Along with the improvement of surgical techniques and post-transplant management, the role of liver transplantation in hepatocellular carcinoma (HCC) treatment has become increasingly important. Although HCC now is an indication of liver transplantation, the criteria of HCC candidates selection vary in different transplantation centers in China. On the contrary, the HCC candidates selection criteria in western countries are relatively strict, among which Milan criteria, University of California, San Francisco (UCSF) criteria, and Pittsburgh modified TNM criteria are widely acknowledged. However, Milan criteria and UCSF criteria only focus on tumor diameter and tumor number but ignore some important risk factors such as vascular invasion and histological differentiation. In our opinion, the biological behaviors of tumor are as important as tumor burden. A set of new candidates selection and prognostic criteria of liver transplantation in HCC patients named "Hangzhou criteria" has been established based on China's real situations and on the results of our long-term research. Hangzhou criteria expands and surpasses Milan criteria, including several important risk factors. According to Hangzhou criteria, more HCC patients are given opportunities to receive liver transplantation and achieved favorable long-term survival. Also in this article, we reviewed the peri-transplantation therapy of HCC to reduce the tumor recurrence and improve the long-term survival after transplantation for the purpose of making liver transplantation more effective and reliable for HCC treatment.
Carcinoma, Hepatocellular ; mortality ; pathology ; surgery ; China ; Humans ; Liver Neoplasms ; mortality ; pathology ; surgery ; Liver Transplantation ; Patient Selection ; Treatment Outcome

BACKGROUNDPittsburgh modified TNM criteria is one of the prognostic models of orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC). In this study, we applied this prognostic system in a series of HCC patients receiving OLT to verify its reliability in the clinical prognostic prediction.

METHODSThe clinical record and follow-up data of 102 patients with HCC underwent OLT was collected. The patients were classified by 3 staging systems: the Pittsburgh Modified TNM Criteria, International Union Against Cancer (UICC) pTNM Staging System, and Milan Criteria. Survival rates of the patients were analyzed using the Kaplan-Meier method and the Log-Rank test, and then the prognostic values of the 3 staging systems were compared.

RESULTSAmong the 3 staging systems, the Pittsburgh Modified TNM Criteria showed the best stratification of patients with different prognosis. The overall survival rates of the patients at the Pittsburgh modified TNM stage I, II, III, and IV were 94.4%, 83.3%, 58.2%, and 36.8% at 1 year, and 79.4%, 62.5%, 26.2%, and 10.5% at 3 years, respectively. For those patients exceeding the Milan Criteria, the patients at Pittsburgh stages I and II had a significant higher survival rate than those at Pittsburgh stages III and IV (P < 0.001).

CONCLUSIONSThe Pittsburgh Modified TNM Criteria is a more reliable postoperative staging system than the UICC pTNM staging system for HCC patients receiving OLT. As providing more accurate prognostic classification, it could be reasonable to combine the Milan Criteria for recipient selection.

Carcinoma, Hepatocellular ; mortality ; pathology ; surgery ; Female ; Humans ; Liver Neoplasms ; mortality ; pathology ; surgery ; Liver Transplantation ; Male ; Neoplasm Staging ; Prognosis ; Survival Rate

Prospective validation of the Barcelona Clinic Liver Cancer staging system. Cillo U, Vitale A, Grigoletto F, Farinati F, Brolese A, Zanus G, Neri D, Boccagni P, Srsen N, D'Amico F, Antonio Ciarleglio F, Bridda A, D'Amico DF. [Abstract reproduced by permission of J Hepatol 2006;44:723-31] BACKGROUND/AIMS: The Barcelona Clinic Liver Cancer (BCLC) classification offers a prognostic stratification of patients with hepatocellular carcinoma (HCC). We recently demonstrated the BCLC's peculiar prognostic ability in a retrospective cohort of HCC patients. The aim of this study was to evaluate the BCLC system prospectively in a subsequent separate group of HCC patients enrolled at the same surgically oriented liver unit. METHODS: One hundred and ninety- five consecutive HCC patients were prospectively enrolled and their liver disease was staged before therapy. Unlike the BCLC treatment protocol, nodule size and number were not used as absolute exclusion criteria for radical treatment. Predictors of survival were identified using the Cox model. RESULTS: The median survival time was 23 months overall, and 53, 16, 7 and 3 months, respectively, for BCLC categories A, B, C, and D. In our cohort, BCLC had the best independent predictive power for survival when compared with the Okuda, CLIP, UNOS-TNM, and JIS prognostic systems (linear trend x2=43.01, likelihood x2=57.94, AIC 885.98). Moreover, the BCLC classification showed a better prognostic ability than the AJCC-TNM 2002 system in surgical patients. CONCLUSIONS: The discriminating power of BCLC staging was prospectively assessed in an Italian cohort of HCC patients treated mainly with radical therapies.
Survival Analysis ; Prospective Studies ; Proportional Hazards Models ; Prognosis ; Neoplasm Staging/*methods ; Liver Neoplasms/mortality/*pathology ; Humans ; Carcinoma, Hepatocellular/mortality/*pathology

