BACKGROUND: Laparoscopic splenectomy is considered the gold standard for resecting normal-to-moderately bigger spleens in benign conditions, and in addition could be tried for patients with malignant splenic disorders. However, the safety of laparoscopic splenectomy in patients with hypersplenism is not well-known. This study aimed to investigate the efficacy and safety of laparoscopic splenectomy for patients with hypersplenism secondary to liver cirrhosis by comparing with the open splenectomy.
DATA SOURCES: Several databases were searched to identify comparative studies fulfilling the predefined selection criteria from January 2000 to June 2015. The subsequent key words were utilized for browsing “laparoscopy” or “laparoscopic”, “open”, “splenectomy”, and “liver cirrhosis”. Studies evaluating laparoscopic and open splenectomy for patients with liver cirrhosis were incorporated. Two evaluators personally strained the title and abstract of each publication. Citations with contemplated compliance within our eligibility criteria underwent compressed review. Meta-analysis was carried out according to the recommendations of the Cochrane Collaboration software (review manager 5.1).
RESULTS: Seven studies containing 509 patients were included. Compared with the open splenectomy group, patients in the laparoscopic splenectomy group had significantly less intraoperative blood loss (MD=210.30; 95% CI: 11.28-409.32; P=0.04), longer operative time (MD=-31.58; 95% CI: -53.34--9.82; P=0.004), shorter duration of postoperative hospital stay (MD=3.41; 95% CI: 2.39-4.43; P<0.01), lower incidence of postoperative complications (RR=1.34; 95% CI: 0.88-2.01; P=0.17), and decreased liver damage [ALT (MD=8.52; 95% CI: 0.19- 16.85; P=0.05) and total bilirubin (MD=5.12; 95% CI: 0.37-9.87; P=0.03)].
CONCLUSION: Hypersplenism secondary to cirrhosis and portal hypertension should not be a contraindication for laparoscopic splenectomy.

BACKGROUND: Four different sizes (4, 5, 8 and 10 cm in diameter) can be found in the literature to categorize a liver hemangioma as giant. The present review aims to clarify the appropriateness of the size category “giant” for liver hemangioma.
DATA SOURCES: We reviewed the reports on the categorization of hemangioma published between 1970 and 2014. The number of hemangiomas, size criteria, mean and range of hemangioma sizes, and number of asymptomatic and symptomatic patients were investigated in patients aged over 18 years. Liver hemangiomas were divided into four groups: <5.0 cm, 5.0-9.9 cm, 10.0-14.9 cm and ≥15.0 cm in diameter. Inclusion criteria were noted in 34 articles involving 1972 (43.0%) hemangiomas (>4.0 cm).
RESULTS: The patients were divided into the following groups: 154 patients (30.0%) with hemangiomas less than 5.0 cm in diameter (small), 182 (35.5%) between 5.0 cm and 9.9 cm (large), 75 (14.6%) between 10.0 and 14.9 cm (giant), and 102 (19.9%) more than 15.0 cm (enormous). There were 786 (39.9%) asymptomatic patients and 791 (40.1%) symptomatic patients. Indications for surgery related to symptoms were reported in only 75 (3.8%) patients. Operations including 137 non-anatomical resection (12.9%) and 469 enucleation (44.1%) were unclearly related to size and symptoms.
CONCLUSIONS: The term “giant” seems to be justified for liver hemangiomas with a diameter of 10 cm. Hemangiomas categorized as “giant” are not indicated for surgery. Surgery should be performed only when other symptoms are apparent.

BACKGROUND: Renal cell carcinoma (RCC) is a common cancer, but pancreatic metastasis of RCC is unusual. Because of the rarity and peculiarity, pancreatic lesions from RCC metastasis were described mostly in case reports which highlight the importance of a systematic analysis of this clinical condition.
DATA SOURCES: Data of 7 patients with pancreatic metastasis of RCC treated in the Peking Union Medical College Hospital were extracted and 193 similar patients reported in the past 10 years from the literature were analyzed. Epidemiological, pathological and follow-up information were investigated. Potential prognostic factors were compared with corresponding data reported 10 years ago.
RESULTS: Multivariate Cox regression showed that asymptomatic metastasis and surgical procedure were independent factors associated with better survival. Compared with the data reported 10 years ago, follow-up of RCC patients has been emphasized in recent years, and atypical surgery is frequently used since it has similar effect as typical surgery on tumor resection while it is able to preserve more pancreatic function.
CONCLUSION: Surgical treatment should be an option as long as the pancreatic metastasis of RCC is resectable.

