When the graft volume is too small to satisfy the recipient's metabolic demand, the recipient may thus experience small-for-size syndrome (SFSS). Because the occurrence of SFSS is determined by not only the liver graft volume but also a combination of multiple negative factors, the definitions of small-for-size graft (SFSG) and SFSS are different in each institute and at each time. In the clinical setting, surgical inflow modulation and maximizing the graft outflow are keys to overcoming SFSS. Accordingly, relatively smaller-sized grafts can be used with surgical modification and pharmacological manipulation targeting portal circulation and liver graft quality. Therefore, the focus of the SFSG issue is now shifting from how to obtain a larger graft from the living donor to how to manage the use of a smaller graft to save the recipient, considering donor safety to be a priority.

BACKGROUND: Anesthetic practices such as early tracheal extubation facilitate postoperative recovery. Early extubation after liver transplantation has been adopted by some centers in the recent two decades. No universal clinical guidelines are used and questions remain. This review aimed to address the current status of early extubation after liver transplantation.

DATA SOURCES: A literature search of MEDLINE and ISI Web of Knowledge databases was performed using terms such as liver transplantation, early extubation, immediate tracheal extubation, fast tracking or fast track anesthesia and postoperative tracheal extubation. Additional papers were identified by a manual search of the references in the key articles.

RESULTS: Review of the available literature provided an insight into the definition, evolution, advantages and risks of early extubation, and anesthetic techniques that prompt early extubation in liver transplant patients. Early extubation has proved to be feasible and safe in these patients, but the outcomes are still uncertain.

CONCLUSIONS: Early extubation after liver transplantation is feasible, safe and cost-effective in the majority of patients and has been increasingly accepted as an option for conventional postoperative ventilation. Comprehensive and individualized evaluation of the patient's condition before extubation by an experienced anesthesiologist is the cornerstone of success. Understanding of its effect on the outcome remains incomplete. In the future, additional trials are required to establish universal early extubation guidelines and to determine its benefits for patients and practitioners.

BACKGROUND: Parenteral nutrition-associated liver disease (PNALD) has been common in patients who require long-term parenteral nutrition. PNALD develops in 40%-60% of infants on long-term parenteral nutrition compared with 15%-40% of adults on home parenteral nutrition for intestinal failure. The pathogenesis of PNALD is multifactorial and remains unclear. There is no specific treatment. Management strategies for its prevention and treatment depend on an understanding of many risk factors. This review aims to provide an update on the pathogenesis and treatment of this disease. 

DATA SOURCES: A literature search was performed on the MEDLINE and Web of Science databases for articles published up to October 2011, using the keywords:  parenteral nutrition associated liver disease,  intestinal failure associated liver disease, lipid emulsions and fish oil. The available data reported in the relevant literatures were analyzed. 

RESULTS: The literature search provided a huge amount of evidence about the pathogenesis and management strategies on PNALD. Currently, lack of enteral feeding, extended duration of parenteral nutrition, recurrent sepsis, and nutrient deficiency or excess may play important roles in the pathogenesis of PNALD. Recent studies found that phytosterols, present as contaminants in soy-based lipid emulsions, are also an important factor in the pathogenesis. Moreover, the treatment of PNALD is discussed. 

CONCLUSIONS: The use of lipid emulsions, phytosterols in particular, is associated with PNALD. Management strategies for the prevention and treatment of PNALD include consideration of early enteral feeding, the use of specialized lipid emulsions such as fish oil emulsions, and isolated small bowel or combined liver and small bowel transplantation. A greater understanding of the pathogenesis of PNALD has led to promising interventions to prevent and treat this condition. Future work should aim to better understand the mechanisms of PNALD and the long-term outcomes of its treatment.

BACKGROUND: Orthotopic liver transplantation (OLT) is the most effective therapy for liver failure. However, OLT is severely limited by the shortage of liver donors. Bioartificial liver (BAL) shows great potential as an alternative therapy for liver failure. In recent years, progress has been made in BAL regarding genetically engineered cell lines, immortalized human hepatocytes, methods for preserving the phenotype of primary human hepatocytes, and other functional hepatocytes derived from stem cells.

