Search

Objectives: This consensus was developed by the Asian EUS Group (AEG), who aimed to formulate a set of practice guidelines addressing various aspects of endoscopic ultrasound‐guided tissue acquisition (EUS‐TA). Methods: The AEG initiated the development of consensus statements and formed an expert panel comprising surgeons, gastroenterologists, and pathologists. Three online consensus meetings were conducted to consolidate the statements and votes. The statements were presented and discussed in the first two consensus meetings and revised according to comments. Final voting was conducted at a third consensus meeting. The Grading of Recommendations, Assessment, Development, and Evaluation system was adopted to define the strength of the recommendations and quality of evidence. Results: A total of 20 clinical questions and statements regarding EUS‐TA were formulated. The committee recommended that fine‐needle biopsy (FNB) needles be preferred over conventional fine‐needle aspiration (FNA) needles for EUS‐TA of subepithelial lesions. For solid pancreatic masses, rapid on‐site evaluation is not routinely recommended when FNB needles are used. For dedicated FNB needles, fork‐tip and Franseen‐tip needles have essentially equivalent performance. Conclusion: This consensus provides guidance for EUS‐TA, thereby enhancing the quality of EUS‐TA. [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Tong et al papers. To view these articles, visit https://doi.org/10.1111/apt.17263 and https://doi.org/10.1111/apt.17423 [ABSTRACT FROM AUTHOR]

Background and Aim: We aimed to determine whether lobular inflammation and ballooning grades in the Non‐alcoholic Steatohepatitis Clinical Research Network (NASH CRN) scoring system can be directly translated into the same for the Steatosis Activity Fibrosis scoring system (SAF) and to look at intra‐observer and inter‐observer agreement for each individual histological component and for diagnosis of non‐alcoholic steatohepatitis (NASH) using the two scoring systems. Methods: Four pathologists from two Asian centers scored 20 digitalized slides, twice using the NASH CRN, twice using the SAF. Intra‐observer and inter‐observer agreement was analyzed using Fleiss' kappa, weighted kappa, or Cohen kappa, where appropriate. Results: The intra‐observer discrepancy rate when using the NASH CRN compared with the SAF was higher than when using the individual scoring system for lobular inflammation (15% comparing both scoring systems vs 10% and 1.8% for the NASH CRN and the SAF, respectively) and hepatocyte ballooning (33.8% vs 12.5% and 5%, respectively), but not for diagnosis of NASH (6.3% vs 6.3% and 0%, respectively). Intra‐observer and inter‐observer agreement was substantial to almost perfect, except for inter‐observer agreement for lobular inflammation and diagnosis of NASH, which was only fair to moderate in most instances. Conclusion: These findings do not support the direct inter‐translation between the NASH CRN and the SAF. However, the diagnosis of NASH during examinations using the NASH CRN may be comparable with diagnosis of NASH using the SAF, vice versa. The inter‐observer agreement for lobular inflammation and NASH diagnosis needs to be improved. [ABSTRACT FROM AUTHOR]

