Practice patterns in endoscopic treatment for gastric varices: A Chinese survey.

OBJECTIVES: Gastric varices (GV), a common complication of liver cirrhosis, often cause serious consequences. However, the management of GV remains debated. In this study we aimed to explore the practice patterns of Chinese practitioners in GV treatment and discuss whether these patterns conform to the guidelines in China and around the world. METHODS: Between October 2020 and January 2021, an online questionnaire was sent to doctors from different regions in China via WeChat. Data on the practice patterns for endoscopic treatment with and without a multidisciplinary discussion team (MDT) clinic for GV were analyzed. RESULTS: Questionnaires were collected from 241 practitioners from 29 provinces in China. Before endoscopic treatment, 100 (41.5%) of the practitioners arranged computed tomography angiography (CTA) examination. In endoscopic tissue adhesive (ETA) treatment, 183 (75.9%) of the practitioners chose ETA combined with lauromacrogol. Approximately one-fourth of all practitioners did not prescribe drugs to reduce portal pressure. Only 75 (31.1%) of physicians preferred using early transjugular intrahepatic portosystemic shunt (TIPS) for patients at a high risk of treatment failure for GV. Compared to those without MDT clinics, practitioners with MDT clinics more often chose early TIPS for high-risk patients (39.0% vs 18.9%, P = 0.001). CONCLUSIONS: Treatment for GV differ across China. Practitioners with MDT clinics can better use assistant strategies such as CTA to evaluate the risk and efficacy. Further clinical studies are needed, and more guidelines and consensuses are warranted to standardize clinical practice for GV.

Microarray Analysis of lncRNA and mRNA Reveals Enhanced Lipolysis Along With Metabolic Remodeling in Mice Infected With Larval Echinococcus granulosus.

Parasitic infection improves metabolic homeostasis in "western diet"-induced obesity through the regulation of adipogenesis. However, the underlying mechanism is not yet fully understood. Using microarray analysis, this study investigated the long non-coding RNA (lncRNA) and messenger RNA (mRNA) profiles of subcutaneous adipose tissues from mice infected with Echinococcus granulosus protoscoleces. A total of 1052 mRNA (541 upregulated, 511 downregulated) and 220 lncRNA (126 upregulated, 94 downregulated) transcripts were differentially expressed (fold change ≥2, P < 0.05) in the infected subcutaneous adipose tissues. When compared with the control group, the infected mice showed a decrease in adipose tissue mass and a reduction in adipocyte size. Indirect calorimetry revealed the change in the energy metabolism after infection, characterized by a lower CO2 production and O2 consumption, a sharp decline in carbohydrate oxidation, and a slight increase in fat oxidation. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses showed that the parasitic infection reprogrammed a complex metabolic network. Notably, "lipoxygenase" and "arginine and proline metabolism" pathways were significantly upregulated while "glycolysis," "tricarboxylic acid cycle," "de novo lipogenesis," and "lipid droplet" pathways were dramatically downregulated. In addition, several key lncRNAs were associated with insulin resistance and adipocyte differentiation. Overall, the present study suggested that E. granulosus infection could enhance lipolysis. Thus, our findings provide novel insights into parasite-mediated metabolic homeostasis, and into the mechanism of hypertrophic adipocytes in obesity.

Balloon-occluded Retrograde Transvenous Obliteration of Portovenous Shunts During Endoscopic Therapy for the Treatment of Gastric Varices.

INTRODUCTION: To explore the safety and feasibility of balloon-occluded retrograde transvenous obliteration (BRTO) of portovenous shunts during endoscopic cyanoacrylate injection for the treatment gastric varices (E-BRTO) secondary to portal hypertension. PATIENTS AND METHODS: A total of 28 cirrhotic patients with gastroesophageal varices and concurrent gastrorenal or gastrosplenorenal shunt, treated with E-BRTO, were enrolled. Operative details were recorded to evaluate the safety, feasibility, and efficacy of the procedure. Short-term follow-up was conducted to denote any incidence of distant emboli, variceal rebleeding, or mortality (Video, Supplemental Digital Content 1, http://links.lww.com/SLE/A179). RESULTS: All the patients successfully received E-BRTO without intraoperative complications. The average volume of cyanoacrylate was 2.4±1.3 mL. During the 90 days follow-up, none of the patients experienced distant systemic emboli. However, 8 patients suffered from gastrointestinal rebleeding, including one death, while 2 patients were lost to follow-up. The short-term rebleeding rate (intention to treat) was about 36% in E-BRTO for this subset of patients. CONCLUSIONS: BRTO during endoscopic cyanoacrylate injection is an alternative selection for cirrhotic patients with portovenous shunts. The procedure is feasible and procedurally safe, but the associated high rebleeding rate may require a multimodality approach.

