Activating mechanism of transcriptor NF-kappaB regulated by hepatitis B virus X protein in hepatocellular carcinoma

AIM:To investigate the mechanism and significance of NF-κB activation regulated by hepatitis B virus X protein (HBx) in hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC).METHODS:The expression levels of HBx, p65,IκB-α and ubiquitin were detected by immunohistochemistry in HCC tissue microarrays (TMA) respectively, and IκB-α was detected by Western blot in HCC and corresponding liver tissues.RESULTS: The percentage of informative TMA samples was 98.8% in 186 cases with a total of 367 samples. Compared with corresponding liver tissues (60.0%),the HBx expression was obviously decreased in HBV-associated HCC (47.9%,u=2.24,P<0.05).On the contrary, the expressions of p65 (20.6% vs45.3%, u=4.85, P<0.01) and ubiquitin (8.9% vs 59.0%,u=9.68,P<0.01) were notably elevated in HCC.In addition, IκB-α had a tendency to go up. Importantly, positive relativity was observed between HBx and p65 (X^2=10.26,P<0.01), p65 and IκB-α (x^2=16.86,P<0.01), IκB-α and ubiquitin (x^2=8.90, P<0.01) in HCC, respectively.CONCLUSION:Both active and non-active forms of NF-κB are increased in HBV-associated HCC. Variant HBx is the major cause of the enhancement of NF-κB activity. The activation always proceeds in nucleus and the proteasome complexes play an important role in the activation.

The value and limitation of transcatheter arterial chemoembolization in preventing recurrence of resected hepatocellular carcinoma

AIM: To evaluate the value and limitation of postoperative transcatheter arterial chemoembolization (TACE) in preventing recurrence of hepatocellular carcinoma (HCC). METHODS: In the first group, 987 postoperative patients with HCC, who did not have any evidence of recurrence in the first preventative TACE but were found to have recurrence at different times during the follow-up survey, were analyzed. In the second group, 643 postoperative patients with HCC had no TACE for compared study. To study the relationship between the recurrence time and the number of TACE treatments was analyzed. RESULTS: The 6-, 12-, and 18-mo recurrence rates in the first and second groups were 22.2% (210 cases) vs 61.6% (396 cases), 78.0% (770 cases) vs74.7% (480 cases) and 88.6% (874 cases) vs80.1% (515 cases). There were significant differences between the recurrence rates of the two groups at 6 mo (P＜0.0001).CONCLUSION: The principal role of TACE after HCC operation is to suppress, detect early and treat micrometastasis. It has a good effect of preventing recurrence of HCC in 6 mo, but such an effect is less satisfactory in a longer period. When it is uncertain whether HCC is singlecentral or multi-central and if there is cancer residue or metastasis after operation, TACE is valuable to prevent recurrence.

TIP30 regulates apoptosis-related genes in its apoptotic signal transduction pathway

AIM: To investigate the role of TIP30 in apoptotic signal pathway in hepatoblastoma cells and to provide a basis for TIP30 as a gene therapy candidate in the regression of hepatoblastoma cells.METHODS: Apoptosis of human hepatoblastoma cell lines HepG2 (p53 wild), Hep3B (p53 null) and PLC/RPF/5 (p53mutant) infected with Ad-TIP30 (bearing a wild type human Tip30 gene) were analyzed and p53, Bax and Bclxl expression levels were compared among these cells.MlT assay, DNA fragmentation, in situ 3' end labeling of DNA, annexin-Ⅴ FITC staining were used to detect cell death and apoptosis in cells at various time intervals subsequent to infection, and to determine whether TIP30 had an effect on the expression levels of some apoptosis-related gene products such as Bax, p53 and Bcl-xl. A similar time course experiment was performed by Western blotting.RESULTS: In MTT assay, the viability of HepG2 cells decreased significantly from 99.7% to 10% and displayed more massive cell death within 5-8 d than Hep3B and PLC/RPF/5 cells, with their viability decreased from 97.8% to 44.3% and 98.1% to 50.4%, respectively. In annexin-ⅤFITC assay, the percentage of apoptosis cells in HepG2cells was two to three-fold higher than that in control cells (infected with Ad-GFP), two-fold higher than that in Hep3B cells and 1.4-fold higher than that in PLC/RPF/5 cells 36 h after infection, respectively. Moreover, in HepG2 cells, the p53 began to increase 6-8 h after infection, reaching a maximum level between 8 and 12 h after infection and then dropped. Bax showed a similar increase in the cells as p53 reached the maximum at 8-12 h and subsequently decreased. Interestingly, Bcl-xl protein levels were down regulated during 24 to 36 h after Ad-TIP30 infection. In contrast, ectopic expression of TIP30 in Hep3B and PLC/RPF/5 cells had no effect on the regulation of Bax expression, but had an effect on Bcl-xl levels. In comparison with HepG2 cells, these data suggested that up-regulation of p53 levels by TIP30 might be a pre-requisite for Bax and Bax/Bcl-xl ratio increase. We hypothesized that TIP30 might regulate Bax gene partly through p53, which sensitizes cells to apoptosis by involving a p53 apoptosis signal transduction pathway.CONCLUSION: TIP30 plays an important role in predisposing hepatoblastoma cells to apoptosis through regulating expression levels of these genes. Ad-TIP30carrying exogenous TIP30-anti-tumor genes may be regarded as a potential candidate for the treatment of hepatocellular carcinoma.

