BACKGROUND: Although insulinomas are very rare tumors, they are the most common pancreatic neuroendocrine neoplasms. The incidence in general population is 1-4 per 1 000000 yearly but the incidence is higher in autopsy studies. The malignancy of insulinomas is difficult to be predicted on the basis of their histological features, and the current WHO classification has been re-evaluated. This review aimed to summarize classical knowledge with current trends in the diagnosis and treatment of insulinomas.
DATA SOURCES: A Medline search using terms "insulinoma", "treatment" and "neuroendocrine tumors" was conducted. Additional references were sourced from key articles.
RESULTS: Surgery is the treatment of choice for insulinoma and has an extremely high success rate. Medical treatment is also available but only for patients who are unable or unwilling to undergo surgical treatment. Preoperative localization is necessary for planning the surgical approach. Many methods exist for localization of an insulinoma and can be invasive and non-invasive. The combination of biphasic thin section helical CT and endoscopic ultrasonography (EUS) has an almost 100% sensitivity in localizing insulinomas. Laparoscopic ultrasound is mandatory to localize intraoperatively these tumors. EUS-guided fine needle tattoing is an alternative method of localization in case of lack of laparoscopic ultrasound.
CONCLUSION: Laparoscopic resection for benign insulinomas is the procedure of choice, whereas pancreatectomy is reserved for large, potentially malignant tumors.

BACKGROUND: Acute pancreatitis is an acute inflammatory process of the pancreas that frequently involves peripancreatic tissues and at times remote organ systems. For a long time, the etiology and pathogenesis of acute pancreatitis has been intensively investigated worldwide, but the pathogenetic theories are controversial. The integrity of the pancreatic duct-acinar system might play an important role in the pathogenesis of this disease.
DATA SOURCES: Web of Science and PubMed databases were searched for published studies (between January 1966 and June 2009) to identify relevant articles using the keywords "acinar hyperstimulation", "pathogenesis", "acute pancreatitis", "pancreatic duct-acinar system", and "pancreatic duct pressure". Most of the relevant articles were reviewed.
RESULTS: From critical reading of the relevant articles, we found that the underlying mechanisms involved in the pathogenesis of acute pancreatitis are still under debate and ill-understood. On the basis of the relevant studies, we propose a hypothesis for the pathogenesis of acute pancreatitis, in which the integrity of the pancreatic duct-acinar system plays an essential role in the onset and progression of various forms of the disease.
CONCLUSIONS: In our hypothesis, pancreatic duct obstruction and hyperstimulation of the exocrine pancreas are preconditions for the onset of acute pancreatitis; under the common conditions of pancreatic duct obstruction and acinar hyperstimulation, acute pancreatitis arises and develops. This may be an important common pathophysiological mechanism causing various forms of acute pancreatitis.

BACKGROUND: The process of microcrystallization, its sequel and the assessment of nucleation time is ignored. This systematic review aimed to highlight the importance of biliary microlithiasis, sludge, and crystals, and their association with gallstones, unexplained biliary pain, idiopathic pancreatitis, and sphincter of Oddi dysfunction.
DATA SOURCES: Three reviewers performed a literature search of the PubMed database. Key words used were "biliary microlithiasis", "biliary sludge", "bile crystals", "cholesterol crystallisation", "bile microscopy", "microcrystal formation of bile", "cholesterol monohydrate crystals", "nucleation time of cholesterol", "gallstone formation", "sphincter of Oddi dysfunction" and "idiopathic pancreatitis". Additional articles were sourced from references within the studies from the PubMed search.
RESULTS: We found that biliary microcrystals account for almost all patients with gallstone disease, 7% to 79% with idiopathic pancreatitis, 83% with unexplained biliary pain, and 25% to 60% with altered biliary and pancreatic sphincter function. Overall, the detection of biliary microcrystals in gallstone disease has a sensitivity ranging from 55% to 87% and a specificity of 100%. In idiopathic pancreatitis, the presence of microcrystals ranges from 47% to 90%. A nucleation time less than 10 days in hepatic bile or ultra-filtered gallbladder bile has a specificity of 100% for cholesterol gallstone disease.
CONCLUSIONS: Biliary crystals are associated with gallstone disease, idiopathic pancreatitis, sphincter of Oddi dysfunction, unexplained biliary pain, and post-cholecystectomy biliary pain. Pathways of cholesterol super-saturation, crystallisation, and gallstone formation have been described with scientific support. Bile microscopy is a useful method to detect microcrystals and the assessment of nucleation time is a good method of predicting the risk of cholesterol crystallisation. 

