BACKGROUND: Hepatic angiosarcoma is a rare malignant vascular tumor presenting unique treatment challenges. The aim of the present study was to determine the treatment and prognosis of this entity.

DATA SOURCES: A systematic literature search was conducted using PubMed, Embase and Chinese Biomedical Literature database, to identify articles published from January 1980 to July 2017. Search terms were "hepatic angiosarcoma" and "liver angiosarcoma". Additional articles were retrieved through manual search of bibliographies of the relevant articles. Pooled individual data concerning the prognosis following various therapeutic modalities were analyzed.

RESULTS: A total of 75 articles involving 186 patients were eligible for inclusion. The median overall survival (OS) was 8 months, with 1-, 3-, and 5-year OS rates of 36.6%, 22.3%, and 12.0%, respectively. The median OS after partial hepatectomy (n?=?86), chemotherapy (n?=?36), liver transplantation (n?=?17), and supportive care (n?=?46) were 15, 10, 5 and 1.3 months, respectively. Small tumor size (<10?cm) was the only significant favorable factor for OS after partial hepatectomy (P?=?0.012).

CONCLUSIONS: Despite the dismal prognosis, partial hepatectomy could prolong the survival of hepatic angiosarcoma patients, particularly those with tumors <10?cm. Chemotherapy could be an option for unresectable disease. Liver transplantation is not a recommendable option for the management of this malignancy.

BACKGROUND: The reported mortality rate of mushroom-induced acute liver failure with conventional treatment is 1.4%-16.9%. Emergency liver transplantation may be indicated and can be the only curative treatment option. This study aimed to assess the prognostic value of criteria for emergency liver transplantation in predicting 28-day mortality in patients with mushroom-induced acute liver injury.

METHODS: A retrospective cohort study was performed between January 2005 and December 2015. All adult patients aged≥18 years admitted with mushroom intoxication at our emergency department were evaluated. All patients with acute liver injury, defined as elevation of serum liver enzymes (>5 times the upper limit of normal, ULN) or moderate coagulopathy (INR > 2.0) were included. The ability of the King's College, Ganzert's, and Escudié's criteria to predict 28-day mortality was evaluated.

RESULTS: Of the 23 patients with acute liver injury following mushroom intoxication, 10 (43.5%) developed acute liver failure and subsequently died. The mean time interval from ingestion to death was 11.3?±?6.6 days. Eight patients fulfilled Ganzert's criteria, while 10 patients fulfilled the King's College and Escudié's criteria for emergency liver transplantation. King's College and Escudié's criteria had 100% accuracy in predicting 28-day mortality; however, Escudié's criteria were able to identify fatal cases earlier.

CONCLUSIONS: Escudie's criteria demonstrated the best performance with 100% accuracy and the ability to promptly identify fatal cases of mushroom-induced acute liver failure.

BACKGROUND: Several studies have reported that apolipoprotein A5 (APOA5) is involved in the development of non-alcoholic fatty liver disease (NAFLD). However, no research has been performed regarding the association between APOA5 polymorphisms and the risk of NAFLD. This study aimed to explore the association between APOA5 gene polymorphisms and NAFLD in a Chinese Han population.

METHODS: Genotypes of the SNPs (rs10750097, rs1263173, rs17120035, rs3135507 and rs662799) of APOA5 in 232 NAFLD patients and 188 healthy controls were determined using polymerase chain reaction (PCR) analysis. Clinical characteristics were measured using biochemical methods.

RESULTS: The five single nucleotide polymorphisms (SNPs) (rs10750097, rs1263173, rs17120035, rs3135507 and rs662799) of APOA5 showed no significant association with NAFLD (P?>?0.05). The rs10750097 with G allele showed a higher serum level of alkaline phosphatase (ALP) compared with C allele in overall series and NAFLD patients (P?<?0.05). The rs1263173(A/A) carriers showed a higher level of glucose compared to the non-carriers in overall series (P?<?0.05). The rs17120035(T/T) carriers showed a lower plasma TG level in overall series and NAFLD patients (P?<?0.05), and the rs662799(G/G) carriers showed higher levels of plasma triglyceride (TG), ALP, and lower level of high-density lipoprotein (HDL) compared to non-carriers in NAFLD patients (P?<?0.05). No significant difference were observed on the clinic parameters of APOA5 rs3135507(T/T) carriers in both group of overall series and NAFLD patients (P?>?0.05).

