Bibliometric and visual analysis of esophagogastric junction cancer research from 2002 to 2021.

Numerous studies related to esophagogastric junction cancer (EGC) have been published, and bibliometric analysis of these publications may be able to identify research hotspots and frontiers of EGC. Studies published on EGC between 2002 and 2021 were retrieved from the Web of Science Core Collection. The collaboration network of countries/regions, institutions, authors, co-citation network of journals, co-occurrence network, and overlay visualization of keywords were analyzed using the VOSviewer software. Cluster and timeline analyses of references were performed using the CiteSpace software. A total of 5109 English articles were published across 691 journals by authors affiliated with 4727 institutions from 81 countries/regions. The annual number of publications related to EGC research has exhibited an increasing trend. The United States, China, and Japan emerged as the top 3 prolific countries/regions. Institutions in the United States, Japan, and South Korea exhibited significant collaboration with one another. Diseases of the Esophagus was the most prolific journal, and Annals of Surgical Oncology, World Journal of Gastroenterology, and Gastric Cancer had also published more than 100 studies. Jaffer A Ajani was the most productive author while David Cunningham ranked the first in terms of total citations and average citations per article. Barrett's esophagus, gastroesophageal reflux disease, Helicobacter pylori, and obesity were common topics in earlier research, and recent years had seen a shift towards the topics of immunotherapy, targeted therapy, and neoadjuvant chemotherapy. In conclusion, growing attention is paid to EGC research, especially in terms of immunotherapy, targeted therapy, and neoadjuvant chemotherapy.

MSLN induced EMT, cancer stem cell traits and chemotherapy resistance of pancreatic cancer cells.

Chemoresistance is one of the main reasons for poor prognosis of pancreatic cancer. The effects of mesothelin (MSLN) on chemoresistance in pancreatic cancer are still unclear. We aim to investigate potential roles of MSLN in chemoresistance and its relationship with proliferation, epithelial-mesenchymal transition (EMT) and cancer stemness of pancreatic cancer cells. Human pancreatic cancer cell lines ASPC-1 and Mia PaCa-2 with high and low expression of MSLN, respectively, were selected. The ASPC-1 with MSLN knockout (KO) and Mia PaCa-2 of MSLN overexpression (OE) were generated. The effects of MSLN on cell phenotypes, expression of EMT-related markers, clone formation, tumor sphere formation, and pathologic role of MSLN in tumorigenesis were detected. Sensitivity of tumor cells to gemcitabine was evaluated. The results showed that adhesion, proliferation, migration and invasion were decreased significantly in ASPC-1 with MSLN KO, whereas increased significantly in Mia PaCa-2 with MSLN OE. The size and the number of clones and tumor spheres were decreased in ASPC-1 with MSLN KO, and increased in Mia PaCa-2 with MSLN OE. In xenograft model, tumor volume was decreased (tumor grew slower) in MSLN KO group compared to control group, while increased in MSLN OE group. Mia PaCa-2 with MSLN OE had a higher IC50 of gemcitabine, while ASPC-1 with MSLN KO had a lower IC50. We concluded that MSLN could induce chemoresistance by enhancing migration, invasion, EMT and cancer stem cell traits of pancreatic cancer cells. Targeting MSLN could represent a promising therapeutic strategy for reversing EMT and chemoresistance in pancreatic cancer cells.

Clinical study on the necessity and feasibility of routine MRCP in patients with cholecystolithiasis before LC.

BACKGROUND: In the past quite a long time, intraoperative cholangiography(IOC)was necessary during laparoscopic cholecystectomy (LC). Now magnetic resonance cholangiopancreatography (MRCP) is the main method for diagnosing common bile duct stones (CBDS). Whether MRCP can replace IOC as routine examination before LC is still inconclusive. The aim of this study was to analyze the clinical data of patients undergoing LC for cholecystolithiasis, and to explore the necessity and feasibility of preoperative routine MRCP in patients with cholecystolithiasis. METHODS: According to whether MRCP was performed before operation, 184 patients undergoing LC for cholecystolithiasis in the Department of General Surgery, Beijing Shijitan Hospital, Capital Medical University from January 1, 2017 to December 31, 2018 were divided into non-MRCP group and MRCP group for this retrospective study. The results of preoperative laboratory test, abdominal ultrasound and MRCP, biliary related comorbidities, surgical complications, hospital stay and hospitalization expenses were compared between the two groups. RESULTS: Among the 184 patients, there were 83 patients in non-MRCP group and 101 patients in MRCP group. In MRCP group, the detection rates of cholecystolithiasis combined with CBDS and common bile duct dilatation by MRCP were higher than those by abdominal ultrasound (P < 0.05). The incidence of postoperative complications in non-MRCP group (8.43%) was significantly higher (P < 0.05) than that in MRCP group (0%). There was no significant difference in hospital stay (P > 0.05), but there was significant difference in hospitalization expenses (P < 0.05) between the two groups. According to the stratification of gallbladder stone patients with CBDS, hospital stay and hospitalization expenses were compared, and there was no significant difference between the two groups (P > 0.05). CONCLUSIONS: The preoperative MRCP can detect CBDS, cystic duct stones and anatomical variants of biliary tract that cannot be diagnosed by abdominal ultrasound, which is helpful to plan the surgical methods and reduce the surgical complications. From the perspective of health economics, routine MRCP in patients with cholecystolithiasis before LC does not increase hospitalization costs, and is necessary and feasible.