BACKGROUND: Pancreas transplantation is the only established treatment to achieve long-term normoglycemia and insulin independence in patients with insulin-dependent diabetes mellitus. However, many complications both during and post-transplantation have limited the progress of pancreas transplantation. Mice are the widely used laboratory animals that have been used to establish pancreas transplant models. The pathogenesis and the treatment of pancreas allograft rejection have been studied during the last twenty years. This review introduces four different mouse pancreas transplantation models established by different centers.
DATA SOURCES: We reviewed the three mostly reported mouse pancreas transplantation models in the literature (PubMed), and compared them with a novel mouse model established at our center.
RESULTS: In this review, four different models of mouse pancreas transplantation were compared in terms of surgical technique, immediate success rate, advantages and disadvantages.
CONCLUSIONS: The mouse model is a useful tool to study pancreas transplantation-related diseases and their treatment. The findings from this model help to improve human pancreas transplantation in the future.

BACKGROUND: Acute kidney injury (AKI) is a common complication in the early period after liver transplantation (LT), posing an enormous obstacle to treatment efficiency and patient survival. However, the exact influencing factors of AKI are still unclear and a predictive model is desperately required in the clinic.
METHODS: Data of 102 consecutive LTs were reviewed. A model for predicting AKI was established and further validated in a prospective study of 44 patients receiving LT.
RESULTS: The incidence of AKI was 32.4%. AKI patients showed a significantly lower survival rate than non-AKI patients. Multivariate analysis demonstrated the independent influencing factors of AKI were preoperative serum creatinine >1.2 mg/dl, intraoperative urine output ≤60 ml/h, intraoperative hypotension status, and intraoperative use of noradrenaline. A model was then established and showed a sensitivity of 75.0%, a specificity of 93.8%, and an accuracy of 88.6% in predicting AKI.
CONCLUSIONS: High preoperative serum creatinine, low intraoperative urine output, and intraoperative hypotension contribute to the development of AKI, and intraoperative use of noradrenaline serves as a protective factor. The predictive model could potentially facilitate early prediction and surveillance of AKI.

BACKGROUND: With the establishment of genetically modified and gene knock-out models, the mouse has become an important animal model for liver transplantation. We examined hepatic rearterialization after liver transplantation in a mouse model.
METHODS: Orthotopic liver transplantation was performed in 70 mice and sham-operation was performed in a control group of 40 mice. Based on the "two-cuff" method, a continuous suture approach was applied to the suprahepatic inferior vena cava and a cuff approach to the portal vein and the infrahepatic inferior vena cava. A biliary stent was inserted into the bile duct. The hepatic artery was reconstructed with end-to-side anastomosis. The survival rate of recipients was monitored at 24 hours, one week, and one month after the operation. Liver function and morphology were evaluated one month postoperatively.
RESULTS: Postoperative survival rates were 94.3% at 24 hours, 91.4% at one week, and 85.7% at one month. No significant difference was seen between the experimental and control groups in liver function. The hepatic tissue preserved normal structure.
CONCLUSION: Owing to its high survival rate and stability, this surgical approach is ideal for establishing an orthotopic liver transplantation mouse model with hepatic artery reconstruction.