DATA SOURCES: A systematic search of PubMed and ISI Web of Science was performed to identify relevant studies in English language literature using the key words such as liver failure, bioartificial liver, hepatocyte, stem cells, differentiation, and immortalization. More than 200 articles related to the cell sources of hepatocyte in BAL were systematically reviewed.

RESULTS: Methods for preserving the phenotype of primary human hepatocytes have been successfully developed. Many genetically engineered cell lines and immortalized human hepatocytes have also been established. Among these cell lines, the incorporation of BAL with GS-HepG2 cells or alginate-encapsulated HepG2 cells could prolong the survival time and improve pathophysiological parameters in an animal model of liver failure. The cBAL111 cells were evaluated using the AMC-BAL bioreactor, which could eliminate ammonia and lidocaine, and produce albumin. Importantly, BAL loading with HepLi-4 cells could significantly improve the blood biochemical parameters, and prolong the survival time in pigs with liver failure. Other functional hepatocytes differentiated from stem cells, such as human liver progenitor cells, have been successfully achieved.

CONCLUSIONS: Aside from genetically modified liver cell lines and immortalized human hepatocytes, other functional hepatocytes derived from stem cells show great potential as cell sources for BAL. BAL with safe and effective liver cells may be achieved for clinical liver failure in the near future.

BACKGROUND: Although many human inflammatory and autoimmune diseases were previously considered to be mediated by T helper type 1 (Th1) cells, the recently described Th17 cells play dominant roles in several of these diseases. We and others speculated that allograft rejection after organ transplantation may also involve Th17 cells. Episodes of acute rejection occur in 30% of liver transplants. This study aimed to determine the frequency of circulating Th17 cells in patients who had received liver transplants for benign end-stage liver disease and to identify any association between acute rejection episodes and levels of Th17 cells in the peripheral blood. 

METHODS: A prospective study compared Th17 cells from 76 consecutive benign end-stage liver disease patients who had undergone orthotopic liver transplantation from 2007 to 2011 with those from 20 age-matched healthy individuals. Peripheral blood samples were collected at different time points within one year after transplant. Blood samples and liver biopsies were also collected at the diagnosis of acute rejection. Percentages of circulating CD4⁺IL-17⁺ cells were measured by flow cytometry. The transplant patients were classified into two groups: a rejection group consisting of 17 patients who had an episode of acute rejection, and a non-rejection group comprising the remaining 59 patients with no acute rejection episodes. Percentages of circulating Th17 cells were compared between the two groups and controls. 

RESULTS: The levels of circulating CD4⁺IL-17⁺ T cells in the rejection group were higher during acute rejection than those in the non-rejection group (2.56±0.43% versus 1.79±0.44%, P<0.001). The frequency of CD4⁺IL-17⁺ cells in peripheral blood was positively correlated with the rejection activity index (r=0.79, P=0.0002).

CONCLUSION: Circulating Th17 cells may be useful as a surrogate marker for predicting acute rejection in liver transplant recipients.

BACKGROUND: Hepatectomy is the main curative treatment for hepatocellular carcinoma (HCC), but postoperative long-term survival is poor. Preoperative radiological features of HCC displayed by computed tomography or magnetic resonance imaging could serve as additional prognostic factors. This study aimed to identify preoperative radiological features of HCC that may be of prognostic significance in hepatectomy.

METHODS: Ninety-two patients who underwent hepatectomy for HCC were included in this study. Preoperative radiological features including tumor number, size, location (peripheral, middle, central), portal vein invasion, hepatic vein invasion, and presence of pseudo-capsule were analyzed in relation to survival.

RESULTS: With a median follow-up period of 41.7 months, the 1-, 3- and 5-year overall survival rates were 85%, 65% and 58%, respectively. Univariate analysis showed that portal vein invasion and absence of pseudo-capsule were significant prognostic factors for overall survival, while all the examined radiological features were prognostic factors for disease-free survival. Multivariate analysis for overall survival found no significant factor. On multivariate analysis for disease-free survival, patients who had tumors with portal vein invasion had poorer survival with a hazard ratio of 2.26 (95% CI, 1.05-4.91; P=0.038) and patients with single nodular HCC or pseudo-capsulated HCC had better survival with a hazard ratio of 0.50 (95% CI, 0.27-0.94; P=0.032) and 0.38 (95% CI, 0.14-0.99; P=0.048), respectively.