Lateral single incision laparoscopic totally extraperitoneal hernioplasty (L-SILTEP) after laparoscopic radical prostatectomy: A rare case report with literature review.

INTRODUCTION: Single-incision laparoscopic totally extraperitoneal hernioplasty is a commonly used surgical procedure for the treatment of inguinal hernia. However, it is difficult to use traditional single incision laparoscopic totally extraperitoneal hernioplasty to treat inguinal hernia after laparoscopic radical prostatectomy. We successfully and smoothly cured a patient with left inguinal hernia after laparoscopic radical prostatectomy using lateral single incision laparoscopic totally extraperitoneal hernioplasty. CASE PRESENTATION: We report the case of a 70-year-old man who underwent laparoscopic radical prostatectomy 2 years earlier and had an evanescent mass in the left inguinal region for 1 month. DIAGNOSIS: On the basis of preoperative abdominal computed tomography and intraoperative findings, the patient was diagnosed with a left indirect inguinal hernia, and post-laparoscopic radical prostatectomy. INTERVENTIONS: The patient underwent lateral single incision laparoscopic totally extraperitoneal hernioplasty. OUTCOMES: The patient recovered well after the operation, and there were no postoperative complications or recurrence of inguinal hernia 3 months after the operation. CONCLUSION: For patients who have undergone laparoscopic radical prostatectomy, lateral single-incision laparoscopic totally extraperitoneal hernioplastycan be performed.

Effects of proximal gastrectomy with narrow gastric tube anastomosis compared with total gastrectomy with Roux-en-Y anastomosis on upper gastric cancer.

OBJECTIVE: To investigate the clinical efficacy of proximal gastrectomy with narrow gastric tube anastomosis (PG-NGT) and total gastrectomy with Roux-en-Y anastomosis (TG-RY) for upper gastric cancer. MATERIALS AND METHODS: One hundred sixty-three upper gastric cancer patients were enrolled into the PG-NGT group and TG-RY group. The propensity score matching method was used to conduct a one-to-one match between the two groups with 38 patients in each group. RESULTS: Compared with the TG-RY group, the PG-NGT group had significantly (P < 0.05) shorter operation time, shorter hospital stay, and less intraoperative blood loss. The TG-RY group had significantly (P = 0.009) more lymph nodes dissected and greater (P = 0.014) total cost than the PG-NGT group, but no significant difference existed in the surgical cost between the two groups (P = 0.214). There was no significant (P > 0.05) difference in the incidence of anastomotic stenosis (10.5% vs. 13.1%) or the reflux esophagitis rate (8.6% vs. 9.1%) in the PG-NGT group and the TG-RY group. One year after surgery, the weight and hemoglobin and albumin levels in the PG-NGT group were significantly (P < 0.05) higher than those in the TG-RY group. CONCLUSIONS: PG-NGT may be better than TG-RY in improving patient weight loss and hemoglobin and albumin levels, without increasing the rate of anastomotic stenosis and reflux symptoms.

microRNA-301b-3p from mesenchymal stem cells-derived extracellular vesicles inhibits TXNIP to promote multidrug resistance of gastric cancer cells.

OBJECTIVE: MicroRNAs (miRNAs) from mesenchymal stem cells (MSC)-derived extracellular vesicles (MSCs-EVs), including exosomes, are known to participate in different diseases. However, the function of miR-301b-3p from MSCs-EVs on the chemoresistance of gastric cancer (GC) cells remains poorly characterized. Thus, we aim to explore the role of MSCs-EVs-derived miR-301b-3p in multidrug resistance of GC cells. METHODS: Cisplatin (DDP)/vincristine (VCR)-resistant and sensitive GC clinical samples were harvested to detect expression of miR-301b-3p and thioredoxin interacting protein (TXNIP). MSCs were respectively transfected with miR-301b-3p oligonucleotides and/or TXNIP plasmids to extract the EVs, which were then co-cultured with multidrug-resistant GC cells. Then, P-glycoprotein (P-gp) and multidrug resistance-associated protein (MRP), IC50, proliferation, migration, and apoptosis of resistant GC cells were determined. The tumor growth was observed in nude mice. Targeting relationship between miR-301b-3p and TXNIP was confirmed. RESULTS: miR-301b-3p was upregulated, and TXNIP was downregulated in DDP/VCR-resistant GC tissues and cells. MSC-EVs induced drug resistance, proliferation, and migration and inhibited apoptosis of DDP/VCR-resistant GC cells in vitro, as well as facilitated tumor growth in vivo. Inhibition of miR-301b-3p or upregulation of TXNIP reversed the promoting effect of MSC-EVs on DDP/VCR resistant GC cells to DDP/VCR resistance and malignant behaviors. The effects of MSC-EVs carrying miR-301b-3p inhibition on DDP/VCR-resistant GC cells were reversed by TXNIP downregulation. TXNIP was confirmed as a target gene of miR-301b-3p. CONCLUSION: miR-301b-3p from MSCs-EVs inhibits TXNIP to promote multidrug resistance of GC cells, providing a novel insight for chemotherapy in GC.

