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Eastliver
  Hepatobiliary Pancreat Dis Int
 
2004 Vol.  3 No.  2
Published: 2004-05-15

pages 161-320

REVIEW ARTICLES
ORIGINAL ARTICLES/Transplantation
ORIGINAL ARTICLES/Liver
ORIGINAL ARTICLES/Biliary
ORIGINAL ARTICLES/Pancreas
CASE REPORTS
REVIEW ARTICLES
170 Wu J, Zheng SS
Liver transplantation in China: problems and their solutions

BACKGROUND: The past decade has witnessed the rapid development of liver transplantation in China. The 1-year survival of liver transplant patients comes to 80% in many leading medical centers and the number of liver transplantation is increasing. However, liver transplantation in China is facing several challenges including recipient with hepatocellular carcinoma (HCC), recurrence of HCC and hepatitis B, long-term postoperative care, the bridge to liver transplantation, and shortage of liver donor. This review was to understand the status of and problems in liver transplantation in China.
DATA RESOURCES: An English-language literature search using MEDLINE (1990-2003) on liver transplantation and other related reports and review articles in Chinese from major transplant centers in China.
RESULTS: HCC is one of the main indications for liver transplantation in China but different centers adopted different criteria for selection of patients. Hepatitis B virus reinfection is a vital problem after liver transplantation in HBV-related patients. More and more attention was focused on long-term postoperative care and donor shortage. Artificial liver support system has been applied in patients waiting for a graft in many centers.
CONCLUSIONS: HCC remains to be one of the main indications for liver transplantation in China; combined hepatitis B immune globulin and lamivudine is considered effective to prevent hepatitis B virus reinfection. Apart from long-term postoperative care for the improvement of the survival rate, early steroid withdrawal is feasible in liver transplantation. Living donor liver transplantation, split liver transplantation, and marginal donor transplantation can deal with donor shortage to some extent. Artificial liver assist system serves as a bridge to liver transplantation.

Hepatobiliary Pancreat Dis Int. 2004; 3(2): 170-174 .
[Abstract] ( 258 ) [HTML 1KB] [PDF 334KB] ( 2231 )
175 Wang ZF, Liu C
Liver retransplantation: indications and outcomes

BACKGROUND: Liver transplantation is a life-saving therapeutic modality for patients with end-stage liver diseases. After liver transplantation, however, more than 10% patients may lose the grafts caused by a variety of reasons. This review covers the most frequent indications for liver retransplantation as well as the results and specific problems with each indication.
DATA RESOURCES: Searching MEDLINE (1997-2003) for articles on liver retransplantation.
RESULTS: The most frequent indications of liver retransplantation are primary non-function, hepatic artery thrombosis, graft rejection and recurrent diseases. The results after liver retransplantation remain inferior to those after first transplantation.
CONCLUSION:  Liver retransplantation, which is the only means of prolonging survival in those patients whose initial graft has failed, makes an important contribution to overall survival.

Hepatobiliary Pancreat Dis Int. 2004; 3(2): 175-178 .
[Abstract] ( 253 ) [HTML 1KB] [PDF 229KB] ( 2632 )
250 Wu J, Zheng SS
Toll-like receptor 4 involvement inhepatic ischemia/reperfusion injury in mice

BACKGROUND: Toll-like receptor 4 (TLR4) is involved in innate immunity by recognizing endotoxin resulting in a burst of inflammatory cascade. We investigated the relation between activation of TLR4 and liver injury in partial hepatic ischemia/reperfusion (I/R) injury in mice.
METHODS: TLR4-deficient mice (C3H/Hej) and wild type mice (WT, C3H/Heouj) were used in the model of I/R injury. Partial hepatic ischemia was produced by occlusion of inflow to the median and left lobes for 45 minutes. Blood was drawn at 1 and 3 hours after reperfusion. The blood was analyzed for aspartate aminotransferase (AST) and tumor necrosis factor alpha (TNF-α). TNF-α mRNA expression and myeloperoxidase (MPO) level in the ischemic lobes were examined by northern blot and myeloperoxidase assay respectively.
RESULTS: AST levels were significantly decreased in TLR4deficient mice compared with WT mice at both time points (WT: 1215.5±174.03, 2958.17±186.81 IU/L at 1 and 3 hours respectively vs TLR4def: 661.83±106.09, 1145.17±132.43 IU/L at 1 and 3 hours, mean±SD, 6 mice/group, t=-6.65 and -5.57, P<0.001). Consistent with the role of TNF-α in hepatic I/R, serum TNF-α was decreased in TLR4 deficient mice at 3 hours after reperfusion compared with WT (152.39±43.3 vs 249.12±51.89, n=6, t=-3.13, P<0.05). MPO level in the ischemic lobes in TLR4 deficient mice at 3 hours after reperfusion was significantly lower than that in WT mice (0.059 ±0.004 vs 0.173±0.025, n=6, F=33.49, P<0.001). This difference appears to be mediated at the gene level since TLR4 deficient mice had decreased TNF-α mRNA expression at 1 hour after reperfusion compared with WT mice (80.3±28.8 vs 189.4±24.6, t=-3.25, P<0.05).
CONCLUSIONS: Compared with WT mice, TLR4-deficient mice appear to have a mild I/R injury. Regulation of TNF-α at mRNA level seems to have a critical effect. These suggest TLR4 be involved in the mechanism of hepatic I/R injury in mice.

Hepatobiliary Pancreat Dis Int. 2004; 3(2): 250-253 .
[Abstract] ( 281 ) [HTML 1KB] [PDF 263KB] ( 2304 )
ORIGINAL ARTICLES/Transplantation
179 He XS, Ma Y, Ju WQ, Wu LW, Wu JL, Liang YJ, Hu RD, Chen GH, Huang JF
Dynamic microcirculatory changes in liver graft from non-heart-beating donor with warm ischemia injury in rat

BACKGROUND: Since the 1990s, liver grafts from non-heart-beating donor (NHBD) have become an alternative because of the deficiency of grafts from heart-beating-donors (HBDs). Warm ischemia injury, however, directly influences the grafts’ activity and functional recovery after operation. We investigated the microcirculatory change of liver graft at different warm ischemia time (WIT) in rats and determined the maximum limitation of liver graft to warm ischemia.
METHODS: According to WIT, 120 rats were divided randomly into 5 groups of 0, 15, 30, 45, 60 minutes respectively. The microcirculatory changes of their liver grafts were measured including serum level of hyaluronic acid (HA) and ultrastructural changes. After orthotopic liver transplantation (OLT), the recovery of microcirculation of the liver grafts after 24 hours, 48 hours and 3 days was observed.
RESULTS: Microcirculatory changes and function of the liver grafts became normal after reperfusion when the WIT was less than 30 minutes. In the 45-minute WI group, part of blood sinusoids was full of cytoplasmic blebs stemming from the microvilli of hepatocytes and hemocytes. The serum level of HA in each group after 45 minutes of WI recovered after reperfusion.
CONCLUSIONS: The microcirculatory change of rat liver graft is reversible when the WIT is less than 30 minutes: rat liver graft could be safely subject to warm ischemia within 30 minutes. The maximal 45 minutes of WI can be tolerated by the microcirculatory function of liver graft. After 60 minutes of WI, irreversible disturbance of microcirculation may appear.

