Characterization of Androgen Receptor Complex Associated Protein (ARCAP) in hepatocellular carcinoma and liver.

BACKGROUND: Hepatocellular carcinoma (HCC) ranks many tasks in clinical oncology due to possibly developing a general tumor in men and, usually lead to malignant to death within years. Researches had reported about major factors for being HCC was male sex and HCC associated with cirrhosis in childhood was found more common in males than females. In certain mouse strains as studied, breeding with testosterone significantly increases the development of HCC. Furthermore, castration of male mice diminished the frequency of the development of liver tumors. Meanwhile male hepatitis B virus transgenic mice have a greater occurrence of HCC than females. METHODS: We apply degenerate priming PCR to observe the expression of various steroid receptors in livers. Yeast-two hybrid screening to search a novel RNA fragment helps to find a new full-length gene by RACE experiment. RT-PCR is applied to detect various expressions in tissues and cell lines. In situ hybridization detects DNA in Chromosome mapping. GFP-constructs transfection proves the gene localization in cells. Immunoprecipitation pulldown assay verifies protein interaction. Gene transfection followed with luciferase assay demonstrates the interaction of genes within cellular signaling. Genomic alignment analysis for observing sequences data perform from NCBI database website (http://www.ncbi.nim.nih.gov/genebank/). RESULTS: The androgen receptor (AR) expression level is found at the highest level among the steroid receptors families detected in liver tumors. By yeast-two hybrid screening, we cloned an Androgen Receptor Complex Associated Protein (ARCAP), of 95 Kd in molecular weight and its cDNA. ARCAP locates at Chromosome 1. Our findings indicate ARCAP is highly expressed in hepatoma cell lines and liver tumors and their adjacent tumors as observed. Yeast two-hybrid assay and in vitro immunoprecipitation assays demonstrated an interaction between AR and ARCAP. CONCLUSION: We aim to search for different types and levels of steroid receptors expressed within human HCCs and in the adjacent liver tissues. To verify possible molecular mechanisms by which AR might affect hepatoma cells, we had characterized a novel protein ARCAP which functions as a coregulator to interact with AR within liver. The ligand-dependent AR with its cofactor, ARCAP, can induce a signal cascade by transactivation.

Milan criteria, multi-nodularity, and microvascular invasion predict the recurrence patterns of hepatocellular carcinoma after resection.

AIMS: This study aims to evaluate the risk factors for tumor recurrence beyond the Milan criteria (MC) for patients with hepatocellular carcinoma (HCC) after surgical resection (SR) in which salvage liver transplantation is relatively contraindicated. METHODS: A total of 447 patients who underwent SR for HCC were enrolled consecutively. Among them, 248 and 199 patients were within the Milan criteria and beyond the Milan criteria (BMC group), respectively. Overall survival, recurrence, and disease-free survival were analyzed by multivariate analysis. RESULTS: After a median follow-up of 34.4 months, 130 patients died. Microvascular invasion, higher Edmondson stage of tumor cell differentiation, BMC group, and no anti-viral therapy were associated with poor overall survival. Multi-nodularity, higher Edmondson stage, BMC group, and no anti-viral therapy were independent risk factors for tumor recurrence, while BMC group and no anti-viral therapy were independent risk factors for disease-free survival. The Milan criteria, multi-nodularity, and microvascular invasion were used to stratify the patients into low-, medium-, and high-risk groups for tumor recurrence outside the MC and showed statistical significance (low vs. medium, p = 0.011; low vs. high, p < 0.001; medium vs. high, p = 0.009). CONCLUSIONS: The combination of the MC, multi-nodularity, and microvascular invasion predict the post-operative recurrence of HCC and may provide a roadmap for further treatment.

Surgical resection for hepatocellular carcinoma in pregnancy: a case report.

Hepatocellular carcinoma (HCC) occurring in pregnancy is very rare. The prognosis is usually poor because of unclear clinical presentation. A 30-year-old woman who suffered from HCC during pregnancy underwent hepatectomy twice, and resection for pulmonary metastasis once. A healthy infant was delivered after the first hepatectomy. Currently, she remains disease free 55 months after the second hepatectomy and 39 months after pulmonary metastatectomy. Moreover, she had another healthy infant 37 months after pulmonary metastatectomy. Aggressive resection of recurrent HCC may prolong life, and pregnancy should not alter the treatment strategy for HCC.