Different alterations of cytochrome P450 3A4 isoform and its gene expression in livers of patients with chronic liver diseases

AIM: To determine whether parenchymal cells or hepaticcytochrome P450 protein was changed in chronic liverdiseases, and to compare the difference of CYP3A4 enzymeand its gene expression between patients with hepaticcirrhosis and obstructive jaundice, and to investigate thepharmacologic significance behind this difference.METHODS: Liver samples were obtained from patientsundergoing hepatic surgery with hepatic cirrhosis (n=6) andobstructive jaundice (n=6) and hepatic angeioma (controls,n=6). CYP3A4 activity and protein were determined by Nashand western bloting using specific polychonal antibody,respectively. Total hepatic RNA was extracted andCYP3A4cDNA probe was prepared according the methodof random primer marking, and difference of cyp3a4expression was compared among those patients byNorthern blotting.RESULTS: Compared to control group, the CYP3A4 activityand protein in liver tissue among patients with cirrhosis wereevidently reduced. (P＜0.01) Northern blot showed the samechange in its mRNA levels. In contrast, the isoenzyme andits gene expression were not changed among patients withobstructive jaundice.CONCLUSION: Hepatic levels of P450s and its CYP3A4isoform activity were selectively changed in different chronicliver diseases. CYP3A4 isoenzyme and its activity declinedamong patients with hepatic cirrhosis as expression of cyp3a4gene was significantly reduced. Liver's ability to eliminatemany clinical therateutic drug substrates would declineconsequently, These findings may have practical implicationsfor the use of drugs in patients with cirrhosis and emphasizethe need to understand the metabolic fate of therapeuticcompounds. Elucidation of the reasons for these differentchanges in hepatic CYP3A4 may provide insight into morefundamental aspects and mechanisms of imparied liverfunction.

Adjustment of lipiodol dose according to tumor blood supply during transcatheter arterial chemoembolization for large hepatocellular carcinoma by multidetector helical CT

AIM: To work out an indMdualized lipiodol dose in transcabheter arterial chemoembolization (TACE) for large hepatocellular carcinoma (HCC) according to its blood supply evaluated by CT.METHODS: One hundred patients with large HCC (more than 8 cm in diameter) were studied by multidetector helical CT. Patterns of blood supply of HCC were divided into sufficient blood supply, poor blood supply, mixed blood supply and arteriovenous (A-V) shunt. The dose of ultrafluid lipiodol was determined by diameter and blood supply type of HCC. Patients were divided into two groups (50 cases each): lipiodol perfusion group and iodized oil perfusion group according to tumor diameter and the blood supply type of tumor.RESULTS: The confirmation and effective rates were 82%,84% in the first group and 36%, 46% in the second group (P<0.01).CONCLUSION: A relatively individualized lipiodol dose may be determined according to the blood supply pattern and the tumor diameter by CT imaging.