Hepatobiliary Pancreat Dis Int. 2004; 3(2): 179-182 .
[Abstract] ( 222 ) [HTML 1KB] [PDF 365KB] ( 2075 )
183 Liu B, Ming CS, Zeng FJ, Sha B, Chen ZS, Chen ZH, Chen S
Simultaneous pancreas-kidney transplantation with modified enteric drainage of exocrine pancreatic secretion

BACKGROUND: As a valid therapeutic option for patients with type 1 diabetes mellitus (IDDM) and secondary diabetic nephropathy, simultaneous pancreas-kidney transplantation (SPK) remains more undeveloped than other solid organ transplantations due to the restrictions of surgical techniques especially the modes of exocrine pancreatic secretion. The aim of this paper was to summarize our single-center experience in SPK with modified enteric drainage (ED).
METHODS: From June 2000 to July 2003, 10 patients with IDDM associated with uremia received SPK. The pancreatic allograft exocrine secretion was drained into the proximal jejunum via a side-to-side duodenojejunostomy without Roux-en-Y anastomosis. Quadruple immunosuppressive regimen consisted of induction of tacrolimus (TAC)/cyclosporine (CsA), mycophenolate mofetil (MMF), steroids and antibodies, which included antilymphocyte globulin (ALG) or anti-CD25 monoclonal antibody.
RESULTS: ED-SPK without Roux-en-Y anastomosis was successful in all 10 patients without serious complications such as pancreatitis, graft thrombosis and pancreatic fistula. The patients regained immediate kidney allograft function and euglycemia with insulin-independence. Four patients survived over one year. Episodes of acute rejection were observed in 4 patients, 3 of whom showed reversion after treatment of OKT3 or insulin. Early postoperative complications included peritoneal infection (2 patients), wound infection (2) and renal hematoma (1).
CONCLUSION:  ED-SPK without Roux-en-Y anastomosis is safe and preferable to the patients with IDDM associated with uremia.

Hepatobiliary Pancreat Dis Int. 2004; 3(2): 183-187 .
[Abstract] ( 303 ) [HTML 1KB] [PDF 314KB] ( 2369 )
ORIGINAL ARTICLES/Liver
188 Yao GB, Cui ZY, Wang BE, Yao JL, Zeng MD
A 3-year clinical trial of lamivudine in treatment of patients with chronic hepatitis B

BACKGROUND: Lamivudine was approved for the treatment of chronic hepatitis B in China in 1999; however the long-term result has not yet been reported in detail. This clinical trial was to evaluate the long-term efficacy and safety of 3-year lamivudine treatment for chronic hepatitis B and the impact of emergence of YMDD mutation of hepatitis B virus (HBV).
METHODS: This multi-center, randomized, double-blind, placebo controlled trial began from 1996 to 1999. A total of 429 patients with serum HBsAg, HBeAg and HBV DNA positive were randomized to receive either lamivudine 100 mg daily (322 patients) or placebo (107) for the first 12 weeks. All patients were given subsequently open labelled lamivudine 100 mg/d for a total of 156 weeks.
RESULTS: After 12-week lamivudine therapy, the levels of serum HBV DNA decreased rapidly. The negativity of HBV DNA (<1.6 pg/ml) at week 12 was 92.2% in the lamivudine group, whereas it was only 14.1% in the placebo group (P<0.01). After 1-year lamivudine treatment, 72.7% of the patients showed undetectable serum HBV DNA (<1.6 pg/ml). At the end of 3 years, serum HBV DNA continued to be substantially suppressed with a median level below a detectable level in patients with non-YMDD variant HBV, which was increased to 86 mEq/ml (bDNA method, equivalent hybridization method 10 pg/ml) in patients with YMDD mutation. At the end of 1, 2 and 3 years, the rates of HBeAg loss were 9.5%, 16.8% and 20.0% respectively and the rates of HBeAg/anti-HBe seroconversion were 8.3%, 11.5% and 17.3%. The rates of HBeAg loss and seroconversion were correlated with the baseline level of ALT. In patients with a baseline level of alanine transaminase (ALT)>2×upper limit of normal (ULN) and ALT >5×ULN, the rates of HBeAg loss were 42.2% and 66.7%, and the rates of seroconversion were 34.4% and 61.1% respectively (P<0.01) at the end of year 3. The levels of ALT at year 3 remained normal in 58.8% of patients whose baseline level of ALT was elevated, and in 79.1% of patients whose level of ALT was normal before treatment. YMDD mutations occurred in 12.1%, 49.7% and 70.5% of patients respectively at year 1, 2 and 3. In patients with YMDD mutation, the levels of HBV DNA were increased slightly with mild to moderate elevation of ALT level. HBeAg loss and seroconversion were 20.0% and 15.1% in patients with YMDD mutation at the end of year 3, which were lower than those in non-variant patients (P<0.01). Adverse drug reactions or events varied generally from mild to moderate. In 2 patients serious adverse events (fatigue and abdominal distension) were related to medication. ALT flares (ALT>5×ULN) occurred in 17 patients: 10 were YMDD mutants and 7 were non-mutants; all of them were relieved. No death occurred in the period of 3 years.
CONCLUSION:  Sustained inhibition of HBV replication and clinical improvement could be obtained after 3-year lamivudine therapy of good tolerance and safety.

Hepatobiliary Pancreat Dis Int. 2004; 3(2): 188-193 .
[Abstract] ( 294 ) [HTML 1KB] [PDF 370KB] ( 2288 )
194 Yang BH, Xia JL, Huang LW, Tang ZY, Chen MS, Li JQ, Liang AM, Mo QG, Lu HS,Dai CL, Yan LN, Yu ZJ, Rao RS, Li LQ, Su ZX, Fang ZW
Changed clinical aspects of primary liver cancer in China during the past 30 years

BACKGROUND: Primary liver cancer (PLC) is one of the most frequently seen tumors in China. Thirty years ago, patients with PLC were often detected at relatively late stage, with a palpable mass or marked clinical symptoms and poor prognosis. In the past 30 years, the diagnosis and treatment of PLC have been greatly improved with better prognosis.
METHODS: In order to study the changes of PLC during the 30 years, the clinical data of 3250 patients with PLC from 10 medical institutions of China were collected, analyzed, and compared with those of 3254 PLC patients before the 30 years.
RESULTS: In the 3250 patients aged 1-80 years, with an average age of 49.1 years, the male to female ratio (2.3∶1) was lower than that before the 30 years. 73.5% of the 3250 patients sought medical advice within 3 months after the onset of the disease in contrast to 63.8% before the 30 years. Compared with those patients before the 30 years the symptoms and signs were alleviated generally. The HBsAg positive rate was 81.0%, but the HCV-Ab positive rate was 13.2%. The AFP level in 75% of patients was elevated, but in the remaining 25% was normal. 1912 patients (58.8%) were confirmed pathologically. Among them 1755 patients (91.8%) had hepatocellular carcinoma. The overall resection rate was 46.3%. Those who had early, middle, late stage carcinoma accounted for 29.9%, 51.5%, and 18.6% respectively in contrast to 0.4%, 47.0%, and 52.6% reported before the 30 years. The 1-, 3-, 5-year survival rates of the patients were 66.1%, 39.7%, and 32.5% respectively, whereas 93.5%, 70.1%, and 59.1% for the early stage patients, and 65.3%, 30.5%, and 23.5% for the middle stage patients. The half and 1-year survival rates of the late stage patients were 52.5%, and 14.7%, respectively.
CONCLUSION:  Comparison with the clinical data before and after the 30 years show that PLC can be diagnosed early. More PLC patients tend to undergo resection while receiving a better conservative treatment, which ensures a prognosis.

Hepatobiliary Pancreat Dis Int. 2004; 3(2): 194-198 .
[Abstract] ( 249 ) [HTML 1KB] [PDF 297KB] ( 2178 )
199 Pan Y, Wang ZM, Mou LJ, Teng XD, Zheng ZJ, Ying LX
Focal nodular hyperplasia of the liver: pathological analysis of 11 cases

BACKGROUND: Focal nodular hyperplasia (FNH) is a benign tumor-like lesion of the liver, predominantly affecting women. Its etiology is obscure and its pathogenesis is poorly understood. FNH should be differentiated from other benign and malignant hepatic lesions. The aim of this study was to explore the pathological characteristics of FNH of the liver.
METHODS: Eleven patients with FNH were studied retrospectively by using hematoxylin and eosin, immunohistochemical and histochemical staining.
RESULTS: In 8 female and 3 male FNH patients aged 19 to 54 years (mean 32), most of lesions showed central scars macroscopically. Microscopically 8 patients were found of classical type, 2 were of telangiectic type, and 1 was of mixed type.
CONCLUSION:  FNH is an uncommon benign hyperplastic lesion of the liver. It should be differentiated from hepatocellular adenoma, alpha-fetoprotein negative hepatocellular carcinoma, and fibrolamellar carcinoma.

