BACKGROUND: The conventional tests for the diagnosis of early stage pancreatic carcinoma are not acceptable. This meta-analysis is to evaluate the accuracy of K-ras mutation for the diagnosis of pancreatic carcinoma.
DATA SOURCES: A systemic search of all relevant literature was performed in Web of Science, EMBASE, Cochrane Database, and MEDLINE (PubMed as the search engine) prior to June 1, 2011. Thirty-four studies fulfilled the inclusion criteria and data were pooled for analysis.
RESULTS: The pooled estimates for K-ras mutation in diagnosis of pancreatic carcinoma were as follows: sensitivity 0.68 (95% CI: 0.66-0.71), specificity 0.87 (95% CI: 0.85-0.88), positive likelihood ratio 4.54 (95% CI: 3.47-5.94), negative likelihood ratio 0.37 (95% CI: 0.30-0.44) and diagnostic odds ratio 14.90 (95% CI: 10.02-22.15). Summary receiver operating characteristic analysis demonstrated that the maximum joint sensitivity and specificity was 0.79, and the overall area under the curve was 0.86.
CONCLUSIONS: Diagnostic accuracy of K-ras mutation was not superior to that of conventional tests. Therefore, K-ras mutation analysis alone is not recommended for the diagnosis of pancreatic carcinoma.

BACKGROUND: Recurrence of hepatitis B virus (HBV) infection after liver transplantation can lead to graft loss and a reduction in long-term survival. The purpose of this review is to summarize the current therapeutic options for preventing HBV recurrence in liver transplant recipients.
DATA SOURCES: Up to January 2013, studies that were published in MEDLINE and EMBASE on prevention of HBV recurrence after liver transplantation were reviewed.
RESULTS: There have been remarkable advancements in the past two decades on the prevention of HBV recurrence after liver transplantation, from the discovery of hepatitis B immune globulin (HBIG) and lamivudine monotherapy to the combination therapy using HBIG and lamivudine. With the development of newer and stronger antiviral agents, the need for life-long HBIG is doubtful. With their low resistance profile, oral antiviral prophylaxis using these new agents alone is sufficient and is associated with excellent outcome.
CONCLUSIONS: Restoration of host HBV immunity with adoptive immunity transfer and vaccination may represent the ultimate strategy to withdraw prophylactic treatment and to achieve a drug free regimen against HBV recurrence after liver transplantation.

BACKGROUND: Liver resection is still a risky procedure with high morbidity and mortality. It is significant to predict the morbidity and mortality with some models after liver resection.
DATA SOURCES: The MEDLINE/PubMed, Web of Science, Google Scholar, and Cochrane Library databases were searched using the terms "hepatectomy" and "risk assessment" for relevant studies before August 2012. Papers published in English were included.
RESULTS: Thirty-four original papers were included finally. Some models, such as MELD, APACHE II, E-PASS, or POSSUM, widely used in other populations, are useful to predict the morbidity and mortality after liver resection. Some special models for liver resection are used to predict outcomes after liver resection, such as mortality, liver dysfunction, transfusion, or acute renal failure. However, there is no good scoring system to predict or classify surgical complications because of shortage of internal or external validation.
CONCLUSION: It is important to validate the models for the major complications after liver resection with further internal or external databases.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) can be divided into head, body and tail cancers according to the anatomy. Distinctions in tissue composition, vascularization and innervations have been clearly identified between the head and body/tail of the pancreas both in embryological development and in histopathology. To understand the postulated genotype difference, we present comprehensive information on two PDAC cell lines as typical representatives originating from pancreatic head and body/tail cancers, respectively.
DATA SOURCE: In the present review, we compare the difference between pancreatic head and body/tail cancers regarding clinical parameters and introducing an in vitro model.
RESULTS: Increasing evidence has shown that tumors at different locations (head vs body/tail) display different clinical presentation (e.g. incidence, symptom), treatment efficiency (e.g. surgery, chemotherapy) and thus patient prognosis. However, the genetic or molecular diversity (e.g. mutations, microRNA) between the two subtypes of PDAC has not been elucidated so far. They present different chemo- and/or radio-resistance, extracellular matrix adhesion and invasiveness, as well as genetic profiles.
CONCLUSION: Genetic and tumor biological diversity exists in PDAC according to the tumor localization.

