BACKGROUND: The use of laparoscopic distal pancreatectomy (LDP) increased in the past twenty years but the real diffusion of this technique is still unknown as well as the type of centers (high or low volume) in which this procedure is more frequently performed.
DATA SOURCE: A systematic review was performed to evaluate the frequency of LDP in Italy and to compare indications and results in high volume centers (HVCs) and in low volume centers (LVCs).
RESULTS: From 95 potentially relevant citations identified, only 5 studies were included. A total of 125 subjects were analyzed, of whom 95 (76.0%) were from HVCs and 30 (24.0%) from LVCs. The mean number of LDPs performed per year was 6.5. The mean number of patients who underwent LDP per year was 8.8 in HVCs and 3.0 in LVCs (P<0.001). The most frequent lesions operated on in HVCs were cystic tumors (62.1%, P<0.001) while, in LVCs, solid neoplasms (76.7%, P<0.001). In HVCs, malignant neoplasms were treated with LDP less frequently than in LVCs (17.9% vs 50.0%, P<0.001). Splenectomy was performed for non-oncologic reason frequenter in HVCs than in LVCs (70.2% vs 25.0%, P=0.004). The length of stay was shorter in HVCs than in LVCs (7.5 vs 11.3, P<0.001). No differences were found regarding age, gender, ductal adenocarcinoma treated, operative time, conversion, morbidity, postoperative pancreatic fistula, reoperation and margin status.
CONCLUSIONS: LDPs were frequently performed in Italy. The "HVC approach" is characterized by a careful selection of patients undergoing LDP. The "LVC approach" is based on the hypothesis that LDPs are equivalent both in short-term and long-term results to laparotomic approach. These data are not conclusive and they point out the need for a national register of laparoscopic pancreatectomy.

BACKGROUND: Acute cellular rejection (ACR) after liver transplantation (LT) is one of the most common problems faced by transplant recipients in spite of advances in immunosuppressive therapy. Recently, clinical trials reported that ursodeoxycholic acid (UDCA) reduced the incidence of ACR significantly. However, others have shown contradictory conclusion. Therefore, we performed a meta-analysis of rigorous randomized controlled trials (RCTs) to determine the efficacy of UDCA in reducing ACR after LT.
DATA SOURCES: All RCTs that evaluated efficacy of UDCA as an adjuvant treatment to prevent ACR after LT were searched from PubMed/MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, ScienceDirect databases and Web of Science (from January 1981 to March 2012). There was no language limitation in these searches. Relevant abstracts of international meetings were also searched. References of each included study were searched manually.
RESULTS: A total of 234 patients from four high-quality RCTs (Jadad score 4 to 5) were included in this meta-analysis. Prophylactic use of UDCA did not decrease the incidence of ACR (RR: 0.94, 95% CI: 0.77-1.16, P>0.05), steroid-resistant rejection (RR: 0.77, 95% CI: 0.47-1.27, P>0.05) and the number of patients with the multiple episodes of ACR (RR: 0.60, 95% CI: 0.28-1.30, P>0.05). Different intervention programs (high-dose vs low-dose UDCA; early vs delayed UDCA treatment) also did not alter the outcomes.
CONCLUSIONS: UDCA, as an adjuvant treatment, was not able to prevent ACR and steroid-resistant rejection after LT. Further trials should be done to determine whether higher dose of UDCA will be beneficial.

