Prognostic value of tumor deposits and positive lymph node ratio in stage III colorectal cancer: a retrospective cohort study.

BACKGROUND: In colorectal cancer (CRC), tumor deposits (TD) have been used to guide the N staging only in node-negative patients. It remains unknown about the prognostic value of TD in combination with positive lymph node ratio (LNR) in stage III CRC. PATIENTS AND METHODS: The authors analyzed data from 31 139 eligible patients diagnosed with stage III CRC, including 30 230 from the Surveillance, Epidemiology, and End Results (SEER) database as a training set and 909 from two Chinese hospitals as a validation set. The associations of TD and LNR with cancer-specific survival (CSS) and overall survival (OS) were evaluated using the Kaplan-Meier method and Cox regression models. RESULTS: Both TD-positive and high LNR (value ≥0.4) were associated with worse CSS in the training [multivariable hazard ratio (HR), 1.50; 95% CI: 1.43-1.58 and HR, 1.74; 95% CI: 1.62-1.86, respectively] and validation sets (HR, 1.90; 95% CI: 1.41-2.54 and HR, 2.01; 95% CI: 1.29-3.15, respectively). Compared to patients with TD-negative and low LNR (value<0.4), those with TD-positive and high LNR had a 4.09-fold risk of CRC-specific death in the training set (HR, 4.09; 95% CI: 3.54-4.72) and 4.60-fold risk in the validation set (HR, 4.60; 95% CI: 2.88-7.35). Patients with TD-positive/H-LNR CRC on the right side had the worst prognosis ( P <0.001). The combined variable of TD and LNR contributed the most to CSS prediction in the training (24.26%) and validation (32.31%) sets. A nomogram including TD and LNR showed satisfactory discriminative ability, and calibration curves indicated favorable consistency in both the training and validation sets. CONCLUSIONS: TD and LNR represent independent prognostic predictors for stage III CRC. A combination of TD and LNR could be used to identify those at high-risk of CRC deaths.

Serum apolipoproteins and mortality risk: evidence from observational and Mendelian randomization analyses.

BACKGROUND: Apolipoproteins (APOs) have emerged as significant players in lipid metabolism that affects the risk of chronic disease. However, the impact of circulating APO concentrations on premature death remains undetermined. OBJECTIVES: This study aimed to investigate the associations of serum APOs with all-cause, cardiovascular disease (CVD)-related, and cancer-related mortality. METHODS: We included 340,737 participants who had serum APO measurements from the UK Biobank. Restricted cubic splines and multivariable Cox regression models were used to assess the associations between APOs and all-cause and cause-specific mortality by computing hazard ratios (HRs) and 95% confidence intervals (CIs). Based on 1-sample Mendelian randomization (MR) design, including 398,457 participants of White ancestry who had genotyping data from the UK Biobank, we performed instrumental variable analysis with 2-stage least squares regression to assess the association between genetically predicted APOs and mortality. RESULTS: After adjusting for potential confounders including high-density and low-density lipoprotein particles, we observed nonlinear inverse relationships of APOA1 with all-cause, CVD-related, and cancer-related mortality (P-nonlinear < 0.001). By contrast, positive relationships were observed for APOB and all-cause (P-nonlinear < 0.001), CVD-related (P-linear < 0.001), and cancer-related (P-linear = 0.03) mortality. MR analysis showed consistent results, except that the association between APOB and cancer mortality was null. Furthermore, both observational and MR analyses found an inverse association between APOA1 and lung cancer-related mortality (HR comparing extreme deciles: 0.46; 95% CI: 0.26, 0.80; and HR: 0.78; 95% CI: 0.63, 0.97, respectively). CONCLUSIONS: Our findings indicate that circulating APOA1 has potential beneficial effects on all-cause, CVD-related, and lung cancer-related death risk, whereas APOB may confer detrimental effects on all-cause and CVD-related death risk.

Aprepitant inhibits the development and metastasis of gallbladder cancer via ROS and MAPK activation.