miR-125a-5p promotes gastric cancer growth and invasion by regulating the Hippo pathway.

OBJECTIVE: This study was carried out to explore the potential involvement of miR-125a-5p in the oncogenic effects of EphA2, TAZ, and TEAD2 and the activity of the Hippo signaling pathway in gastric cancer progression. METHODS: In vitro transfection of miR-125a-5p mimics or inhibitors, qRT-PCR, colony formation assays, and cell invasion assays were used to assess the effect of miR-125a-5p on the growth and invasion in gastric cancer (GC). Male nude mice bearing tumors derived from human GC cells were used for evaluating the effects of miR-125a-5p on tumor growth. Luciferase reporter assay, immunofluorescence, immunohistochemistry, qRT-PCR, and immunoblotting were performed to explore the role of miR-125a-5p in the epithelial-mesenchymal transition (EMT) and association among miR-125a-5p, EphA2, TAZ, and TEAD2 in GC cells. RESULTS: MiR-125a-5p enhanced GC cell viability and invasion in vitro, whereas inhibition of miR-125a-5p using a specific inhibitor and antagomir suppressed cancer cell invasion and tumor growth. Moreover, inhibition of miR-125a-5p reversed EMT in vitro. miR-125a-5p upregulated the expression of EphA2, TAZ, and TEAD2, promoted TAZ nuclear translocation, and induced changes in the activity of the Hippo pathway by enhancing the expression of TAZ target genes. Finally, miR-125a-5p was overexpressed in late-stage GCs, and positive correlations were observed with its targets EphA2, TAZ, and TEAD2. CONCLUSION: miR-125a-5p can promote GC growth and invasion by upregulating the expression of EphA2, TAZ, and TEAD2.

Long non-coding RNA ZFAS1 promotes the expression of EPAS1 in gastric cardia adenocarcinoma.

LncRNA (Long non-coding RNA) ZFAS1 (zinc finger antisense 1) functions as the oncogene in multiple cancers, including gastric cancer. However, its function and underlying mechanism in the GCA (gastric cardia adenocarcinoma), the most aggressive type of gastric cancer, remain unknown. We demonstrated here that the LncRNA ZFAS1 was up-regulated in GCA tissues. Furthermore, the elevated level of ZFAS1 was significantly associated with the GCA metastasis and cancer recurrence. It was also demonstrated to be an independent prognostic indicator of disease-free survival and overall survival for GCA patients. RNA sequencing showed that the up-regulated ZFAS1 was tightly associated with the down-regulated hypoxia inducible factor 1 (HIF1) and up-regulated EPAS1 (Endothelial PAS domain protein 1, also known as HIF2). In vitro studies showed that the ZFAS1 could bind to EPAS1, enhance its abilities to epigenetically silence the HIF1, and promote its own expression in GCA cell lines. In the animal model, co-delivering the EPAS1 and the ZFAS1 antisense oligos could significantly boost up their therapeutic effects on tumor growth. Thus, targeting ZFAS1 and EPAS1 might be an alternative therapeutic option in GCA.

Upregulation of miR-133a-3p enhances Bufothionine-induced gastric cancer cell death by modulating IGF1R/PI3K/Akt signal pathway mediated ER stress.