BACKGROUND: Various scoring systems based on assessment of the systemic inflammatory response help assessing the prognosis of patients with pancreatic ductal adenocarcinoma. In the present systematic review we evaluated the validity of four pre-intervention scoring systems: Glasgow prognostic score (GPS) and its modified version (mGPS), platelet lymphocyte ratio (PLR), neutrophil lymphocyte ratio (NLR), and prognostic nutrition index (PNI).
DATA SOURCES: MOOSE guidelines were followed and EMBASE and MEDLINE databases were searched for all published studies until September 2013 using comprehensive text word and MeSH terms. All identified studies were analyzed, and relevant studies were included in the systematic review.
RESULTS: Six studies were identified for GPS/mGPS with 3 reporting statistical significance for GPS/mGPS on both univariate analysis (UVA) and multivariate analysis (MVA). Two studies suggested prognostic significance on UVA but not MVA, and in the final study UVA failed to show significance. Eleven studies evaluated the prognostic value of NLR. Six of them reported prognostic significance for NLR on UVA that persisted at MVA in 4 studies, and in the remaining 2 studies NLR was the only significant factor on UVA. In the remaining 5 studies, all in patients undergoing resection, there was no significance on UVA. Seven studies evaluated PLR, with only one study demonstrated its prognostic significance on both UVA and MVA, the rest did not show the significance on UVA. Of the two studies identified for PNI, one demonstrated a statistically significant difference in survival on both UVA and MVA, and the other reported no significance for PNI on UVA.
CONCLUSIONS: Both GPS/mGPS and NLR may be useful but further better-designed studies are required to confirm their value. PLR might be little useful, and there are at present inadequate data to assess the prognostic value of PNI. At present, no scoring system is reliable enough to be accepted into routine use for the prognosis of patients with pancreatic ductal adenocarcinoma.

Cytokine-based immunotherapy is executed by harnessing cytokines to activate the immune system to suppress tumors. Th1-type cytokines including IL-1, IL-2, IL-12 and granulocyte-macrophage colony-stimulating factor are potent stimulators of Th1 differentiation and Th1-based antitumor response. Many preclinical studies demonstrated the antitumor effects of Th1 cytokines but their clinical efficacy is limited. Multiple factors influence the efficacy of immunotherapy for tumors. For instance immunosuppressive cells in the tumor microenvironment can produce inhibitory cytokines which suppress antitumor immune response. Most studies on cytokine immunotherapy focused on how to boost Th1 response; many studies combined cytokine-based therapy with other treatments to reverse immunosuppression in tumor microenvironment. In addition, cytokines have pleiotropic functions and some cytokines show paradoxical activities under different settings. Better understanding the physiological and pathological functions of cytokines helps clinicians to design Th1-based cancer therapy in clinical practice.

BACKGROUND: Hepatitis B virus (HBV) infection may impose an economic burden to patients or their families. The prevention and control of HBV could effectively reduce the burden. However, the management of HBV-related patients has not been well controlled in China. With the development of general practitioner (GP) system in this country, GPs may greatly improve the management of the patients with HBV infection. However, the role of GPs in controlling HBV infection has been rarely studied.
DATA SOURCES: A literature search of PubMed, CNKI, Wanfang data and VIP was performed with the following key words: "general practitioner", "family physician", "community management", "community health care workers", "family practice", "hepatitis B virus", "HBV", "HBV vaccination", "HBV prevention", "HBV management", "HBV treatment", "antiviral therapy" and "chronic hepatitis B (CHB)". The information about the GPs-involved prevention, diagnosis and treatment of CHB was reviewed.
RESULTS: The reports on the role of GPs in the prevention, diagnosis and treatment of HBV infection are few. But the experiences from Western countries demonstrated that GPs could play a significant role in the management of patients with CHB. The importance of GPs is obvious although there are some difficulties in China. GPs and health officials at different levels should work together in the management of patients with CHB.
CONCLUSIONS: The involvement of GPs in the management of patients with HBV infection is effective in China. But GPs' knowledge and skills for the control of HBV infection have to be improved currently. GPs' involvement will enforce the management of CHB in China in the near future.

BACKGROUND: Hepatitis B virus (HBV)-related end-stage liver disease is the leading indication for liver transplantation in China, but long-term results of liver transplantation in patients aged over 60 years are not clear. The present study was to reveal the natural history of liver recipients with hepatitis B older than 60 years. 
METHODS: The recipients who had received liver transplantation between December 2003 and December 2005 were divided into two groups: those equal or older than 60 years (older group, n=60) and those younger than 60 years (younger group, n=305). Risk factors for poor long-term outcome in patients aged over 60 years were also analyzed.
RESULTS: Except for age and preexisting chronic disease (P<0.05), no significant differences were observed in perioperative characteristics between the two groups. There was also no significant difference in HBV and hepatocellular carcinoma recurrence (P>0.05). The actuarial 1-, 3-, 5- and 8-year survival rates were 81.6%, 71.6%, 66.7% and 63.3% respectively for the older group vs 84.9%, 77.7%, 70.8% and 65.6% for the younger group (P>0.05). Multivariate analyses showed that pre-liver transplant renal insufficiency was a risk factor for poor outcome in the older group (odds ratio=3.615, P=0.014).
CONCLUSIONS: Liver transplantation is safe and feasible for patients with HBV-related end-stage liver disease aged over 60 years. Older patients with renal insufficiency should undergo transplantation earlier than younger patients.