BACKGROUND: Aprepitant, as a neurokinin-1 receptor (NK-1R) antagonist, originally applied for curing chemotherapy-induced nausea and vomiting, has been reported to have significant antitumor effect on several malignant tumors. However, the effect of aprepitant on gallbladder cancer (GBC) is not clear yet. This study aimed to investigate the anti-tumor activity of aprepitant on GBC and the potential mechanisms. METHODS: The NK-1R expression of gallbladder cancer cells were examined by immunofluorescence. MTT assay, wound healing and transwell migration assay were applied to detect the effect of aprepitant on cell proliferation, migration and invasion. Flow cytometry was used to detect the apoptosis rate. The effects of aprepitant on the expressions of cytokine were examined by real-time quantitative PCR and MAPK activation were detected via immunofluorescence and western blotting. Besides, xenograft model was established to investigate the effect of aprepitant in vivo. RESULTS: Our results indicated that NK-1R was markedly expressed in gallbladder cancer cells and aprepitant effectively inhibited the proliferation, migration and invasion. Furthermore, the apoptosis, ROS and inflammation response were significantly boosted by aprepitant in GBC. Aprepitant induced NF-κB p65 nuclear translocationin and increased the expressions of p-P65, p-Akt, p-JNK, p-ERK and p-P38, as well as the mRNA levels of inflammatory cytokines IL-1ß, IL-6 and TNF-α. Consistently, aprepitant suppressed the growth of GBC in xenograft mice model. CONCLUSION: Our study demonstrated that aprepitant could inhibit the development of gallbladder cancer via inducing ROS and MAPK activation, which suggested that aprepitant may become a promising therapeutic drug against GBC.

Comparison of treatment strategies and survival of early-onset gastric cancer: a population-based study.

Treatments for early-onset gastric cancer (EOGC) patients are rarely included in clinical trials, resulting in an unclear impact on survival. This study aimed to investigate the treatment patterns of EOGC patients and their impact on survival. Based on the Surveillance, Epidemiology, and End Results database, we conducted a retrospective analysis of 1639 EOGC patients (< 50 years) diagnosed between 2010 and 2018. Patients with larger tumours, distant metastasis, and AJCC TNM stage in IV were prone to receive nonsurgical treatment. Patients treated with surgery alone had a better prognosis than those receiving SROC or SCRT or nonsurgical treatment. However, analyses stratified by histological type, tumour size and TNM stage showed that patients did not benefit more from SROC and SCRT than from surgery alone. Similar results were observed in the stratified Cox regression risk analysis. Patients who received nonsurgical treatment had the highest risk of overall death [hazard ratio (HR) = 2.443, 95% confidence interval (CI) 1.865-3.200, P < 0.001]. This study indicated that additional radiotherapy, chemotherapy or chemoradiotherapy did not provide a coordinated survival benefit to EOGC patients.

The lncRNA ZFAS1 regulates lipogenesis in colorectal cancer by binding polyadenylate-binding protein 2 to stabilize SREBP1 mRNA.

Colorectal cancer (CRC) is the fourth leading cause of cancer-related mortality globally. Therefore, a better understanding of the early molecular events of this disease is needed. Long noncoding RNAs (lncRNAs) play a critical role in the regulation of tumorigenesis and cancer progression. In this study, we investigated the characteristics of ZFAS1 in CRC. We analyzed three independent microarray datasets of CRC tissues from GEO and found that ZFAS1 expression was remarkably upregulated in all three datasets. Moreover, we validated the overexpression of ZFAS1 in CRC tissues compared with normal tissues and found that ZFAS1 was positively correlated with tumor size and metastasis in CRC. Knockdown of ZFAS1 significantly suppressed the malignant phenotype and lipogenesis of CRC cells. Mechanistically, ZFAS1 binds polyadenylate-binding protein 2 (PABP2) to stabilize SREBP1 mRNA, thereby increasing the expression of SREBP1 and its target genes stearoyl-CoA desaturase (SCD1) and fatty acid synthase (FASN), thus promoting CRC lipid accumulation. These data demonstrated that ZFAS1 could act as an oncogene for CRC and that ZFAS1 reprograms lipid metabolism by binding with PABP2 to stabilize SREBP1 mRNA accumulation, implicating it as a novel and potent target for the treatment of CRC.

Associations of vitamin D status with colorectal cancer risk and survival.