Enhancing through epigenetics: A challenge for cancer immunotherapy is the need to turn cold, immune cell–excluded tumors into hot, inflamed tumors. Here, Yang et al. investigated the role of histone deacetylase 8 (HDAC8) in maintaining immune cell–excluded tumors. The authors showed that selective pharmacological inhibition of HDAC8 changed the epigenetic landscape of hepatocellular carcinoma cells, leading to production of T cell–recruiting chemokines. Treatment of hepatocellular carcinoma–bearing mice with the selective HDAC8 inhibitor resulted in increased infiltration of CD8+ T cells. Further, treatment with the HDAC8 inhibitor and immune checkpoint blockade led to enhanced control of tumors with no evidence of toxicity. Thus, epigenetic reprogramming used in combination with immunotherapy may be a promising approach for treating hepatocellular carcinomas and other immunologically cold tumors. Insufficient T cell infiltration into noninflamed tumors, such as hepatocellular carcinoma (HCC), restricts the effectiveness of immune-checkpoint blockade (ICB) for a subset of patients. Epigenetic therapy provides further opportunities to rewire cancer-associated transcriptional programs, but whether and how selective epigenetic inhibition counteracts the immune-excluded phenotype remain incompletely defined. Here, we showed that pharmacological inhibition of histone deacetylase 8 (HDAC8), a histone H3 lysine 27 (H3K27)–specific isozyme overexpressed in a variety of human cancers, thwarts HCC tumorigenicity in a T cell–dependent manner. The tumor-suppressive effect of selective HDAC8 inhibition was abrogated by CD8+ T cell depletion or regulatory T cell adoptive transfer. Chromatin profiling of human HDAC8-expressing HCCs revealed genome-wide H3K27 deacetylation in 1251 silenced enhancer-target gene pairs that are enriched in metabolic and immune regulators. Mechanistically, down-regulation of HDAC8 increased global and enhancer acetylation of H3K27 to reactivate production of T cell–trafficking chemokines by HCC cells, thus relieving T cell exclusion in both immunodeficient and humanized mouse models. In an HCC preclinical model, selective HDAC8 inhibition increased tumor-infiltrating CD8+ T cells and potentiated eradication of established hepatomas by anti–PD-L1 therapy without evidence of toxicity. Mice treated with HDAC8 and PD-L1 coblockade were protected against subsequent tumor rechallenge as a result of the induction of memory T cells and remained tumor-free for greater than 15 months. Collectively, our study demonstrates that selective HDAC8 inhibition elicits effective and durable responses to ICB by co-opting adaptive immunity through enhancer reprogramming. [ABSTRACT FROM AUTHOR]

Artificial intelligence (AI) has become increasingly widespread in our daily lives, including healthcare applications. AI has brought many new insights into better ways we care for our patients with chronic liver disease, including non‐alcoholic fatty liver disease and liver fibrosis. There are multiple ways to apply the AI technology on top of the conventional invasive (liver biopsy) and noninvasive (transient elastography, serum biomarkers, or clinical prediction models) approaches. In this review article, we discuss the principles of applying AI on electronic health records, liver biopsy, and liver images. A few common AI approaches include logistic regression, decision tree, random forest, and XGBoost for data at a single time stamp, recurrent neural networks for sequential data, and deep neural networks for histology and images. [ABSTRACT FROM AUTHOR]

Purpose: In MRI, the macromolecular proton fraction (MPF) is a key parameter of magnetization transfer (MT). It represents the relative amount of immobile protons associated with semi‐solid macromolecules involved in MT with free water protons. We aim to quantify MPF based on spin‐lock MRI and explore its advantages over the existing MPF‐mapping methods. Methods: In the proposed method, termed MPF quantification based on spin‐lock (MPF‐SL), off‐resonance spin‐lock is used to sensitively measure the MT effect. MPF‐SL is designed to measure a relaxation rate (Rmpfsl) that is specific to the MT effect by removing the R1ρ relaxation due to the mobile water and chemical exchange pools. A theory is derived to quantify MPF from the measured Rmpfsl. No prior knowledge of tissue relaxation parameters, including T1 or T2, is needed to quantify MPF using MPF‐SL. The proposed approach is validated with Bloch‐McConnell simulations, phantom, and in vivo liver studies at 3.0T. Results: Both Bloch‐McConnell simulations and phantom experiments show that MPF‐SL is insensitive to variations of the mobile water pool and the chemical exchange pool. MPF‐SL is specific to the MT effect and can measure MPF reliably. In vivo liver studies show that MPF‐SL can be used to detect collagen deposition in patients with liver fibrosis. Conclusion: A novel MPF imaging method based on spin‐lock MRI is proposed. The confounding factors are removed, and the measurement is specific to the MT effect. It holds promise for MPF‐sensitive diagnostic imaging in clinical settings. [ABSTRACT FROM AUTHOR]