BACKGROUND: Sarcopenia and non-alcoholic fatty liver disease (NAFLD) share similar pathophysiological mechanisms, and the relationship between sarcopenia and NAFLD has been recently investigated. The study investigated whether low skeletal muscle mass is differentially associated with NAFLD by gender in Korean adults.
METHODS: We conducted a cross-sectional analysis of the data from the Fifth Korea National Health and Nutrition Examination Survey. The skeletal muscle index (SMI) was obtained by the appendicular skeletal muscle mass divided by the weight. NAFLD was defined as a fatty liver index (FLI) ≥60 in the absence of other chronic liver disease.
RESULTS: Among the included subjects, 18.3% (SE: 1.4%) in men and 7.0% (SE: 0.7%) in women were classified as having FLI-defined NAFLD. Most of the risk factors for FLI-defined NAFLD showed a significant negative correlation with the SMI in both genders. Multiple logistic regression analysis showed that low SMI was associated with FLI-defined NAFLD, independent of other metabolic and lifestyle parameters in both genders [males: odds ratio (OR)=1.35; 95% confidence interval (CI): 1.17-1.54; females: OR=1.36; 95% CI: 1.18-1.55]. The magnitude of the association between FLI-defined NAFLD and low SMI was higher in middle aged to elderly males (OR=1.50; 95% CI: 1.22-1.84) than in males less than 45 years of age (OR=1.25; 95% CI: 1.02-1.52) and in premenopausal females (OR=1.50; 95% CI: 1.12-2.03) than in postmenopausal females (OR=1.36; 95% CI: 1.20-1.54).
CONCLUSIONS: Low SMI is associated with the risk of FLI-defined NAFLD independent of other well-known metabolic risk factors in both genders. This association may differ according to age group or menopausal status. Further studies are warranted to confirm this relationship.

BACKGROUND: Hepatocellular adenoma (HCA) is a rare benign tumor of the liver. It is of clinical importance to differentiate HCA from other liver tumors, especially hepatocellular carcinoma (HCC). This study aimed to evaluate the characteristic features of HCA by conventional ultrasound and contrast-enhanced ultrasound (CEUS) findings.
METHODS: Twenty-six patients (10 males and 16 females; mean age 36.2±5.0 years) with 26 histopathologically proven HCAs were retrospectively identified. According to the maximum diameter of HCAs, they were divided into three groups: <30 mm, 30-50 mm, and >50 mm. Ultrasound examinations were performed with C5-2 broadband curved transducer of Philips iU22 unit (Philips Bothell, WA, USA). For each lesion, a dose of 2.4 mL SonoVue® (Bracco Imaging Spa, Milan, Italy) was injected as a quick bolus into the cubital vein. Lesions’ echogenicity, color-Doppler flow imaging and contrast enhancement patterns were recorded.
RESULTS: Grayscale ultrasound revealed that most of HCAs were hypoechoic (73.1%, 19/26). Spotty calcifications were detected in 26.9% (7/26) of the lesions. Color-Doppler flow imaging detected centripetal bulky color flow in 46.2% (12/26) of the HCAs. CEUS showed that 73.1% (19/26) of the HCAs displayed as rapid, complete and homogenous enhancement, and 53.8% (14/26) showed decreased contrast enhancement in the late phase. There was no significant difference in enhancement patterns among different sizes of HCAs (P>0.05). Centripetal enhancement with subcapsular tortuous arteries was common in larger HCAs.
CONCLUSIONS: CEUS combined with grayscale and color-Doppler flow imaging helped to improve preoperative diagnosis of HCAs. The characteristic imaging features of HCAs included: rapid homogeneous enhancement and slow wash-out pattern on CEUS; heterogeneous echogenicity on grayscale ultrasound; and centripetal enhancement with subcapsular tortuous arteries in large HCAs.