The five-year survival rate of patients after curative resection of hepatocellular carcinoma (HCC) has been reported to be 30 to 50 %, however the actual survival rate may be different. We analyzed the actual 5-year survival rate and prognostic factors after curative resection of HCC. Retrospective analysis was performed on 63 HCC patients who underwent curative resection from 1998 to 1999. A total of 63 cases were reviewed, consisting of 53 men and 10 women, with a median age of 49 years. These cases included all four pathologic T stages (pT stage) and had the following representation: stage 1 (1 case), stage 2 (17 cases), stage 3 (38 cases), and stage 4 (7 cases). In our study, the actual 5-year survival rate was 57.0% and the median survival time was 60 months. In addition, the patients in our study had an actual 5-year disease-free survival rate of 50.2% and a median disease-free survival time of 46 months. Thirty-one patients had recurrences, with a majority occurring within one year (65%). These patients with early recurrences had a poor actual 5-year survival rate of 5%. A univariate analysis showed that the prognostic factors influencing survival rate were the presence of satellite nodules, increased pT stage, HCC recurrence, and the time to recurrence (within one year). Interestingly, microvascular invasion made a difference in survival rate but was not statistically significant (p = 0.08). Furthermore, factors influencing the disease free survival rate include the presence of satellite nodules, microvascular invasion, and pT stage. Multivariate analysis identified pT stage as the only statistically related factor in determining the disease-free survival rate. The most important prognostic factor of HCC is recurrence. Moreover, the major risk factor for recurrence is an advanced pT stage. Therefore, performing prospective studies of postoperative adjuvant therapy is necessary to prevent recurrences after hepatic resection. Furthermore, active preventative treatment and early diagnosis of recurrences should be of the highest priority in the care of high-risk patient groups that have an advanced pT stage.
Survival Rate ; Retrospective Studies ; Middle Aged ; Male ; Liver Neoplasms/*mortality/pathology/*surgery ; Liver/pathology/surgery ; Humans ; *Hepatectomy ; Female ; Carcinoma, Hepatocellular/*mortality/pathology/*surgery ; Aged ; Adult

BACKGROUND/AIMS: Sclerosing hepatocellular carcinoma (HCC) is an unusual subtype of HCC that is characterized by an embedded dense fibrous stroma in the tubular neoplastic structures. We aimed to assess the surgical approaches and outcomes of sclerosing HCC. METHODS: We retrospectively analyzed the clinicopathologic features of 6 patients with sclerosing HCC who underwent surgical treatment at Asan Medical Center between July 1989 and December 2005. RESULTS: Six HCC patients with sclerosing HCC were diagnosed out of the total 1390 HCC patients (0.43%) during the study period. The mean age was 58 years and 4 patients were male. Weight loss and abdominal pain were the most common symptoms. The serum calcium and phosphorus levels were normal in all the patients. All of them were hepatitis B surface antigen-positive, but none was positive for hepatitis C. All the lesions were solitary. The tumor size ranged from 45 to 150 mm in diameter (median size: 81 mm). We performed right trisegmentectomy (n=1), central bisegmentectomy (n=1), right anterior segmentectomy (n=1), ex-vivo resection and autotransplantation (n=1) and right posterior segmentectomy (n=2). The median overall survival and disease free-survival periods were 24 months and 9.5 months, respectively. CONCLUSIONS: The incidence of sclerosing HCC was very low. Sclerosing HCC was often not correctly diagnosed before an operation, but performing resection prolonged the patients' survival and their prognosis was not worse than that for ordinary HCC. Our experience implicates that aggressive surgical treatment for sclerosing HCC is beneficial for patient survival.
Adult ; Carcinoma, Hepatocellular/mortality/pathology/*surgery ; Female ; Humans ; Liver/*pathology ; Liver Neoplasms/mortality/pathology/*surgery ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Sclerosis ; Survival Rate

OBJECTIVETo evaluate the effects of portal vein microscopic and macroscopic tumor thrombi on post-operation patients with hepatocellular carcinoma (HCC).

