Effects of postoperative use of proton pump inhibitors on gastrointestinal bleeding after endoscopic variceal treatment during hospitalization.

BACKGROUND: Endoscopic variceal treatment (EVT) is recommended as the mainstay choice for the management of high-risk gastroesophageal varices and acute variceal bleeding in liver cirrhosis. Proton pump inhibitors (PPIs) are widely used for various gastric acid-related diseases. However, the effects of PPIs on the development of post-EVT complications, especially gastrointestinal bleeding (GIB), remain controversial. AIM: To evaluate the effects of postoperative use of PPIs on post-EVT complications in patients with liver cirrhosis during hospitalization. METHODS: Patients with a diagnosis of liver cirrhosis who were admitted to the Department of Gastroenterology of the General Hospital of Northern Theater Command, treated by an attending physician between January 2016 and June 2020 and underwent EVT during their hospitalization were included. Logistic regression analyses were performed to explore the effects of postoperative use of PPIs on the development of post-EVT complications during hospitalization. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. RESULTS: A total of 143 patients were included. The incidence of post-EVT GIB and other post-EVT complications was 4.90% and 46.85%, respectively. In the overall analyses, postoperative use of PPIs did not significantly reduce the risk of post-EVT GIB (OR = 0.525, 95%CI = 0.113-2.438, P = 0.411) or other post-EVT complications (OR = 0.804, 95%CI = 0.413-1.565, P = 0.522). In the subgroup analyses according to the enrollment period, type and route of PPIs after the index EVT, use of PPIs before the index EVT, use of vasoactive drugs after the index EVT, indication of EVT (prophylactic and therapeutic), and presence of portal venous system thrombosis, ascites, and hepatocellular carcinoma, the effects of postoperative use of PPIs on the risk of post-EVT GIB or other post-EVT complications remain not statistically significant. CONCLUSION: Routine use of PPIs after EVT should not be recommended in patients with liver cirrhosis for the prevention of post-EVT complications during hospitalization.

Successful treatment of acute symptomatic extensive portal venous system thrombosis by 7-day systemic thrombolysis.

Acute portal venous system thrombosis (PVST) can cause acute mesenteric ischemia and even intestinal infarction, which are potentially fatal, and requires recanalization in a timely fashion. Herein, we report a 56-year-old man with acute non-cirrhotic symptomatic extensive PVST who achieved portal vein recanalization after systemic thrombolysis combined with anticoagulation. Initially, anticoagulation with enoxaparin sodium for 4 d was ineffective, and then systemic thrombolysis for 7 d was added. After that, his abdominal pain completely disappeared, and portal vein system vessels became gradually patent. Long-term anticoagulation therapy was maintained. In conclusion, 7-d systemic thrombolysis may be an effective and safe choice of treatment for acute symptomatic extensive PVST which does not respond to anticoagulation therapy.

KAI1/CD82 gene and autotaxin-lysophosphatidic acid axis in gastrointestinal cancers.

The KAI1/CD82 gene inhibits the metastasis of most tumors and is remarkably correlated with tumor invasion and prognosis. Cell metabolism dysregulation is an important cause of tumor occurrence, development, and metastasis. As one of the important characteristics of tumors, cell metabolism dysregulation is attracting increasing research attention. Phospholipids are an indispensable substance in the metabolism in various tumor cells. Phospholipid metabolites have become important cell signaling molecules. The pathological role of lysophosphatidic acid (LPA) in tumors was identified in the early 1990s. Currently, LPA inhibitors have entered clinical trials but are not yet used in clinical treatment. Autotaxin (ATX) has lysophospholipase D (lysoPLD) activity and can regulate LPA levels in vivo. The LPA receptor family and ATX/lysoPLD are abnormally expressed in various gastrointestinal tumors. According to our recent pre-experimental results, KAI1/CD82 might inhibit the migration and metastasis of cancer cells by regulating the ATX-LPA axis. However, no relevant research has been reported. Clarifying the mechanism of ATX-LPA in the inhibition of cancer metastasis by KAI1/CD82 will provide an important theoretical basis for targeted cancer therapy. In this paper, the molecular compositions of the KAI1/CD82 gene and the ATX-LPA axis, their physiological functions in tumors, and their roles in gastrointestinal cancers and target therapy are reviewed.