Hepatic resection can provide long-term survival of patients with non-early-stage hepatocellular carcinoma: extending the indication for resection?

BACKGROUND: Indications for resection of non-early-stage hepatocellular carcinoma (HCC) remain controversial. This study aimed to identify factors that affect outcome of patients with Barcelona Clinical Liver Cancer Classification (BCLC) stage B or stage C HCC after hepatic resection. METHODS: From 1991 to 2006, 478 patients with HCC (BCLC stage B, n = 318 and BCLC stage C, n = 160) who underwent resection were enrolled. Factors in terms of overall survival and recurrence were analyzed. RESULTS: After a median follow-up of 29.5 months, 304 patients had died. The cumulative overall survival rate at 5 years was 46.5% in BCLC stage B patients and 29.1% in stage C patients (P < .001). Multivariate analysis disclosed that serum albumin levels ≤4 g/dL, indocyanine green retention rate at 15 minutes >10%, serum creatinine >1.2 mg/dL, multinodularity, Edmondson stage III or IV in tumor cell differentiation, and the presence of macroscopic vascular invasion were independent risk factors of poor overall survival. There were 331 patients with tumor recurrence after resection. Recurrence rate was less in BCLC stage B than that in BCLC stage C (P = .001). Multivariate analysis showed that serum albumin level ≤4 g/dL, multinodularity, cut margin ≤1 cm, and Edmondson stage III or IV were associated with the recurrence of HCC. CONCLUSION: Hepatic resection can provide long-term survival benefit in selected BCLC stage B or C patients with compensated liver function, especially in those presenting with a single neoplasm without vascular invasion.

The effect of age on the long-term prognosis of patients with hepatocellular carcinoma after resection surgery: a propensity score matching analysis.

OBJECTIVE: The effect of age on the clinicopathologic manifestations of hepatocellular carcinoma (HCC) and on the survival rate in patients with HCC after resection surgery remains controversial. We aim to compare the clinicopathological features and prognoses between younger and older patients with HCC undergoing resection. DESIGN: Retrospective review. SETTING: A tertiary medical center. PATIENTS: We enrolled 1074 consecutive patients with HCC who were undergoing a partial hepatectomy. Patients who were 55 years of age or younger were defined as the younger group (n = 374), and patients who were older than 55 years of age were defined as the older group (n = 700). MAIN OUTCOME MEASURES: The postoperative prognoses of the younger and older groups using multivariate analysis and propensity score matching analysis. RESULTS: The younger patients had better liver functional reserve but more aggressive tumor factors than did the older patients. After a median follow-up of 41.0 months, 543 patients died. The cumulative 10-year survival rates were 41.3% in younger patients and 28.8% in the older patients (P = .02). However, using both multivariate analysis and propensity score matching analysis, we failed to demonstrate that age was an independent risk factor associated with overall survival. Besides, there were 643 patients with tumor recurrence after surgery. Using both multivariate analysis and propensity score matching analysis, we found that the incidence of tumor recurrence in younger patients was comparable to that in the older patients. CONCLUSIONS: Age is not a risk factor to determine the prognosis of patients with HCC who underwent resection. Older patients with HCC who have good liver functional reserve are encouraged to receive resection surgery.

The necessity of hepatic vein reconstruction after resection of cranial part of the liver and major hepatic veins in cirrhotic patients.

BACKGROUND: The necessity of hepatic vein reconstruction (HVR) after resection of cranial part of the liver and major hepatic vein(s) in cirrhotic patients when residual liver is insufficient for a major hepatectomy remains unclear. METHODS: Fifty-two cirrhotic patients who underwent resection of cranial part of the liver and hepatic vein(s) for liver neoplasms were divided retrospectively into 3 groups based on the volume of the congestive area of the remnant liver after hepatectomy: group A, 28 patients, the volume of the congestive area was ≤20% of the residual liver volume and underwent no HVR; group B, 7 patients, the volume of the congestive area was >20% of residual liver volume and underwent no HVR; and group C, 17 patients, in whom HVR was performed (the volume of the congestive area was >20% of residual liver volume in 16 and <20% in 1). Background characteristics and postoperative results were compared between the groups. RESULTS: Although group C patients had a significantly longer operative time, their postoperative courses were similar to group A patients. Group B patients had a significantly longer postoperative hospital stay and a greater postoperative morbidity and 90-day mortality. No 90-day mortality ensued in the group A and C patients. CONCLUSION: In selected cirrhotic patients whose remnant liver is insufficient for major hepatectomy, HVR appears to be safe and desirable after resection of the cranial part of liver and hepatic vein when the volume of congestive area of liver remnant exceeds 20% of future residual liver volume.