BACKGROUND: Various surgical procedures can be used to treat liver cirrhosis and portal hypertension. How to select the most appropriate procedure for patients with portal hypertension has become a difficult problem. This study aimed to analyze the relationship between the value of intraoperative free portal pressure (FPP) and postoperative complications, and to explore the significance of intraoperative FPP measurement with respect to surgical procedure selection.
METHODS: The clinical data of 187 patients with portal hypertension who received pericardial devascularization and proximal splenorenal shunt combined with devascularization (combined operation) at the Department of General Surgery in our hospital from January 2001 to September 2008 were retrospectively analyzed. Among the patients who received pericardial devascularization, those with a postoperative FPP ≥22 mmHg were included in a high-pressure group (n=68), and those with FPP <22 mmHg were in a low-pressure group (n=49). Seventy patients who received the combined operation comprised a combined group. The intraoperative FPP measurement changes at different times, and the incidence of postoperative complications in the three groups of patients were compared.
RESULTS: The postoperative FPP value in the high-pressure group was 27.5±2.3 mmHg, which was significantly higher than that of the low-pressure (20.9±1.8 mmHg) or combined groups (21.7±2.5 mmHg). The rebleeding rate in the high-pressure group was significantly higher than that in the low-pressure and combined groups. The incidence rates of postoperative hepatic encephalopathy and liver failure were not statistically different among the three groups. The mortality due to rebleeding in the low-pressure and combined groups (0.84%) was significantly lower than that of the high-pressure group.
CONCLUSIONS: The study demonstrates that FPP is a critical measurement for surgical procedure selection in patients with portal hypertension. A FPP value ≥22 mmHg after splenectomy and devascularization alone is an important indicator that an additional proximal splenorenal shunt needs to be performed.

BACKGROUND: Virological clearance, delayed progression to cirrhosis or liver cancer, and increased survival are the long-term goals of antiviral therapy in chronic hepatitis B patients. Identification of host factors correlated with therapeutic response may contribute greatly to individual treatment. This study aimed at investigating whether T29C genotype polymorphism of estrogen receptor alpha (ESR1) is associated with the initial response to interferon-alpha (IFN-α) therapy in chronic hepatitis B patients.
METHODS: The initial responses of 100 patients to IFN-α therapy were evaluated and compared by classifying them into three groups according to T29C genotype polymorphism of ESR1: T/T, T/C, and C/C genotype groups. Polymerase chain reaction-restriction fragment length polymorphism was used to analyze the genotype polymorphism in T29C.
RESULTS: The frequency of initially combined response was markedly higher in both the T/T and T/C groups than in the C/C group (Z=10.326, P=0.006 and Z=26.247, P=0.000, respectively). In addition, the initial virological response was higher in the T/T and T/C groups than the C/C group (χ2=5.674, P=0.017 and χ2=4.980, P=0.026, respectively). In 78 initially HBeAg-positive patients, however, the frequency of initial e-antigen disappearance or seroconversion among the T/T, T/C, and C/C genotype groups was 34.15%, 27.78% and 15.79%, respectively, which were not significantly different.
CONCLUSION: The T29C genotype polymorphism of ESR1 is associated with the initial response to IFN-α in patients with chronic hepatitis B, and might be a significant marker for predicting the initial response to IFN-α, at least in this study population.