BACKGROUND: Endoscopic therapy has been successful in the management of biliary complications after both deceased donor liver transplantation (DDLT) and living donor liver transplantation (LDLT). LDLT is thought to be associated with higher rates of biliary complications, but there are few studies comparing the success of endoscopic management of anastomotic strictures between the two groups. This study aims to compare our experience in the endoscopic management of anastomotic strictures in DDLT versus LDLT.
METHODS: This is a retrospective database review of all liver transplant patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) after liver transplantation. The frequency of anastomotic stricture and the time to develop and to resolve anastomotic stricture were compared between DDLT and LDLT. The response of anastomotic stricture to endoscopic therapy was also analyzed.
RESULTS: A total of 362 patients underwent liver transplan-tation between 2003 and 2011, with 125 requiring ERCP to manage biliary complications. Thirty-three (9.9%) cases of DDLT and 8 (27.6%) of LDLT (P=0.01) were found to have anastomotic stricture. When comparing DDLT and LDLT, there was no difference in the mean time to the development of anastomotic strictures (98±17 vs 172±65 days, P=0.11), likelihood of response to ERCP [22 (66.7%) vs 6 (75.0%), P=0.69], mean time to the resolution of anastomotic strictures (268±77 vs 125±37 days, P=0.34), and the number of ERCPs required to achieve resolution (3.9±0.4 vs 4.7±0.9, P=0.38).
CONCLUSIONS: Endoscopic therapy is effective in the majority of biliary complications relating to liver transplantation. Anastomotic strictures occur more frequently in LDLT compared with DDLT, with equivalent endoscopic treatment response and outcomes for both groups.

BACKGROUND: The tumor burden before liver transplantation indicates that hepatitis B virus (HBV) may hide in the extrahepatic and micrometastatic sites which serve as a source of HBV replication. Currently, many liver transplant centers, especially in Western countries, use the Milan or UCSF criteria to select patients with hepatocellular carcinoma for liver transplantation. This study was undertaken to compare the HBV prophylactic outcomes in two groups of living donor liver transplantation (LDLT) recipients. Patients in group A met the Milan criteria and those in group B exceeded the Milan criteria but were within the UCSF criteria.
METHODS: A database of adult-to-adult right-lobe LDLT performed at our institution for HBV-related hepatocellular carcinoma within the Milan or UCSF criteria between June 2002 and May 2012 was used to compare the HBV prophylactic outcomes between patients within the Milan criteria (group A, 41 patients) and those exceeding the Milan criteria but within the UCSF criteria (group B, 19 patients).
RESULTS: The 1-, 3-, and 5-year survival rates were similar between groups A and B (87.8%, 85.1% and 74.0% vs 73.3%, 61.1% and 61.1%, respectively, P=0.067). HBV recurred in 1 patient in 3.1 months after LDLT in group A and in 2 patients in group B (1 in 11.9 months and 1 in 24.1 months after LDLT). The 1-, 3-, and 5-year HBV recurrence rates were 2.6%, 2.6% and 2.6% in group A, and 7.3%, 17.9% and 17.9% in group B, respectively (P=0.118).
CONCLUSION: LDLT recipients who exceed the Milan criteria but remain within the UCSF criteria may have post-transplant HBV prophylactic outcomes similar to those who meet the Milan criteria.

BACKGROUND: The prognosis and clinical management of patients with chronic liver diseases are closely related to the severity of liver fibrosis. Liver biopsy is considered the gold standard for the staging of liver fibrosis. However, it is an invasive test sometimes related to complications. This study aimed to assess the diagnostic value of enhanced liver fibrosis (ELF) test to predict liver fibrosis in patients with chronic hepatitis C.
METHODS: This study included 162 patients with liver disease and 67 healthy controls. Hyaluronic acid, tissue inhibitor of matrix metalloproteinase type 1, and amino-terminal propeptide type III procollagen were measured by enzyme-linked immunosorbent assay with the ELF test ADVIA Centaur® (Siemens Healthcare Diagnostics Inc.). Fibrosis stage was determined using the Metavir scoring system.
RESULTS: In our study, for the diagnosis of significant fibrosis (Metavir F≥2) a cut-off value >7.72 provides a sensitivity of 93.0% and a specificity of 83.0%. The areas under the receiver operator characteristic curve, sensitivity, specificity, and positive and negative predictive values were 0.94, 93.3%, 81.0%, 93.3%, and 81.0%, respectively (P<0.001). For the diagnosis of cirrhosis (Metavir F=4) a cut-off value >9.3 provides a sensitivity of 93.0% and a specificity of 86.0%. The areas under the receiver operator characteristic curve, sensitivity, specificity, and positive and negative predictive values were 0.94, 79.1%, 90.8%, 75.6%, and 92.3%, respectively (P<0.001).
CONCLUSIONS: The ELF test is a promising non-invasive method for assessing liver fibrosis in patients with chronic hepatitis C. It is effective in the diagnosis of both fibrosis and cirrhosis.