Biological evidence suggests that vitamin D has numerous anticancer functions, but the associations between vitamin D status and colorectal cancer (CRC) risk and survival remain inconclusive. Based on UK Biobank, we prospectively evaluated the associations of season-standardized 25-hydroxyvitamin D (25(OH)D) concentrations with CRC risk among 360 061 participants, and with survival among 2509 CRC cases. We observed an inverse linear relationship between 25(OH)D concentrations and CRC risk (P for linearity = .01; HR per 1-SD increment, 0.95; 95% CI, 0.91-0.99). Compared to the lowest quartile of 25(OH)D, the highest quartile was associated with a 13% (HR, 0.87; 95% CI, 0.77-0.98) lower risk of CRC. For CRC survival, compared to those in the lowest quartile of 25(OH)D, cases in the highest quartile had a 20% (HR, 0.80; 95% CI, 0.65-0.99) lower risk for overall death. Our findings indicate that higher concentrations of serum 25(OH)D are associated with lower incidence and improved survival of CRC, suggesting a role of vitamin D in the pathogenesis of CRC.

The diagnostic value of exosomal miRNAs in human bile of malignant biliary obstructions.

BACKGROUND: Diagnosis of malignant biliary obstruction is complicated and lacks accuracy. Exosomes may be secreted by malignant tumors; intact miRNAs from exosomes might serve as potential biomarkers for the disease. AIM: To identify exosomal microRNAs in human bile among benign and malignant biliary obstructions. METHODS: Bile samples were collected from patients undergoing therapeutic endoscopic retrograde cholangiopancreatography for biliary obstruction. Exosome microRNAs were determined by RNA-sequencing in the discovery cohort, which comprising benign (n = 5) cases and malignant biliary obstruction (n = 5) cases. Then, the diagnostic performance of the two up-regulated microRNAs (mir-483-5p and mir-126-3p) of bile exosomes was verified by analysis of 82 patients with a diagnosis of malignant (n=37) or nonmalignant (n=45) biliary obstruction. RESULTS: In both cohorts, the expressions of mir-483-5p and mir-126-3p were significantly higher in bile exosomes samples from patients with malignant biliary obstructions than controls. In the verification cohort, the two miRNAs can distinguished the benign and malignant groups with high diagnostic accuracy and specificity; the diagnostic values of the two microRNAs were better than serum carbohydrate antigen 19-9 (CA19-9), area under the curve (AUC) were 0.81 and 0.74. CONCLUSION: The expression of exosomal mir-483-5p and mir-126-3p in the bile samples discriminates between patients with malignant and nonmalignant biliary obstructions. CLINICAL TRIAL REGISTRATION NO: NCT03102268.

Prognostic and clinicopathological significance of SNHG20 in human cancers: a meta-analysis.

BACKGROUND: It has been widely reported that the expression levels of SNHG20 are elevated in diverse types of cancers, indicating that SNHG20 may participate in cancer initiation and development. Besides, accumulating evidence reveals that SNHG20 overexpression is also connected with poor clinical outcomes among cancer patients. Herein, we carry out a systematic meta-analysis to further determine the prognostic and clinical significance of SNHG20 expression in various human cancers. METHODS: Qualifying publications were selected by searching for keywords in PubMed, Embase, Web of Science and Cochrane Library databases, up to September 1, 2019. Pooled hazard ratio (HR) or odds ratio (OR) with corresponding 95% confidence interval (CI) was computed to estimate the strength of association between SNHG20 and survival of cancer patients or clinicopathology using Stata 14.0 software. RESULTS: In total, 15 studies encompassing 1187 patients met the inclusion criteria were ultimately enrolled for analysis. According to the meta-analysis, patients with high SNHG20 expression were markedly linked to poorer overall survival (OS) (pooled HR = 2.47, 95% CI 2.05-2.98, P = 0.000) and disease-free survival/recurrence-free survival/progression-free survival (DFS/RFS/PFS) (pooled HR = 2.37, 95% CI 1.60-3.51, P = 0.000). Additionally, regarding clinicopathology of patients, enhanced SNHG20 was correlated with advanced tumour-node-metastasis (TNM) stage (OR = 2.80, 95% CI 2.00-3.93, P = 0.000), larger tumor size (OR = 3.08, 95% CI 2.11-4.51, P = 0.000), positive lymph nodes metastasis (OR = 2.99, 95% CI 2.08-4.31, P = 0.000), higher tumor stage (OR = 4.51, 95% CI 2.17-9.37, P = 0.000) and worse histological grade (OR = 1.95, 95% CI 1.44-2.63, P = 0.000), but not with gender, smoking status or distant metastasis. CONCLUSIONS: Up-regulated SNHG20 expression is ubiquitous in different kinds of cancers. Moreover, up-regulated SNHG20 expression is capable of serving as an innovative predictive factor of inferior clinical outcomes in cancer patients. Nevertheless, higher-quality multicenter studies are required to corroborate our results.