Expression of cytochrome P4502E1 gene in hepatocellular carcinoma

AIM: To investigate cytpchrome P4502E1 (CYP2E1) gene expression in occurrence and progression of hepatocellular carcinoma (HCC). METHODS: The human liver arrayed library was spotted onto the nylon membranes to make cDNA array. Hybridization of cDNA array was performed with labeled probes synthesized from RNA isolated from HCC and adjacent liver tissues. Sprague-Dawley rats were administrated diethyInitrosamine (DENA) to induce HCC. CYP2E1 expression was detected by the method of RT-PCR and Northern blot analysis. RESULTS: CYP2E1 was found by cDNA array hybridization to express differently between HCC and liver tissues. CYP2E1 only expressed in liver, but did not express in HCC tissues and expressed lowly in cirrhotic tissues. In the progression of cirrhosis and HCC, the expression level of CYP2E1 was gradually decreased and hardly detected until the late stage of HCC. CONCLUSION: Using arrayed library to make cDNA arrays is an effective method to find differential expression genes. CYP2E1 is a unique gene expressing in liver but did not express in HCC. CYP2E1 expression descended along with the initiation and progression of HCC, which is noteworthy further investigations in its significance in the development of HCC.

Clinicopathological significance of loss of heterozygosity and microsatellite instability in hepatocellular carcinoma in China

AIM: To determine the features of microsatellite alterations and their association with clinicopathological characteristics of hepatocellular carcinoma (HCC). METHODS: Loss of heterozygosity (LOH) and microsatellite instability (MSI) of 55 microsatellite loci were detected with PCR-based microsatellite polymorphism analyses in tumors and corresponding noncancerous liver tissues of 56 surgically resected HCCs using the MegaBACE 500 automatic DNA analysis system.RESULTS: LOH was found in 44 of 56 HCCs (78.6%) at one or several loci. Frequencies of LOH on 1p, 4q, 8p,16q, and 17p were 69.6% (39/56), 71.4% (40/56), 66.1% (37/56), 66.1% (37/56), and 64.3% (36/56), respectively. MSI was found in 18 of 56 HCCs (32.1%) at one or several loci. Ten of fifty-six (17.9%) HCCs had MSI-H. Serum HBV infection, alpha-fetoprotein concentration, tumor size, cirrhosis, histological grade, tumor capsule, as well as tumor intrahepatic metastasis, might be correlated with LOH on certain chromosome regions. CONCLUSION: Frequent microsatellite alterations exist in HCC. LOH, which represents a tumor suppressor gene pathway, plays a more important role in hepatocarcinogenesis. MSI, which represents a mismatch repair genepathway, is a rare event during liver carcinogenesis. Furthermore, LOH on certain chromosome regions may be correlated with clinicopathological characteristics in HCC.

Homozygosity for Pro of p53 Arg72Pro as a potential risk factor for hepatocellular carcinoma in Chinese population

AIM: Codon 72 exon 4 polymorphism (Arg72Pro) of the p53 gene has been implicated in cancer risk. Our objective was to investigate the possible association between p53Arg72Pro polymorphism and susceptibility to hepatocellular carcinoma (HCC) among Chinese population.METHODS: The p53 Arg72Pro genotypes were determined by PCR-based restriction fragment length polymorphism (RFLP) analysis in 507 HCC cases and 541 controls. Odds ratios (ORs) for HCC and 95% confidence intervals (CIs)from unconditional logistic regression models were used to evaluate relative risks. Potential risk factors were included in the logistic regression models as covariates in the multivariate analyses on genotype and HCC.RESULTS: The frequencies for Pro and Arg alleles were 44.5%, 55.5% in HCC cases, and 40.3% and 59.7% in controls, respectively. The Pro allele was significantly associated with the presence of HCC (P = 0.05) and had a higher risk for HCC (OR = 1.19, 95% CI 1.00-1.41) as compared with the Arg allele. After adjusted for potential risk factors, Arg/Pro heterozygotes had an 1.21-fold increased risk (95% CI 0.82-1.78, P = 0.34) of HCC compared with Arg homozygotes, whereas the risk for Pro homozygotes was 1.79 (95% CI 1.06-3.01, P = 0.03) times higher than that for Arg homozygotes. Pro-allele carriers had a higher relative risk of HCC than the Arg-only carriers (adjusted OR = 1.33, 95% CI 0.92-1.92, P = 0.13), although the difference was not statistically significant.CONCLUSION: Homozygosity for Pro of p53 Arg72Pro is potentially one of the genetic risk factors for HCC in Chinese population. The p53 Arg72Pro polymorphism may be used as a stratification marker in screening individuals at a high risk of HCC.