BACKGROUND: Post-hepatitic cirrhosis is regarded as common and severe form of liver damage. Interferon γ-inducible protein 10 (IP-10), a member of the non-ELR (glutamic-leucine-arginine) motif CXC chemokine family, has recently been shown to recruit and activate specific subsets of leukocytes to sites of inflammation or an immune response during the development of hepatic cirrhosis. However, the effects of IP-10 and IP-10 mRNA on inflammatory infiltration at local sites and in the peripheral blood of patients with post-hepatitic cirrhosis as well as their relationship with viral load are still poorly defined. This study aimed to detect the relationship between the expression of IP-10 in serum, IP-10 mRNA in peripheral blood mononuclear cells (PBMCs), and the levels of HBV DNA in the serum of patients, and to explore their role in the pathogenesis of cirrhosis.
METHODS: Typical patients with cirrhosis after HBV infection were selected, and their serum IP-10 concentrations were evaluated with ELISA, the content of IP-10 mRNA in PBMCs was measured by real-time PCR, and the load of HBV DNA in serum and PBMCs was assessed by semi-quantitative analysis of gel imaging.
RESULTS: The levels of IP-10 in serum and IP-10 mRNA in PBMCs of patients with cirrhosis were 299.9±77.2 pg/ml and 0.7500±0.1495, respectively. They were higher than those of controls (P<0.05) and also increased in the HBV DNA(+) groups (P<0.05, P<0.01) to 343.0±80.3 pg/ml and 0.8465±0.1528, respectively. The levels of IP-10 in serum and IP-10 mRNA in PBMCs were clearly correlated with the load of HBV DNA (P<0.01).
CONCLUSIONS: The levels of IP-10 and IP-10 mRNA in the peripheral blood of patients with cirrhosis increase are closely correlated with the load of HBV DNA in serum, and play a key role in the progression of post-hepatitic cirrhosis.

BACKGROUND: Multidrug resistance (MDR) is extremely common in hepatocellular carcinoma (HCC) and is a major problem in cancer eradication by limiting the efficacy of chemotherapy. Modulation of c-Jun NH2-terminal kinase (JNK) activation could be a new method to reverse MDR. However, the relationship between JNK activity and MDR in HCC cells is unknown. This study aimed to explore the relationship between MDR and JNK in HCC cell lines with different degrees of MDR.
METHODS: A MDR human HCC cell line, SMMC-7721/ADM, was developed by exposing parental cells to gradually increasing concentrations of adriamycin. The MTT assay was used to determine drug sensitivity. Flow cytometry was used to analyze the cell cycle distribution and to measure the expression levels of P-glycoprotein (P-gp) and MDR-related protein (MRP)-1 in these cells. JNK1, JNK2 and JNK3 mRNA expression levels were quantified by real-time PCR. Expression and phosphorylation of JNK1, JNK2, and JNK3 were analyzed by Western blotting.
RESULTS: The MDR of SMMC-7721/ADM cells resistant to 0.05 mg/L adriamycin was mainly attributed to the overexpression of P-gp but not MRP1. In addition, these cells had a significant increase in percentage in the S phase, accompanied by a decrease in percentage in the G0/G1 phase, which is likely associated with a reduced ability for cell proliferation and MDR generation. We found that JNK1, JNK2, and JNK3 activities were negatively correlated with the degree of MDR in HCC cells.
CONCLUSION: This study suggests that JNK1, JNK2, and JNK3 activities are negatively correlated with the degree of MDR in HCC cells.

BACKGROUND: Hepatocellular carcinoma (HCC) is a highly malignant tumor with a poor prognosis. Because small HCCs possess most of the characteristics of early HCC, we investigated small HCCs to screen potential biomarkers for early diagnosis.
METHODS: Proteins were extracted from 10 sets of paired tissue samples from HBV-infected small-HCC patients. The extracted proteins were well resolved by two-dimensional electrophoresis. These HCC-associated proteins were then identified by MALDI-TOF/TOF MS following image analysis. Western blotting and immunohistochemistry were used to assess glutamine synthetase (GS) and phenazine biosynthesis-like domain-containing protein (PBLD) expression in liver tissue. Enzyme-linked immunosorbent assays in 152 serum samples (from 49 healthy donors, 24 patients with liver cirrhosis, and 79 with HCC) were used to further assess the significance of GS clinically.
RESULTS: Fifteen up-regulated and three down-regulated proteins were identified. Western blotting confirmed GS overexpression and decreased PBLD expression in liver tissue. Immunohistochemistry showed that GS was expressed in 70.0% (84/120) of HCCs and 35.8% (43/120) of nontumor tissues; PBLD was expressed in 74.2% (89/120) of nontumor tissues and 40.8% (49/120) of HCCs. The Chi-square test showed significant expression differences between HCCs and adjacent tissues. Consistent with this, serum GS levels in HCC patients were significantly higher than those in liver cirrhosis patients and healthy donors, while the latter two groups were also significantly different. In addition, a diagnostic cutoff value of 2.6 mg/ml was used for GS; it was elevated in 19 (76.0%) of 25 HCC patients with AFP ≤20 ng/ml and 47 (88.7%) of 53 HCC patients with AFP ≤200 ng/ml.
CONCLUSION: GS and PBLD are abnormally expressed in most HCCs. GS may be a novel serum marker for early HCC, especially for those patients with low AFP levels (≤200 ng/ml).

