The methods of preoperative biliary drainage for resectable hilar cholangiocarcinoma patients: A protocol for systematic review and meta analysis.

OBJECTIVES: To compare the clinical outcomes of endoscopic biliary drainage (EBD) with those of percutaneous transhepatic biliary drainage (PTBD) in patients with resectable hilar cholangiocarcinoma (HCCA) and evaluate the effect of EBD and PTBD on tumor prognosis. MATERIALS AND METHODS: PubMed, EMBASE, and Cochrane Library databases were searched for articles about the comparison between PTBD and EBD. Data were analyzed by Revman 5.3. RESULTS: PTBD showed a lower risk of drainage-related complications than EBD (OR, 2.73; 95%CI, 1.52-4.91; P < .05). PTBD was also associated with lower risk of pancreatitis (OR, 8.47; 95%CI, 2.28-31.45; P < .05). The differences in preoperative cholangitis, R0 resection, blood loss and recurrence showed no statistically significance between EBD and PTBD (all P > .05). Several literatures have reported the tumor implantation metastasis after PTBD. Since no well-designed prospective randomized controlled studies have explored in this depth, this article is unable to draw conclusions on this aspect. CONCLUSION: PTBD is a reasonable choice for PBD, and EBD should only be used as preoperative drainage for HCCA by more experienced physicians. There is a greater need to design prospective randomized controlled studies to obtain high-level evidence-based medicinal proof. It is worth noting that, whether EBD or PTBD, accurate selective biliary drainage should be the trend.

Clinical analysis of hepatic angioleiomyoma: Two case reports.

RATIONALE: Angioleiomyoma is an uncommon benign tumor that originates from the vascular smooth muscle cells and contains thick-walled vessels. It can appear anywhere in the body but more frequently in the extremities (especially in the lower limbs) and rarely invades the internal organs. PATIENT CONCERNS: A 52-year-old Chinese woman was referred to our hospital because of finding liver neoplasm 2 weeks ago (case first) and a 64-year-old Chinese woman was admitted to hospital with enlargement of the hepatic neoplasm revealed in follow-up, who was diagnosed with angioleiomyoma of left kidney 2 years ago (case second). DIAGNOSIS: All patients were diagnosed with hepatic angioleiomyoma by pathological results. INTERVENTIONS: All patients received surgical treatment, with laparoscopic hepatectomy of the IVb segment in case 1 and laparoscopic hepatic left lateral lobectomy in case 2. OUTCOMES: The 2 patients have eventually recovered, and no recurrences or other complications have been observed so far. LESSONS: Because of atypical clinical symptoms, no specificity in laboratory examination, and lack of characteristic imaging findings, angioleiomyoma is easily misdiagnosed for another disease of the liver. But with complete resection, the prognosis is generally good.

Bouveret's syndrome: A rare presentation of gastric outlet obstruction.

Bouveret's syndrome refers to gastric outlet obstruction caused by the formation of a cholecystoduodenal fistula with subsequent migration and impaction of a large gallstone into the duodenum. A case of a 59-year-old male who presented to our institution with consistent abdominal pain and nausea is reported herein. Bouveret's syndrome was diagnosed after conducting a computed tomography scan. Surgery was performed wherein gallstone removal was followed by cholecystectomy and fistula repair associated with a pyloric bypass via gastro-jejunostomy. The patient recovered well following surgery and has remained free of symptoms for the last year.

Differentiation of umbilical cord mesenchymal stem cells into hepatocytes in comparison with bone marrow mesenchymal stem cells.

Mesenchymal stem cells (MSCs) are considered to be an ideal source for the cell therapy of end­stage liver diseases. Umbilical cord (UC)­MSCs can be obtained via a non­invasive procedure and can be easily cultured, making them potentially superior candidates for cell transplantation when compared with MSCs from other sources. In the present study, UC­MSCs were induced to differentiate into hepatocytes and were compared with bone marrow (BM)­MSCs for their hepatic differentiation potential. UC­MSCs showed significantly higher proliferation than BM­MSCs. Under hepatic induction, UC­MSCs and BM­MSCs could differentiate into hepatocytes. Reverse transcription­quantitative polymerase chain reaction (RT­qPCR) analysis revealed that a higher expression of the hepatocyte­specific genes albumin, cytochrome P450 3A4 (CYP3A4), tyrosine­aminotransferase, glucose­6phosphate, α1 antitrypsin and α­fetoprotein was detected in differentiated UC­MSCs when compared with differentiated BM­MSCs. The results of ELISA and western blotting were in accordance with those of RT­qPCR. Theses results indicated that UC­MSCs had higher hepatic differentiation potential than BM­MSCs. Therefore, UC­MSCs may be advantageous over BM­MSCs for the treatment of end­stage liver disease.