Isoflurane preserves energy balance in isolated hepatocytes during in vitro anoxia/reoxygenation

AIM: To investigate the protective effect of isoflurane on energy balance in isolated hepatocytes during in vitro anoxia/reoxygenation, and to compare isoflurane with halothane.METHODS: Hepatocytes freshly isolated from fed rats were suspended in Krebs-Henseleit buffer, and incubated in sealed flasks under O2/CO2 or N2/CO2 (95%/5%, V/V)for 30 or 60 min, followed by 5 or 10 min of reoxygenation,with an added volatile anesthetic or not. ATP, ADP, and adenosine monophosphate in hepatocytes were determined by high performance liquid chromatography, and energy charge was calculated.RESULTS: During 30 min of anoxia, the energy charge and total adenine nucleotide steadily increased with the isoflurane dose from 0 to 2 minimum alveolar anesthetic concentration (MAC), then decreased from 2 to 3 MAC.In short incubations (30-35 min) at 1 MAC isoflurane, energy charge modestly decreased during anoxia, which was partially prevented by isoflurane and completely reversed by reoxygenation, and total adenine nucleotide did not decrease. In long incubations (60-70 min), both energy charge and total adenine nucleotide greatly decreased during anoxia, with partial and no reversal by reoxygenation,respectively. Isoflurane partly prevented decreases in both energy charge and total adenine nucleotide during anoxia and reoxygenation. In addition, 1 MAC isoflurane obviously increased ATP/ADP, which could not be changed by 1MAC halothane.CONCLUSION: Isoflurane partially protects isolated hepatocytes against decreases in both energy charge and total adenine nucleotide during short (reversible) or long (irreversible) anoxia.

Genetic alterations of hepatocellular carcinoma by random amplified polymorphic DNA analysis and cloning sequencing of tumor differential DNA fragment

AIM: To study the genetic alterations and their association with clinicopathological characteristics of hepatocellular carcinoma (HCC), and to find the tumor related DNA fragments.METHODS: DNA isolated from tumors and corresponding noncancerous liver tissues of 56 HCC patients was amplified by random amplified polymorphic DNA (RAPD)with 10 random 10-mer arbitrary primers. The RAPD bands showing obvious differences in tumor tissue DNA corresponding to that of normal tissue were separated,purified, cloned and sequenced. DNA sequences were analyzed and compared with GenBank data.RESULTS: A total of 56 cases of HCC were demonstrated to have genetic alterations, which were detected by at least one primer. The detestability of genetic alterations ranged from 20% to 70% in each case, and 17.9% to 50% in each primer. Serum HBV infection, tumor size,histological grade, tumor capsule, as well as tumor intrahepatic metastasis, might be correlated with genetic alterations on certain primers. A band with a higher intensity of 480 bp or so amplified fragments in tumor DNA relative to normal DNA could be seen in 27 of 56 tumor samples using primer 4. Sequence analysis of these fragments showed 91% homology with Homo sapiens double homeobox protein DUX10 gene.CONCLUSION: Genetic alterations are a frequent event in HCC, and tumor related DNA fragments have been found in this study, which may be associated with hepatocarcinogenesis. RAPD is an effective method for the identification and analysis of genetic alterations in HCC, and may provide new information for further evaluating the molecular mechanism of hepatocarcinogenesis.