Nasopharyngeal carcinoma (NPC) is an Epstein‐Barr virus (EBV)‐associated epithelial malignancy. The high expression of BART‐miRNAs (miR‐BARTs) during latent EBV infection in NPC strongly supports their pathological importance in cancer progression. Recently, we found that several BART‐miRNAs work co‐operatively to modulate the DNA damage response (DDR) by reducing Ataxia‐telangiectasia‐mutated (ATM) activity. In this study, we further investigated the role of miR‐BARTs on DDR. The immunohistochemical study showed that the DNA repair gene, BRCA1, is consistently down‐regulated in primary NPCs. Using computer prediction programs and a series of reporter assays, we subsequently identified the negative regulatory role of BART2‐3p, BART12, BART17‐5p and BART19‐3p in BRCA1 expression. The ectopic expression of these four miR‐BARTs suppressed endogenous BRCA1 expression in EBV‐negative epithelial cell lines, whereas BRCA1 expression was enhanced by repressing endogenous miR‐BARTs activities in C666‐1 cells. More importantly, suppressing BRCA1 expression in nasopharyngeal epithelial cell lines using miR‐BART17‐5p and miR‐BART19‐3p mimics reduced the DNA repair capability and increased the cell sensitivity to the DNA‐damaging chemotherapeutic drugs, cisplatin and doxorubicin. Our findings suggest that miR‐BARTs play a novel role in DDR and may facilitate the development of effective NPC therapies. [ABSTRACT FROM AUTHOR]

Background: The aim of current study was to (1) construct and validate a novel hepatocellular carcinoma (HCC)-specific inflammatory index; (2) compare the performances of the Integrated Liver Inflammatory Score (ILIS) to existing 4 inflammatory indices in HCC; (3) explore the association between the inflammatory indices and systemic/intratumoral inflammatory markers. Methods: Two cohorts from Hong Kong (HK; n = 1,315) and Newcastle (n = 574) were studied. A novel index was constructed from the HK training set (n = 627). The index was constructed from the training set by combing independent prognostic circulating parameters, followed by validating in the validation set of HK cohort (n = 688) and the Newcastle cohort. Its prognostic performance was compared to 4 inflammatory indices, namely, the neutrophil to lymphocyte ratio, platelet-to-lymphocyte ratio, prognostic nutrition index, and systemic immune-inflammation index, were compared in the HK cohort. Circulating cytokines and intratumoral gene expression were analyzed in a subset of patients with available samples and correlated with the inflammatory indices. Results: In the training set of the HK cohort, the ILIS, was generated: –0.057 × albumin (g/L) + 0.978 × log (Bilirubin, µmol/L) + 1.341 × log (alkaline phosphatase, IU/L) + 0.086 × Neutrophil (109/L) + 0.301 × log (alpha-fetoprotein, µg/L). With cutoff of 2.60 and 3.87, the ILIS could categorize patients into 3 risk groups in the both validation cohorts. ILIS outperforms other inflammatory indices and remains an independent prognosticator for overall survival after adjustment with Barcelona Clinic Liver Cancer (hazard ratio 31.90, p < 0.001). The ILIS had the best prognostic performances as compared to other inflammatory indices. In exploratory analyses, the ILIS correlated with circulating inflammatory cytokines (e.g., IL-8) but not with any intratumoral inflammatory gene expression. Conclusions: ILIS is an HCC-specific prognostic index built on 5 readily available blood parameters. Its versatility is validated both Eastern and Western population of HCC. The score is correlated with levels of circulating cytokines. [ABSTRACT FROM AUTHOR]