Endoscopic cyanoacrylate injection with or without lauromacrogol for gastric varices: A randomized pilot study.

BACKGROUND AND AIM: Current guidelines recommend injection of cyanoacrylate as first-line therapy to prevent gastric variceal rebleeding. The method still poses a risk of ectopic embolism, which possibly correlates with the volume of cyanoacrylate used. In this trial, we evaluated the short-term efficacy and safety of tissue adhesive injection combined with lauromacrogol for treating gastric varices. METHODS: Patients admitted to our hospital for variceal hemorrhage were enrolled and blindly randomized into two treatment groups: lauromacrogol group (lauromacrogol-cyanoacrylate-lauromacrogol) and lipiodol group (lipiodol-cyanoacrylate-lipiodol). Patient follow-up was 6 months. Primary outcome was rebleeds, and secondary outcomes were mortality, gastric varices eradication, and treatment-related adverse events. RESULTS: Between March 6, 2013 and October 16, 2013, 96 patients met the criteria. Two cases were lost to follow-up, and all treated cases were successful. No procedural-related adverse events were observed in either group. Cyanoacrylate volumes used in the lauromacrogol group were significantly less than those of the lipiodol group (0.9 ± 0.5 vs 2.0 ± 1.2 mL, P = 0.000). Eleven patients developed upper gastrointestinal rebleeding, which did not show significant difference between groups. On multivaritate analysis, portal venous thrombosis and fever were potential risk factors of rebleeding. Treatment failure, complications, gastric varices obturation, and survival did not differ between the two groups. CONCLUSION: Tissue adhesives combined with lauromacrogol is a safe therapeutic option for gastric varices, with comparably less cyanoacrylate volume used. Because of the small number of study patients, it cannot be proven to have better efficacy than without lauromacrogol. Multicenter studies with larger patient groups are necessary.

Long-term efficacy of endoscopic ligation plus cyanoacrylate injection with or without sclerotherapy for variceal bleeding.

OBJECTIVE: This study aimed to evaluate the long-term outcomes and efficacy of continued ligation plus cyanoacrylate injection compared with those of combined ligation and sclerotherapy plus cyanoacrylate injection for secondary prophylaxis of variceal bleeding in cirrhotic patients with concomitant esophageal and gastric varices. METHODS: Medical records of the patients who were admitted for variceal bleeding due to liver cirrhosis were retrospectively reviewed and their related data was collected. The patients were divided into two groups, including the continued ligation plus cyanoacrylate injection group [the sclerotherapy (-) group] and the combined ligation and sclerotherapy plus cyanoacrylate injection group [the sclerotherapy (+) group]. The Kaplan-Meier survival analysis was conducted and log-rank test was used to compare the differences between the two groups. RESULTS: Altogether 125 patients were enrolled between 1 April 2004 and 31 December 2012. After a median follow-up of 23.4 months, no significant difference was observed between the two groups in regard to variceal rebleeding (29.7% vs 47.5%, P = 0.097) and mortality (12.5% vs 14.8%, P = 0.879). Among patients with ascites the cumulative rebleeding rate was significantly lower in the sclerotherapy (-) group (26.3% vs 59.4%, P = 0.020). A relapse of bleeding after the initial endoscopic therapy was an independent prognostic factor of rebleeding (P = 0.004). Portal thrombosis was an independent prognostic factor for mortality (P = 0.044). CONCLUSION: No superiority of combined ligation and sclerotherapy compared with continued ligation and cyanoacrylate injection for secondary prophylaxis of variceal bleeding is observed.

Randomized controlled trial comparing endoscopic ligation with or without sclerotherapy for secondary prophylaxis of variceal bleeding.

OBJECTIVES: A recently published network meta-analysis showed that ligation combined with sclerotherapy might be the most efficacious intervention for secondary prophylaxis of variceal bleeding. Most studies excluded patients with concomitant gastric varices; thus, the outcomes in such patients have not yet been reported. The present study aimed to investigate the efficacy of two endoscopic procedures for secondary prophylaxis in cirrhotic patients presenting with both esophageal and gastric varices. MATERIALS AND METHODS: A randomized controlled study was carried out in a tertiary care referral center. Patients were randomized into two groups: sclerotherapy- and sclerotherapy+ group. Continued endoscopic ligation was used to treat esophageal varices in the sclerotherapy- group, whereas combined ligation and sclerotherapy with lauromacrogol was performed in the sclerotherapy+ group. A cyanoacrylate injection was used for gastric varices in both groups. All participants were followed up for 6 months. RESULTS: Overall, 96 patients were included between 25 March 2012 and 25 June 2013. Three patients were lost during follow-up (one in the sclerotherapy- group and two in the sclerotherapy+ group). The cumulative recurrence rate of bleeding was significantly higher in the sclerotherapy+ group (14.6 vs. 35.4%, P=0.013). The cumulative mortality rate (2.1 vs. 6.3%, P=0.286) and the incidence rate of adverse events were similar between the two groups. CONCLUSION: Continued ligation+cyanoacrylate injection was superior to combined ligation and sclerotherapy+cyanoacrylate injection during the first 6 months in terms of rebleeding in cirrhotic patients presenting with both esophageal and gastric varices. Long-term results entail further investigation (http://www.clinicaltrials.gov, NCT01592578).

