BACKGROUND: Hilar cholangiocarcinoma (HC) is an adenocarcinoma of the extrahepatic biliary tree arising from the main left or right hepatic ducts or their confluence. This tumor is still considered to be difficult to treat or to cure.
DATA SOURCES: We reviewed the medical literature on HC. Relevant and updated information on this tumor was analyzed in a concise and easy-to-read manner. The article is not intended to be a systematic review, but an extensive search was conducted on PubMed and MEDLINE using the keywords "hilar cholangiocarcinoma" and "Klatskin tumor" until July 2011.
RESULTS: The selection and the timing of management options for patients with HC are determined by the degree of certainty of the diagnosis, the general condition of the patients, the underlying liver function and the stage of the disease. Current treatment of HC can be divided into curative and palliative treatment. For the curative treatment, local excision should only be used on small tumors which are confined to the bile duct wall and Bismuth I papillary carcinoma. Partial hepatectomy should be combined with caudate lobe resection and porta-hepatis lymph node dissection. The results of these major resections can be improved with portal vein embolization, and staging laparoscopy and laparoscopic ultrasound. The role of preoperative biliary drainage is controversial. Autotransplantation for HC gave disappointing results while the Mayo Protocol of chemoradiation for selecting patients with unresectable HC for orthotopic liver transplantation has been widely accepted. Palliative treatment included bypass surgery, endoscopic or percutaneous stenting, photodynamic therapy, intraluminal brachytherapy, and external radiation and systemic therapy.
CONCLUSIONS: Adequate surgery with R0 resection should be the main goal of treatment. For patients with unresectable HC, treatment aims to improve the quality and quantity of their survival.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD), especially nonalcoholic steatohepatitis, is a recognized risk factor for hepatocellular carcinoma (HCC). However, detailed analysis of the clinical features in patients with NAFLD and their association with HCC is lacking. This study aimed to update the clinical features of patients with NAFLD-associated HCC.
DATA SOURCES: The clinical data of patients with NAFLD-associated HCC from 25 studies published between 1990 and 2010 in the PubMed database were comprehensively reviewed.
RESULTS: In a total of 169 patients with NAFLD-associated HCC, 72.8% were male. The median age at abnormal liver function tests and diagnosis of NAFLD and HCC was 60, 64 and 67 years, respectively. Most patients were obese (75%) and diabetic (59.8%), 32.3% had dyslipidemia, and 53% had hypertension. Nearly all patients (98.6%, 71/72) were complicated with at least one metabolic disorder. The majority (76%) of the HCC patients had a solitary tumor nodule, with the tumor size ranging from 0.8 to 20 cm in diameter (mean 3.4 cm). Most (61.1%) of the patients had moderately-differentiated HCC. In 40.2% of the patients, HCC occurred in the absence of cirrhosis. Among 130 patients, 57.7% underwent hepatectomy and 14.6% received liver transplantation. The mean follow-up of the treated patients for 25 months showed that 32.4% (24/74) died and 18.8% (9/48) had recurrence.
CONCLUSIONS: Patients with NAFLD-associated HCC are usually accompanied with metabolic disorders. Regular surveillance in patients with NAFLD for HCC is necessary, especially for elderly men with metabolic syndrome.

BACKGROUND: Liver transplantation can lead to the development of posttraumatic stress disorder (PTSD), but the risk factors associated with this progression are not well understood. To study this syndrome in adult liver transplant recipients, a cross-sectional investigation of 296 recipients at our hospital was carried out between January and June 2010.
METHODS: Study participants completed two questionnaires [a PTSD self-rating scale (PTSD-SS) and a validated Chinese version of the Medical Outcomes Study Short Form-36 (SF-36)]. Clinical and demographic data were collected from the records of the Chinese Liver Transplant Registry and via questionnaires.
RESULTS: The prevalence of full PTSD and partial PTSD (that met the criteria for 2 of the 3 symptom clusters) was 3.7% and 5.4%, respectively, for all transplant recipients. Significant differences between the recipients with no PTSD, partial PTSD, and full PTSD were found in all SF-36 domains except for physical functioning (P=0.466). In general, domain scores were the highest in the recipients who did not meet the criteria for PTSD and the lowest in the recipients who met the criteria for full PTSD. Greater severity of posttraumatic stress symptoms was correlated with poorer quality of life, especially in the bodily pain (P=0.004), social functioning (P=0.001), role-emotional (P=0.048), and mental health (P<0.001) domains. The model for end-stage liver disease (MELD) scores, complications, and educational status were identified by multiple regression analysis as risk factors for developing PTSD.
CONCLUSIONS: PTSD occurred after liver transplantation and was significantly associated with decreased quality of life. Higher MELD scores and complications after transplantation were risk factors that contributed to PTSD, and higher education was a protective factor.

