BACKGROUND: Laparoscopic cholecystectomy (LC) is one of the most frequent abdominal surgical procedures. The present meta-analysis aimed to estimate the clinical effects of implementing a clinical pathway for LC compared with standard medical care by evaluating the length of hospital stay, costs, and the outcomes of patients undergoing LC.
DATA SOURCES: Data were extracted from the following databases: PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, Chinese Medical Citation Index (CMCI), Chinese Medical Current Contents (CMCC), and China BioMedical Literature Database (CBM). We also searched the reference lists of the relevant articles and conference articles. Only randomized controlled trials and controlled clinical trials published from 1980 to 2013 were included. We did not set restrictions on language and country of publications. All of the data were evaluated and analyzed by two reviewers independently with RevMan software (version 5.0).
RESULTS: A total of 7 trials with 1187 patients were included. The patients who underwent LC with clinical pathway had shorter hospital stay [weighted mean difference=-1.90, 95% CI: -2.65 to -1.16, P<0.00001], lower cost [standard mean difference=-0.69, 95% CI: -0.82 to -0.56, P<0.00001], and better questionnaires based satisfaction with the medical services.
CONCLUSIONS: The applications of the clinical pathway for LC effectively reduced hospital stay and total costs. However, there was insufficient evidence for proving the differences in postoperative complications. Future research should focus on patient outcomes and identify the mechanisms underlying the effect of the clinical pathway.

BACKGROUND: Liver cirrhotic patients with hepatic encephalopathy have poor prognosis. Probiotics alter the intestinal microbiota and reduce the production of ammonia. We conducted a meta-analysis about the role of probiotics on liver cirrhotic patients with hepatic encephalopathy.
DATA SOURCES: We collected the relevant literatures up to February 21, 2014 from databases of PubMed, EMBASE and the Cochrane Central Register of Controlled Trials. A statistical analysis was conducted by RevMan 5.2 and STATA 12.0 software.
RESULTS: Six randomized controlled trials involving 496 liver cirrhotic patients were included. The results showed that probiotic therapy significantly reduced the development of overt hepatic encephalopathy (OR [95% CI]: 0.42 [0.26, 0.70], P=0.0007). However, probiotics did not affect mortality, levels of serum ammonia and constipation (mortality: OR [95% CI]: 0.73 [0.38, 1.41], P=0.35; serum ammonia: WMD [95% CI]: -3.67 [-15.71, 8.37], P=0.55; constipation: OR [95% CI]: 0.67 [0.29, 1.56], P=0.35).
CONCLUSION: Probiotics decrease overt hepatic encephalopathy in patients with liver cirrhosis.

