Identifying the optimal measurement timing and hemodynamic targets of portal pressure gradient after TIPS in patients with cirrhosis and variceal bleeding.

BACKGROUND & AIMS: The optimal timing of measurement and hemodynamic targets of portacaval pressure gradient (PPG) after transjugular intrahepatic portosystemic shunt (TIPS) placement remain unclear. This study aimed to identify the ideal moment for hemodynamic measurements and the optimal target of PPG in patients undergoing covered TIPS for variceal bleeding. METHODS: Between May 2018 and December 2021, 466 consecutive patients with recurrent variceal bleeding treated with covered TIPS were prospectively included. Post-TIPS PPG was measured immediately (immediate PPG), 24-72 hours (early PPG), and again 1 month (late PPG) after TIPS placement. The agreement among PPGs measured at different time points was assessed by intra-class correlation coefficient (ICC) and Bland-Altman method. The unadjusted and confounder-adjusted effects of PPGs on clinical outcomes (portal hypertensive complications [PHCs], overt hepatic encephalopathy [OHE], further decompensation, and death) were assessed using Fine and Gray competing risk regression models. RESULTS: The agreement between early PPG and late PPG (ICC: 0.34) was better than that between immediate PPG and late PPG (ICC: 0.23, p <0.001). Early PPG revealed an excellent predictive value for PHCs (early PPG≥ vs. <12 mmHg: adjusted hazard ratio 2.17, 95% CI 1.33-3.55, p = 0.002) and OHE (0.40, 95% CI 0.17-0.91, p = 0.030), while immediate PPG did not. Late PPG showed a predictive value for PHC risk but not OHE. By targeting the lowest risk of further decompensation, we identified an optimal hemodynamic target with early PPG ranging from 11 to 14 mmHg that was associated with a decreased risk of OHE and effective prevention of PHC. CONCLUSIONS: PPG measured 24 to 72 hours after TIPS correlates with long-term PPG and clinical outcomes, and a hemodynamic target PPG of 11-14 mmHg is associated with reduced encephalopathy but not compromised clinical efficacy. IMPACT AND IMPLICATIONS: The optimal timing of measurement and hemodynamic targets of portacaval pressure gradient (PPG) after transjugular intrahepatic portosystemic shunt (TIPS) remain unclear. Here we show that post-TIPS PPG measured at least 24 hours but not immediately after the procedure correlated with long-term PPG and clinical events. Thus, PPG measurements taken at least 24 hours after TIPS should be used to guide decision making in order to improve clinical outcomes. Targeting a post-TIPS PPG of 11-14 mmHg or a 20%-50% relative reduction from pre-TIPS baseline measured 24-72 hours after the procedure was associated with reduced encephalopathy but not compromised clinical efficacy. Thus, these criteria could be used to guide TIPS creation and revision in patients with cirrhosis and variceal bleeding undergoing covered TIPS. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, ID: NCT03590288.

Development and validation of serological dynamic risk score to predict outcome in gastric cancer with adjuvant chemotherapy: a multicentre, longitudinal, cohort study.

Background: Baseline serological biomarkers have the potential to predict the benefits of adjuvant chemotherapy in patients with gastric cancer. However, the fluctuating nature of postoperative recurrence risk makes precise treatment challenging. We aimed to develop a risk score in real-time predicting outcomes for postoperative GC patients using blood chemistry tests. Materials and methods: This was a retrospective, multicentre, longitudinal cohort study from three cancer centres in China, with a total of 2737 GC patients in the pTNM stage Ib to III. Among them, 1651 patients with at least two serological records were assigned to the training cohort. Model validation was carried out using separate testing data with area under curve (AUC). The least absolute shrinkage and selection operator (LASSO) and random forest-recursive feature elimination (RF-RFE) algorithm were used to select the parameters. Results: The Cox regression model derived six risk factors to construct a composite score (low-risk: 0-2 score; high risk: 3-6 score), including CEA, CA125, CA199, haemoglobin, albumin, and neutrophil to lymphocyte ratio. The risk score accurately predicted mortality in 1000-time bootstrap (AUROCs:0.658; 95% CI: 0.645, 0.670), with the highest AUROC (0.767; 95% CI: 0.743, 0.791) after 1 year since the gastrectomy. In validation dataset, the risk score had an AUROC of 0.586 (95% CI 0.544, 0.628). Furthermore, patients with high risk at 1 month derived significant clinical benefits from adjuvant chemotherapy (P for interaction <0.0001). Compared with the low-low-low risk group, the low-low-high risk group of the long-term state chain (risk state at baseline, 6 months, 1 year) had the worse OS (HR, 6.91; 95%CI: 4.27, 11.19) and DFS (HR, 7.27; 95%CI: 4.55, 11.63). Conclusion: The dynamic risk score is an accurate and user-friendly serological risk assessment tool for predicting outcomes and assisting clinical decisions after gastrectomy.