BACKGROUND: Marked hemodynamic alteration, commonly referred to as postreperfusion syndrome (PRS), often occurs after revascularization of the donor organ during orthotopic liver transplantation (OLT) and is associated with poor outcomes. This study aimed to investigate the incidence, predictive factors and clinical outcomes of PRS in Chinese patients following OLT at a liver transplantation center in China.
METHODS: Over a 5-year period, 330 consecutive patients who had undergone OLT for hepatocellular carcinoma or cirrhosis were included in this retrospective study. PRS was defined as a >30% decrease in the mean arterial pressure compared with that before revascularization for more than 1 minute during the first 5 minutes of graft reperfusion. The patients were divided into 2 groups according to the development of PRS: group 1 (patients with PRS, n=56) and group 2 (patients without PRS, n=274). The demographic characteristics, operative and postoperative courses, and outcomes of the patients were analyzed using SPSS version 18.0.
RESULTS: Multivariate regression analysis showed that left ventricular diastolic dysfunction determined by echocardiography and prolonged cold ischemia time were the independent risk factors for PRS. More patients in group 1 showed postoperative renal dysfunction than those in group 2 (19.23% vs 8.4%). Moreover, patients in group 1 also had higher intraoperative (7.14% vs 0%) and postoperative mortalities (26.92% vs 12.04%).
CONCLUSION: Left ventricular diastolic dysfunction and prolonged cold ischemia time contribute to a high incidence of PRS, which is associated with adverse outcomes in Chinese patients following OLT.

BACKGROUND: Liver transplantation is one of the most effective therapeutic options for patients with end-stage liver diseases, and gut microbiota is actively involved in potential infections in pretransplant and posttransplant patients. However, the diversity of gut microbiota and its relationship with the immune parameter of liver transplantation recipients are not well understood.
METHODS: We collected fresh feces and blood samples from 190 participants in China from November 2004 to May 2008, including 28 healthy volunteers, 51 cirrhotic patients and 111 liver-transplanted patients. Six interesting gut bacteria, plasma endotoxin, serum cytokines (i.e., tumor necrosis factor alpha and interleukin-6) and fecal secretory IgA (SIgA) were investigated by real-time quantitative PCR, chromogenic limulus amoebocyte assay, sandwich-type enzyme-linked immunosorbent assay and radioimmunoassay, respectively.
RESULTS: All Eubacteria, Bifidobacterium spp., Faecalibacterium prausnitzii and Lactobacillus spp. were significantly lower in the liver transplantation recipients while Enterobacteriaceae and Enterococcus spp. were significantly higher (P<0.05). Except for Enterococcus spp., other bacteria showed a tendency to restore to normal level along with the time after liver transplantation. Plasma endotoxin, interleukin-6 and fecal SIgA in cirrhotic patients increased significantly, but not in liver transplantation recipients. Plasma endotoxin and interleukin-6 were negatively correlated with all Eubacteria and the Bacteroides-Prevotella group, while tumor necrosis factor alpha was not significantly correlated with these six gut bacteria in cirrhotic patients.
CONCLUSIONS: Our study demonstrates that abundant gut bacteria were altered significantly in both cirrhotic and liver transplantation patients, while plasma endotoxin and interleukin-6 increased remarkably in cirrhotic patients, showing significant correlations with gut microbiota. Interestingly, our data show a tendency for these gut bacteria to restore to normal levels in liver transplantation recipients.