BACKGROUND: Chronic hepatitis C virus (HCV) infection causes the skewing and activation of B cell subsets, but the characteristics of IgG+ B cells in patients with chronic hepatitis C (CHC) infection have not been thoroughly elucidated. CD4+CXCR5+ follicular helper T (Tfh) cells, via interleukin (IL)-21 secretion, activate B cells. However, the role of CD4+CXCR5+ T cells in the activation of IgG+ B cells in CHC patients is not clear.
METHODS: The frequency of IgG+ B cells, including CD27−IgG+ B and CD27+IgG+ B cells, the expression of the activation markers (CD86 and CD95) in IgG+ B cells, and the percentage of circulating CD4+CXCR5+ T cells were detected by flow cytometry in CHC patients (n=70) and healthy controls (n=25). The concentrations of serum IL-21 were analyzed using ELISA. The role of CD4+CXCR5+ T cells in the activation of IgG+ B cells was investigated using a co-culture system.
RESULTS: A significantly lower proportion of CD27+IgG+ B cells with increased expression of CD86 and CD95 was observed in CHC patients. The expression of CD95 was negatively correlated with the percentage of CD27+IgG+ B cells, and it contributed to CD27+IgG+ B cell apoptosis. Circulating CD4+CXCR5+ T cells and serum IL-21 were significantly increased in CHC patients. Moreover, circulating CD4+CXCR5+ T cells from CHC patients induced higher expressions of CD86 and CD95 in CD27+IgG+ B cells in a co-culture system; the blockade of the IL-21 decreased the expression levels of CD86 and CD95 in CD27+IgG+ B cells.
CONCLUSIONS: HCV infection increased the frequency of CD4+CXCR5+ T cells and decreased the frequency of CD27+IgG+ B cells. CD4+CXCR5+ T cells activated CD27+IgG+ B cells via the secretion of IL-21.

BACKGROUND: The deficiency of liver regeneration needs to be addressed in the fields of liver surgery, split liver transplantation and living donor liver transplantation. Researches of microRNAs would broaden our understandings on the mechanisms of various diseases. Our previous research confirmed that miR-26a regulated liver regeneration in mice; however, the relationship between miR-26a and its target, directly or indirectly, remains unclear. Therefore, the present study further investigated the mechanism of miR-26a in regulating mouse hepatocyte proliferation.
METHODS: An established mouse liver cell line, Nctc-1469, was transfected with Ad5-miR-26a-EGFP, Ad5-anti-miR-26a-EGFP or Ad5-EGFP vector. Cell proliferation was assessed by MTS, cell apoptosis and cell cycle by flow cytometry, and gene expression by Western blotting and quantitative real-time PCR. Dual-luciferase reporter assays were used to test targets of miR-26a.
RESULTS: Compared with the Ad5-EGFP group, Ad5-anti-miR-26a-EGFP down-regulated miR-26a and increased proliferation of hepatocytes, with more cells entering the G1 phase of cell cycle (82.70%±1.45% vs 75.80%±3.92%), and decreased apoptosis (5.50%±0.35% vs 6.73%±0.42%). CCND2 and CCNE2 were the direct targeted genes of miR-26a. miR-26a down-regulation up-regulated CCND2 and CCNE2 expressions and down-regulated p53 expression in Nctc-1469 cells. On the contrary, miR-26a over-expression showed the opposite results.
CONCLUSIONS: miR-26a regulated mouse hepatocyte proliferation by directly targeting the 3’ untranslated regions of cyclin D2/cyclin E2; miR-26a also regulated p53-mediated apoptosis. Our data suggested that miR-26a may be a promising regulator in liver regeneration.