Hepatobiliary Pancreat Dis Int. 2004; 3(2): 199-203 .
[Abstract] ( 243 ) [HTML 1KB] [PDF 492KB] ( 3346 )
204 Zhao H, Yao JL, Han MJ, Zhou KR, Yan FH
Multiphase hepatic scans with multirow- detector helical CT in detection of hypervascular hepatocellular carcinoma

BACKGROUND: Multirow-detector helical CT (MDCT) allows faster Z-axis coverage and improves longitudinal resolution to scan the entire liver. This study was to evaluate the value of multiphase hepatic CT scans using MDCT in diagnosing hypervascular hepatocellular carcinoma (HCC).
METHODS: Multiphase hepatic CT scans in 40 patients were carried out with a Marconi Mx8000 MDCT scanner. The scans of early arterial phase (EAP), late arterial phase (LAP) and portal venous phase (PVP) were started at 21, 34 and 85 seconds after injection of contrast medium, respectively. The number of detected lesions was calculated in each phase. The density of the liver and tumor was greater than 1 cm for HCC, and the density of the liver and tumor in each phase was statistically calculated.
RESULTS: A total of 61 lesions were found in the 40 patients, and lesions greater than 1 cm were seen in 47 cases. The density differences between the liver and tumor were statistically significant (P<0.05) at the LAP and EAP and between the LAP, EAP and PVP. In the 61 lesions, the detectability in the EAP, LAP and the double arterial phases (DAP) was 32%, 87%, and 94%, respectively. Significant difference was found between the LAP plus PVP and the EAP plus PVP; but no significant difference was observed between the DAP plus PVP and the LAP plus PVP.
CONCLUSIONS: The utility of MDCT scan in the liver has optimized the protocol of arterial phase scan. MDCT is possible to scan the entire liver in a real arterial phase and it is very valuable in the detection of small HCC.

Hepatobiliary Pancreat Dis Int. 2004; 3(2): 204-208 .
[Abstract] ( 253 ) [HTML 1KB] [PDF 405KB] ( 2299 )
209 Zhou L, Rui JA, Zhou RL, Peng XM, Wang SB, Chen SG, Qu Q, Zhao YP
Liver injury after intermittent or continuous hepatic pedicle clamping and its protection by reduced glutathione

BACKGROUND: The debate is still going on about selection of several clamping patterns during hepatectomy. The aim of this study was to assess the safety and preference of normothermic intermittent or continuous hepatic pedicle clamping and confirm the protective effect of reduced glutathione (GSH).
METHODS: Thirty-two adult male healthy Sprague-Dawley (SD) rats were divided into groups of intermittent clamping and GSH absent (IA), continuous clamping and GSH absent (CA), intermittent clamping and GSH present (IP) and continuous clamping and GSH present (CP). The clamping manners were successively 40 minutes in continuous clamping groups and two cycles of 20 minutes with an interval of 5 minutes in intermittent clamping groups, and reperfusion periods were 60 minutes. Experimental parameters included levels of malonaldehyde (MDA) and Cu/Zn superoxide dismutase (SOD), pathological and ultrastructural changes in liver tissues, activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in sera.
RESULTS: In the same group, the activities of ALT and AST were significantly higher in post-clamping rats than in pre-clamping rats (P<0.05), but no significant differences were noted in levels of MDA and Cu/Zn SOD (P>0.05). The differences of all values between post-reperfusion rats and pre-clamping rats were significant (P<0.05). Pathological and ultrastructural changes could be observed, but no irreversible injury was present. The comparison of the groups showed that the values at relevant time points between the intermittent and continuous groups were not significantly different (P>0.05). The values were significantly different between the GSH absent and present groups after reperfusion (P<0.05). The morphological damages were also obviously alleviated in the GSH present group.
CONCLUSIONS: Normothermic intermittent or continuous hepatic pedicle clamping could cause reversible liver ischemia/reperfusion injury when the clamping time lasts 40 minutes. The injury extent seems to be similar. Continuous clamping should be regarded as a proper method in liver surgery. GSH has been confirmed as an effective agent in preventing post-clamping liver injury.

Hepatobiliary Pancreat Dis Int. 2004; 3(2): 209-213 .
[Abstract] ( 250 ) [HTML 1KB] [PDF 336KB] ( 2146 )
214 Lin GL, Xu PQ, Qi H, Lian JH, Zheng H, Dang XW
Relations of Budd-Chiari syndrome to prothrombin gene mutation

hypertension and/or hypertension of the inferior vena cava (IVC) due to the obstruction of the hepatic veins (HV) and/or intrahepatic IVC outlet. Being etiologically complicated and obscure, BCS can be acquired or idiopathic and several gene mutations may be contributable. This study was to explore whether prothrombin gene mutation (FⅡ G20210A) takes part in the pathogenesis of BCS and to investigate their correlativity.
METHODS: In 38 proven BCS patients and 70 controls, polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to find FⅡ G20210A mutation. To detect whether there are any mutations, four steps were taken: purification of genome DNA from whole blood, amplification of special fragment by polymerase chain reaction, digestion of the fragment via restriction endonuclease, and analysis of results by polyacrylamide gel electrophoresis.
RESULTS: FⅡ G20210A mutation was not detected in all patients and controls.
CONCLUSIONS: No FⅡ G20210A mutation exists in Chinese patients with BCS, nor correlativity between the occurrence of BCS and FⅡ G20210A mutation. The etiology of BCS in the Chinese needs further investigation.

Hepatobiliary Pancreat Dis Int. 2004; 3(2): 214-218 .
[Abstract] ( 256 ) [HTML 1KB] [PDF 303KB] ( 2171 )
219 Piao YF, Tang TY, Niu JQ, Wang F
Construction of eukaryotic expressionplasmids of hepatitis B surface antigen and helper T lymphocyte epitope

BACKGROUND: DNA immunization provides a promising approach to elicit protective humoral and cellular immune responses against HBV. This study was to construct an eukaryotic expression plasmid containing helper T lymphocyte epitope, which will enhance the immunogenicity of a novel hepatitis B virus (HBV) fusion protein DNA vaccine.
METHODS: The target gene containing pan-DR helper T cell epitopes (PADRE) and HBsAg was amplified by polymerase chain reaction (PCR). The PCR products were linked with PMD-18T vector. Plasmid DNA was purified from transformed E.coli competent cell JM109 and digested with Hind III and EcoR I. Then, the target gene was cloned in pcDNA3.1(+) digested by Hind III and EcoR I. Finally, the identity of DNA was verified by digestion and DNA sequencing.
RESULTS: The recombinant expression vectors of pcDNA3.1(+)-PADRE/HBs were identified by restriction enzyme digestion and DNA sequencing. The insert DNA fragment was consistent with the expected sequence.
CONCLUSIONS: The constructed eukaryotic expression plasmid of pcDNA3.1(+)-PADRE/HBs is convenient for further study of eukaryotic transfection and response for cellular and humoral immunity against HBV.