BACKGROUND: With advances in technology, laparoscopic liver resection is widely accepted. Laparoscopic liver resection under hemihepatic vascular inflow occlusion has advantages over the conventional total hepatic inflow occlusion using the Pringle's maneuver, especially in patients with cirrhosis.
METHOD: From November 2011 to August 2012, eight consecutive patients underwent laparoscopic liver resection under hemihepatic vascular inflow occlusion using the lowering of hilar plate approach with biliary bougie assistance.
RESULTS: The types of liver resection included right hepatectomy (n=1), right posterior sectionectomy (n=1), left hepatectomy and common bile duct exploration (n=1), segment 4b resection (n=1), left lateral sectionectomy (n=2), and wedge resection (n=2). Four patients underwent right and 4 left hemihepatic vascular inflow occlusion. Four patients had cirrhosis. The mean operation time was 176.3 minutes. The mean time taken to achieve hemihepatic vascular inflow occlusion was 24.3 minutes. The mean duration of vascular inflow occlusion was 54.5 minutes. The mean intraoperative blood loss was 361 mL. No patient required blood transfusion. Postoperatively, one patient developed bile leak which healed with conservative treatment. No postoperative liver failure and mortality occurred. The mean hospital stay of the patients was 7 days.
CONCLUSION: Our technique of hemihepatic vascular inflow vascular occlusion using the lowering of hilar plate approach was safe, and it improved laparoscopic liver resection by minimizing blood loss during liver parenchymal transection.

BACKGROUND: Post-pancreaticoduodenectomy (PD) hemorrhage (PPH) is an uncommon but serious complication. This retrospective study analyzed the risk factors, managements and outcomes of the patients with PPH.
METHODS: A total of 840 patients with PD between 2000 and 2010 were retrospectively analyzed. Among them, 73 patients had PPH: 19 patients had early PPH and 54 had late PPH. The assessment included the preoperative history of disease, pancreatic status and surgical techniques. Other postoperative complications were also evaluated.
RESULTS: The incidence of PPH was 8.7% (73/840). There were no independent risk factors for early PPH. Male gender (OR=4.40, P=0.02), diameter of pancreatic duct (OR=0.64, P=0.01), end-to-side invagination pancreaticojejunostomy (OR=5.65, P=0.01), pancreatic fistula (OR=2.33, P=0.04) and intra-abdominal abscess (OR=12.19, P<0.01) were the independent risk factors for late PPH. Four patients with early PPH received conservative treatment and 12 were treated surgically. As for patients with late PPH, the success rate of medical therapy was 27.8% (15/54). Initial endoscopy was operated in 12 patients (22.2%), initial angiography in 19 (35.2%), and relaparotomy in 15 (27.8%). Eventually, PPH resulted in 19 deaths. The main causes of death were multiple organ failure, hemorrhagic shock, sepsis and uncontrolled rebleeding.
CONCLUSIONS: Careful and ongoing observation of hemorrhagic signs, especially within the first 24 hours after PD or within the course of pancreatic fistula or intra-abdominal abscess, is recommended for patients with PD and a prompt management is necessary. Although endoscopy and angiography are the standard procedures for the management of PPH, surgical approach is still irreplaceable. Aggressive prevention of hemorrhagic shock and re-hemorrhage is the key to treat PPH.

