Diagnosis Of Intrahepatic Cholangiocarcinoma Research Articles

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.

A case of advanced intrahepatic cholangiocarcinomasuccessfully treated with chemosensitivity test-guidedsystemic chemotherapy

Intrahepatic cholangiocarcinoma (ICC) is a relatively rare and highly fatal neoplasm that arises from the biliary epithelium. Prognosis is generally poor and survival is limited to a few months. Here we present a case of advanced ICC successfully treated by chemosensitivity test-guided systemic chemotherapy combining S-1 and cisplatin (CDDP). A 65-year-old woman with a liver tumor was referred to our hospital on November 21, 2007. Abdominal ultrasonography and computed tomography (CT) showed low-density masses of 50 and 15 mm in diameter, respectively in segment VIII of the liver and in the enlarged lymph node in the para-aorta. Ultrasonography-guided fine needle biopsy diagnosed the tumors as ICC. Since the patient was inoperable for lymph node metastasis, she underwent systemic chemotherapy with gemcitabine. Six months after initiation of chemotherapy, CT revealed ICC progression in the liver and pleural dissemination with pleural effusion. The patient was admitted to our hospital for anticancer drug sensitivity testing on June 9, 2008. Based on the sensitivity test results, we elected to administer systemic chemotherapy combining S-1 and CDDP. Two months into the second chemotherapy treatment, CT revealed a reduction of the tumors in the liver and lymph node and a decrease in pleural effusion. After eight cycles of the second chemotherapy, 17 mo after ICC diagnosis, she is alive and well with no sign of recurrence. We conclude that chemosensitivity testing may effectively determine the appropriate chemotherapy regimen for advanced ICC.

Expression of mucin glycoproteins and cytokeratins in intrahepatic cholangiocarcinoma

To compare the immunoprofiles of intrahepatic cholangiocarcinoma and metastatic colorectal adenocarcinoma for mucin glycoproteins (including MUC1, MUC2, MUC5AC and MUC6) and cytokeratins (including CK7, CK19 and CK20), and to assess their diagnostic value. One hundred cases of intrahepatic cholangiocarcinoma and 21 cases of metastatic colorectal adenocarcinoma were enrolled into the study. Immunohistochemical study for MUC1, MUC2, MUC5AC, MUC6, CK7, CK19 and CK20 was carried out in all cases by EnVision method. In intrahepatic cholangiocarcinoma, the expression rates of MUC1, MUC2, MUC5AC and MUC6 were 61.0%, 2.0%, 22.0% and 8.0% respectively, as compared to 57.1%, 47.6%, 19.0% and 23.8% respectively in metastatic colorectal adenocarcinoma. On the other hand, the expression rates of CK7, CK19 and CK20 in intrahepatic cholangiocarcinoma were 73.0%, 53.0% and 15.0% respectively, in contrast to 14.3%, 90.5% and 85.7% respectively in metastatic colorectal adenocarcinoma. The difference in expressions of MUC2, MUC6, CK7 and CK20 carried statistical significance. The immunoprofile for mucin glycoproteins and cytokeratins provides important clues in distinguishing between intrahepatic cholangiocarcinoma and metastatic colorectal adenocarcinoma to liver. The immunophenotype of MUC2-/MUC6-/CK7+/CK20- indicates the diagnosis of intrahepatic cholangiocarcinoma, while MUC2+/MUC6+/CK7-/CK20+ suggests the possibility of metastatic colorectal adenocarcinoma.

Liver Transplantation as a Primary Indication for Intrahepatic Cholangiocarcinoma: A Single-Center Experience

Background Intrahepatic cholangiocarcinoma (ICC) is not a widely accepted indication for orthotopic liver transplantation (OLT). The present study describes our institutional experience with patients who underwent transplantation for ICC as well as those with ICC who underwent transplantation with the incorrect diagnosis of hepatocellular carcinoma (HCC). Patients and Methods Data corresponding to ICC patients were reviewed for the purposes of this study. Patients with hilar cholangiocarcinoma and incidentally found ICC after OLT for benign diseases were excluded from further consideration. Results Among the 10 patients, 6 underwent transplantation before 1996 and 4 after 2001. Those who underwent transplantation in the early period had a preoperative diagnosis of inoperable ICC (n = 4) and ICC in the setting of primary sclerosing cholangitis (n = 2). In the latter period the subjects had a diagnosis of HCC in cirrhosis (n = 3) or recurrent ICC after an extended right hepatectomy (n = 1). Median survival was 25.3 months for the whole series and 32.2 months (range, 18–130 months) when hospital mortality was excluded (n = 3). Four patients are currently alive after 30, 35, 42, and 130 months post-OLT, respectively. Two patients died of tumor recurrence at 18 and 21 months post-OLT, respectively. One-, 3-, and 5-year survival rates were 70%, 50%, and 33%, respectively. Conclusions The role of OLT in the setting of ICC may be re-evaluated in the future under strict selection criteria and with prospective multicenter randomized studies. Potential candidates to be included are those with liver cirrhosis and no hilar involvement who meet the Milan criteria for HCC.

