Eukaryotic translation initiation factor 2α kinase 2 in pancreatic cancer: An approach towards managing clinical prognosis and molecular immunological characterization.

Most patients with pancreatic cancer are already in the late stages of the disease when they are diagnosed, and pancreatic cancer is a deadly disease with a poor prognosis. With the advancement of research, immunotherapy has become a new focus in the treatment of tumors. To the best of our knowledge, there is currently no reliable diagnostic or prognostic marker for pancreatic cancer; therefore, the present study investigated the potential of eukaryotic translation initiation factor 2α kinase 2 (EIF2AK2) as a predictive and diagnostic marker for pancreatic cancer. Immunohistochemical staining of clinical samples independently verified that EIF2AK2 expression was significantly higher in clinically operated pancreatic cancer tissues than in adjacent pancreatic tissues., and EIF2AK2 expression and differentially expressed genes (DEGs) were identified using downloadable RNA sequencing data from The Cancer Genome Atlas and Genomic Tumor Expression Atlas. In addition, Gene Ontology/Kyoto Encyclopedia of Genes and Genomes analyses and immune cell infiltration were used for functional enrichment analysis of EIF2AK2-associated DEGs. The clinical importance of EIF2AK2 was also determined using Kaplan-Meier survival, Cox regression and time-dependent survival receiver operating characteristic curve analyses, and a predictive nomogram model was generated. Finally, the functional role of EIF2AK2 was assessed in PANC-1 cells using a short hairpin RNA-EIF2AK2 knockdown approach, including CCK-8, wound healing assay, cell cycle and apoptosis assays. The findings suggested that EIF2AK2 may have potential as a diagnostic and prognostic biomarker for patients with pancreatic cancer. Furthermore, EIF2AK2 may provide a new therapeutic target for patients with pancreatic cancer.

Choledocholithiasis characteristics with periampullary diverticulum and endoscopic retrograde cholangiopancreatography procedures: Comparison between two centers from Lanzhou and Kyoto.

BACKGROUND: Most of study regarding periampullary diverticulum (PAD) impact on endoscopic retrograde cholangiopancreatography (ERCP) therapy for choledocholithiasis based on data from one endoscopy center and lacked to compare the clinical characteristic of choledocholithiasis with PAD from different geographical patients. AIM: To compare the choledocholithiasis clinical characteristics between two regional endoscopy centers and analyze impacts of clinical characteristics on ERCP methods for choledocholithiasis patients with PAD. METHODS: Patients seen in two endoscopy centers (The First Hospital of Lanzhou University, Lanzhou, Gansu Province, China, and Kyoto Second Red Cross Hospital, Kyoto, Japan) underwent ERCP treatment for the first time between January 2012 and December 2017. The characteristics of choledocholithiasis with PAD were compared between the two centers, and their ERCP procedures and therapeutic outcomes were analyzed. RESULTS: A total of 829 out of 3608 patients in the Lanzhou center and 241 out of 1198 in the Kyoto center had choledocholithiasis with PAD. Lots of clinical characteristics were significantly different between the two centers. The common bile duct (CBD) diameter was wider, choledocholithiasis size was lager and multiple CBD stones were more in the Lanzhou center patients than those in the Kyoto center patients (14.8 ± 5.2 mm vs 11.6 ± 4.2 mm, 12.2 ± 6.5 mm vs 8.2 ± 5.3 mm, 45.3% vs 20.3%, P < 0.001 for all). In addition, concomitant diseases, such as acute cholangitis, gallbladder stones, obstructive jaundice, cholecystectomy, and acute pancreatitis, were significantly different between the two centers (P = 0.03 to < 0.001). In the Lanzhou center, CBD diameter and choledocholithiasis size were lower, and multiple CBD stones and acute cholangitis were less in non-PAD patients than those in PAD patients (13.4 ± 5.1 mm vs 14.8 ± 5.2 mm, 10.3 ± 5.4 mm vs 12.2 ± 6.5, 39% vs 45.3%, 13.9% vs 18.5%, P = 0.002 to < 0.001). But all these characteristics were not significantly different in the Kyoto center. The proportions of endoscopic sphincterotomy (EST), endoscopic balloon dilatation (EPBD), and EST+EPBD were 50.5%, 1.7%, and 42.5% in the Lanzhou center and 90.0%, 0.0%, and 0.4% in the Kyoto center, respectively. However, the overall post-ERCP complication rate was not significantly different between the two centers (8.9% in the Lanzhou and 5.8% in the Kyoto. P = 0.12). In the Lanzhou center, the difficulty rate in removing CBD stones in PAD was higher than in non-PAD group (35.3% vs 26.0%, P < 0.001). But the rate was no significant difference between the two groups in Kyoto center. The residual rates of choledocholithiasis were not significantly different between the two groups in both centers. Post-ERCP complications occurred in 8.9% of the PAD patients and 8.1% of the non-PAD patients in the Lanzhou Center, and it occurred in 5.8% in PAD patients and 10.0% in non-PAD patients in the Kyoto center, all P > 0.05. CONCLUSION: Many clinical characteristics of choledocholithiasis patients with PAD were significantly different between the Lanzhou and Kyoto centers. The patients had larger and multiple stones, wider CBD diameter, and more possibility of acute cholangitis and obstructive jaundice in the Lanzhou center than those in the Kyoto center. The ERCP procedures to manage native duodenal papilla were different depending on the different clinical characteristics while the overall post-ERCP complications were not significantly different between the two centers. The stone residual rate and post-ERCP complications were not significantly different between choledocholithiasis patients with PAD and without PAD in each center.

