BACKGROUND: Some studies found that age at first birth is associated with pancreatic cancer; others did not. The present meta-analysis was to evaluate the relationship between age at first birth and pancreatic cancer in women.
DATA SOURCES: We searched PubMed, Embase, and the Cochrane Library for relevant publications on age at first birth and pancreatic cancer up to April, 2014. The eligible studies (six cohorts and five case-controls) were independently selected by two authors. Pooled relative risk (RR) estimates and corresponding 95% confidence interval (95% CI) were calculated using the inverse-variance method.
RESULTS: The pooled RR of pancreatic cancer risk for the highest versus lowest categories of age at first birth was 1.21 (95% CI: 1.01-1.45, P=0.314, I²=13.7%). Consistent relationships were also observed within subgroup analyses stratified by study design, geographic region, and whether the studies included adjustment for cigarette smoking, diabetes, or all of the confounders. In this meta-analysis, no publication bias among studies was observed using Egger’s test (P=0.383) or Begg’s test (P=0.436).
CONCLUSION: Our findings suggest that older age at first birth is associated with an increased risk of pancreatic cancer in women and the exact functional mechanism needs further investigation.

BACKGROUND: The estimation of liver fibrosis is usually dependent on liver biopsy evaluation. Because of its disadvantages and side effects, researchers try to find non-invasive methods for the assessment of liver injuries. Hyaluronic acid has been proposed as an index for scoring the severity of fibrosis, alone or in algorithm models. The algorithm model in which hyaluronic acid was used as a major constituent was more reliable and accurate in diagnosis than hyaluronic acid alone. This review described various hyaluronic acid algorithm-based models for assessing liver fibrosis.
DATA SOURCE: A PubMed database search was performed to identify the articles relevant to hyaluronic acid algorithm-based models for estimating liver fibrosis.
RESULT: The use of hyaluronic acid in an algorithm model is an extra and valuable tool for assessing liver fibrosis.
CONCLUSIONS: Although hyaluronic acid algorithm-based models have good diagnostic power in liver fibrosis assessment, they cannot render the need for liver biopsy obsolete and it is better to use them in parallel with liver biopsy. They can be used when frequent liver biopsy is not possible in situations such as highlighting the efficacy of treatment protocol for liver fibrosis.

BACKGROUND: Liver regeneration is a complex process. microRNAs (miRNAs) are short, single-stranded RNAs that modify gene expression at the post-transcriptional level. Recent investigations have revealed that miRNAs are closely linked to liver regeneration.
DATA SOURCES: All included studies were obtained from PubMed, Embase, the ScienceDirect databases and Web of Science, with no limitation on publication year. Only studies published in English were considered.
RESULTS: We grouped studies that involved miRNA and liver regeneration into two groups: miRNAs as promoters and as inhibitors of liver regeneration. We summarized the relevant miRNAs separately from the related pathways.
CONCLUSIONS: Blocking or stimulating the pathways of miRNAs in liver regeneration may be novel therapeutic strategies in future regeneration-related liver managements. We may discover additional chemotherapy targets of miRNA.

BACKGROUND: Hepatocellular carcinoma (HCC) recurrence remains a key issue after liver transplantation. This study aimed to determine a subgroup of HCC patients within the Milan criteria who could achieve a theoretical goal of zero recurrence rates after liver transplantation.
METHODS: Between 1999 and 2009, 179 patients who received liver transplantation for HCC within the Milan criteria were retrospectively included. Analysis of the factors associated with HCC recurrence was performed to determine the subgroup of patients at the lowest risk of recurrence.
RESULTS: Seventy-two percent of the patients received a bridging therapy, including 54 liver resections. Eleven (6.1%) patients recurred within a delay of 19±22 months and ultimately died. Factors associated with recurrence were serum alpha-fetoprotein level >400 ng/mL, satellite nodules, poor differentiation, microvascular invasion and cholangiocarcinoma component. Recurrence rates decreased from 6.1% to 3.1% in patients without any of these factors.
CONCLUSIONS: Among HCC patients within the Milan criteria, selecting patients with factors based on histology would allow tending towards zero recurrence, and prior histological assessment by liver biopsy or resection may be essential to rule out poorly differentiated tumors, microvascular invasion, and cholangiocarcinoma component.