HER2 mRNA status contributes to the discrepancy between gene amplification and protein overexpression in gastric cancer.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2) is an important proto-oncogene of prognostic use in gastric cancer (GC). Fluorescence in-situ hybridization (FISH) and immunohistochemistry (IHC) are the main clinical methods of detection of HER2, but consistency between the methods is poor and the cause of the discrepancy is unclear. AIM: To investigate the involvement of HER2 mRNA status in the disparity between gene amplification and protein overexpression. METHODS: We investigated HER2 gene, mRNA, and protein profiles in gastric precancer and cancer tissues by use of the molecular approaches FISH, real-time polymerase chain reaction, and IHC. The relationships between HER2 and matrix metalloproteinase 9 (MMP9) and Smad7 expression were analyzed and the involvement of HER2 in the interaction between tumor cells and lymphocytes was investigated by coculturing GC cell lines with peripheral blood mononuclear cells (PBMCs). RESULTS: HER2 protein expression was significantly increased in cancer compared with precancer (P = 0.003), and the corresponding mRNA levels were significantly lower in precancer and cancer tissues than in normal tissues (κ = 0.290, P = 0.025). HER2 mRNA levels were significantly higher in tumor than in peritumor tissue (P = 0.028), and were positively correlated with MMP9 and Smad7 mRNA levels in tumor tissues. HER2 mRNA expression in GC cell lines was increased by coculture with PBMCs. CONCLUSIONS: Different HER2 mRNA profiles, possibly in relation to contact between tumor cells and lymphocytes, might help to explain the discrepancy between gene amplification and protein overexpression results.

Pharmacodynamic impacts of proton pump inhibitors on the efficacy of clopidogrel in vivo--a systematic review.

BACKGROUND: There is considerable debate about whether concomitant use of proton pump inhibitors (PPIs) should be recommended for patients who are prescribed clopidogrel after acute coronary syndrome. Most pharmacokinetic and pharmacodynamic studies in vivo were conducted using small sample sizes and were single centered, resulting in conflicting data. HYPOTHESIS: PPIs may attenuate the antiplatelet effect of clopidogrel in vivo and lead to an increased risk of cardiovascular events. METHODS: PubMed, the Cochrane Library, Embase, Web of Science, and China Biology Medicine Disc were searched. Randomized controlled trials that compared pharmacodynamic impacts of a PPI on the efficacy of clopidogrel in vivo were included. Two independent reviewers evaluated study quality and extracted data for meta-analysis. RESULTS: We identified 8 eligible studies. Compared to clopidogrel treatment alone, patients who received both a PPI and clopidogrel had less of a decrease in the platelet reactivity index (weighted mean difference [WMD]: 8.18; 95% confidence interval [CI]: 6.81-9.56; P<0.00001), less adenosine 5'-diphosphate-induced platelet aggregation inhibition (WMD: 7.28; 95% CI: 2.44-12.11; P=0.003), higher P2Y12 reaction units (WMD: 40.58; 95% CI: 19.31-61.86; P=0.0002), and higher risks of clopidogrel resistance (odds ratio [OR]: 2.49; 95% CI: 1.49-4.14; P=0.0005). There were no significant differences, however, for the incidences of major adverse cardiovascular events between the 2 groups (OR: 1.07; 95% CI: 0.44-2.59; P=0.88), and treatment with a PPI and clopidogrel significantly reduced the risk of adverse gastrointestinal events (OR: 0.16; 95% CI: 0.04-0.62; P=0.008). CONCLUSIONS: Concomitant use of a PPI with clopidogrel attenuated the antiplatelet effect of clopidogrel, but may be clinically unimportant because there were no clinical differences in the risk for major adverse cardiovascular events.

Transforming growth factor-ß1 and -ß2 in gastric precancer and cancer and roles in tumor-cell interactions with peripheral blood mononuclear cells in vitro.

