BACKGROUND: Pancreatic cancer (PCa) is one of the most aggressive human solid tumors, with rapid growth and metastatic spread as well as resistance to chemotherapeutic drugs, leading rapidly to virtually incurable disease. Over the last 20 years, however, significant advances have been made in our understanding of the molecular biology of PCa, with a focus on the cytogenetic abnormalities in PCa cell growth and differentiation.
DATA SOURCES: A MEDLINE search and manual cross-referencing were utilized to identify published data for PCa molecular biology studies between 1986 and 2008, with emphasis on genetic alterations and developmental oncology.
RESULTS: Activation of oncogenes, deregulation of tumor suppressor and genome maintenance genes, upregulation of growth factors/growth factor receptor signaling cascade systems, and alterations in cytokine expression, have been reported to play important roles in the process of pancreatic carcinogenesis. Alterations in the K-ras proto-oncogene and the p16INK4a, p53, FHIT, and DPC4 tumor suppressor genes occur in a high percentage of tumors. Furthermore, a variety of growth factors are expressed at increased levels. In addition, PCa often exhibits alterations in growth inhibitory pathways and evades apoptosis through p53 mutations and aberrant expression of apoptosis-regulating genes, such as members of the Bcl family. Additional pathways in the development of an aggressive phenotype, local infiltration and metastasis are still under ongoing genetic research. The present paper reviews recent studies on the pathogenesis of PCa, and includes a brief reference to alterations reported for other types of pancreatic tumor.
CONCLUSIONS: Advances in molecular genetics and biology have improved our perception of the pathogenesis of PCa. However, further studies are needed to better understand the fundamental changes that occur in PCa, thus leading to better diagnostic and therapeutic management.

BACKGROUND: Hepatitis B virus (HBV) recurrence may result in hepatic insufficiency or dysfunction of liver grafts. This study was to reevaluate the preventive effect of lamivudine therapy pretransplant on HBV recurrence after liver transplantation with combined lamivudine and hepatitis B immunoglobulin (HBIG) as a prophylactic regimen.
METHODS: This is a single-center, retrospective study of 122 liver transplant recipients operated on from January 2002 to September 2006 at our hospital. All subjects showed positive hepatitis B surface antigen (HBsAg) and HBV DNA in blood, without HBV mutation in YMDD at the time of liver transplantation. The protocol with combined lamivudine and HBIG for preventing HBV recurrence was used on the day of operation. The initial immunosuppression therapy was identical. After one year follow-up, the recipients were divided into 2 groups: patients without HBV recurrence (group Ⅰ) and patients with HBV recurrence (group Ⅱ). Preoperative lamivudine therapy and postoperative mycophenolate mofetil (MMF) and glucocorticoid therapy were analyzed using the Wilcoxon's test and Stepwise logistic regression method.
RESULTS: In the HBV recurrence group, the duration of pre-transplant lamivudine administration was significantly longer than that in the without HBV recurrence group (Z=-4.424, P=0.000). The HBV recurrence rate was significantly higher in patients with preoperative lamivudine therapy than in patients without lamivudine therapy (χ2=13.11, P=0.000); the risk of HBV recurrence increased by a 10.909-fold in patients with pre-transplant lamivudine therapy compared with that in patients without lamivudine therapy (OR=10.909; 95% CI for OR: 2.86-41.67). Seven (63.6%) of 11 HBV recurrence recipients had YMDD mutants. The duration of MMF or glucocorticoid was not different between the 2 groups (ZMMF=-1.453, PMMF=0.146; ZPre=-0.795, PPre=0.427). No significant difference was noted in the HBV recurrent rate in patients with MMF duration ≤6 and >6 months (χ2=0.185, P=0.667), as it was in patients with prednisone therapy ≤3 and >3 months (χ2=0.067, P=0.793).
CONCLUSIONS: With the protocol of combined lamivudine and HBIG for preventing HBV recurrence in liver transplantation recipients, liver transplantation candidates with positive HBV DNA should not be subjected to preoperative administration of lamivudine. A high dose of HBIG during the ahepatic period and in the early stage of post-transplantation can fulfill the treatment target as a long-term lamivudine therapy before liver transplantation. Long-term preoperative lamivudine treatment may result in an earlier HBV mutation in YMDD and increase the HBV recurrence rate and risk in the first year after transplantation.