BACKGROUND: The Barcelona Clinic Liver Cancer (BCLC) staging system for hepatocellular carcinoma (HCC) recommends transarterial chemoembolization (TACE) as the first line therapy for stage B patients and sorafenib treatment for stage C patients. However, stage C patients exhibit variations in terms of tumor burden, liver function, and extrahepatic metastasis, which could potentially affect disease outcome. Here, we assessed whether the Cancer of the Liver Italian Program (CLIP) scores can help identify stage C patients likely to benefit from TACE.
METHODS: Out of 295 BCLC stage C HCC patients enrolled between January 2009 and December 2011, those with platelet counts >30×109 cells/L, total bilirubin <51 µmoL/L, and an unobstructed main portal vein were scheduled for TACE (n=195). The remaining patients received best supportive care (BSC, n=100). All the patients were followed up for symptoms, performance status, and Child-Pugh classification scores every 4 weeks until death or December 2013. The prognosis of each group was evaluated by using the log-rank test and Cox-Mantel test.
RESULTS: The median overall survival (OS) was 6 months [95% confidence interval (CI): 4.64-7.36]. The OS was 9 months for the TACE group and 4 months for the BSC group. The TACE group had a longer OS than the BSC subgroup for CLIP scores 0-2 [13 months (95% CI: 8.55-17.45) vs 4 months (95% CI: 0.00-10.96), P=0.001]. No significant differences were found between the TACE and BSC groups for CLIP scores 3-5. The CLIP score and treatment methods were found to be independent prognostic factors.
CONCLUSIONS: BCLC stage C HCC patients exhibit definite disease heterogeneity and can be reclassified by using the CLIP scoring system. Moreover, patients with CLIP scores 0-2 are likely to benefit from TACE. However, additional studies with long-term follow-up will be required to validate these findings.

BACKGROUND: Pathologic response (PR) predicts survival after preoperative chemotherapy and resection of a malignancy. Occasionally, transarterial chemoembolization (TACE) may be selected for preoperative management of resectable hepatocellular carcinoma (HCC). This study investigated whether PR to preoperative TACE can predict recurrence after resection for resectable HCC.
METHODS: We conducted analysis of 106 HCC patients who underwent TACE followed by liver resection with a curative intent. The PR was evaluated as the mean percentage of non-viable tumor area within each tumor. We divided the patients into three groups according to response rate: complete PR (CPR), major response (MJR: PR≥50%) and minor response (MNR: PR<50%). The primary endpoint was disease-free survival, and the secondary endpoints were predicting factors for tumor recurrence and MJR+CPR.
RESULTS: Among the 121 TACE patients, PR could be measured in 106 (87.6%). The mean interval between TACE and liver resection was 33.1 days. The 5-year disease-free survival rates by PR status were as follows: 40.6% CPR, 43.7% MJR, and 49.0% MNR (P=0.815). There were also no significant differences in overall survival between the three groups. Multivariate analyses revealed that microvascular invasion and capsular invasion (hazard ratio [HR]=11.224, P=0.002 and HR=2.220, P=0.043) were independent predictors of disease-free survival. Multivariate analysis of the predictors of above 50% PR revealed that only hepatitis B was an independent factor.
CONCLUSION: These data could reflect that the PR after TACE for resectable HCC may not be useful for predicting recurrence of HCC after resection.