A comparison of prognosis between patients with hepatitis B and C virus-related hepatocellular carcinoma undergoing resection surgery.

BACKGROUND: The impact of viral factors on the prognosis of hepatocellular carcinoma (HCC) remains controversial because of heterogeneous populations included in previous reports. This study aims to compare clinicopathologic features and prognoses between patients with hepatitis B- and hepatitis C-related HCC who underwent resection surgery. METHODS: We enrolled 609 patients with positive serum hepatitis B virus (HBV) surface antigen (HBsAg) and negative serum antibody against hepatitis C virus (anti-HCV) as the B-HCC group and 206 patients with negative serum HBsAg and positive anti-HCV as the C-HCC group. The overall survival rates and cumulative recurrence rates were compared between these two groups. RESULTS: B-HCC patients were significantly younger, predominantly male, had better liver functional reserve, but more advanced tumor stage than C-HCC patients. After a median follow-up period of 40.6 months, 427 patients had died. Furthermore, 501 patients had tumor recurrence after surgery. The postoperative overall survival rates (p = 0.640) and recurrence rates (p = 0.387) of the two groups were comparable. However, the overall survival rate was higher in the B-HCC group than in the C-HCC group in the cases of transplantable HCC (p = 0.021) and Barcelona-Clinic Liver Cancer stage A HCC (p = 0.040). CONCLUSIONS: Viral etiologies were not apparent in determining outcomes of HCC patients who underwent resection due to heterogeneous studied populations. In early-stage HCC, B-HCC patients had better outcomes than C-HCC patients did because of better liver reserve and less hepatic inflammation.

Overcoming the difficulties in laparoscopic management of contracted gallbladders with gallstones: possible role of fundus-down approach.

BACKGROUND: The aim of this study is to compare efficacy and complications between fundus-down and conventional laparoscopic cholecystectomy (LC) in treating contracted gallbladders with gallstones. METHODS: Between January 1999 and May 2008, 64 patients with contracted gallbladders and gallstones were included in the study. Main outcome measures included conversion rate, complication rate, bile duct injury rate, operation time, and postoperative stay. RESULTS: The average postoperative hospital stay for fundus-down technique was 5 ± 3 days, and 7 ± 3 days for conventional technique (P = 0.003). The conversion rate and complication rate were 0% (0/33) and 3.00% (1/33) for fundus-down technique, and 32.3% (10/31) and 22.6% (7/31) for conventional technique (P = 0.0009 and 0.02, respectively). In subgroup analysis, fundus-down LC seemed to lower the bile duct injury rate from 2/31 (6.5%) to 0/33 (0%) compared with 6/1,468 (0.4%) (P = 0.01 between 6.5% and 0.4% vs. P = 1.00 between 0% and 0.4%). CONCLUSIONS: It appears that fundus-down laparoscopic cholecystectomy is associated with lower conversion and complication rates and shorter postoperative hospital stay as compared with conventional laparoscopic cholecystectomy when used to treat patients with contracted gallbladders and gallstones.

Laparoscopic primary closure of common bile duct combined with percutaneous cholangiographic drainage for treating choledocholithiasis.

The aim of this study was to compare the efficacy and safety of laparoscopic primary closure of the common bile duct (CBD) combined with percutaneous transhepatic cholangiographic drainage (PTCD) and laparoscopic choledocholithotomy with T-tube placement for the treatment of CBD stones. Between January 1991 and July 2002, 50 patients with choledocholithiasis and a CBD diameter larger than or equal to 1 cm underwent laparoscopic CBD explorations. The study group consisted of 10 patients undergoing laparoscopic primary closure of the CBD combined with PTCD. The control group consisted of 40 patients undergoing laparoscopic choledocholithotomy with T-tube placement. Parameters were compared statistically. The study group showed higher female/male ratio (6/4 vs. 8/32, P = 0.02), less stone numbers (1.90 +/- 0.88 vs. 3.40 +/- 1.65, P = 0.0078), shorter operation time (138 +/- 37 minutes vs. 191 +/- 75 minutes, P = 0.014), and shorter postoperative stays (7 +/- 3 days vs. 10 +/- 3 days, P = 0.0013). It seems that laparoscopic primary closure of the CBD combined with PTCD can shorten the operation time and postoperative stays as compared with laparoscopic choledocholithotomy with T-tube placement for the treatment of CBD stones.