BACKGROUND: Liver biopsy is the "gold standard" for evaluating liver disorders, but controversies over the potential risk of complications and patient discomfort still exist. Using a 21G fine needle, we developed a new biopsy procedure, fine needle aspirating and cutting (FNAC). Our procedure obtains enough tissue for pathological examination and meanwhile, reduces the risk of biopsy complications. The present study was to determine the safety and efficiency of 21G FNAC compared with 18G Tru-cut core needle (TCN) in liver tumor biopsies.
METHODS: Ninety-four patients with unresectable malignant tumors were included in this study. Patients were divided into 2 groups: 18G TCN and 21G FNAC. The total positive rate (TPR) and safety of both groups were compared.
RESULTS: TPR was not different between the two groups. Liver puncture track subcapsular hemorrhage and arteriovenous shunt were reported with 18G TCN but not with 21G FNAC. The incidence of pain caused by biopsy was higher for the 18G TCN group compared to the 21G FNAC group (P<0.05). About 82.6% of the patients in the 18G TCN group had a sample length >0.5 cm, but 52.1% in the 21G FNAC group (P<0.05). More than 50% of patients in both groups had sufficient tissue for immunohistochemical examination.
CONCLUSIONS: TPR is not different between the 21G FNAC and 18G TCN biopsy procedures, but the safety of 21G FNAC is superior to that of 18G TCN. Tissues obtained by either of these two procedures are sufficient for a pathological diagnosis.

BACKGROUND: Portal vein thrombosis (PVT) is a potential lethal complication and may have negative influence on the prognosis after splenectomy in patients with liver cirrhosis. Prevention and timely detection of PVT are quite significant. There is a lack of knowledge about the clinical features and risk factors of PVT. Our study aimed to investigate the risk factors and clinical characteristics of PVT in order to figure out the high-risk individuals.
METHODS: We collected the clinical data of 472 consecutive patients with non-neoplastic liver cirrhosis who had undergone splenectomy from January 2008 to December 2010 in our institution. Clinical and surgical characteristics of patients who developed PVT postoperatively and those who did not develop PVT were compared. Univariate and multivariate analyses of risk factors of PVT were performed. The mortality and rebleeding rate of the patients were also evaluated.
RESULTS: Of the 472 patients, 52 were excluded from the study. PVT developed in 71 (71/420, 16.9%) patients. Multivariate analysis revealed that wider preoperative portal vein diameter, postoperative thrombocytosis, prolonged prothrombin time and periesophagogastric devascularization were significantly correlated with PVT development [odds ratio (OR): 5.701, 2.807, 1.850 and 2.090, respectively]. The incidence of PVT in patients who took antiplatelet drugs was not lower than that in those who did not. Follow-up showed that patients in the PVT group had a tendency towards reduced overall survival but it was not statistically significant. Gastrointestinal bleeding occurred more often in the PVT group than that in the non-PVT group (P=0.044).
CONCLUSIONS: Wider preoperative portal vein diameter, postoperative thrombocytosis, prolonged prothrombin time and periesophagogastric devascularization are independent risk factors of PVT. PVT is related with higher risk of postoperative gastrointestinal hemorrhage but has no significant impact on the overall survival.