Background: The advantages of radiofrequency ablation (RFA) over hepatectomy as a treatment for early-stage hepatocellular carcinoma (HCC) include reduced morbidity and more rapid recovery. Although minimally invasive surgery provides similar benefits, few studies have compared the long-term oncological outcomes of these techniques. This study aimed to compare the outcomes of minimally invasive hepatectomy (MIH) and RFA. Methods: Patients who underwent MIH or RFA for HCC between January 2005 and January 2015 were included in a propensity score matching analysis. Only patients who underwent minimally invasive procedures for small HCC were included. Baseline clinical and laboratory parameters were retrieved from the hospital database and analyzed. Results: Two hundred and twenty-five patients underwent MIH or RFA for HCC during the study period. Propensity score matching yielded 59 patient-pairs. The complication rates did not differ statistically between the 2 groups (p = 0.309). However, MIH provided significantly better overall (p = 0.005) and disease-free survival outcomes (p < 0.001) than RFA. Conclusions: Compared with RFA, MIH provided better long-term survival outcomes in patients with early-stage HCC, with no increase in the incidence of complications. When feasible, MIH should be considered a first-line treatment for this patient population. [ABSTRACT FROM AUTHOR]

Background and Aim: The Baveno VI Consensus recommends repeating examination in patients with high liver stiffness measurement (LSM) by transient elastography to reduce false‐positive diagnosis of advanced liver disease. We tested whether repeating transient elastography can increase the overall diagnostic accuracy. Methods: Ninety‐seven patients with non‐alcoholic fatty liver disease who underwent two FibroScan examinations within 6 months prior to liver biopsy were evaluated. An LSM cut‐off of 7.9 kPa was used to exclude F3‐4 fibrosis. Results: Seventy‐eight patients had high LSM at baseline, among whom 27 had low LSM on repeated testing; only four had F3 and none had cirrhosis. In contrast, 31 of 51 patients with high LSM at both examinations had F3‐4. Nineteen patients had low LSM at baseline; none of them had F3‐4 regardless of the second LSM results. If we took LSM <7.9 kPa at either examination as sufficient to exclude F3‐4, the negative predictive value remained high at 91%. The positive predictive value for F3‐4 increased from 45% in patients with high LSM at baseline to 61% in those with high LSM at both examinations. Sensitivity analysis using different cut‐offs yielded similar results, with 76% of patients with LSM >12 kPa at both examinations having F3‐4. Conclusions: Transient elastography is a highly sensitive screening test to exclude F3‐4 fibrosis in non‐alcoholic fatty liver disease patients. One‐third of patients with high LSM may have normal results on repeated examination. By repeating examination in cases with high LSM, one may spare patients from unnecessary liver biopsy. [ABSTRACT FROM AUTHOR]

Background and Aim The FibroMeter vibration-controlled transient elastography (FM VCTE) is a new formula combining the serum test FM and liver stiffness measurement (LSM) by VCTE. We tested the accuracy and utility of FM VCTE for fibrosis staging in patients with non-alcoholic fatty liver disease (NAFLD). Methods Two hundred fifteen NAFLD patients with LSM, FM NAFLD, FM VCTE, and other serum tests (aspartate aminotransferase-to-platelet ratio index, fibrosis-4 index, BARD score, NAFLD fibrosis score, and aspartate aminotransferase-to-alanine aminotransferase ratio) performed 1 day before liver biopsy were evaluated. Results Sixty-nine (32.1%) and 43 (20.0%) patients had F2-4 and F3-4, respectively. LSM had higher diagnostic accuracy (area under receiver-operating characteristics curves [AUROC] 0.851 for F2-4, 0.940 for F3-4; Obuchowski index 0.937 ± 0.007) than all evaluated serum tests, while FM NAFLD was the most accurate serum test (AUROC 0.775 and 0.774; Obuchowski index 0.891 ± 0.013). FM VCTE had similar accuracy to LSM (AUROC 0.855 and 0.901; Obuchowski index 0.927 ± 0.009). LSM had excellent negative predictive values of 92.4% and 99.2% to exclude F2-4 and F3-4, but the positive predictive values (PPV) were only 71.4% and 61.0%, respectively. In patients with high LSM, the use of FM VCTE improved the PPV from 71.4% to 84.4% for F2-4 and from 61.0% to 88.9% for F3-4. Liver biopsy could be spared in around 50-65% of patients. Conclusions Liver stiffness measurement alone can confidently exclude significant and advanced fibrosis in NAFLD patients. Using FM VCTE in patients with high liver stiffness can increase the positive predictive value to rule in F2-4 and F3-4. [ABSTRACT FROM AUTHOR]