Effect of Helicobacter Pylori on Plasma Metabolic Phenotype in Patients With Gastric Cancer.

BACKGROUND: Although Helicobacter pylori (Hp) as high risk factor for gastric cancer have been investigated from human trial, present data is inadequate to explain the effect of Hp on the changes of metabolic phenotype of gastric cancer in different stages. PURPOSE: Herein, plasma of human superficial gastritis (Hp negative and positive), early gastric cancer and advanced gastric cancer analyzed by UPLC-HDMS metabolomics can not only reveal metabolic phenotype changes in patients with gastric cancer of different degrees (30 Hp negative, 30 Hp positive, 20 early gastric cancer patients, and 10 advanced gastric cancer patients), but also auxiliarily diagnose gastric cancer. RESULTS: Combined with multivariate statistical analysis, the results represented biomarkers different from Hp negative, Hp positive, and the alterations of metabolic phenotype of gastric cancer patients. Forty-three metabolites are involved in amino acid metabolism, and lipid and fatty acid metabolism pathways in the process of cancer occurrence, especially 2 biomarkers glycerophosphocholine and neopterin, were screened in this study. Neopterin was consistently increased with gastric cancer progression and glycerophosphocholine tended to consistently decrease from Hp negative to advanced gastric cancer. CONCLUSION: This method could be used for the development of rapid targeted methods for biomarker identification and a potential diagnosis of gastric cancer.

Ectopic opening of the common bile duct into the duodenal bulb with recurrent choledocholithiasis: A case report.

BACKGROUND: Ectopic opening of the common bile duct is a condition with low incidence. Patients with an ectopic common bile duct opening have a high incidence of common bile duct stones and acute cholangitis. Patients with atypical symptoms and imaging findings are easily misdiagnosed; moreover, it is difficult to retrieve stones by endoscopic retrograde cholangiopancreatography, and common bile duct stones are prone to postsurgical recurrence. CASE SUMMARY: A 45-year-old male patient presented with "intermittent upper abdominal pain and elevated liver enzymes for 1 wk". Transabdominal ultrasound indicated dilation of the common bile duct and the presence of stones. Magnetic resonance imaging showed that the common bile duct was dilated with stones and that its opening was ectopic. Endoscopic retrograde cholangiopancreatography revealed an abnormal opening of the common bile duct into the duodenal bulb and the presence of common bile duct stones. Laparoscopic extrahepatic choledochectomy and hepatoenteric anastomosis were performed. After surgery, the patient recovered well and was discharged. The patient has been followed up for 2 years since the operation. He has not experienced stone recurrence, and his liver function and quality of life are good. CONCLUSION: Improved understanding of ectopic opening of the common bile duct is needed for clinicians to provide patients with appropriate treatment.

Clinical significance of different periampullary diverticulum classifications for endoscopic retrograde cholangiopancreatography cannulation.

BACKGROUND: Different types of periampullary diverticulum (PAD) may differentially affect the success of endoscopic retrograde cholangiopancreatography (ERCP) cannulation, but the clinical significance of the two current PAD classifications for cannulation is limited. AIM: To verify the clinical value of our newly proposed PAD classification. METHODS: A new PAD classification (Li-Tanaka classification) was proposed at our center. All PAD patients with native papillae who underwent ERCP from January 2012 to December 2017 were classified according to three classification systems, and the effects of various types of PAD on ERCP cannulation were compared. RESULTS: A total of 3564 patients with native papillae were enrolled, including 967 (27.13%) PAD patients and 2597 (72.87%) non-PAD patients. In the Li-Tanaka classification, type I PAD patients exhibited the highest difficult cannulation rate (23.1%, P = 0.01), and type II and IV patients had the highest cannulation success rates (99.4% in type II and 99.3% in type IV, P < 0.001). In a multivariable-adjusted logistic model, the overall successful cannulation rate in PAD patients was higher than that in non-PAD patients [odds ratio (OR) = 1.87, 95% confidence interval (CI): 1.04-3037, P = 0.037]. In addition, compared to the non-PAD group, the difficulty of cannulation in the type I PAD group according to the Li-Tanaka classification was greater (OR = 2.04, 95%CI: 1.13-3.68, P = 0.004), and the successful cannulation rate was lower (OR = 0.27, 95%CI: 0.11-0.66, P < 0.001), while it was higher in the type II PAD group (OR = 4.44, 95%CI: 1.61-12.29, P < 0.01). CONCLUSION: Among the three PAD classifications, the Li-Tanaka classification has an obvious clinical advantage for ERCP cannulation, and it is helpful for evaluating potentially difficult and successful cannulation cases among different types of PAD patients.