BACKGROUND: Progression of hepatocellular carcinoma (HCC) often leads to vascular invasion and intrahepatic metastasis, which correlate with recurrence after surgical treatment and poor prognosis. HCC may be an unusual cancer affected by continuous inflammation that can lead to consistent upregulation of transforming growth factor-β (TGF-β). Chronic inflammation shifts hepatocytic TGF-β signaling from the tumor-suppressive pSmad3C pathway to the oncogenic pSmad3L pathway. In this study, we investigated the functional roles of Smad3 and its phosphoisoforms in the progression of HCC.
METHODS: Tumor tissue microarrays of samples from 272 HCC patients who underwent curative surgical resection were used to detect the expression of Smad3, Smad4, pSmad3C (S423/425), pSmad3L (T179), pSmad3L (S204), and pSmad3L (S213). Disease-specific death was defined as 1) tumor occupying more than 80% of the liver, 2) portal venous tumor thrombus (PVTT) proximal to the second bifurcation, 3) obstructive jaundice due to tumor, 4) distant metastases, or 5) variceal hemorrhage with PVTT proximal to the first bifurcation. At the time of analysis, tumor recurrence was detected in 184 (67.6%) patients, and 96 (35.3%) had died of HCC.
RESULTS: Nuclear and cytoplasmic localization of Smad3, and nuclear localization of Smad4 were observed in 18.0%, 9.9%, and 9.2% of HCCs, respectively. The rates of Smad3 phosphoisoform-immunoreactive HCC varied according to the location of phosphorylation: pSmad3C (S423/425) 8.1%, pSmad3L (T179) 2.6%, pSmad3L (S204) 2.2%, and pSmad3L (S213) 10.3%. Multivariate analyses revealed that pSmad3C (S423/425) (P=0.022) was an independent predictor of longer recurrence-free survival. pSmad3L (S213) (P=0.006), intrahepatic metastasis, multicentric occurrence, and liver cirrhosis were independent predictors of shorter recurrence-free survival. Cytoplasmic Smad3 (P=0.006), larger tumor size, and intrahepatic metastasis were independent predictors of shorter disease-specific survival. Only pSmad3L (S213) did not show an unfavorable influence on recurrence-free survival (P=0.331) on univariate analysis.
CONCLUSIONS: pSmad3C (S423/425), pSmad3L (S213), and Smad3 may be predictors of prognosis in HCC patients after curative hepatectomy. pSmad3C (S423/425) and pSmad3L (S213) may be used as immunohistochemical biomarkers to identify patients with a high risk of recurrence.

BACKGROUND: Small-for-size syndrome is a widely recognized clinical complication after living donor liver transplantation or extended hepatectomy due to inadequate liver mass. The purpose of this study was to investigate the role of splenectomy in rats after massive hepatectomy, a surrogate model of small-for-size graft.
METHODS: Rats were divided into eight groups, each with 20 animals: 50% hepatectomy (50% Hx), 50% hepatectomy+splenectomy (50% Hx+Sp), 60% Hx, 60% Hx+Sp, 70% Hx, 70% Hx+Sp, 90% Hx and 90% Hx+Sp. The following parameters were evaluated: liver function tests (ALT, AST and TBIL), liver regeneration ratio, DNA synthesis, proliferation cell nuclear antigen, hepatic oxygen delivery (HDO2) and hepatic oxygen consumption (HVO2).
RESULTS: The liver regeneration ratio was enhanced in the Hx+Sp groups (P<0.05). In addition, compared with the Hx groups, the Hx+Sp groups had better liver functions (P<0.05). DNA synthesis and proliferation cell nuclear antigen were also increased in the Hx+Sp groups compared with the Hx groups (P<0.05). Furthermore, in the Hx+Sp groups, HDO2 and HVO2 were increased over those in the Hx groups (P<0.05), and were positively correlated with the liver regeneration ratio.
CONCLUSIONS: Splenectomy significantly improved liver function, and enhanced DNA synthesis and proliferation cell nuclear antigen after massive hepatectomy in rats. This operation could be mediated through increased HDO2 and HVO2, which facilitate liver regeneration.

BACKGROUND: Stem cell transplantation provides a theoretical approach for liver regeneration medicine; it may promote liver regeneration and self-repair. However, the transplantation of bone marrow-mesenchymal stem cells expanded ex vivo as a therapy for liver disease has rarely been investigated. This study aimed to explore whether bone marrow stem cells expanded ex vivo home to the liver and foster hepatic recovery after CCl4 injury.
METHODS: Bone marrow cells from BALB/c mice were expanded ex vivo by multiple-passage cultivation, characterized by cytoflow immunofluorescence, and pre-labeled with PKH26 before intravenous infusion into animals treated with CCl4. The integration of bone marrow cells into the liver was examined microscopically, and plasma hepatic enzymes were determined biochemically.
RESULTS: Cultured bone marrow cells exhibited antigenic profiles comparable to those of primary medullary stem cells. Double immunofluorescence showed colocalization of these cells with proliferative activity and albumin expression in the liver of CCl4-treated mice. Densitometry showed increased in situ cell proliferation (50±14 vs 20±3 cells/high-power field, P<0.05) and albumin expression (149±25 vs 20±5 cells/high-power field, P<0.05) in the liver, as well as reduced serum aminotransferase levels (P<0.05) and better survival rates (P<0.05) in animals receiving cultured bone marrow cells relative to controls.
CONCLUSIONS: Ex vivo-expanded bone marrow cells are capable of relocating to and proliferating in the chemically-injured liver. Transplantation of these pluripotent stem cells appears to improve serum indices of liver function and survival rate in mice after CCl4-induced hepatic damage.