Background and Aim Liver stiffness measurement using transient elastography appears to be an excellent tool for detection of liver fibrosis and cirrhosis with high accuracy. The aim of this study is to evaluate the efficacy of preoperative liver stiffness measurement in predicting post-hepatectomy liver failure. Methods A prospective cohort study of all consecutive patients undergoing hepatectomy for hepatocellular carcinoma from February 2010 to August 2014 was studied. All patients received detailed preoperative assessments including liver stiffness measurement. The primary outcome was post-hepatectomy liver failure according to the International Study Group of Liver Surgery definition. Results A total of 255 patients were included. Liver stiffness measurement showed significant correlation with grade B or C post-hepatectomy liver failure. ( P = 0.003) Using the cutoff at 12 kPa, liver stiffness measurement had a sensitivity of 52.4% and specificity of 73.3% in predication of high-grade (grade B or C) post-hepatectomy liver failure. Liver stiffness measurement > 12 kPa was also an independent prognostic factor for both high-grade post-hepatectomy liver failure and major postoperative complications by multivariate analysis. The diagnostic accuracy was better in patients without right lobe tumor with an area under the receiver operating characteristic of 0.83 compared with an area under the receiver operating characteristic of only 0.62 in patients with right lobe tumor. Conclusions Liver stiffness measurement using Fibroscan is good to predict high-grade post-hepatectomy liver failure especially in patients without right lobe tumor. [ABSTRACT FROM AUTHOR]

Background and Aim Controlled attenuation parameter (CAP) evaluated with transient elastography (FibroScan) is a recent method for non-invasive assessment of steatosis. Its usefulness in non-alcoholic fatty liver disease (NAFLD) is unknown. We prospectively investigated the performance of CAP for the diagnosis of steatosis in NAFLD, factors associated with discordances between CAP and steatosis grades, and relationships between CAP and clinical or biological parameters. Methods All CAP examinations performed in NAFLD patients with a liver biopsy performed within 1 week of CAP measurement were included. Liver biopsies were assessed for activity and fibrosis stage, NAFLD activity score, and steatosis graded as follows: S0, steatosis < 5%; S1, 5-33%; S2, 34-66%; S3, >66%. Results Two hundred sixty-one patients (59% male, age 56 years) from two ethnic groups were included. No patient had steatosis < 5%. The area under the receiver-operating characteristics curve of CAP for steatosis ≥S2 and S3 was 0.80 and 0.66, respectively. At a cut-off value of 310 dB/m, the sensitivity, specificity, and positive and negative predictive values for ≥S2 steatosis were 79%, 71%, 86%, and 71%, respectively. Discordance of at least one grade between CAP and steatosis was observed in 81 patients. By multivariate analysis, only steatosis S2S3 was associated with no discordance. By multivariate analysis, only BMI ≥ 30 kg/m2 was significantly associated with CAP > 310 dB/m. Conclusion The association of CAP with steatosis, especially in patients with non-alcoholic steatohepatitis, and with elevated BMI could be useful for the diagnosis and follow-up of NAFLD patients. [ABSTRACT FROM AUTHOR]

