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BACKGROUND/AIMS: We conducted a retrospective cohort study to investigate factors to early and late phase recurrence of hepatocellular carcinoma (HCC). METHODS: The study population consisted of 249 patients including 157 with cirrhosis who underwent hepatectomy for HCC. The endpoint was time-to-recurrence. Using a Cox regression model, factors to early and late phase recurrences were investigated censoring recurrence-free patients at the 2-year time point and in patients without recurrence at 2 years. RESULTS: Actuarial probability of overall recurrence at 1, 3, and 5 years were 0.301, 0.623, and 0.790, respectively, with a median follow-up of 624 days. Early recurrence was observed in 123 out of 249 patients; while late recurrence was found in 61 out of 113 patients. Factors to early recurrence were as follows: non-anatomical resection, presence of microscopic vascular invasion, and serum alpha-fetoprotein level >or=32 ng/ml. Those contributing to late phase recurrence were higher grade of hepatitis activity, multiple tumors, and gross tumor classification. CONCLUSIONS: Variables associated with metastatic recurrence were factors to early phase recurrence; whereas those related with elevated carcinogenesis contributed to late phase recurrence, thus providing an epidemiological evidence that different mechanisms, i.e. metastasis and de novo, are involved in intrahepatic recurrence after hepatectomy for HCC.  相似文献   

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Background and Aim:  Previous studies have reported different risk factors for early and late intrahepatic recurrence after resection of hepatocellular carcinoma (HCC). However, the prognostic significance of the risk factors for early and late recurrence has not been clarified.
Methods:  A total of 190 Hepatitis B surface antigen-positive patients who received curative resection for HCC were reviewed. We investigated prognostic factors for disease-free and overall survival after resection, and further analyzed the relationship between significant prognostic factors and risk factors for early (≤14 months) and late (>14 months) intrahepatic recurrence.
Results:  The 5-year disease-free and overall survival rates were 43.9% and 71.5%, respectively. In multivariate analysis, adverse prognostic factors for disease-free survival were presence of serum HBeAg, perioperative transfusion, and the presence of portal vein invasion (PVI) and/or intrahepatic metastasis (IM). Multivariate analysis revealed that overall survival was associated with ICG R15, serum albumin, Edmondson–Steiner grade, and the presence of PVI and/or IM. Independent risk factors for early intrahepatic recurrence were perioperative transfusion and PVI and/or IM, whereas positivity for HBeAg was the only risk factor for late recurrence. In addition, post-recurrence survival in patients with late intrahepatic recurrence was completely comparable to that of patients who never experienced recurrence.
Conclusions:  The presence of serum HBeAg, the risk factor for late intrahepatic recurrence did not affect overall survival after resection because late recurrence was relatively well controlled by current available treatments. To further improve long-term surgical outcomes, effective treatment and preventive methods for early intrahepatic recurrence should be investigated.  相似文献   

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Background and Aim: Patients with persistently active hepatitis B virus (HBV) replication are at high risk for progression to liver cirrhosis and hepatocellular carcinoma (HCC). The influence of the viral load of HBV on intrahepatic recurrence after local ablation therapy in patients with HBV‐related HCC has not been elucidated. We aimed to evaluate predictors of intrahepatic recurrence and clarify the correlation between viral load and intrahepatic recurrence after percutaneous ablation. Methods: Patients with HBV‐related, solitary HCC undergoing radiofrequency ablation (RFA) or percutaneous ethanol injection (PEI), between October 2004 and December 2008 were prospectively enrolled. Statistical analyses were performed using the Kaplan–Meier method and Cox regression model to identify risk factors for intrahepatic recurrence. Results: A total of 145 patients (male, 81.4%; mean age, 55.3 years) were included. Ninety patients (62.1%) had serum HBV DNA ≥ 2000 IU/mL. The median follow‐up duration was 28.9 months (range, 12.0–57.0) and 63 patients (43.4%) experienced intrahepatic tumor recurrence. Multivariate analysis indicated that seropositivity for hepatitis B envelope antigen (HBeAg) was an independent negative predictor of intrahepatic recurrence (hazard ratio, 0.473; P = 0.026) and late (≥ 1 year) recurrence (HR, 0.288; P = 0.012). The serum alpha fetoprotein (AFP) level also significantly predicted late recurrence (HR, 1.001; P = 0.005). However, neither the ablation method nor serum HBV DNA titers were correlated with intrahepatic recurrence. Conclusions: These findings show that HBeAg‐negativity and serum AFP levels were associated with late intrahepatic recurrence of HCC, implicating HBeAg‐negativity as a risk factor for de novo recurrence after percutaneous ablation in HBV‐related HCC.  相似文献   