METHODSThree thousand three hundred and forty eight HCC patients were retrospectively reviewed, which were divided into no portal vein tumor thrombi (PVTT), microscopic PVTT and macroscopic PVTT groups according to the pathology, effects of portal vein microscopic and macroscopic tumor thrombi on post-operation patients's survival were studied by univariate analysis and overall survival was evaluated in each group.

RESULTSHazard ratio (HR) of portal vein microscopic tumor thrombi and macroscopic tumor thrombi was 1.421 and 3.136 respectively; The overall 1-, 3-, 5- and 10-year cumulative survival rate was 85.97%, 62.78%, 49.88% and 35.42% respectively, and mean time for survival was 59.7 months in group without PVTT, while 74.42%, 51.66%, 39.25% and 27.28% respectively and mean time for survival 39.1 months in group with microscopic PVTT, 52.59%, 25.97%, 20.42% and 11.33% respectively and mean time for survival 13.5 months in group with macroscopic PVTT.

CONCLUSIONSPVTT was an important prognostic factor for survival in post-operation patients with HCC while macroscopic PVTT was more danger than microscopic PVTT. The period of microscopic PVTT was the landmark affecting post-operation survival.

Carcinoma, Hepatocellular ; mortality ; pathology ; surgery ; Humans ; Liver Neoplasms ; mortality ; pathology ; surgery ; Neoplastic Cells, Circulating ; Portal Vein ; pathology ; Retrospective Studies ; Survival Rate

BACKGROUND/AIMS: Cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) are up-regulated in hepatocellular carcinoma (HCC). To investigate the levels of COX-2 and VEGF expression in chronic hepatitis (CH), cirrhosis, and HCC. METHODS: The immunohistochemical expressions of COX-2 and VEGF were evaluated in tissues from patients with CH (n=95), cirrhosis (n=38), low-grade HCC (LG-HCC; n=6), and high-grade HCC (HG-HCC; n=29). RESULTS: The COX-2 expression scores in CH, cirrhosis, LG-HCC, and HG-HCC were 3.3+/-1.9 (mean+/-SD), 4.2+/-1.7, 5.5+/-1.0, and 3.4+/-2.4, respectively (CH vs. cirrhosis, P=0.016; CH vs. LG-HCC, P=0.008; LG-HCC vs. HG-HCC, P=0.004), and the corresponding VEGF expression scores were 0.9+/-0.8, 1.5+/-0.7, 1.8+/-0.9, and 1.6+/-1.1 (CH vs. cirrhosis, P<0.001; CH vs. LG-HCC, P=0.011; LG-HCC vs. HG-HCC, P=0.075). Both factors were correlated with the fibrosis stage in CH and cirrhosis (COX-2: r=0.427, P<0.001; VEGF: r=0.491, P<0.001). There was a significant correlation between COX-2 and VEGF in all of the tissue samples (r=0.648, P<0.001), and between high COX-2 and VEGF expression scores and survival (COX-2: P=0.001; VEGF: P<0.001). CONCLUSIONS: The expressions of both COX-2 and VEGF are significantly higher in cirrhosis and LG-HCC than in CH. High COX-2 and high VEGF expressions are associated with a high survival rate.
Adult ; Aged ; Carcinoma, Hepatocellular/*metabolism/mortality/pathology ; Cyclooxygenase 2/*metabolism ; Female ; Hepatitis, Chronic/*metabolism/mortality/pathology ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Liver Cirrhosis/*metabolism/mortality/pathology ; Liver Neoplasms/*metabolism/mortality/pathology ; Male ; Middle Aged ; Vascular Endothelial Growth Factor A/*metabolism

BACKGROUND/AIMS: There are several staging systems to decide the stage of hepatocellular carcinoma (HCC), but yet incomplete. Okuda stage which includes both tumor characteristics and liver function is widely used. The aims of this study were to assess the usefulness of known prognostic factors and Okuda staging system in 237 cases of HCC. METHODS: A retrospective analysis of 237 cases of HCC diagnosed from 2000 to 2002 was performed. We analyzed prognostic factors such as age, sex, liver cirrhosis, Child-Pugh classification, tumor size, albumin, bilirubin, alpha-FP, ascites, encephalopathy and Okuda stage. Prognostic analysis was performed for single variables and estimating survival distributions were analyzed by the Kaplan-Meier method, statistically compared by the log-rank test. RESULTS: Patients had a mean age of 57.5 years and were predominantly men (79.7%). Liver cirrhosis were noticed in 214 cases (90.3%). The overall median survival period was 25.7 months. The median survival period was correlated to bilirubin, ascites, alpha-FP, tumor size, and Child-Pugh classification, but not to age, sex, and pattern of viral infection. The median survival period of the Okuda stage I, II and III cases was 35.8, 11.9 and 8.5 months (p<0.001). CONCLUSIONS: The median survival period of patients with HCC is significantly correlated to Okuda staging system, and survival period has improved than the initial data when the Okuda staging system was published in 1985. However, in order to discriminate early staged HCC more accurately, other prognostic factors such as alpha-FP and tumor morphology should be included in future staging system for HCC.
Carcinoma, Hepatocellular/*mortality/pathology ; English Abstract ; Female ; Humans ; Liver Neoplasms/*mortality/pathology ; Male ; Middle Aged ; Neoplasm Staging ; Survival Analysis ; Survival Rate