Identification of novel candidate tumour marker genes for intrahepatic cholangiocarcinoma

Specific markers are required for early detection and diagnosis of intrahepatic cholangiocarcinoma (ICC); however, the tumour markers currently in use are not specific for ICC. We compared an ICC cDNA library with that of hepatocellular carcinoma (HCC) by serial analysis of gene expression (SAGE). The expression patterns in each were confirmed by quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR), immunoblotting and immunohistochemical analysis of 74 samples including 16 ICC samples. A comparison of the two libraries revealed distinct gene expression patterns for each type of liver cancer. In addition to the known tumour markers, we detected nine novel genes associated with ICC. By comparing the mean transcript abundance in the ICC library with those in other libraries, including gastric, colon, prostate and breast cancer, together with our RT-PCR results, we identified three genes as specific markers of ICC: biglycan, insulin-like growth factor-binding protein 5 and claudin-4. Immunoblotting and immunohistochemical analyses showed that claudin-4 was highly expressed in ICC. Moreover, discrimination analysis revealed that a combination of these genes could be used to distinguish ICC from HCC or metastatic adenocarcinoma. We identified novel marker genes of ICC that are potentially useful for the diagnosis of liver cancer.

Intrahepatic cholangiocarcinoma: A diagnostic and therapeutic challenge

Objectives: Intrahepatic cholangiocarcinoma (ICC) is a rare tumor of the liver. The diagnosis and treatment of it are difficult. The present study reviewed the diagnostic pathways and operative results for ICC.Methods: A retrospective analysis was made of the clinical presentation, diagnostic pathways, and operative results of 20 patients with ICC who underwent hepatectomy from 1997 to 2004 in our institute.Results: The patients were predominantly female (female : male = 15:5), and ranged in age from 41 to 74 years (median 59.8). Abdominal pain was the main presenting symptom, and hepatomegaly was the commonest physical sign. Diagnosis relied mainly on ultrasound or computed tomography. Without biopsy, only two patients were correctly diagnosed with ICC before surgery. The median size of the tumor was 6 cm (range 1.6–12 cm). Major hepatectomy was carried out in 80% of patients. The operative mortality and morbidity were 15% and 40%, respectively. The median follow up was 18.3 months. Thirteen patients (65%) had recurrences at one or more sites, including, in decreasing frequency, the liver, abdominal lymph node, lung, bone, or skin. The median survival was 17.3 months and the 1‐year, 3‐year, and 5‐year survival rates were 60%, 45%, and 10%, respectively.Conclusions: The poor survival of patients with ICC was mainly due to the delay in diagnosis and the aggressive nature of the disease. The diagnosis of ICC relies on a high index of suspicion as there is no reliable tumor marker and imaging results are usually inconclusive. Radical hepatectomy remains the only chance of cure for ICC. The role of lymph node dissection, liver transplantation, and adjunctive chemotherapy in the treatment of patients with ICC remains to be determined.

Enhanced Expression of RAD51 Associating Protein-1 Is Involved in the Growth of Intrahepatic Cholangiocarcinoma Cells