Hepatobiliary Pancreat Dis Int. 2004; 3(2): 219-222 .
[Abstract] ( 260 ) [HTML 1KB] [PDF 228KB] ( 2246 )
223 Chen NL, Bai L, Deng T, Zhang C, Kong QY, Chen H
Expression of hepatitis B virus antigen and Helicobacter pylori infection in gastric mucosa of patients with chronic liver disease

BACKGROUND: It is common for the gastroendoscopist to find patients infected simultaneously with hepatitis B virus (HBV) and Helicobacter pylori (H pylori). Considering that HBV infection is linked to hepatocellular carcinoma and H pylori to gastric cancer, we investigated the incidence in this kind of patients in the northern Jiangsu Province, China. Rational management of these patients was also discussed.
METHODS: Seventy-two patients including 28 patients with chronic hepatitis B and 44 patients with post hepatitis B liver cirrhosis served as observation group. Thirty patients with gastritis but without liver disease were included as controls. Diagnostic endoscopy was performed in all the patients. Three biopsy specimens were taken from the pyloric antrum 3 cm from the pyloric ring. Urease test staining of hematoxylin and eosin or fuchsin, and immunohistochemical analysis of H pylori IgG antigen and HBV antigen (HBsAg, HBcAg) were performed.
RESULTS: The extent and intensity of chronic inflammation were identified in 95.5% (42/44) of the antrum mucosa of the patients with cirrhosis and in 92.9% (26/28) of the patients with chronic hepatitis. The expression of H pylori in the mucosa was found in 29 of the 42 patients with cirrhosis associated with antrum inflammation (69.0%). The expression of H pylori was observed in 20 of the 26 patients with chronic hepatitis combined with antrum inflammation (76.9%). No significant difference existed between the cirrhosis group and the chronic hepatitis group. The rates of HBV antigen expression in the H pylori positive and negative gastric antrum mucosa were 69.8% (37/53)and 73.7% (14/19), respectively (P>0.05).
CONCLUSIONS: Over-expression of HBV antigen (HBsAg and HBcAg) coexists with the expression of H pylori antigen in the H pylori infected gastric mucosa. Difficult clearance of HBsAg and HBcAg from gastric epithelial cells may be related to persistent H pylori infection. Early treatment of H pylori infection may be beneficial to the prognosis of patients with chronic liver disease.

Hepatobiliary Pancreat Dis Int. 2004; 3(2): 223-225 .
[Abstract] ( 257 ) [HTML 1KB] [PDF 197KB] ( 2697 )
226 Li SY, Yu B, An P, Wei JC, Zuo FY, Cai HY
Influence of FasL gene expression on hepatic metastasis of colorectal carcinoma

BACKGROUND: FasL expression was reported to be associated with hepatic metastasis of colorectal cancer. The aim of this study was to study FasL gene expression in colorectal carcinoma and its influences on biological behavior and hepatic metastasis of colorectal carcinoma.
METHODS: FasL gene expressions were examined with reverse transcriptase-polymerase chain reaction (RT-PCR) in the primary focus of colorectal carcinoma, adjacent cancerous mucosae, and metastasized liver focus from colorectal cancer. HR-8348 cells of human rectal cancer cell line were transfected with FasL cDNA. Cell growth suppression rate and response to 5-FU and carboplatin were observed and analyzed with the MTT method.
RESULTS: FasL gene expression was detected in the primary focus of colorectal cancer (n=58), adjacent cancerous mucosae (n=58), and metastasized hepatic tumor tissues (n=28). The positive rate of FasL expression was 24% (14/58), 8% (5/58), and 100% (58/58) in the primary focus, adjacent cancerous mucosae and metastasized hepatic tumor tissues respectively. FasL expression rate in the metastasized hepatic tumor tissues was higher than that in the primary focus (χ2=43.49, P<0.01) and adjacent cancerous mucosae (χ2=57.66, P<0.01). In a group of patients with hepatic metastasis, the FasL expression rate in primary focus was higher than that in patients without hepatic metastasis (χ2=3.96, P<0.05). In vitro study positive expression of FasL was shown in transfected HR-8348 cells. When 5-FU or carboplatin was added, there was a significant difference in growth suppression rate between FasL positive and controlled cancer cells (t=9.02, t=11.93, P<0.01). Under the same concentration of chemotherapeutic agents, the survival rate of FasL positive HR-8348 cells was higher than that of controlled cells.
CONCLUSIONS: FasL positive cancer cells are powerfully resistant to chemotherapeutic agents. The expression of the FasL gene in colorectal cancer cells is related to immune evasion to escape from being killed by immune cells, showing stronger drug-resistance, and it facilitates hepatic metastasis.

Hepatobiliary Pancreat Dis Int. 2004; 3(2): 226-229 .
[Abstract] ( 280 ) [HTML 1KB] [PDF 234KB] ( 2009 )
230 Sun Y, Chen HY, Xin SJ
Effect of IL-18 on peripheral blood mononuclear cells of chronic hepatitis B and hepatitis B virus DNA released by HepG2.2.15 cell lines

BACKGROUND: Interleukin-18 (IL-18), a pro-inflammatory cytokine that induces interferon-γ (IFN-γ) production in T cells and natural killer cells, plays a critical role in the T-lymphocyte helper type 1 (Th1) response. This study was designed to explore the effect of IL-18 on peripheral blood mononuclear cells (PBMCs) derived from chronic hepatitis B (CHB) and on hepatitis B virus (HBV) DNA released by HepG2.2.15 cell lines, which were transfected with hepatitis B virus gene in vitro.
METHODS: PBMCs isolated from 25 healthy people and 25 patients with CHB were stimulated with HBcAg and IL-18 of various concentrations for 72 hours. The levels of IFN-γ in the supernatants of cultured PBMCs were determined by ELISA. After the stimulation of IL-18 of various concentrations, PBMCs derived from one patient were co-cultured for 96 hours with HepG2.2.15 cells which had been cultured for 24 hours, and then the supernatants were collected by centrifugation and used for HBV DNA quantitative assay.
RESULTS: When PBMCs were stimulated by HBcAg and IL-18 at various concentrations, the levels of IFN-γ in the supernatants of CHB groups were much higher than those in normal control groups, at 0.2 ng/ml: t=11.70, P<0.01; at 1.0 ng/ml: t=16.19, P<0.01; and at 5.0 ng/ml: t=20.12, P<0.01. In the CHB groups, the levels of IFN-γ in the supernatants of PBMCs stimulated by HBcAg alone were lower than both those stimulated by HBcAg and IL-18 at various concentrations and those stimulated by HBcAg and IL-18 (5.0 ng/ml) together with IL-12 (mild: t=2.20, P<0.05; moderate: t=2.97, P<0.05; severe: t=0.66, P>0.05). The content of HBV DNA in the supernatant of co-cultivation of HepG2.2.15 cells and PBMCs without stimulated materials was higher than that stimulated by HBcAg and IL-18 at various concentrations of HBcAg and IL-18 together with IL-12/IFN-α 1b.
CONCLUSION:  IL-18 can induce IFN-γsecretion and probably play a key role in the modulation of both innate and adaptive immunity. It has implications in improving immunoregulatory effect and increasing the ability of immune cells to kill cells infected by virus.

Hepatobiliary Pancreat Dis Int. 2004; 3(2): 230-234 .
[Abstract] ( 280 ) [HTML 1KB] [PDF 288KB] ( 2474 )
235 Zhang H, Zheng SS, Jiang GP, Wu LH, Zhu F, Yang ZL
Antitumor effect of immunization with fusion of dendritic cells and hepatocellular carcinoma cells in mice

BACKGROUND: Important advances have made within the past few years in the treatment of hepatocellular carcinoma (HCC), however, the long-term prognosis after resection of HCC remains unsatisfactory as a result of a high incidence of recurrence. This study was to investigate immunization with fusions of DCs and HCC cells against HCC tumors transplanted to mice.
METHODS: Fusion cells of dendritic cells (DCs) and H22 cells were prepared with polyethylene glycol. Expression of MHC and costimulatory molecules by dendritomas were determined by FACs. To study the antitumor immune preventitive and therapeutic effects, fusions were subcutaneously injected into naive or tumor-bearing mice; the CTL activity was assumed by the LDH method, and the expression of tumour necrosis factor-α (TNF-α) and interferon-γ(IFN-γ) in tumors were assayed by reverse transcription-polymerase chain reaction (RT-PCR).
RESULTS: The hybridomas of DCs and H22 cells acquired both DCs and H22 cells phenotypes. Immunization of BALB/C mice with DC/H22 fusions induced protective immunity against a high dose of H22 tumor challenge. After treatment with hybridomas, the survival time of tumor-bearing mice was extended. The expression level of TNF-α and IFN-γmRNA was markedly increased.
 CONCLUSION:  The hybridomas of DCs and H22 cells could induce effective antitumor immune responses and may be potentially used in prevention and management of recurrence and metastasis of HCC.