Esophageal collateral veins in predicting esophageal variceal recurrence and rebleeding after endoscopic treatment: a systematic review and meta-analysis.

BACKGROUND: Endoscopic treatment is recommended for the management of esophageal varices. However, variceal recurrence or rebleeding is common after endoscopic variceal eradication. Our study aimed to systematically evaluate the prevalence of esophageal collateral veins (ECVs) and the association of ECVs with recurrence of esophageal varices or rebleeding from esophageal varices after endoscopic treatment. METHODS: We searched the relevant literature through the PubMed, EMBASE, and Cochrane Library databases. Prevalence of paraesophageal veins (para-EVs), periesophageal veins (peri-EVs), and perforating veins (PVs) were pooled. Risk ratio (RR) and odds ratio (OR) with 95% confidence intervals (CIs) were calculated for cohort studies and case-control studies, respectively. A random-effects model was employed. Heterogeneity among studies was calculated. RESULTS: Among the 532 retrieved papers, 28 were included. The pooled prevalence of para-EVs, peri-EVs, and PVs in patients with esophageal varices was 73%, 88%, and 54%, respectively. The pooled prevalence of para-EVs and PVs in patients with recurrence of esophageal varices was 87% and 62%, respectively. The risk for recurrence of esophageal varices was significantly increased in patients with PVs (OR = 9.79, 95% CI: 1.95-49.22, P = 0.006 for eight case-control studies), but not in those with para-EVs (OR = 4.26, 95% CI: 0.38-38.35, P = 0.24 for four case-control studies; RR = 1.81, 95% CI: 0.83-3.97, P = 0.14 for three cohort studies). Patients with para-EVs had a significantly higher incidence of rebleeding from esophageal varices (RR = 13.00, 95% CI: 2.43-69.56, P = 0.003 for two cohort studies). Statistically significant heterogeneity was notable across the meta-analyses. CONCLUSIONS: ECVs are common in patients with esophageal varices. Identification of ECVs could be helpful for predicting the recurrence of esophageal varices or rebleeding from esophageal varices after endoscopic treatment.

Portal hypertension in a patient with biliary hamartomas: A case report.

BACKGROUND: Biliary hamartomas (BH) are a rare benign disease caused by malformation of the intrahepatic bile ducts. BH are occasionally diagnosed, but often lack obvious clinical symptoms. They are usually diagnosed by biopsy and imaging tests in clinical practice. Few studies have reported the association of BH with portal hypertension. CASE SUMMARY: A 40-year-old man was repeatedly admitted to our hospital due to hematochezia. The source of bleeding was considered to be gastroesophageal varices and portal hypertensive gastropathy by endoscopy. He had no history of hepatitis virus infection, alcohol abuse, drug-induced liver injury, or autoimmune liver disease. He underwent magnetic resonance imaging, which showed rounded, irregular, low-signal-T1 and high-signal-T2 lesions diffusely distributed on the liver, that were not communicated with the biliary system on magnetic resonance cholangiopancreatography. According to the imaging examination, the patient was considered to have a diagnosis of BH with portal hypertension. CONCLUSION: Based on the present case report, BH may be a potential etiology of portal hypertension.

KAI1 reverses the epithelial-mesenchymal transition in human pancreatic cancer cells.