Quercetin induces oxidative stress and potentiates the apoptotic action of 2-methoxyestradiol in human hepatoma cells.

Hepatocellular carcinoma (HCC) is the leading cause of cancer mortality in Asia. This study evaluated the growth inhibition effect of quercetin and 2-methoxyestradiol in vitro in human HCC cell lines. Combination treatment enhanced the cytotoxic effect in HA22T/VGH and HepG2 cell lines as compared with quercetin or 2-methoxyestradiol alone. The cell population of sub-G0/G1 phase and the level of annexin V binding were increased synergistically after combination treatment with quercetin and 2-methoxyestradiol in both cell lines. Moreover, quercetin combined with 2-methoxyestradiol increased superoxide levels, mitochondrial superoxide dismutase (MnSOD) in mRNA, protein levels, and SOD activity. Finally, we also found the mitochondrial membrane potential was decreased after combination treatment. The changes of reactive oxygen species and mitochondrial disruption were likely to be involved in the mechanism for the synergistic cytotoxicity effects of combination treatment in human hepatoma cells. These results provided a basis for further study of the potential usage of quercetin combination with hormonal agents for the treatment of human hepatoma.

Outcome of foreign residents undergoing deceased donor liver transplantation in China: a single-center experience in Taiwan.

Foreign residents seeking liver transplantation in China are not uncommon. The outcomes of these people have not been well reported, and the results remain unclear. A total of 64 adults [26 with end-stage liver disease (ESLD) and 38 with hepatocellular carcinoma (HCC)] who underwent donation after cardiac death (DCD) liver transplantation in China during a 5-year period were reviewed. The median follow-up period was 15.6 months. The estimated 3-month mortality rate was 4.7%. The overall survival (OS) rate of the entire patient group at 1 and 3 years was 80.3% and 63.6%, respectively. The 1- and 3-year graft survival rates were 78.5% and 64.4%, respectively. For ESLD, the 1- and 3-year OS rates were 82.5% and 82.5%, respectively. For HCC, the 1- and 3-year survival rates were 78.3% and 50.8%, respectively. The 1- and 3-year OS rates for the HCC patients who were beyond the Milan criteria (MC; n = 24) versus those who met the MC (n = 14) were 69.8% and 28.2% versus 92.9% and 92.9% (P = 0.0032). The 1- and 3-year disease-free survival rates for those beyond the MC versus those who met the MC were 56.8% and 39.0% versus 92.3% and 92.3% (P = 0.0089). The incidence of complications was 59.4%. Biliary complications (n = 24, 37.5%), vascular complications (n = 24, 37.5%), and infection (n = 16, 25%) were the 3 most frequent transplant-related complications. There were 10 patients with unsolved biliary complications, and a total of 5 patients died of posttransplant infections. In conclusion, patients with ESLD or HCC within the MC seeking DCD liver transplants in China obtained survival results comparable to those of other major cohorts from Western countries. However, a considerably high incidence of biliary complications, vascular complications, and infection substantially threatening the lives of patients is notable. Furthermore, the associated cost impact on medical resource utilization should not be overlooked.

Predicting morbidity and mortality after hepatic resection in patients with hepatocellular carcinoma: the role of Model for End-Stage Liver Disease score.

BACKGROUND: The Model for End-Stage Liver Disease (MELD) score is currently used as a disease severity index of cirrhotic patients awaiting liver transplantation. This study evaluated the usefulness of the MELD score in predicting mortality and morbidity of patients with hepatocellular carcinoma (HCC) undergoing hepatic resection. METHODS: The study cohort consisted of 1,017 patients who underwent hepatic resection for HCC between 1991 and 2005. Patient variables were examined by univariate and multivariate analyses to identify risk factors for morbidity and mortality. Accuracy in predicting mortality was assessed with the area under the receiver operator characteristic curve (AUC) analysis. RESULTS: The morbidity and mortality rates were 30.7% and 1.9%, respectively. Age, liver cirrhosis, operation time, and MELD score were risk factors for mortality, whereas indocyanine green retention rate at 15-min value, operation time, blood loss, and Child-Turcotte-Pugh score were risk factors for morbidity. Patients with MELD score >8 had higher mortality (4.0% vs. 0.6%, p = 0.004) and higher liver-related morbidities (16.1% vs. 4.3%, p < 0.001), including massive ascites, intra-abdominal hemorrhage, and hepatic failure, compared with patients with MELD score <6. High MELD score also was related to longer postoperative hospital stay (score >8, 14.5 days vs. score <6, 12.6 days, p = 0.015). The AUC for MELD score as a predictor of mortality was 0.718, indicating high clinical usefulness. CONCLUSIONS: The MELD score relates with mortality and liver-related morbidities in HCC patients who undergo hepatic resection. A MELD score >8 represents the trigger for intensive treatment to improve patient outcome.