Hepatobiliary Pancreat Dis Int. 2004; 3(2): 235-240 .
[Abstract] ( 430 ) [HTML 1KB] [PDF 370KB] ( 2118 )
241 Li YM, Chen SH, Yu CH, Zhang Y, Xu GY
Effect of acute alcoholism on hepatic enzymes and oxidation/antioxidation in rats

BACKGROUND: Around the world more and more people suffer from acute alcoholism. The purpose of this study was to determine hepatic enzymes and oxidation/antioxidation in rats with acute alcoholism.
METHODS: Rats were randomly divided into three groups: control, low-dose alcohol, and high-dose alcohol. Each alcohol group (n=12) was intravenously infused with ethanol at a dose of 0.3 or 0.7 g/kg body weight respectively. The control group (n=11) was intravenously infused with normal saline at a dose of 0.5 g/kg body weight. Blood was collected for detection of hepatic enzymes and index of oxidation/antioxidation.
RESULTS: The ratio of AST to ALT was 2.44±0.46, 2.57±0.60 and 3.03±0.46 in the three groups, and the difference was significant between the control and high-dose alcohol groups (P≤0.05). No significant changes were observed in the levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total protein (Tp), albumin (Alb), alkaline phosphatase (ALP), cholinesterase (ChE), total bilirubin (TB), C-reactive protein (CRP) and amylase. The levels of serum nitric oxide (NO) in the 3 groups were 39.2±73.25 mol/L, 42.30±4.60 mol/L and 47.86±4.66 mol/L, and significant difference was seen between the control group and the high-dose alcohol group (P<0.01). No significant difference was found in the levels of serum superoxide dismutase (SOD), glutathione (GSH), malondiethylaldehyde (MDA), and CRP in the 3 groups.
CONCLUSION:  The ratio of AST to ALT appears to be a useful index for acute alcohol intoxication. NO is involved in the mechanism of acute alcohol intoxication.

Hepatobiliary Pancreat Dis Int. 2004; 3(2): 241-244 .
[Abstract] ( 282 ) [HTML 1KB] [PDF 227KB] ( 2246 )
245 Wei ZZ, Xia SS
γ-hydroxybutyrate protects the liver from warm ischemia-reperfusion injury in rat

BACKGROUND: Ischemia-reperfusion (I/R) syndrome remains an important clinical consideration in hepatic surgery, hemorrhagic shock, and liver transplantation. γ-hydroxybutyrate (GHB) has been reported to exert protective effects against ischemia-reperfusion injury to various organs. To investigate whether GHB protects the liver from warm ischemia-reperfusion injury, we performed this study in rats.
METHODS: Thirty male Wistar rats were randomly divided into a sham-operation group, a control group,and three I/R groups pretreated with GHB, GHB plus naloxone or naloxone. After 30 minutes of partial ischemia, followed by 60 minutes of reperfusion in the liver, histomorphological and enzymological changes, lipid peroxidation, apoptosis, and the plasma level of endothelin-1 were observed.
RESULTS: I/R increased the serum levels of alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase and the plasma level of endothelin-1 significantly (P<0.01), in addition to increase of apoptotic index (AI) from 0.28%±0.25% to 17.68%±1.91%. The levels of hepatic malondialdehyde were markedly increased, whereas the activities of superoxide dismutase were markedly decreased. GHB pretreatment prevented the liver from warm ischemia-reperfusion injury significantly, but naloxone partially blocked this effect.
CONCLUSION: GHB may significantly protect the liver from hepatic warm ischemia-reperfusion injury via several different mechanisms.

Hepatobiliary Pancreat Dis Int. 2004; 3(2): 245-249 .
[Abstract] ( 249 ) [HTML 1KB] [PDF 275KB] ( 2503 )
254 Xu QX, Ding YT, Qiu YD, Yu DC, Zhang HY
A reliable graded acute liver failuremodel in rats: treatment with internal bioartificial liver

BACKGROUND: Toll-like receptor 4 (TLR4) is involved in innate immunity by recognizing endotoxin resulting in a burst of inflammatory cascade. We investigated the relation between activation of TLR4 and liver injury in partial hepatic ischemia/reperfusion (I/R) injury in mice.
METHODS: TLR4-deficient mice (C3H/Hej) and wild type mice (WT, C3H/Heouj) were used in the model of I/R injury. Partial hepatic ischemia was produced by occlusion of inflow to the median and left lobes for 45 minutes. Blood was drawn at 1 and 3 hours after reperfusion. The blood was analyzed for aspartate aminotransferase (AST) and tumor necrosis factor alpha (TNF-α). TNF-α mRNA expression and myeloperoxidase (MPO) level in the ischemic lobes were examined by northern blot and myeloperoxidase assay respectively.
RESULTS: AST levels were significantly decreased in TLR4deficient mice compared with WT mice at both time points (WT: 1215.5±174.03, 2958.17±186.81 IU/L at 1 and 3 hours respectively vs TLR4def: 661.83±106.09, 1145.17±132.43 IU/L at 1 and 3 hours, mean±SD, 6 mice/group, t=-6.65 and -5.57, P<0.001). Consistent with the role of TNF-α in hepatic I/R, serum TNF-α was decreased in TLR4 deficient mice at 3 hours after reperfusion compared with WT (152.39±43.3 vs 249.12±51.89, n=6, t=-3.13, P<0.05). MPO level in the ischemic lobes in TLR4 deficient mice at 3 hours after reperfusion was significantly lower than that in WT mice (0.059 ±0.004 vs 0.173±0.025, n=6, F=33.49, P<0.001). This difference appears to be mediated at the gene level since TLR4 deficient mice had decreased TNF-α mRNA expression at 1 hour after reperfusion compared with WT mice (80.3±28.8 vs 189.4±24.6, t=-3.25, P<0.05).
CONCLUSIONS: Compared with WT mice, TLR4-deficient mice appear to have a mild I/R injury. Regulation of TNF-α at mRNA level seems to have a critical effect. These suggest TLR4 be involved in the mechanism of hepatic I/R injury in mice.

Hepatobiliary Pancreat Dis Int. 2004; 3(2): 254-258 .
[Abstract] ( 266 ) [HTML 1KB] [PDF 273KB] ( 2083 )
ORIGINAL ARTICLES/Biliary
259 Moellmann B, Ruhnke M, Kremer B
Cholangio-duodenal interposition of an isolated jejunal segment after central resection

BACKGROUND: Bilio-intestinal drainage is routinely performed by Roux-en-Y reconstruction after resection of the central bile duct. Alternatively reconstruction can be achieved by cholangio-duodenal interposition of an isolated jejunal segment (CDJI). This method offers the benefit of potential endoscopic control and intervention during follow-up. Critics of CDJI assume a higher rate of postoperative cholangitis compared to the Roux-en-Y construction.
METHODS: Seventy-six patients with malignant tumors (n=56) or benign strictures and choledochal cysts (n=20) were treated between 1989 and 2002 by cholangio-duodenal interposition of an isolated jejunal segment (measuring 15-25 cm) after central bile duct resection. In 22 patients endoscopic control was first performed postoperatively during hospitalization. In 12 patients bilio-intestinal anastomosis could be inspected endoscopically. In the remaining patients the anastomosis could not be visualized endoscopically because of kinking of the jejunal segment, but in all patients it could be evaluated by endoscopic retrograde cholangiography (ERC).
RESULTS: During follow-up, 25 (33%) patients died from extrahepatic tumor recurrence. Three patients receiving CDJI after severe iatrogenic bile duct injury developed anastomotic strictures. Two of these patients were treated by endoscopic pigtail drainage, and one was treated by percutaneous drainage. Two patients who had received CDJI after choledochal cyst resection developed cholestasis postoperatively because of sludge formation (1 patient) and an intrahepatic concrement (1), which could be solved endoscopically. One patient after resection of a Klatskin tumor developed an anastomotic stricture which could not be visualized endoscopically, making percutaneous drainage necessary. The rate of postoperative cholangitis after CDJI in our patients was comparable to that after the Roux-en-Y reconstruction.
 CONCLUSION:  Interposition of an isolated jejunal segment for reconstruction after bile duct resection should be performed in patients with a high risk of postoperative stenosis. To benefit endoscopic follow-up the jejunal segment should be shorter than 20 cm.