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Background/Aims: The recurrence rate of hepatitis B virus (HBV)‐related hepatocellular carcinoma (HCC) is high even in patients receiving curative therapy. In this study, we analysed the risk factors for tumour recurrence after curative therapy for HBV‐related HCC while under treatment with nucleot(s)ide analogues (NAs) by measuring serum HBcrAg and intrahepatic covalently closed circular DNA (cccDNA) levels to elucidate the viral status associated with HCC recurrence. Methods: We enrolled 55 patients who developed HCC during NA therapy and underwent either curative resection or percutaneous ablation for HCC. Results: Hepatocellular carcinoma recurred in 21 (38%) of the patients over a period of 2.2 (range, 0.2–7.4) years. In multivariate analysis, serum HBcrAg levels ≥4.8log U/ml at the time of HCC diagnosis (hazard ratio, 8.96; 95% confidential interval, 1.94–41.4) and portal vein invasion (3.94, 1.25–12.4) were independent factors for HCC recurrence. The recurrence‐free survival rates of the high cccDNA group were significantly lower than those of the low cccDNA group only in patients who underwent resection (P=0.0438). A positive correlation (P=0.028; r=0.479) was observed between the intrahepatic cccDNA and the serum HBcrAg levels at the incidence of HCC. Conclusion: HBcrAg is a predictor of the post‐treatment recurrence of HCC during antiviral therapy. Serum HBcrAg and intrahepatic cccDNA suppression by NAs may be important to prevent HCC recurrence.  相似文献   

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Recurrence after successful surgical or nonsurgical treatment of hepatocellular carcinoma (HCC) is caused either by intrahepatic metastasis or by metachronously multicentric occurrence. Intrahepatic metastasis is a major cause of recurrence of advanced HCCs with varying degrees of vascular invasion, and multicentric occurrence is a frequent cause of recurrence in small HCCs with no obvious vascular invasion. It is estimated that at least 20% of small HCCs have a high probability of recurrence due to multicentric occurrence, based on the finding that adenomatous hyperplasia (AH) and/or atypical adenomatous hyperplasia (AAH), which are considered premalignant lesions, are found in the vicinity of resected small HCCs with liver cirrhosis. However, because neither AH nor AAH occur in HCC cases without liver cirrhosis, most recurrence of HCC in noncirrhotic liver is considered to be due to intrahepatic metastasis or to de novo hepatocarcinogenesis. In a survey of autopsy cases of liver cirrhosis with small HCC, smaller HCC nodules were found in other liver slices in 50% of cases, and it is estimated that approximately 50% of HCC is already multicentric in the early stage.  相似文献   

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BACKGROUND/AIMS: Diffuse intrahepatic recurrence of hepatocellular carcinoma in the liver remnant carries an extremely poor prognosis compared with other recurrence patterns. We studied the predictors of this type of recurrence. METHODOLOGY: We determined the risk factors for recurrence and predictors of long-term post-recurrence survival using the Cox's proportional hazard model. We divided 106 patients with recurrent intrahepatic hepatocellular carcinoma into 3 groups based on the number of nodules, and compared clinicopathologic features to determine which risk factors were associated with the diffuse intrahepatic recurrence pattern. RESULTS: An elevated alpha-fetoprotein concentration, invasive nodular- or massive-type hepatocellular carcinoma, intrahepatic metastasis, the presence of macroscopic ductal invasion, and the lack of a capsule predict diffuse intrahepatic pattern of recurrence. Patients who have three or more of these five factors, are poor candidates for hepatic resection because the likelihood of diffuse intrahepatic recurrence is great, and post-recurrence survival is worse than that with solitary or multiple intrahepatic recurrence. CONCLUSIONS: It is possible to reduce the risks of cancer recurrence at the time of primary resection. It is important to predict the pattern of early diffuse intrahepatic recurrence. In candidates with a poor prognosis, adjuvant therapy or transplantation should be considered.  相似文献   