Optimal adjuvant chemotherapy for resected pancreatic adenocarcinoma: a systematic review and network meta-analysis.

Adjuvant chemotherapy improves survival in patients with resected pancreatic cancer but the optimal regimen remains unclear. We aim to compare all possible adjuvant chemotherapy in terms of overall survival and toxic effects. Pubmed, Trial registries and Cochrane library databases for randomized controlled trials were searched until November 2016. Thirteen trials were included for network analysis and the hazard ratios (HRs) for survival and odds ratios for toxic effects were assessed via Aggregate Data Drug Information System software. Only S-1 chemotherapy improved 1-year, 3-year and 5-year survival compared with observation (HR (95% CI): 3.94 (1.18-12.34); 4.08 (1.58-8.24) and 5.09 (1.16-29.83) respectively). Although not significant, gemcitabine plus uracil/tegafur was associated with poorer 1-year and 3-year survival compared with observation (HR (95% CI): 0.85 (0.16-4.03) and 0.86 (0.23-2.95)). Adding radiation to chemotherapy has no significant improvement in survival. S-1 and gemcitabine plus capecitabine are currently the most effective adjuvant therapies for pancreatic cancer. While S1 has only been validated in Asian people, higher toxicity is an issue for gemcitabine plus capecitabine.

HVPG signature: A prognostic and predictive tool in hepatocellular carcinoma.

Hepatic venous pressure gradient (HVPG) measurement provides independent prognostic value in patients with cirrhosis, and the prognostic and predictive role of HVPG in hepatocellular carcinoma (HCC) also has been explored. The management of HCC is limited to the European Association for the Study of the Liver (EASL) and American Association for the Study of Liver Diseases (AASLD) guidelines that consider that HVPG≥10 mmHg to be a contraindication for hepatic resection (HR), otherwise other treatment modalities are recommended. Current studies show that a raised HVPG diagnosed directly or indirectly leads to a negative prognosis of patients with HCC and cirrhosis, but HVPG greater than 10 mmHg should not be regarded as an absolute contraindication for HR. Selecting direct or surrogate measurement of HVPG is still under debate. Only several studies reported the impact of HVPG in negative prognosis of HCC patients after liver transplantation (LT) and the value of HVPG in the prediction of HCC development, which need to be further validated.

Long non-coding RNA TUG1 is up-regulated in hepatocellular carcinoma and promotes cell growth and apoptosis by epigenetically silencing of KLF2.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide, and the biology of this cancer remains poorly understood. Recent evidence indicates that long non-coding RNAs (lncRNAs) are found to be dysregulated in a variety of cancers, including HCC. Taurine Up-regulated Gene 1 (TUG1), a 7.1-kb lncRNA, recruiting and binding to polycomb repressive complex 2 (PRC2), is found to be disregulated in non-small cell lung carcinoma (NSCLC) and esophageal squamous cell carcinoma (ESCC). However, its clinical significance and potential role in HCC remain unclear. METHODS AND RESULTS: In this study, expression of TUG1 was analyzed in 77 HCC tissues and matched normal tissues by using quantitative polymerase chain reaction (qPCR). TUG1 expression was up-regulated in HCC tissues and the higher expression of TUG1 was significantly correlated with tumor size and Barcelona Clinic Liver Cancer (BCLC) stage. Moreover, silencing of TUG1 expression inhibited HCC cell proliferation, colony formation, tumorigenicity and induced apoptosis in HCC cell lines. We also found that TUG1 overexpression was induced by nuclear transcription factor SP1 and TUG1 could epigeneticly repress Kruppel-like factor 2 (KLF2) transcription in HCC cells by binding with PRC2 and recruiting it to KLF2 promoter region. CONCLUSION: Our results suggest that lncRNA TUG1, as a growth regulator, may serve as a new diagnostic biomarker and therapy target for HCC.

