Prognostic Factor For Intrahepatic Cholangiocarcinoma Research Articles

Impact of serum carbohydrate antigen 19-9 level on prognosis and prediction of lymph node metastasis in patients with intrahepatic cholangiocarcinoma.

Lymph node metastasis is an important prognostic factor for intrahepatic cholangiocarcinoma (ICC), but accurate preoperative diagnosis is difficult. The aim of this study was to measure the concentration of serum carbohydrate antigen 19-9 (s-CA19-9) as a preoperative predictor of lymph node metastasis. In our department, curative-intent hepatectomy for ICC has been performed only once the absence of metastases in para-aortic lymph nodes (PALN) has been confirmed from intraoperative frozen-section pathological examinations. The present study included 13 non-resected ICC patients with PALN metastasis (PALN group) and 44 resected ICC patients without PALN metastasis (non-PALN group). S-CA19-9 was examined to evaluate predictive performance for PALN metastasis and regional lymph node metastasis (pN1) from analysis of the receiver operating characteristic curve. In the non-PALN group, univariate and multivariate analyses for survival were performed on clinicopathological variables. From receiver operating characteristic curve analysis, s-CA19-9 showed good diagnostic accuracy for PALN metastasis (68%; cut-off, 200U/mL) and pN1 (77%; cut-off, 100U/mL). In univariate analysis, age (<65years), s-CA19-9 (≥100U/mL), portal vein resection, pN1, and positive resection margin (R1) were all identified as significant negative prognostic factors. Five-year survival rates of patients with high s-CA19-9 and pN1 were 6.9% and 7.3%, respectively. In multivariate analysis, high s-CA19-9 and R1 represented independent predictors of poor prognosis. Preoperative s-CA19-9 appears useful as a biomarker in patients with ICC, for predicting not only lymph node metastasis but also prognosis after surgical resection with curative intent.

A New Preoperative Prognostic System Combining CRP and CA199 For Patients with Intrahepatic Cholangiocarcinoma.

Objectives:In this study, we aimed at investigating the preoperatively available prognostic factors for intrahepatic cholangiocarcinoma (ICC) patients and proposing a new preoperative prognostic scoring system for ICC.Methods:A total of 246 consecutive ICC patients who underwent curative hepatectomy were enrolled retrospectively and were randomly divided into training (n=164) and validation cohorts (n=82) at a ratio of 2:1. The prognostic factors were investigated in both cohorts using multivariate Cox’s proportional hazards regression model.Results:Multivariate analyses identified that two preoperative factors (serum C-reactive protein (CRP) levels >4.1 mg/l (hazard ratio (HR): 2.75, 95% CI: 1.65–4.73, P<0.001) and carbohydrate antigen 19-9 (CA19-9) levels >300 mg/ml (HR: 3.76, 95% CI: 2.18–6.49)) were independent prognostic factors for postoperative survival in the training cohort. The results were further confirmed in the validation cohort. On the basis of these data, a preoperative prognostic score (PPS) was established by allocating 0 or 1 point to the two factors, respectively. Then, both in the training and validation cohorts, the PPS showed the power to stratify patients into three distinct groups (groups with scores 2, 1, and 0) with significant difference in the risk of postoperative death.Conclusions:A new preoperative scoring system consisting of preoperative CRP and CA19-9 levels could effectively predict postoperative survival of ICC patients.

Coagulopathy associated with poor prognosis in intrahepatic cholangiocarcinoma patients after curative resection.

As a rare type of liver cancer, intrahepatic cholangiocarcinoma (ICC) has become an increasingly important malignancy and continues to present significant therapeutic challenges. Since coagulopathy is associated with poor prognosis in hepatocellular carcinoma (HCC), and prognostic factors of ICC after curative resection were still not clear, we aim to analyze the characteristics of ICC patients with coagulopathy and its correlation to prognosis. From January 2000 to June 2011, 541 ICC patients, after curative resection, were enrolled in our study. Survival curves were depicted by the Kaplan-Meier method and analyzed by the log-rank test. The Cox proportional hazard regression was adopted for multivariate survival analysis. Student's t test was performed to analyze the difference between the coagulopathy group and the normal group. The correlation between coagulation parameters and prognosis was also evaluated. The incidence rate of at least one coagulation parameter abnormality was 22.6% (122/541) while PT was the most common factor (8.87%, 48/541). The one-year survival rate of patients with coagulopathy was significantly lower than that of patients with normal coagulation (p < 0.01). In a univariate analysis, patients with prolonged PT was associated with shortened DFS (p < 0.05). Meanwhile, PT was negatively correlated with pre-albumin level. TNM stage, CA19-9, GGT, and pre-albumin level were independent prognostic factors of DFS in the multivariate analysis. In conclusion, the incidence rate of coagulopathy of ICC patients is lower than HCC patients. Prolonged PT, advanced TNM stage, low pre-albumin level, and high CA19-9 and GGT level were correlated with high recurrence rate and poor prognosis.