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BACKGROUND/AIMS: The aim of this study was to clarify the significant risk factors as they relate to early recurrence after hepatectomy in cirrhotic patients with hepatocellular carcinoma (HCC). METHODOLOGY: We retrospectively investigated 42 cirrhotic patients undergoing hepatectomy for a single HCC. We compared the clinicopathologic features of 14 patients with early intrahepatic recurrence (recurrence was detected within 1 year after hepatic resection; Group 1) with 28 patients without recurrence or with late intrahepatic recurrence (recurrence was confirmed more than 1 year after hepatic resection; Group 2). RESULTS: There were no significant differences in the pre-operative and intra-operative clinical background data or pathological data between the 2 groups. Regarding recurrence pattern, although not significant, the incidence of intrahepatic metastasis in Group 1 (85.7%) was higher than in Group 2 (50.0%). Maximum values of total bilirubin and albumin within 7 days after hepatectomy for patients in Group 2 were significantly better than those in Group 1. Aspatate aminotransferase (AST) and alanine aminotransferase (ALT) immediately after hepatectomy in Group 1 were also higher than in Group 2, although statistically insignificant. The overall 1-year and 3-year survival rates between Group 1 versus Group 2 were 85.7% versus 100% (p < 0.01) and 57.2% versus 90.0% (p < 0.01), respectively. CONCLUSIONS: Hepatic functional damage immediately after hepatectomy is as significant risk factor for early intrahepatic recurrence in cirrhotic HCC. Careful perioperative management of hepatic function may therefore be important in preventing early recurrence and prolonging survival.  相似文献   

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Tumor recurrence remains one major obstacle for further improving the prognosis of hepatitis B virus (HBV)‐related hepatocellular carcinoma (HCC) patients after curative liver resection. It has been widely reported that tumor size, positive surgical margin, macroscopic vascular invasion, tumor–node–metastasis stage and Edmondson's grade were significantly related to HCC recurrence. However, the association between HCC recurrence and important viral factors, including the HBV DNA levels, status of hepatitis B surface antigen and hepatitis B e‐antigen, levels of cccDNA and hepatitis B core‐related antigen, viral genotypes and specific viral sequence mutations remained controversial. Meanwhile, studies on the effect of postoperative adjuvant antiviral therapy on HCC recurrence have been relatively limited and have yielded conflicting results. Identification of certain viral risk factors for HCC recurrence and stratification of patient risk are very important to perform future surveillance programs. As a HBV hyperendemic region, the majority of HBV‐related HCC patients develop in East Asia. In this article, we thus systematically reviewed the risk of important viral factors involved in recurrent carcinogenesis and the role of adjuvant antiviral therapy in preventing tumor recurrence in this area.  相似文献   

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Background

Intrahepatic recurrence is a significant problem for patients who have undergone a hepatic resection for hepatocellular carcinoma (HCC). The objective of the present study was to identify risk factors and evaluate the management of early and late recurrence of solitary HCC after curative resection.

Methods

Included in this study were 816 patients with solitary HCC who underwent a curative partial hepatectomy. Intrahepatic recurrence in these patients was followed up retrospectively. Prognosis and therapy for the recurrence were investigated and analysed.