BACKGROUND: Recent studies have shown the clinical significance of epidermal growth factor-like domain 7 (EGFL7) in a variety of cancers. However, the relationship between EGFL7 and the prognosis of pancreatic cancer (PC) remains unclear. The present study was undertaken to investigate the role of EGFL7 in the prognosis of PC.
METHODS: The expression of EGFL7 in nine PC cell lines was first determined by Western blotting analysis. Tissue microarray-based immunohistochemical staining was performed in paired formalin-fixed paraffin-embedded tumor and non-tumor samples from 83 patients with PC. Finally, correlations between EGFL7 expression and clinicopathological variables as well as overall survival were evaluated.
RESULTS: EGFL7 was widely expressed in all PC cell lines tested. EGFL7 expression in tumor tissues was significantly higher than that in non-tumor tissues (P=0.040). In addition, univariate analysis revealed that high EGFL7 expression in tumor tissues was significantly associated with poor overall survival, accompanied by several conventional clinicopathological variables, such as gender, histological grade and lymph node metastasis. In a multivariate Cox regression test, EGFL7 expression was identified as an independent marker for long-term outcome of PC.
CONCLUSION: Our data showed that EGFL7 is extensively expressed in PC and that EGFL7 is associated with poor prognosis.

BACKGROUND: Although there are many studies on the mechanism of chemoresistance in cancers, studies on the relations between WNT5A and chemoresistance in pancreatic cancer are rare. The present study was to examine the role of WNT5A in the regulation of cell cycle progression and in chemo- resistance in pancreatic cancer tissues and cell lines.
METHODS: Fresh pancreatic cancer and paracarcinoma tissues were obtained from 32 patients. The expressions of WNT5A, AKT/p-AKT and Cyclin D1 were detected by immunohistochemistry, and the correlation between WNT5A expression and clinicopathological characteristics was analyzed. The relationship between WNT5A expression and gemcitabine resistance was studied in PANC-1 and MIAPaCa2 cell lines. The effect of WNT5A on the regulation of cell cycle and gemcitabine cytotoxicity were investigated. The associations among the expressions of p-AKT, Cyclin D1 and WNT5A were also analyzed in cell lines and the effect of WNT5A on restriction-point (R-point) progression was evaluated.
RESULTS: WNT5A, p-AKT and Cyclin D1 were highly expressed in pancreatic cancer tissues, and the WNT5A expression was correlated with the TNM stages. In vitro, WNT5A expression was associated with gemcitabine chemoresistance. The percentage of cells was increased in G0/G1 phase and decreased in S phase after knockdown of WNT5A in PANC-1. WNT5A promoted Cyclin D1 expression through phosphorylation of AKT which consequently enhanced G1-S transition and gemcitabine resistance. Furthermore, WNT5A enhanced the cell cycle progression toward R-point through regulation of retinoblastoma protein (pRb) and pRb-E2F complex formation.
CONCLUSIONS: WNT5A induced chemoresistance by regulation of G1-S transition in pancreatic cancer cells. WNT5A might serve as a predictor of gemcitabine response and as a potential target for tumor chemotherapy.

Pancreatic lymphoepithelial cysts (LECs) are rare, benign lesions that are typically unexpected post-operative pathological findings. We aimed to review clinical, radiological and pathological features of LECs that may allow their pre-operative diagnosis. Histopathology databases of two large pancreatic units were searched to identify LECs and notes reviewed to determine patient demographic details, mode of presentation, investigations, treatment and outcome. Five male and one female patients were identified. Their median age was 60 years. Lesions were identified on computed tomography performed for abdominal pain in two patients, and were incidentally observed in four patients. Five LECs were located in the tail and one in the body of the pancreas, with a median cyst size of 5 cm. Obtaining cyst fluid was difficult and a largely acellular aspirate was yielded. The pre-operative diagnosis was mucinous cystic neoplasm in all patients. This series of patients were treated distal pancreatectomy and splenectomy. A retrospective review of radiological examinations suggested that LECs have a relatively low signal on T2 imaging and a high signal intensity on T1 weighted images. LECs appear more common in elderly males, and are typically incidental, large, unilocular cysts. Close attention to signal intensity on MRI may allow pre-operative diagnosis of these lesions.