Mucin-producing gastric cancer: clinicopathological difference between signet ring cell carcinoma and mucinous carcinoma.

BACKGROUND/AIMS: Signet ring cell carcinoma and mucinous carcinoma are mucin-producing gastric cancers. Their clinicopathological difference was obscure. METHODOLOGY: From December 1987 to July 2005, a total of 1612 gastric cancer patients received curative surgery, 128 patients with signet ring cell carcinoma and 48 with mucinous carcinoma were enrolled in this study. Clinicopathological data were compared between the two groups. RESULTS: Early stage (stage I and II) patients with mucinous carcinoma were associated with more male predominant (p = 0.002), larger tumor size (p = 0.020), deeper cancer invasion (p < 0.001), and a worse 5-year overall survival (63.6% vs 88.2%, p = 0.012) than those with signet ring cell carcinoma. There was no significant difference between the two groups with advanced stage in 5-year overall survival. There is no significant difference in the initial recurrence pattern between the two groups. CONCLUSIONS: Patients with mucinous carcinoma had different biological behaviors with those with signet ring cell carcinoma, in particular early stage, hence had a worse survival.

Risk factors for early and late recurrence in hepatitis B-related hepatocellular carcinoma.

BACKGROUND/AIMS: Hepatitis B virus (HBV) levels correlate with the development of hepatocellular carcinoma (HCC), but the role of viral load in HCC recurrence after tumor resection remains unclear. Herein we aimed to investigate the role of viral load in HCC recurrence following tumor resection. METHODS: From 1990 to 2002, 193 HBV-related HCC patients who underwent tumor resection in Taipei Veterans General Hospital were enrolled. Serum HBV DNA level and mutations were analyzed for association with early and late recurrence, together with other clinical variables. RESULTS: During a follow-up of 58.2+/-44 months, 134 patients had HCC recurrence. Multivariate analysis showed that multinodularity (Hazard ratio [HR], 95% confidence interval [CI]; 2.232, 1.021-4.878), macroscopic venous invasion (4.693, 1.645-13.391), AFP >20 ng/ml (3.891, 1.795-8.475), and cut margin 6 (4.658, 1.970-11.017), multinodularity (3.266, 1.417-7.526), ICG-15 >10% (2.487, 1.095-5.650) and HBV DNA level >10(6) copies/ml (2.548, 1.040-6.240) were significantly associated with late recurrence (>two years after resection). Patients with high viral loads tended to have higher Ishak inflammatory (7.00+/-3.07 vs. 5.33+/-2.96, p=0.001) and fibrosis scores (4.17+/-2.01 vs. 3.20+/-2.41, p=0.007) than those with lower loads. CONCLUSIONS: Tumor factors were associated with early HCC recurrence while high viral loads and hepatic inflammatory activity were associated with late recurrence. Pre- and post-operative antiviral and anti-inflammatory therapies may be crucial in reducing late recurrence.

Esophagogastric junction adenocarcinoma according to Siewert classification in Taiwan.

BACKGROUND: The incidence of adenocarcinoma of the esophagogastric junction (AEG) is rapidly increasing. We evaluated the clinicopathological difference and outcomes of Taiwanese patients with AEG according to the Siewert classification. METHODS: Data were prospectively collected between December 1987 and July 2007. Two hundred thirty-one patients underwent curative resection of AEG at Taipei Veterans General Hospital and were divided into different Siewert types. The clinicopathological characteristics, operative morbidity, survival, and initial recurrence pattern were compared between the different types. RESULTS: Fifty-one type II and 180 type III cancer patients were studied. Subtotal esophagectomy via a left thoracotomy (19.6% vs 2.8%), smaller tumor size (4.43 +/- 2.04 vs. 5.35 +/- 2.03 cm), and more combined organ resection (60% vs. 43.1%) were more common in type II than type III cancer. Multivariate analysis showed that three independent risk factors for death were gender, tumor size, and lymphovascular invasion. There were long-term survivors among the patients with lesser curvature site lymph node metastasis, whereas metastasis to the lymph nodes of the distal stomach and along the greater curvature site was associated with poor prognosis. The 5-year survival was similar between type II and type III cancer (59.6% vs. 63.5%, P = 0.947). CONCLUSIONS: Lymphovascular invasion, tumor size, and gender were determined to be three independent factors of survival after curative resection for AEG, and Siewert type was not associated with differences in survival.