Potential inhibition of cytochrome P450 3A4 by propofol in human primary hepatocytes

AIM: Hepatic cytochrome P450 isoenzymes constitute a superfamily of hemoproteins that play a major role in the metabolism of endogenous compounds and in the detoxification of xenobiotic molecules. P450 3A4 is one of the most important forms in human being, and mediates the metabolism of around 70% of therapeutic drugs and endogenous compounds. Propofol, a widely used intravenous anesthetic drug, is known to inhibit cytochrome P450activities in isolated rat hepatocytes. The goal of this study was to evaluate the potential efficacy of propofol on P4503A4 in a dose-dependent manner to understand its drugdrug interaction.METHODS: Hepatocytes were isolated from liver specimens from hepatic angioma patients undergone hepatic surgery.Primary incubated hepatocytes were treated with 0, 0.01,0.05, 0.1, 0.5, and 1.0 mM propofol for 24 hours. P450 3A4activity was measured with Nash′s colorimetry. The protein expression was assessed by Western blot analysis.RESULTS: A dose-dependent inhibitory effect of propofol was observed in cytochrome P450 3A4 activity. A minimal dosage of propofol (0.01 mM) induced a significant inhibition of P450 3A4 activity, although its regular dosages (0.01-0.1mM) showed no inhibitory effect on the cellular protein expression of P450 3A4.CONCLUSION: Propofol may be a potential CYP3A4 inhibitor as this anesthetic can inhibit isoenzyme activity significantly and reduce the metabolic rate of CYP3A4 substrates. This inhibition occurs at post-expression level, and concentration of propofol used clinically does not affect CYP3A4 protein expression. propofol may thus induce drug interaction of cytochrome P450 3A4 activity at the dosage used clinically.

Expression of TRAIL Receptors in Human Hepatocellular Carcinoma and Apoptosis Induced by TRAIL

Objective: To investigate the expression of TRAIL receptors in human hepatocellular carcinoma and neighboring non-tumor liver tissues and to study its roles in apoptosis of SK-Hepl cell line. Methods:The expression of TRAIL receptors in hepatocellular carcinoma and in SK-Hepl cell line was detected by immunohistochemical staining and RT-PCR, and the apoptosis of SK-Hepl cell line induced by recombi-nant human TRAIL together with or without INF-γ was measured by FCM. Results: The expression of four TRAIL receptors was detectable in human hepatocellular carcinoma and neighboring non-tumor liver tissues. High expression of DR4 and DR5 was detected in tumor and neighboring non-tumor liver tissues whereas low expression of DcR1 and DcR2 was found in tumor, significantly lower than that in normalliver tissues (67.86% vs 100%, 78.57% vs 100%, respectively, P<0.01. TRAIL together with INF-γ stronglyincreased the apoptosis of SK Hepl cell line. Conclusion: The four TRAIL receptors can be detected in hepatocellular carcinoma and in SK-Hepl cell line. Combinations of TRAIL and INF-γ may be a useful alternative to HCC.

In Vitro and in Vivo Study of the Antitumor Effects of a THANK Modified Hepatoma Cell Line

Objective THANK, known as a member of TNF superfamily,is a petent costimulator of both B and T lymphocytes and can promote a strong immune response.To investigate its role in liver immunotherapy,the anti-tumor effects of the THAND-transduced hepatoma cell line SMMU-7721 in vitro and in vivo studied. Methods THANK full-elngth cDNA was transfected into SMMU-7721 cell line .The transfectant with stable expression of THAND was obtained by clone selection and THANK's effects on hepatoma cells were analyzed,further the tumorigenicity of THANK -transduced 7721 cells was examined in nude mice.Results THANK's expression in 7721 cells inhibited the growth of hepatoma cells and induced a strong CTL response in vitro.The cell cycle analysis showed that THANK transfected 7721 cells were arrested in the S phase.The expression of THANK in SMMU-7721 cell line not only inhibited the tumorigenicity of 7721 cells,but also induced a systemic immune response against re-chalenge of parental 7721 tumors. Conclusion THANK transduction in SMMU-7721 cells can induce an effective immune response in nude mice and may be useful for the immunotherapy of hepatomas.

