BACKGROUNDHuman U three protein 14a (hUTP14a) promotes p53 degradation. Moreover, hUTP14a expression is upregulated in several types of tumors. However, the expression pattern of hUTP14a in hepatocellular carcinoma (HCC) remains unknown. The aim of this study was to investigate hUTP14a expression and its prognostic value in HCC.

METHODSThe hUTP14a expression was evaluated using immunohistochemistry (IHC) in HCC tissue specimens. The correlations between hUTP14a expression and clinicopathological variables were analyzed. The Kaplan-Meier method was used to analyze the association between hUTP14a expression and survival. Independent prognostic factors associated with overall survival (OS) and disease-free survival (DFS) were analyzed using the Cox proportional-hazards regression model.

RESULTSThe IHC data revealed that the hUTP14a positivity rate in HCC tissue specimens was significantly higher than that in nontumorous tissue specimens (89.9% vs. 72.7%, P < 0.05). The hUTP14a expression was detected in both the nucleolus and the cytoplasm. The positivity rate of nucleolar hUTP14a expression in HCC tissue specimens was higher than that in the nontumorous tissue specimens (29.3% vs. 10.1%, P < 0.05). No significant difference was found between HCC and nontumorous tissue specimens of cytoplasmic hUTP14a expression (60.6% vs. 62.6%, P > 0.05). In addition, no significant correlation was found between nucleolar hUTP14a expression and other clinicopathological variables. The 5-year OS and DFS rates in patients with positive nucleolar hUTP14a expression were significantly lower than those in patients with negative hUTP14a expression (P = 0.004 for OS, P = 0.003 for DFS). Multivariate analysis showed that nucleolar hUTP14a expression was an independent prognostic factor for OS (P = 0.004) and DFS (P < 0.001).

CONCLUSIONSThe positivity rate of hUTP14a expression was significantly higher in HCC specimens. Positive expression of nucleolar hUTP14a might act as a novel prognostic predictor for patients with HCC.

Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor ; genetics ; metabolism ; Carcinoma, Hepatocellular ; metabolism ; mortality ; pathology ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Liver Neoplasms ; metabolism ; mortality ; pathology ; Male ; Middle Aged ; Multivariate Analysis ; Prognosis ; Proportional Hazards Models ; Ribonucleoproteins, Small Nucleolar ; genetics ; metabolism

BACKGROUND/AIMS: Radiofrequency ablation (RFA) is one of the most frequently applied curative treatments in patients with a single small hepatocellular carcinoma (HCC). However, the clinical significance of and risk factors for early massive recurrence after RFA—a dreadful event limiting further curative treatment—have not been fully evaluated. METHODS: In total, 438 patients with a single HCC of size ≤3 cm who underwent percutaneous RFA as an initial treatment between 2006 and 2009 were included. Baseline patient characteristics, overall survival, predictive factors, and recurrence after RFA were evaluated. In addition, the incidence, impact on survival, and predictive factors of early massive recurrence, and initial recurrence beyond the Milan criteria within 2 years were also investigated. RESULTS: During the median follow-up of 68.4 months, recurrent HCC was confirmed in 302 (68.9%) patients, with early massive recurrence in 27 patients (6.2%). The 1-, 3-, and 5-year overall survival rates were 95.4%, 84.7%, and 81.8%, respectively, in patients with no recurrence, 99.6%, 86.4%, and 70.1% in patients with recurrence within the Milan criteria or late recurrence, and 92.6%, 46.5%, and 0.05% in patients with early massive recurrence. Multivariable analysis identified older age, Child-Pugh score B or C, and early massive recurrence as predictive of poor overall survival. A tumor size of ≥2 cm and tumor location adjacent to the colon were independent risk factors predictive of early massive recurrence. CONCLUSIONS: Early massive recurrence is independently predictive of poor overall survival after RFA in patients with a single small HCC. Tumors sized ≥2 cm and located adjacent to the colon appear to be independent risk factors for early massive recurrence.
Aged ; Carcinoma, Hepatocellular/mortality/pathology/*surgery ; Catheter Ablation ; Female ; Hepatitis B/complications ; Hepatitis C/complications ; Humans ; Liver Neoplasms/mortality/pathology/*surgery ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Retrospective Studies ; Risk Factors ; Survival Rate ; Treatment Outcome