Association between Mediterranean diet adherence and colorectal cancer: a dose-response meta-analysis.

BACKGROUND: Mounting epidemiologic studies have investigated the potential inverse association between Mediterranean diet (MD) adherence and colorectal cancer (CRC) incidence and mortality. OBJECTIVES: This meta-analysis aimed to investigate the association between MD adherence and CRC incidence and mortality. METHODS: PubMed, Embase, and Web of Science were searched to identify eligible studies through September 2019. A random-effects model was used to estimate summary RRs and 95% CIs. RESULTS: This meta-analysis included 13 prospective cohort studies, of which 9 reported CRC incidence and 5 reported CRC mortality. The summary RR of CRC incidence was 0.90 (95% CI: 0.84, 0.96) for highest compared with lowest MD adherence and 0.96 (95% CI: 0.94, 0.99) per 2-score increase in MD adherence. The summary RRs for highest compared with lowest MD adherence were 0.82 for rectal cancer (95% CI: 0.71, 0.95), 0.94 for proximal colon cancer (95% CI: 0.87, 1.02), and 0.91 for distal colon cancer (95% CI: 0.79, 1.04). Neither the summary HR of overall mortality for highest compared with lowest pre- and postdiagnosis MD adherence, nor the summary HR of CRC-specific mortality for highest compared with lowest prediagnosis MD adherence achieved a value with statistical significance. CONCLUSIONS: Our meta-analysis supports the inverse association of MD adherence with CRC incidence, but not with overall mortality or CRC-specific mortality among those diagnosed with CRC.

Pharmacological basis and new insights of quercetin action in respect to its anti-cancer effects.

Quercetin is a kind of flavonoid compounds that comes from nature and is widely existed in the daily diet. Previous studies have found that quercetin has many effects such as anti-inflammatory, anti-oxidation and anti-cancer. Both in vivo and in vitro experiments have demonstrated that quercetin can exert anti-tumor effects by altering cell cycle progression, inhibiting cell proliferation, promoting apoptosis, inhibiting angiogenesis and metastasis progression, and affecting autophagy. This review summarizes the evidence for the pharmacological potential and inhibition of quercetin on cancers, supporting the viewpoint that quercetin should be adequately considered as a therapeutic agent against various cancers.

MicroRNA-195 as a prognostic factor for cancer survival outcome in China: a meta-analysis.

PURPOSE: MicroRNA-195 is dysregulated in different kinds of cancers and plays a pivotal role in tumorigenesis. It may function as a prognostic biomarker for cancers. However, the results from articles were not consistent. This study was designed to validate the prognostic value of microRNA-195 in human tumors. METHODS: We conducted a detailed search on PubMed until December 31, 2018. The quality of these publications was assessed on the basis of a list of key reviews presented by PRISMA statement. The pooled hazard ratios (HR) and pooled odds ratios (OR) of each 95% confidence interval (95% CI) were calculated to assess the effect. RESULTS: This meta-analysis included 12 studies involving 940 cancer patients to assess the prognostic value of miR-195 in different solid tumors. The results showed that patients with high expression of miR-195 had favorable tumor-node-metastasis (late vs early: pooled OR =0.16, 95% CI: 0.11-0.22, P<0.001), lymph node metastasis (pooled OR =0.25, 95% CI: 0.18-0.35, P<0.001) and distant metastasis (pooled OR =0.26, 95% CI: 0.13-0.52, P<0.001). At the same time, high levels of miR-195 expression were closely correlated with better overall survival (pooled HR =0.46, 95% CI: 0.36-0.58, P<0.001). CONCLUSION: Elevated microRNA-195 may serve as a potential biomarker to predict a favorable prognosis for various cancer types in China.