BACKGROUND: Low central venous pressure (CVP) affects hemodynamic stability and tissue perfusion. This prospective study aimed to evaluate the optimal CVP during partial hepatectomy for hepatocellular carcinoma (HCC).
METHODS: Ninety-seven patients who underwent partial hepatectomy for HCC had their CVP controlled at a level of 0 to 5 mmHg during hepatic parenchymal transection. The systolic blood pressure (SBP) was maintained, if possible, at 90 mmHg or higher. Hepatitis B surface antigen was positive in 90 patients (92.8%) and cirrhosis in 84 patients (86.6%). Pringle maneuver was used routinely in these patients with clamp/unclamp cycles of 15/5 minutes. The average clamp time was 21.4±8.0 minutes. These patients were divided into 5 groups based on the CVP: group A: 0-1 mmHg; B: 1.1-2 mmHg; C: 2.1-3 mmHg; D: 3.1-4 mmHg and E: 4.1-5 mmHg. The blood loss per transection area during hepatic parenchymal transection and the arterial blood gas before and after liver transection were analyzed.
RESULTS: With active fluid load, a constant SBP ≥90 mmHg which was considered as optimal was maintained in 18.6% in group A (95% CI: 10.8%-26.3%); 39.2% in group B (95% CI: 29.5%-48.9%); 72.2% in group C (95% CI: 63.2%-81.1%); 89.7% in group D (95% CI: 83.6%-95.7%); and 100% in group E (95% CI: 100%-100%). The blood loss per transection area during hepatic parenchymal transection decreased with a decrease in CVP. Compared to groups D and E, blood loss in groups A, B and C was significantly less (analysis of variance test, P<0.05). Compared with the baseline, the blood oxygenation decreased significantly when the CVP was reduced. Base excess and HCO3- in groups A and B were significantly decreased compared with those in groups C, D and E (P<0.05).
CONCLUSION: In consideration of blood loss, SBP, base excess and HCO3-, a CVP of 2.1-3 mmHg was optimal in patients undergoing partial hepatectomy for HCC.

BACKGROUND: Key enzyme deficiency in the dual-pathway of ammonia metabolism leads to low detoxification capacity of HepG2 cells. Previously, we established a HepG2/AFhGS cell line with overexpression of human glutamine synthetase (hGS) in pathway  1 and a HepG2/(hArgI+hOTC)4 cell line with overexpression of human arginase I (hArgI) and human ornithine transcarbamylase (hOTC) in pathway 2. The present study aimed to investigate whether simultaneous recovery of the two pathways contributes to the further improvement of ammonia detoxification in HepG2 cells.
METHODS: We adopted a recombinant retrovirus carrying the hGS gene to infect HepG2/(hArgI+hOTC)4 cells and selected a new recombinant HepG2 cell line. The capacities of ammonia tolerance and detoxification in cells were detected by biochemical methods. Cell cycle PCR chip was used to assess the changes of gene expression.
RESULTS: Introducing hGS into HepG2/(hArgI+hOTC)4 cells did not lead to hGS overexpression, but inhibited hArgI expression. The levels of synthetic glutamine and urea in HepG2/(hArgI+hOTC+AFhGS)1 cells were significantly lower than those in HepG2/(hArgI+hOTC)4 cells when cultured in the medium with 10 and 15 mmol/L glutamate (Glu) and with 60 and 180 mmol/L NH4Cl, respectively. In addition, the comparison of different cell growth showed that HepG2/AFhGS cells significantly lagged behind the other cells by the 5th and 7th day, indicating that introduction of hGS impedes HepG2 cell proliferation. Analysis of the mechanism suggested that the decreased expression of BCL2 played an important role.
CONCLUSIONS: This study demonstrated that the recovery of two ammonia metabolic pathways in HepG2 cells is not helpful in increasing ammonia metabolism. The reinforcement of the pathway of urea metabolism is more important and valuable in improving the ammonia metabolism capacity in HepG2 cells.

BACKGROUND: Postoperative pancreatic fistula is the main cause of morbidity after pancreatic resection. This study aimed to quantify the clinical and economic consequences of pancreatic fistula in a medium-volume pancreatic surgery center.
METHODS: Hospital records from patients who had undergone elective pancreatic resection in our department were identified. Pancreatic fistula was defined according to the International Study Group on Pancreatic Fistula (ISGPF). The consequences of pancreatic fistula were determined by treatment cost, hospital stay, and out-patient follow-up until the pancreatic fistula was completely healed. All costs of the treatment are calculated in Euros. The cost increase index was calculated for pancreatic fistula of grades A, B, and C as multiples of the total cost for the no fistula group.
RESULTS: In 54 months, 102 patients underwent elective pancreatic resections. Forty patients (39.2%) developed pancreatic fistula, and 54 patients (52.9%) had one or more complications. The median length of hospital stay for the no fistula, grades A, B, and C fistula groups was 12.5, 14, 20, and 59 days, respectively. The hospital stay of patients with fistula of grades B and C was significantly longer than that of patients with no fistula (P<0.001). The median total cost of the treatment was 4952, 4679, 8239, and 30 820 Euros in the no fistula, grades A, B, and C fistula groups, respectively.
CONCLUSIONS: The grading recommended by the ISGPF is useful for comparing the clinical severity of fistula and for analyzing the clinical and economic consequences of pancreatic fistula. Pancreatic fistula prolongs the hospital stay and increases the cost of treatment in proportion to the severity of the fistula.