BACKGROUND: Acute liver failure (ALF) is a severe and life-threatening clinical syndrome resulting in a high mortality and extremely poor prognosis. Recently, a water-soluble CO-releasing molecule (CORM-3) has been shown to have anti-inflammatory effect. The present study was to investigate the effect of CORM-3 on ALF and elucidate its underlying mechanism.
METHODS: ALF was induced by a combination of LPS/D-GalN in mice which were treated with CORM-3 or inactive CORM-3 (iCORM-3). The efficacy of CORM-3 was evaluated based on survival, liver histopathology, serum aminotransferase activities (ALT and AST) and total bilirubin (TBiL). Serum levels of inflammatory cytokines (TNF-α, IL-6, IL-1β and IL-10) and liver immunohistochemistry of NF-κB-p65 were determined; the expression of inflammatory mediators such as iNOS, COX-2 and TLR4 was measured using Western blotting.
RESULTS: The pretreatment with CORM-3 significantly improved the liver histology and the survival rate of mice compared with the controls; CORM-3 also decreased the levels of ALT, AST and TBiL. Furthermore, CORM-3 significantly inhibited the increased concentration of pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β) and increased the anti-inflammatory cytokine (IL-10) productions in ALF mice. Moreover, CORM-3 significantly reduced the increased expression of iNOS and TLR4 in liver tissues and inhibited the nuclear expression of NF-κB-p65. CORM-3 had no effect on the increased expression of COX-2 in the ALF mice. An iCORM-3 failed to prevent acute liver damage induced by LPS/D-GalN.
CONCLUSION: These findings provided evidence that CORM-3 may offer a novel alternative approach for the management of ALF through anti-inflammatory functions.

BACKGROUND: The primary focus of the study was to analyze the risk factors for bile leakage after hepatectomy for benign or malignant tumors. 
METHODS: A total of 411 patients who had undergone hepatectomy between December 2006 and December 2011 were retrospectively analyzed. The severity of bile leakage was graded according to the ISGLS classification. Twenty-eight pre- and postoperative parameters were analyzed.
RESULTS: The overall bile leakage incidence was 10.2% (42/411). The severity of the leakage was classified according to the ISGLS classification. Bile leakage was detected early in case of abdominal drainage (11.4% vs 1.9%, P=0.034). It prolonged the time of hospitalization (16 vs 9 days, P=0.001). In all patients, wedge resection was associated with a higher incidence of bile leakage in contrast to anatomical resections (25.6% vs 4.1%, P<0.0001) regardless of the underlying liver disease. Furthermore, total vascular exclusion increased risk of bile leakage (P=0.008).
CONCLUSIONS: Bile leakage as a major issue after hepatic resection is related to the postoperative morbidity and the hospitalization time. It is associated with non-anatomical resection and a total vascular exclusion.

BACKGROUND: One of the major limitations of biliary stents is the stent occlusion, which is closely related to the over-growth of bacteria. This study aimed to evaluate the feasibility of a novel silver-nanoparticle-coated polyurethane (Ag/PU) stent in bacterial cholangitis model in swine.
METHODS: Ag/PU was designed by coating silver nanoparticles on polyurethane (PU) stent. Twenty-four healthy pigs with bacterial cholangitis using Ag/PU and PU stents were randomly divided into an Ag/PU stent group (n=12) and a PU stent group (n=12), respectively. The stents were inserted by standard endoscopic retrograde cholangiopancreatography. Laboratory assay was performed for white blood cell (WBC) count, alanine aminotransferase (ALT), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) at baseline time, 8 hours, 1, 2, 3, and 7 days after stent placements. The segment of bile duct containing the stent was examined histologically ex vivo. Implanted biliary stents were examined by a scan electron microscope. The amount of silver release was also measured in vitro.
RESULTS: The number of inflammatory cells and level of ALT, IL-1β and TNF-α were significantly lower in the Ag/PU stent group than in the PU stent group. Hyperplasia of the mucosa was more severe in the PU stent group than in the Ag/PU stent group. In contrast to the biofilm of bacteria on the PU stent, fewer bacteria adhered to the Ag/PU stent.
CONCLUSIONS: PU biliary stents modified with silver nanoparticles are able to alleviate the inflammation of pigs with bacterial cholangitis. Silver-nanoparticle-coated stents are resistant to bacterial adhesion.