Long non-coding RNA ANRIL is upregulated in hepatocellular carcinoma and regulates cell apoptosis by epigenetic silencing of KLF2.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death, especially in China. And the mechanism of its progression remains poorly understood. Growing evidence indicates that long non-coding RNAs (lncRNAs) are found to be dysregulated in many cancers, including HCC. ANRIL, a lncRNA co-clustered mainly with p14/ARF has been reported to be dysregulated in gastric cancer, esophageal squamous cell carcinoma, and lung cancer. However, its clinical significance and potential role in HCC are still not documented. METHODS AND RESULTS: In this study, expression of ANRIL was analyzed in 77 HCC tissues and matched normal tissues by using quantitative polymerase chain reaction (qRT-PCR). ANRIL expression was upregulated in HCC tissues, and the higher expression of ANRIL was significantly correlated with tumor size and Barcelona Clinic Liver Cancer (BCLC) stage. Moreover, taking advantage of loss-of-function experiments in HCC cells, we found that knockdown of ANRIL expression could impair cell proliferation and invasion and induce cell apoptosis both in vitro and in vivo. We also found that ANRIL could epigenetically repress Kruppel-like factor 2 (KLF2) transcription in HCC cells by binding with PRC2 and recruiting it to the KLF2 promoter region. We also found that SP1 could regulate the expression of ANRIL. CONCLUSION: Our results suggest that lncRNA ANRIL, as a growth regulator, may serve as a new biomarker and target for therapy in HCC.

Long non-coding RNA ANRIL is upregulated in hepatocellular carcinoma and regulates cell proliferation by epigenetic silencing of KLF2.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death, especially in China. And the mechanism of its progression remains poorly understood. Growing evidence indicates that long non-coding RNAs (lncRNAs) are found to be dysregulated in many cancers, including HCC. CDKN2B antisense RNA1 (ANRIL), a lncRNA, coclustered mainly with p14/ARF has been reported to be dysregulated in gastric cancer, esophageal squamous cell carcinoma, and lung cancer. However, its clinical significance and potential role in HCC is still not documented. METHODS AND RESULTS: In this study, expression of ANRIL was analyzed in 77 HCC tissues and matched normal tissues by using quantitative real-time polymerase chain reaction (qRT-PCR). ANRIL expression was up-regulated in HCC tissues, and the higher expression of ANRIL was significantly correlated with tumor size and Barcelona Clinic Liver Cancer (BCLC) stage. Moreover, taking advantage of loss of function experiments in HCC cells, we found that knockdown of ANRIL expression could impair cell proliferation and invasion and induce cell apoptosis both in vitro and in vivo. We also found that ANRIL could epigenetically repress KLF2 transcription in HCC cells by binding with PRC2 and recruiting it to KLF2 promoter region. We also found that Sp1 could regulate the expression of ANRIL. CONCLUSION: Our results suggest that lncRNA ANRIL, as a growth regulator, may serve as a new biomarker and target for therapy in HCC.

Adjuvant interferon therapy after surgical treatment for hepatitis B/C virus-related hepatocellular carcinoma: A meta-analysis.

AIM: This meta-analysis aimed to determine whether interferon (IFN) therapy could improve clinical effects of patients with chronic hepatitis B virus (HBV)or hepatitis C virus (HCV) infection-related primary hepatocellular carcinoma (HCC) after surgery. METHODS: An electronic search from January 1998 to December 2012 was conducted to identify comparative studies evaluating IFN therapy on recurrence and survival after surgical treatment of HCC. RESULTS: The estimated odds ratios (OR) for the 1-, 2-, 3- and 5-year overall survival rates of HBV-related HCC were 3.37 (95% confidence interval [CI], 1.18-6.27), 2.36 (95% CI, 1.45-3.83), 1.81 (95% CI, 1.21-2.72) and 1.93 (95% CI, 1.35-2.75), respectively; and the OR for the 1-, 2-, 3- and 5-year recurrence rates were 0.63 (95% CI, 0.44-0.91), 0.84 (95% CI, 0.60-1.18), 0.88 (95% CI, 0.63-1.22) and 0.78 (95% CI, 0.56-1.07), respectively. The overall survival rates of HCV-related HCC were significantly higher in IFN groups than in control groups at 1, 2, 3 and 5 years (OR, 2.10; 95% CI, 0.96-4.55; OR, 1.71; 95% CI, 1.01-2.89; OR, 1.76; 95% CI, 1.09-2.83; and OR, 3.03; 95% CI, 1.97-4.65, respectively); and the recurrence rates of IFN groups were lower than control groups at 1, 2, 3 and 5 years (OR, 0.60; 95% CI, 0.38-0.92; OR, 0.57; 95% CI, 0.41-0.81; OR, 0.58; 95% CI, 0.41-0.80; and OR, 0.52; 95% CI, 0.36-0.75, respectively). CONCLUSION: In conclusion, IFN therapy in this meta-analysis shows a significant clinical effect in postoperative patients of HCC, particularly in HCV-related HCC.