CONCLUSIONS: Demonstrable pseudo-capsule of HCC and solitary HCC on imaging and absence of portal vein invasion are features associated with better disease-free survival after hepatectomy. These features may guide treatment planning for HCC.

BACKGROUND: Alpha-fetoprotein (AFP) is the most established tumor marker of hepatocellular carcinoma (HCC), but one of its limitations is non-specificity. Many studies have demonstrated that alpha-fetoprotein-L3 (AFP-L3) is more specific than AFP in the early diagnosis and prognosis of HCC. However, there is a lack of knowledge about the post-hepatectomy profiles of serum AFP and AFP-L3 values in HCC patients. To identify the profiles after surgical resection of HCC, we analyzed the correlation between the profiles and postoperative HCC recurrence or survival, and evaluated their utility in predicting postoperative therapeutic efficacy and prognosis. 

METHODS: From August 2003 to December 2004, 318 patients with positive serum AFP who had received surgical resections were enrolled in this study. Preoperative and postoperative serum AFP and AFP-L3 levels were measured simultaneously and regularly, and their postoperative profiles during a long-term follow-up were recorded and summarized. 

RESULTS: A high ratio of AFP-L3 to total AFP was shown to correlate with pathologic features of aggressiveness. The overall 1-, 3-, and 5-year recurrence rates of the whole series were 28%, 57%, and 84%, and the overall survival rates were 86%, 61%, and 33%, respectively. The changes of serum AFP and AFP-L3 after hepatectomy for HCC were classified into 3 groups (group A: AFP-L3 undetectable; group B: AFP-L3 <10%; and group C: AFP-L3 >10%). Patients with positive postoperative AFP-L3 had significantly earlier recurrence than those with negative results. The overall survival was significantly shorter in the positive groups than in the groups negative for postoperative AFP-L3.

CONCLUSION: Post-hepatectomy changes in serum AFP and AFP-L3 levels occurred in three distinct patterns, which were closely correlated with HCC recurrence and patient survival with different prognostic values.

BACKGROUND: Hepatocyte nuclear factor 4 alpha (HNF4α) plays an important role in regulating cytokine-induced inflammatory responses. This study aimed to investigate the role of HNF4α in the development of fulminant hepatic failure (FHF) induced by lipopolysaccharide/D-galactosamine (LPS/D-GalN).
METHODS: The FHF model was induced by simultaneous intraperitoneal injection of LPS/D-GalN in mice. Three days prior to LPS/D-GalN administration, HNF4α short-hairpin interfering RNA expression plasmid or physiological saline was injected via the tail vein with a hydrodynamics-based procedure. The degree of hepatic damage and cumulative survival rate were subsequently assessed.
RESULTS: The expression of HNF4α was increased in the early stage after LPS/D-GalN administration. Inhibiting the expression of HNF4α reduced serum levels of alanine aminotransferase and aspartate aminotransferase, alleviated histological injury, and improved the survival of mice with FHF. In addition, both serum and hepatic tumor necrosis factor alpha expression were suppressed when HNF4α expression was inhibited in mice with FHF.
CONCLUSION: Inhibiting HNF4α expression protects mice from FHF induced by LPS/D-GalN, but the exact mechanism behind this needs further investigation.

A joint liver cancer center has been launched by signing a cooperative agreement between Cleveland Clinic at Cleveland, Ohio, USA and the First Affiliated Hospital, Zhejiang University on November 16, 2012 at Hangzhou, China. In recent years, a series of cooperative projects have been carried out between medical centers of other countries and the First Affiliated Hospital. This endeavor facilitates international cooperation between the First Affiliated Hospital and other oversea centers in faculty training and basic research in liver cancer.