OBJECTIVETo investigate the risk factors affecting neoplasm recurrence and metastasis following liver transplantation (LT) and liver resection (LR) in patients with hepatocellular carcinoma (HCC) meeting Milan criteria.

METHODSWe retrospectively analyzed the clinical data of 88 patients with HCC meeting Milan criteria undergoing LT or LR in Nanfang Hospital between January, 2006 and December, 2011 and compared the survival rate and recurrence-free survival rate between the two groups. Univariate analysis of 12 variables during peri-operative period was carried out to screen the risk factors affecting neoplasm recurrence and metastasis.

RESULTSThe LT group and HR group had similar 1-, 3-, and 5-year-survival rates (P>0.05), but the LT group showed significantly higher 1-, 3-, and 5-year recurrence-free survival rates (P<0.05). The recurrence rate was much lower in LT group than in LR group (P<0.05). Multivariate analysis identified gender, tumor size, degree of pathological differentiation, and microvascular tumor embolism as independent risk factors affecting the recurrence-free survival rate.

CONCLUSIONPatients with HCC meeting Milan criteria undergoing LT have longer long-term recurrence-free survival. A male patient with a greater tumor size, microvascular tumor embolism, and poorly differentiated carcinoma is more likely to develop neoplasm recurrence and metastasis following the surgery.

Carcinoma, Hepatocellular ; mortality ; pathology ; surgery ; Female ; Hepatectomy ; Humans ; Liver Neoplasms ; mortality ; pathology ; surgery ; Liver Transplantation ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Prognosis ; Retrospective Studies ; Survival Rate ; Treatment Outcome

OBJECTIVETo assess the survival of radiofrequency ablation (RFA) and investigate the prognostic factors affecting overall survival, local recurrence-free survival and disease-free survival in hepatocellular carcinoma (HCC).

METHODSA total of 192 HCC patients underwent RFA treatment in our department and were enrolled into this study. Among them, 151 patients were males and 41 were females (mean age, 59.2 years, range, 24 - 87 years old). The average tumor size was (3.9 +/- 1.3) cm (range, 1.2 - 8.0 cm). Of these 192 HCC patients, their Child-Pugh grade of A, B and C were 106, 77 and 9, respectively. According to UICC-TNM system, 57, 85, 44 and 6 patients were in stage I, II, III and IV respectively. Kaplan-Meier model and log-rank test were used in univariate analysis and COX regression model was used in multivariate analysis to identify prognostic factors for survival.

RESULTSThe 1-, 2-, 3- and 4-year overall survival were 84.9%, 69.1%, 60.4% and 52.8%, respectively. Local recurrence-free survival were 75.1%, 53.8%, 43.9% and 40.8%, respectively. Disease-free survival were 64.3%, 43.2%, 37.1% and 25.0%, respectively. The following factors were identified as independent prognostic factors for survival by multivariate model: (1) Overall survival: Child-Pugh classification, standard treatment protocol and UICC-TNM staging. (2) Local recurrence-free survival: Child-Pugh classification and UICC-TNM staging. (3) Disease-free survival: UICC-TNM staging, Child-Pugh classification and daughter lesion. Among these, both Child-Pugh classification and UICC-TNM staging were independent prognostic factors for three kinds of survivals.

CONCLUSIONSDegree of tumor progress (UICC-TNM stage, daughter lesion), treatment method (applying of standard treatment protocol) and patients' liver function are the most important factors for survival after RFA. So application of proper treatment strategy before, during and after RFA should be required to improve survival.

Adult ; Aged ; Aged, 80 and over ; Carcinoma, Hepatocellular ; mortality ; pathology ; surgery ; Catheter Ablation ; Female ; Humans ; Liver Neoplasms ; mortality ; pathology ; surgery ; Male ; Middle Aged ; Prognosis ; Survival Analysis ; Survival Rate