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Purpose: This study was conducted to identify factors involved in lymph node metastasis (LNM) and evaluate their role in predicting LNM in clinically lymph node negative (clinical stage I-III) intrahepatic cholangiocarcinoma (ICC).Materials and Methods: We selected 320 patients who were diagnosed with ICC with no apparent clinical LNM (T1-3N0M0). Age, gender, tumor boundary, histological differentiation, tumor size and CA19-9 value were the studied factors. Univariate and multivariate logistic analysis were conducted. Receiver operating characteristics (ROC) curve analysis was used to test the predicting value of each factor and a test which combined the associated factors was used to predict LNM.Results: LNM was observed in 76 cases (76/320, 23.8%). Univariate and multivariate analysis showed that histological differentiation as well as tumor boundary and tumor size significantly correlated with LNM. The sensitivity and negative predictive value (NPV) for LNM for the three factors when combined was 96.1% and 95% respectively. This means that 5% of the patients who did not have the risk factors mentioned above developed LNM.Conclusions: This model used the combination of three factors (low-graded histological differentiation, distinct tumor boundary, small tumor size) and they proved to be useful in predicting lymph node metastasis in ICC with clinically lymph node negative cases. In patients with these criteria, lymph node dissection or lymph node irradiation may be omitted and such cases may also be good candidates for stereotactic body radiotherapy (SBRT).

Background & Aims Prognostic factors and adjuvant therapy of intrahepatic cholangiocarcinoma ( ICC) after curative resection were not clear. We aim to analyse prognostic factors after curative resection and evaluate adjuvant therapy and survival based on the new staging system. Methods A retrospective analysis of 283 patients who underwent surgical exploration for ICC was performed. Staging was performed according to the 7th edition AJCC staging manual. Univariate and multivariate analyses were used to evaluate independent prognostic factors. Results The difference for OS at different TNM stages after R0 resection was significant ( P < 0.001). Despite regional lymph node metastasis, tumour number and vascular invasion, serum GGT level was also an independent prognostic factor for OS of patients after R0 resection. The incidence of biliary and vascular invasion was significantly higher in high GGT group than in normal GGT group. Factors predictive of recurrence were multiple tumours and regional lymph node metastasis. After R0 resection, adjuvant TACE not only did not improve the OS of patients at TNM stage I ( P = 0.508), but significantly promoted recurrence of these patients ( P = 0.006). Only patients at TNM stage II, III and IV benefited from adjuvant TACE for longer survival, while the recurrence rates were not affected. Conclusions The new staging system can predict the survival of ICC patients after R0 resection. High GGT level may be suggestive of biliary and vascular invasion and was an independent risk factor for OS after R0 resection. Adjuvant TACE may be indicated only for patients at advanced stages for better survival. [ABSTRACT FROM AUTHOR]

BACKGROUND: Dickkopf-related protein 1 (DKK1) has been reported involved in metastasis and invasion in several tumors. This study sought to investigate the prognostic value of DKK1 in intrahepatic cholangiocarcinoma (ICC) and its role in promoting ICC metastasis. METHODS: Tissue microarrays of 138 ICC patient samples were employed to detect DKK1, vascular endothelial growth factor C (VEGF-C), and matrix metalloproteinase 9 (MMP9) expression using immunohistochemistry. The prognostic significances were assessed by Kaplan-Meier survival estimates. DKK1 expression was measured in an ICC cell line (HCCC-9810) and ICC tissues by immunofluorescence assay, quantitative real-time polymerase chain reaction, and western blot. Serum levels of DKK1 from 37 ICC patients were tested by enzyme-linked immunosorbent assay. The role of DKK1 in proliferation, migration, invasion, and gene expression regulation was assessed by DKK1 depletion using small interfering RNA. RESULTS: Multivariate analyses revealed that DKK1 was an unfavorable predictor for overall survival and time to recurrence. The prognostic significance was retained in ICC patients with low recurrence risk ( P < .05). DKK1 expression was elevated in an ICC cell line, tumor samples, and patient sera. High levels of DKK1 in ICC tissues correlated with elevated MMP9, VEGF-C, and metastasis of hepatic hilar lymph nodes. DKK1 depletion caused a decrease in cell migration and invasiveness, and down-regulation of MMP9 and VEGF-C expression. CONCLUSIONS: DKK1 is a novel prognostic biomarker for ICC, and it enhances tumor cell invasion and promotes lymph node metastasis of ICC through the induction of MMP9 and VEGF-C. DKK1 may be a potential therapeutic target for ICC. Cancer 2013. © 2012 American Cancer Society. [ABSTRACT FROM AUTHOR]

