Callispheres® drug-eluting beads transarterial chemoembolization might be an efficient and safety down-staging therapy in unresectable liver cancer patients.

PURPOSE: The purpose was to explore the effect of drug-eluting beads transarterial chemoembolization (DEB-TACE) on down-staging in unresectable liver cancer patients. METHODS: A total of 180 patients with PHC treated by TACE were retrospectively analyzed. These included 80 cases in the DEB-TACE group and 100 cases in the cTACE group. Of these, 56 had complete clinical data (DEB-TACE: 24, cTACE: 32), and 23 patients received hepatectomy after TACE as a down-staging therapy (DEB-TACE: 15, cTACE: 8). Data (including clinical characteristics, clinical efficacy, tumor response, tumor diameters, residual liver volume, and liver function indexes before and after TACE, RFS, OS, and complications were collected and compared. Treatment response was evaluated at 1 month after TACE. Tumor diameter was evaluated by abdominal computed tomography scan. The residual liver volume was evaluated by IQQA liver system, and relapse-free survival (RFS) and overall survival (OS) were calculated by Kaplan-Meier curves. RESULTS: The conversion rate in DEB-TACE group was higher than cTACE group (18.8% vs 8%, p = 0.032). In DEB-TACE group, 17 patients achieved objective response rate (ORR) which was higher than cTACE group (70.8% vs 34.4%, p = 0.007). The tumor necrosis rate was higher in DEB-TACE group, but there was no significant difference between the two groups (p = 0.053). Tumor diameter was decreased after TACE compared to before TACE (DEB-TACE: 9.4 ± 3.3 vs. 5.4 ± 3.5 cm, p = 0.003; cTACE: 9.7 ± 2.6 vs. 6.9 ± 2.2, p = 0.036). As to residual liver volume, it was increased after TACE compared to before TACE (1066.2 cm3 vs. 1180.3 cm3, p = 0.007) in DEB-TACE group, while there was no significant difference in cTACE group (1046.4 cm3 vs. 1170 cm3, p = 0.339) compared by paired-sample t-test, but there was no significant difference before and after TACE when compared by unpaired-sample t-test (p > 0.05). After TACE at 1 month, the AFP level in the DEB-TACE group was significantly lower than that in the cTACE group (p = 0.003). For survival, the median RFS was 26.0 months in DEB-TACE group and 15 months in cTACE group; there was significant difference between the two groups (p = 0.0465). As to OS, the median OS in DEB-TACE group was higher than that in cTACE group, but there was no significant difference between the two groups (p = 0.165). For safety profiles, in terms of liver function and adverse events, there was no significant difference between the two groups. CONCLUSION: Compared with cTACE, DEB-TACE might be a more efficient and safety down-staging treatment in unresectable liver cancer patients.

Prognostic value of integrin variants and expression in post-operative patients with HBV-related hepatocellular carcinoma.

Integrins are a large family of cell surface receptors that bind extracellular matrix proteins and participate in cancer progression. However, the prognostic value of integrin family genes in post-operative patients with HBV-related hepatocellular carcinoma (HCC) remains unknown. In this study, we investigated 18 single nucleotide polymorphisms (SNPs) in integrin family genes and found that the AG/GG genotypes at rs988574 in ITGA1 predicted a better prognosis compared to carriers of the AA genotype (P = 0.025, HR = 0.69, 95%CI = 0.50-0.96). Moreover, rs988574 genotype combined with serum level of AFP had a better prognostic value in HBV-related HCC patients (P = 0.026, HR = 1.75, 95% CI = 1.07-2.85). Furthermore, we compared the expression of 24 integrin family genes in HBV-related HCC tissues and adjacent normal tissues. Survival analysis demonstrated that expression of three of the family members, ITGA5, ITGB5 and ITGA2B, were significantly associated with the overall survival (OS) or relapse-free survival (RFS) of HBV-related HCC patients. Additionally, patients with lower expression of both ITGA5 and ITGB5 had the best OS and RFS (P = 0.017 and P = 0.002, respectively). Our study demonstrated that rs988574 of ITGA1 and the expression of ITGA5, ITGB5 and ITGA2B are potential independent prognostic bio-markers and therapeutic targets for HBV-related HCC patients and may be useful for the diagnosis of HBV-related HCC.