Results

Early and late intrahepatic recurrence occurred in 423 patients and 199 patients, respectively. Multivariate analysis showed that a tumour diameter >5 cm, the absence of a tumour capsule and the presence of microvascular invasion were correlated with early recurrence, whereas cirrhosis and alpha-fetal protein >400 μg/l were independent risk factors contributing to late recurrence. The 5-year survival of HCC patients with early recurrence was significantly lower than that of patients with late recurrence. Further curative treatment for intrahepatic recurrence offered a 5-year overall survival of 56.0%, which was better than alternative management.

Conclusion

Early and late recurrences of solitary HCC after curative resection are associated with different predictive factors. The time to recurrence and further curative treatment after recurrence were the best predictors of survival post recurrence.  相似文献   

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Background and Aim: Despite improvements of treatment in hepatocellular carcinoma (HCC), the recurrence rate after curative hepatic resection still remains remarkably high. An immediate recurrence of HCC after surgery is frustrating. We tried to clarify risks of immediate postoperative recurrence of HCC; that is, within 4 months after curative hepatic resection. Methods: A total of 167 patients with HCC underwent hepatic resection; 60 had immediate postoperative recurrences (IPR group), and 107 had disease‐free survival for more than 5 years (DFS group). Variables were compared between the two groups. Results: Univariate analysis showed the following variables were significant risk factors for immediate postoperative recurrence of HCC: male sex, elevated serum aspartate aminotransferase level, greater amount of blood loss, longer operation time, worse tumor differentiation, higher tumor node metastasis stage, and presence of any of the following: intrahepatic metastasis, tumor‐rupture, portal venous invasion, or microvascular invasion. In multivariate analysis, only portal venous invasion was a significant risk factor (odds ratio = 3.2, P = 0.03, standard error = 0.5, Logistic regression analysis). Conclusions: Portal venous invasion may be the most significant risk factor for immediate postoperative recurrence of HCC. However, accurate assessment of this risk factor may require histological examination, limiting its utility as a preoperative predictor. Further research is necessary to definitively identify preoperative predictors.  相似文献   

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Background: Extrahepatic metastasis of hepatocellular carcinoma (HCC) is of growing importance as the survival of patients has been improved owing to advances in treatments to intrahepatic lesions. Methods: To elucidate the incidence and risk factors of extrahepatic metastasis of HCC, we enrolled 1573 (1131 treatment‐naïve and 442 previously treated on referral) patients with HCC without extrahepatic tumour spread treated at the authors' department between 1990 and 2003. Patients received medical treatment including percutaneous ablation and transcatheter arterial chemoembolization, and followed by dynamic computed tomography (CT) or magnetic resonance imaging (MRI) and tumour markers every 3–4 months. Extrahepatic metastasis was diagnosed by plain X‐ray, CT, MRI and scintigraphy. Clinical parameters at the time of treatment to intrahepatic lesions were evaluated as a predictor of subsequent extrahepatic metastasis among the 1131 treatment‐naïve patients by Cox's proportional hazard model. Results: During the average observation period of 3.9 years, extrahepatic metastasis was diagnosed in 123 in the treatment‐naïve and 53 in the patients treated previously. The incidence rate of extrahepatic metastasis, as detected during the lifetime after medical treatment of HCC, was approximately 13% at 5 years. Multivariate analysis with Cox proportional hazard model revealed that positivity for viral markers, lager tumour diameter, multiple tumour nodules, presence of vascular tumour invasion and elevated tumour markers were associated with the development of extrahepatic metastasis. Conclusion: The incidence of extrahepatic metastasis of HCC diagnosed during clinical course was not frequent. Advanced intrahepatic lesions, presence of vascular tumour invasion, elevated tumour markers and presence of viral hepatitis were risk factors for extrahepatic metastasis.  相似文献   