BACKGROUND: A large amount of endotoxin can be detected in the peripheral venous blood of patients with liver cirrhosis, contributing to the pathogenesis of hepatotoxicity because of its role in oxidative stress. The present study aimed to test the effect of the supplementation with red palm oil (RPO), which is a natural oil obtained from oil palm fruit (Elaeis guineensis) rich in natural fat-soluble tocopherols, tocotrienols and carotenoids, on lipid peroxidation and endotoxemia with plasma endotoxin-inactivating capacity, proinflammatory cytokines profile, and monocyte tissue factor in patients with chronic liver disease.
METHODS: The study group consisted of sixty patients (34 males and 26 females; mean age 62 years, range 54-75) with Child A/B, genotype 1 HCV-related cirrhosis without a history of ethanol consumption, randomly enrolled into an 8-week oral daily treatment with either vitamin E or RPO. All patients had undergone an upper gastrointestinal endoscopy 8 months before, and 13 out of them showed esophageal varices.
RESULTS: Both treatments significantly decreased erythrocyte malondialdehyde and urinary isoprostane output, only RPO significantly affected macrophage-colony stimulating factor and monocyte tissue factor. Liver ultrasound imaging did not show any change.
CONCLUSIONS: RPO beneficially modulates oxidative stress and, not least, downregulates macrophage/monocyte inflammatory parameters. RPO can be safely advised as a valuable nutritional implementation tool in the management of chronic liver diseases.

BACKGROUND: Differentiation of liver progenitor cells (LPCs) to functional hepatocytes holds great potential to develop new strategies for hepatocyte transplantation and the screening of drug-induced cytotoxicity. However, reports on the efficient and convenient hepatic differentiation of LPCs to hepatocytes are few. The present study aims to investigate the possibility of generating functional hepatocytes from LPCs in an indirect co-culture system.
METHODS: Mouse LPCs were co-cultured in Transwell plates with an immortalized human hepatic stellate cell line (HSC-Li) we previously established. The morphology, expression of hepatic markers, and functions of mouse LPC-derived cells were monitored and compared with those of conventionally cultured LPCs.
RESULTS: Co-culturing with HSC-Li cells induced differentiation of mouse LPCs into functional hepatocyte-like cells. The differentiated cells were morphologically transformed into hepatocyte-like cells 3 days after co-culture initiation. In addition, the differentiated cells expressed liver-specific genes and possessed hepatic functions, including glycogen storage, low-density lipoprotein uptake, albumin secretion, urea synthesis, and cytochrome P450 1A2 enzymatic activity.
CONCLUSIONS: Our method, which employs indirect co-culture with HSC-Li cells, can efficiently induce the differentiation of LPCs into functional hepatocytes. This finding suggests that this co-culture system can be a useful method for the efficient generation of functional hepatocytes from LPCs.

BACKGROUND: Early diagnosis of gallbladder cancer (GBC) can remarkably improve the prognosis of patients. This study aimed to develop a nomogram for individualized diagnosis of stage I-II GBC in chronic cholecystitis patients with gallbladder wall thickening.
METHODS: The nomogram was developed using logistic regression analyses based on a retrospective cohort consisting of 89 consecutive patients with stage I-II GBC and 1240 patients with gallbladder wall thickening treated at one biliary surgery center in Shanghai between January 2009 and December 2011. The accuracy of the nomogram was validated by discrimination, calibration and a prospective cohort treated at another center between January 2012 and December 2014 (n=928).
RESULTS: Factors included in the nomogram were advanced age, hazardous alcohol consumption, long-standing diagnosed gallstones, atrophic gallbladder, gallbladder wall calcification, intraluminal polypoid lesion, higher wall thickness ratio and mucosal line disruption. The nomogram had concordance indices of 0.889 and 0.856 for the two cohorts, respectively. Internal and external calibration curves fitted well. The area under the receiver-operating characteristic curves of the nomogram was higher than that of multidetector row computed tomography in diagnosis of stage I-II GBC (P<0.001).
CONCLUSION: The proposed nomogram improves individualized diagnosis of stage I-II GBC in chronic cholecystitis patients with gallbladder wall thickening, especially for those the imaging features alone do not allow to confirm the diagnosis.