Development and validation of a prognostic score to identify the optimal candidate for preemptive TIPS in patients with cirrhosis and acute variceal bleeding.

BACKGROUND AND AIM: Baveno VII workshop recommends the use of preemptive TIPS (p-TIPS) in patients with cirrhosis and acute variceal bleeding (AVB) at high- risk of treatment failure. However, the criteria defining "high-risk" have low clinical accessibility or include subjective variables. We aimed to develop and externally validate a model for better identification of p-TIPS candidates. APPROACH AND RESULTS: The derivation cohort included 1554 patients with cirrhosis and AVB who were treated with endoscopy plus drug (n = 1264) or p-TIPS (n = 290) from 12 hospitals in China between 2010 and 2017. We first used competing risk regression to develop a score for predicting 6-week and 1-year mortality in patients treated with endoscopy plus drugs, which included age, albumin, bilirubin, international normalized ratio, white blood cell, creatinine, and sodium. The score was internally validated with the bootstrap method, which showed good discrimination (6 wk/1 y concordance-index: 0.766/0.740) and calibration, and outperformed other currently available models. In the second stage, the developed score was combined with treatment and their interaction term to predicate the treatment effect of p-TIPS (mortality risk difference between treatment groups) in the whole derivation cohort. The estimated treatment effect of p-TIPS varied substantially among patients. The prediction model had good discriminative ability (6 wk/1 y c -for-benefit: 0.696/0.665) and was well calibrated. These results were confirmed in the validation dataset of 445 patients with cirrhosis with AVB from 6 hospitals in China between 2017 and 2019 (6-wk/1-y c-for-benefit: 0.675/0.672). CONCLUSIONS: We developed and validated a clinical prediction model that can help to identify individuals who will benefit from p-TIPS, which may guide clinical decision-making.

Association of nonmalignant portal vein thrombosis and clinical outcomes in patients with cirrhosis and acute variceal bleeding: a multicenter observational study.

BACKGROUND AND AIM: Baveno VII workshop recommends management of acute variceal bleeding (AVB) in cirrhotic patients with nonmalignant portal vein thrombosis (PVT) should be performed according to the guidelines for patients without PVT. Nevertheless, whether PVT affects the outcome of patients with cirrhosis and AVB remains unclear. The aim of this study was to assess the clinical impact of PVT on the outcomes in the pre-emptive TIPSS eligible patients with cirrhosis and AVB. METHODS: From December 2010 to June 2016, 1219 consecutive cirrhotic patients admitted due to AVB with (n = 151; 12.4%) or without PVT (n = 1068; 87.6%), who received drug plus endoscopic treatment (a combination of vasoactive drugs, antibiotics, and endoscopic ligation for AVB, followed by beta-blockers plus variceal ligation for prevention of rebleeding) were retrospectively included. Fine and Gray competing risk regression models were taken to evaluate the impact of PVT on clinical outcomes after adjusting for potential confounders. RESULTS: During follow-up, 211 patients (17.3%) died, 490 (40.2%) experienced further bleeding, and 78 (6.4%) experienced new or worsening ascites within 1 year. Compared with those without PVT, patients with PVT had a similar risk of mortality (PVT vs no-PVT: 19.9% vs 16.7% at 1 year; adjusted HR 0.88, 95%CI 0.51-1.52, p = 0.653), further bleeding (47.0% vs 39.2% at 1 year, adjusted HR 1.19, 95% CI 0.92-1.53, p = 183), and new or worsening ascites (7.9% vs 9.6%, adjusted HR 0.70, 95% CI 0.39-1.28, p = 0.253) after adjusting for confounders in multivariable models. These findings were consistent across different relevant subgroups and confirmed by propensity score matching analysis. CONCLUSIONS: Our study showed no evidence that the PVT was associated with an improved or worsened outcome among cirrhotic patients with AVB who received standard treatment.