Intrahepatic cholangiocarcinoma (ICC) is the second most common primary cancer in the liver, and its incidence is increasing in developed countries. To discover novel molecular targets for the diagnosis and treatment of ICCs, we earlier analyzed expression profiles of 25 ICCs using a cDNA microarray containing 27,648 genes. In this study, we focused on the RAD51 associating protein-1 (RAD51AP1) gene because its expression was frequently elevated in our microarray data. Quantitative PCR confirmed that RAD51AP1 expression was elevated in the great majority of the ICCs examined. Immunohistochemical analysis with anti-RAD51AP1 antibody further corroborated its accumulation in 14 of 23 ICC tissues (61%). Notably, suppression of RAD51AP1 by short interfering RNA resulted in growth suppression of cholangiocarcinoma cells, suggesting its involvement in the development and/or progression of ICC. Because RAD51AP1 interacts with RAD51, a molecule involved in DNA repair, we investigated whether RAD51AP1 is implicated in DNA strand breaks using gamma-irradiation. As a result, gamma-irradiation augmented RAD51AP1 protein expression and brought a focus formation in the nuclei, where accumulated RAD51AP1 colocalized with phosphorylated histone 2AX (gamma-H2AX) and RAD51. These data suggest that RAD51AP1 may play a role in cell proliferation as well as DNA repair. Our findings may contribute to the better understanding of cholangiocarcinogenesis and open a new avenue to the development of novel therapeutic and/or diagnostic approach to this type of tumor.

Primary liver cancers with nonalcoholic steatohepatitis

Nine patients with hepatocellular carcinoma (HCC) in nonalcoholic steatohepatitis (NASH) (six men and three women, median age 71.5 years) and one patient with intrahepatic cholangiocarcinoma (ICC), a 50-year-old man, in NASH are described. Most patients were associated with obesity, diabetes, hypertension, hypercholesterolemia, or hypertriglyceridemia. Seven patients showed insulin resistance and hyperinsulinemia. All patients except one met the criteria for metabolic syndrome. An HCC or ICC diagnosis was confirmed by tumor biopsy, surgery or autopsy except in two patients, who were diagnosed by computed tomography or hepatic angiography. The underlying liver disease was liver cirrhosis in six patients and chronic liver disease including mild hepatic fibrosis in four patients. The treatment of liver cancers consisted of surgery, radio-frequency ablation (RFA), transcatheter arterial embolization and transcatheter arterial infusion. Although the follow-up period was relatively short (median 27.5 months, average 32.1 months), all postoperative and post-RFA patients have not had a recurrence of HCC to date, except for one patient who had a palliative operation with intra-arterial infusion of anticancer drugs through an implanted reservoir port. Older age and liver cirrhosis are considered risk factors for HCC in NASH, and regular screening of these patients is necessary. Diabetes may contribute to the development of ICC in NASH. Curative therapy (surgery or RFA) and weight loss by the active therapeutic intervention (nutritional care and exercise therapy) after curative therapy may help us improve the prognosis of HCC in NASH.

Risk factors for intrahepatic cholangiocarcinoma in a low‐risk population: A nationwide case‐control study

Recently, the incidence of intrahepatic cholangiocarcinoma (ICC) has been increasing in a number of developed (Western) countries. However, risk factors in these low-risk populations are poorly understood. In this nationwide population based case-control study in Denmark, we examined the relationship between selected medical conditions and subsequent ICC risk to provide additional clues to etiopathogenesis. All histologically confirmed ICC cases diagnosed in Denmark between 1978 and 1991 were identified from the Danish cancer registry. Population controls were selected from the central population registry and were matched 4:1 to cases on sex and year of birth. Cases and controls were linked to the Danish hospital discharge registry to obtain information on prior hospital diagnoses. Odds ratios (OR) and 95% confidence intervals (95% CI) were derived using conditional logistic regression. A total of 764 ICC cases and 3,056 population controls were included in the study. Chronic liver diseases were significantly related to ICC: alcoholic liver disease (OR = 19.22, 95% CI = 5.55-66.54), unspecified cirrhosis (OR = 75.9, 95% CI 10.2-565.7). Bile duct diseases were also associated with risk: cholangitis (OR = 6.3, 95% CI = 2.3-17.5), choledocholithiasis (OR = 23.97, 95% CI = 2.9-198.9), cholecystolithiasis (OR = 4.0, 95% CI = 2.0-7.99), though gallbladder removal did not change risk (OR = 1.6, 95% CI = 0.65-3.7). Among other conditions, chronic inflammatory bowel disease (OR = 4.7, 95% CI = 1.65-13.9) was significantly associated with ICC. Diabetes was associated with risk in the year prior to diagnosis of ICC (OR = 3.02, 95% CI = 1.05-8.69). Obesity was unrelated to risk. These results confirm that prior bile duct diseases increase risk of ICC and suggest that alcoholic liver disease and diabetes may also increase risk.