Preoperative transcatheter arterial chemotherapy may suppress oxidative stress in hepatocellular carcinoma cells and reduce the risk of short-term relapse.

In this study, we aim to investigate oxidative stress in hepatocellular carcinoma (HCC) tissues in patients receiving preoperative transcatheter arterial chemotherapy (TAC) and its association with prognosis. A total of 89 HCC patients enrolled in this study, 39 received preoperative TAC 1 week before surgery (pTAC group) and 50 did not (non-pTAC group). All patients underwent hepatectomy and postoperative TAC and were followed up to 400 weeks. Samples of liver tissue without HCC and hepatitis (n = 15) served as normal controls. Cellular levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), TP53, and p21waf1/cip1 were measured in both cancer and surrounding tissues using an immunohistochemistry assay. Taken together, our data suggested that preoperative TAC might postpone postoperative HCC relapse within 1 year via suppression of tumor cells by induction of high levels of oxidative stress.

Aldehyde dehydrogenase 1 (ALDH1) isoform expression and potential clinical implications in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most prevalent and life-threatening malignancies worldwide. There are few diagnostic and prognostic biomarkers and druggable targets for HCC. Aldehyde dehydrogenase 1 (ALDH1) is a marker of stem cells in a variety of cancers, but the mRNA levels and prognostic value of ALDH1 isoforms in HCC patients remain unknown. In the present study, gene ontology annotation of the ALDH1 family was performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID), and the gene pathway analsis was performed using GeneMANIA software. The initial prognostic value of ALDH1 expression in 360 HCC patients was assessed using the OncoLnc database. The expression levels of ALDH1 isoforms in normal liver tissues and clinical specimens of cancer vs. normal control datasets were determined using the GTEx and Oncomine databases, respectively. We then analyzed the prognostic value of ALDH1 expression in 212 hepatitis B virus (HBV)-related HCC patients using the GEO database. We found that the ALDH1 isoform showed high aldehyde dehydrogenase activity. The ALDH1A1, ALDH1B1, and ALDH1L1 genes encoded for the ALDH1 enzyme. High ALDH1B1 expression had protective qualities in HCC patients. Moreover, HBV-related HCC patients who showed high ALDH1L1 gene expression had a better clinical outcomes. In addition, high ALDH1A1 expression was associated with a 57-month recurrence-free survival in HBV-related HCC patients. High ALDH1B1 expression was protective for HCCs with multiple nodules and high serum alpha-fetoprotein (AFP) level. Furthermore, high serum AFP levels contributed to lower ALDH1L1. ALDH1A1, ALDH1B1, and ALDH1L1, all of which were considered promising diagnostic and prognostic markers as well as potential drug targets.

Genome-Wide Association Study of MKI67 Expression and its Clinical Implications in HBV-Related Hepatocellular Carcinoma in Southern China.

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is a common malignant tumor with a high rate of recurrence. Immunohistochemical analysis of the marker of proliferation Ki-67 (MKI67) is used to assess proliferation activity of HCC The regulation of MKI67 expression remains unclear in HCC This study aims to explore the association between MKI67 expression and gene variants. METHODS: A total of 195 hepatitis B virus (HBV)-related HCC patients were genotyped using Illumina HumanExome BeadChip-12-1_A (242,901 markers). An independent cohort (97 subjects) validated the association of polymorphism determinants and candidate genes with MKI67 expression. The relationships between MKI67 with p53 and variants of candidate genes in the clinical outcomes of HCC patients were analyzed. RESULTS: We found that MKI67 combined with p53 was associated with a 3-year recurrence-free survival and five variants near TTN and CCDC8 were associated with MKI67 expression. TTN harboring rs2288563-TT and rs2562832-AA+CA indicated a favorable outcome for HCC patients. CONCLUSION: Variants near TTN and CCDC8 were associated with MKI67 expression, and rs2288563 and rs2562832 in TTN are potential biomarkers for the prediction of clinical outcomes in HBV-related HCC patients.

ALDH1L1 variant rs2276724 and mRNA expression predict post-operative clinical outcomes and are associated with TP53 expression in HBV-related hepatocellular carcinoma.