CONCLUSIONS: The five SNPs (rs10750097, rs1263173, rs17120035, rs3135507 and rs662799) of APOA5 gene are not associated with the risk of NAFLD in the Chinese Han population. The genotypes of rs10750097(G/G), rs1263173(A/A), rs17120035(T/T), and rs662799(G/G) performed a significant effect on clinic characteristics in overall series and NAFLD patients, indicating that these polymorphisms may be associated with NAFLD.

BACKGROUND: Our previous study showed that 17-beta-hydroxysteroid dehydrogenase 13 (HSD17B13) is down-regulated in hepatocellular carcinoma (HCC). But its function in HCC remains unknown. This study aimed to reveal the function of HSD17B13 and its clinical significance in HCC.

METHODS: mRNA levels of HSD17B13 were analyzed in cohort 1 (30 normal, 30 HBV cirrhosis, 60 HBV-related HCC and 60 peritumoral tissue) by real-time PCR. HSD17B13 protein was evaluated in cohort 2 (15 normal, 33 HBV-cirrhosis, 12 dysplastic nodules, 34 HBV-related HCC, and 9 metastatic HCC) using immunohistochemistry. The association between HSD17B13 and the survival of HCC patients was analyzed in cohort 3 (n?=?88). The inhibitory mechanism of HSD17B13 on HCC was explored .

RESULTS: The mRNA of HSD17B13 and its protein expression were significantly down-regulated in HCC compared to non-tumor specimens (P < 0.001). The sensitivity, specificity and area under curve (AUC) values of HSD17B13 expression levels for HCC detection were 81.7%, 83.7% and 0.856, respectively (P < 0.001). Lower HSD17B13 in peritumoral tissue was an independent risk factor of worse recurrence free survival of HCC patients (HR: 0.41; 95% CI: 0.20-0.83; P = 0.014). The study in Huh 7 and SK-HEP-1 cells showed that HSD17B13 induced an accumulation of cells in G1 phase and reduction of cells in S and G2 phases via up-regulating the expression of P21, P27 and MMP2.

CONCLUSIONS: Lower HSD17B13 in peritumoral tissues was associated with worse recurrence free survival and overall survival of HCC patients. HSD17B13 delayed G1/S progression of HCC cells. HSD17B13 may be a therapeutic target for the treatment of HCC.

BACKGROUD: Wingless-type MMTV integration site family member 5a (Wnt5a) is involved in carcinogenesis. However, little data are available in Wnt5a signaling with hepatocellular carcinoma (HCC). In the present study, we investigated the expression of hepatic Wnt5a in HCC and the role of Wnt5a in HCC progression and outcome.

METHODS: Wnt5a expression and cellular distribution in HCCs and their matched paracancerous tissues from 87 patients were analyzed with tissue microarray and immunohistochemistry and compared with hepatic Wnt3a signaling. Wnt5a expression was categorized into low or high based on immunohistochemistry. Overall survival rate of HCC patients was estimated in correlation with the hepatic Wnt5a level using Kaplan-Meier method; the survival difference between patients with low and those with high Wnt5a was compared with log-rank test; and prognostic analysis was carried out with Cox regression.

RESULTS: Total incidence of Wnt5a expression in the HCC tissues was 70.1%, which was significantly lower (χ^2?=?13.585, P?<?0.001) than that in their paracancerous tissues (88.5%). Significant difference of Wnt5a intensity was found between HCC and their paracancerous tissues (Z?=?8.463, P?<?0.001). Wnt5a intensity was inversely correlated with Wnt3a signaling (r?=?-0.402, P?<?0.001) in HCC tissues. A decrease of Wnt5a expression in relation to the clinical staging from stage I to IV and low or no staining at advanced HCC were observed. Wnt5a level was related to periportal embolus (χ^2?=?11.069, P?<?0.001), TNM staging (χ^2?=?8.852, P?<?0.05), 5-year survival (χ^2?=?4.961, P?<?0.05), and confirmed as an independent prognosis factor of HCC patients (hazard ratio: 1.957; 95% confidence interval: 1.109-3.456; P?<?0.05).

CONCLUSIONS: The decrease of hepatic Wnt5a signaling is associated with HCC progression and poor prognosis.

