examination yields some specific findings that are useful in the diagnosis of PICC.

Different roles of S100P Overexpression in Intrahepatic Cholangiocarcinoma

S100P is expressed in several kinds of malignant tumors. Intracellular S100P interacts with ezrin, and extracellular S100P activates the receptor for advanced glycation endproducts. However, little is known about the biological significance of S100P and related proteins in cholangiocarcinoma. Biliary intraepithelial neoplasia (BilIN) is a precursor lesion of hilar or perihilar cholangiocarcinoma. We examined S100P, ezrin, and the receptor for advanced glycation end product expression in 39 BilIN and 110 intrahepatic cholangiocarcinoma (ICC) cases, and analyzed its relationship with clinicopathologic factors and outcomes. S100P expression increased from reactive epithelium to low-grade BilIN to high-grade BilIN. S100P and ezrin expression rates in perihilar-type ICC were higher than those in peripheral-type ICC (P<0.0001, P=0.0008, respectively). S100P nuclear expression in peripheral-type ICC significantly correlated with vascular invasion (P=0.0209), lymphatic invasion (P=0.0003), and lymph node metastasis (P=0.003). S100P and ezrin expression was significantly correlated. S100P-positive and ezrin-positive cases indicate shorter survival in survival analysis of the peripheral type (P=0.001, P=0.0728, respectively). Our results suggest that S100P-ezrin signaling has different roles of carcinogenesis of perihilar ICC and an aggressive course of peripheral ICC.

Intrahepatic Peripheral Cholangiocarcinoma in Cirrhosis Patients May Display A Vascular Pattern Similar to Hepatocellular Carcinoma on Contrast-Enhanced Ultrasound

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. 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.

CD10+ fibroblasts are more involved in the progression of hilar/extrahepatic cholangiocarcinoma than of peripheral intrahepatic cholangiocarcinoma

To identify the role of CD10 expression of tumour-associated fibroblastic cells in the progression of cholangiocarcinoma (CC). The CD10 expression of fibroblastic cells was investigated immunohistochemically in 167 cases of intrahepatic and extrahepatic CC and 29 cases of biliary dysplasia, comparing the clinicopathological parameters. CD10 expression of fibroblastic cells was observed in 5.7% (4/70) of peripheral intrahepatic CC, 29.2% (14/48) of hilar intrahepatic CC, and 57.1% (28/49) of extrahepatic CC. As for biliary dysplasia, CD10 expression of fibroblastic cells was observed in 4.3% (1/23) in the hepatic hilum and 20% (3/15) in the extrahepatic bile duct. CD10 expression had a strong relationship with the anatomical location of CC, and was more frequently detected in the periductal infiltrating type of hilar intrahepatic CC (P < 0.0001) and in less differentiated cases in extrahepatic CC (P = 0.0151). CD10 expression was observed more frequently in CC than in biliary dysplasia of hepatic hilum (P = 0.0365) and extrahepatic bile duct (P = 0.0262). CD10 expression was not a prognostic indicator in CC. We suggest that CD10+ fibroblasts are more involved in the progression of hilar and extrahepatic CC than of peripheral intrahepatic CC.

1133: Contrast-Enhanced Real-Time Harmonic Gray Scale Ultrasound Findings of Peripheral Intrahepatic Cholangiocarcinoma