Emergency Removal of Ingested Foreign Bodies in 586 Adults at a Single Hospital in China According to the European Society of Gastrointestinal Endoscopy (ESGE) Recommendations: A 10-Year Retrospective Study.

BACKGROUND The 2016 European Society of Gastrointestinal Endoscopy (ESGE) guidelines recommend that ingested foreign bodies in the upper gastrointestinal (GI) tract are removed as an emergency within 6 hours, with an endoscopic approach that is individualized according to the type of foreign body identified. This retrospective study evaluated the 10-year experience of a single hospital in China performing emergency removal of ingested foreign bodies in 586 adults. MATERIAL AND METHODS Between 2011 and 2020, medical records of 642 adults with a diagnosis of foreign bodies ingestion were retrospectively screened. The timing of endoscopic intervention was classified according to ESGE recommendations. Uni- and multivariate analyses were performed. RESULTS We included 586 patients. The median (range) diameter of foreign bodies was 2.5 (1-24) cm: for sharp ones it was 2.5 (1.5-4.0) cm and for long ones it was 16.9 (10-24) cm. The most common site of foreign body lodgment was the esophagus (n=481; 82.1%); 45.6% (n=252) received emergent removal within 6 hours, while 32.2% (n=178) underwent urgent removal within 24 hours. There were 583 (99.5%) foreign bodies removed successfully and the complication rate was 17.9%. Major complications occurred in 45 patients (7.7%). Female sex and non-emergent endoscopy after 6 hours were significantly associated with a higher overall complications rate. For major complications, older age, time interval >24 hours, and sharper objects were associated with major complications. CONCLUSIONS The findings from this retrospective study support the ESGE statement that endoscopic removal of ingested foreign bodies from the upper GI tract within 6 hours reduces complication rates for adults in the emergency setting.

Risk stratification in patients with upper gastrointestinal submucosal tumors undergoing submucosal tunnel endoscopic resection.

Background: A substantial heterogeneity exists in patients with upper gastrointestinal submucosal tumors (SMTs). This study aimed to identify predictors of long procedure time (≥60 min), occurrence of procedure-related complications, and long hospital stay (≥6 days) in patients with SMTs undergoing submucosal tunnel endoscopic resection (STER) and stratify risk based on the predictors. Methods: Sixty-six consecutive patients with upper gastrointestinal SMTs undergoing STER between January 2013 and December 2018 were retrospectively included. Binary logistic regression models were developed to identify predictors of outcomes. Receiver operating characteristic (ROC) curves were constructed to evaluate the discrimination of tumor size. Results: Complete resection and en bloc resection of tumor were achieved in 66 (100%) and 64 patients (97%), respectively. Twenty-seven patients (41%) had a long procedure time, 10 (15%) developed STER-related complications, and 17 (26%) had a long hospital stay. On multivariable analysis, tumor size was an independent predictor of long procedure time (OR 1.37, 95% CI 1.13-1.67; p = 0.001), occurrence of complications (OR 1.06, 95% CI 1.01-1.10; p = 0.012), and long hospital stay (OR 1.05, 95% CI 1.01-1.09; p = 0.035). ROC curves identified a tumor of size 25 mm as the best cutoff; those who had a tumor above this value had a 76-fold risk of long procedure time, 8.56-fold risk of occurrence of complications, and 6.35-fold risk of long hospital stay. Conclusion: Patients with a tumor size ≥25 mm had longer procedure time, higher risk of STER-related complications, and longer hospital stay; therefore, they should be classified as a high-risk group.