BACKGROUND: Epithelial-mesenchymal transition (EMT) plays an important role in pancreatic cancer (PC). In the present study, we investigated the effects of KAI1 gene overexpression on the EMT of human PC cell lines, MIA PaCa-2 and PACN-1. METHODS: Plasmids overexpressing KAI1 and pCMV were transfected into MIA PaCa-2 and PACN-1 cells, respectively. After selection of differently transfected cells by G418, KAI1 protein levels were examined by Western blotting, and transfected cells were renamed as MIA PaCa-2-K, MIA PaCa-2-p, PACN-1-K and PACN-1-p. Wound healing and Transwell migration assays were then performed comparing the two groups of cells. EMT-related markers were analyzed by Western blotting. RESULTS: The percentage of wound closure significantly decreased in MIA PaCa-2-K cells compared with MIA PaCa-2-p and MIA PaCa-2 cells after 24, 48 and 72 h (P < 0.05). In PACN-1-K cells, the percentage of wound closure significantly decreased as well (P < 0.05). Numbers of invading MIA PaCa-2, MIA PaCa-2-p and MIA PaCa-2-K cells were determined as 48.0 ±â€¯15.4, 50.0 ±â€¯12.4, and 12.0 ±â€¯3.8, respectively. The corresponding numbers of invading PACN-1, PACN-1-p and PACN-1-K cells were 29.0 ±â€¯10.6, 31.0 ±â€¯11.4, and 8.0 ±â€¯4.2, respectively. KAI1 overexpression induced a significant upregulation of E-cadherin and also significant downregulation of Snail, vimentin, matrix metalloproteinase 2 (MMP2) and MMP9 (all P < 0.05) in PC cells. CONCLUSIONS: KAI1 reversed EMT-related marker expression and inhibited migration and invasion of PC cells. Thus, KAI1 might represent a novel potential therapeutic target for PC.

Delphinidin protects ß2m-/Thy1+ bone marrow-derived hepatocyte stem cells against TGF-ß1-induced oxidative stress and apoptosis through the PI3K/Akt pathway in vitro.

ß2m-/Thy1+ bone marrow-derived hepatocyte stem cells (BDHSCs) have a potential to be applied for cellular treatment in liver cirrhosis. However, the resultant tissue regeneration is restricted by transplanted cells' death. The accumulation of transforming growth factor beta 1 (TGF-ß1) in liver fibrosis local microenvironment may play an essential role in the rapid cell death of implanted ß2m-/Thy1+ BDHSCs. The main mechanism of poor survival of the target stem cells is still unknown. Delphinidin, an anthocyanidin, has potent antioxidant and anti-inflammatory activities. However, whether this bio-active ingredient can substantially contribute to ß2m-/Thy1+ BDHSCs' protection from TGF-ß1 induced apoptosis in vitro remains to be elucidated. In the present research, we determined whether delphinidin pretreatment can improve the survival of ß2m-/Thy1+ BDHSCs during exposure to TGF-ß1 and elucidated its underlying mechanisms. By using TGF-ß1, we induced the apoptosis of ß2m-/Thy1+ BDHSCs and assessed the apoptotic rates up to 24 h by flow cytometry. ß2m-/Thy1+ BDHSC proliferation was gauged using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl- 2H-tetrazolium bromide (MTT) assay. The expression grades of Bcl-2, Akt, caspase-3, and Bax were observed through Western blot analysis. We found that delphinidin can significantly impede TGF-ß1-induced apoptosis dose-dependently, scavenge reactive oxygen species (ROS), and inhibit the discharge of caspase-3 in ß2m-/Thy1+ BDHSCs. We also demonstrated that delphinidin can activate the phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathway. The suppression of ROS and succeeding apoptosis was achieved by pretreatment with LY294002, a PI3K/Akt pathway inhibitor. In summary, our findings revealed that delphinidin can protect ß2m-/Thy1+ BDHSCs from apoptosis and ROS-dependent oxidative stress induced by the TGF-ß1 via PI3K/Akt signaling pathway. On the basis of these data, delphinidin can be regarded as a promising anti-apoptotic agent for enhancing ß2m-/Thy1+ BDHSC survival during cell transplantation in liver cirrhosis patients.

A Small Jejunal Angioleiomyoma Detected by Double-Balloon Enteroscopy: A Case Report.

BACKGROUND Angioleiomyoma in the small intestine is a rare cause of gastrointestinal bleeding. Only 7 cases of angioleiomyoma in the small intestine were reported in the English literature, with 4 of them causing gastrointestinal bleeding. The diagnosis of angioleiomyomas in the small intestine before surgery is difficult. CASE REPORT We report the case of a 42-year-old man with recurrent melena who underwent repeated esophagogastroduodenoscopy and colonoscopy, without positive finding. During a double-balloon enteroscopy, an elevated lesion with a diameter of 6 mm was found in the jejunum. The lesion was resected laparoscopically assisted with double-balloon enteroscpy. A microscopic examination showed fibric membrane of the mass and numerous vascular channels surrounded by proliferated smooth muscle. There were exudative fibrin and many thrombi formed by red blood cells. Immunohistochemistry was positive for SMA and CD34. A pathological diagnosis of jejunal angioleiomyoma with thrombus was established. During a 5-year follow-up, there was no further gastrointestinal bleeding. CONCLUSIONS The gastroenterologists should consider angioleiomyoma in the small intestine when assessing obscure gastrointestinal bleeding.