Liver trauma is the most common abdominal emergency with high morbidity and mortality. Now, non-operative management (NOM) is a selective method for liver trauma. The aim of this study was to determine the success rate, mortality and morbidity of NOM for isolated liver trauma. Medical records of 81 patients with isolated liver trauma in our unit were analyzed retrospectively. The success rate, mortality and morbidity of NOM were evaluated. In this series, 9 patients with grade IV-V liver injuries underwent emergent operation due to hemodynamic instability; 72 patients, 6 with grade V, 18 grade IV, 29 grade III, 15 grade II and 4 grade I, with hemodynamic stability received NOM. The overall success rate of NOM was 97.2% (70/72). The success rates of NOM in the patients with grade I-III, IV and V liver trauma were 100%, 94.4% and 83.3%. The complication rates were 10.0% and 45.5% in the patients who underwent NOM and surgical treatment, respectively. No patient with grade I-II liver trauma had complications. All patients who underwent NOM survived. NOM is the first option for the treatment of liver trauma if the patient is hemodynamically stable. The grade of liver injury and the volume of hemoperitoneum are not suitable criteria for selecting NOM. Hepatic angioembolization associated with the correction of hypothermia, coagulopathy and acidosis is important in the conservative treatment for liver trauma.

Domino liver transplantation (LT), using livers from familial amyloidotic polyneuropathy (FAP) patients, is a well described technique useful to expand donor pool. One of the main difficulties of this type of LT arises from the necessity to share the vascular pedicles between the graft and the donor. The most important challenge resides in restoring a proper hepatic venous outflow in the FAP-liver recipient. This is specially challenging when using the piggy-back technique, because the hepatic stumps may be too short. To overcome this issue, surgeons explored several techniques using different types of venous grafts. We describe a new technical option by using an arterial graft from the deceased donor. By using both iliac arteries a long graft is created and sutured as needed to the hepatic vein stump. We describe herein this new technique employed in a domino liver recipient who underwent retransplantation for ischemic cholangitis. The procedure was performed using the piggy-back technique; the venous stump of the FAP liver was reconstructed with the arterial graft. The patient had uneventful postoperative and mid-term hepatic function, and anastomosis was patent 24 months after LT.

To the Editor: We have read with interest the article by Schmitz et al^[1] from Berlin entitled "Different cava reconstruction techniques in liver transplantation: piggy-back versus cava resection", which has been recently published in Hepatobiliary and Pancreatic Diseases International. The aim of this monocentric retrospective study was to compare outcomes and complications of the classical cava reconstruction (CR) versus piggy-back (PB) technique for cavocaval anastomosis in adult orthotopic liver transplantation (OLT). Whereas Schmitz et al reported an important series of 414 patients who had OLT either by CR (n=238) or PB (n=176), it seems relevant to us that some outcomes of the present study be further discussed. First, in 2010 we also reported from the experience of Strasbourg an important series of 423 consecutive adult PB OLT using the 3-hepatic veins for cavocaval anastomosis^[2] as well. Furthermore, a very similar modified PB using the 3-hepatic veins was also reported in 2011 by Tayar et al from Paris.^[3] These reports are missing in the present article. Second, whereas there is demographic comparability of the patient groups between our two study, Schmitz et al experienced a venous outflow problem in 3/176 (1.7%) in the PB group mainly due to a kinking of the hepatic veins. In our series, complications related to the 3-hepatic vein PB anastomosis occurred in 8/396 patients (2.0%); among them 1 patient presented an acute Budd-Chiari syndrome that required re-transplantation and 7 patients presented a stenosis of suprahepatic anastomosis. Every patient was treated with angiographic balloon dilatation, which allowed restoring definitely the normal outflow of the liver transplant and total recovery. Third, the complication rates following PB observed in our center are contradictory with the present study. With regard of the PB OLT complication rates, we reported an incidence of abdominal bleeding of 3.5%, 14/396 patients (vs 14.8%, 26/176 by Schmitz et al.); an incidence of biliary leaks of 3.3%, 13/396 (vs 9.1%, 16/176 by Schmitz et al.); a perioperative red blood cells transfusion of mean 3.2 units (vs 6.1 units by Schmitz et al.). According to our extensive experience with the 3-hepatic vein PB technique, we have shown that this modified PB procedure allows optimal venous drainage of the liver transplant in a rapid and a safe procedure (partial inferior vena cava clamping). Moreover, this approach guarantees a low rate of arterial or biliary complications and should be routinely considered in OLT.