BACKGROUND: Portal hyperperfusion in the small-for-size (SFS) liver can threaten survival of rabbits. Therefore, it is important to understand the hemodynamic changes in the SFS liver.
METHODS: Twenty rabbits were divided into two groups: a control group and a modulation group. The control group underwent an extended hepatectomy. The modulation group underwent the same procedure plus splenectomy to reduce portal blood flow. CT perfusion examinations were performed on all rabbits before and after operation. Perfusion parameter values, especially portal vein perfusion (PVP), were analyzed.
RESULTS: PVP in the modulation group was lower than in the control group after operation (P=0.002). In the control group, postoperative PVP increased by 193.7±55.1% compared with preoperative PVP. A weak correlation was found between the increased percentage of PVP and resected liver-to-body weight ratio (RLBWR) (r=0.465, P=0.033). In the modulation group, postoperative PVP increased by 101.4±32.5%. No correlation was found between the increased percentage of PVP and RLBWR (r=0.167, P=0.644). Correlations were found between PVP and serum alanine aminotransferase, aspartate aminotransferase, and total bilirubin after surgery (P<0.05).
CONCLUSION: We successfully evaluated the characteristics of hemodynamic changes as well as the effects of splenectomy in the SFS liver in rabbits by the CT technique.

BACKGROUND: The traditional hand-sewn Roux-en-Y choledochojejunostomy is technically complicated, and the incidence of postoperative complications has remained high. A set of novel magnetic compressive anastomats was introduced to facilitate choledochojejunostomy and improve the prognosis of patients.
METHODS: After ligating the common bile duct for 7 days, 16 dogs were randomly divided into two groups (n=8 per group). Anastomats were used in the study group, and the traditional hand-sewn method was used in the control group for standard Roux-en-Y choledochojejunostomy. We compared the operation time, incidence of complications, gross appearance, and pathological disparity in stoma between the two groups in 1-month and 3-month follow-up examinations.
RESULTS: The time spent on constructing the anastomosis for the study group was significantly shortened. Although no anastomotic stenosis occurred in the two groups, the narrowing rate of biliary-enteric anastomosis was much higher in the control group. There was one case of bile leakage in the control group, whereas no bile leakage occurred in the study group. A smoother surface, an improved layer apposition, and a lower local inflammatory response were identified in the anastomosis of the study group.
CONCLUSION: The structures of the novel magnetic compressive anastomats are simple, and they are time-saving, safe and efficient for performing Roux-en-Y choledochojejunostomy procedures in a canine model of obstructive jaundice.

BACKGROUND: After pancreaticoduodenectomy, the incidence of postoperative pancreatic fistula remains high, especially in patients with "soft" pancreatic tissue remnants. No "gold standard" surgical technique for pancreaticoenteric anastomosis
has been established. This study aimed to compare the postoperative morbidity and mortality of pancreaticogastrostomy and pancreaticojejunostomy for "soft" pancreatic tissue remnants using modified mattress sutures.
METHODS: Seventy-five patients who had undergone pancreaticogastrostomy and 75 who had undergone pancreaticojejunostomy after pancreaticoduodenectomy between 2002 and 2008 were retrospectively compared using matched-pair analysis. A modified mattress suture technique was used for the pancreaticoenteric anastomosis. Patients with an underlying "hard" pancreatic tissue remnant, as in chronic pancreatitis, were excluded. Both groups were homogeneous for age, gender, and underlying disease. Postoperative morbidity, mortality, and preoperative and operative data were analyzed.
RESULTS: There were no significant differences between the groups for the incidence of postoperative pancreatic fistula (10.7% in both). Postoperative morbidity and mortality, median operation time, median length of hospital stay, intraoperative blood loss, and the amount of intraoperatively transfused erythrocyte concentrates also did not significantly differ between the groups. Patient age >65 years (P=0.017), operation time >350 minutes (P=0.001), and intraoperative transfusion of erythrocyte concentrates (P=0.038) were identified as risk factors for postoperative morbidity.
CONCLUSIONS: Our results showed no significant differences between the groups in the pancreaticogastrostomy and pancreaticojejunostomy anastomosis techniques using mattress sutures for "soft" pancreatic tissue remnants. In our experience, the mattress sutures are safe and simple to use, and pancreaticogastrostomy in particular is feasible and easy to learn, with good endoscopic accessibility to the anastomosis region. However, the location of the anastomosis and the surgical technique need to be individually evaluated to further reduce the incidence of postoperative pancreatic fistula.