Liver Transplantation (in Chinese), revised edition, edited by Professor Shu-Sen Zheng and prefaced by Professor Guo-Wei Sang, has just been published. The revised edition is mainly based on the clinical practice of the Liver Transplant Center, the First Affiliated Hospital, Zhejiang University and the experience from other units with reference to the literature in the recent decade.
        The book is composed of 38 chapters, including the anatomic physiology of the liver, indications for liver transplantation, surgical skills, perioperative treatment and basic research of liver transplantation. In addition, it also introduces the latest progress in living donor liver transplantation, split liver transplantation, and selection of recipients (according to the Hangzhou criteria).
        For subscription, please contact local agency of China Xinhua Bookstore or Medical Bookstore. Telephone for mail order: 86-10-65264830, or 67605754.

BACKGROUND: Gastric bypass is a widespread bariatric procedure that carries a high incidence of gallstone formation postoperatively. Controversy exists regarding the importance and consequences of gallstones in these patients. There are surgeons who consider gallstone-related complications after gastric bypass important enough to require routine removal of the gallbladder during gastric bypass (prophylactic cholecystectomy). However, this can lead to increased costs and risks. This study aimed to identify complications related to cholelithiasis after Roux-en-Y gastric bypass (RYGBP).
METHODS: This is a prospective observational study of 40 morbidly obese patients free of gallbladder disease. The patients underwent open RYGBP at a public hospital in Brazil from February to October 2007. They were followed up clinically and ultrasonographically at 6 months and 1, 2, and 3 years after surgery. Of the patients, 38 patients were followed up for 3 years.
RESULTS: Eleven patients (28.9%) developed cholelithiasis, four (10.5%) experienced biliary pain, and 2 suffered from acute biliary pancreatitis (5.3%). These patients had their gallbladders removed laparoscopically. No patient presented with acute cholecystitis, choledocholithiasis, or bile duct dilation during the follow-up period. There were no deaths.
CONCLUSIONS: Gallstone-related complications after RYGBP were relatively common. Some of these complications, like acute pancreatitis, are known to have potentially severe outcomes. It seems reasonable to perform cholecystectomy during gastric bypass in the presence of cholelithiasis or after this procedure if gallstones develop.

BACKGROUND: For palliative treatment of the obstructive jaundice associated with unresectable hepatocellular carcinoma (HCC), percutaneous transhepatic biliary drainage (PTBD) or endoscopic retrograde biliary drainage (ERBD) has been performed. PTBD is preferred as an initial procedure. Little is known about the better option for patients with obstructive jaundice caused by unresectable HCC.
METHODS:  Sixty patients who had received ERBD or PTBD for the palliative treatment of obstructive jaundice caused by unresectable HCC between January 2006 and May 2010 were included in this retrospective study. Successful drainage, drainage patency, and the overall survival of patients were evaluated.
RESULTS: Univariate analysis revealed that the overall frequency of successful drainage was higher in the ERBD group (22/29, 75.9%) than in the PTBD group (15/31, 48.4%) (P=0.029); but multivariate analysis showed marginal significance (P=0.057). The duration of drainage patency was longer in the ERBD group than in the PTBD group (82 vs 37 days, respectively, P=0.020). Regardless of what procedure was performed, the median survival time of patients who had a successful drainage was much longer than that of the patients who did not have a successful drainage (143 vs 38 days, respectively, P<0.001).
CONCLUSION: Besides PTBD, ERBD may be used as the initial treatment option to improve obstructive jaundice in patients with unresectable HCC if there is a longer duration of drainage patency after a successful drainage.

BACKGROUND: Endoscopic biliary stent placement during the procedure of endoscopic retrograde cholangiopancreatography (ERCP) is preferred to provide biliary drainage for unresectable malignant biliary obstruction. There is considerable controversy over the use of endoscopic sphincterotomy (ES) prior to stent placement. This study aimed to determine whether ES before intraductal self-expanding metal stent (SEMS) placement affects the clinical outcome and complications in patients with proximal malignant obstructive biliary diseases.
METHODS: In a prospective randomized controlled trial, 82 patients with inoperable malignant biliary strictures were randomly assigned to biliary stenting groups with or without ES. Resolution of jaundice and the incidence of complications including acute cholangitis, pancreatitis and stent occlusion within 6 months were evaluated.
RESULTS: SEMSs were successfully deployed in all patients, resulting in clinical and biochemical improvement of obstructive symptoms in both groups. The incidence of cholangitis was higher in the ES group than in the non-ES group (58.5% vs 31.7%, P=0.015). The interval between stent placement and the first acute cholangitis was much shorter in the ES group than in the non-ES group (P=0.024). The use of ES increased the incidence of cholangitis (P=0.004, risk ratio, 8.196). The rate of post-ERCP pancreatitis after stent placement was greater in the non-ES group than in the ES group (31.7% vs 9.8%, P=0.014). No significant differences were found in the rate of restenosis and the mortality rate between the two groups.
CONCLUSIONS: ES prior to intraductal SEMS placement was associated with an increased incidence of acute cholangitis. ES should be carefully evaluated prior to its use in patients with proximal malignant obstructive biliary diseases.