Comparison of efficacy and safety of hyoscine butylbromide versus anisodamine for acute gastric or intestinal spasm-like pain: A randomized, double-blinded, multicenter Phase III trial.

OBJECTIVE: Acute gastric or intestinal spasm-like pain is common in clinical setting. Hyoscine butylbromide (HBB), an anti-cholinergic agent, relieves pain in stomach and bowel cramps by inhibiting smooth muscle contractility. In this study, we aimed to compare the efficacy and safety of parenteral HBB and anisodamine for treating acute gastric or intestinal pain. METHODS: In this randomized, controlled, double-blind, parallel-group, multicenter non-inferiority trial, 299 Chinese patients were randomly assigned to HBB or anisodamine in a ratio of 1:1. They were administrated a single dose of either HBB 20 mg or anisodamine 10 mg, and a second dose was given when needed. The primary end-point was the difference in pain intensity (PID) from the pre-dose baseline at 20 min after the first injection. RESULTS: Altogether 295 patients completed the protocol (153 in the HBB and 142 in the anisodamine group). For the primary end-point, the PID was -4.09 (95% confidence interval [CI]: -4.41, -3.76) for the HBB group and -3.66 (95% CI: -4.02, -3.31) for the anisodamine group (P < 0.0001 for non-inferiority). The percentage of patients with at least one adverse event was lower in the HBB group than in the anisodamine group (13.1% vs 17.6%), but there was no statistical significance (P = 0.279). The most frequent adverse events were thirst (7.8%) and dry mouth (2.6%) in the HBB group, and thirst (7.0%), dry mouth (3.5%) and nodal arrhythmia (2.1%) in the anisodamine group. CONCLUSIONS: HBB 20 mg was not inferior to anisodamine 10 mg in pain relief of patients with acute gastric or intestinal spasm-like pain. Both drugs were safe and well tolerated.

Endoscopic retrograde cholangiopancreatography with double balloon enteroscope in patients with altered gastrointestinal anatomy: A meta-analysis.

BACKGROUND/AIMS: The aim of this study was to evaluate the effectiveness and safety of endoscopic retrograde cholangiopancreatography with double balloon enteroscope (DBE-ERCP) in patients with altered gastrointestinal anatomy in a meta-analysis. MATERIALS AND METHODS: A comprehensive literature search was conducted on PubMed, EMBASE, and Cochrane library covering the period from January 2001 to December 2015. Data were selected and abstracted from eligible studies and were pooled using a random-effects model. Heterogeneity was assessed using the I2 test. RESULTS: Ten studies involving a total of 301 patients were included in the analysis. The pooled enteroscopy, diagnostic, and therapeutic success rates were 89.75% [95% confidence interval (CI): 79.65-94.30%], 79.92% (95% CI: 68.06-89.59%), and 63.55% (95% CI: 53.70-72.86%), respectively. DBE-ERCP-related complications occurred in 18 patients including perforation (5), pancreatitis (3), cholangitis (9), and bleeding (1). The incidence of DBE-ERCP-related complication was 6.27% (95% CI: 2.61-11.38%). CONCLUSION: Diagnostic and therapeutic DBE-ERCPs are feasible in patients with altered gastrointestinal anatomy. DBE-ERCP may be considered when pancreaticobiliary diseases occur in patients undergoing Roux-en-Y reconstruction or pancreaticoduodenectomy.

Dendritic cells engineered to secrete anti-DcR3 antibody augment cytotoxic T lymphocyte response against pancreatic cancer in vitro.