Abnormal Liver Function Tests Were Associated With Adverse Clinical Outcomes: An Observational Cohort Study of 2,912 Patients With COVID-19.

Background and Aim: The impact of liver function test (LFTs) abnormality on adverse clinical outcomes in coronavirus disease 2019 (COVID-19) patients remains controversial. The aim of this study was to assess the impact of abnormal LFTs on clinical outcomes in a large cohort of hospitalized patients with COVID-19. Methods: We retrospectively collected data on 2,912 consecutive patients with COVID-19 who were admitted to a makeshift hospital in China between 5 February and 23 March 2020. The association between LFTs abnormalities (baseline and peak values) and clinical outcomes was measured by using Cox regression models. Results: On admission 1,414 patients (48.6%) had abnormal LFTs, with alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), alkaline phosphatase (ALP), and gamma-glutamyltransferase (GGT) elevation in 662 (22.7%), 221 (7.6%), 52 (1.8%), 135 (4.6%), and 536 (18.5%) patients, respectively, and hypoalbuminemia in 737 (25.3%) patients. During a median 13 (IQR: 8-19) days of hospitalization, 61 patients (2.1%) died, 106 patients (3.6%) admitted to intensive care unit (ICU), and 75 patients (2.6%) required mechanical ventilation. After adjustment for confounders, baseline abnormal LFTs were independently associated with increased risks of mortality (adjusted HR 3.66, 95%CI 1.64-8.19, p = 0.002), ICU admission (adjusted HR 3.12 95%CI 1.86-5.23, p < 0.001), and mechanical ventilation (adjusted HR 3.00, 95%CI 1.63-5.52, p < 0.001), which was homogeneous across the severity of COVID-19 infection. Among the parameters of LTFs, the associations with the outcomes were more pronounced for AST and albumin abnormality. In contrast, ALT elevation was not significantly associated with those outcomes. Similar results were observed for peak values of LFTs during hospitalization. Conclusions: Abnormality of AST, albumin, TBIL, ALP, and GGT but not ALT were independently associated with adverse outcomes.

Association of systemic inflammation and body mass index with survival in patients with resectable gastric or gastroesophageal junction adenocarcinomas.

Objective: The systemic inflammation index and body mass index (BMI) are easily accessible markers that can predict mortality. However, the prognostic value of the combined use of these two markers remains unclear. The goal of this study was therefore to evaluate the association of these markers with outcomes based on a large cohort of patients with gastric cancer. Methods: A total of 2,542 consecutive patients undergoing radical surgery for gastric or gastroesophageal junction adenocarcinoma between 2009 and 2014 were included. Systemic inflammation was quantified by the preoperative neutrophil-to-lymphocyte ratio (NLR). High systemic inflammation was defined as NLR ≥ 3, and underweight was defined as BMI < 18.5 kg/m2. Results: Among 2,542 patients, NLR ≥ 3 and underweight were common [627 (25%) and 349 (14%), respectively]. In the entire cohort, NLR ≥ 3 or underweight independently predicted overall survival (OS) [hazard ratio (HR): 1.236, 95% confidence interval (95% CI): 1.069-1.430; and HR: 1.600, 95% CI: 1.350-1.897, respectively] and recurrence-free survival (RFS) (HR: 1.230, 95% CI: 1.054-1.434; and HR: 1.658, 95% CI: 1.389-1.979, respectively). Patients with both NLR ≥ 3 and underweight (vs. neither) had much worse OS (HR: 2.445, 95% CI: 1.853-3.225) and RFS (HR: 2.405, 95% CI: 1.802-3.209). Furthermore, we observed similar results in subgroup analyses according to pathological stage, age, and postoperative chemotherapy. Conclusions: Our results showed that preoperative elevated NLR and decreased BMI had a significant negative effect on survival. Underweight combined with severe inflammation could enhance prognostication. Taking active therapeutic measures to reduce inflammation and increase nutrition may help improve outcomes.

KRAS Mutation-Responsive miR-139-5p inhibits Colorectal Cancer Progression and is repressed by Wnt Signaling.