Comparison of esophageal stent placement versus endoscopic incision method for treatment of refractory esophageal anastomotic stricture.

BACKGROUND: Refractory esophageal anastomotic strictures are difficult to treat. Current treatments include esophageal stent placement (ESP) and the endoscopic incision method (EIM). This study was conducted to determine which treatment is better for patients with refractory esophageal anastomotic stricture. METHODS: This study retrospectively collected data of patients with refractory esophageal anastomotic stricture who underwent ESP or EIM between January 2012 and June 2018. Dysphagia scores before and after the procedure were recorded in both groups. The duration of relief during the follow-up period was recorded. RESULTS: Fifty patients were enrolled in this study, including 32 patients who underwent ESP and 18 who underwent EIM. Patients in the ESP group had a markedly larger diameter of dilatation than those in the EIM group (19.9±1.8 versus 11.0±1.9 mm, respectively; P0.001). However, the dysphagia score improved by 1.0±0.0 point in the ESP group and by 1.4±0.5 points in the EIM group (P<0.001). Nearly 70% of patients in the ESP group maintained lumen patency at 12 months. In contrast, only 50% of patients in the EIM group had persistent relief of stricture symptoms at 6 months and only 20% had relief at 12 months. Five patients had slight bleeding; none required blood transfusion. Thirteen patients in the ESP group had slight chest pain; seven of these required administration of a painkiller. CONCLUSIONS: EIM can rapidly relieve the symptoms of esophageal anastomotic stricture but ESP provides longer duration of relief. Both procedures are safe for patients with refractory esophageal anastomotic stricture.

Long noncoding RNA DANCR regulates proliferation and migration by epigenetically silencing FBP1 in tumorigenesis of cholangiocarcinoma.

Recently, long noncoding RNAs (lncRNAs) have been shown to play significant regulatory roles in human tumorigenesis. However, the biological function of lncRNAs in cholangiocarcinoma (CCA) remains largely unknown. In this study, DANCR was shown to be significantly upregulated in CCA. DANCR regulated the proliferation and migration of CCA cells in vitro. Moreover, downregulation of DANCR suppressed CCA cells proliferation in vivo. RNA-seq revealed that DANCR knockdown preferentially affected genes linked with cell proliferation and cell differentiation. Furthermore, mechanistic investigation validated that DANCR could bind EZH2 and modulate the histone methylation of promoter of FBP1, thereby regulating CCA cells growth and migration. Taken together, these results demonstrated the significant roles of DANCR in CCA and may provide a theoretical basis for clinical diagnosis and treatment of CCA.

Long noncoding RNAs as potential biomarkers and therapeutic targets in gallbladder cancer: a systematic review and meta-analysis.

BACKGROUND: Mounting evidence has shown that long noncoding RNAs (lncRNAs) can play a substantial role in gallbladder cancer (GBC) development as tumor promotors or suppressors, and their abnormal expression is relevant to GBC patient outcomes. We completed this systematic review and meta-analysis to explore the clinical significance and mechanisms of lncRNAs in GBC. METHODS: We conducted a comprehensive literature search and selected eligible records according to the inclusion and exclusion criteria. Hazard ratios (HRs) and odds ratios (ORs) were extracted or calculated to estimate the relationships of high lncRNA expression with GBC patient survival and clinical outcomes. RESULTS: Eighteen studies were identified as eligible for this systematic review and meta-analysis. Heterogeneity among HRs of overall survival (OS) was notably high (I2 = 86.2%, p < 0.001). Subgroup analysis suggested that overexpression of lncRNAs in a group that is upregulated in GBC showed a significant association with poor OS (HR = 2.454, 95% CI 2.004-3.004, I2 = 0%). Conversely, overexpression of lncRNAs in a downregulated group was markedly related to good OS (HR = 0.371, 95% CI 0.267-0.517, I2 = 0%). High expression levels of lncRNA AFAP1-AS1, MALAT1 and ROR were positively correlated with tumor size. Expression of lncRNA LET, LINC00152 and HEGBC exhibited a positive correlation with high T status. LncRNA LINC00152, HEGBC, MALAT1 and ROR showed a marked correlation with positive lymph node metastasis (LNM), while lncRNA GCASPC, MEG3, LET and UCA1 had the opposite effect. High expression levels of lncRNA HEGBC, PAGBC, PVT1 and UCA1 predicted high tumor node metastasis (TNM) stages, while lncRNA LET, GCASPC and MEG3 indicated low TNM stages. We also summarized the mechanisms of lncRNAs in GBC. CONCLUSION: Aberrant expression of several lncRNAs was indicative of the prognosis of GBC patients, and lncRNAs showed promise as biomarkers and therapeutic targets for GBC.