Risk factors for post-pancreaticoduodenectomy bleeding and finding an innovative approach to treatment.

BACKGROUND: This study is to determine the risk factors and outcome for post-pancreaticoduodenectomy bleeding, and to assess the roles of surgery and intravascular intervention in its management. METHODS: Post-pancreaticoduodenectomy data of 628 patients were analyzed with regards to post-pancreaticoduodenectomy bleeding. RESULTS: Post-pancreaticoduodenectomy bleeding occurred in 58 patients (9.2%) and led to death in 23 patients. Pancreatic leakage and intra-abdominal abscess were independent risk factors for both extraluminal and intraluminal post-pancreaticoduodenectomy bleeding. The most common source of bleeding was the gastroduodenal artery (n = 9, 24.3%), and 8 of these patients (88.9%) experienced gastroduodenal artery bleeding in late post-pancreaticoduodenectomy bleeding. Hemostasis for post-pancreaticoduodenectomy bleeding was achieved by surgery in 22 patients (78.6%) and intravascular intervention in 7 patients (58.3%). Transarterial embolization for gastroduodenal artery bleeding did not deteriorate liver function in most patients except for 1 who died of hepatic failure. CONCLUSIONS: The placement of metallic clips on the gastroduodenal artery stump during a pancreaticoduodenectomy is helpful in identifying overlooked intermittent sentinel bleeding during angiography. Transarterial embolization for gastroduodenal artery bleeding could not guarantee against hepatic failure. The intravascular placement of a covered stent is the preferred procedure to avoid the complete interruption of arterial blood supply to the liver.

Selecting a short-term prognostic model for hepatocellular carcinoma: comparison between the model for end-stage liver disease (MELD), MELD-sodium, and five cancer staging systems.

BACKGROUND: The model for end-stage liver disease (MELD) and MELD-sodium (MELD-Na) are prognostic models for cirrhotic patients with or without hepatocellular carcinoma (HCC). This study compared the predictive accuracy between the MELD, MELD-Na, TNM (tumor, node, metastasis), Cancer of the Liver Italian Program (CLIP), Barcelona Clinic Liver Cancer (BCLC), Japan Integrated Scoring (JIS), and Tokyo score for 3-month and 6-month mortality in HCC patients. METHODS: A total of 953 patients were prospectively enrolled. The predictive accuracy was compared between different models using the area under receiver operating characteristic curve (AUC). RESULTS: The CLIP system had the highest AUC (0.875) for predicting 3-month mortality, followed by the Tokyo score (0.874), JIS (0.868), BCLC (0.855), MELD-Na (0.829), MELD (0.803), and finally, TNM (0.795) system. At 6 months, the top 3 models and their AUCs were the CLIP (0.882), Tokyo (0.861), and JIS (0.85). MELD-Na consistently had significantly better predictive accuracy than the MELD at 3 and 6 months. The MELD and MELD-Na were better prognostic models in predicting the mortality for surgical patients (AUC, 0.719 to 0.740), whereas the CLIP and Tokyo systems were the 2 better models in staging nonsurgical (AUC, 0.849 to 0.884) and high-risk patients (AUC, 0.790 to 0.846), defined as having at least 2 independent risk factors of mortality, at 3 and 6 months. CONCLUSIONS: The MELD-Na may improve the prognostic ability of the MELD system for patients with HCC. Both the CLIP and Tokyo systems are better short-term prognostic models. These findings are helpful in designing future clinical trials for HCC.

Characteristics and outcome of patients with dual hepatitis B and C-associated hepatocellular carcinoma: are they different from patients with single virus infection?