BACKGROUND: Liver cirrhosis causes peculiar systemic hemodynamics, and accurate evaluation of systemic hemodynamic state is important for cirrhotic recipients who underwent living donor liver transplantation (LDLT). We investigated the clinical advantages of a novel non-invasive method for measuring systemic hemodynamic parameters using indocyanine green (ICG).
METHODS: Twenty-eight LDLT recipients were evaluated. Simultaneous measurements of cardiac output (CO) using Swan-Ganz catheters and pulse dye densitometry (PDD) were performed every 12 hours after LDLT. A total of 155 sets of simultaneous CO measurements were obtained.
RESULTS: The CO values obtained by PDD correlated well with those obtained by the invasive catheter technique. In addition, none of the recipients developed any side-effects, and we verified the safety of repeated ICG injections. ICG is safe, even for repeated use over time in the same recipient. Moreover, PDD can measure the blood volume (BV).
CONCLUSIONS: Since the cirrhotic systemic hemody-namics characterized by high CO and large BV remains, even after LDLT, the ability to measure CO and BV in a non-invasive, simple and real-time manner using PDD has advantages for cirrhotic LDLT recipients.

BACKGROUND: Although liver transplantation (LT) has made rapid progress, early pulmonary complications still occur. More attention should be paid to fluid therapy that may be an important factor leading to these complications. It is necessary to investigate the correlation between intraoperative and postoperative fluid therapy and early pulmonary complications after LT, then attempt to provide a reasonable fluid therapy in the perioperative period.
METHODS: Sixty-two patients who had undergone LT were enrolled and analyzed retrospectively. Based on early phase prognosis after LT, the 62 patients were divided into a non-pulmonary complication group and a pulmonary complication group. Twenty perioperative variables were analyzed in both groups to screen out several factors causing early pulmonary complications, then the parameters reflecting postoperative recovery were analyzed.
RESULTS: The pulmonary complication group had 29 patients (46.77%), 3 (4.84%) of whom died during the perioperative period. Using monofactorial analysis for each variable, the two groups differed in the following variables: preoperative lung function, volume of intraoperative transfusion, volume of intraoperative bleeding, and volume of intraoperative net fluid retention and fluid balance (≤-500 ml) in ≥2 of the first 3 days after operation. Analysis of the relationship between multivariate factors and pulmonary complications after LT by logistic multivariate regression analysis showed that preoperative lung function, volume of intraoperative bleeding, and fluid balance (≤-500 ml) in ≥2 of the first 3 days after operation were influential factors.
CONCLUSIONS: It is important to maintain fluid balance during the perioperative period of LT. If the hemodynamics are stable, appropriate negative fluid balance in the first 3 days after operation apparently decreases the incidence of early pulmonary complications after LT. These measures are associated with better postoperative recovery.

BACKGROUND: Because of difficulty in evaluating fatty liver disease in islander populations, we conducted a cross-sectional study to investigate the prevalence of fatty liver and its risk factors in an islander population of East China.
METHODS: Randomized multistage stratified cluster sampling from the islander population was used in a population-based case-control study. Then interview, physical examination, and ultrasonography were done.
RESULTS: Univariate logistic-regression analysis showed that male gender, smoking, daily alcohol intake ≥20 g, duration of drinking ≥5 years, total alcohol intake ≥36.5 kg, hypertension and obesity were closely related to fatty liver (all P<0.05). Multivariate stepwise logistic-regression analysis showed duration of drinking ≥5 years and obesity were closely related to fatty liver (both P<0.05), the odds-ratio (OR) (95% CI) was 1.954 (1.364-2.799) and 7.014 (4.919-10.002), respectively. The prevalence of fatty liver in this district was 40.0%. The prevalence of fatty liver in the non-obese and <5 years drinking group, the non-obese and ≥5 years drinking group, the obese and <5 years drinking group and the obese and ≥5 years drinking group were 15.43%, 26.73%, 56.78% and 71.52%, respectively. A dose-response relation between the duration of drinking and fatty liver was not apparent. After stratification by obesity, we found that the severity of fatty liver on ultrasonography was positively correlated with the duration of drinking level in the obese and non-obese groups, Pearson's correlation coefficients were 0.293 in the obese group and 0.178 in the non-obese group (both P<0.05).
CONCLUSIONS: The duration of drinking ≥5 years and obesity were two important risk factors for fatty liver in the islander population of East China. The prevalence of fatty liver in this population was high. An alcoholic threshold effect may be more important than a dose-response effect on the morbidity of fatty liver.

