10 - World Journal of Gastroenterology

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Zhou HB et al . Hepatitis B virus and prognosis of intrahepatic cholangiocarcinoma Poorly 34 23.5 17.6 0.647 NA NA NA Vascular invasion Yes 31 16.1 9.7 No 101 35.6 23.5 0.005 0.025 5.030 1.072-2.812 Lymphatic metastasis Yes 109 4.3 < 0.01 No 23 36.7 24.5 < 0.001 0.182 1.781 0.834-2.597 Extrahepatic metastasis Yes 8 < 0.01 < 0.01 No 124 33.1 21.6 0.059 0.609 0.261 0.551-2.764 CK19 staining (n = 130) 1 Positive 13 27.4 17.9 Negative 117 61.5 34.6 0.038 0.522 0.410 0.597-2.762 1 Number of available data. AFP: a-fetoprotein; ALP: Alkaline phosphatase; r-GT: R-glutamyltransferase; CA 19-9: Carbohydrate antigen 19-9; CK19: Cytokeratin19; NA: Not available. tumor differentiation, vascular invasion, and CK19 were not significantly correlated with the overall survival rate of ICC patients after hepatic resection (Table 2). Tumor recurrence occurred in 108 patients. The disease-free survival rate was 31.1% and 20.3%, respectively, for the ICC patients 1 and 3 years after operation with a median disease-free survival time of 5.0 mo (Figure 1). Univariate analysis showed that hepatolithiasis, r-GT > 64 U/L, ALP > 119 U/L, CA19-9 > 37 U/mL, multiple tumors, microscopic satellite lesion, vascular invasion, lymph node metastasis, and positive CK19 were the significant risk factors for tumor recurrence in ICC patients. Multivariate analysis demonstrated that the number of tumors (95.0% CI = 1.194-3.863), microscopic satellite lesion (95.0% CI = 1.106-2.745), and vascular invasion (95.0% CI = 1.072-2.812) were the independent prognostic factors for disease-free survival rate of ICC patients (Table 3). The most common tumor recurrence sites were the remnant liver and regional lymph nodes. The treatment modalities for recurrent tumors included repeated operation (n = 9), transplantation (n = 2), radiation therapy (n = 7), radiofrequency ablation (n = 9), microwave coagulation (n = 3), percutaneous ethanol injection therapy (n = 23), and transarterial chemoembolization (n = 93). Prognostic factors for ICC patients according to their HBV infection The clinicopathological characteristics of ICC patients with HBV infection and those without HBV infection were compared to further interpret the influence of chronic HBV infection on their survival rate. Univariate analysis showed that the following variables were significantly different between the patients with HBV infection and those without HBV infection, including gender, AST, AFP, CA19-9, inflammation of liver tissue, cirrhosis, hepatolithiasis, tumor capsule formation, tumor differentiation, lymphatic metastasis, and positive immunohistochemical staining of CK19. Although perineural infiltration was not significantly different between them, it occurred more frequently in ICC patients without HBV infection than in those with HBV infection (Table 4). The potential prognostic factors affecting the survival rate of the patients with HBV infection and those without HBV infection were compared to further clarify the difference in prognostic factors affecting their survival rate. The Table 4 Clinicopathological features of intrahepatic cholangiocarcinoma patients according to their hepatitis B virus infection HBV infection Yes (n = 87) No (n = 68) P value (89.66) 57 (86.36) 0.531 Gender (M/F) 64/23 38/30 0.021 Age (> 65 yr) (%) 17 (19.54) 13 (14.94) 0.763 Hepatolithiasis (%) 2 (2.30) 10 (14.71) 0.004 Hepatic schistosomiasis (%) 2 (2.30) 5 (7.35) 0.133 ALT (> 42 U/L) (%) 27 (34.03) 15 (22.06) 0.212 AST (> 37 U/L) (%) 38 (43.68) 15(22.06) 0.005 TBIL (> 20 μmol/L) (%) 20 (22.99) 16 (23.53) 0.937 r-GT (> 64 U/L) (%) 49 (56.32) 38 (55.88) 0.956 ALP(> 119 U/L) (%) 33 (37.93) 33 (48.53) 0.185 AFP (> 20 μg/L) (%) 25 (28.74) 5 (7.35) 0.001 CA19-9 (> 37 U/mL) (%) 44 (50.57) 45 (66.18) 0.051 CA19-9 (> 200 U/mL) (%) 20 (22.99) 32 (47.06) 0.002 Tumor location (%) 0.520 Left lobe 28 (32.18) 27 (39.71) Right lobe 54 (62.07) 36 (52.94) Both lobes 5 (5.75) 5 (7.35) Tumor size < 5 cm 38 (43.68) 20 (29.41) 0.069 ≥ 5 cm 49 (56.32) 48 (70.59) Tumor number (%) 0.958 Single 77 (88.51) 60 (88.24) Multiple 10 (11.49) 8 (11.76) Histological inflammation (%) 35 (40.23) 4 (11.76) < 0.001 Cirrhosis (%) 40 (45.98) 5 (7.35) < 0.001 Capsule formation (%) 15 (17.24) 2 (2.41) 0.005 Tumor differentiation (%) 0.036 Well 0 (< 0.01) 5 (7.35) Moderately 66 (75.86) 47 (69.12) Poorly 21 (24.14) 16 (23.53) Vascular invasion (%) 22 (25.29) 13 (19.12) 0.362 Perineural infiltration (%) 0 (< 0.01) 3 (4.41) 0.082 Microscopic satellite lesion (%) 23 (26.44) 16 (23.53) 0.679 Lymphatic metastasis (%) 12 (13.79) 20 (29.41) 0.017 Extrahepatic metastasis (%) 5 (5.75) 5 (7.35) 0.749 Immunohistochemical examinations CK18 positive staining (%) 78 (n = 135) 1 CK19 positive staining (%) (n = 139) 1 75 (86.21) 64 (96.97) 0.022 1 Number of available data. HBV: Hepatitis B virus; M: Male; F: Female; TBIL: Total bilirubin; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; AFP: a-fetoprotein; ALP: Alkaline phosphatase; r-GT: R-glutamyltransferase; CA19-9: Carbohydrate antigen 19-9; CK: Cytokeratin. prognostic factors for the patients with HBV infection and WJG|www.wjgnet.com 1297 March 14, 2011|Volume 17|Issue 10|