Loss of Secreted Frizzled-Related Protein-1 expression is associated with poor prognosis in intrahepatic cholangiocarcinoma

AimsSecreted Frizzled-Related Protein-1 (SFRP1) is a well-known negative regulator of the wingless type (Wnt)-β-catenin pathway and its inactivation plays an important role in the development and progression of many cancers. In this study, we aimed to determine the clinical significance of SFRP1 expression in intrahepatic cholangiocarcinoma (IHCC) and to define the relationship to Wnt-β-catenin pathway. MethodsFifty IHCC patients who had liver resection were enrolled in this study. SFRP1 protein expression was examined by immunohistochemistry in tumor tissues. The patients were divided into two groups: SFRP1 positive (n = 30) and negative (n = 20). Clinicopathological characteristics were analyzed. ResultsSFRP1 significantly correlated with curability (Cur A, B vs. C, p = 0.029); and recurrent pattern (intrahepatic vs. extrahepatic, p = 0.010). The negative SFRP1 group had significantly poorer prognosis, and 5-year survival rates were 8.1% of the negative SFRP1 group and 44.6% of the positive SFRP1 group, respectively. Moreover, the disease-free survival rate in the negative SFRP1 group was significantly poorer (p < 0.001). Multivariate analysis revealed that loss of SFRP1served as an independent prognostic factor in IHCC for both overall (HR, 2.923; 95% CI, 1.30–6.56; p = 0.009) and disease-free (HR, 2.631; 95% CI, 1.31–5.27; p = 0.006) survival. In addition, SFRP1 expression negatively correlated to β-catenin expression (p = 0.005). ConclusionsThose results suggested that the loss of SFRP1 could be a poor prognostic factor for IHCC, through the Wnt-β-catenin pathway.

Proposal of Perihilar Surrounding Area in Relation to Regional Lymphadenectomy in Selected Patients With Intrahepatic Cholangiocarcinoma

Lymph node (LN) metastasis is well recognized as a poor prognostic factor in intrahepatic cholangiocarcinoma (ICC); however, the efficacy of LN dissection for ICC remains unclear. We clarify a targeted papulation of ICC to evaluate it in this study. A retrospective study of patients who underwent liver resection without the extrahepatic bile duct for ICC was conducted. The pattern of LN recurrence and the location of the primary tumor were evaluated. Between January 2003 and July 2014, 52 patients with ICC underwent surgery. Fourteen patients had LN recurrence, 6 of whom had LN recurrence only. Excluding patients with LN dissection at surgery, the primary tumor was limited to the perihilar surrounding area in patients with LN recurrence only. Recurrence rate in LNs was 50% in patients with primary tumors originating in the perihilar surrounding area, which was significantly higher than the rate of 13% in patients with primary tumors originating in other areas. Primary tumors in the perihilar surrounding area have a high risk of LN recurrence. Regional lymphadenectomy combined with hepatectomy should be carried out in patients with ICC located in this area. The incidence of LN metastasis and the possibility of preventing LN recurrence could be effectively revealed by regional lymphadenectomy in selected patients.

High-mobility group box 1 expression and lymph node metastasis in intrahepatic cholangiocarcinoma.