Introduction: Colorectal cancer (CRC) frequently harbors KRAS mutations that result in chemoresistance and metastasis. MicroRNAs (miRNAs) are usually dysregulated and play important regulatory roles in tumor progression. However, the KRAS mutation-responsive miRNA profile in CRC remains uninvestigated. Methods: miR-139-5p was identified and evaluated by small RNA sequencing, qRT-PCR and in situ hybridization. The roles of miR-139-5p in CRC cells with and without KRAS mutation were determined by Cell Counting Kit-8 (CCK-8), colony formation, flow cytometry and transwell assays in vitro and by tumorigenesis and metastasis assays in vivo. Microarrays followed by bioinformatic analyses, luciferase reporter assays and Western blotting were applied for mechanistic studies. Results: miR-139-5p was significantly downregulated in KRAS-mutated CRC cells and tissues compared with their wild-type counterparts. Low miR-139-5p expression was associated with aggressive phenotypes and poor prognosis in CRC patients. miR-139-5p overexpression inhibited CRC cell proliferation, migration and invasion in vitro, sensitized tumors to chemotherapy, and impaired tumor growth and metastasis in vivo. Transcriptomic profiling identified multiple modulators in the Ras (JUN and FOS) and Wnt (CTNNB1 and DVL1) signaling pathways and the epithelial-to-mesenchymal transition (EMT) process (ZEB1) as direct targets of miR-139-5p, and inverse correlations were confirmed in CRC clinical tissues. Aberrantly activated Wnt signaling in KRAS-mutant cells was demonstrated to transcriptionally repress miR-139-5p through TCF4, forming a miR-139-5p/Wnt signaling double-negative feedback loop. Conclusions: We identified miR-139-5p as a KRAS-responsive miRNA and demonstrated its involvement in CRC progression. KRAS mutation disrupted the miR-139-5p/Wnt signaling reciprocal negative feedback mechanism, which might cause miR-139-5p downregulation and derepression of oncogenic signaling pathways and EMT. These results reveal a transcriptional regulatory mode of KRAS-driven malignant transformation and highlight miR-139-5p as a novel regulator of crosstalk between the Ras and Wnt signaling pathways in CRC.

Efficacy and Safety of Multiband Mucosectomy Versus Cap-assisted Endoscopic Resection For Early Esophageal Cancer and Precancerous Lesions: A Systematic Review and Meta-Analysis.

BACKGROUND: The effectiveness of multiband mucosectomy (MBM) for early esophageal cancer and precancerous lesions is still in uncertainty. We aimed to evaluate the efficacy and safety of this procedure and to compare it with cap-assisted endoscopic resection (EMR-cap). METHODS: A systematic search of both English and Chinese databases was performed from inception to April 30, 2019. Complete resection rate, local recurrence rate, and procedure time were considered the primary outcome measures. Prevalence of complications was considered the secondary outcome measure. All data analyses were performed using Review Manager Software. RESULTS: Two randomized controlled trials (RCTs) and 3 non-RCTs were included in the final meta-analysis. When compared with the EMR-cap technique, MBM had a similar complete resection rate [odds ratio (OR)=2.09, 95% confidence interval (CI): 0.78-5.60, P=0.14], a similar local recurrence rate (OR=0.50, 95% CI: 0.09-2.67, P=0.42), a shorter resection time (mean difference: -9.08, 95% CI: -13.86 to -4.30, P=0.0002), a shorter procedure time (mean difference: -13.36, 95% CI: -17.85 to -8.86, P<0.00001), a lower bleeding rate (OR=0.45, 95% CI: 0.24-0.83, P=0.01), a similar perforation rate (OR=0.55, 95% CI: 0.15-2.06, P=0.37), and a similar stricture rate (OR=0.77, 95% CI: 0.10-5.84, P=0.80). The results of non-RCTs were consistent with those of RCTs. CONCLUSIONS: MBM is similar to EMR-cap in terms of efficacy and safety for endoscopic resection of early cancer and precancerous lesions of the esophagus. However, MBM is less time-consuming.

Early TIPS with covered stents versus standard treatment for acute variceal bleeding in patients with advanced cirrhosis: a randomised controlled trial.