BACKGROUND: Acute pancreatitis is a relatively rare but potentially lethal complication after transarterial chemotherapy. This study aimed to review the complications such as acute pancreatitis after transarterial chemotherapy with or without embolization for hepatocellular carcinoma.
METHODS: A total of 1632 patients with hepatocellular carcinoma who had undergone transarterial chemoembolization from January 2000 to February 2014 in a single-center were reviewed retrospectively. We investigated the potential complications of transarterial chemoembolization, such as acute pancreatitis and acute pancreatitis-related complications.
RESULTS: Of the 1632 patients with hepatocellular carcinoma who had undergone 5434 transarterial chemoembolizations, 1328 were male and 304 female. The median age of these patients was 61 years. Most (79.6%) of the patients suffered from HBV-related hepatocellular carcinoma. The median tumor size was 5.2 cm. Of the 1632 patients, 145 patients underwent transarterial chemoembolization with doxorubicin eluting bead, making up a total of 538 episodes. The remaining patients underwent transarterial chemoembolization with cisplatin. Seven (0.4%) patients suffered from acute pancreatitis post-chemoembolization. Six patients had chemoembolization with doxorubicin and one had chemoembolization with cisplatin. Patients who received doxorubicin eluting bead had a higher risk of acute pancreatitis [6/145 (4.1%) vs 1/1487 (0.1%), P<0.0001]. Two patients had anatomical arterial variations. Four patients developed acute pancreatitis-related complications including necrotizing pancreatitis (n=3) and pseudocyst formation (n=1). All of the 4 patients resolved after the use of antibiotics and other conservative treatment. Three patients had further transarterial chemoembolization without any complication.
CONCLUSIONS: Acute pancreatitis after transarterial chemoembolization could result in serious complications, especially after treatment with doxorubicin eluting bead. Continuation of current treatment with transarterial chemoembolization after acute pancreatitis is feasible providing the initial attack is completely resolved.

BACKGROUND: Myeloid-derived suppressor cells (MDSCs) are heterogeneous cell types that suppress T-cell responses in cancer patients and animal models, some MDSC subpopulations are increased in patients with pancreatic cancer. The present study was to investigate a specific subset of MDSCs in patients with pancreatic cancer and the mechanism of MDSCs increase in these patients.
METHODS: Myeloid cells from whole blood were collected from 37 patients with pancreatic cancer, 17 with cholangiocarcinoma, and 47 healthy controls. Four pancreatic cancer cell lines were co-cultured with normal peripheral blood mononuclear cells (PBMCs) to test the effect of tumor cells on the conversion of PBMCs to MDSCs. Levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) and arginase activity in the plasma of cancer patients were analyzed by enzyme-linked immunosorbent assay.
RESULTS: CD14+/CD11b+/HLA-DR- MDSCs were increased in patients with pancreatic or bile duct cancer compared with those in healthy controls, and this increase was correlated with clinical cancer stage. Pancreatic cancer cell lines induced PBMCs to MDSCs in a dose-dependent manner. GM-CSF and arginase activity levels were significantly increased in the serum of patients with pancreatic cancer.
CONCLUSIONS: MDSCs were tumor related: tumor cells induced PBMCs to MDSCs in a dose-dependent manner and circulating CD14+/CD11b+/HLA-DR- MDSCs in pancreatic cancer patients were positively correlated with tumor burden. MDSCs might be useful markers for pancreatic cancer detection and progression.

Portal vein thrombosis is a common complication in cirrhotic patients. When portal vein thrombectomy is not a suitable option, a large collateral vessel can be used for allograft venous inflow reconstruction. We describe an unusual case of successful portal revascularization using the right gastroepiploic vein. The patient underwent a cadaveric orthotopic liver transplantation with end-to-end anastomosis of the portal vein to the right gastroepiploic vein. Six months after liver transplantation the patient is well with good liver function. The use of the right gastroepiploic vein for allograft venous reconstruction is feasible and safe, with a great advantage of avoiding the need of venous jump graft.