To evaluate the prognostic value of high-mobility group box 1 (HMGB1) expression in intrahepatic cholangiocarcinoma (IHCC) and the possible underlying mechanism. Tissue microarray was constructed from 65 IHCC patients. Immunohistochemistry was performed to validate expression of HMGB1 and Vascular endothelial growth factor C (VEGF-C). Real-time PCR and Western blot analyses were used to study transcript and protein levels. The interaction between HMGB1 and VEGF-C was evaluated by siRNA, real-time PCR, and enzyme-linked immuno assays. The correlation between HMGB1 expression and other clinicopathologic parameters was analyzed by χ (2) test, and the univariate as well as multivariate analyses were accomplished by Kaplan-Meier method and Cox-regression model, respectively. Overall, overexpression of HMGB1 was found in 38/65 (58.8%) IHCCs, whereas VEGF-C overexpression was present in 30/65 (46.2%) cases. Overexpression of HMGB1 was significantly correlated with lymphatic microvessel density (P = 0.031, r = 0.268) and VEGF-C expression (P = 0.041, r = 0.254). With univariate analysis, both HMGB1 (P = 0.001) and VEGF-C (P = 0.004) were identified to be significantly associated with overall survival rate. Multivariate analysis indicated that HMGB1 could be served as an unfavorable independent prognostic factor in IHCCs (P = 0.005). siRNA knockdown of HMGB1 inhibited transforming growth factor-β-induced epithelial-mesenchymal transition (EMT) by elevating E-Cadherin expression and reducing expression of N-Cadherin, Vimentin and Snail in RBE cells. Further in vitro study revealed that HMGB1 silencing significantly decreased the level of VEGF-C, whereas the recombinant HMGB1 increased the VEGF-C level in RBE cells (both P < 0.05), which suggested that HMGB1 could promote lymphatic microvessel density, and subsequently lymphatic invasion, via promoting VEGF-C expression. Our results define an important role of HMGB1 in the progression of cholangiocarcinoma, and HMGB1 may serve as a prognostic marker for IHCC patients.

Prognostic Impact of Preoperative Lymph Node Enlargement in Intrahepatic Cholangiocarcinoma: A Multi-Institutional Study by the Kyushu Study Group of Liver Surgery.

Although lymph node metastasis (LNM) has been considered an important prognostic factor for intrahepatic cholangiocarcinoma (ICC), the impact of lymph node enlargement on the prognosis of ICC, and the accuracy of diagnosis of LNM, have not been fully clarified. Using a chart review of 225 patients with ICC, we compared survival times between patients with and without lymph node enlargement, and we evaluated the accuracy of diagnosis of LNM. We also performed a multivariate analysis to determine the variables affecting overall survival in the study population. The survival time of patients without lymph node enlargement was significantly longer than that of patients with lymph node enlargement (median survival time [MST] 43.7 vs. 20.1 months; p = 0.007). However, in the group with enlarged lymph nodes, survival time was prolonged as a result of hepatectomy (MST 20.1 vs. 7.6 months; p < 0.01). The sensitivity of lymph node size and positron emission tomography-computed tomography findings for diagnosing LNM were 50.0 % (23/46) and 31.2 % (5/16), respectively, and were thus insufficient. Multivariate analysis identified the serum carcinoembryonic antigen (hazard ratio [HR] 1.830) and carbohydrate antigen 19-9 (HR 2.189) levels, blood transfusion (HR 1.792), intrahepatic metastasis (HR 1.988), and final stage (HR 8.684) as prognostic factors for overall survival, but lymph node enlargement was not identified as a prognostic factor. Preoperative evaluation of LNM proved to be difficult, and survival time in ICC patients with lymph node enlargement was prolonged as a result of hepatectomy. Thus, ICC patients with preoperative lymph node enlargement should not be prematurely deemed non-curative cases.

Role of 5-hydroxymethylcytosine level in diagnosis and prognosis prediction of intrahepatic cholangiocarcinoma.

The loss of 5-hydroxymethylcytosine (5-hmC) has been identified as an epigenetic hallmark in several malignancies. However, its role in intrahepatic cholangiocarcinoma (ICC) is still unknown. Our study aims to investigate the level of 5-hmC in diagnosis and prognosis prediction of ICC. The 5-hmC levels were detected using dot blot, tissue microarray technique and immunohistochemical method, and the correlation between 5-hmC level and ICC clinicopathological parameters was analysed. Compared with matched liver tissues, most of ICC tissues presented with the loss of 5-hmC. Furthermore, the subgroups of cirrhotic and poor differentiation tissues showed the lowest level of 5-hmC. We found that 5-hmC level in non-elevated ICC patients was significantly related to lymph node metastasis and TNM stage and not related to vessel invasion, sex, age, HBV, cirrhosis or degree of differentiation. ICC patients with high TNM stage (stages III and IV) and lymph node metastases had significantly lower 5-hmC level than those with low TNM stage (stages I and II) and no lymph node metastases. Further analysis showed that low 5-hmC level is significantly correlated with worse overall survival (OS) and disease-free survival (DFS). Importantly, multivariate analysis indicated that 5-hmC level, tumour diameter, lymphatic metastasis and tumour differentiation could be used as independent prognostic factors for ICC. The loss of 5-hmC is implicated in the progression of ICC. Our results can contribute to the diagnostic ability and postoperative surveillance of ICC patients.