BACKGROUND: Postoperative liver failure remains a life-threatening complication. Preoperative evaluation of liver function is essential in reducing the complications after hepatectomy. However, it is difficult to accurately evaluate liver function before surgery because of the limitations of the liver function tests available. Recent advances in liver function tests improved the ability to assess liver function. The present review was to analyze these methods and their advantages.
DATA SOURCES: MEDLINE was searched using the terms of "liver function test", "liver function evaluation" and "galactosyl serum albumin". Relevant articles published in English and Chinese from 1961 to 2014 were reviewed.
RESULTS: Although serological tests are used frequently in practice, they reflect the degree of total liver damage or function, not the remnant of liver function. Child-Pugh score and model for end-stage liver disease (MELD) score assess whole liver function, and are particularly useful in determining whether patients with hepatocellular carcinoma and cirrhosis are candidates for resection or transplantation, but cannot determine the safe extent or removal. The indocyanine green and other metabolic quantitative liver function tests can evaluate functional hepatocytes, making them more accurate in predicting liver function. Computed tomography (CT) volumetry can provide anatomic information on the remnant liver volume but not on functional volume. 99mTc-galactosyl serum albumin scintigraphy, combined with single photon emission computed tomography, CT and three-dimensional reconstruction, may be a better quantitative measure of liver function, especially of remnant liver function.
CONCLUSIONS: Tests used to evaluate liver functional reserve and to predict surgical risk have limitations. 99mTc-galactosyl serum albumin scintigraphy, which can more accurately evaluate the whole and regional liver function, may be promising in predicting resection margins and risks of liver failure.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a devastating malignancy with a poor prognosis and little treatment options. The development and progression of the disease is fostered by inflammatory cells and cytokines. One of these cytokines is interleukin-6 (IL-6), which plays an important role in a wide range of biologic activities.
DATA SOURCES: A systematic search of PubMed was performed to identify relevant studies using key words such as interleukin-6, inflammatory cytokines, inflammation and pancreatic cancer or PDAC. Articles related to IL-6 and pancreatic cancer were systematically reviewed.
RESULTS: IL-6 is elevated in the serum of pancreatic cancer patients and correlates with cachexia, advanced tumor stage and poor survival. Its expression is enhanced by hypoxia and proteins involved in pancreatic cancer development like Kras, mesothelin or ZIP4. IL-6 in turn contributes to the generation of a pro-tumorigenic microenvironment and is probably involved in angiogenesis and metastasis. In experimental mouse models of PDAC, IL-6 was important for the development and progression of precursor lesions.
CONCLUSION: IL-6 emerges as a key player in pancreatic cancer development and progression, and hence should be considered as a new therapeutic target.

Pancreatic cancer is one of the worst prognostic cancers because of the late diagnosis and the absence of effective treatment. Within all subtypes of this disease, ductal adenocarcinoma has the shortest survival time. In recent years, global genomics profiling allowed the identification of hundreds of genes that are perturbed in pancreatic cancer. The integration of different omics sources in the study of pancreatic cancer has revealed several molecular mechanisms, indicating the complex history of its development. However, validation of these genes as biomarkers for early diagnosis, prognosis or treatment efficacy is still incomplete but should lead to new approaches for the treatment of the disease in the future.

BACKGROUND: Stathmin is a ubiquitous cytosolic regulatory phosphoprotein and is overexpressed in different human malignancies. The main physiological function of stathmin is to interfere with microtubule dynamics by promoting depolymerization of microtubules or by preventing polymerization of tubulin heterodimers. Stathmin plays important roles in regulating many cellular functions as a result of its microtubule-destabilizing activity. Currently, the critical roles of stathmin in cancer cells, as well as in lymphocytes have been valued. This review discusses stathmin and microtubule dynamics in cancer development, and hypothesizes their possible relationship with epithelial-mesenchymal transition (EMT).
DATA SOURCES: A PubMed search using such terms as "stathmin", "microtubule dynamics", "epithelial-mesenchymal transition", "EMT", "malignant potential" and "cancer" was performed to identify relevant studies published in English. More than 100 related articles were reviewed.
RESULTS: The literature clearly documented the relationship between stathmin and its microtubule-destabilizing activity of cancer development. However, the particular mechanism is poorly understood. Microtubule disruption is essential for EMT, which is a crucial process during cancer development. As a microtubule-destabilizing protein, stathmin may promote malignant potential in cancer cells by initiating EMT.
CONCLUSIONS: We propose that there is a stathmin-microtubule dynamics-EMT (S-M-E) axis during cancer development. By this axis, stathmin together with its microtubule-destabilizing activity contributes to EMT, which stimulates the malignant potential in cancer cells.