Aldehyde dehydrogenase 1 family member L1 (ALDH1L1) is downregulated in hepatocellular carcinoma (HCC) tumors, and its decreased expression is associated with the poor prognosis of HCC patients. We, therefore, evaluated the effect of single nucleotide polymorphisms (SNPs) of ALDH1L1, and its mRNA expression on the survival of hepatitis B virus (HBV)­related HCC patients and the association with tumor protein p53 (TP53) expression. ALDH1L1 SNPs in 415 HBV-related HCC patients were genotyped via direct sequencing. Expression profile chip datasets and survival information were obtained from GSE14520. The C allele (CT/CC) carriers of rs2276724 were significantly associated with a favorable prognosis [adjusted P=0.040; adjusted hazard ratio (HR)=0.725; 95% confidence interval (CI)=0.533-0.986]. Joint-effect analyses suggested that the CT/CC genotype of rs2276724 in TP53-negative patients was significantly associated with a decreased risk of death, compared to the TT genotype of rs2276724 in TP53-positive patients (adjusted P=0.037; adjusted HR=0.621; 95% CI=0.396-0.973). Furthermore, low expression of ALDH1L1 predicted a poor prognosis for the HBV-related HCC patients (adjusted P=0.04 for disease-free survival; adjusted P=0.001 for overall survival). Patients with high ALDH1L1 expression and low TP53 expression were significantly associated with a decreased risk of recurrence and death, and patients with a high TP53 expression were also significantly associated with a decreased risk of death in HBV-related HCC, compared with low ALDH1L1 and low TP53 expression. Our results suggest that ALDH1L1 may be a biomarker for predicting postoperative clinical outcomes. Moreover, ALDH1L1-rs2276724 and mRNA expression were associated with TP53 expression in HBV-related HCC patients.

PLCE1 polymorphisms and expression combined with serum AFP level predicts survival of HBV-related hepatocellular carcinoma patients after hepatectomy.

Polymorphisms in the phospholipase C epsilon (PLCE) 1 gene play a crucial role in the development and progression of several types of cancer. The present study investigated the prognostic significance of PLCE1 gene polymorphisms and expression combined with serum α-fetoprotein (AFP) level in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Single nucleotide polymorphisms were genotyped by sequencing DNA isolated from surgically resected tumor samples of 421 HBV-related HCC patients, and expression profiles were generated based on the GSE14520 dataset. A joint-effects analysis of PLCE1 haplotypes (Ars2274223Crs3765524; Grs2274223Trs3765524) with AFP level stratified at 20 ng/ml showed a significant association with overall survival(OS) of HBV-related HCC patients(log-rank P=0.0003). Patients with AC and GT haplotypes with AFP level ≥ 20 ng/ml had an increased risk of death as compared to those with the AC haplotype and AFP level < 20 ng/ml (adjusted P=0.029 and 0.041, respectively). Patients with the GT haplotype and AFP level < 20 ng/ml also had an increased risk of death, although with a non-significant P value (adjusted P=0.092). Joint-effects analysis of PLCE1 mRNA expression with serum AFP level stratified at 300 ng/ml was significantly associated with HBV-related HCC recurrence and OS. Our results demonstrate that PLCE1 haplotypes (including rs2274223 and rs3765524) and expression combined with serum AFP level may predict postoperative outcome of HBV-related HCC patients.

ATXN7 Gene Variants and Expression Predict Post-Operative Clinical Outcomes in Hepatitis B Virus-Related Hepatocellular Carcinoma.