Hepatoma-derived growth factor: a novel prognostic biomarker in intrahepatic cholangiocarcinoma.

Hepatoma-derived growth factor (HDGF) is an acidic heparin-binding protein involved in tumor progression and poor prognosis of kinds of cancers. Aimed at investigating the functions of HDGF in intrahepatic cholangiocarcinoma (IHCC), we detected the expression of HDGF by immunohistochemistry in 83 patients. Associations of HDGF with clinicopathologic features, microvascular density (MVD), and overall survival rates were further analyzed by Chi-square method, univariate or multivariate analysis. HDGF functions in IHCC proliferation, invasion, and angiogenesis were detected by MTT, transwell, and tube formation assays, respectively. As a result, we found that HDGF-positive expression rate in IHCC was 51.8% (43/83) in IHCC. HDGF expression was significantly correlated to MVD (P = 0.031), lymphatic invasion (P = 0.030), distant metastasis (P = 0.002), and TNM stage (P = 0.037). HDGF was further identified as an independent prognostic factor in IHCC with Kaplan-Meier method (P = 0.003) and Cox-regression model (P = 0.008). Moreover, both intracellular and extracellular HDGF were proved to promote the proliferation, invasion, and angiogenesis of IHCC cell lines. In conclusion, HDGF was identified as an independent prognostic biomarker in IHCC. HDGF can promote IHCC cells progression, including proliferation, invasion, and angiogenesis, indicating HDGF could become a new promising and potential drug target of IHCC.

Clinical significance of nerve growth factor and tropomyosin-receptor-kinase signaling pathway in intrahepatic cholangiocarcinoma.

To investigate the correlation between nerve growth factor-tropomyosin-receptor-kinase (NGF-TrkA) signaling pathway and prognosis in intrahepatic cholangiocarcinoma (IHCC). NGF and TrkA expression in 83 samples of IHCC was assessed by immunohistochemistry. Correlations between NGF-TrkA expression and clinicopathological features were analyzed by χ² test. Moreover, we evaluated the association between NGF-TrkA and overall survival by univariate and multivariate analysis. With experiments in vitro, we investigated the crucial role of NGF-TrkA on proliferation and invasion of IHCC cells with recombinant NGF-β stimulation. We found that NGF and TrkA expression was significantly related with differentiation (P = 0.024) and intraneural invasion (P = 0.003), respectively. Additionally, double higher expression of NGF and TrkA was identified as an independent prognostic factor in IHCC (P = 0.003). Moreover, we demonstrated that NGF-TrkA signaling pathway can promote IHCC proliferation and invasion. NGF-TrkA double higher expression is an independent prognostic factor in IHCC. NGF-TrkA pathway can promote IHCC progression, indicating that NGF-TrkA may become a potential drug target.

Inactivation of Smad4 is a prognostic factor in intrahepatic cholangiocarcinoma

Background Smad4 is found mutated in many cancers. It acts as a tumor suppressor in the regulation of TGF-β signaling pathway. The objective of this work was to study the expression of Smad4 in intrahepatic cholangiocarcinoma (ICC) and its relationship with the biological behavior and prognosis of the disease. Methods Forty-nine paraffin-embedded ICC specimens and nine normal liver tissues were analyzed by immunohistochemical methods using Smad4 monoclonal antibodies. The expression of Smad4 was compared with the clinical pathological characteristics of the patients. Results The expression of Smad4 was 100% positive in normal liver tissues, which was higher than that in the ICC (44.9%). Negative labeling of the Smad4 protein was found in 26.1% (6/23) of well-differentiated ICCs and 61.5% (16/26) of poorly to moderately differentiated ICCs, and 34.3% (12/35) and 71.4% (10/14) showed negative Smad4 labeling (P=0.018) of ICC at pathological Tumor Node Metastasis (pTNM) stage I-II and pTNM stage III-IV separately. Furthermore, 72% (8/11) of lymph node metastatic ICCs and 73.3% (11/15) of intrahepatic metastatic ICCs showed negative labeling of the Smad4 protein. The loss of Smad4 expression in those metastatic ICCs was significantly more severe compared with non-metastatic ICCs (P=0.000). Conclusions The expression of Smad4 was associated with the histological grade, clinical stage, and metastasis of ICC (P &lt;0.05). The detection of Smad4 may be helpful in determining the degree of malignancy and prognosis of ICC.