BACKGROUND: The established procedure for ABO-incompatible liver transplantation (ABO-I LT) was too complicated to be used in case of emergency. We developed a protocol consisting of rituximab and intravenous immunoglobulin (IVIG) for ABO-I LT in patients with acute liver failure (ALF).
METHODS: The data from 101 patients who had undergone liver transplantation (LT) for ALF were retrospectively analyzed. The patients were divided into two groups: ABO-compatible liver transplantation group (ABO-C LT, n=66) and ABO-I LT group (n=35). All the patients in the ABO-I LT group received a single dose of rituximab (375 mg/m2) and IVIG (0.4 g/kg per day) at the beginning of the operation. IVIG was administered for 10 consecutive days after LT. Plasma exchange, splenectomy and graft local infusion were omitted in the protocol. Quadruple immunosuppressive therapy including basiliximab, corticosteroids, tacrolimus and mycophenolatemofetil was used to reinforce immunosuppression.
RESULTS: The 3-year cumulative patient survival rates in the ABO-I LT and ABO-C LT groups were 83.1% and 86.3%, respectively (P>0.05), and the graft survival rates were 80.0% and 86.3%, respectively (P>0.05). Two patients (5.7%) suffered from antibody-mediated rejection in the ABO-I LT group. Other complications such as acute cellular rejection, biliary complication and infection displayed no significant differences between the two groups.
CONCLUSIONS: The simplified treatment consisting of rituximab and IVIG prevented antibody-mediated rejection for LT of blood-type incompatible patients. With this treatment, the patients did not need plasma exchange, splenectomy and graft local infusion. This treatment was safe and efficient for LT of the patients with ALF.

BACKGROUND: Liver steatosis affects 20%-30% of adults. Because of the increasing gap between graft supplies and demands, livers with steatosis are frequently used in liver transplantation. But severely steatotic liver grafts are associated with a high risk of intraoperative and postoperative complications. Accurate assessment of fat content of donor livers and monitoring of the extent of steatosis in recipients are required for liver transplantation. The present study aimed to determine the correlation between liver echogenicity and fat content, and to evaluate the use of an ultrasonic integrated backscatter system (IBS) in the assessment of changes in fat content after liver transplantation.
METHODS: Seventy-nine consecutive patients receiving liver grafts from living donors were evaluated in our center. Of these recipients, 67 survived for more than two years and were included in this study. Each liver graft was evaluated with IBS and ultrasound before operation and the fat content was estimated. The fat content of the grafts in the recipients was again assessed with ultrasound at 18 months after surgery.
RESULTS: A correlation was detected between each graft's IBS value and its fat content (P=0.001). The IBS value in fatty grafts with various degrees of steatosis was significantly decreased in 3 (P=0.02), 12, 15 and 18 (P=0.001) months after orthotopic liver transplantation. The IBS value returned to normal in all patients in 18 months after liver transplantation.
CONCLUSIONS: Decreased fat content in steatotic grafts can be observed in all recipients. Ultrasonic IBS is useful in determining the steatotic degree of grafts in donors as well as in monitoring the grafts after liver transplantation.

BACKGROUND: In 2011, a pilot program for deceased organ donation was initiated in China. We describe the first successful series of liver transplants in the pilot program.
METHODS: From July 2011 to August 2012, our center performed 26 liver transplants from a pool of 29 deceased donors. All organ donation and allograft procurement were conducted according to the national protocol. The clinical data of donors and recipients were collected and summarized retrospectively.
RESULTS: Among the 29 donors, 24 were China Category II donors (organ donation after cardiac death), and five were China Category III donors (organ donation after brain death followed by cardiac death). The recipients were mainly the patients with hepatocellular carcinoma. The one-year patient survival rate was 80.8% with a median follow-up of 422 (2-696) days. Among the five mortalities during the follow-up, three died of tumor recurrence. In terms of post-transplant complications, 9 recipients (34.6%) experienced early allograft dysfunction, 1 (3.8%) had non-anastomotic biliary stricture, and 1 (3.8%) was complicated with hepatic arterial thrombosis. None of these complications resulted in patient death. Notably, primary non-function was not observed in any of the grafts.
CONCLUSION: With careful donor selection, liver transplant from deceased donors can be performed safely and plays a critical role in overcoming the extreme organ shortage in China.