To the Editor: I have previously reported a type II diabetic patient complicated with chronic hepatitis C virus (HCV) infection.^[1] Recently, Riva et al^[2] reported an association of truncated CXCL10 with failure to achieve spontaneous clearance of acute HCV infection. They showed that the increased plasma activity of dipeptidyl peptidase-4 (DPP-4) was correlated with the establishment of chronic HCV infection via the generation of a truncated form of the chemokine CXCL10. The study by Riva et al^[2] reminded me of my previous case report. I reported a 56-year-old female patient with type II diabetes complicated with chronic HCV infection, who was successfully treated with the DPP-4 inhibitor, sitagliptin. I retrospectively studied the change in HCV-RNA after the use of sitagliptin. Her chronic HCV infection was treated only with ursodeoxycholic acid, but interferon and direct-acting anti-viral agents were not used. She showed 7.3 log IU/mL of HCV-RNA before the use of sitagliptin in March, 2010. Her HCV-RNA decreased significantly to 5.7 log IU/mL at 15 months after the treatment with sitagliptin in June, 2011. This finding suggested that sitagliptin inhibits DPP-4 and this may prevent truncation of CXCL10, inducing a reduction of HCV-RNA. In another study by Riva et al,^[2] truncated CXCL10 was positively and significantly correlated with HCV-RNA and DPP-4 activity; this supports our hypothesis. Although further studies, preferably with larger numbers of subjects, are needed to elucidate the effects of the DPP-4 inhibitors on HCV infection, DPP-4 may represent a new therapeutic target for the treatment of chronic HCV infection. There is a significant difference in cost between sitagliptin and the currently available directly acting anti-viral treatments. For example, according to the National Institute for Health and Care Excellence in the United Kingdom, a one-month course of once daily sitagliptin costs Great Britain Pound (GBP) 33 whilst the cost of one monthly course of once daily sofosbuvir costs GBP 11 661. The use of DPP-4 inhibitors may produce a significant cost reduction for the treatment of HCV infection.

On September 5, 2014, the 3rd editorial committee meeting of Hepatobiliary & Pancreatic Diseases International (HBPD INT) was held at Mirror Lake Hotel, Shaoxing, China. Participants include Prof. Wan-Yee Lau from Chinese University of Hong Kong, Prince of Wales Hospital, China, Prof. Chung-Mau Lo from University of Hong Kong, Queen Mary Hospital, China, Prof. Alan S. Livingstone from University of Miami Miller School of Medicine, USA, Prof. Holger Kalthoff from University Clinic Schleswig-Holstein (UKSH), Germany, Prof. Moulay Aloui-Jamali from McGill University, Canada, Prof. Hongqun Liu from University of Calgary, Canada, and Prof. Kwan Man from University of Hong Kong, Queen Mary Hospital, China. A total of 40 members attended this meeting. Prof. Shou-Chu Qian, managing editor, presided over the meeting.
At the beginning, Prof. Shu-Sen Zheng, chief editor, briefly introduced the current status of HBPD INT and outlined the contribution of the editorial members in the past 13 years. Indexed in SCI-E and other databases, HBPD INT now has an impact factor of 1.167 (2013 Journal Citation Reports). Currently, HBPD INT needs a breakthrough in further development. An action has been taken to assign Profs. Wan-Yee Lau, Chung-Mau Lo, Alan S. Livingstone, Holger Kalthoff and Moulay Aloui-Jamali as deputy chief editors (2015-2016), attempting to improve the quality of the journal by soliciting more submissions from important centers around the world. They also will play an important part in writing and reviewing articles within their fields. Prof. Hongqun Liu, from his experience as the past-managing editor of Liver International, suggested the ways of how to improve the impact factor of the journal and how to handle the submissions timely.
On behalf of the newly-assigned deputy chief editors, Prof. Lau expressed their willingness to work well as deputy chief editors and offered some advices. Profs. Kalthoff, Alaoui-Jamali, Lo, and Livingstone also gave advices for the development of the journal. The staff under the editorship of Prof. Zheng and his associates are sure to make the journal one of the best journals in the world.