Intrahepatic cholangiocarcinoma: a clinicopathologic study of 37 resected cases.

This study aimed to evaluate prognostic factors for intrahepatic cholangiocarcinoma (ICC) patients who underwent surgical procedure. A total of 37 ICC patients who underwent curative hepatic resection in our department from November 2006 to June 2009 were recruited in this study. Eighteen clinicopathological factors that might influence survival were selected. Survival rates of patients were calculated using the Kaplan-Meier method and the prognostic factors were selected by the Cox proportional hazard model. The overall 1-, 3- and 5- year survival rates were 37.1%, 17.1% and 11.4%, respectively. Univariate analysis showed that tumor thrombus, intrahepatic bile duct dilatation, hepatolithiasis, high serum levels of carbohydrate antigen 19-9 (CA19-9), high serum levels of total bilirubin (TB), low serum levels of prealbumin, high serum levels of γ-glutamyltransferase (γ-GT), high serum levels of alkaline phosphatase (ALP), transfusion, lymph node metastases, advanced UICC stages were significant risk factors for survival. Multivariate analysis identified CA19-9, prealbumin as independent risk factors for postoperative survival. This study suggested serum prealbumin levels could effectively predict the survival of the ICC patients with the treatment of operation. High serum CA19-9 level was associated with poor survival of ICC patients who underwent operation.

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.

Prognosis of the intrahepatic cholangiocarcinoma after resection: hepatitis B virus infection and adjuvant chemotherapy are favorable prognosis factors

AimThe incidence and mortality associated with intrahepatic cholangiocarcinoma is increasing in many countries and documentation of disease outcome is sparse. The present study was undertaken to investigate the prognostic factors for intrahepatic cholangiocarcinoma (ICC) following surgical resection. The impact of pre-existing HBV virus infection and adjuvant chemotherapy on the overall survival was also evaluated.MethodsClinical and pathological data were collected retrospectively from 81 patients undergoing surgery for ICC between 2005 and 2011, at The Henan Province Tumor Hospital and the First Affiliated Hospital of Zheng Zhou University. Survival and prognosis were analyzed using the Kaplan-Meier method and COX regression model.ResultsThe population included 37 patients who were HBsAg + or anti-HBc+, 21 patients who were anti-HBs + positive and 18 patients who received adjuvant chemotherapy. The overall 1- and 3-year survival rates were 51% and 20%, respectively. The median survival was 12.2 months. Univariate analysis identified the following prognostic factors: HBV virus infection or HBV vaccine prior to resection (P = 0.017); adjuvant chemotherapy (P = 0.001); preoperative serum CA19-9 (> 200 U/mL; P = 0.015); GGT (> 64 U/L; P = 0.008), ALP (> 119 U/L; P = 0.01); lymph node metastasis (P = 0.005); radical resection (P = 0.021); intrahepatic metastasis (P = 0.015) and diabetes (P = 0.07). Multivariate analysis identified chronic HBV infection (RR = 0.583; P = 0.041), anti-HBs positivity (RR = 0.680; P = 0.050), adjuvant chemotherapy (RR = 0.227; P < 0.001), lymph node metastasis (RR = 2.320; P = 0.001), and intrahepatic duct stones (RR = 0.473; P = 0.032) as independent prognostic factors.ConclusionsHBV virus infection or HBV vaccination prior to resection, together with adjuvant chemotherapy, were independently associated with improved survival in patients undergoing surgery for ICC.