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is a lethal disease with nearly equal morbidity and mortality. Thus, the discovery and application of more useful predictive biomarkers for improving therapeutic effects and prediction of clinical outcomes is of crucial significance. METHODS: A total of 475 HBV-related HCC patients were enrolled. Ataxin 7 (ATXN7) single nucleotide polymorphisms (SNPs) were genotyped by Sanger DNA sequencing after PCR amplification. The associations between ATXN7 SNPs and mRNA expression with the prognosis of HBV-related HCC were analyzed. RESULTS: In all, rs3774729 was significantly associated with overall survival (OS) of HBV-related HCC (P = 0.013, HR = 0.66, 95% CI: 0.48-0.94). And patients with the AA genotype and a high level of serum alpha fetoprotein (AFP) had significantly worse OS when compared to patients with AG/GG genotypes and a low level of AFP (adjusted P = 0.007, adjusted HR = 1.83, 95% CI = 1.18-2.82). Furthermore, low expression of ATXN7 was significantly associated with poor recurrence-free survival (RFS) and OS (P = 0.007, HR = 2.38, 95% CI = 1.27-4.45 and P = 0.025, HR = 1.75, 95% CI = 1.18-2.62). CONCLUSION: ATXN7 may be a potential predictor of post-operative prognosis of HBV-related HCC.

Associations between sequence variations in the mitochondrial DNA D-loop region and outcome of hepatocellular carcinoma.

The association between mitochondrial DNA (mtDNA) polymorphisms or mutations and the prognoses of cancer have been investigated previously, but the results have been ambiguous. In the present study, the associations between sequence variations in the mtDNA D-loop region and the outcomes of patients with hepatocellular carcinoma (HCC) were analysed. A total of 140 patients with HCC (123 males and 17 females), who were hospitalised to undergo radical resection, were studied. Polymerase chain reaction and direct sequencing were performed to detect the sequence variations in the mtDNA D-loop region. Multivariate and univariate analyses were conducted to determine important factors in the prognosis of HCC. A total of 150 point sequence variations were observed in the 140 cases (13 point mutations, 8 insertions, 20 deletions and 116 polymorphisms). The variation rate was 13.4% (150/1, 122). mtDNA nucleotide 150 (C/T) was an independent factor in the logistic regression for early/late recurrence of HCC. Patients with 150T appeared to have later recurrences. In a Cox proportional hazards regression model, hepatitis B virus DNA, Child-Pugh class, differentiation degree, tumour-node-metastasis (TNM) stage, nucleotide 16263 (T/C) and nucleotide 315 (N/insertion C) were independent factors for tumour-free survival time. Patients with the 16263T allele had a greater tumour-free survival time than patients with the 16263C allele. Similarly, patients with 315 insertion C had a superior tumour-free survival time when compared with patients with 315 N (normal). In the Cox proportional hazards regression model, recurrence type (early/late), Child-Pugh class, TNM stage and adjuvant treatment after tumour recurrence (none or one/more than one treatment) were independent factors for overall survival. None of the mtDNA variations served as independent factors. Patients with late recurrence, Child-Pugh class A, and low TNM stages and/or those who received more than one adjuvant treatment following tumour recurrence had favourable outcomes. mtDNA D-loop polymorphisms were associated with early recurrence and tumour-free survival time, but not with overall survival. mtDNA D-loop mutations in HCC were infrequent and lacked prognostic utility. The detection of mtDNA D-loop polymorphisms may assist in identifying risk factors for HCC prognosis, particularly for the short-term outcome, thereby aiding the construction of an appropriate therapeutic strategy.

Developing Risk Prediction Models for Postoperative Pancreatic Fistula: a Systematic Review of Methodology and Reporting Quality.

Postoperative pancreatic fistula is still a major complication after pancreatic surgery, despite improvements of surgical technique and perioperative management. We sought to systematically review and critically access the conduct and reporting of methods used to develop risk prediction models for predicting postoperative pancreatic fistula. We conducted a systematic search of PubMed and EMBASE databases to identify articles published before January 1, 2015, which described the development of models to predict the risk of postoperative pancreatic fistula. We extracted information of developing a prediction model including study design, sample size and number of events, definition of postoperative pancreatic fistula, risk predictor selection, missing data, model-building strategies, and model performance. Seven studies of developing seven risk prediction models were included. In three studies (42 %), the number of events per variable was less than 10. The number of candidate risk predictors ranged from 9 to 32. Five studies (71 %) reported using univariate screening, which was not recommended in building a multivariate model, to reduce the number of risk predictors. Six risk prediction models (86 %) were developed by categorizing all continuous risk predictors. The treatment and handling of missing data were not mentioned in all studies. We found use of inappropriate methods that could endanger the development of model, including univariate pre-screening of variables, categorization of continuous risk predictors, and model validation. The use of inappropriate methods affects the reliability and the accuracy of the probability estimates of predicting postoperative pancreatic fistula.