BACKGROUND: Most of the reports on the prognostic indicators of patients with pancreatic adenocarcinoma are from developed countries. The present study focused on the prognostic indicators of Chinese patients with pancreatic adenocarcinoma.
METHODS: A total of 300 patients with pancreatic adenocarcinoma who had undergone curative resection were included. The resection and R0/R1 resection rates for adenocarcinomas from different parts of the pancreas were calculated and clinical characteristics were analyzed.
RESULTS: In 3427 patients diagnosed with pancreatic adenocarcinomas, only 300 (8.8%) were eligible for radical resection. The total median survival of these patients was 19 months, and their 1-, 3-, and 5-year survival rates were 72.5%, 28.0% and 23.4%, respectively. The prognostic factors included socioeconomic status, smoking history, symptoms, high blood glucose, and various tumor characteristics, including perineural and vascular invasion, lymph node metastases, and CA19-9 levels before and after operation. Operation-associated prognostic indicators included operation time, blood loss and transfusions, pancreatic fistula, and complications. Independent predictors of mortality included poor socioeconomic status, smoking history, symptoms, CA19-9, perineural invasion and lymph node metastasis, grade of fistula and complications. Patient survival was not correlated with either resection margin or adjuvant chemotherapy in multivariate analysis.
CONCLUSIONS: The survival rates of patients with curative resection for pancreatic adenocarcinoma in China are close to those in developed countries, but curative resection rate is far below. Socioeconomic status, symptoms, and CA19-9 are the three most prominent prognostic factors, which are helpful in patient selection and perioperative care.

BACKGROUND: Enhanced recovery after surgery (ERAS) has improved postoperative outcomes particularly in colorectal surgery. This study aimed to assess compliance with an ERAS protocol and evaluate its effect on postoperative outcomes in patients undergoing pancreaticoduodenectomy.
METHODS: Fifty patients who had received conventional perioperative management from 2005 to 2009 (conventional group) were compared with 75 patients who had received perioperative care with an ERAS protocol (fast-track group) from 2010 to 2014. Mortality, complications, readmissions and length of hospital stay were evaluated and compared in the groups.
RESULTS: Compliance with each element of the ERAS protocol ranged from 74.7% to 100%. Uneventful patients had a significant higher adherence to the ERAS protocol (87.5% vs 40.7%; P<0.001). There were no significant differences in demographics and perioperative characteristics between the two groups. Patients in the fast-track group had a shorter time to remove the nasogastric tube, start liquid diet and solid food, pass flatus and stools, and remove drains. No difference was found in mortality, relaparotomy, readmission rates and overall morbidity. However, delayed gastric emptying and length of hospital stay were significantly reduced in the fast-track group. The independent effect of the ERAS protocol in reducing delayed gastric emptying and length of hospital stay was confirmed by multivariate analysis.
CONCLUSION: ERAS pathway was feasible and safe in improving gastric emptying, yielding an earlier postoperative recovery, and reducing the length of hospital stay.

BACKGROUND: Diagnostic parameters that can predict the presence of chronic pancreatitis (CP) in patients with recurrent pain due to pancreatitis would help to direct appropriate therapy. This study aimed to compare the serum levels of monocyte chemoattractant protein-1 (MCP-1), transforming growth factor-β1 (TGF-β1), nerve growth factor (NGF), resistin and hyaluronic acid (HA) in patients with recurrent acute pancreatitis (RAP) and CP to assess their ability to differentiate the two conditions.
METHODS: Levels of serum markers assessed by enzyme-linked immunosorbent assay (ELISA) were prospectively compared in consecutive patients with RAP, CP and in controls, and stepwise discriminant analysis was performed to identify the markers differentiating RAP from CP.
RESULTS: One hundred and thirteen consecutive patients (RAP=32, CP=81) and 78 healthy controls were prospectively enrolled. The mean (SD) age of the patients was 32.0 (14.0) years; 89 (78.8%) were male. All markers were significantly higher in CP patients than in the controls (P<0.001); MCP-1, NGF and HA were significantly higher in RAP patients than in the controls (P<0.001). Stepwise discriminant analysis showed significant difference (P=0.002) between RAP and CP for resistin with an accuracy of 61.9%, discriminant scores of ≤-0.479 and ≥0.189 indicating RAP and CP, respectively. The other markers had no differential value between RAP and CP.
CONCLUSION: Serum resistin is a promising marker to differentiate between RAP and CP and needs validation in future studies, especially in those with early CP.