Background/Aims Interleukin-28 B ( IL28B) and patatin-like phospholipase domain containing 3 ( PNPLA3) gene polymorphisms are associated with hepatitis C virus ( HCV) clearance and fatty liver, respectively. We aimed to test if their polymorphisms are associated with virologic responses in Chinese chronic hepatitis C ( CHC) patients. Methods This was a retrospective-prospective cohort study. Consecutive patients infected by genotype 1 and 6 HCV received antiviral therapy were included. Host IL- 28B rs12979860/rs8099917 and PNPLA3 rs738409 genotype were tested. The primary outcome was sustained virologic response (sustained virologic response [ SVR]: undetectable HCV RNA 24 weeks post-treatment). Results From 305 patients had positive antibody to HCV, 52 and 31 patients infected by genotype 1 and 6 HCV, respectively were recruited. Mean age was 58 ± 11 years; 70% were male. Mean baseline HCV RNA was 6.8 ± 2.7 log IU/ml. The SVR for patients infected by genotype 1 and 6 HCV was 67.3% and 90.3%, respectively. The proportions of IL28B genotypes were 78%, 21%, and 1% for TT/ TG/ GG at rs8099917, and 81%, 18%, and 1% for CC/ TC/ TT at rs12979860, respectively. The proportions of PNPLA3 rs738409 genotypes were 16%, 36%, and 48% for GG/ GC/ CC. IL28B genotype was significantly associated with SVR in patients infected by genotype 1 but not genotype 6 HCV, with 80% versus 38% of patients infected by genotype 1 achieved SVR carried TT versus TG/ GG at rs8099917, respectively ( P = 0.003). PNPLA3 genotype was not associated with SVR. Conclusions IL28B gene with rs8099917 T allele as an independent predictor of SVR in Chinese CHC patients infected by genotype 1 but not genotype 6 HCV. [ABSTRACT FROM AUTHOR]

Background and Aims Non-alcoholic steatohepatitis ( NASH) is a common liver disease that may progress to cirrhosis and hepatocellular carcinoma. There is currently no approved pharmacological treatment for NASH. Phyllanthus urinaria is a commonly used hepatoprotective herb that ameliorates NASH in animal studies. We aimed to test the hypothesis that Phyllanthus was superior to placebo in improving histological non-alcoholic fatty liver disease ( NAFLD) activity score. Methods This was a placebo-controlled parallel-group double-blind randomized controlled trial. Patients with histology-proven NASH were randomized to receive Phyllanthus or placebo for 24 weeks. The primary endpoint was change in NAFLD activity score from baseline to week 24. Secondary endpoints included changes in individual histological parameters, liver biochemistry and metabolic profile. Results We enrolled 60 patients (40 received Phyllanthus and 20 received placebo). The change in NAFLD activity score was −0.8 ± 1.4 in the Phyllanthus group and −0.3 ± 1.3 in the placebo group ( P = 0.24). The change in steatosis, lobular inflammation, ballooning and fibrosis was also similar between the two groups. Within the Phyllanthus group, although there was reduction in hepatic steatosis (−0.2 ± 0.7; P = 0.039) and ballooning grades (−0.4 ± 0.5; P < 0.001), the change was small and of limited clinical significance. Furthermore, there was no significant difference in the changes in alanine aminotransferase, aspartate aminotransferase, fasting glucose and lipid profile between the two groups. Conclusions Phyllanthus is not superior to placebo in improving NAFLD activity score in NASH patients. [ABSTRACT FROM AUTHOR]