BACKGROUND: The survival benefit of early placement of transjugular intrahepatic portosystemic shunts (TIPS) in patients with cirrhosis and acute variceal bleeding is controversial. We aimed to assess whether early TIPS improves survival in patients with advanced cirrhosis and acute variceal bleeding. METHODS: We did an investigator-initiated, open-label, randomised controlled trial at an academic hospital in China. Consecutive patients with advanced cirrhosis (Child-Pugh class B or C) and acute variceal bleeding who had been treated with vasoactive drugs plus endoscopic therapy were randomly assigned (2:1) to receive either early TIPS (done within 72 h after initial endoscopy [early TIPS group]) or standard treatment (vasoactive drugs continued to day 5, followed by propranolol plus endoscopic band ligation for the prevention of rebleeding, with TIPS as rescue therapy when needed [control group]). Randomisation was done by web-based randomisation system using a Pocock and Simon's minimisation method with Child-Pugh class (B vs C) and presence or absence of active bleeding as adjustment factors. The primary outcome was transplantation-free survival, analysed in the intention-to-treat population, excluding individuals subsequently found to be ineligible for enrolment. This study is registered with ClinicalTrials.gov, number NCT01370161, and is completed. FINDINGS: From June 26, 2011, to Sept 30, 2017, 373 patients were screened and 132 patients were randomly assigned to the early TIPS group (n=86) or to the control group (n=46). After exclusion of three individuals subsequently found to be ineligible for enrolment (two patients in the early TIPS group with non-cirrhotic portal hypertension or hepatocellular carcinoma, and one patient in the control group due to non-cirrhotic portal hypertension), 84 patients in the early TIPS group and 45 patients in the control group were included in the intention-to-treat population. 15 (18%) patients in the early TIPS group and 15 (33%) in the control group died; two (2%) patients in the early TIPS group and one (2%) in the control group underwent liver transplantation. Transplantation-free survival was higher in the early TIPS group than in the control group (hazard ratio 0·50, 95% CI 0·25-0·98; p=0·04). Transplantation-free survival at 6 weeks was 99% (95% CI 97-100) in the early TIPS group compared with 84% (75-96; absolute risk difference 15% [95% CI 5-48]; p=0·02) and at 1 year was 86% (79-94) in the early TIPS group versus 73% (62-88) in the control group (absolute risk difference 13% [95% CI 2-28]; p=0·046). There were no significant differences between the two groups in the incidence of hepatic hydrothorax (two [2%] of 84 patients in the early TIPS group vs one [2%] of 45 in the control group; p=0·96), spontaneous bacterial peritonitis (one [1%] vs three [7%]; p=0·12), hepatic encephalopathy (29 [35%] vs 16 [36%]; p=1·00), hepatorenal syndrome (four [5%] vs six [13%]; p=0·10), and hepatocellular carcinoma (four [5%] vs one [2%]; p=0·68). There was no significant difference in the number of patients who experienced other serious adverse events (ten [12%] vs 11 [24%]; p=0·07) or non-serious adverse events (21 [25%] vs 19 [42%]; p=0·05) between groups. INTERPRETATION: Early TIPS with covered stents improved transplantation-free survival in selected patients with advanced cirrhosis and acute variceal bleeding and should therefore be preferred to the current standard of care. FUNDING: National Natural Science Foundation of China, National Key Technology R&D Program, Optimized Overall Project of Shaanxi Province, Boost Program of Xijing Hospital.

Knockdown of cyclooxygenase-2 leads to growth inhibition and cell cycle arrest in hepatocellular carcinoma cells.