Partial Hepatectomy with Skeletonization of the Hepatoduodenal Ligament for Hilar Cholangiocarcinoma

Objective To summarize the surgical experience of partial hepatectomy with skeletonization of the hepatoduodenal ligament in the treatment of hilar cholangiocarcinoma.Methods Between Jan.1999 and Dec,2001,67 consecutive patients with hilar cholangiocarcinoma underwent surgical exploration at the Second Military Medical University,Eastern Hepatobiliary Surgery Hospital.The clinical data of these patients were reviewed.Results Of the 67 patients,65(97%) underwent surgical resection.Fourty-nine patients(73%) received curative resection:22 skeletonization resection(SR) and 27 SR combined with partial hepatectomy.In 16 patients(9%) with curative resection the tumor margin was histologically postive and the resection was therefore considered palliative.The tumors were classified according to Bismuth with SR was type Ⅱ(17cases),various types of partial hepatectomy with SR was type Ⅲ and type IV.Right lobectomy with right caudate lobectomy was indicated in type Ⅲ(6cases),left lobectomy with complete caudate lobectomy in type Ⅲb(15cases),right loobectomy with complete caudate lobectomy(3 cases),left lobectomy with complete caudate lobectomy(9 cases) and quadrate lobectomy(2 cases)in type IV.SR and left lobectomy with complete caudate lobectomy was successfully performed in 2 patients(3%) who had undergone palliative biliary resection and cholangiojejunostomy before.Eight patients(12%) had local resecton of the tumor with Roux-en-Y hepaticojejunostomy reconstruction using intrahepatic stents.Two patients(3%) had palliative biliary drainage.Combined portal vein resection was performed in 13 patients(20%) and hepatic artery resection in 27 patients(40%) .Twenty-four atients(36%) had no postoperative complication,23 patients(34%) had minor complications only ,and the remaining 20 patients(30%) had major complications.Of the 20 patients with major complications,14 recovered,the remaining 6 patients died from hepatorenal failure with other organ failures,from myocardial infarction or from intraabdominal or gastrointestianl bleeding 7,12,14,42,57 or 89 days after surgery.The 30-day operative mortality was 4.5%.The mean survival of the patient with curative resecton was 16 months(range 1-32 months);for those undergong palliative resection mean survival was 7 months(range 1-14months).Conlusion Partial hepatectomy with SR for hilar cholangiocarcinoma can be performed with acceptable morbidity and mortality.For curative treatmet of hilar cholangiocarcinoma,caudate lobectomy is always recommended in Bismuth Ⅲ/IV.

Disseminated tumor cells homing into rats' liver:A new possible mechanism of HCC recurrence

AIM:To detect the origin of hepatocellular carcinoma (HCC)recurring and attempt to propose a new recurrent mechanism.METHODS:Orthotopic liver allotransplantation was performed on male rats with HCC- induced by diethylnitrosamine using female donors.Metastatic tumors in transplanted livers were obtained.A DNA probe that exhibits specificity for the rat Y chromosome was generated by using a set of primers specificto murine srygene.In situ hybridization (ISH) for Y chromosome was used to detected the origin of HCC recurring. Male HCC tissue was designed to be positive control. ISH on female tissue and using non-labeled with DIG probe was thought to be negative control.RESULTS: Positive marks were seen through ISH for Y chromosome in recurrent tumor tissue and positive control.No signal was detected in both negative controls.CONCLUSION: Recurrent HCC after liver transplantation originated from disseminated tumor cells in recipients.Extrahepatic cells homing into liver may be a new HCC recurrence mechanism. Likewise, it implicates that this mechanism is responsible for HCC recurring after hepatectomy.

Effect of insulin on hyperkalemia during anhepatic stage of liver transplantation

AIM: To investigate the effectiveness of insulin on decreasing serum potassium concentration during anhepatic stage of orthotopic liver transplantation.METHODS: Sixteen patients with serum potassium concentrations greater than 4.0 mmol/L at the onset of anhepatic stage were randomized into two groups. The patients in control group (n = 8) received no treatment,while those in treatment group (n = 8) received an intravenous bolus injection of regular insulin (20 U) 10 min into the anhepatic stage, followed by a glucose infusion(500 mL 50 g/L dextrose) over 15 min.RESULTS: In control group, potassium concentration underwent no changes whereas in treatment group, it decreased from 4.8±0.48 mmol/L to 4.19±0.55 mmol/L(mean±SD) within 15 min and to 3.62±0.45 mmol/L 60 min after the therapy. The potassium concentration was lower in treatment group than in control group within 30 min of treatment (3.94+0.57 vs 4.47±0.42 mmol/L,respectively; P<0.05), and increased similarly 30 s after graft reperfusion in both groups of patients, but remained lower in treatment group (5.81±1.78 vs7.44±1.75 mmol/L,respectively; P<0.05). The potassium concentration returned to pre-reperfusion levels within 5 min after graft reperfusion.CONCLUSION: In patients undergoing orthotopic liver transplantation, the administration of insulin rapidly decreases serum potassium concentration even in the absence of the liver, suggesting an important contribution by extrahepatic tissues in insulin-stimulated uptake of potassium.