Meta-analysis of surgical resection and radiofrequency ablation for early hepatocellular carcinoma.

BACKGROUND: There is no definite agreement on the better therapy (radiofrequency ablation (RFA) versus surgical resection (SR)) for early hepatocellular carcinoma (HCC) eligible for surgical treatments. The purpose of this study is to evaluate the evidence using meta-analytical techniques. METHODS: A literature search was undertaken until December 2011 to identify comparative studies evaluating survival rates, recurrence rates, and complications. Pooled odds ratios (OR) and 95% confidence intervals (95% CI) were calculated with either the fixed or random effect model. RESULTS: Thirteen articles, comprising two randomized controlled trials(RCTs), were included in the review, with a total of 2,535 patients (1,233 treated with SR and 1,302 with RFA). The overall survival rates were significantly higher in patients treated with SR than RFA after1, 3, and 5 years (respectively: OR, 0.60 (95% CI, 0.42 to 0.86); OR, 0.49 (95% CI, 0.36 to 0.65); OR, 0.60 (95% CI, 0.43 to 0.84)). In the SR group, the 1, 3, and 5 years recurrence rates were significantly lower than the RFA group (respectively: OR, 1.48 (95% CI, 1.05 to 2.08); OR, 1.76 (95% CI, 1.49 to 2.08); OR, 1.68 (95% CI, 1.21 to 2.34)). However, local recurrence between two groups did not exhibit significant difference. For HCC ≤ 3 cm in diameter, SR was better than RFA at the 1, 3, and 5 years overall survival rates (respectively: OR, 0.34 (95% CI, 0.13 to 0.89); OR, 0.56 (95% CI, 0.37 to 0.84); OR, 0.44 (95% CI, 0.31 to 0.62)). This meta-analysis indicated that the complication of SR was higher than RFA (OR, 6.25 (95%CI, 3.12 to 12.52); P = 0.000). CONCLUSION: Although local recurrence between two groups did not exhibit significant difference, SR demonstrated significantly improved survival benefits and lower complications for patients with early HCC, especially for HCC ≤ 3 cm in diameter. These findings should be interpreted carefully, owing to the lower level of evidence.

Genetic variation in the NBS1 gene is associated with hepatic cancer risk in a Chinese population.

NBS1 plays important roles in maintaining genomic stability as a key DNA repair protein in the homologous recombination repair pathway and as a signal modifier in the intra-S phase checkpoint. We hypothesized that polymorphisms of NBS1 are associated with hepatic cancer (HCC) risk. The NBS1 rs1805794 C/G polymorphism has been frequently studied in some cancers with discordant results, but its association with HCC has not been investigated. Moreover, studies of the 3'UTR variant rs2735383 have not touched upon HCC. This study examined the contribution of these two polymorphisms to the risk of developing HCC in a Chinese population. NBS1 genotypes were determined in 865 HCC patients and 900 controls and the associations with risk of HCC were estimated by logistic regression. Compared with the rs1805794 GG genotype, the GC genotype had a significantly increased risk of HCC (adjusted odds ratios [OR]=1.41; 95% confidence interval [CI]=1.11-1.80), the CC carriers had a further increased risk of HCC (OR=2.27; 95% CI=1.68-3.14), and there was a trend for an allele dose effect on risk of HCC (p<0.001). Also, we found that the risk effect of rs1805794 CC+CG was more pronounced in HCC patients that drank (OR=2.28, 95% CI=1.55-3.29 for drinkers; OR=1.31, 95% CI=1.00-1.77 for nondrinkers). However, there was no significant difference in genotype frequencies of rs2735383 G/C site between cases and controls. These findings suggest that rs1805794 C/G polymorphism in NBS1 may be a genetic modifier for developing HCC.