Clinical Significance of Prothrombin Time in Cholangiocarcinoma Patients with Surgeries.

Background: Prothrombin time (PT) can predict survival in several types of malignancies. This study aims to investigate the predictive values of PT levels in patients with cholangiocarcinoma (CCA). Methods: We retrospectively analyzed the PT from 86 CCA patients who underwent curative resection in our hospital from December 2008 to August 2017. The relationship between PT and survival times was analyzed through univariate and multivariate analyses (Cox proportional hazards model). Kaplan-Meier curves and log-rank test were used to assess the effects of PT on overall survival (OS) and tumor recurrence-free survival (RFS). Results: Increased PT level was an effective predictor for OS (P = 0.021; hazard ratio (HR), 1.799) and RFS (P = 0.016; HR, 1.871) in CCA patients, independent of age, tumor differentiation, and TNM stage. In the low PT level group (PT < 12.3 s), patients showed a higher mean OS (23.03 m vs. 14.38 m, P = 0.0250) and RFS (17.78 m vs. 8.30 m, P = 0.0511) than those with high PT levels (PT ≥ 12.3 s). A highly significant association was observed between high PT level and shortened OS (P = 0.0373) and worse RFS (P = 0.0151). Conclusion: Preoperative increase in PT can serve as a simple but effective predictor of poor survival in CCA patients who undergo curative surgeries.

Long noncoding-RNA component of mitochondrial RNA processing endoribonuclease is involved in the progression of cholangiocarcinoma by regulating microRNA-217.

Cholangiocarcinoma (CCA) is a malignant tumor originating from bile duct epithelium and its incidence is increasing year by year. In recent years, long noncoding RNAs (lncRNAs) have been found to play an important role in the occurrence and progression of malignant tumors. In the present study, for the first time, abnormal expression of lnc-RNA component of mitochondrial RNA processing endoribonuclease (RMRP) and its possible role in CCA were found. We explored the effects of RMRP on various behaviors of CCA cells in vitro and in vivo. In addition, by second-generation sequencing, we explored the microRNA expression profiles that RMRP may affect in the HCCC-9810 cell line. We also validated and explored the role of microRNA-217 (miR-217) with high differential expression by in vitro experiments. Our findings indicated that RMRP can play a part in promoting cancer by regulating the expression of miR-217. RMRP is involved in the progression of CCA and can be a novel indicator of poor prognosis in patients with CCA.

SP/NK-1R promotes gallbladder cancer cell proliferation and migration.

Aberrant substance P/neurokinin-1 receptor (SP/NK-1R) system activation plays a critical role in various disorders, however, little is known about the expression and the detailed molecular mechanism of the SP and NK-1R in gallbladder cancer (GBC). In this study, we firstly analyzed the expression and clinical significance of them in patients with GBC. Then, cellular assays were performed to clarify their biological role in GBC cells. Moreover, we investigated the molecular mechanisms regulated by SP/NK-1R. Meanwhile, mice xenografted with human GBC cells were analyzed regarding the effects of SP/NK1R complex in vivo. Finally, patient samples were utilized to investigate the effect of SP/NK-1R. The results showed that SP and NK-1R were highly expressed in GBC. We found that SP strongly induced GBC cell proliferation, clone formation, migration and invasion, whereas antagonizing NK-1R resulted in the opposite effects. Moreover, SP significantly enhanced the expression of NF-κB p65 and the tumor-associated cytokines, while, Akt inhibitor could reverse these effects. Further studies indicated that decreasing activation of NF-κB or Akt diminished GBC cell proliferation and migration. In consistent with results, immunohistochemical staining showed high levels of Akt, NF-κB and cytokines in tumor tissues. Most importantly, the similar conclusion was obtained in xenograft mouse model. Our findings demonstrate that NK-1R, after binding with the endogenous agonist SP, could induce GBC cell migration and spreading via modulation of Akt/NF-κB pathway.