At the annual National Science and Technology Award Conference held on January 8, 2016 in the People’ s Great Hall, Beijing, the Comprehensive Diagnosis and Treatment of End-stage Liver Disease Innovative Research Group from the First Affiliated Hospital, Zhejiang University School of Medicine, led by Professors Shu-Sen Zheng and Lan-Juan Li, was awarded the First prize for progress in science and technology. In the past thirty years, the group has done remarkably in treating and conquering liver diseases. The application of Li’s Artificial Liver System has improved the survival of patients with end-stage liver diseases. The mortality of acute and subacute severe hepatitis decreased from 88.1% in the 1990s to 21.1% at the present, and that of chronic severe hepatitis from 84.6% to 56.6%. The finding of gut microflora changes in patients with end-stage liver diseases promotes the development of micro-ecology of liver diseases, and enriches the theory about the pathogenesis of the diseases. The Hangzhou criteria for selecting patients with hepatocellular carcinoma for liver transplantation, proposed by Professor Zheng, has been highly recognized by scientists from other countries, for instance, UCLA and Cleveland Clinic from USA. The 1- and 3-year survival rates of patients after liver transplantation are 88% and 78%, respectively.

When suitable, surgery still remains the therapeutic option to be preferred for patients carrier of colorectal liver and lung metastases. Since thoracophrenolaparotomy should be helpful during liver resection for some of these patients, simultaneous removal of right lung metastases can be proposed through this approach. Eleven consecutive patients (median age of 53 years) carrier of colorectal liver and lung metastases, underwent single session surgical resection of both liver and right lung lesions by means of J-shaped thoracophrenolaparotomy. The median number of liver metastases removed was 5 (range 2-30) and of lung metastases removed was 2 (range 1-3). Lung metastases were located in the upper lobe in 1 patient, in the middle lobe in 2, in the lower lobe in 6, and in the upper and lower lobe in 2. Mortality and major morbidity were nil. Two patients had a minor morbidity: one had wound infection and bile leakage treated conservatively and the other had transient fever. Mean overall survival was 24.4 months. An aggressive surgical approach should be undertaken for colorectal metastases: in case of multifocal liver disease with complex presentations, J-shaped thoracophrenolaparotomy could be considered as safe approach for combined liver and right lung metastasectomies.

Despite the effectiveness of endoscopic retrograde cholangiopancreatography (ERCP) for the treatment of choledocholithiasis, various complications have been described. We herein report the first case of prolonged post-ERCP jaundice due to toxicity of the contrast agent Iobitridol (®XENETIX, Guerbet, Roissy CdG Cedex, France) in a patient who underwent ERCP with sphincterectomy and common bile duct stone removal. While clinical improvement and normalization of aminotransferases and cholestatic enzymes after the procedure, an unexplained increase of direct bilirubin was noticed. A second ERCP was performed one week later, excluding possible remaining choledocholithiasis. Nevertheless, serum direct bilirubin increased further up to 15 mg/dL. Other potential causes of direct hyperbilirubinemia were ruled out and patient’s liver biopsy was compatible with drug-induced liver toxicity. Additionally, the cause-result time connection between the use of Iobitridol and bilirubin increase indicated the possibility of a toxic effect related to the repeated use of the particular contrast agent. Iobitridol, a contrast agent, can induce prolonged direct hyperbilirubinemia.