Clinicopathologic characteristics and prognoses for multicentric occurrence and intrahepatic metastasis in synchronous multinodular hepatocellular carcinoma patients.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and the outcomes for patients are still poor. It is important to determine the original type of synchronous multinodular HCC for preoperative assessment and the choice of treatment therapy as well as for the prediction of prognosis after treatment. AIMS: To analyze clinicopathologic characteristics and prognoses in patients with multicentric occurrence (MO) and intrahepatic metastasis (IM) of synchronous multinodular hepatocellular carcinoma (HCC). METHODS: The study group comprised 42 multinodular HCC patients with a total of 112 nodules. The control group comprised 20 HCC patients with 16 single nodular HCC cases and 4 HCC cases with a portal vein tumor emboli. The mitochondrial DNA (mtDNA) D-loop region was sequenced, and the patients of the study group were categorized as MO or IM based on the sequence variations. Univariate and multivariate analyses were used to determine the important clinicopathologic characteristics in the two groups. RESULTS: In the study group, 20 cases were categorized as MO, and 22 as IM, whereas all 20 cases in the control group were characterized as IM. Several factors significantly differed between the IM and MO patients, including hepatitis B e antigen (HBeAg), cumulative tumor size, tumor nodule location, cirrhosis, portal vein and/or microvascular tumor embolus and the histological grade of the primary nodule. Multivariate analysis further demonstrated that cirrhosis and portal vein and/or microvascular tumor thrombus were independent factors differentiating between IM and MO patients. The tumor-free survival time of the MO subjects was significantly longer than that of the IM subjects (25.7 ∓ 4.8 months vs. 8.9 ∓ 3.1 months, p=0.017). Similarly, the overall survival time of the MO subjects was longer (31.6 ∓ 5.3 months vs. 15.4 ∓ 3.4 months, p=0.024). The multivariate analysis further demonstrated that the original type (p=0.035) and Child-Pugh grade (p<0.001) were independent predictors of tumor-free survival time. Cirrhosis (p=0.011), original type (p=0.034) and Child-Pugh grade (p<0.001) were independent predictors of overall survival time. CONCLUSIONS: HBeAg, cumulative tumor size, tumor nodule location, cirrhosis, portal vein and/or microvascular tumor embolus and histological grade of the primary nodule are important factors for differentiating IM and MO. MO HCC patients might have a favorable outcome compared with IM patients.

Genome-wide and differential proteomic analysis of hepatitis B virus and aflatoxin B1 related hepatocellular carcinoma in Guangxi, China.

Both hepatitis B virus (HBV) and aflatoxin B1 (AFB1) exposure can cause liver damage as well as increase the probability of hepatocellular carcinoma (HCC). To investigate the underlying genetic changes that may influence development of HCC associated with HBV infection and AFB1 exposure, HCC patients were subdivided into 4 groups depending upon HBV and AFB1 exposure status: (HBV(+)/AFB1(+), HBV(+)/AFB1(-), HBV(-)/AFB1(+), HBV(-)/AFB1(-)). Genetic abnormalities and protein expression profiles were analyzed by array-based comparative genomic hybridization and isobaric tagging for quantitation. A total of 573 chromosomal aberrations (CNAs) including 184 increased and 389 decreased were detected in our study population. Twenty-five recurrently altered regions (RARs; chromosomal alterations observed in ≥10 patients) in chromosomes were identified. Loss of 4q13.3-q35.2, 13q12.1-q21.2 and gain of 7q11.2-q35 were observed with a higher frequency in the HBV(+)/AFB1(+), HBV(+)/AFB1(-) and HBV(-)/AFB1(+) groups compared to the HBV(-)/AFB(-) group. Loss of 8p12-p23.2 was associated with high TNM stage tumors (P = 0.038) and was an unfavorable prognostic factor for tumor-free survival (P =0.045). A total of 133 differentially expressed proteins were identified in iTRAQ proteomics analysis, 69 (51.8%) of which mapped within identified RARs. The most common biological processes affected by HBV and AFB1 status in HCC tumorigenesis were detoxification and drug metabolism pathways, antigen processing and anti-apoptosis pathways. Expression of AKR1B10 was increased significantly in the HBV(+)/AFB1(+) and HBV(-)/AFB1(+) groups. A significant correlation between the expression of AKR1B10 mRNA and protein levels as well as AKR1B10 copy number was observered, which suggest that AKR1B10 may play a role in AFB1-related hepatocarcinogenesis. In summary, a number of genetic and gene expression alterations were found to be associated with HBV and AFB1- related HCC. The possible synergistic effects of HBV and AFB1 in hepatocarcinogenesis warrant further investigations.