BACKGROUND: Prostacyclin has been shown to increase portal hypertension, but the mechanism is unclear. This study aimed to investigate whether the overproduction of prostacyclin (PGI2) in cirrhosis participates in the splanchnic vascular hyporesponsiveness to vasoconstrictors in cirrhotic rats.
METHODS: Cirrhotic model was created by subcutaneous injection of 60% carbon tetrachloride (CCl4) corn oil solution combined with intermittent drinking of 5% alcohol, and age-matched rats served as controls. The isolated third-generation mesenteric arterioles were used to examine the contractile response to norepinephrine. The changes in vascular diameter were observed under a microscope imaging device. The plasma concentration of 6-ketone-prostaglandin F1α (6-keto-PGF1α, a stable metabolite of PGI2) was tested via enzyme immunoassays and the expression of cyclooxygenase (COX) in mesenteric arteries was detected by Western blotting.
RESULTS: In parallel with the increase of plasma 6-keto-PGF1α, the contractile response of arterioles from cirrhotic rats to norepinephrine was significantly impaired compared with that from controls. Inhibition of PGI2 or protein kinase A with indomethacin or Rp-adenosine 3', 5'-cyclic monophosphothioate (Rp-cAMPS) partially reversed the vascular hypo-contractile response to norepinephrine in arterioles from cirrhotic rats. Indomethacin significantly decreased the plasma 6-keto-PGF1α. Furthermore, indomethacin significantly attenuated the effect of Rp-cAMPS on arterioles from cirrhotic rats. COX-1 expression was up-regulated in mesenteric arteries from cirrhotic rats, whereas COX-2 was not detectable in the mesenteric arteries from both cirrhotic and control rats.
CONCLUSION: Enhanced COX-1 expression in cirrhotic rats resulted in elevated PGI2 production which partially contributed to the splanchnic vascular hyporesponsiveness to a vasoconstrictor via the protein kinase A pathway.

BACKGROUND: Although biliary decompression with metallic stenting is the preferred treatment for inoperable bile duct cancer (BDC), maintenance of patency is still unsatisfactory. We tried to assess the effectiveness and safety of external beam radiotherapy (EBRT) for prolonging stent patency in patients having uncovered metallic stents.
METHOD: We retrospectively reviewed 50 patients who received endoscopic stenting, of whom 18 received EBRT (RT group) and 32 did not (non-RT group).
RESULTS: No difference was found in baseline characteristics between the two groups. Although stent patency was longer in the RT group than that in the non-RT group (140.7±51.3 vs 136.4±34.9 days, P=0.94), the difference was not statistically significant. There were a lower rate of stent occlusion (27.8% vs 50.0% of patients, P=0.12) and a longer overall survival (420.1±73.2 vs 269.1±41.7 days, P=0.11) in the RT group than in the non-RT group, and the difference again was not statistically significant. The development of adverse reactions did not differ (55.6% vs 53.1% of patients, P=0.91). There was no serious adverse reaction in both groups (P=0.99).
CONCLUSIONS: EBRT did not significantly improve stent patency in patients with inoperable BDC having uncovered metallic stents. However, EBRT was safe. Future trials with refined protocols for better efficacy are expected.

BACKGROUND: There is an increasing frequency of pancreaticoduodenectomy (PD) and PD with superior mesenteric-portal vein (SMPV) resection in elderly cancer patients. The study aimed to investigate the safety and the survival benefits of PD and PD with SMPV resection in patients under or over 70 years of age.
METHODS: We divided 296 patients who had undergone PD and PD with SMPV resection into two groups according to their ages: under or over 70 years old. The clinical data were compared between the two groups.
RESULTS: Preoperative comorbidity rate was higher in elder patients than in younger patients (P=0.001). The elder patients were more likely to have postoperative complications (P=0.003). Specifically, complications above grade III were more likely to occur in the elderly patients (P=0.030). Multivariable analysis showed that age (adjusted OR=2.557, P=0.015) and hypertension (adjusted OR=2.443, P=0.019) were independent predictors of postoperative complications. There was no significant difference in the mortality rates between the two groups (P=0.885). In the PD with SMPV resection series, elderly patients were more likely to have postoperative complications (P=0.063), but this difference was not statistically significant. There was no difference in the survival rate of patients with pancreatic ductal adenocarcinoma between the two groups. Operation type (PD vs PD with SMPV resection) did not affect the survival of patients.
CONCLUSIONS: Age affects postoperative complication in patients undergoing either PD or PD with SMPV resection. However, extensive experience and advanced perioperative management lower the complication rate to an acceptable limit. Hence it is safe and worthwhile to perform PD for elderly patients. Because of low numbers in the SMPV subset, we could not conclude whether PD with SMPV resection is feasible in elderly patients.