BACKGROUND: Bangladesh is a densely populated country where about 10 million people are chronically infected with hepatitis B virus (HBV). The aim of the present study was to evaluate the biochemical, virological and histological characteristics of HBeAg-negative chronic hepatitis B (CHB).
METHODS: Patients were included in this study if they were chronically infected with HBV with detectable DNA. The patients who were co-infected with human immunodeficiency virus, hepatitis delta virus or hepatitis C virus, and previously subjected to antiviral treatment, and those with hepatocellular carcinoma were excluded. The study was conducted during the period of January 2001 to December 2007. During this period 2617 patients with CHB were studied. HBeAg-positive cases were included to compare the characteristics. Among them, 237 cases underwent liver biopsy.
RESULTS: 2296 patients (87.7%) were male, with a mean age of 28.9±13.7 years. 2375 patients (90.8%) had CHB, and 242 (9.2%) were cirrhotic. HBV DNA levels were 7.6±1.5 copies/ml, ALT was 111.3±212.5 U/L, and AST was 91.5±148.9 U/L. The number of HBeAg-negative CHB cases was 1039 (39.7%). HBeAg-negative patients with a lower DNA load were older, and they had more fibrotic changes in the liver than HBeAg-positive patients. The two groups did not differ in necroinflammatory activity, but the former had lower ALT and AST values. Cirrhosis was more common in e-antigen-negative patients.
CONCLUSIONS: e-antigen-negative CHB patients are older and have more hepatic fibrosis patients than HBeAg-positive patients, although they have similar necroinflammatory activity.

BACKGROUND: Since we have previously shown an increase of mast cells in the small bowel and in the mesenteric lymph nodes in the rats with prehepatic portal hypertension, it can be hypothesized that this essential inflammatory cell would be involved in the pathogeny of the splanchnic changes related to portal hypertension.
METHODS: To verify this hypothesis, we first studied mast cell infiltration in the ileum and in the mesenteric lymph nodes in sham-operated male Wistar rats (n=12) and in short-term prehepatic portal hypertensive rats (n=12), and the serum levels of rat mast cell protease Ⅱ (RMCP-Ⅱ) by ELISA. In a second set of experiments ketotifen, a mast cell stabilizer drug, was administered to sham-operated (n=10) and portal hypertensive (n=12) rats 24 hours before the intervention and prostanoids (PGE2, PGI2, TXB2) and leukotrienes (LTC4, LTB4) were assayed by RIA, mast cell infiltration in the ileum and in the mesenteric lymph nodes and the serum levels of RMCP-Ⅱ were also studied, to show its effectiveness to prevent the mesenteric alterations produced by the inflammatory mediators released by the mast cell.
RESULTS: Forty-eight hours after the intervention RMCP-Ⅱ (P<0.05), PGE2 (P<0.001) and LTC4 serum levels decreased and mast cell number and RMCP-Ⅱ levels increased in mesenteric lymph nodes in portal hypertensive rats. Prophylactic administration of ketotifen reduced portal pressure (P<0.001), serum levels of PGE2 (P<0.001) and RMCP-Ⅱ (P<0.001) in mesenteric lymph nodes.
CONCLUSIONS: In acute portal hypertension in the rat, the mast cell translocation from intestinal mucosa to mesenteric lymph nodes, where they are activated and degranulates, would represent a defence mechanism to avoid the activation of an acute and massive inflammatory response in this location. Prophylactic administration of ketotifen is able to reduce the splanchnic inflammatory changes related to acute portal hypertension in the rat.