BACKGROUND/AIMS: Several studies have suggested that surgical resection (SR) can provide a survival benefit over transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) at the intermediate stage according to the Barcelona Clinic Liver Cancer (BCLC) staging system. However, the criteria for SR remain to be determined. This study compared the long-term outcome of intermediate-stage HCC patients treated by either TACE or SR as a primary treatment modality, with the aim of identifying the patient subgroup that gained a survival benefit by either modality. METHODS: In total, 277 BCLC intermediate-stage HCC patients treated by either TACE (N=225) or SR (N=52) were analyzed. RESULTS: The overall median survival time was significantly better for SR than TACE (61 vs. 30 months, P=0.002). Decision-tree analysis divided patients into seven nodes based on tumor size and number, serum alpha-fetoprotein (AFP) level, and Child-Pugh score, and these were then simplified into four subgroups (B1-B4) based on similarities in the overall hazard rate. SR provided a significant survival benefit in subgroup B2, characterized by ‘oligo' (2-4) nodules of intermediate size (5-10 cm) when the AFP levels was <400 ng/ml, or ‘oligo' (2-4) nodules of small to intermediate size (<10 cm) plus a Child-Pugh score of 5 when the AFP level was ≥400 ng/mL (median survival 73 vs. 28 months for SR vs. TACE respectively; P=0.014). The survival rate did not differ significantly between SR and TACE in the other subgroups (B1 and B3). CONCLUSIONS: SR provided a survival benefit over TACE in intermediate-stage HCC, especially for patients meeting certain criteria. Re-establishing the criteria for optimal treatment modalities in this stage of HCC is needed to improve survival rates.
Adult ; Aged ; Carcinoma, Hepatocellular/mortality/pathology/*surgery ; Chemoembolization, Therapeutic ; Female ; Hepatectomy ; Humans ; Liver Neoplasms/mortality/pathology/*surgery ; Male ; Middle Aged ; Neoplasm Staging ; Proportional Hazards Models ; Survival Rate ; Treatment Outcome ; alpha-Fetoproteins/analysis

BACKGROUND/AIMS: We compared the recurrence of hepatocellular carcinoma (HCC) and the survival of patients who received radiofrequency ablation (RFA) after transarterial chemoembolization (TACE) with patients treated with TACE or RFA alone. METHODS: This study included 201 patients with HCC, who were consecutively enrolled at Seoul St. Mary's Hospital between December 2004 and February 2010. Inclusion criteria were a single HCC < or = 5.0 cm or up to three HCCs < or = 3.0 cm. We used a propensity score model to compare HCC patients (n = 87) who received RFA after TACE (TACE + RFA) with those who received TACE (n = 71) or RFA alone (n = 43). RESULTS: The median follow-up period was 33.3 months (range, 6.8 to 80.9). The TACE + RFA group showed significantly lower local recurrence than the RFA or TACE groups (hazard ratio [HR], 0.309; 95% confidence interval [CI], 0.130 to 0.736; p = 0.008; and HR, 0.352; 95% CI, 0.158 to 0.787; p = 0.011, respectively). The overall survival was significantly better in the TACE + RFA group compared to the RFA group (HR, 0.422; 95% CI, 0.185 to 0.964; p = 0.041). However, the survival benefit was not different between the TACE + RFA and TACE groups (p = 0.124). Subgroup analysis showed that among patients with a tumor size < 3 cm, the TACE + RFA group had significantly better long-term survival than those in the TACE or RFA groups (p = 0.017, p = 0.004, respectively). CONCLUSIONS: TACE + RFA combination treatment showed favorable local recurrence and better overall survival rates in early-stage HCC patients. Patients with tumors < 3 cm are likely to benefit more from TACE + RFA combination treatment. Additional studies are needed for the selection of suitable HCC patients for TACE + RFA treatment.
Adult ; Aged ; Aged, 80 and over ; Carcinoma, Hepatocellular/mortality/pathology/*therapy ; *Catheter Ablation/adverse effects/mortality ; *Chemoembolization, Therapeutic/adverse effects/mortality ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Female ; Humans ; Kaplan-Meier Estimate ; Liver Neoplasms/mortality/pathology/*therapy ; Male ; Middle Aged ; *Neoadjuvant Therapy/adverse effects/mortality ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Patient Selection ; Proportional Hazards Models ; Republic of Korea ; Retrospective Studies ; Risk Factors ; Time Factors ; Treatment Outcome ; Tumor Burden ; Young Adult