Hepatobiliary Pancreat Dis Int. 2004; 3(2): 259-264 .
[Abstract] ( 296 ) [HTML 1KB] [PDF 495KB] ( 2520 )
265 Liu QG, Geng ZM, Wu SL, Yao YM, Sun H, Pan CE
Reoperation for benign biliary tract diseases in 149 cases: causes and prevention

BACKGROUND: Failure to diagnose and treat benign biliary tract disease relatively common surgical disease may cause serious consequences. Since the introduction of B-mode ultrasonography, CT, or MRI early and accurate diagnosis of the disease has been possible. In clinical practice, however, these methods have not been adequately used. Inappropriate surgical procedures can also lead to bile duct injury or stenosis after injury, residual cholecystitis, stenosis after cholangiojejunostomy, or stenosis of the Oddi’s sphincter. But improvement of the diagnosis and treatment of benign biliary tract disease remains a great challenge to clinicians.
METHODS: A total of 149 patients with benign biliary tract disease who had received reoperation from June 1988 to June 2001 were analyzed retrospectively. Among them 95 patients (63.76%) received operation twice and 38 (25.5%) underwent 3 operations. Sixteen patients (10.74%) needed 4 or more operations. The procedures for the first operation included cholecystectomy (71 patients, 47.65%), cholecystectomy with exploration of the common bile duct (42, 28.19%), cholangiojejunostomy (21, 14.1%), and laparoscopic cholecystectomy (15, 10.06%).
RESULTS: The causes for reoperation included residual and recurrent bile duct stones in 53 patients (35.57%), bile duct injury or stenosis after injury in 41 (27.52%), residual cholecystitis with or without stones in 28 (18.8%), stenosis after cholangiojejunostomy in 17 (11.41%), stenosis of the Oddi’s sphincter in 5 (5.35%), and others in 5 (5.35%). Four patients (2.68%) died after operation.
CONCLUSIONS: To prevent reoperation for benign biliary tract diseases, the following measures should be taken to increase preoperative diagnostic rate, to understand conditions of the biliary tract by using imaging techniques and cholangiography, to examine comprehensively and carefully with choledochoscopy, cholangiography and B-mode ultrasonography intraoperatively, to choose appropriate operative procedures to decrease the rate of residual stones, and to decide the time for the first repair according to injury type of the bile duct. Roux-en-Y hepaticojejunostomy with cholangioplasty is the best operation for the reconstruction of the biliary tract.

Hepatobiliary Pancreat Dis Int. 2004; 3(2): 265-269 .
[Abstract] ( 244 ) [HTML 1KB] [PDF 293KB] ( 2279 )
270 Ji W, Li LT, Chen XR, Li JS
Application of laparoscopic cholecystectomy in patients with cirrhotic portal hypertension

BACKGROUND: Laparoscopic cholecystectomy (LC) has been widely adopted in treating benign gallbladder diseases. Cirrhosis and cirrhotic portal hypertension (CPH) are contraindicated for LC in its early period. In recent years, several studies have reported liberal use of LC in patients with cirrhosis. But its benefits and successful use in patients with CPH are less documented. This study was designed to evaluate the feasibility, safety and technical characteristics of LC in CPH patients.
METHODS: In 38 patients with symptomatic gallbladder disease and CPH, 19 belonged to Child A class, 15 Child B class and 4 Child C class. Perioperative data of these patients were collected and analyzed.
RESULTS: LC was successfully performed in 36 patients, and 2 patients (5.3%) were converted to open cholecystectomy (OC) for difficulty in management of bleeding under laparoscopy and dense adhesion of Calot’s triangle. The surgical time was 62.6±15.2 minutes. The estimated amount of intraoperative hemorrhage was 75.5±15.5 ml. No blood transfusion was necessary. The time to resume diet was 18.3±6.5 hours. Seven postoperative complications in 5 patients (13.2%) included port-site infection (1 patient), respiratory infection (2), upper digestive tract bleeding (1), slight hepatic encephalopathy (1) and increased ascites (2). All patients were cured and discharged from the hospital within 5.6±2.4 days after LC.
CONCLUSIONS: Despite LC is difficult for CPH patients, it is feasible and relatively safe. To make LC successful in patients with CPH, it is necessary for surgeons to acquaint with the technical characteristics of LC and emphasize meticulous perioperative management.

Hepatobiliary Pancreat Dis Int. 2004; 3(2): 270-274 .
[Abstract] ( 357 ) [HTML 1KB] [PDF 297KB] ( 2796 )
275 Ding X, Gong JP, Lu CY, Liu CA, Shi YJ, Gao GW
Relation of abnormal gallbladder arterioles to gallbladder emptying in patients with gallstone and diabetes mellitus

BACKGROUND: Diabetes mellitus is thought to be related to gallstone formation in emptying the gallbladder. Diabetes mellitus may lead to many changes in microarterioles and micronerves; the aim of this study was to investigate the abnormality of arterioles in the gallbladder and its relation to gallbladder hypomotility in patients with gallstone and diabetes mellitus.
METHODS: Thirty patients with simple gallstones and 30 patients with gallstones and diabetes mellitus were analyzed, and their gallbladder emptying function was measured with B ultrasound before operation. After operation, the arterioles of the gallbladder rinsed with periodic acid-schiff (PAS) reagent in photos were used for analysis of the tublar area and stereo system with the Beihang CM-2000B biological and medical photo system.
RESULTS: In patients with gallstones and diabetes mellitus, the gallbladder emptying function was significantly impaired, the area ratio of the arteriole wall to whole arterioles in cross section was significantly higher than that in patients with simple gallstones (0.81±0.09 vs. 0.58±0.15, P<0.01), and the average sound density was also higher (0.41±0.07 vs. 0.30±0.12, P<0.01) in patients with gallstones and diabetes mellitus than in those with simple gallstones. The size of arterioles (diameter) was not significantly related to the area ratio (P>0.05).
 CONCLUSION:  In patients with diabetes mellitus, the sedimentation of PAS positive material in the wall of arterioles leads to the stenosis of arterioles. It is probably contributive to hypomotility of the gallbladder.

Hepatobiliary Pancreat Dis Int. 2004; 3(2): 275-278 .
[Abstract] ( 258 ) [HTML 1KB] [PDF 271KB] ( 2113 )
279 Fu XH, Tang ZH, Zong M, Yang GS, Yao XP, Wu MC
Clinicopathologic features, diagnosis and surgical treatment of intrahepatic cholangiocarcinoma in 104 patients

BACKGROUND: The outcome of surgical treatment of patients with intrahepatic cholangiocarcinoma (ICC) is poor. This study was designed to analyze the relationship between clinicopathologic features and the survival time after operation.
METHODS: The operation was performed in 104 patients with mass-forming type ICC at our hospital between November 1996 and May 2000. Seventy-nine patients (76.0%) were followed up successfully. Sixteen clinicopathological variables including age, sex, history of chronic liver disease, HBsAg, operation, adjuvant therapy, ascites, lymph node metastasis, invasion of adjacent organs, tumor size, necrosis of tumor, envelope, intrahepatic metastasis, International Union Against Cancer (UICC) TNM staging, histology, and cirrhosis were selected for univariate and multivariate analyses to evaluate their influence on the prognosis.
RESULTS: The accumulative 1-, 3-, 5-year survival rates of the 79 patients were 49.4%, 17.3%, 9.6% respectively. Univariate analysis revealed that sex (P=0.0221), HBsAg (P=0.0115), operation (P=0.0042), adjuvant therapy (P=0.0389), ascites (P=0.0001), invasion (P=0.0220), intrahepatic metastasis (P=0.0000) and TNM stage (P=0.0001) were related to survival time. Multivariate analysis revealed that HBsAg, ascites and TNM stage were significantly related to prognosis.
CONCLUSION:  Early diagnosis and treatment and major hepatectomy are essential to improving the results of surgical treatment of ICC patients.