Evaluation of risk factors and clinicopathologic features for intrahepatic cholangiocarcinoma in Southern China: a possible role of hepatitis B virus.

BACKGROUND: Recent efforts suggest an etiologic role of hepatitis B virus (HBV) infection in intrahepatic cholangiocarcinoma (ICC) and the involvement of hepatic progenitor cell in ICC development, without definitive conclusions. This case-control study was undertaken to investigate risk factors for ICC, and clinicopathological features of HBV-associated ICC were analyzed. METHODS: The report comprised 98 patients with pathologically confirmed ICC and 196 healthy control subjects. Logistic regression was used to determine odds ratios and 95% confidence intervals. The sex and age distributions of HBV-related and unrelated ICC patients were compared respectively with those of 882 HBV-associated hepatocellular carcinoma patients from a random selection, and the clinicopathological data of 62 ICC patients with or without HBV infection undergoing surgical resection were compared. RESULTS: There was an association between ICC and each of HBV infection, liver cirrhosis, hepatolithiasis, and liver fluke infestation with the odds ratios (95% confidence intervals) of 2.75 (1.27-5.95), 8.42 (2.50-28.37), 22.81 (7.16-72.68), and 3.55 (1.60-7.89), respectively, with a marked synergism of cirrhosis and HBV infection (20.67; 5.40-79.06). Compared with HBV-unrelated ICC patients, HBV-related ICC patients were more common in male and younger subjects, had a higher incidence of abnormal serum alfa-fetoprotein level, cirrhosis, and neutrophilic infiltration, and had a lower proportion of elevated carbohydrate antigen 19-9 (CA19-9) values. CONCLUSIONS: The independent association of HBV infection with ICC, synergy between cirrhosis and HBV infection, and some clinicopathological similarities between HBV-related ICC and hepatocellular carcinoma suggests that both may share similar or common tumorigenic process and may possibly originate from malignant transformation of hepatic progenitor cell.

[Association between aldehyde dehydrogenase-2/cytochrome P450 2E1 genetic polymorphism and habit of alcohol drinking and the susceptibility of hepatocellular carcinoma].

OBJECTIVE: To study the relationship between aldehyde dehydrogenase-2 (ALDH2) and cytochrome P450 2E1 (CYP2E1) gene polymorphism and alcohol drinking habit with the susceptibility of hepatocellular carcinoma( HCC). METHODS: 300 cases of HCC and 292 controls were genotyped for the ALDH2 and CYP2E1 polymorphisms by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: The frequencies of ALDH2 and CYP2E1 variant genotypes in cases and controls were 50.3%, 48.0% and 32.3%, 32.9%, respectively. There was no significant difference of ALDH2 and CYP2E1 genotypes distribution between cases and controls (P > 0.05). The risk for liver cancer was 3.334 times higher in alcoholics ( > or =3 times drinking per week) with ALDH2 * 2 genotype than that that in cases carrying ALDH2 * 1 genotype while drinking less than 3 times per week (95% CI = 1.746 - 6.406) , and the risk for liver cancer was 1.803 times higher in alcoholics ( > or =3 times drinking per week) with CYP2E1c2 genotype than that in cases carrying CYP2E1cl genotype while drinking less than 3 times per week (95% CI = 0.974 - 3.336). Haplotype of the two genotypes increased liver cancer risk to 1.200 folds (95% CI = 0.730 - 1.972), and interaction between drinking and genotypes increases risk of liver cancer to 1.816 folds (95% CI = 0.985 - 3.348). CONCLUSION: ALDH2 or CYP2E1 genotypes alone render no significant risk for HCC, while frequent alcoholic consumption together with ALDH2 or CYP2E1 variant genotypes are associated with risk of hepatocarcinogenesis, suggesting a gene-environment interaction in increasing risk for HCC among Guangxi residents.