Pretransplant alpha-fetoprotein (AFP) is a useful tumor marker predicting recurrence of hepatocellular carcinoma (HCC). Little is known, however, about the relationship between changes in AFP concentration and prognosis. This study investigated the clinical significance of change in peri-transplant AFP level as a predictor of HCC recurrence. Data from 125 HCC patients with elevated pretransplant AFP level who underwent liver transplantation (LT) between February 2000 and December 2010 were retrospectively reviewed. Patients with AFP normalization within 1 month after LT were classified into the rapid normalization group (n = 97), with all other patients classified into the non-rapid normalization group (n = 28). Tumor recurrence was observed in 17 of the 97 patients (17.5%) with rapid normalization; of these, 11 patients had high AFP levels and six had normal levels at recurrence. In contrast, tumor recurrence was observed in 24 of the 28 patients (85.7%) without rapid normalization, with all 24 having high AFP levels at recurrence. Multivariate analysis showed that non-rapid normalization (harzard ratio [HR], 4.41, P < 0.001), sex (HR, 3.26, P = 0.03), tumor size (HR, 1.15, P = 0.001), and microvascular invasion (HR, 2.65, P = 0.005) were independent risk factors for recurrence. In conclusion, rapid normalization of post-LT AFP level at 1 month is a useful clinical marker for HCC recurrence. Therefore, an adjuvant strategy and/or intensive screening are needed for patients who do not show rapid normalization.
Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/analysis ; Carcinoma, Hepatocellular/blood/mortality/*pathology/therapy ; Female ; Humans ; Kaplan-Meier Estimate ; Liver Neoplasms/blood/mortality/*pathology/therapy ; *Liver Transplantation ; Male ; Middle Aged ; Multivariate Analysis ; Neoplasm Recurrence, Local ; Proportional Hazards Models ; Retrospective Studies ; Risk Factors ; Severity of Illness Index ; alpha-Fetoproteins/analysis

BACKGROUNDS/AIMS: In hepatocellular carcinoma (HCC), bile duct invasion occurs far more rarely than vascular invasion and is not well characterized. In addition, the pathologic finding of bile duct invasion is not considered an independent prognostic factor for HCC following surgery. In this study, we determined the characteristics of HCC with bile duct invasion, and assessed the clinical significance of bile duct invasion. METHODS: We retrospectively reviewed the medical records of 363 patients who underwent hepatic resection for HCC at Seoul National University Hospital (SNUH) from January 2009 to December 2011. Preoperative, operative, and pathological data were collected. The risk factors for recurrence and survival were analyzed. Subsequently, the patients were divided into 2 groups according to disease stage (American Joint Committee on Cancer/International Union Against Cancer 7th edition): early stage (T1 and 2) and advanced stage (T3 and 4) group; and risk factors in the sub-groups were analyzed. RESULTS: Among 363 patients, 13 showed bile duct invasion on pathology. Patients with bile duct invasion had higher preoperative total bilirubin levels, greater microvascular invasion, and a higher death rate than those without bile duct invasion. In multivariate analysis, bile duct invasion was not an independent prognostic factor for survival for the entire cohort, but, was an independent prognostic factor for early stage. CONCLUSIONS: Bile duct invasion accompanied microvascular invasion in most cases, and could be used as an independent prognostic factor for survival especially in early stage HCC (T1 and T2).
Bile Ducts* ; Bile* ; Bilirubin ; Carcinoma, Hepatocellular* ; Cohort Studies ; Humans ; Joints ; Medical Records ; Mortality ; Multivariate Analysis ; Pathology ; Recurrence ; Retrospective Studies ; Risk Factors ; Seoul

OBJECTIVETo detect the expression of interleukin-17A(IL-17A) in hepatocellular carcinoma (HCCs) tissues, and to analyze its relationship with clinicopathological characteristics and epithelial-mesenchymal transition (EMT).