Zhou HB et al . Hepatitis B virus and prognosis of intrahepatic cholangiocarcinoma A cumulative survival (%) 125 100 75 50 25 ALP ≤ 119 U/L ALP > 119 U/L P = 0.028 B cumulative survival (%) 125 100 75 50 25 Microscopic satellite lesion (-) Microscopic satellite lesion (+) P = 0.001 0 0 10 20 30 40 50 60 70 Survival time (mo) 0 0 10 20 30 40 50 60 70 Survival time (mo) C cumulative survival (%) 125 100 75 50 25 Vascular invasion (-) Vascular invasion (+) P = 0.041 D cumulative survival (%) 125 100 75 50 25 Lymphatic metastasis (-) Lymphatic metastasis (+) P = 0.005 0 0 10 20 30 40 50 60 70 Survival time (mo) 0 0 10 20 30 40 50 60 70 Survival time (mo) Figure 2 Adjusted survival curves according to the independent prognostic factors by multivariate analysis (Cox model) for intrahepatic cholangiocarcinoma with hepatitis B virus infection after resection. A: Alkaline phosphatase (ALP); B: Microscopic satellite lesion; C: Vascular invasion; D: Lymphatic metastasis. those without HBV infection were not completely consistent (Tables 5 and Table 6). Univariate analysis demonstrated that ALP > 119 U/L, microscopic satellite lesion, tumor size ≥ 5 cm, lymphatic metastasis, and vascular invasion were the significant poor prognostic factors for the survival rate of patients with HBV infection (Table 5), while r-GT > 64 U/L, CA19-9 > 37 U/mL, hepatolithiasis, microscopic satellite lesion, lymphatic and extrahepatic metastasis were the significant poor prognostic factors for the survival rate of those without HBV infection (Table 6). Cox regression analysis demonstrated that ALP > 119 U/L(hazard ratio: 4.800), microscopic satellite lesion (hazard ratio: 12.066), lymphatic metastasis (hazard ratio: 7.887), and vascular invasion (hazard ratio: 4.167) were the independent poor prognostic factors for patients with HBV infection (Table 5, Figure 2), while r-GT > 64 U/L (hazard ratio: 4.157), microscopic satellite lesion (hazard ratio: 5.965), and poor tumor differentiation (hazard ratio: 5.844) were the independent poor prognostic factors for those with out HBV infection (Table 6, Figure 3). DISCUSSION Although a number studies are available on the correlation between chronic HBV infection and ICC [5-11] , the impact of HBV infection on the survival rate of ICC patients remains unclear. In the present study, HBV infection was found to be a favorable prognostic factor for the patients with ICC after resection, thus ICC patients with HBV infection should be distinguished from those without HBV infection. First, ICC patients with HBV infection and those without HBV infection are different in their clinicopathological characteristics. It was reported that the number of male ICC patients with HBV infection is more, with a younger age, a higher abnormal liver function and a higher serum AFP level, a worse histological inflammation and cirrhosis, a poorer tumor differentiation and encapsulation, a lower serum CA19-9 level, and a lower frequency of lymphatic metastasis and positive CK19 than those of ICC patients without HBV infection [11] . Second, ICC patients with HBV infection have a more favorable outcome after surgical resection than those without HBV infection. Third, the prognostic factors for the survival rate of ICC patients with and those without HBV infection are different. Surgical resection remains the curable procedure for ICC. However, the prognosis of ICC after surgery is poor because of its high recurrence rate. The median survival time of ICC patients after operation is 11.0-37.4 mo [12-18] . The overall 1- and 3-year survival rates of ICC patients after operation are 46.3%-73.3% and 23.0%-55.0%, respectively [14,15,19-23] , which are consistent with the findings in our study. It was reported that the preoperative CA19-9 level, vascular invasion, perineural invasion, lymph node metastasis, intrahepatic metastasis, the number and differentiation of tumors are the significant prognostic factors for the overall survival rate of ICC patients [13,15-19] . In the present study, several clinicopathological factors that significantly influence the survival rate of ICC patients and WJG|www.wjgnet.com 1298 March 14, 2011|Volume 17|Issue 10|
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ISSN 1007-9327 (print) ISSN 2219-28
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Robert JL Fraser, Daw Park Jacob Ge
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Italy Donato F Altomare, Bari Piero
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Fernando Azpiroz, Barcelona Ramon B
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S Contents Weekly Volume 17 Number
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Contents World Journal of Gastroent
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Biecker E. Ascites in liver cirrhos
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Zhang BS et al . Congenital broncho
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Liu J et al . IL-10 polymorphism an
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Cui J et al . Endoscopic therapy fo
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Zhou JH et al . Autoantibody and es
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10 - World Journal of Gastroenterology

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