Carcinoma with shared pathologic characteristics of both hepatocellular carcinoma and cholangiocarcinoma

Background: α-Fetoprotein (AFP) is a useful marker of hepatocellular carcinoma (HCC), and protein induced by vitamin K absence or antagonist II (PIVKA-II) and fucosylated AFP (AFP-L3) are specific tumor markers. Objective: The aim of this article was to report a case of intrahepatic cholangiocarcinoma (CC) with high levels of expression of AFP, AFP-L3, and PIVKA-II. Methods: A 70-year-old man weighing 66 kg with a diagnosis of intrahepatic CC presented with a liver tumor 4.0 cm in diameter and elevated concentrations of carbohydrate antigen 19-9 (575 U/mL), PIVKA-II (379 mAU/mL), and AFP (497 ng/mL; AFP-L3, 88.1%). On extended medial hepatic segmentectomy, microscopy showed that the tumor was a CC without HCC. The patient subsequently underwent immunohistochemical assessments using cytokeratin-19, epithelial membrane antigen (EMA), hepatocyte paraffin-1 (HP-1), PIVKA-II, and AFP. Results: In all specimens, desmoplasia was observed. However, results of immunohistochemistry showed positive results for cytokeratin-19 and EMA; HP-1 results were negative. Results of PIVKA-II and AFP testing in the tumor were positive. Conclusions: The case presented here showed characteristics of CC and HCC, whereas the histologic expression of the tumor suggested CC. Based on the literature search, this is the first known report of a case of a CC expressing AFP and PIVKA-II confirmed on immunohistochemical staining. This case is interesting with regard to the ability of the progenitor cells to differentiate HCC and CC.

An increasing incidence of cholangiocarcinoma: Why?

An increasing incidence of cholangiocarcinoma: Why?

A CASE OF MUCINOUS CARCINOMA OF THE INTRAHEPATIC BILEDUCT PERFORMED A HEPATECTOMY

A 73-year-old woman was referred to the hospital for cose examination and treatment because gastric endoscopy revealed an extramurally oppressed finding on the stomach. After admission ultrasonography revealed a giant liver tumor with the maximum diameter of 12.4cm in the lateral segment of the liver. The liver tumor was visualized as low-dencity area. Magnetic resonance imagings (MRI) revealed the tumor as low-echogenic lesion on T1 enhanced or as high-echogenic lesion on T2 enhanced. On endoscopic retrograde cholangio-pancreatography (ERCP), a swelling of the papilla vater and leakage of mucus were confirmed. Biopsy of the papilla Vater indicated that degeneration of the collected tissue is cancerous. With a diagnosis of intrahepatic cholangiocarcinoma and papillocarcinoma, a left lobectomy of the liver and pancreatoduodenectomy were carieed out. Histopathologically no cancer cell was detected in the pancreatic head, but the liver tumor was mucinous carcinoma of the intrahepatic bile duct. Mucinous carcinoma of the intrahepatic bile duct is a rare entiry and few reports have been seen in the Japanes literature. So this case is presented, together with a review of the literature.

Contrast-enhanced MR imaging of intrahepatic cholangiocarcinoma

The unenhanced spin-echo T1-weighted images, contrast-enhanced (dynamic and conventional) T1-weighted images and spin-echo T2-weighted images of 19 patients with histologically proven intrahepatic cholangiocarcinoma were reviewed. The results showed that typical intrahepatic cholangiocarcinoma presented as a large mass of low signal intensity on T1-weighted images. On T2-weighted images tumours generally presented as high signal intensity masses. In five patients the tumours exhibited varying degrees of central hypointensity on T2-weighted images. On contrast-enhanced images, large tumours (diameter larger than 4 cm, n = 14) typically showed peripheral enhancement with delayed or incomplete central filling. This pattern was seen most commonly. Smaller tumours (diam. 2-4 cm, n = 5) typically exhibited homogenous enhancement. On dynamic studies, enhancement of the tumours showed a centripetal pattern. Complete enhancement was observed in the small tumours. Among the larger lesions central sparing of the tumours was seen. It is concluded that contrast-enhanced MR imaging is useful in the diagnosis of intrahepatic cholangiocarcinoma. The characteristic enhancing pattern of intrahepatic cholangiocarcinoma was seen less commonly in smaller tumours. Definite differentiation from other liver masses in this case could be less certain.