METHODSThe expression of IL-17A, E-cadherin, vimentin proteins and Snail mRNA were detected by immunohistochemistry and in situ hybridization histochemistry in the hepatocellular carcinoma (HCC) tissues of 74 patients.

RESULTSIL-17A staining was detected in 54.1% (40/74) specimens of human HCCs, but only 25.0% (5/20) in corresponding peritumoral tissues (P<0.05). The positive rate of IL-17A expression in HCC patients with grade III+IV and UICC stage III+IV tumors was significantly higher than those with grade I+II and UICC stage I+II tumors. The expression of IL-17A was positively correlated with portal vein tumor thrombus and microvascular invasion (all P<0.05). The 1- and 2-year recurrence-free survival rates were 27.6% and 17.2% in the patients with positive IL-17A expression, but 79.3% and 58.5% in IL-17A-negative HCCs. The 1- and 2-year overall survival rates were 69.0% and 27.8% in the cases with positive IL-17A expression, while 91.3% and 87.0% in IL-17A-negative cases. Patients with IL-17A-positive HCCs showed significantly shorter recurrence-free and overall survival compared with the patients with IL-17A-negative HCCs (P<0.05). Multivariate analysis indicated that IL-17A expression was an independent factor for recurrence-free and overall survival of HCCs. IL-17A-positive HCCs were characterized by increased expression of vimentin (r=0.492, P<0.01) or Snail (r=0.410, P<0.05) and loss of E-cadherin expression (r=-0.404, P<0.05).

CONCLUSIONSOur results suggest that IL-17A is closely related to epithelial-mesenchymal transition in hepatocellular carcinoma. IL-17A-positive hepatocellular carcinoma demonstrates more aggressive biological behavior, and IL-17A may serve as a potential prognostic marker for this cancer.

Cadherins ; genetics ; metabolism ; Carcinoma, Hepatocellular ; metabolism ; mortality ; pathology ; physiopathology ; Disease-Free Survival ; Epithelial-Mesenchymal Transition ; Humans ; Immunohistochemistry ; Interleukin-17 ; metabolism ; Liver Neoplasms ; metabolism ; mortality ; pathology ; physiopathology ; Neoplasm Invasiveness ; Neoplasm Proteins ; genetics ; metabolism ; Neoplasm Recurrence, Local ; Prognosis ; RNA, Messenger ; metabolism ; Snail Family Transcription Factors ; Survival Rate ; Transcription Factors ; genetics ; metabolism ; Vimentin ; genetics ; metabolism

BACKGROUNDHepatocellular carcinoma (HCC) is a common cancer in China, an area of high hepatitis B virus (HBV) infection. Although several staging systems are available, there is no consensus on the best classification to use because multiple factors, such as etiology, clinical treatment and populations could affect the survival of HCC patients.

METHODSThis study analyzed 743 HBV-related Chinese HCC patients who received surgery first and evaluated the predictive values of eight different commonly used staging systems in the clinic.

RESULTSThe overall 1-, 3-, 5-year survival rates and a median survival were 91.5%, 70.3%, 55.3% and 72 months respectively. Barcelona Clinic Liver Cancer (BCLC) staging systems had the best stratification ability and showed the lowest Akaike information criterion (AIC) values (2896.577), followed by tumor-node-metastasis 7 th (TNM 7 th ) (AIC = 2899.980), TNM 6 th (AIC = 2902.17), Japan integrated staging score (AIC = 2918.085), Tokyo (AIC = 2938.822), Cancer of the Liver Italian Program score (AIC = 2941.950), Chinese University Prognostic Index grade (AIC = 2962.027), and Okuda (AIC = 2979.389).

CONCLUSIONSBCLC staging system is a better staging model for HBV infection patients with HCC in Chinese population among the eight currently used staging systems. These identifications afford a large group of Chinese HCC patients with HBV infection and could be helpful to design a new staging system for a certain population.