BACKGROUND: Patients with hepatocellular carcinoma (HCC) caused by dual hepatitis B and C virus (HBV, HCV) infection may constitute a distinct disease group that is different from patients with single virus infection. This study compared the clinical characteristics and outcomes of patients with HBV, HCV and dual virus infection. METHODS: A prospective database of 1215 HCC patients with chronic hepatitis B, C or dual virus infection was investigated. RESULTS: Patients with HCV infection (n=388) were significantly older (mean age, 69 years) than patients with dual virus (n=75, 65 years) and HBV (n=752; 60 years) infection (P<0.0001). The male-to-female ratios for the HBV, dual virus and HCV groups were 5.2, 3.4 and 1.3 respectively (P<0.0001). Patients in the HBV group more often had higher total tumour volume (mean, 409 cm(3)) than those in the dual virus group (244 cm(3)) and HCV (168 cm(3)) group (P<0.0001). No significant differences of the severity of liver cirrhosis, performance status, cancer staging and tumour cell differentiation were noted among the three groups. Patients in the HCV group had a significantly poor survival in comparison with the HBV group only in the subset of patients with small tumour volume (<50 cm(3)) in the Cox proportional hazards model (relative risk, 1.44; P=0.041). CONCLUSIONS: Dual HBV and HCV virus infection does not accelerate the speed of HCC formation in patients with chronic hepatitis B, and appears to have a modified course of carcinogenesis pathway that is diverted away from the biological behaviour of HBV and HCV infection.

Glucocorticoid protects hepatoma cells against metabolic stress-induced cell death.

Hepatocellular carcinoma is one of the most common cancers in the world. Previously, we found that the level of glucocorticoid receptor was significantly higher in hepatocellular carcinoma than in adjacent liver tissues. Moreover, in vitro and in vivo studies showed that glucocorticoid stimulated the growth of hepatoma cells. On the other hand, endogenous metabolites such as 2-methoxyestradiol, a metabolite of estrogen produced in liver, and lactic acid, an end-product of glycolysis can result in apoptosis of tumor cells. There are studies that glucocorticoid inhibited apoptosis induced by different chemotherapeutic drugs, whether glucocorticoid could block endogenous stresses, such as 2-methoxyestradiol- or lactic acid-induced apoptosis in human and murine hepatoma cells is not known. In this study, the antagonistic effects of dexamethasone on 2-methoxyestradiol- and lactic acid-induced apoptosis were investigated in human HepG2 and murine Hepa1-6 hepatoma cells. Treatment of hepatoma cells with 2.5-10 microM 2-methoxyestradiol or 25 mM lactic acid resulted in growth inhibition and decreased viability. In addition, results of cell cycle analysis, annexin V binding assay and DNA fragmentation formation showed that 2-methoxyestradiol- or lactic acid-induced apoptosis of hepatoma cells but these effects were partially blocked by dexamethasone. Combined treatment of hepatoma cells with dexamethasone and 2-methoxyestradiol or lactic acid partially reduced the 2-methoxyestradiol- or lactic acid-induced apoptosis signal. Treatment of hepatoma cells with 2-methoxyestradiol or lactic acid resulted in up-regulation of caspase-8, -9 and -3. Dexamethasone partially suppressed the caspase expression. The Bcl-2 level was induced by dexamethasone treatment but decreased after treatment with 2-methoxyestradiol or lactic acid. These results together suggest that glucocorticoids may protect hepatoma cells from metabolic stress-induced cell damage via anti-apoptotic pathways.

Risk factors and management of intra-abdominal infection after extended radical gastrectomy.

BACKGROUND: This study elucidated risk factors and management for intra-abdominal infection after extended radical gastrectomy. METHODS: From 1988 to 2004, 2,076 patients with gastric cancer underwent extended radical gastrectomy at Taipei Veterans General Hospital. Risk factors for intra-abdominal infection were determined by analyzing clinicopathological factors, operative procedure, combined organ resection, operative time, blood loss, and associated disease(s). Management modalities were summarized. RESULTS: The overall complication rate was 18.7%. Eighty (3.9%) patients were found to have intra-abdominal infections. Age, prolonged operation time, and combined organ resection were the precipitating factors. These patients were categorized into 3 groups: intra-abdominal abscess with adequate drainage, intra-abdominal abscess without anastomotic leakage, and intra-abdominal abscess because of leakage. Adequate drainage was the primary treatment. Mortality rate was 22.5% (18), and the most common cause of mortality was intra-abdominal abscess caused by leakage. CONCLUSIONS: Although expert surgical skills can minimize the incidence of intra-abdominal infection, management also requires experience and training.