To characterize the contrast-enhanced real-time harmonic gray scale ultrasound (CEUS) findings of peripheral intrahepatic cholangiocarcinoma (ICC) and to access the usefulness of CEUS in the diagnosis of ICC. Retrospective analysis of 33 patients with ICC who had undergone both preoperative CEUS. Sonographic examinations were performed with Technos DU8 and Philips IU22 ultrasound instruments and ultrasound contrast agent SonoVue. All ICC lesions enhanced in the arterial phase with an initial time of 14.59s±3.77s(5s-20s) and a peak enhancement time of 21.39s±5.00s(10s-30s). The time of lesions displaying isoechoic and hypoechoic comparing with the hepatic parenchyma were 29.84s±7.69s(14s-52s) and 40.13s±15.55s(20s-90s), respectively. Then all lesions presented hypoechoic in the portal and the late phase. Of the 33 patients,16 (48.5%) cases showed whole-lesion enhancement and 17 (51.5%) cases showed rim-like or thick bandlike enhancement. There were 63.6%(21/33) cases showing progressive dendritic and concentric filling of the contrast agent and 81.8%(27/33)cases showing heterogeneous enhancement during the peak enhancement. Of all patients, 51.5% (17/33) cases presented lobular appearance during the CEUS examination especially in the portal phase and parenchyma phase. The diagnostic accuracy of CEUS was 87.9% (29/33) if the diagnostic feature included early wash-in and wash-out, progressive dendritic enhancement and/or heterogeneous enhancement. There are some specific findings on CEUS which is useful in the diagnosis and differential diagnosis of this disease.

Intrahepatic peripheral cholangiocarcinoma: comparison between perfusion ultrasonography and CT imaging

Intrahepatic peripheral cholangiocarcinoma: comparison between perfusion ultrasonography and CT imaging

Intrahepatic peripheral cholangiocarcinoma (IPCC): comparison between perfusion ultrasound and CT imaging

This study was done to compare the perfusion patterns of intrahepatic peripheral cholangiocarcinoma (IPCC) on contrast-enhanced ultrasound (CEUS) and dynamic computed tomography (CT). We retrospectively reviewed 23 histologically proven cases of IPCC. All lesions were studied by CEUS with sulfur hexafluoride-filled microbubbles coated with a phospholipid capsule, and by dynamic CT. Contrast-enhancement patterns were evaluated in the arterial phase (CEUS 10-20 s after the injection; CT 25-30 s after the injection) and in the delayed phase (CEUS 120 s after the injection; CT>2-3 min after the injection). Lesions were single in 18/23 cases (78%), single with nearby satellite lesions in 1/23 (4%) cases and multifocal with distant secondary lesions in 4/23 (17%) cases. Lesion diameter was 2-5 cm in 7/23 cases (30%), 5-7 cm in 13/23 cases (57%) and >7 cm in 3/23 (13%) cases. On CEUS, lesions were hypervascular in 16/23 cases (70%). On delayed-phase CEUS, 22/23 lesions (96%) were markedly hypoechoic. CT showed that the lesions were hypovascular in the arterial phase in 15/23 cases (66%) and hypervascular in 7/23 (30%) cases; one lesion (1/23; 4%) was isovascular. On delayed-phase CT, lesions were hyperdense in 17/23 cases (74%), hypodense in 5/23 (22%) cases and isodense in 1/23 (43%) cases. Enhancement discrepancy between delayed-phase CEUS (hypoechogenicity) and CT (hyperdensity) is common semiological findings in the study of IPCC.

Pathology of peripheral intrahepatic cholangiocarcinoma with reference to tumorigenesis

Cholangiocarcinomas (CCs) are neoplasms with cholangiocyte differentiation, and may arise from cholangiocytes of the biliary tree and possibly cholangiocyte progenitor cells. Intrahepatic CCs can be divided into the perihilar and peripheral types. Peripheral CCs present grossly as a mass forming tumor, and histologically as an adenocarcinoma of varying shapes and phenotypes. Some peripheral CCs (ductular type) are characterized by: (i) a histological resemblance to reactive bile ductules; (ii) the expression of neural cell adhesion molecule (NCAM) and vimentin. This type shows: (i) grossly, a blurred border; and (ii) histologically, carcinoma cells replacing the adjoining hepatocytes at the border of the tumor. It is frequently associated with neutrophilic infiltration and also with granulocyte and granulocyte macrophage colony-stimulating factors. We propose to call this type "ductular CC." The other peripheral CC (duct type) includes ordinary adenocarcinoma with well to moderately differentiated tubular and micropapillary patterns and is negative for NCAM but positive for mucin. This type can be called "duct CC," and shows a rather compressive growth. Interestingly, CC components of combined hepatocellular CC share the features of ductular CC, suggesting that hepatic progenitor cells may be involved in the tumorigenesis of ductular CC. The biological behavior of ductular CC and duct CC remains obscure, and follow-up and molecular studies on these tumors are required in order for these two CCs to be recognized as disease entities, and so as to evaluate their carcinogenesis.