To evaluate the role of radiotherapy for patients with resected intrahepatic cholangiocarcinoma with concurrent macroscopic abdominal lymph node metastases. We identified 90 patients with resected intrahepatic cholangiocarcinoma and concurrent regional lymph node metastases treated between 1999 and 2008, thereinto 24 patients received local limited external beam radiotherapy (classified as the radiotherapy group) with a median total dose of 50 Gy (range 34–60 Gy) in fractions of 2 Gy five times a week. The remaining 66 patients did not receive external beam radiotherapy (classified as the non-radiotherapy group). We studied survival and tumor response to radiotherapy, demonstrated by symptoms and results of imaging, by Kaplan–Meier method and Cox analysis. After radiotherapy, lymph nodes showed partial response in nine patients (37.5%) and complete response in nine patients (37.5%). Median survival was 19.1 months in the radiotherapy group and 9.5 months in the non-radiotherapy group ( P = 0.011). Multivariate analysis showed that increasing age, multiple intrahepatic primary tumors, higher level of CA19-9, and non-radiotherapy group were related to a poorer prognosis. The most common cause of death was intrahepatic recurrence, and death resulting from lymph node-related complications was similar between the two groups. External beam radiotherapy seems to improve the prognosis of patients with resected intrahepatic cholangiocarcinoma and concurrent macroscopic lymph node metastases. [ABSTRACT FROM AUTHOR]

To clarify clinicopathologic differences between patients with intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC), and identify potential factors influencing survival after hepatectomy for ICC. Comparison of clinicopathologic data was made between patients who underwent hepatectomy for ICC ( n = 272) and HCC ( n = 5,829) during the same period. Twenty-five clinicopathologic variables were selected for univariate and multivariate analyses to evaluate their influence on prognosis of ICC. Compared with patients with HCC, ICC patients were more common in females and more elderly, had a lower proportion of asymptomatic tumors, lower serum alpha-fetoprotein, higher serum carcinoembryonic antigen, carbohydrate antigen 19–9 and alkaline phosphatase levels; lower incidence of hepatitis history, associated cirrhosis and serum hepatitis B surface antigen; lower proportion of small tumors, well-encapsulated tumors and tumor emboli in the portal vein; higher proportion of single tumor, perihila lymph node involvement and poor differentiation; and less frequency of limited resection (all, P < 0.0001). Distant metastasis was less frequent in patients with ICC ( P = 0.027). A total of 5-years overall and disease-free survival (in brackets) after resection was 26.4% (13.1%) and 44.5% (33.1%) ( P < 0.0001, P < 0.0001) for patients with ICC and HCC, respectively. Factors influencing survival after resection of ICC can be divided mainly into two categories: early detection of asymptomatic ICC ( P < 0.0001) and curative resection ( P = 0.002). ICC Patients have distinct clinicopathologic features as compared with HCC patients. Surgery remains the only effective treatment for ICC. Early detection of asymptomatic ICC and curative resection were the key to achieve optimal survival. [ABSTRACT FROM AUTHOR]

The role of radiotherapy in the treatment of intrahepatic cholangiocarcinoma is controversial. We undertook this study to determine if radiotherapy is appropriate for patients with unresectable or lymph node metastatic intrahepatic cholangiocarcinoma. [ABSTRACT FROM AUTHOR]

Purpose: To quantify microscopic invasion of intrahepatic cholangiocarcinoma (IHC) into nontumor tissue and define the gross tumor volume (GTV)-to-clinical target volume (CTV) expansion necessary for radiotherapy. Methods and Materials: One-hundred IHC patients undergoing radical resection from January 2004 to July 2008 were enrolled in this study. Pathologic and clinical data including maximum tumor diameter, tumor boundary type, TNM stage, histologic grade, tumor markers, and liver enzymes were reviewed. The distance of microinvasion from the tumor boundary was measured by microscopy. The contraction coefficient for tumor measurements in radiographs and slide-mounted tissue was calculated. SPSS15.0 was used for statistical analysis. Results: Sixty-five patients (65%) exhibited tumor microinvasions. Microinvasions ranged from 0.4–8 mm, with 96% of patients having a microinvasion distance ≤6 mm measured on slide. The radiograph-to-slide contraction coefficient was 82.1%. The degree of microinvasion was correlated with tumor boundary type, TNM stage, histologic grade, and serum levels of carbohydrate antigen 19-9, alanine aminotransferase, aspartate aminotransferase, γ-glutamyltransferase and alkaline phosphatase. To define CTV accurately, we devised a scoring system based on combination of these factors. According to this system, a score ≤1.5 is associated with 96.1% sensitivity in detecting patients with a microextension ≤4.9 mm in radiographs, whereas a score ≥2 has a 95.1% sensitivity in detecting microextension ≤7.9 mm measured on radiograph. Conclusions: Patients with a score ≤1.5 and ≥2 require a radiographic GTV-to-CTV expansions of 4.9 and 7.9 mm, respectively, to encompass >95% of microinvasions. [ABSTRACT FROM AUTHOR]