BACKGROUND: Hypertriglyceridemia is an unusual cause of acute pancreatitis and sometimes considered to be an epiphenomenon. This study aimed to investigate the clinical and analytical features and the APOE genotypes in patients with acute pancreatitis and severe hypertriglyceridemia.
METHODS: We undertook a one-year, prospective study of patients with acute pancreatitis whose first laboratory analysis on admission to the emergency department included measurement of serum triglycerides. The APOE genotype was determined and the patients answered an established questionnaire within the first 24 hours concerning their alcohol consumption, the presence of co-morbidities and any medications being taken. The patients progression, etiological diagnosis, hospital stay and clinical and radiological severity were all recorded.
RESULTS: Hypertriglyceridemia was responsible for 7 of 133 cases of pancreatitis (5%); the remaining cases were of biliary (53%), idiopathic (26%), alcoholic (11%) or other (5%) origin. Compared with these remaining cases, the patients with hypertriglyceridemia were significantly younger, had more relapses, and more often had diabetes mellitus. They usually consumed alcohol or consumed it excessively on the days before admission. Also, the ε4 allele of the APOE gene was more common in this group (P<0.05).
CONCLUSION: One of 20 episodes of acute pancreatitis is caused by hypertriglyceridemia and it is linked to genetic (ε4 allele) and comorbid factors such as diabetes and, especially, alcohol consumption.

BACKGROUND: Pancreatic fistula (PF) remains the most challenging complication in pancreatic surgery, yet few published studies have focused on the risk factors for postoperative PF in patients undergoing surgery for insulinomas.
METHODS: From January 1990 to February 2010, a total of 292 patients with insulinomas underwent surgery at Peking Union Medical College Hospital. Demographic data, intraoperative procedures, and postoperative data were collected. Particular attention was paid to variables associated with PF as defined by the International Study Group of Pancreatic Fistula (ISGPF). Univariate and multivariate analyses were used to identify possible risk factors for PF. RESULTS: PF was found in 132 (45.2%) patients, of whom 90 were classified into ISGPF grade A, 33 grade B, and 9 grade C. Multivariate analysis showed that male patients (OR=2.56; P=0.007) and operative time >180 minutes (OR=3.756; P<0.0001) were independent risk factors for clinical PF. Pancreatic resection with stapler was a protective factor for both total PF (OR=0.022; P=0.010) and clinical PF (OR=0.097; P=0.007).
CONCLUSIONS: Male gender and operative time >180 minutes were independent risk factors for clinical PF, while pancreatic resection with a stapler was a protective factor. Whether body mass index (BMI) and other variables during operation are risk factors of PF needs further study.

BACKGROUND: Brunner s gland adenoma (BGA) is an unusual benign neoplasm arising from Brunner s glands in the duodenum. When symptomatic it presents either with duodenal obstruction or bleeding. However, pancreatitis secondary to ampullary obstruction from a BGA is very rare.
METHODS: A 23-year-old female presented with recurrent episodes of "idiopathic" pancreatitis. She was extensively investigated and was found to have a large polypoid BGA, intermittently obstructing the ampulla. This created a ball-valve effect causing secondary intermittent obstruction of the pancreatic duct resulting in pancreatitis. The condition was cured surgically, through transduodenal excision of the BGA. We reviewed the surgical literature pertaining to these unusual and similar causes of obstructive pancreatitis, not related to gallstones.
RESULTS: BGA of the duodenum is a rare cause of pancreatitis. Extensive investigations should be carried out in all cases of unexplained pancreatitis before classifying the condition as "idiopathic". Discovery of a lesion of this nature gives an opportunity to provide a permanent surgical cure.
CONCLUSIONS: BGA adds an unusual etiology for pancreatitis. All patients with pancreatitis should undergo extensive investigations before being termed "idiopathic". Surgical excision of the BGA provides a definitive curative treatment for the adenoma and pancreatitis.