BACKGROUND: Laparoscopic pancreaticoduodenectomy (LPD) is a safe procedure. Oncological safety of LPD is still a matter for debate. This study aimed to compare the oncological outcomes, in terms of adequacy of resection and recurrence rate following LPD and open pancreaticoduodenectomy (OPD).
METHODS: Between November 2005 and April 2009, 12 LPDs (9 ampullary and 3 distal common bile duct tumors) were performed. A cohort of 12 OPDs were matched for age, gender, body mass index (BMI) and American Society of Anesthesiologists (ASA) score and tumor site.
RESULTS: Mean tumor size LPD vs OPD (19.8 vs 19.2 mm, P=0.870). R0 resection was achieved in 9 LPD vs 8 OPD (P=1.000). The mean number of metastatic lymph nodes and total number resected for LPD vs OPD were 1.1 vs 2.1 (P=0.140) and 20.7 vs 18.5 (P=0.534) respectively. Clavien complications grade I/II (5 vs 8), III/IV (2 vs 6) and pancreatic leak (2 vs 1) were statistically not significant (LPD vs OPD). The mean high dependency unit (HDU) stay was longer in OPD (3.7 vs 1.4 days, P<0.001). There were 2 recurrences each in LPD and OPD (log-rank, P=0.983). Overall mortality for LPD vs OPD was 3 vs 6 (log-rank, P=0.283) and recurrence-related mortality was 2 vs 1. There was one death within 30 days in the OPD group secondary to severe sepsis and none in the LPD group.
CONCLUSIONS: Compared to open procedure, LPD achieved a similar rate of R0 resection, lymph node harvest and long-term recurrence for tumors less than 2 cm. Though technically challenging, LPD is safe and does not compromise oncological outcome.

BACKGROUND: Oxidative stress is recognized as a pivotal effector of several pathogenic processes, including acute pancreatitis. Reactive oxygen species not just cause damage on the main cellular components, but also influence the expression of antioxidant system genes. Antioxidant molecules, such as melatonin, could be good candidates for the treatment of this multidimensional disease. The present study was to evaluate the chemopreventive effect of melatonin in a rat model of cerulein-induced acute pancreatitis.
METHODS: Four subcutaneous injections of cerulein (20 µg/kg body weight) were given to Wistar rats at two hours intervals; melatonin was injected intraperitoneally (25 mg/kg body weight) 30 minutes before each injection of cerulein. Lipid peroxidation, protein oxidation (carbonyl groups), total antioxidant status, and glutathione peroxidase activity were determined in pancreatic tissue using commercial kits.
RESULTS: The chemopreventive administration of melatonin caused a reduction in lipid peroxidation and protein oxidation due to injections of cerulein. Additionally, melatonin treatment was also able to revert glutathione peroxidase activity and total antioxidant status near to control levels, suggesting that melatonin could prevent from oxidative phenomena in the pancreas, such as lipid peroxidation and protein oxidation, and could stimulate, directly or indirectly, the expression of antioxidant enzymes.
CONCLUSION: Melatonin, a polyvalent antioxidant, protected the pancreatic damage via the decrease of oxidative stress and increase of the activities of antioxidant enzymes in cerulein-induced acute pancreatitis.