Retraction in Hepatobiliary Pancreat Dis Int. 2009 Aug;8(4):396.    
BACKGROUND: Hepatic veno-occlusive disease (HVOD) is a severe complication of chemotherapy before hematopoietic stem cell transplantation and dietary ingestion of pyrrolizidine alkaloids. Many experimental models were established to study its mechanisms or therapy, but few are ideal. This work aimed at evaluating a rat model of HVOD induced by monocrotaline to help advance research into this disease. 
METHODS: Thirty-two male rats were randomly classified into 5 groups, and PBS or monocrotaline was administered (100 mg/kg or 160 mg/kg). They were sacrificed on day 7 (groups A, B and D) or day 10 (groups C and E). Blood samples were collected to determine liver enzyme concentrations. The weight of the liver and body and the amount of ascites were measured. Histopathological changes of liver tissue on light microscopy were assessed by a modified Deleve scoring system. The positivity of proliferating cell nuclear antigen (PCNA) was estimated.
RESULTS: The rats that were treated with 160 mg/kg monocrotaline presented with severe clinical symptoms (including two deaths) and the histopathological picture of HVOD. On the other hand, the rats that were fed with 100 mg/kg monocrotaline had milder and reversible manifestations. Comparison of the rats sacrificed on day 10 with those sacrificed on day 7 showed that the positivity of PCNA increased, especially that of hepatocytes.
CONCLUSIONS: Monocrotaline induces acute, dose-dependent HVOD in rats. The model is potentially reversible with a low dose, but reliable and irreversible with a higher dose. The modified scoring system seems to be more accurate than the traditional one in reflecting the histopathology of HVOD. The enhancement of PCNA positivity may be associated with hepatic tissue undergoing recovery.

BACKGROUND: In liver fibrosis, alterations within the space of Disse microenvironment facilitate the progression of chronic liver disease. The normal basement membrane-like matrix in the space of Disse converts to a matrix rich in fibril-forming collagens during the fibrosis. This study aimed to investigate the impact of alterations in the space of Disse microenvironment on the migration of hepatic stellate cells (HSCs) in the process of liver fibrosis, and to explore the novel mechanism of liver fibrosis from the viewpoint of cell migration.
METHODS: A modified in vitro Boyden chamber system was employed to partially mimic the in vitro microenvironment of the Disse space in normal liver and in fibrosis. The effects of fibrogenetic growth factors on the migration of HSCs in simulated liver fibrosis were assessed by cell migration and cell proliferation experiments.
RESULTS: Enhanced platelet-derived growth factor (PDGF)-BB, transforming growth factor-β1 (TGF-β1) and/or epithelial growth factor (EGF) in liver fibrosis resulted in an increase in migratory capacity of activated HSCs. The enhanced migration of HSCs induced by PDGF-BB was proliferation-independent. The elevation of basic fibroblast growth factor (bFGF) or vascular endothelial growth factor (VEGF) during liver fibrosis had no effect on the migration of HSCs.
CONCLUSIONS: The study provides valuable insights into the role of the space of Disse microenvironment in regulating the migratory behavior of HSCs. TGF-β1, PDGF-BB and EGF, which increase in liver fibrosis, induce the migration of activated HSCs. However, bFGF and VEGF have no effect although they also increase during liver fibrosis.

BACKGROUND: Hepatocellular carcinoma (HCC) is characterized by multiple causes, clear multiple stages and a multifocal process of tumor progression related intimately to the overexpression of many cellular factors. The aim of this study was to investigate the dynamic expression of insulin-like growth factor-Ⅱ (IGF-Ⅱ) and its abnormal alteration in the early stages of HCC development.
METHODS: Hepatoma models were induced by 2-fluorenylacetamide (2-FAA) in male Sprague-Dawley rats. Morphological changes of rat livers were assessed by pathological examination (HE staining). The levels of IGF-Ⅱ expression in the livers and sera of rats were quantitatively detected by an enzyme-linked immunosorbent assay (ELISA). Simultaneously, the expression and cellular distribution of liver IGF-Ⅱ were analyzed by immunohistochemistry.
RESULTS: Histological examination confirmed that rat hepatocytes showed changes from granule-like degeneration to atypical hyperplasia to HCC, and progressively increasing hepatic IGF-Ⅱ levels during HCC development. The levels of hepatic or serum IGF-Ⅱ in HCC tissues and sera were significantly higher than those in normals and rats with degeneration. The immunohistochemical evidence indicated the positive expression and hepatocyte distribution of IGF-Ⅱ in rat hepatoma. A positive relationship of IGF-Ⅱ levels was found between liver tissues and sera of experimental rats (P<0.01).
CONCLUSION: Hepatic IGF-Ⅱ may participate in hepatocyte cancer development and detection of IGF-Ⅱ expression during HCC development could be a useful molecular marker for its early diagnosis.