Hepatobiliary Pancreat Dis Int. 2004; 3(2): 279-283 .
[Abstract] ( 268 ) [HTML 1KB] [PDF 277KB] ( 2193 )
284 Qin MF, Xu HB
Combined laparoscopic and endoscopic treatment for bile duct diseases

BACKGROUND: Clinical application of laparoscopy, duodenoscopy and choledochoscopy has been accepted as a mini-invasive surgical therapy for bile duct diseases; but either endoscopic or laparoscopic therapy alone is disadvantageous in its narrow indications and in failure to give full play to the individual superiority. The present study was to evaluate the procedures and therapeutic results of combined laparoscopic and endoscopic treatment for bile duct diseases.
METHODS: Clinical data of 1990 patients with bile duct diseases treated by combination of laparoscopy, duodenoscopy and choledochoscopy in two hospitals were reviewed and analyzed.
RESULTS: Patients with cholecystolithiasis and choledocholithiasis were treated with combined laparoscopy and duodenoscopy (n=1350) in a single operation with a cure rate of 93.6%. Those with choledocholithiasis (n=332) were treated with combined laparoscopy and choledochoscopy with a cure rate of 100%. Combined laparoscopy, duodenoscopy and choledochoscopy was used in 258 patients with choledocholithiasis (29 of them complicated with pancreatitis) and 24 patients with Mirizzi’s syndrome, with a cure rate of 100%. Laparoscopic choledochoenterostomy and preoperative endoscopic nasobiliary drainage were done in 26 patients with a cure rate of 100%. There were no serious operative complications. A follow-up study of 1051 patients for 3 months to 12 years (mean 7.8 years) showed that 10 patients had recurrence of stones but no stenosis of the bile duct.
CONCLUSION:  Combined laparoscopic and endoscopic procedures are mini-invasive and cause less pain and minimal operative complications.

Hepatobiliary Pancreat Dis Int. 2004; 3(2): 284-287 .
[Abstract] ( 236 ) [HTML 1KB] [PDF 225KB] ( 2159 )
288 Zhang FK, Jia JD, Wang BE
Clinical evaluation of serum antimitochondrial antibody-negative primary biliary cirrhosis

BACKGROUND: Primary biliary cirrhosis (PBC) is characterized by frequent presence of antimitochondrial antibodies (AMAs). The sensitivity and specificity of AMA for PBC are both greater than 90%-95%, so the presence of AMA in serum is the major hallmark in PBC. However, it has long been recognized that in 5%-10% of patients the clinical, biochemical and histological features are diagnostic for PBC, but their sera are consistently tested negative for AMA/AMA-M2. This study aimed to evaluate whether the presence of AMA alters the clinical, serological and histological features of the disease.
METHODS: Clinical data of 70 patients clinically and/or histologically diagnosed with PBC were reviewed. AMA-negative and AMA-positive patients were compared in terms of clinical, biochemical, immunological and histological features.
RESULTS: At presentation, 11 patients were serum AMA/AMA-M2 negative. At the initial visit, AMA-negative and AMA-positive patients were similar in terms of age, sex, clinical manifestations, liver biochemistries and histological findings. The mean level of serum immunoglobulin M (IgM) was significantly lower in AMA-negative PBC patients than in AMA-positive PBC patients (2851±1418 mg/L vs 6361±4928 mg/L, P=0.033). Serum antinuclear antibodies (ANA) and/or smooth muscle antibodies (SMA) were more frequently positive in the AMA-negative PBC patients than in the AMA-positive patients (81.8% vs 40.7%, P=0.031).
CONCLUSION:  AMA-negative PBC patients are characterized by relatively lower levels of serum IgM and a higher prevalence of serum ANA/SMA and are not associated with substantial differences in the clinical,biochemical and histological spectrum of the disease.

Hepatobiliary Pancreat Dis Int. 2004; 3(2): 288-291 .
[Abstract] ( 264 ) [HTML 1KB] [PDF 244KB] ( 2872 )
292 Jin XL, Zheng SS, Wang BS, Chen HL
Correlation of glycosyltransferases mRNA expression in extrahepatic bile  duct carcinoma with clinical pathological characteristics

BACKGROUND: The incidence of extrahepatic bile duct carcinoma (EBDC) has been increasing, especially in aged people, but the glycobiology of the tumor is not elucidated. In this study we investigated the expressions of three glycosyltransferases in 35 patients with EBDC and 35 patients with benign biliary duct disease (BBDD) as well as their clinicopathological significance.
 METHOD:  The patients were divided into several subgroups by tumor differentiation, TNM stage, and invasion by the standards recommended by UICC. Tumor samples were immediately frozen in liquid nitrogen after resection, followed by mRNA determination of enzymes in the tissue using a mRNA selective reverse trancriptase-polymerase chain reaction kit. The mRNA levels of different groups were semi-quantitatively compared.
RESULTS: The mRNA levels of N-acetylglucosaminyltransferase V (GnT-V) and a subtype of α 2,3 sialyltransferases for N-glycans, ST3Gal-III were elevated 7.75 and 5.39 times in EBDC as compared with BBDD, respectively, and they were correlated to several clinicopathological factors including tumor advancement, differentiation, metastasis, and invasiveness. The mRNA expression of another sialyltransferase, ST6Gal-I, was also 0.63-fold higher in EBDC than in BBDD, but not involved in the clinicopathological characteristics.
CONCLUSION:  The elevated expression of these three glycosyltransferases can be considered as an important molecular event in the occurrence and progression of EBDC.

Hepatobiliary Pancreat Dis Int. 2004; 3(2): 292-295 .
[Abstract] ( 242 ) [HTML 1KB] [PDF 208KB] ( 2188 )
296 Wang BL, Zhai HY, Chen BY, Zhai SP, Yang HY, Chen XP, Zhao WT, Meng L
Clinical relationship between MDR1 gene and gallbladder cancer

BACKGROUND: The most common mechanisms of multidrug resistance (MDR) in cancer cells is the expression of an energy-dependent exfflux pump. P-glycoprotein (P-gp) encoded by MDR1 gene and multidrug associated protein (MRP) are well known proteins associated with MDR. In human cancers, the MDR1 gene expression is common in patients with intrinsic and acquired MDR. It is a major therapeutic problem in cancer chemotherapy. Previously we found that the MDR of HCC is related to MRP gene expression and initiates the intrinsic MDR. The aim of this study is to study the expression of MDR1 gene encoding P-gp and MDRl mRNA in primary gallbladder carcinoma, and analyze its clinical significance.
METHODS: Immunohistochemistry (IHC) S-P method and in situ polymerase chain reaction (ISPCR) were used to detect the expression of P-gp and MDR1 mRNA in 53 cases of untreated primary gallbladder carcinoma and 12 cases of cholecystitis (archival paraffin-embedded tissues).
RESULTS: The positive expression rates of P-gp and MDR1 mRNA in the 53 cases and 12 cases were 60.38%, 71.69% and 25.00%, 33.33%, respectively. There was a significant difference between the two groups (P<0.05).The positive expression rate of P-gp and MDR1mRNA were 69.44%, 83.33% and 41.18%, 47.06% respectively in tissues in stage of Nevin I-III against Nevin IV, V (P<0.05). In well, moderately differentiated gallbladder carcinoma tissues, their expressions were 79.49%, 69.23% against 50.00%, 35.71% in low, undifferentiated tissues (P<0.05).
CONCLUSIONS: MDR to gallbladder carcinoma is closely related to the intrinsic MDR and it provides an important evidence to reverse the MDR by detection of the MDR1 gene. Meanwhile, MDR1 gene expression in gallbladder carcinoma is correlated with some biological characteristics, takes part in the carcinogenesis of gallbladder tissues, and acts as a valuable biomarker of prognosis.