[Diagnosis and treatment of primary clear cell carcinoma of the liver].

OBJECTIVE: To investigate the clinicopathological features, diagnosis, treatment and prognosis of primary clear cell carcinoma of the liver (PCCCL). METHODS: The clinicopathological data of 24 cases with pathologically proven PCCCL in the First Affiliated Hospital of Guangxi Medical University from May 1996 to December 2003 were collected and analyzed. RESULTS: There were 21 males and 3 females in this group, with an average age of 46 years (range: 30 approximately 78 years). HBV infection was detected in 83.3%, and AFP expression was found in 75.0% of them. Of the 24 cases, 28 tumors were found with an average size of (6.64 +/- 5.54) cm. Liver cirrhosis was found in 75.0% of the patients. Macroscopic and microscopic tumor thrombi were found in 20.8% and 29.2%, respectively. Lymph node metastasis was found in 4.2% of the patents. The 1-, 3-, and 5-year overall survival rates of the 24 cases were 75.0%, 41.7% and 27.8%, respectively, with a median survival time of 29 months. CONCLUSION: The clinical characteristics of primary clear cell carcinoma of the liver are similar to that of common hepatocellular carcinoma. It is difficult to be diagnosed preoperatively and final diagnosis depends on pathological examination. Surgical resection is an effective way to achieve favorable treatment outcome and even long-term survival.

[Comparative proteomic approach in differentiating multicentric occurrence and intrahepatic metastasis in multinodular hepatocellular carcinomas].

BACKGROUND AND OBJECTIVE: Multinodular hepatocellular carcinoma(HCC) might originate from multicentric occurrence (MO) or intrahepatic metastasis(IM). This study was to find out proteins which play important roles in clonal origin of multinodular hepatocellular carcinoma bt screening the differentially expressed proteins between the MO and IM tissues using comparative proteomic analysis. METHODS: Total protein extracted was separated by two-dimensional gel electrophoresis. Comparative analyses of the 2-DE protein patterns between the two groups were carried out using computerized imaging techniques. Proteins exhibiting significant alternations were subsequently isolated and identified by mass spectrometry. RESULTS: A total 1025+/-52 and 900+/-98 spots were detected in the protein profile in IM and MO, respectively. Twenty-five protein spots were statistically different at expression levels between the two groups. Twenty of them were identified by MALDI-TOF-MS and bioinformatics. CONCLUSIONS: The protein profile of MO HCC tissues is different from that in IM HCC tissues. The twenty differentially expressed proteins might play a key role in the carcinogenesis and progression of multinodular HCC. These newly identified proteins might be potential and valuable biomarkers for identifying the multinodular HCC of clonal origin.

[Application of polymerase chain reaction with confronting two-pair primers in aldehyde dehydrogenase-2 typing].

OBJECTIVE: To study the distribution of aldehyde dehydrogenase-2 (ALDH2) polymorphisms between healthy Zhuang and Han ethnic individuals in Guangxi Autonomous Region and its influence to the behaviors of alcohol consumption. METHODS: Polymerase chain reaction with confronting two-pair primers (PCR-CTPP) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) techniques were used to genotype ALDH2, respectively, and alcohol consumption was recorded in a constructed questionnaire. RESULTS: The frequencies of ALDH2 alleles (ALDH2(1)/ALDH2(2)) among Zhuang and Han ethnics were 0.511, 0.489 and 0.508, 0.492 respectively (chi2 = 0.001, P > 0.05). The ALDH2 genotypes were verified with PCR-RFLP method. The frequencies of ALDH2(1) genotype in alcoholics (> or = 3 times drinking per week) were 35.59% and 15.67% in Zhuang and Han groups respectively (chi2 = 5.800, P = 0.016). CONCLUSION: There was no significant different distribution of ALDH2 genotype among healthy Zhuang and Han ethnic people. The genotype of ALDH2 in different ethnicity might influence individual behavior of alcohol consumption.