AIMS: Bufothionine had been used for gastric cancer (GC) treatment, and this study managed to uncover the underlying mechanisms. MATERIALS AND METHODS: Cell proliferation was determined by CCK-8 assay and colony formation assay. Flow cytometry (FCM) and TUNEL assay were used to measure cell apoptosis ratio. Intracellular ROS was measured by DCFH-DA probes. qRT-PCR was used to determine miRNAs levels. Western Blot was performed to probe proteins. Dual-luciferase reporter gene system was employed to validate the binding sites of miR-133a-3p and 3'UTR regions of IGF1R mRNA. Immunohistochemistry (IHC) was used to determine the expressions of Ki-67 in mice tumor tissues. KEY FINDINGS: Bufothionine inhibited cell viability, triggered ER stress and promoted ROS production in GC cells, and both ER stress inhibitor Salburinal (Sal) and ROS scavenger (NAC) abrogated Bufothionine induced GC cell death. Besides, miR-133a-3p was upregulated by Bufothionine, and Bufothionine-induced cell death was enhanced by miR-133a-3p overexpression while alleviated by miR-133a-3p knockdown. Furthermore, miR-133a-3p inactivated PI3K/Akt signal pathway by sponging IGF1R, and Bufothionine inhibited insulin-like growth factor 1 receptor (IGF1R) and inactivated PI3K/Akt cascade by upregulating miR-133a-3p. Notably, the promoting effects of overexpressed miR-133a-3p on Bufothionine-induced GC cell death were abrogated by overexpressing IGF1R, and aggravated by the PI3K/Akt cascade inhibitor (LY294002). SIGNIFICANCE: Bufothionine promoted GC cell death by triggering miR-133a-3p/IGF1R/PI3K/Akt axis mediated ER stress and ROS production.

Epigenetically silenced PD-L1 confers drug resistance to anti-PD1 therapy in gastric cardia adenocarcinoma.

OBJECTIVES: The anti-PD-1/PD-L1 therapy has been demonstrated safe and effective for cancer patients. However, our previous data showed that it had no obvious effects on gastric cardia adenocarcinoma (GCA). Thus, we investigated how the expression level of the PD-L1 was affected by the anti-PD-1 therapy, because it has been demonstrated that the PD-L1 level affects the therapeutic efficient of the anti-PD-1 therapy. MATERIALS AND METHODS: The mRNA and protein levels of PD-L1 in the GCA tissues and corresponding normal tissues were determined by qPCR and ELISA. Promoter methylation was analyzed by bisulfite sequencing. Finally the methylation of PD-L1 promoter was confirmed in the mice. RESULTS: The level of PD-L1 was up-regulated in the GCA tissues when compared to the adjacent non-tumor tissues. The anti-PD1 therapy could reduce the PD-L1 levels in patients with cancer recurrence. The promoter of PD-L1 was more hypermethylated in the secondary GCA after the anti-PD-1 therapy when compared with the adjacent non-tumor tissues or the primary GCA without the anti-PD-1 therapy. Furthermore, the promoter methylation of PD-L1 could be induced by the anti-PD-1 therapy in the mice model. Finally, the anti-PD-1 plus DNA hypomethylating agent azacytidine could significantly suppressed the tumor growth better than the anti-PD-1 therapy. CONCLUSIONS: Here we demonstrated that the unresponsiveness of GCA to the anti-PD-1 therapy might result from the promoter methylation and down-regulation of PD-L1. The anti-PD-1 plus azacytidine might be a more promising approach to treat GCA.

A Comprehensive Comparison of LRYGB and LSG in Obese Patients Including the Effects on QoL, Comorbidities, Weight Loss, and Complications: a Systematic Review and Meta-Analysis.

PURPOSE: To systematically and comprehensively evaluate the differences between laparoscopic Roux-en-Y gastric bypass (LRYGB) versus sleeve gastrectomy (LSG) in obese patients. METHODS: A systematic literature search was performed in PubMed, EMBASE, Web of Science, and the Cochrane Library from inception to December 2018. The meta-analysis was performed by the RevMan 5.3 software. RESULTS: Twenty-three articles with 7443 patients were included. In short term (< 3 years), LRYGB was superior to LSG in terms of improving comorbidities (T2D, odds ratio (OR) 1.93, 1.06-3.52, P < 0.05, hypertension, OR 1.59, 1.08-2.34, P < 0.05, dyslipidemia, OR 1.61, 1.05-2.46, P < 0.05), but there were no differences in the midterm and long term. Quality of life (QoL) after bariatric surgery was included, but no differences were observed in the QoL after LRYGB or LSG (gastrointestinal quality of life index (GIQLI) and Moorehead-Ardelt quality of life questionnaire (M-A-Q), P > 0.05). LRYGB achieved a higher EWL% than LSG (after 3 years, WMD 5.48, 0.13-10.84. P < 0.05; after 5 years, WMD 4.55, 1.04-8.05, P < 0.05) in long term, but no significant differences were found during 0.25- to 2.0-year follow-up. The rate of early and late complications was much higher in LRYGB than in LSG (early complications, OR = 2.11, 95% CI = 1.53-2.91, P < 0.001; late complications, OR = 2.60, 95% CI = 1.93-3.49, P < 0.001). CONCLUSIONS: This meta-analysis showed that LRYGB was more effective than LSG in comorbidities' resolution or improvement in short term. For weight loss, LRYGB had better long-term effects than LSG. In addition, no differences were observed in the quality of life after LRYGB or LSG. LRYGB was associated with more complications than LSG.