AIM: To investigate the enhanced cytotoxic T lymphocyte responses against pancreatic cancer (PC) in vitro induced by dendritic cells (DCs) engineered to secrete anti-DcR3 monoclonal antibody (mAb). METHODS: DCs, T lymphocytes and primary PC cells were obtained from PC patients. DCs were transfected with a designed humanized anti-DcR3 monoclonal antibody heavy and light chain mRNA and/or total tumor RNA (DC-tumor-anti-DcR3 RNA or DC-total tumor RNA) by using electroporation technology. The identification, concentration and function of anti-DcR3 mAb secreted by DC-tumor-anti-DcR3 RNA were determined by western blotting and enzyme-linked immunosorbent assay. After co-culturing of autologous isolated PC cells with target DCs, the effects of secreting anti-DcR3 mAb on RNA-DCs' viability and apoptosis were assessed by MTT assay and flow cytometry. Analysis of enhanced antigen-specific immune response against PC induced by anti-DcR3 mAb secreting DCs was performed using a 51Cr releasing test. T cell responses induced by RNA-loaded DCs were analyzed by measuring cytokine levels, including IFN-γ, IL-10, IL4, TNF-α and IL-12. RESULTS: The anti-DcR3 mAb secreted by DCs reacted with recombinant human DcR3 protein and generated a band with 35 kDa molecular weight. The secreting mAb was transient, peaking at 24 h and becoming undetectable after 72 h. After co-incubation with DC-tumor-anti-DcR3 RNA for designated times, the DcR3 level in the supernatant of autologous PC cells was significantly down-regulated (P < 0.05). DCs secreting anti-DcR3 mAb could improve cell viability and slow down the apoptosis of RNA-loaded DCs, compared with DC-total tumor RNA (P < 0.01). The anti-DcR3 mAb secreted by DC-tumor-anti-DcR3 RNA could enhance the induction of cytotoxic T lymphocytes (CTLs) activity toward RNA-transfected DCs, primary tumor cells, and PC cell lines, compared with CTLs stimulated by DC-total tumor RNA or control group (P < 0.05). Meanwhile, the antigen-specific CTL responses were MHC class I-restricted. The CD4+ T cells and CD8+ T cells incubated with anti-DcR3 mAb secreting DCs could produce extremely higher level IFN-γ and lower level IL4 than those incubated with DC-total tumor RNA or controls (P < 0.01). CONCLUSION: DCs engineered to secrete anti-DcR3 antibody can augment CTL responses against PC in vitro, and the immune-enhancing effects may be partly due to their capability of down-regulating DC apoptosis and adjusting the Th1/Th2 cytokine network.

Esophageal Stent for Refractory Variceal Bleeding: A Systemic Review and Meta-Analysis.

Background. Preliminary studies suggest that covered self-expandable metal stents may be helpful in controlling esophageal variceal bleeding. Aims. To evaluate the effectiveness and safety of esophageal stent in refractory variceal bleeding in a systematic review and meta-analysis. Methods. A comprehensive literature search was conducted on PubMed, EMBASE, and Cochrane Library covering the period from January 1970 to December 2015. Data were selected and abstracted from eligible studies and were pooled using a random-effects model. Heterogeneity was assessed using I (2) test. Results. Five studies involving 80 patients were included in the analysis. The age of patients ranged from 18 to 91 years. The mean duration of follow-up was 46.8 d (range, 30-60 d). The success rate of stent deployment was 96.7% (95% CI: 91.6%-99.5%) and complete response to esophageal stenting was in 93.9% (95% CI: 82.2%-99.6%). The incidence of rebleeding was 13.2% (95% CI: 1.8%-32.8%) and the overall mortality was 34.5% (95% CI: 24.8%-44.8%). Most of patients (87.4%) died from hepatic or multiple organ failure, and only 12.6% of patients died from uncontrolled bleeding. There was no stent-related complication reported and the incidence of stent migration was 21.6% (95% CI: 4.7%-46.1%). Conclusion. Esophageal stent may be considered in patients with variceal bleeding refractory to conventional therapy.

Hepatic Resection after Initial Transarterial Chemoembolization Versus Transarterial Chemoembolization Alone for the Treatment of Hepatocellular Carcinoma: A Meta-analysis of Observational Studies.