Hepatitis B virus infection contributes to oxidative stress in a population exposed to aflatoxin B1 and high-risk for hepatocellular carcinoma.

Biomarkers of hepatitis B virus (HBV) infection, aflatoxin B1 (AFB1) exposure and oxidative stress were detected in 71 hepatocellular carcinoma (HCC) patients and 694 controls from southern China. Plasma level of AFB1-albumin-adducts (AAA) and protein carbonyl content (PCC) were significantly higher in the 71 HCC cases than in any age/gender matched HBV sero-status groups (p<0.001). HCC patients positive for the p53-249 G-T mutation had a marginally higher level of PCC than those negative for the mutation (p=0.077). HBV infection had a prominent influence on the association between AFB1 exposure and oxidative stress biomarkers in the controls. Our study indicates a significant contribution from HBV infection to oxidative stress in a population with AFB1 exposure which might substantially increase risk for HCC in this region.

Evaluation of oxidative stress in a group of adolescents exposed to a high level of aflatoxin B1--a multi-center and multi-biomarker study.

The association between aflatoxin B1 (AFB1) exposure and oxidative stress was extensively examined in 84 adolescents from an area at high risk for hepatocellular carcinoma in China. Plasma level of aflatoxin B1-albumin adducts (AAAs) was associated with AFB1 excretion in urine (r = 0.394, P < 0.001). Urinary AFB1 was also associated with both the urinary excretion of 8-hydroxydeoxyguanosine (8-OHdG) (r > or = 0.479, P < 0.001) and 8-OHdG and hOGG1 levels in peripheral leukocytes (r > or = 0.308, P < or = 0.005). Similarly, AAA was significantly associated with both the urinary excretion of 8-OHdG (r > or = 0.259, P < or = 0.018) and the 8-OHdG and hOGG1 levels in peripheral leukocytes (r > or = 0.313, P < or = 0.004). In addition, urinary 8-OHdG was correlated with both the level of DNA 8-OHdG (r > or = 0.24, P < or = 0.05) and the expression of hOGG1 in peripheral leukocytes (r > or = 0.429, P < 0.001). Protein carbonyl content (PCC) level was significantly associated with not only the level of DNA 8-OHdG (r > or = 0.366, P < 0.001) and the urinary 8-OHdG (r > or = 0.258, P < or = 0.018) but also the expression of hOGG1 in peripheral leukocytes (r = 0.485, P < 0.001). A significant but weak association was found between high-performance liquid chromatograph-electrochemical detection (HPLC-ECD) and enzyme-linked immunosorbent assay (ELISA) for urinary 8-OHdG (r = 0.334, P = 0.002) and between HPLC-ECD and flow cytometry assays for 8-OHdG in leucocytes (r = 0.395, P < 0.001). Significant associations were observed between AAA and PCC and liver function indices (alanine aminotransferase and aspartate aminotransferase). These findings suggest significant contribution from AFB1 exposure to oxidative stress and subsequent repair among adolescents that may impose substantial risk for hepatocarcinogenesis in adulthood in this region.

Intestinal perforation after combined liver-kidney transplantation for a case of congenital polycystic disease.

AIM: To highlight the intestinal perforation (IP), an uncommon and catastrophic complication after combined liver-kidney transplantation. METHODS: Combined liver-kidney transplantation (LKTx) with left kidney excision and a cyst fenestration procedure on the right kidney were performed on a case of 46-year-old female with congenital polycystic disease (CPCD). RESULTS: Two sites of IP were noted 40-50 cm proximal to ileocecal area during emergent laparotomy 10 d postoperatively. Despite aggressive surgical and medical management, disease progressed toward a fatal outcome due to sepsis and multiple organ failure 11 d later. CONCLUSION: Long duration of operation without venovenous bypass, overdose of steroid together with postoperative volume excess may all contribute to the risk of idiopathic multiple IPs. Microbiology and pathology inspections suggested that the infected cyst of the fenestrated kidney might be one reason for the fatal intra-peritoneal infection. Thus for the CPCD patients who seem to be very susceptible to infectious complications, any sign of suspected renal-infection found before or during LKTx is indication for the excision of original kidney. And the intensity of immunosuppression therapy should be controlled cautiously.