Pancreaticoduodenectomy with Roux—Y Anastomosis to Reconstruct the Digestive Tract：A Report of 30 Cases

Objective To explore the ways how to decrease the morbidity and mortality of pancreaticoduodenectomy(PD).Medthods In 30 cases of PD,a free vascularized jejunal loop was used to pefform single loop Roux-Y anastomosis to reconstruct the digestive tract.Results The morality rate was xero and there were no cases of leakage at the pancraticojejunostomy and choledocojejunostomy.All patients were discharged from hospita 10-14 days after operation.Postoperative follow-up of long-term choronic complications showed only one patient(3.33%)suffered from chronic steatorrhea and malnutrition,the remaining 29 cases(96.67%)had a good function of digestion and normal nutrition.There were no cases of biler reflux gastric disease,retrograde infection,anastomostic ulcer of gastrojejunostomy,and dumping syndrome.Conclusion This surgical procedure can effectively reduce the morbidity and the mortality of PD.

Percutaneous Radiofrequency Ablation for Hepatic Malignancies

Objective To study the therapeutic efficay of percutaneous radiofrequency ablation(PRFA)for hepatic malignancies and to definr its indications and its criteria of the curative effect.Methods In 100 patients with histologically of clinically confirmed hepatocellular carcinoma(HCC)or liver metastases we performed PRFA under ultrasound guidance using Le Veen multipolar array meedle electrode and RF 2000 generator.All patients were followed to identify complications and to assess treatment response.Results PRFA was performed in 76 patients with HCC and in 24 with liver metastases.The Alpha-fetoprotein(AFP)levles of the AFP positive HCC patients with inoperable small HCCs decreased to normal in 75.0%(21/28)and decreased markedly in 21.4%(6/28).Complete necrosis of small hepatic malignancies,documented by magnetic resonance imaging(MRI)was achieved in 85.9%(61/71).If the tumor shows iso-or hyper-intensity on Ti-weighted images,and relative hypointensity on T2-weighted images,and no enhanced intensity on dynamic contrast-enhanced MR imaging,it is considered completely coagulated.Conclusion PRFA is a novel local thermal palliative therapy for small hepatic malignancies that is minimally invasive,safe and effective.In patients with large lesions it can be combined with transarterial chemoembolization(TACE).Critera for curative treatment are normalization of serum AFP and /or MRI or CT scan findings showing complete necrosis.

Some Therapeutic Concepts Converse of Primary Liver Cancer in China

Since 1990's,comprehensive therapy predominated by surgery has become the maintrend in the treatment of primary liver cancer(PLC).W elucidate concepts converse of operative indication,operative mode,postoperative anti-recurrence,approach of comprechensive treatment and theraeutic model in PLC.These new concepts have gradually involoved in clinical diagnosis and treatment,which promotes the advance in hepatic surgery.

c-src activating mutation analysis in Chinese patients with colorectal cancer

AIM: To investigate the occurrence of cellular src (c-src)activating mutation at codon 531 in colorectal cancer patients from Chinese mainland.METHODS: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay followed by sequencing and single-strand conformation polymorphism analysis were carried out to screen 110 samples of primary colorectal cancer and 20 colorectal liver metastases.RESULTS: Only one sample showed PCR-RFLP-positive results and carried somatic codon 531 mutations. No additional mutation of c-src exon 12 was found.CONCLUSION: c-src codon 531 mutation in colorectal cancer is not the cause of c-src activation.