Adult ; Aged ; Aged, 80 and over ; Carcinoma, Hepatocellular ; mortality ; pathology ; China ; Female ; Humans ; Liver Neoplasms ; mortality ; pathology ; Male ; Middle Aged ; Neoplasm Staging ; Survival Rate

BACKGROUND/AIMS: Spinal metastases often severely limit the quality of life by causing severe pain and neurological deficits. The purpose of this study was to evaluate the palliative effect of radiotherapy (RT) for spinal metastases from hepatocellular carcinoma (HCC) and to identify factors predictive of survival in HCC patients with spinal metastases who received RT. METHODS: A retrospective analysis was performed on 192 patients with spinal metastases from HCC who received RT. RESULTS: Of 192 patients with spinal metastases from HCC, an overall pain response to palliative RT occurred in 187 patients (97.4%), with a complete pain response (CR) in 41 patients (21.4%) and a partial response in 151 patients (78.6%). A higher biologically effective dose (BED) and more advanced RT techniques were identified as predictive factors for a CR. The 1- and 2-year overall survival (OS) rates were 18.1% and 6.3%, respectively, and the median survival time was 4.5 months. A long OS was associated with good performance status, controlled primary HCC, absence of extrahepatic metastases, and a higher BED. CONCLUSIONS: RT provided effective palliation for patients with painful spinal metastases from HCC. Our results provide information regarding pain control, survival outcomes, and predictive factors for the prognosis of HCC patients with spinal metastases treated with RT.
Adult ; Aged ; Aged, 80 and over ; Carcinoma, Hepatocellular/mortality/*pathology ; Female ; Humans ; Liver Neoplasms/mortality/*pathology ; Male ; Middle Aged ; Pain/etiology/radiotherapy ; Pain Management/methods ; Palliative Care/*methods ; Retrospective Moral Judgment ; Spinal Neoplasms/mortality/radiotherapy/*secondary ; Survival Analysis ; Treatment Outcome ; Young Adult

BACKGROUND: Metastatic pathological fractures of the spine are a major problem for cancer patients; however, there is no consensus on treatment strategy. The purpose of this study was to evaluate various treatment options by analyzing their patterns for metastatic pathological fractures of the spine. METHODS: In this study, 54 patients (male:female = 36:18) who were diagnosed with metastatic pathological fractures of spine were recruited. Demographic data, origin of cancer, type of treatment, and results were obtained from electronic medical records. Treatment options were divided into radiotherapy (RT), vertebroplasty (VP) or kyphoplasty (KP), operation (OP), and other treatments. Treatment results were defined as aggravation, no response, fair response, good response, and unknown. The survival time after detection of pathologic fractures was analyzed with the Kaplan-Meier method. RESULTS: The mean age of the patients was 62.3 years. Hepatocellular carcinoma was the most common cancer of primary origin (n = 9), followed by multiple myeloma (n = 8). RT was the most common primary choice of treatment (n = 29, 53.7%), followed by OP (n = 13, 24.1%), and VP or KP (n = 10, 18.5%). Only 13 of 29 RT cases and 7 of 13 OP cases demonstrated a fair or good response. The mean survival time following detection of pathological spinal fractures was 11.1 months for 29 patients, who died during the study period. CONCLUSIONS: RT was the most common primary choice of treatment for metastatic pathological fractures of the spine. However, the response rate was suboptimal. Although OP should be considered for the relief of mechanical back pain or neurologic symptoms, care should be taken in determining the surgical indication. VP or KP could be considered for short-term control of localized pain, although the number of cases was too small to confirm the conclusion. It is difficult to determine the superiority of the treatment modalities, hence, a common guideline for the diagnosis and treatment of metastatic pathological fractures of the spine is required.
Carcinoma, Hepatocellular/mortality/pathology ; Female ; Humans ; Liver Neoplasms/mortality/pathology ; Male ; Middle Aged ; Multiple Myeloma/mortality/pathology ; Retrospective Studies ; Spinal Fractures/etiology/mortality/*radiotherapy/*surgery ; Spinal Neoplasms/*complications/secondary ; Spine ; Treatment Outcome