BACKGROUND: Higher hepatitis B surface antigen (HBsAg) facilitates hepatitis C virus (HCV) clearance in patients with hepatitis B virus (HBV)/HCV co-infection. We investigated the effect of exogenous HBsAg on the inhibition of HCV replication mediated by natural killer (NK) cells.

METHODS: After isolated from peripheral blood of 42 chronic hepatitis B (CHB) patients and 16 healthy individuals, NK cells were co-cultured with HCV-infected Huh7 cells, respectively, with or without HBsAg. Three days later, the co-cultured supernatants were collected and HCV RNA levels were measured by real-time quantitative PCR. NKG2D, NKp46 and NKG2A expression levels were measured by flow cytometry. NKG2D on NK cells from CHB responsive subgroup was blocked and HCV RNA levels were examined again.

RESULTS: HCV RNA levels in the co-cultured system were significantly reduced by NK cells isolated from healthy donors (P?<?0.01) but not from CHB patients. However, HCV RNA levels in CHB cultures were significantly decreased following HBsAg addition (P?<?0.05), whereas no such effect was seen in control cultures. No significant difference was observed in basic NKG2D expression between the CHB patients and healthy donors. On NK cells from CHB patients, the expression of NKG2D was increased significantly by HBsAg stimulation (P?<?0.01), and higher than that from healthy controls (P?<?0.05). HCV RNA levels were increased significantly after the blockage of NKG2D on NK cells from responsive CHB patients in the co-cultured system (P?<?0.05).

CONCLUSION: Exogenous HBsAg stimulated NKG2D expression on NK cells from CHB patients which inhibit HCV replication, suggesting that HBsAg may facilitate the clearance of HCV in patients with HBV/HCV co-infection.

METHODS: Huh-7 cells were incubated with different concentrations of FTI-277 alone and in combination with alendronate. Differential protein and gene expression was examined through two dimensional gel electrophoresis and real-time quantitative polymerase chain reaction (qPCR), respectively. Proteins were identified using tandem mass spectrometry analysis.

RESULTS: Treatment of hepatocellular carcinoma (HCC) cell line with FTI-277 alone showed cell death in a time and dose dependent manner while in combination with alendronate, a synergistic apoptotic effect at 24 h was observed. Proteomic studies on the 20 µmol/L FTI-277 and 5?µmol/L alendronate?+20?µmol/L FTI-277 treated cells revealed altered expression of different proteins including peroxiredoxin 2 (Prx2), glutathione S transferase 1 (GSTP1), Rho GTPase activating protein (RhoGAP), triosephosphate isomerase (TPI), and heat shock protein 60 (HSP60). Down-regulated expression of Prx2 and GSTP1 in treated cells was also confirmed by real-time qPCR analysis.

CONCLUSIONS: Combined treatment of FTI-277 and alendronate on Huh-7 HCC cells showed cell death suggesting their anticancer potential. Such treatment approaches are likely to offer new therapeutic strategies.

BACKGROUND: Little information is available about the relationship between restoration of common bile duct (CBD) diameter after endoscopic stone retraction and recurrence of CBD stones in elderly patients. The present study was to determine whether restoration of CBD diameter is a preventive factor for CBD stone recurrence in elderly patients who underwent endoscopic retrograde cholangiopancreatography (ERCP).

METHODS: From January 2006 to December 2010, 238 patients underwent the first and the second session of ERCP for the removal of CBD stones. Among them, 173 were over 65 years old. These patients were divided into recurrent group and non-recurrent group. Restoration of CBD diameter and patients' characteristics were compared.

RESULTS: There was no statistical difference in patients' characteristics, associated diseases, or ERCP-related complications between the two groups. Reduction of CBD diameter was significantly larger in the non-recurrent group (2.7?±?1.7?mm) compared to that in the recurrent group (1.4?±?2.3?mm, P?=?0.002). The proportion of patients with restoration of CBD diameter were significantly lower in the recurrent group (6/42, 14.3%) compared with that in the non-recurrent group (67/131, 51.1%) (P?<?0.01).

CONCLUSIONS: There is an inverse relationship between restoration of CBD diameter and CBD stone recurrence. Therefore, patients without restoration of CBD diameter within 2 weeks after endoscopic stone removal should be monitored more frequently.

BACKGROUND: Endoscopic papillary balloon dilation (EPBD) for common bile duct (CBD) stones removal in Billroth II gastrectomy patients is feasible. However, the long-term outcomes of this technique are not clear. The aim of this study was to evaluate the procedural and long-term outcomes of EPBD for removal of CBD stones in Billroth II gastrectomy patients.