BACKGROUND: There is no consensus regarding the selection of treatment options for hepatocellular carcinoma (HCC) after initial transarterial chemoembolization (TACE). This meta-analysis aimed to explore the survival benefit of hepatic resection after initial TACE for the treatment of HCC. MATERIALS AND METHODS: We searched three major databases to identify all relevant papers comparing the outcomes of hepatic resection after initial TACE versus TACE alone for the treatment of HCC. Hazard ratios (HRs) with 95% confidence intervals (95%CIs) were calculated to evaluate the survival benefit of hepatic resection after initial TACE over TACE alone. RESULTS: Three of 2,037 initially identified papers were included. All of them were cohort studies from Asia. There was a significantly better overall survival (OS) in patients undergoing hepatic resection after initial TACE than in those undergoing TACE alone (HR=0.63, 95%CI=0.52-0.76, P<0.00001). The heterogeneity among studies was not statistically significant (P=0.96; I2=0%). CONCLUSIONS: Hepatic resection could improve the OS of HCC patients treated initial TACE. Further randomized controlled trials are now necessary to identify the target populations for the sequential use of hepatic resection after initial TACE and to compare the outcomes between patients undergoing hepatic resection after initial TACE session versus those undergoing TACE alone.

Hepatic Re-resection Versus Transarterial Chemoembolization for the Treatment of Recurrent Hepatocellular Carcinoma after Initial Resection: a Systematic Review and Meta-analysis.

BACKGROUND: A systematic review and meta-analysis were performed to compare the post-recurrence survival with hepatic re-resection versus transarterial chemoembolization (TACE) for recurrent hepatocellular carcinoma (HCC) after initial resection. MATERIALS AND METHODS: All relevant papers were searched via PubMed, EMBASE, and Cochrane Library databases. Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled using a random-effects model. Subgroup analysis was performed according to country. Sensitivity analysis was performed in studies which clearly reported the recurrent regions, in moderate/high-quality studies, in studies published in full-text form, and in studies published after 2005. RESULTS: In total, twelve papers were included in our study. Five and seven of them were of moderate- and poor-quality, respectively. The overall meta-analysis demonstrated a statistically significantly higher post-recurrence survival in the hepatic re-resection group than in those undergoing TACE (HR=0.64, 95%CI=0.52-0.79, P<0.0001). Heterogeneity was statistically significant and statistical significance remained in the subgroup analysis. Sensitivity analyses were also consistent with the overall analysis. CONCLUSIONS: Hepatic re-resection might provide a better post-recurrence survival than TACE for recurrent HCC after initial resection. However, considering the low quality of published studies and the potential bias of treatment selection, further randomized trials should be warranted to confirm these findings.

MET inhibitors for treatment of advanced hepatocellular carcinoma: A review.

The current standard treatment option for advanced hepatocellular carcinoma (HCC) is sorafenib, but its clinical benefit is modest. In spite of many attempts, few drugs can provide any significant improvement of survival as the first- or second-line therapy of choice in phase III randomized controlled trials. Recently, the subgroup analysis of a phase II randomized controlled trial has shown that tivantinib, a selective MET inhibitor, can significantly improve the overall survival in patients with MET-positive advanced HCC after the failure or intolerance of a prior systemic therapy. These findings enlighten the role of MET inhibitors in the treatment of advanced HCC. In this paper, we review all ongoing and completed clinical trials regarding this topic. As for the first-line therapy of advanced HCC, INC280 and foretinib are being evaluated in 2 phase II single-arm trials; and MSC2156119J and golvatinib plus sorafenib are being compared with sorafenib alone in 2 phase II randomized controlled trials. As for the second-line therapy of advanced HCC, tivantinib and cabozantinib are being compared with placebo in 2 phase III randomized controlled trials.

MicroRNA-33a-mediated downregulation of Pim-3 kinase expression renders human pancreatic cancer cells sensitivity to gemcitabine.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers, with less than 5% of patients surviving 5 years beyond diagnosis. Systemic therapies, particularly gemcitabine, have a modest clinical benefit, but chemoresistance limits their efficacy. Here, we demonstrate that plasma miR-33a levels positively correlated with miR-33a levels in tumor tissues of patients with PDAC and are a good prognostic indicator of overall survival. Overexpression of miR-33a inhibited tumor cell proliferation and increased the chemosensitivity to gemcitabine both in vitro and in vivo. Moreover, miR-33a targets Pim-3 directly in PDAC. Pim-3 expression was a prognostic indicator related to poor survival in pancreatic cancer patients. Plasma miR-33a levels were significantly lower in pancreatic cancer patients with high Pim-3 protein expression than in healthy controls. Furthermore, overexpression of miR-33a in pancreatic cancer cell lines suppressed Pim-3 expression, leading to downregulation of the AKT/Gsk-3ß/ß-catenin pathway. Overall, these results indicate that miR-33a functions as a tumor suppressor that downregulates Pim-3 kinase expression to inhibit both pancreatic tumor growth and gemcitabine resistance via the AKT/ß-catenin pathway. Hence, detection of plasma miR-33a may be a simple and convenient method of predicting therapeutic responses.