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BACKGROUND: Although both hepatitis B virus (HBV) and hepatitis C virus (HCV) infection are well recognized risk factors for hepatocellular carcinoma (HCC), little is known with respect to how HBV and HCV infection affect HCC recurrence in postoperative HCC Chinese patients. The objective of this study was to determine if differences exist in preoperative characteristics and postoperative HCC recurrence in patients with different HBV and HCV infection status. METHODS: The study population consisted of 413 patients undergoing a curative resection at Tianjin Cancer Hospital for small HCC (< or =3 cm) from January 1997 to December 2003. The patients were divided into four groups: HCV only (n = 75), HBV only (n = 251), HBV and HCV (n = 33), and neither HBV nor HCV (NBNC, n = 54). The preoperative status and postoperative HCC recurrence were recorded. Survival analyses were used to assess the impact of HBV/HCV status on HCC recurrence. RESULTS: Patients with HCV had a significant association with older age, lower mean preoperative platelet counts and albumin levels, higher mean prothrombin time, alanine aminotransferase and total bilirubin levels and multinodular tumors during diagnosis. Patients with HCV also had significantly less differentiated tumors and a higher incidence of vascular invasion and cirrhosis when compared to the other groups. During the follow-up, the HCV group showed a higher incidence of intrahepatic recurrence and multiple recurrent lesions than the other patients. CONCLUSIONS: Patients with HCV infection tended to be older, and were characterized by more severe cirrhosis and higher incidence of tumor multicentricity. The statistically significant determinants for reoccurrence in patients with small HCC were HCV infection, presence of vascular invasion and multiple tumors.  相似文献   

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BACKGROUND/AIMS: Little has been documented to differentiate between recurrence originating from microscopic residual tumor cells and recurrence due to metachronous multicentric origin of hepatocellular carcinoma (HCC). The aim of this study was to clarify the risk factors of HCC recurrence closely related to residual tumor cells. METHODOLOGY: A retrospective review of hepatic resections for HCC during the period between April 1985 and April 1997 was undertaken at a University Hospital with a long history of hepatectomy for HCC. Three hundred and thirteen HCC patients without any definite multicentric recurrence, who underwent hepatectomy, were retrospectively investigated. Main outcome measures were: (Study 1) Risk factors for recurrence were univariately and multivariately investigated among various clinicopathological variables, including the vi factor as a new indicator of the potential malignancy of HCC (i.e., the presence of both microscopic portal vein invasion and intrahepatic metastasis). (Study 2). The risk factors for recurrence were then analyzed according to the period of recurrence. RESULTS: (Study 1) Independent risk factors were: (tumor factors) a positive vi factor, alpha-fetoprotein > 100 ng/ml, and poorly differentiated histology; (host factors) albumin < 3.8 g/dl, the presence of diabetes mellitus, platelet count < 14 x 10(4)/microliter, Y-globulin fraction > 20%. In those risk factors, the relative risk of the vi factor (2.6) was the largest. (Study 2) Within 1 year after hepatectomy, only tumor factors, including the vi factor and poorly differentiated histology, were significant risk factors, tumor factors were significant only up to 2 years after hepatectomy, and thereafter only host factors were significant. CONCLUSIONS: The risk factors for non-multicentric recurrence of HCC are considered to be a positive vi factor, alpha-fetoprotein, and poorly differentiated histology, and the vi factor is considered to be a new prognostic indicator expressing the potential malignancy of HCC such as invasion and metastasis.  相似文献   

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The recurrence of hepatocellular carcinoma, the sixth most common neoplasm and the third leading cause of cancer-related mortality worldwide, represents an important clinical problem, since it may occur after both surgical and medical treatment. The recurrence rate involves 2 phases: an early phase and a late phase. The early phase usually occurs within 2 years after resection; it is mainly related to local invasion and intrahepatic metastases and, therefore, to the intrinsic biology of the tumor. On the other hand, the late phase occurs more than 2 years after surgery and is mainly related to de novo tumor formation as a consequence of the carcinogenic cirrhotic environment. Since recent studies have reported that early and late recurrences may have different risk factors, it is clinically important to recognize these factors in the individual patient as soon as possible. The aim of this review was, therefore, to identify predicting factors for the recurrence of hepatocellular carcinoma, by means of invasive and non-invasive methods, according to the different therapeutic strategies available. In particular the role of emerging techniques (e.g., transient elastography) and biological features of hepatocellular carcinoma in predicting recurrence have been discussed. In particular, invasive methods were differentiated from non-invasive ones for research purposes, taking into consideration the emerging role of the genetic signature of hepatocellular carcinoma in order to better allocate treatment strategies and surveillance follow-up in patients with this type of tumor.  相似文献   