BACKGROUND: Cholangiocarcinoma is rare, accounting for approximately 3% of all gastrointestinal cancers. This study aimed to identify the survival rate among surgically treated and palliated patients, and secondly to identify parameters that could predict a curative resection.
METHODS: A total of 121 patients, 55 men and 66 women, median age 70 years (range 31-91), who had been treated for cholangiocarcinoma in the period of 1990-2005 were evaluated retrospectively.
RESULTS: Curative resection was performed in 40 patients (33%), whereas 81 received palliative treatment (67%). 16% (19 of 121) of the patients had an explorative laparotomy without tumour resection. Age above 65 years (OR 3.4; 95% CI 1.4-8.4; P=0.008), weight loss (OR 8.5; 95% CI 1.5-46; P=0.01) or tumour location (The resection rate of hilar cholangiocarcinoma was lower than that of intrapancreatic cancer.) (OR 2.7; 95% CI 1.7-4.5; P=0.001) predicted palliative treatment. The adjusted 5-year survival rate of patients who received tumour resection and palliative treatment was 30% and 1.2 %, respectively (P<0.001). The survival rate of patients who were subjected to hepatectomy (70%) was better than that of patients who had a local or distal resection (20%) (P=0.02).
CONCLUSIONS: In few patients with a resectable cholangiocarcinoma, an explorative laparotomy is often necessary to evaluate resectability. However, long-term survival is significantly better in patients who received radical surgical resection.

BACKGROUND: The incidence of hepatic portal cholangiocarcinoma is increasing and it is always associated with poor survival. This study analyzed an effective therapeutic method.
METHODS: A retrospective analysis was made on 70 patients with hepatic portal cholangiocarcinoma admitted between January 2004 and February 2007 to the General Hospital of Air Force PLA. 
RESULTS: Forty-seven patients had hepatic duct-jejunum anastomosis after resection of hepatic portal cholangiocarcinoma. Internal or external biliary drainage and canals for internal radiation were performed in those patients unfit for operation. Among the 70 patients, 5 died within 15 months, 27 survived more than 24 months, and the others survived 4-18 months.
CONCLUSION: Surgery is the primary therapeutic method for hepatic portal cholangiocarcinoma. Internal or external biliary drainage can prolong the life-span.

BACKGROUND: Only 105 cases of neuroendocrine tumor (NET) of the ampulla of Vater have been described, mostly as single case reports. The incidence of NET is rising. The changes in incidence may result from changes in detection. This study was to determine the relative incidence and clinicopathological characteristics of high-grade neuroendocrine carcinoma (small cell carcinoma and large cell carcinoma) of the ampulla of Vater at a single institution.
METHODS: Sections from paraffin blocks of tumors of the ampulla of Vater taken from 45 patients who underwent Whipple's procedure and 6 patients who underwent palliative bypass between September 2003 and January 2007 were subjected to immunohistochemical analysis. The clinical and pathological data from 5 patients diagnosed with NET of the ampulla of Vater were analyzed.
RESULTS: The patients were 3 men and 2 women, ranging in age from 39 to 47 years (mean 44 years). Operative procedures included Whipple's procedure in 4 patients and palliative bypass in 1 patient. Histopathological examination revealed large-cell neuroendocrine carcinoma in 2 patients, small cell carcinoma in 2, and carcinoid in 1. Three patients with high-grade neuroendocrine carcinoma who had undergone Whipple's procedure died at postoperatively 7, 11, and 13 months. The patient who had undergone palliative triple bypass died 3 months after surgery.
CONCLUSIONS: The relative incidence of high-grade neuroendocrine carcinomas of the ampulla of Vater is higher than that generally expected. The tumors behave aggressively and have a dismal prognosis despite aggressive treatment.

BACKGROUND: Pancreatic leakage after pancreaticoduodenectomy is associated with a morbidity and mortality. Different techniques have been used to make a safe anastomosis to the left pancreatic remnant.
METHODS: We performed "modified Child pancreaticojejunostomy" for 31 patients, by which end-to-end pancreaticojejunal anastomosis was made with a two-layer polypropylene continuous running suture.
RESULTS: In the patients who underwent pancreaticojejunostomy, the average operative time was 14.2 minutes. There was no pancreaticoenterostomy leakage in all patients, and no deaths occurred.
CONCLUSIONS: In pancreaticojejunostomy, pancreatic anastomosis is time-saving and free from complications. Thus it is an improvement of pancreaticojejunostomy.