BACKGROUND: Pancreatic cancer is a highly aggressive malignant tumor with the lowest survival rate. A better understanding of the molecular mechanisms which contribute to pancreatic cancer occurrence and progression will aid in the development of new approaches to the early diagnosis, prevention, and treatment of this deadly disease. The scaffold protein IQGAP1 shows elevated levels in a variety of cancer types. Currently, we investigated whether or not IQGAP1 is also overexpressed in pancreatic cancer.
METHODS: IQGAP1 expression was examined in pancreatic cancer and normal tissues adjacent to cancerous tissues (adjacent tissues) by Western blotting and real-time RT-PCR as well as in paraffin sections of tissue microarray by immunohistochemistry. The correlations between IQGAP1 expression and various clinicopathological characteristics were analyzed.
RESULTS: Western blotting and real-time RT-PCR revealed that the levels of IQGAP1 protein and mRNA expression in pancreatic cancer tissues were significantly increased compared with adjacent tissues. Immunohistochemistry analysis on tissue microarray showed that IQGAP1 protein expression was significantly higher in pancreatic cancer (80.0%, 48/60) compared with adjacent tissues (18.3%, 11/60) (P<0.001). Moreover, overexpression of IQGAP1 was shown to be associated with the grades of tumor differentiation (P<0.05).
CONCLUSION: The overexpression of IQGAP1 may play an important role in pancreatic cancer occurrence and progression, and IQGAP1 may serve as a novel molecular target for the diagnosis and treatment of pancreatic cancer.

BACKGROUND: Nerve invasion is a specific type of tumor expansion and characteristic manifestation of pancreatic cancer (PC), with an incidence rate ranging from 50% to 100%. It is an important prognostic factor for pancreatic cancer, and its early detection is helpful in the management of the disease. This study was undertaken to analyze retrospectively the relationship between neural invasion and multiple clinico¬pathological features and to provide evidences for clinicians in the management of neural invasion in patients with PC.
METHODS: Formalin-fixed paraffin-embeded specimens of PC taken from 215 patients were examined for the presence of neural invasion under a light microscope. Analyzed was the relationship between neural invasion and multiple clinico¬pathological feature including preoperative fasting blood glucose level, amylase level, serum CA19-9 level, abdominal pain, lumbar and back pain, and the expressions of p53 and Ki67 in tumor tissues.
RESULTS: Preoperative fasting blood glucose level, serum CA19-9 level and p53 positive cells in cancer tissue were increased with the rise of pathological grade (P<0.05). These indices were significantly higher in patients with neural invasion than in those without (P<0.05). Further analysis revealed a positive correlation between p53 and Ki67 overexpression and lymphatic metastasis (P<0.05). Referred pain was positively correlated with neural invasion (P<0.05). Patients with PC perineural invasion were more likely to have a higher pathological grade (P<0.05).
CONCLUSIONS: Our data indicated that the preoperative fasting blood glucose level, serum CA19-9 level, and referred pain are novel predictive markers for neural invasion in patients with PC. p53 and Ki67 play important roles in neural invasion of PC. Management of hyperglycemia may serve as an auxiliary treatment to curb neural invasion in PC.

The removal of tumor together with the native liver in living donor liver transplantation for hepatocellular carcinoma is challenged by a very close resection margin if the tumor abuts the inferior vena cava. This is in contrast to typical deceased donor liver transplantation where the entire retrohepatic inferior vena cava is included in total hepatectomy. Here we report a case of deroofing the retrohepatic vena cava in living donor liver transplantation for caudate hepatocellular carcinoma. In order to ensure clear resection margins, the anterior portion of the inferior vena cava was included. The right liver graft was inset into a Dacron vascular graft on the back table and the composite graft was then implanted to the recipient inferior vena cava. Using this technique, we observed the no-touch technique in tumor removal, hence minimizing the chance of positive resection margin as well as the chance of shedding of tumor cells during manipulation in operation.

Despite the improvement of surgical techniques, the rate of anastomotic failure of pancreaticojejunostomy remains high (30%-50%). Here we describe the use of vertical mattress sutures in the modification of dunking pancreaticojejunal anastomosis. In 7 patients who used this technique, neither anastomotic failure nor any major postsurgical complication developed. This technique is an easy, safe, and promising for the performance of pancreaticojejunostomy.