A subgroup of intrahepatic cholangiocarcinoma with an infiltrating replacement growth pattern and a resemblance to reactive proliferating bile ductules: ‘bile ductular carcinoma’

The histogenesis and biological behaviour of peripheral intrahepatic cholangiocarcinoma (peripheral CC) remain unclarified. The aim of this study was to examine the growth pattern of peripheral CC (24 cases) in comparison with hepatocellular carcinoma (HCC, 27 cases) and metastatic colorectal adenocarcinoma (MCA, 24 cases). Tumour/surrounding liver borders were classified as: (i) fibrous encapsulation, (ii) compressive growth, and (iii) infiltrating replacement. Nineteen of 24 peripheral CCs showed (iii), whereas 23 of 27 HCCs showed (i) and 17 of 24 MCAs showed (ii). In (iii), carcinoma cells infiltrated the surrounding liver without compression, and hepatic supporting vascular structures such as portal tracts were secondarily incorporated into the tumour. In (i) and (ii), the surrounding liver was compressed and no or few portal tracts were incorporated within the tumour. Fifteen of 24 peripheral CCs were composed of carcinoma cells resembling reactive bile ductules and these cells were positive for neural cell adhesion molecule (NCAM), a marker of proliferating bile ductules. The remaining nine peripheral CCs were composed of ordinary adenocarcinoma and negative for NCAM. A subgroup of peripheral CCs with an infiltrating replacement growth pattern resembles reactive bile ductules and expresses NCAM. 'Bile ductular carcinoma' may be a better term for this subgroup.

Intrahepatic Cholangiocarcinoma Mimicking Hepatic Inflammatory Pseudotumor

A 50-year-old male with hepatitis B was referred for a small intrahepatic nodule. Magnetic resonance images raised strong suspicion of a benign lesion, such as an inflammatory pseudotumor, while the other radiological studies were equivocal. Furthermore, the high-intensity image on diffusion magnified-weighted imaging with a low B value strongly suggested a benign tumor. In spite of the absence of typical clinical or radiological findings, needle biopsy revealed an intrahepatic cholangiocarcinoma (ICC). The diagnosis of peripheral ICC rich in fibrous tissue seems to require needle biopsy for pathological examination with immunohistochemical staining because it frequently mimics other diseases, including benign tumors.

Diagnosis and treatment of peripheral intrahepatic cholangiocarcinoma

目的 探讨末梢型肝内胆管细胞癌的诊断和治疗方法,评价淋巴清扫在末梢型肝内胆管细胞癌手术中的意义.方法 回顾性分析我院1993年1月至2003年4月手术治疗28例末梢型肝内胆管细胞癌的临床资料,对发病特点,症状体征,影像学检查,病理特点和手术治疗效果进行分析.结果 单因素生存分析显示手术切除组1,3,5年生存率分别为78.9%,36.8%,21.1%,未切除组15.8%,0,0,两组有显著性差异(P＜0.001).进行淋巴结清扫组1,3,5年生存率分别为100%,60%,40%,未进行淋巴结清扫切除组为55.5%,11.1%,0,两组有显著性差异(P＜0.001).合并门静脉癌栓组1,3,5年生存率分别为50%,0,0,未合并门静脉癌栓组为86.7%,46.7%,26.7%,两组有显著性差异(P=0.004).而COX比例风险回归模型多因素分析显示手术切除和淋巴清扫与预后显著相关,而门静脉癌栓与生存没有显著相关性.结论 淋巴转移,手术切除是影响生存的主要因素,手术切除能改善预后,术中进行肝门淋巴脂肪清扫能提高术后生存率。