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BACKGROUND/AIMS: The recurrence rate after hepatectomy of hepatocellular carcinoma (HCC) remains high. Although the cause of recurrence seems to be the multicentric occurrence and metastasis of cancer cells in the patients after curative resection of HCC, the mechanism of HCC recurrence in each case is still uncertain. The recurrence pattern may illuminate these mechanisms. METHODOLOGY: A data analysis of 152 patients who underwent HCC resection, and had observed for more than 5 years was conducted. These patients were divided into three groups; group I (n=32), the patients without HCC recurrence, group II (n=86), the patients with fewer than four recurrent nodules of HCC, group III (n=34), the patients with four or more recurrent nodules of HCC. We compared the clinicopathological data of groups I and II, and of groups I and III. The linkage of risk factors linked to recurrence patterns was clarified. RESULTS: The risk factors linked to group II by comparison with group I were high serum levels of alanine aminotransferase, low serum levels of albumin, high values in the indocyanine green retention test at fifteen minutes, hepatitis C antibody positivity. low platelet counts, and high histological hepatitis activity. The risk factors linked to group III were large tumor size, histological presence of portal vein invasion by cancer cells, intrahepatic metastasis, and poor differentiation of cancer cells. CONCLUSIONS: The risk factors linked to recurrence with no more than three HCC nodules recurrence were related to host-related factors such as hepatic function, and hepatitis activity, but not tumor related. The risk factors linked to multiple recurrence were tumor related. The analysis of recurrence patterns revealed that completely different mechanisms exist in the patients with recurrence involving no more than four nodules, which may be related to multicentric occurrence, and patients with multiple recurrence, which may be related to the metastasis of cancer cells.  相似文献   

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BACKGROUND/AIM: To investigate the mode of progression of combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC). METHODS: An immunohistochemical study for E-cadherin (ECD) and alpha- and beta-catenins was performed on 29 cases of cHCC-CC. RESULTS: Reduced expression of ECD was significantly correlated with the tumour grade of the hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) components, intrahepatic metastasis (IM) of HCC, IM of CC, and vascular invasion of CC (p < 0.05, respectively). There was a significant relationship between the reduced expression of beta-catenin and the tumour grade of HCC components (p < 0.05). Cases showing concurrent intrahepatic metastasis composed of HCC, CC, or both, numbered 6, 5, and 2, respectively. The expression patterns of ECD and beta-catenin of IM were similar to those of primary lesion in most cases. On the other hand, expression of ECD and beta-catenin of IM of HCC component were preserved, even though those of the primary sites were reduced in two cases and one case, respectively. ECD and beta-catenin were significantly correlated with tumour differentiation and tumour progression. CONCLUSIONS: Preserved or recovered ECD and beta-catenin expression may be of beneficial effect for re-establishing the tissue architecture at the metastatic site.  相似文献   

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目的观察肝癌患者血清HBV DNA载量与肝动脉化疗栓塞术(TACE)后肿瘤复发的关系。方法检测193例乙型肝炎病毒标记物阳性的肝癌患者在TACE治疗前血清HBV DNA载量,分析患者血清HBV DNA载量与栓塞术后肿瘤复发的关系。结果在193例患者中,介入治疗术后2年内共有169例(87.6%)患者肿瘤复发;血清HBV DNA阳性(≥5×102copies/ml)138例,平均血清病毒载量为6.20±1.12lg copies/ml;单因素及多因素分析显示,肝功能Child-Pugh B级或C级、多发肿瘤、肿瘤最长径大于3cm、血清HBV DNA≥5×102copies/ml患者肿瘤复发的相对危险性较高,无肿瘤复发生存期较短。结论肝癌患者血清HBV DNA≥5×102copies/ml是TACE治疗后肿瘤复发的危险因素之一。  相似文献   

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