Transforming growth factor-ß1 (TGF-ß1) and -ß2 are correlated with poorer prognosis in gastric cancer (GC), which act in both tumor and immune cells. However, their expressions in precancer and tumor-cell interactions with peripheral blood mononuclear cells (PBMCs) remain unclear. Protein levels of TGF-ß1 and -ß2 were analyzed by immunohistochemistry and corresponding mRNA levels were determined by quantitative real-time polymerase chain reaction in 93 surgical and biopsy specimens. Serum TGF-ß concentration was detected by enzyme-linked immunosorbent assays. AGS and MKN45 cell lines were directly or indirectly cocultured with PBMCs in vitro. TGF-ß and Smad molecules were detected after cocultures and the growths of GC cells and PBMCs were assessed by cell proliferation assay. The results showed positive staining for TGF-ß1 was detected in 20% of control samples, 52.3% of precancer, 59.1% of early GC and 66.7% of advanced GC samples, correlated with lesion progression (χ²â€Š= 9.487, P = 0.002). All tissues were positive for TGF-ß2. TGF-ß1 mRNA levels were increased in advanced cancers, while TGF-ß2 increased earlier. TGF-ß1 mRNA levels were higher in tumor than in peritumor, which positively correlated with Smad2 and Smad7. Serum TGF-ß levels were significantly higher in patients with early and advanced cancers compared to controls (TGF-ß1∶50.08±4.38 and 45.76±5.00 vs. 27.78±6.11 ng/mL; TGF-ß2∶133.61±21.90 and 111.34±15.76 vs. 59.41±15.42 ng/mL, both P<0.05). The levels of TGF-ß1 mRNA and cytokine secretion were higher in GC cells after direct coculture compared to indirect culture. TGF-ß1 was decreased and TGF-ß2 was increased in PBMCs after cocultures. Moreover, TGF-ß1 inhibited the viability of PBMCs but not cancer cells. Collectively, neoplastic transformation may be an early event involving the increase of TGF-ß1 in the general and local environment. TGF-ß1 production is promoted by the direct interaction between GC cells and PBMCs, which might facilitate cancer development.

FoxP3 inhibits proliferation and induces apoptosis of gastric cancer cells by activating the apoptotic signaling pathway.

Forkhead Box Protein 3 (FoxP3) was identified as a key transcription factor to the occurring and function of the regulatory T cells (Tregs). However, limited evidence indicated its function in tumor cells. To elucidate the precise roles and underlying molecular mechanism of FoxP3 in gastric cancer (GC), we examined the expression of FoxP3 and the consequences of interfering with FoxP3 gene in human GC cell lines, AGS and MKN45, by multiple cellular and molecular approaches, such as immunofluorescence, gene transfection, CCK-8 assay, clone formation assay, TUNEL assay, Flow cytometry, immunoassay and quantities polymerase chain reaction (PCR). As a result, FoxP3 was expressed both in nucleus and cytoplasm of GC cells. Up-regulation of FoxP3 inhibited cell proliferation and promoted cell apoptosis. Overexpression of FoxP3 increased the protein and mRNA levels of proapoptotic molecules, such as poly ADP-ribose polymerase1 (PARP), caspase-3 and caspase-9, and repressed the expression of antiapoptotic molecules, such as cellular inhibitor of apoptosis-1 (c-IAP1) and the long isoform of B cell leukemia/lymphoma-2 (Bcl-2). Furthermore, silencing of FoxP3 by siRNA in GC cells reduced the expression of proapoptotic genes, such as PARP, caspase-3 and caspase-9. Collectively, our findings identify the novel roles of FoxP3 in inhibiting proliferation and inducing apoptosis in GC cells by regulating apoptotic signaling, which could be a promising therapeutic approach for gastric cancer.

Laryngoscopy findings and histological results in a rabbit gastroesophageal reflux model.

The role of lower esophageal sphincter (LES) in laryngopharyngeal reflux is controversial. In this study, we used an animal model to investigate the association between LES dysfunction and reflux laryngitis. Twelve healthy New Zealand albino rabbits (2.5-3.5 kg) were utilized in this study. The animals were divided into two groups. Eight rabbits underwent total cardiomyectomy to induce reflux, and the remaining four rabbits underwent a control sham operation. A laryngoscopy and a 24-hour intra-esophageal pH-metry were performed prior to surgery and again 2 and 8 weeks postsurgery. After the final laryngoscopy, all animals were sacrificed to obtain histological results. Total cardiomyectomy significantly increased the reflux index, the duration of the longest reflux episode and the total number of episodes that occurred in 24 h postsurgery. No significant difference was observed in the reflux finding score (RFS) between preoperative and 2-week postoperative rabbits (P = 0.11). But there was a statistically significant change in the RFS before and 8 weeks after the induction of reflux from 4.6 ± 0.9 to 8.3 ± 3.6 (P = 0.02). Submucous gland hyperplasia and inflammation were significantly increased in the reflux group compared to the control group. The results of this study suggest that chronic lower esophageal sphincter dysfunction is associated with reflux laryngitis in rabbits.