METHODS: The records of patients with previous Billroth II gastrectomy referred for CBD stones removal with endoscopic retrograde cholangiopancreatography (ERCP) between July 1, 2008 and September 1, 2016 were retrospectively reviewed. The main outcomes of stone clearance, ERCP-related adverse events, and stone recurrence were analyzed.

RESULTS: A total of 83 patients with previous Billroth II gastrectomy underwent ERCP in our center were reviewed. Forty-nine consecutive patients with previous Billroth II gastrectomy referred to EPBD for removal of CBD stones underwent 59 ERCP procedures were enrolled in the end. The overall successful CBD stones clearance was achieved in 42 patients (85.7%). ERCP-related adverse events was in 3 ERCP procedures (5.1%). Severe complications, including perforation and bleeding, were not observed. Six of 49 patients (12.2%) had stone recurrence after a median period of 22.5 months (range 6-71 months) from the end of stone removal treatment. Female [odds ratio (OR) =?11.352; 95% confidence interval (95% CI): 1.040-123.912; P?=?0.046] and previous mechanical lithotripsy (OR?=?13.423; 95% CI: 1.070-168.434; P?=?0.044) were significantly associated with stone recurrence.

CONCLUSIONS: At long-term follow-up, EPBD for removal of CBD stones appeared to be safe and effective in Billroth II gastrectomy patients. Female and previous mechanical lithotripsy may be risk factors for stone recurrence.

BACKGROUND: Generally, carbohydrate antigen 19-9 (CA 19-9) is not useful for screening pancreatic cancer in the asymptomatic general population. This study aimed to evaluate the utility of CA 19-9 level as a screening indicator of pancreatic cancer in asymptomatic patients with new-onset diabetes.

METHODS: We retrospectively reviewed the medical records of patients who visited our health promotion center for health check-ups without cancer related symptoms from January 2005 to January 2014, and were newly diagnosed with diabetes mellitus (DM) within 2 years before their visit.

RESULTS: Of the 5111 asymptomatic patients with new-onset DM (<2 years) selected for analyses, 87 (1.7%) eventually developed pancreatic cancer after the health check-up. In the subgroup of 322 patients with high total bilirubin levels (>1.7?mg/dL) at the screening time, 42 (73.7%) of 57 patients with high CA 19-9 levels (>37 IU/mL) had been diagnosed as pancreatic cancer during follow-up period and 12 (4.5%) of 265 patients with normal CA 19-9 levels had finally developed pancreatic cancer (OR?=?16.3). In the subgroup of 4789 patients with normal bilirubin levels, pancreatic cancer had been detected in 20 (3.8%) of 522 patients with high CA 19-9 level, while only 13 (0.3%) in 4267 patients with normal CA 19-9 levels (OR?=?12.6), respectively.

CONCLUSION: CA 19-9 levels after a diagnosis of new-onset DM could be a useful biomarker of pancreatic cancer, especially in patients with high serum bilirubin.

BACKGROUND: Pancreatectomies have been identified as procedures with an increased risk of readmission. In surgical patients, readmissions within 30 days of discharge are usually procedure-related. We sought to determine predictors of 30-day readmission following pancreatic resections in a large healthcare system.

METHODS: We retrospectively collected information from the records of 383 patients who underwent pancreatic resections from 2004-2013. To find the predictors of readmission in the 30 days after discharge, we performed a univariate screen of possible variables using the Fisher's exact test for categorical variables and the Mann-Whitney U test for continuous variables. Multivariate analysis was used to determine the independent factors.

RESULTS: Fifty-eight (15.1%) patients were readmitted within 30 days of discharge. Of the patients readmitted, the most common diagnoses at readmission were sepsis (17.2%), and dehydration (8.6%). Multivariate logistic regression found that the development of intra-abdominal fluid collections (OR?=?5.32, P?<?0.0001), new thromboembolic events (OR?=?4.08, P?=?0.016), and pre-operative BMI (OR?=?1.06, P?=?0.040) were independent risk factors of readmission within 30 days of discharge.

CONCLUSION: Our data demonstrate that factors predictive of 30-day readmission are a combination of patient characteristics and the development of post-operative complications. Targeted interventions may be used to reduce the risk of readmission.