Plasma microRNAs as potential new biomarkers for early detection of early gastric cancer.

BACKGROUND: Early gastric cancer (EGC), compared with advanced gastric cancer (AGC), has a higher 5-year survival rate. However, due to the lack of typical symptoms and the difficulty in diagnosing EGC, no effective biomarkers exist for the detection of EGC, and gastroscopy is the only detection method. AIM: To provide new biomarkers with high specificity and sensitivity through analyzed the differentially expressed microRNAs (miRNAs) in EGC and AGC and compared them with those in benign gastritis (BG). METHODS: We examined the differentially expressed miRNAs in the plasma of 30 patients with EGC, AGC, and BG by miRNA chip analysis. Then, we analyzed and selected the significantly different miRNAs using bioinformatics. Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) confirmed the relative transcription level of these miRNAs in another 122 patients, including patients with EGC, AGC, Helicobacter pylori (H. pylori)-negative gastritis (Control-1), and H. pylori-positive atrophic gastritis (Control-2). To establish a diagnostic model for the detection of plasma miRNA in EGC, we chose miRNAs that can be used to determine EGC and AGC from Control-1 and Control-2 and miRNAs in EGC from all other groups. RESULTS: Among the expression profiles of the miRNA chips in the three groups in the discovery set, of 117 aberrantly expressed miRNAs, 30 confirmed target prediction, whereas 14 were included as potential miRNAs. The RT-qPCR results showed that 14 potential miRNAs expression profiles in the two groups exhibited no differences in terms of H. pylori-negative gastritis (Control-1) and H. pylori-positive atrophic gastritis (Control-2). Hence, these two groups were incorporated into the Control group. A combination of four types of miRNAs, miR-7641, miR-425-5p, miR-1180-3p and miR-122-5p, were used to effectively distinguish the Cancer group (EGC + AGC) from the Control group [area under the curve (AUC) = 0.799, 95% confidence interval (CI): 0.691-0.908, P < 0.001]. Additionally, miR-425-5p, miR-24-3p, miR-1180-3p and miR-122-5p were utilized to distinguish EGC from the Control group (AUC = 0.829, 95%CI: 0.657-1.000, P = 0.001). Moreover, the miR-24-3p expression level in EGC was lower than that in the AGC (AUC = 0.782, 95%CI: 0.571-0.993, P = 0.029), and the miR-4632-5p expression level in EGC was significantly higher than that in AGC (AUC = 0.791, 95%CI: 0.574-1.000, P = 0.024). CONCLUSION: The differentially expressed circulatory plasma miR-425-5p, miR-1180-3p, miR-122-5p, miR-24-3p and miR-4632-5p can be regarded as a new potential biomarker panel for the diagnosis of EGC. The prediction and early diagnosis of EGC can be considerably facilitated by combining gastroscopy with the use of these miRNA biomarkers, thereby optimizing the strategy for effective detection of EGC. Nevertheless, larger-scale human experiments are still required to confirm our findings.

Garlic-derived allyl sulfides in cancer therapy.

Garlic (Allium sativam L.) is widely used in traditional herbal remedies and alternative medicine. The potential health benefits of garlic are largely attributed to its metabolic byproducts. Extensive in vivo and in vitro studies has demonstrated that the garlic derivatives possess anti-cancer effects, but the underlying mechanisms are not completely understood. In this mini-review, we aim to summarize the reported biological effects of garlic products as anti-tumor agents, and present the possible molecular mechanisms responsible for the anti-carcinogenesis effects of garlic and its derivatives.

Therapeutic effects of endoscopic therapy combined with enteral nutrition on acute severe biliary pancreatitis.

BACKGROUND: Acute severe biliary pancreatitis (ASBP) is a severe and fatal disease, and the expenditure is huge and therapeutic effects are still not satisfactory. This study aimed to improve the therapeutic effects and reduce the expenditure of ASBP treatment. METHODS: One hundred and five patients diagnosed with ASBP were referred to our department from January 2004 to July 2009. Diagnosis was based on the 2007 criteria of the Chinese Society of Surgery. Patients were divided into two groups; the E group: 50 patients who underwent endoscopic retrograde choledochopancreatography (ERCP) + endoscopic sphincterotomy (EST) + endoscopic lithotripsy basket (ESR) + endoscopic retrograde biliary drainage (ERBD) and enteral nutrition (EN), and the R group: 55 patients who underwent traditional treatment without ERCP. Subsequently, subjective symptoms, signs, biochemical analysis, serum endotoxin, tumor necrosis factor a, grades by computed tomography (CT), cost of hospitalization and length of stay were compared between the two groups. RESULTS: All enrolled patients complied well with all therapeutic regimens. Endoscopic therapy that combined EN could significantly improve symptoms, clinical signs, laboratory values, tumor necrosis factor a and endotoxin while significantly reducing hospital expenditure and length of hospital stay. The experimental findings revealed that there were obvious advantages in the E group compared with the R group. CONCLUSIONS: Endoscopic therapy combined with EN is an effective, safe and economic therapeutic regimen of ASBP.