OBJECTIVES:Liver stiffness measurement (LSM) by transient elastography is a noninvasive test of liver fibrosis, but cannot be performed in a significant proportion of obese patients. The aim of this study was to evaluate the performance of the new XL probe in patients with nonalcoholic fatty liver disease (NAFLD).METHODS:Liver biopsy and paired LSM by both the original M probe and XL probe were performed on 193 consecutive NAFLD patients in France and Hong Kong.RESULTS:Compared with M probe, XL probe was more likely to achieve 10 valid measurements (95% vs. 81%; P<0.001) and a success rate of over 60% (90% vs. 74%; P<0.001). The areas under receiver operating characteristics curves of XL probe for F2, F3, and F4 disease were 0.80, 0.85, and 0.91, respectively. XL probe tended to generate lower LSM than M probe in the same patient. At a cutoff of 7.2 kPa, the sensitivity, specificity, positive, and negative predictive values for F3 or greater disease were 78%, 78%, 60%, and 89%, respectively. Discordance of at least two stages between XL probe and histology was observed in 16 (9%) patients. Body mass index (BMI) over 35 kg/m2 was independently associated with discordance (adjusted odds ratio 9.09; 95% confidence interval 1.10-75.43). Reliable measurements by XL probe were obtained in 75% of the overall population and 65% of patients with BMI over 30 kg/m2.CONCLUSIONS:LSM by XL probe can be performed successfully in most NAFLD patients, but obesity is associated with less accurate and reliable measurements. [ABSTRACT FROM AUTHOR]

The article presents a case study concerning a 45-year old man with pineal region tumor for over 15 years. It notes that the patient has been said to have headache and vomiting for 15 years. It mentions that he was diagnosed with obstructive hydrocephalus due to a pineal region tumour. It cites that histological examination has shown to have a cellular epithelioid papillary tumour.

BACKGROUND AND AIMS: We aimed to investigate the relationship between serum hepatitis B virus (HBV) DNA and alanine transaminase (ALT) levels and the risk of cirrhosis in a large cohort of hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) patients based on transient elastography. METHODS: We prospectively studied treatment-naive HBeAg-negative patients recruited based on territory-wide referrals. We defined possible cirrhosis and probable cirrhosis with two different cutoffs according to the results from a subgroup of patients with histologic proof. RESULTS: One thousand one hundred ninety-seven patients with successful liver stiffness measurement (LSM) were studied. In the subgroup of 100 patients with liver biopsy, LSM of ≥8.4 kiloPascal (kPa) had a sensitivity of 90% and LSM of ≥13.4 kPa had a specificity of 94% for liver cirrhosis. Possible and probable cirrhosis were defined as a LSM value ≥8.4 kPa and ≥13.4 kPa, and were present in 31% and 11% of the patients, respectively. The risk of cirrhosis was significantly increased when ALT level was >0.5× upper limit of normal (ULN) or serum HBV DNA >4 log10 copies/mL. Among patients who have ALT ≤0.5 × ULN and HBV DNA ≤4 log10 copies/mL, 10% (26/264) and 3% (7/264) had possible and probable cirrhosis respectively, which were significantly lower when compared with 34% (329/887, P < 0.001) and 14% (125/887, P < 0.001) of those who had higher ALT and HBV DNA levels. CONCLUSIONS: Liver cirrhosis was common among HBeAg-negative CHB patients. Patients with ALT levels >0.5 × ULN and/or serum HBV DNA >4 log10 copies/mL have higher risk of cirrhosis and need further assessment for antiviral therapy. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is a kind of solid tumor and the third most common cancer type in the world. It is a heterogeneous disease characterized by genetic and epigenetic aberrations. The TP53 mutation is the key step driving the transition from adenoma to adenocarcinoma. The functional roles of TP53 mutation in tumor development have been comprehensively investigated. In CRC, TP53 mutation was associated with poor prognosis and chemoresistance. A gain of function (GOF) of p53 mutants promotes cell proliferation, migration and invasion through multiple mechanisms. Restoring wild type p53 function, depleting p53 mutants, or intervention by targeting the oncogenic downstreams provides potential therapeutic strategies. In this review, we comprehensively summarize the GOF of p53 mutants in CRC progression as well as in some other solid tumors, and discuss the current strategies targeting p53 mutants in malignancies. [ABSTRACT FROM AUTHOR]