Hepatobiliary Pancreat Dis Int. 2004; 3(2): 296-299 .
[Abstract] ( 313 ) [HTML 1KB] [PDF 296KB] ( 2552 )
ORIGINAL ARTICLES/Pancreas
300 Zou XP, Yu ZL, Li ZS, Zhou GZ
Clinicopathological features of giant cell carcinoma of the pancreas

BACKGROUND: Giant cell carcinoma of the pancreas (GCCP) as a tumor of high malignancy, large size, and inflammatory reaction occupies 2.1%-12.8% of all cases of pancreatic malignancies. This study was to analyze cases of GCCP collected in 8 years at our hospital in an attempt to describe some features of GCCP in Chinese people.
METHODS: The clinicopathological features of 19 patients who had been pathologically diagnosed as having GCCP from 1021 patients with pancreatic malignancies collected by Pancreatic Disease Research Group (PDRG) of Changhai Hospital were retrospectively analyzed compared with those of 96 patients with common pancreatic carcinoma (PC) who were randomly selected from 1002 patients with pancreatic carcinoma. The differences of location, clinical symptoms, imagings, laboratory test, operation and the prognosis of these two groups were defined.
RESULTS: Tumors in the head of the pancreas were found in 8 patients (42.1%), and those in the body or tail of the pancreas in 11 (57.9%). The initial symptom was abdominal pain in most patients (57.9%). Abdominal pain (73.7%), dyspepsia (63.2%), weight loss (36.8%) but jaundice were common at the time of diagnosis. The abnormal rates of routine laboratory tests in the GCCP group were lower than those in the common PC group. The assay of tumor markers between the groups of GCCP and common PC was approximately the same. The sensitivity and accuracy of ultrasonography, spiral computed tomography and magnetic resonance imaging were considerably high. Large carcinoma in stage IV was seen in 9 patients or 47.4% of the GCCP group, a rate higher than that in the common PC group. Osteoid formation was found microscopically in some patients, and poorly differentiated tumor cells were found in most patients. The 1-year survival rate was 17.6%, which was lower than that in the common PC group.
 CONCLUSION:  The clinicopathological features of GCCP are different from those of common PC. Imaging tests can be used together with the assay of tumor markers to diagnose GCCP as early as possible and to improve the prognosis of GCCP patients.

Hepatobiliary Pancreat Dis Int. 2004; 3(2): 300-302 .
[Abstract] ( 253 ) [HTML 1KB] [PDF 235KB] ( 2090 )
303 Li S, Zhuang GY, Pei YQ, Li CY, Wang JL, Ding W, Du FT, Song QH, Lin KX
Extended local resection for treatment of periampullary carcinoma of vater

BACKGROUND: The trauma caused by pancreatoduodenectomy for periampullary carcinoma of vater is often severe and extensive. The purpose of this study was to evaluate the effect of extended local resection in the treatment of periampullary carcinoma of vater.
METHODS: The extra-hepaticobiliary tract, the confluence of the pancreatic and biliary duct, vater ampulla and duodenal papilla were resected en bloc in 8 patients with periampullary carcinoma from 1995 to 1998.
RESULTS: One patient died perioperatively. Duodenal obstruction developed postoperatively in one of 7 survived patients and was relieved after reoperation. All the 7 patients were followed up for more than 6 months without recurrence.
CONCLUSION:  Extended local resection fulfils the task of radical treatment of periampullary malignancy.

Hepatobiliary Pancreat Dis Int. 2004; 3(2): 303-306 .
[Abstract] ( 314 ) [HTML 1KB] [PDF 240KB] ( 2095 )
307 Zhao YP, Zhang LY, Liao Q, Guo JC, Chen G, Li JY
Detection of multidrug resistant gene 1 in pancreatic cancer

BACKGROUND: The results are conflicting in detecting P-glycoprotein (P-gp) in pancreatic cancer. The aim of this study was to detect the expression of multidrug resistant gene 1 (MDR1) in pancreatic cancer cell lines.
METHODS: MDR1 mRNA and P-gp were detected by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemical assay (IHC) in three pancreatic cancer cell lines SW1990, CAPAN-1 and P3. P-gp functions were evaluated through the rhodamine extrusion test.
RESULTS: Two of the three cell lines expressed MDR1 positively at different levels. The rhodamine extrusion test showed that the percentage of positive cells in MDR(+) cells was significantly lower than that in MDR1(-) cells. The results of IHC, RT-PCR and the rhodamine extrusion test were consistent with each other.
CONCLUSION:  All of these methods are reliable in the detection of MDR1 in pancreatic cancer tissue, thus providing a guide for clinical chemotherapy of pancreatic cancer.

Hepatobiliary Pancreat Dis Int. 2004; 3(2): 307-310 .
[Abstract] ( 256 ) [HTML 1KB] [PDF 306KB] ( 2166 )
311 Gao HK, Zhou ZG, He T, Chen YQ, Han FH, Wang C
Effects of TCMP-1 on the changes of platelet endothelial cell adhesion molecule-1 expression in acute edematous pancreatitis

BACKGROUND: Traditional Chinese medicine is a potent agent in the management of clinical and experimental acute pancreatitis (AP), but the molecular mechanism of its therapeutic action is unclear. Numerous experimental and clinical studies have shown that platelet endothelial cell adhesion molecule-1 (PECAM-1) is pivotal to leukocyte recruitment, which results in microcirculatory injury during inflammation, but its role in acute pancreatitis is poorly understood. We investigated the effects of a compound of traditional Chinese medicine pancreatitis-1 (TCMP-1) on the changes of platelet endothelial cell adhesion molecule-1 (PECAM-1) expression on polymorphonuclear leukocytes (PMNs) in acute edematous pancreatitis (AEP).
METHODS: The model of acute pancreatitis was established by subcutaneous injection of caerulein, and TCMP-1 treated groups were given TCMP-1 by catheterization from mouth to stomach (20 ml/kg) immediately after first time subcutaneous injection of caerulein. The changes of expression of PECAM-1 on leukocytes from the blood of the splenic vein and inferior vena cava were determined by flow cytometry.
RESULTS: In the AEP group, expression of PECAM-1 on PMNs was not significantly different between pancreatic microcirculation and systemic circulation at AEP2h and AEP4h time point. Then from AEP4h time point to AEP8h time point, expression of PECAM-1 was up-regulated in systemic circulation while it was down-regulated in pancreatic microcirculation and was significantly different between pancreatic microcirculation and systemic circulation at AEP8h time point (P<0.05). In the TCMP-1 treated group, compared with the AEP group, expression of PECAM-1 on PMNs decreased in different levels between pancreatic microcirculation and systemic circulation and was of significant difference at AEP8h time point (P<0.05).
 CONCLUSION:  Inhibition of PECAM-1 expression on PMNs may prevent PMNs from transmigration through the endothelium and may be one of the treatment mechanisms of TCMP-1 decoction on AEP.

Hepatobiliary Pancreat Dis Int. 2004; 3(2): 311-315 .
[Abstract] ( 297 ) [HTML 1KB] [PDF 280KB] ( 1959 )
CASE REPORTS
316 Liu YH, Wang Y, Yu LX, Sun LY, Feng BL, Shen ZY, Wang MM
Artificial liver support molecular adsorbents recirculating system therapy as a bridge to re-transplantation in two cases of long anhepatic duration

BACKGROUND: Molecular adsorbents recirculating system (MARS) liver support therapy is the development of albumin dialysis. This study was to assess the successful application of MARS artificial liver support therapy as a bridge to re-transplantation in two cases of long anhepatic duration.
METHODS: MARS therapy was given after failure plasma-exchange (PE) treatment, which resulted in circulatory derangement and acute renal dysfunction in a 36-year-old male patient. Finally his uncontrolled anhepatic condition led to a successful re-transplantation. In another 48-year-old man who was diagnosed as having primary nonfunction (PNF) during the liver transplantation, 10-hour MARS treatment contributed to smooth bridging of his anhepatic phase.
RESULTS: The two anhepatic patients were bridged for 26 and 17 hours respectively to re-transplantation with MARS therapy.
CONCLUSION:  Our experience proves that MARS artificial liver can be an effective support for long time bridging PNF until re-transplantation is available.

Hepatobiliary Pancreat Dis Int. 2004; 3(2): 316-316 .
[Abstract] ( 236 ) [HTML 1KB] [PDF 126KB] ( 1958 )

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