Nonselective beta-blockers in cirrhotic patients with no or small varices: A meta-analysis.

AIM: To explore effects of nonselective beta-blockers (NSBBs) in cirrhotic patients with no or small varices. METHODS: The PubMed, EMBASE, Science Direct, and Cochrane library databases were searched for relevant papers. A meta-analysis was performed using ORs with 95%CI as the effect sizes. Subgroup analysis was conducted according to the studies including patients without varices and those with small varices. RESULTS: Overall, 784 papers were initially retrieved from the database searches, of which six randomized controlled trials were included in the meta-analysis. The incidences of large varices development (OR = 1.05, 95%CI: 0.25-4.36; P = 0.95), first upper gastrointestinal bleeding (OR = 0.59, 95%CI: 0.24-1.47; P = 0.26), and death (OR = 0.70, 95%CI: 0.45-1.10; P = 0.12) were similar between NSBB and placebo groups. However, the incidence of adverse events was significantly higher in the NSBB group compared with the placebo group (OR = 3.47, 95%CI: 1.45-8.33; P = 0.005). The results of subgroup analyses were similar to those of overall analyses. CONCLUSION: The results of this meta-analysis indicate that NSBBs should not be recommended for cirrhotic patients with no or small varices.

Comparison of cytotoxic T lymphocyte responses against pancreatic cancer induced by dendritic cells transfected with total tumor RNA and fusion hybrided with tumor cell.

Pancreatic cancer (PC) is a deadly human malignancy. Dendritic cell (DC)-based immunotherapy with whole tumor antigens demonstrates potential efficiency in cancer treatment. Tumor RNA and tumor fusion hybrid cells are sources of whole tumor antigens for preparing DC tumor vaccines. However, the efficacy of these sources in eliciting immune responses against PC has not yet to be directly compared. In the present study, patient-derived PC cells and DCs were fused (DC-tumor hybrids) and primary cultured PC cell-derived total RNA was electroporated into autologous DCs (DC-tumor RNA). The antitumor immune responses induced by DC-tumor hybrids and DC-tumor RNA were compared directly. The results showed that both RNA and hybrid methodologies could induce tumor-specific cytotoxic T lymphocyte (CTL) responses, but pulsing DCs with total tumor RNA could induce a higher frequency of activated CTLs and T-helper cells than fusing DCs with autologous tumor cells. In addition, DC-tumor RNA triggered stronger autologous tumor cell lysis than DC-tumor hybrids. It could be concluded that DCs pulsed with whole tumor RNA are superior to those fused with tumor cells in priming anti-PC CTL responses. Electroporation with total tumor RNA may be more suitable for DC-based PC vaccination.

Pancreatic cancer: diagnosis and treatments.

Pancreatic cancer is one of the deadliest cancers, with exceptionally high mortality. Despite the relatively low incidence rate (10th), it is the fourth leading cause of cancer-related deaths in most developed countries. To improve the early diagnosis of pancreatic cancer and strengthen the standardized comprehensive treatment are still the main focus of pancreatic cancer research. Here, we summarized the rapid developments in the diagnosis and treatments of pancreatic cancer. Regarding diagnosis, we reviewed advances in medical imaging technology, tumor markers, molecular biology (e.g., gene mutation), and proteomics. Moreover, great progress has also been made in the treatments of this disease, including surgical resection, chemotherapy, targeted radiotherapy, targeted minimally invasive treatment, and molecular targeted therapy. Therefore, we also recapitulated the development, advantages, and disadvantages of each of the treatment methods in this review.