BACKGROUND: The middle hepatic vein (MHV) is normally in form of a large trunk lying within the midplane of the liver. An anomaly in form of two separate trunks, each draining segment Ⅴ/Ⅷ and segment Ⅳ, has been described by Couinaud but not been well documented in the literature.
METHOD: We report a right liver donor in whom the MHV was absent and not encountered during liver transection along the midplane of the liver.
RESULTS: On computed tomography (CT) scan and intraoperative ultrasonography, there was a large segment Ⅷ hepatic vein mistaken as the MHV on preoperative assessment and a large segment Ⅳ hepatic vein close to the ligamentum venosum. CT volumetry based on either segment Ⅷ or Ⅳ hepatic vein led to major error in liver volume calculation. Transection of the liver guided by segment Ⅷ or Ⅳ hepatic vein would lead to sacrifice of liver parenchyma unnecessarily or presence of necrotic liver in the graft. 
CONCLUSION: Absent MHV is a rare anomaly. It is revealed by careful study of the CT scan.

BACKGROUND: Hepatic artery thrombosis (HAT) is a frequent complication following liver transplantation, but it is rarely caused by arcuate ligament compression of the celiac artery. This article mainly describes our experience in managing a patient with celiac artery stenosis and HAT after liver transplantation.
METHODS: A 44-year-old man with a 15-year history of hepatitis B was admitted to our hospital for hepatocellular carcinoma. Before the operation, he received trans-arterial chemoembolization once, and pretransplant MR angiography indicated a suspected stenosis at the initiation of the celiac artery, while color Doppler showed normal blood flow in the arterial system. In this case, orthotopic liver transplantation was performed for radical cure of hepatocellular carcinoma. However, B-ultrasonography detected poor blood flow in the intra- and extra-hepatic artery on the first posttransplant day, and during exploratory laparotomy a thrombus was found in the hepatic artery. Thus, re-transplantation was conducted with a bypass between the graft hepatic artery and the recipient abdominal aorta with the donor's splenic artery.
RESULTS: The patient made an uneventful recovery and color Doppler showed good blood flow in the artery and portal system. Histology confirmed extensive thrombosis in the left and right hepatic artery of the explanted graft, indicating HAT.
CONCLUSIONS: Although HAT caused by celiac trunk compression is rarely reported in liver transplantation, the diagnosis should be considered in patients with pretransplant hepatic artery stenosis on angiography and abnormal blood flow on B-ultrasonography. Once HAT is formed, treatment such as thrombectomy or re-transplantation should be performed as early as possible.

BACKGROUND: Gallstone ileus remains a rare but important cause of intestinal obstruction.
METHOD: We present a unique case of two gallstones causing intestinal obstruction at the same time.
RESULTS: A 90-year-old lady presented with signs and symptoms of small bowel obstruction. At operation, two gallstones stuck at different points within the bowel were causing the obstruction and were removed.
CONCLUSION: When operating on patients with small bowel obstruction from gallstone ileus, examination of the entire small bowel should be considered mandatory.

BACKGROUND: Although the treatment of extrahepatic metastases from primary liver tumors is essentially palliative, solitary metastasis from such tumors offers a possibility of cure by surgical resection. The adrenal gland is an uncommon site for metastasis from primary liver tumors.
METHOD: We report two cases of adrenalectomy for solitary adrenal metastasis: one from intrahepatic cholangiocarcinoma and the other from hepatocellular carcinoma.
RESULTS: The patient with intrahepatic cholangiocarcinoma had a synchronous adrenal metastasis and underwent simultaneous liver resection and adrenalectomy. However, he developed recurrent disease 17 months following surgery for which he is presently on palliative chemotherapy. The other patient underwent adrenalectomy for adrenal metastasis 3 months following liver transplantation for hepatocellular carcinoma. He is presently alive and disease-free 27 months after adrenalectomy.
CONCLUSION: Carefully selected patients with solitary metastasis from primary liver tumors may be considered for resection.