Background & aims: Cyclooxygenase-2 (COX-2) is proved to play important roles in the development and progression of various human tumors, including hepatocellular carcinoma (HCC). However, the antitumor effect of RNA interference (RNAi) technology targeting COX-2 in HCC has not yet been verified. Methods: We silenced COX-2 expression using a lentivirus-mediated RNAi and further investigated the effects of COX-2 knockdown on cell growth and cell cycle in Huh7 and SMMC-7721 cells. COX-2 mRNA was detected by RT-PCR while COX-2 protein was detected by Western blotting. The cell proliferation was measured by MTT assay. The cell cycle was measured by flow cytometry. The tumorigenicity of HCC cells was evaluated using soft-agar clonogenic assay in vitro and nude mouse xenograft model in vivo. Results: The down-regulation of COX-2 expression significantly inhibited cell proliferation and colony formation, and led to cell cycle arrest in vitro, and reduced the potential of tumorigenicity in vivo in both Huh7 and SMMC-7721 cells. Furthermore, PGE2 production was also decreased after COX-2 expression was suppressed. Finally, knockdown of COX-2 also induced the down-regulation of cell cycle-related protein, cyclinD1. Conclusions: The abrogation of COX-2 expression can lead to potent antitumor activity and knockdown of COX-2 may be served as a prospective therapeutic strategy against HCC.

TIPSS for variceal bleeding in patients with idiopathic non-cirrhotic portal hypertension: comparison with patients who have cirrhosis.

BACKGROUND: In patients with idiopathic non-cirrhotic portal hypertension (INCPH), the usual recommended strategy for management of variceal bleeding is the same as that in cirrhosis. However, this policy has been challenged by the different natural history between INCPH and cirrhosis. AIM: To compare outcomes after transjugular intrahepatic portosystemic shunt (TIPSS) between INCPH and cirrhotic patients admitted for variceal bleeding. METHODS: Between March 2001 and September 2015, 76 consecutive patients with biopsy-proven INCPH undergoing TIPSS for variceal bleeding in a tertiary-care centre were included. 76 patients with cirrhotic portal hypertension receiving TIPSS for variceal bleeding, and matched for age, sex, Child-Pugh class, stent type and index year of TIPSS creation served as controls. RESULTS: Patients with INCPH, compared to those with cirrhosis, had significantly lower mortality (11% vs 36% at 5 years, adjusted HR, 0.37; 95% CI 0.15-0.87, P = 0.022), overt hepatic encephalopathy (16% vs 33% at 5 years, adjusted HR, 0.35; 95% CI 0.16-0.75, P = 0.007) and hepatic impairment, despite similar rates of further bleeding (33% vs 32% at 5 years, adjusted HR, 0.72; 95% CI 0.36-1.44, P = 0.358), and shunt dysfunction (35% vs 36% at 5 years, adjusted HR, 0.84; 95% CI 0.41-1.72, P = 0.627). These findings were consistent across different relevant subgroups. CONCLUSIONS: Patients with INCPH treated with TIPSS for variceal bleeding had similar progression of portal hypertension (further bleeding and shunt dysfunction) but fewer complications of liver disease (overt hepatic encephalopathy and hepatic insufficiency) and lower mortality rate compared with cirrhotic patients with comparable liver function.

Overexpression of serum response factor is correlated with poor prognosis in patients with gastric cancer.

Serum response factor (SRF) is highly expressed in many tumors, including gastric cancer. However, the exact prognostic utility of SRF in patients with gastric cancer remains unclear. Therefore, in this study, we investigated the expression and prognostic value of SRF in patients with gastric cancer. SRF expression was detected by immunohistochemistry in 149 gastric cancer samples. The relationship between SRF expression and clinicopathological characteristics along with the prognostic significance of SRF in disease-free survival and overall survival of patients was analyzed. We found that the expression of SRF was significantly increased in gastric cancer tissues compared with adjacent noncancerous tissues. Overexpression of SRF was significantly correlated with histologic differentiation, invasion depth, lymph node metastasis, and TNM stage. Furthermore, disease-free survival rate and overall survival rate were both significantly lower for patients with high SRF expression. Multivariate Cox regression analysis identified high SRF expression as an independent prognostic factor for disease-free survival but not for overall survival. Our findings indicate that overexpression of SRF may play an important role in human gastric cancer recurrence and prognosis. SRF may serve as a predictive marker for prognosis of gastric cancer.

[Overexpression of miR-107 promotes the proliferation and tumorigenic ability of HT29 cells].