BACKGROUND: Radiofrequency ablation (RFA) has been suggested as a new treatment option for patients with locally advanced cancer. This study aimed to prospectively evaluate the efficacy and safety of intraoperative RFA in patients with unresectable, locally advanced, non-metastatic carcinoma of the pancreatic head.
METHODS: RFA was the first step of the surgical procedure and was carried out on the mobilized pancreatic head followed by biliary by-pass and gastrojejunal-anastomosis. Intra- and post-operative morbidity and mortality, performance status, pain control, quality of life, and survival at 24 months were evaluated.
RESULTS: Seven patients (3 men and 4 women; median age 66 years, range 47-80 years) were studied and 4 were eligible for treatment. The RFA procedure was carried out in 3 of the 4 patients; in one patient it was not carried out because of the upstaging of the neoplasm. In all 3 patients RFA achieved complete necrosis of the lesion. A biliary fistula developed 7 days after the procedure in one patient; all 3 patients developed ascites 8.6 days (range 7-9 days) on average after RFA. All patients died respectively, at 3, 4, and 5 months after the treatment.
CONCLUSIONS: In our experience, RFA is a feasible procedure, but it presents a very high rate of postoperative complications. Moreover, pain control, life quality and survival rate are poor. The few data suggest no impact on survival.

BACKGROUND: Triptolide (TPT) is a diterpenoid triepoxide extracted from the Chinese herb Tripterygium wilfordii Hook. F. It exhibits potent immunosuppressive and anti-inflammatory properties. This study was undertaken to investigate its effects on prolongation of islet allograft survival in rodents. Additionally, we investigated whether TPT would be toxic to islet function in vivo.
METHODS: We transplanted BALB/c islets to either chemically induced diabetic C57BL/6 mice or spontaneously diabetic nonobese diabetic (NOD) mice. TPT was injected within 2 weeks or continuously, until rejection, in the two combinations. Then, we evaluated the toxicity of TPT on islet function by daily injection to naive BALB/c or diabetic BALB/c that was cured by syngeneic islet transplantation under the kidney capsule. Mice injected with cyclosporine A (CsA) or vehicle served as controls. Intraperitoneal glucose tolerance tests (IPGTTs) performed at 4 and 8 weeks in the naïve BALB/c group, and at 2, 4, 6, and 8 weeks in the syngeneic transplanted group.
RESULTS: The medium survival time of islets allograft from TPT treated C57BL/6 and NOD recipients were 28.5 days (range 24-30 days, n=10) and 33.0 days (range 15-47 days, n=6), respectively, and they were significantly different from those of the vehicle treated controls, which were 14.0 days (range 13-16 days, n=6) and 5.0 days (range 4-10 days, n=6), respectively (all P<0.0001). The IPGTT demonstrated that there was no difference between the TPT treated and vehicle treated groups, either in the normal or syngeneic transplanted islet BALB/c mice. However, CsA injection impaired islet function in both normal and syngeneic transplanted mice as early as 4 weeks.
CONCLUSION: TPT prolonged islets allograft survival in a chemically induced diabetic or an autoimmune diabetic murine model without impairment of islet function.