Expression of Matrix Metalloproteinase-7 is an Unfavorable Prognostic Factor in Intrahepatic Cholangiocarcinoma

BackgroundIntrahepatic cholangiocarcinoma (IHCC) is a highly malignant neoplasm, but the prognostic factors of IHCC are not yet fully understood. The matrix metalloproteinases (MMPs) are known to be related to tumor viability. The aim of this study was to evaluate the prognostic significance of clinicopathological and immunohistochemical characteristics of resected IHCC. Patients and MethodsFrom 1996 to 2006, we surgically treated 35 patients with IHCC. Clinicopathological and immunohistochemical characteristics, including expression of MMPs, vascular endothelial growth factor, and epidermal growth factor receptor in the resected specimens, were investigated, and overall survival rates were evaluated with regard to the characteristics using univariate and multivariate analyses. ResultsUnivariate analysis revealed the significant prognostic factors to be preoperative serum CEA and CA19-9, intraoperative transfusion, tumor size, surgical margin, lymph node metastasis, invasion of portal and hepatic vein, intrahepatic metastasis, UICC stage, and expression of MMP-7. Subsequent multivariate analysis indicated that MMP-7 was an independent prognostic factor (hazard ratio (HR), 4.698; 95% confidence interval (CI), 0.057–0.866; P = 0.03) along with intrahepatic metastasis (HR, 5.694; 95% CI, 0.029–0.706; P = 0.017). ConclusionMMP-7 expression is associated with a poor prognosis in patients with resected IHCC.

Prognostic Value of Cirrhosis for Intrahepatic Cholangiocarcinoma After Surgical Treatment

BackgroundThe surgical outcome and prognostic factors of intrahepatic cholangiocarcinoma are not fully understood. This study aimed to establish the clinical significance of cirrhosis for prognosis in patients with intrahepatic cholangiocarcinoma after surgery. MethodsOne hundred fifteen patients with intrahepatic cholangiocarcinoma who underwent surgical resection between December 2001 and January 2008 were retrospectively analyzed. The prognostic significance of clinicopathologic factors including cirrhosis was assessed by univariate and multivariate analyses. ResultsThirty-two of the 115 patients (28%) had liver cirrhosis. Complete tumor removal (R0 resection) was performed in 42 patients (75%). Overall median survival time was 21 months, with 1-, 3-, and 5-year actuarial survival rates of 68%, 27%, and 17%, respectively. There was a significant difference in survival between patients with cirrhosis and those without cirrhosis (P = 0.027). Univariate analysis showed that cirrhosis, vascular invasion, hepatic duct invasion, lymph node metastasis, positive surgical margin (R1), and TNM stage were significantly associated with poor survival. Multivariate analysis showed that cirrhosis, positive surgical margin, and lymph node metastases were related to survival, with hazard ratios of 2.49, 3.53, and 4.16, respectively. ConclusionsCirrhosis is an independent factor for poor prognosis in intrahepatic cholangiocarcinoma after surgery.

Hepatitis B virus infection: A favorable prognostic factor for intrahepatic cholangiocarcinoma after resection

To study the prognostic factors for intrahepatic cholangiocarcinoma (ICC) and evaluate the impact of chronic hepatitis B virus (HBV) infection on survival rate of ICC patients. A total of 155 ICC patients who underwent macroscopic curative resections (R0 and R1) were enrolled in this retrospective study and divided into group A with HBV infection and group B without HBV infection according to their chronic HBV infection, represented by positive hepatitis B surface antigen (HBsAg) in serum or in liver tissue. Clinicopathological characteristics and survival rate of the patients were evaluated. All patients underwent anatomical resection. Their 1- and 3-year survival rates were 60.6% and 32.1%, respectively. Multivariate analyses revealed that HBV infection, hepatolithiasis, microscopic satellite lesion, and lymphatic metastasis were the independent prognostic factors for the survival rate of ICC patients. The median disease-free survival time of the patients was 5.0 mo. The number of tumors, microscopic satellite lesion, and vascular invasion were the independent prognostic factors for the disease-free survival rate of the patients. The prognostic factors affecting the survival rate of ICC patients with HBV infection and those without HBV infection were not completely consistent. Alkaline phosphatase > 119 U/L, microscopic satellite lesion, vascular invasion, and lymphatic metastasis were the independent factors for the patients with HBV infection, while r-glutamyltransferase > 64 U/L, microscopic satellite lesion, and poor tumor differentiation were the independent factors for the patients without HBV infection. HBV infection is a valuable clinical factor for predicting tumor invasiveness and clinical outcome of ICC patients. ICC patients with HBV infection should be distinguished from those without HBV infection because they have different clinicopathological characteristics, prognostic factors and outcomes after surgical resection.