Background: Patients with colorectal cancer (CRC) have a high incidence of regional and distant metastases. Although metastasis is the main cause of CRC-related death, its molecular mechanisms remain largely unknown. Methods: Using array-CGH and expression microarray analyses, changes in DNA copy number and mRNA expression levels were investigated in human CRC samples. The mRNA expression level of RASAL2 was validated by qRT-PCR, and the protein expression was evaluated by western blot as well as immunohistochemistry in CRC cell lines and primary tumors. The functional role of RASAL2 in CRC was determined by MTT proliferation assay, monolayer and soft agar colony formation assays, cell cycle analysis, cell invasion and migration and in vivo study through siRNA/shRNA mediated knockdown and overexpression assays. Identification of RASAL2 involved in hippo pathway was achieved by expression microarray screening, double immunofluorescence staining and co-immunoprecipitation assays. Results: Integrated genomic analysis identified copy number gains and upregulation of RASAL2 in metastatic CRC. RASAL2 encodes a RAS-GTPase-activating protein (RAS-GAP) and showed increased expression in CRC cell lines and clinical specimens. Higher RASAL2 expression was significantly correlated with lymph node involvement and distant metastasis in CRC patients. Moreover, we found that RASAL2 serves as an independent prognostic marker of overall survival in CRC patients. In vitro and in vivo functional studies revealed that RASAL2 promoted tumor progression in both KRAS/NRAS mutant and wild-type CRC cells. Knockdown of RASAL2 promoted YAP1 phosphorylation, cytoplasm retention and ubiquitination, therefore activating the hippo pathway through the LATS2/YAP1 axis. Conclusions: Our findings demonstrated the roles of RASAL2 in CRC tumorigenesis as well as metastasis, and RASAL2 exerts its oncogenic property through LATS2/YAP1 axis of hippo signaling pathway in CRC. [ABSTRACT FROM AUTHOR]

Background: Granulin epithelin precursor (GEP) is reported to function as a growth factor stimulating proliferation and migration, and conferring chemoresistance in many cancer types. However, the expression and functional roles of GEP in colorectal cancer (CRC) remain elusive. The aim of this study was thus to investigate the clinical significance of GEP in CRC and reveal the molecular mechanism of GEP in CRC initiation and progression.Methods: The mRNA expression of GEP in CRC cell lines were detected by qRT-PCR. The GEP protein expression was validated by immunohistochemistry in tissue microarray (TMA) including 190 CRC patient samples. The clinicopathological correlation analysis were achieved by GEP expression on TMA. Functional roles of GEP were determined by MTT proliferation, monolayer colony formation, cell invasion and migration and in vivo studies through siRNA/shRNA mediated knockdown assays. The cancer signaling pathway identification was acquired by flow cytometry, western blot and luciferase activity assays.Results: The mRNA expression of GEP in CRC was significantly higher than it in normal colon tissues. GEP protein was predominantly localized in the cytoplasm and most of the CRC cases demonstrated abundant GEP protein compared with non-tumorous tissues. GEP overexpression was associated with non-rectal location, advanced AJCC stage, regional lymph node and distant metastasis. By Kaplan-Meier survival analysis, GEP abundance served as a prognostic marker for worse survival in CRC patients. GEP knockdown exhibited anti-cancer effect such as inhibiting cell proliferation, monolayer colony formation, cell invasion and migration in DLD-1 and HCT 116 cells and decelerating xenograft formation in nude mice. siGEP also induced G1 cell cycle arrest and apoptosis. Luciferase activity assays further demonstrated GEP activation was involved in MAPK/ERK signaling pathway.Conclusion: In summary, we compressively delineate the oncogenic role of GEP in colorectal tumorigenesis by activating MAPK/ERK signaling pathway. GEP might serve as a useful prognostic biomarker and therapeutic target for CRC. [ABSTRACT FROM AUTHOR]

The article presents a case study of 27-year-old man suffering from hepatitis B carrier along with an 8-cm right lobe liver mass that was detected on computed tomography during evaluation of his recurrent pneumothorax. Topics include Castleman's disease, hepatectomy and coexistence of a rare lymphoid disease in a patient with hepatocellular carcinoma.