 Vascular anatomy of the liver is varied, and the "standard" anatomy is seen in 55%-80% of cases. It is very important that extrahepatic arteries are identified precisely at the time of graft procurement to avoid injuries that might compromise the liver function. In the present case the liver donor had the vascular anatomy of Michels type Ⅶ, e.g. a hepatic artery originating from the celiac trunk and going to the left lobe, an accessory left hepatic artery coming from the left gastric artery, and a replaced right hepatic artery coming from the superior mesenteric artery. This pattern of vascular supply is uncommon, representing less than 5% of cases. The replaced hepatic artery was reconstructed in the back-table with polypropylene suture 7.0 by connecting it to the stump of the splenic artery, and the celiac trunk of the graft was anastomosed to the recipient common hepatic artery.

BACKGROUND: Renal cell carcinoma (RCC) involves the inferior vena cava (IVC) in a minority of patients. Less commonly, it presents with Budd-Chiari syndrome. If untreated, the condition progresses towards liver failure and death.
METHOD: We report a case of Budd-Chiari syndrome due to infiltration of the IVC and right atrium by recurrence of RCC 7 years after successful treatment by primary resection.
RESULTS: Surgery was performed with a combined abdominal and thoracic approach with cardio-pulmonary by-pass and cardioplegia. The tumor was removed and a cadaveric iliac vein graft used to re-establish venous continuity between the right atrium and hepatic veins.
CONCLUSIONS: Although it is a complex and high-risk procedure, aggressive surgery performed by an experienced team with liver transplant and cardiothoracic skills may enable resection of apparently advanced caval tumors. The case is discussed in the light of the current literature.

BACKGROUND: Gastrointestinal cancers, especially pancreatobiliary cancers, are frequently associated with or are complicated by thromboembolic phenomena due to hypercoagulability and/or altered venous drainage, especially of the abdomen and lower limbs. This report describes an unusual and interesting case of gallbladder carcinoma developing a viable tumor thrombus in the superior vena cava (SVC) with resultant SVC obstruction, while on gefitinib-based anti-epidermal growth factor receptor (EGFR) therapy.
METHODS: A 60-year-old woman was incidentally diagnosed to have gallbladder cancer on cholecystectomy. She had disease recurrence and received systemic chemotherapy followed by gefitinib-based anti-EGFR therapy. Subsequently, while on gefitinib-based therapy, she presented with clinical signs and symptoms suggestive of SVC thrombosis.
RESULTS: A whole body PET scan revealed a metabolically active tumor thrombus in the SVC, besides other sites of metabolically active disease inclusive of the lung parenchyma, lymph nodes and abdomen. She was treated with anti-thrombotics and external beam radiotherapy directed to the SVC thrombus leading to symptomatic relief. She continues to survive on the day of writing this report.
CONCLUSIONS: This rare complication, though theoretically possible, is unreported because of the short overall survival of advanced gallbladder cancer patients. This highlights that with the availability of better chemotherapeutic/biotherapeutic agents for increasing in the lifespan of cancer patients, we may come across such cases more frequently in the future.

BACKGROUND: Metastases from malignant melanoma to the liver are rare in China, and surgical resection may be of potential benefit. Liver transplantation for this disease has never been reported.
METHODS: We report a case of adult-to-adult living donor liver transplantation (A-A LDLT) for metastatic melanoma. With a surgical history of ocular melanoma, the recipient presented with emaciation from a large right hepatic mass which also probably had portal vein invasion. A-A LDLT was successfully performed and no postoperative complications were observed in either the donor or the recipient. Postoperative pathology confirmed the diagnosis of metastatic malignant melanoma; however no adjuvant chemotherapy was employed after transplantation. We also reviewed the literature on the surgical treatment of metastatic malignant melanoma to the liver and discussed the LDLT indications.
RESULT: Recurrence occurred 6 months after surgery and the patient died from recurrence of the disease 8 months post-transplant.
CONCLUSIONS: Review of the literature suggested that only a small subset of selected patients may benefit from liver resection. Large metastatic disease in the liver potentially involving a major vessel, as in this case, should be contraindicated for liver transplantation.

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