BACKGROUND: Acute cholangitis varies from mild to severe form. Acute suppurative cholangitis (ASC), the severe form of acute cholangitis, is a fatal disease and requires urgent biliary decompression. Which patients are at a high risk of ASC and need emergency drainage is still unclear. The present study aimed to identify the factors for determining early-stage ASC and distinguishing ASC from acute cholangitis.
METHODS:  We analyzed 359 consecutive patients with acute cholangitis who had been admitted to the First Affiliated Hospital, Zhejiang University School of Medicine from January 2004 to May 2011. Emergency endoscopic retrograde cholangiopancreatography (ERCP) was carried out in all patients to decompress or clear the stones by experienced endoscopists. Clinical and therapeutic data were collected, and univariate and multivariate analyses were performed to identify the potential risk factors of ASC.
RESULTS: Of the 359 patients, 1 was excluded because of failure of ERCP drainage. Of the remaining 358 patients with an average age of 62.7 years (range 17-90), 162 were diagnosed with ASC, and 196 with non-ASC. ENBD catheters were placed in 343 patients (95.8%), of whom 182 patients had stones removed at the same time, and plastic stent was placed in 25 patients (7.0%). Clinical conditions were improved quickly after emergency biliary drainage in all patients. Complications were identified in 11 patients (3.1%): mild pancreatitis occurred in 8 patients and hemorrhage in 3 patients. There was no mortality. Univariate analysis showed that several variables were associated with ASC: age, fever, decreased urine output, hypotension, tachycardia, abnormal white blood cell count (WBC), low platelet, high C reactive protein (CRP), and duration of the disease. Multivariate analysis revealed that advanced age, hypotension, abnormal WBC, high CRP, and duration of the disease were independent risk factors for ASC.
CONCLUSIONS: This study demonstrates that advanced age, hypotension, abnormal WBC, high CRP, and long duration of antibiotic therapy are significantly associated with ASC. We recommend decompression by ERCP should be carried out in patients as early as possible.

BACKGROUND: High-intensity focused ultrasound (HIFU) is a non-invasive method of solid tissue ablation therapy. However, only a few studies have reported the effect of HIFU for unresectable pancreatic cancer. This study aimed to evaluate the clinical benefits, survival time and complications associated with the use of HIFU ablation in patients with unresectable pancreatic cancer.
METHODS: Twenty-five patients with unresectable pancreatic cancer were enrolled in our study. All patients received HIFU therapy for tumors at least once. The therapeutic effects of HIFU was evaluated in terms of Karnofsky performance status (KPS) scores, pain relief, serum CA19-9, and imaging by B-US and CT before and after the therapy. We also recorded median overall survival time and complications caused by the treatment.
RESULTS: In the 25 patients, KPS scores were above 60, and increased KPS was observed in 23 patients after treatment. Pain relief occurred in 23 patients. Serum CA19-9 levels were significantly reduced one month after HIFU treatment and became negative in 5 patients. B-US revealed enhanced tumor echogenicity in 13 patients and decreased tumor blood supply in 9. Tumor necrosis was confirmed by CT in 8 patients one month after HIFU treatment. The median overall survival time was 10 months, and the 1-year survival rate was 42%. No severe complications were observed after HIFU treatment.
CONCLUSION: HIFU can effectively relieve pain, increase KPS, decrease tumor growth and prolong the survival time of patients with unresectable pancreatic cancer.