Objective To investigate the effect of miR-107 on the proliferation of colorectal cancer cells. Methods The expression of miR-107 was detected in colorectal cancer tissues and colorectal cancer cell lines by real-time quantitative PCR (qRT-PCR). miR-107 expression was up-regulated and down-regulated by the transfection of miR-107 mimic and miR-107 inhibitor in HT29 cells, respectively. The effect of miR-107 on the proliferation of HT29 cells was evaluated by MTT assay. The tumorigenic ability of HT29 cells was detected by soft-agar colony formation assay and nude mouse tumorigenic assay. The expression of cyclin D1 in HT29 cells was tested by Western blot analysis. Results The expression of miR-107 was significantly up-regulated in both colorectal cancer tissues and cells. Overexpression of miR-107 promoted the proliferation and tumorigenicity of HT29 cells, while the decrease of miR-107 expression inhibited the proliferation and tumorigenicity of HT29 cells. Overexpression of miR-107 up-regulated the expression of cyclin D1 in HT29 cells. Conclusion Overexpression of miR-107 in both colon cancer tissues and cells promotes the proliferation and tumor formation potential of HT29 cells via up-regulating cyclin D1 expression.

FOXM1 promotes proliferation in human hepatocellular carcinoma cells by transcriptional activation of CCNB1.

The transcription factor Forkhead box protein M1 (FOXM1) plays critical roles in cancer development and progression, including human hepatocellular carcinoma (HCC). However, the regulatory role and underlying mechanisms of FOXM1 is still limited. Here, we found that the high level expression of FOXM1 and CCNB1 is closely associated with poor prognosis in HCC patients. And FOXM1 and CCNB1 were overexpressed concomitantly in liver tumor tissues. Knockdown of FOXM1 significantly inhibited the expression levels of CCNB1 in HCC cell lines at both the mRNA and protein levels. Mechanistic studies revealed that FOXM1 binds directly to the promoter region of CCNB1 and regulates the expression levels of the CCNB1 gene in the transcriptional level. Furthermore, the loss of functional and rescue experiments showed that CCNB1 is essential for FOXM1-driven proliferation in HCC cells. In the present study, our results partially explained the dysregulated expression of FOXM1 play an important role in proliferation of human hepatocellular carcinoma cells via transcriptional activation of CCNB1 expression. And it also highlights a FOXM1/CCNB1 axis could be a potential target for the treatment of HCCs.

Covered TIPS versus endoscopic band ligation plus propranolol for the prevention of variceal rebleeding in cirrhotic patients with portal vein thrombosis: a randomised controlled trial.

OBJECTIVE: Limited data are available on the prevention of variceal rebleeding in cirrhotic patients with portal vein thrombosis (PVT). This study aimed to compare transjugular intrahepatic portosystemic shunt (TIPS) with covered stents versus endoscopic band ligation (EBL) plus propranolol for the prevention of variceal rebleeding among patients with cirrhosis and PVT. DESIGN: Consecutive cirrhotic patients (94% Child-Pugh class A or B) with PVT who had variceal bleeding in the past 6 weeks were randomly assigned to TIPS group (n=24) or EBL plus propranolol group (EBL+drug, n=25), respectively. Primary endpoint was variceal rebleeding. Secondary endpoints included survival, overt hepatic encephalopathy (OHE), portal vein recanalisation and rethrombosis, other complications of portal hypertension and adverse events. RESULTS: During a median follow-up of 30 months in both groups, variceal rebleeding was significantly less frequent in the TIPS group (15% vs 45% at 1 year and 25% vs 50% at 2 years, respectively; HR=0.28, 95% CI 0.10 to 0.76, p=0.008), with a significantly higher portal vein recanalisation rate (95% vs 70%; p=0.03) and a relatively lower rethrombosis rate (5% vs 33%; p=0.06) compared with the EBL+drug group. There were no statistically significant differences in survival (67% vs 84%; p=0.152), OHE (25% vs 16%; p=0.440), other complications of portal hypertension and adverse events between groups. CONCLUSION: Covered TIPS placement in patients with PVT and moderately decompensated cirrhosis was more effective than EBL combined with propranolol for the prevention of rebleeding, with a higher probability of PVT resolution without increasing the risk of OHE and adverse effects, but this benefit did not translate into improved survival. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT01326949.