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.

高甘油三酯血症性急性胰腺炎的降脂治疗进展

随着生活水平的提高,高甘油三酯血症(hypertriglyce-ridemia,HTG)已经成为中国急性胰腺炎(acute pancrea-titis,AP)的第二大病因.高甘油三酯血症性急性胰腺炎(hypertriglyceridemia-induced acute pancreatitis,HTG-AP)相较于其他原因所致AP有其独特的特点.首先,血淀粉酶、脂肪酶升高不明显;其次,病情严重程度与血甘油三酯(triglyceride,TG)水平成正相关.治疗HTG-AP的关键是迅速降低血脂,常用的方法包括饮食调整、降脂药物、低分子肝素联合胰岛素、血液净化以及中西医结合治疗等.本文就国内外HTG-AP降脂方法的进展作一综述.

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 Pub Med,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.

Dendritic cells engineered to secrete anti-Dc R3 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-DcR 3 monoclonal antibody(mA b).METHODS DCs, T lymphocytes and primary PC cells were obtained from PC patients. DCs were transfected with a designed humanized anti-Dc R3 monoclonal antibody heavy and light chain m RNA and/or total tumor RNA(DC-tumor-anti-Dc R3 RNA or DC-total tumor RNA) by using electroporation technology. The identification, concentration and function of anti-DcR 3 mA b secreted by DC-tumor-anti-Dc R3 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-DcR 3 mA b 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-DcR 3 mA b secreting DCs was performed using a 51 Cr releasing test. T cell responses induced by RNAloaded DCs were analyzed by measuring cytokine levels, including IFN-γ, IL-10, IL4, TNF-α and IL-12.RESULTS The anti-Dc R3 m Ab secreted by DCs reacted withrecombinant human Dc R3 protein and generated a band with 35 k Da molecular weight. The secreting m Ab was transient, peaking at 24 h and becoming undetectable after 72 h. After co-incubation with DCtumor-anti-Dc R3 RNA for designated times, the Dc R3 level in the supernatant of autologous PC cells was significantly down-regulated(P < 0.05). DCs secreting anti-Dc R3 m Ab could improve cell viability and slow down the apoptosis of RNA-loaded DCs, compared with DC-total tumor RNA(P < 0.01). The anti-Dc R3 m Ab secreted by DC-tumor-anti-Dc R3 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-DcR 3 mA b 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-Dc R3 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.

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 MSC2156119 J 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 Ⅲrandomized controlled trials.

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 ±15.4, 50.0 ±12.4, and 12.0 ±3.8, respectively. The corresponding numbers of invading PACN-1, PACN-1-p and PACN-1-K cells were 29.0 ±10.6, 31.0 ±11.4, and 8.0 ±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.

Current developments, problems and solutions in the non-surgical treatment of pancreatic cancer

Pancreatic cancer is a common malignant neoplasm of the pancreas with an increasing incidence, a low early diagnostic rate and a fairly poor prognosis. To date, the only curative therapy for pancreatic cancer is surgical resection, but only about 20% patients have this option at the time of diagnosis and the mean 5-year survival rate after resection is only 10%-25%. Therefore, developing new treatments to improve the survival rate has practical significance for patients with this disease. This review deals with a current unmet need in medical oncology: the improvement of the treatment outcome of patients with pancreatic cancer. We summarize and discuss the latest systemic chemotherapy treatments (including adjuvant, neoadjuvant and targeted agents), radiotherapy, interventional therapy and immunotherapy. Besides discussing the current developments, we outline some of the main problems, solutions and prospects in this field.

KAI1 inhibits lymphangiogenesis and lymphatic metastasis of pancreatic cancer in vivo

BACKGROUND: Several studies have shown that KAI1 inhibits tumor metastasis, but its mechanism is not clear. The present study aimed to determine the role of KAI1 in lymphatic metastasis, specifically in pancreatic cancer. METHODS: The KAI1 gene was transfected into the pancreatic cancer cell line MIA PaCa-2 and PANC-1 by using liposomes and selected by G418, and the protein was measured by Western blotting. After successful infection, the cell growth curve was studied by MTT, vascular endothelial growth factor C(VEGF-C) secretion by pancreatic cancer cell were measured by ELISA. The KAI1 and pCMV transfected MIA PaCa-2 cells were renamed as MIA PaCa-2-K and MIA PaCa-2-p. These two kinds of cells were injected into the subcuticular layer of nude mice; both tumor growth and metastasis through the lymphatic nodes were assessed. Lymphangiogenesis in tumors was measured by immunohistochemistry. RESULTS: The VEGF-C secretion was significantly reduced in MIA PaCa-2 cells compared with PANC-1 cells after being transfected with the KAI1 gene. The growth rate of subcutaneous tumors was similar after the injection of MIA PaCa-2-K, MIA PaCa-2, and MIA PaCa-2-p. MIA PaCa-2-K tumors showed slower lymphangiogenesis and lymph node metastasis compared with MIA PaCa-2 and MIA PaCa-2-p tumors. CONCLUSION: The overexpression of KAI1 inhibits the lymphangiogenesis and lymph node metastasis of MIA PaCa-2 pancreatic tumors.

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.

肝硬化患者肝外肿瘤的发病风险及治疗措施

肝硬化患者是肝癌的高危人群,然而,肝硬化患者是否也存在更高的肝外肿瘤风险仍存争议.此外,肝硬化患者肝功能不全常常限制了肝外肿瘤的外科手术和抗癌药物治疗的应用,这使得肝硬化患者肝外肿瘤的治疗也面临着巨大挑战.这篇述评旨在简要回顾肝硬化患者肝外肿瘤的发病风险及治疗策略.

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.

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.

食管静脉曲张侧支循环可预测内镜治疗后复发和再出血:系统综述和meta分析

背景:内镜治疗被推荐应用于食管静脉曲张,但内镜根治后常出现静脉曲张复发或再出血。本研究旨在系统评估食管静脉曲张侧支静脉循环(ECV)的出现率以及ECV与内镜治疗后复发或再出血的关系。方法:我们通过PubMed、EMBASE和Cochrane等数据库检索相关文献。统计食管旁静脉(para-EV)、食管周围静脉(peri-EV)和穿静脉(PV)的出现率。分别采用风险比(RR)和比值比(OR)对队列研究和病例对照研究的复发/再出血风险进行评估。采用随机效应模型进行合并分析,并评估研究间的异质性。结果:提取的532篇文献最终纳入28篇进行分析。合并分析显示,食管静脉曲张患者para-EV、peri-EV和PV的出现率分别为73%、88%和54%。静脉曲张复发患者para-EV和PV的出现率分别为87%和62%。PV患者食管静脉曲张复发率显著升高(8项病例对照研究合并分析:OR=9.79,95%CI:1.95-49.22,P=0.006),但para-EV患者复发率未见显著升高(4项病例对照研究合并分析:OR=4.26,95%CI:0.38-38.35,P=0.24;3项队列研究合并分析:RR=1.81,95%CI:0.83-3.97,P=0.14)。para-EV患者再出血风险显著升高(两项队列研究合并分析:RR=13.00,95%CI:2.43-69.56,P=0.003)。本次meta分析中各研究间存在显著异质性。结论:ECV常出现于食管静脉曲张患者,ECV的出现有助于对内镜治疗后食管静脉曲张复发或再出血进行预测。