Impact of nodal involvement on surgical outcomes of intrahepatic cholangiocarcinoma: a multicenter analysis by the Study Group for Hepatic Surgery of the Japanese Society of Hepato‐Biliary‐Pancreatic Surgery

The aim of this study was to clarify the prognostic factors of intrahepatic cholangiocarcinoma (ICC) following hepatectomy and to examine the impact of lymph node metastasis on survival. This study was therefore carried out as a Project Study of the Japanese Society of Hepato-Biliary-Pancreatic Surgery. Three hundred and forty-one patients who underwent hepatectomy for ICC between 1995 and 2004 at the 9 institutions of the Medical University Hospitals were analyzed retrospectively. Multivariate regression analyses and a Kaplan-Meyer analysis were performed to identify prognostic factors. Pathological lymph node metastasis was one of the significant factors affecting overall survival (hazard ratio 2.10, p < 0.001) based on the multivariate analysis. Among the patients who underwent extended lymphadenectomy beyond the hepatoduodenal ligament, the median survival of 121 patients with nodal involvement was 12.2 months. Only seven patients with nodal involvement have survived for more than 4 years. In the present study, preoperative carbohydrate antigen (CA) 19-9, intrahepatic metastasis, and nodal involvement were the significant independent predictors of poor prognosis by multivariate analysis. Further prospective studies may thus be needed to confirm these findings, because this study has a limitation in that it was a retrospective study with multicenter data collection.

Survival Analysis of Intrahepatic Cholangiocarcinoma After Resection

Intrahepatic cholangiocarcinoma (ICC) is the second most common primary hepatic malignancy, but the studies for the outcome after resection of ICC are rare. The aim of this study was to elucidate outcomes and prognostic factors of ICC in patients undergoing hepatic resection. A retrospective study was conducted with a total of 63 patients who underwent surgical resection with curative intent for ICC. We performed the survival analysis with preoperative and postoperative clinicopathologic factors according to the clinical outcome. The cumulative 1-, 3-, and 5-year survival rates were 68.2, 50.5, and 31.8%, respectively. Univariate analysis revealed that patient's old age, high preoperative carbohydrate antigen 19-9 (CA19-9) level, major vessel invasion, T classification, lymph node metastasis, lymphatic invasion, perineural invasion, intrahepatic metastasis, and narrow resection margin were statistically significant. By multivariate analysis, patient's old age, high preoperative CA19-9 level, lymphatic invasion, and narrow resection margin were independent dismal prognostic factors. The preoperative CA19-9 level shows a significant correlation with some histopathologic factors including major vessel invasion, bile duct invasion, and perineural invasion. Preoperative CA19-9 level was a valuable clinical factor for predicting histopathologic invasiveness as well as clinical outcome. An adequate resection margin was the only modifiable factor by a surgeon during hepatic resection for ICC.

The clinical presentation and prognostic factors for intrahepatic and extrahepatic cholangiocarcinoma in a tertiary care centre

The incidence of cholangiocarcinoma is rising. Accurate predictors of survival at diagnosis are not well defined. To clarify the clinical presentation and prognostic factors of intrahepatic cholangiocarcinoma and extrahepatic cholangiocarcinoma in a contemporary cohort of patients. Records for consecutive patients at the University of Michigan hospital diagnosed with cholangiocarcinoma between January 2003 and April 2008 were reviewed. In all, 136 patients had cholangiocarcinoma (79 intra- and 57 extrahepatic cholangiocarcinoma). Median survival was 27.3 months-25.8 months for intrahepatic cholangiocarcinoma and 30.3 months for extrahepatic cholangiocarcinoma. Independent predictors of mortality at presentation on multivariate analysis were elevated bilirubin level (HR 1.04, 95%CI 1.01-1.07), CA 19-9 levels >100 U/mL (HR 1.90, 95%CI 1.17-3.08) and stage of disease (HR 1.51, 95%CI 1.16-1.96). After adjusting for baseline prognostic factors, surgical therapy was associated with improved survival (HR 0.48; 95% CI 0.26-0.88). There were no significant differences regarding clinical presentation, disease stage (P = 0.98), and survival (P = 0.51) between intra- and extrahepatic cholangiocarcinoma. Survival for cholangiocarcinoma remains poor with no significant difference in outcomes between intra- and extrahepatic cholangiocarcinoma. Stage of disease, bilirubin level and CA 19-9 level are important prognostic factors at presentation. Surgical therapy provides similar efficacy for both tumours when adjusted for other prognostic variables.