The diagnostic/prognostic potential and molecular functions of long non-coding RNAs in the exosomes derived from the bile of human cholangiocarcinoma.

Cholangiocarcinoma (CCA) is an aggressive malignancy associated with unfavorable prognosis, and it's difficult to diagnose and no effective treatments are available. Long non-coding RNAs (lncRNAs) play important roles in tumorigenesis and metastasis. Intact lncRNAs from exosomes have sparked much interest as potential biomarker for the non-invasive analysis of disease. Here, via exosome sequencing on lncRNAs, GO analysis, KEGG pathway and co-expression analysis, receiver operating characteristic curve and survival analyses, we found that, compared with control group, lncRNAs of ENST00000588480.1 and ENST00000517758.1 showed significantly increased expressions in CCA group. Moreover, area under the curve (AUC) was increased to 0.709 when combined the two lncRNAs, they had a sensitivity and specificity of 82.9% and 58.9% respectively. Further, the higher levels of the two lncRNAs showed a significantly increasing trend with the advancement of cancer TNM stages, and prognosticated a poor survival. In addition, KEGG pathway analysis showed that the most significant difference term was "p53 signaling pathway" (KEGG ID: hsa04115, p: 0.001). The altered lncRNAs and their target genes were included to reconstruct a co-expression network. These altered lncRNAs were mainly related to cellular processes, environmental information processing and organismal systems, etc. Collectively, our findings provided the potential roles of lncRNAs of ENST00000588480.1 and ENST00000517758.1 in CCA, and implicated these lncRNAs as potential diagnostic and therapeutic targets for CCA.

Endoscopic radiofrequency ablation for malignant biliary strictures.

Endoscopic radiofrequency ablation (RFA) is a novel palliation therapy for malignant biliary stricture; however, its feasibility and safety has not yet been clearly defined. The aim of the present study was to evaluate the feasibility and safety of endoscopic RFA for the treatment of malignant biliary strictures. A total of 12 patients treated by endoscopic RFA between December 2011 and October 2013 were retrospectively analyzed. Adverse events within 30 days post-intervention, stricture diameters prior to and following RFA, stent patency and survival time were investigated. A total of 12 patients underwent 20 RFA procedures as a treatment for malignant biliary strictures. Two patients required repeated elective RFA (4 and 6 times, respectively). All 20 RFA procedures were successfully performed without technical problems. During a 30 day period following each RFA procedure, two patients experienced fever (38.2 and 38.9°C, respectively) and another patient exhibited post-endoscopic retrograde cholangiopancreatography pancreatitis. The 30- and 90-day mortality rates were 0 and 8.3%, respectively. Mean stricture diameter prior to RFA was 5.3 mm (standard deviation (SD), 0.9 mm; range, 5-8 mm), and the mean diameter following RFA was 12.6 mm (SD, 3.1 mm; range, 8-15 mm). There was a significant increase of 7.3 mm in the bile duct diameter following RFA in comparison with prior to RFA (t=8.6; P≤0.001). Of the 11 patients with stents inserted following RFA, the median stent patency was 125.0 days [95% confidence interval (CI), 94.7-155.3 days]. Extrapolated median survival following the first RFA was 232 days (95% CI, 94.3-369.7 days). In conclusion, RFA appears to be an efficient and safe treatment strategy for the palliation of unresectable malignant biliary strictures.

ERCP-induced duodenal perforation successfully treated with endoscopic purse-string suture: a case report.

Duodenal perforation is one of the most serious complications of endoscopic retrograde cholangiopancreatography (ERCP) and is difficult to manage. Recently, endoscopic purse-string suture, using endoloops with endoclips, is a relatively new technology and has provided good clinical results. However, the study and use of endoscopic purse-string suture on duodenal perforation is less and its feasibility and safety are unknown. Here, we report a case of ERCP-induced duodenal perforation successfully treated with endoscopic purse-string suture. During ERCP, fluoroscopy revealed abnormal perinephric gas shadowing after breaking and extracting the stones with a stone-removal basket. Then duodenal endoscopy showed an approximately 2.0 cm × 1.5 cm perforation on the lateral duodenal wall, with visible retroperitoneal loose connective tissue. Titanium clips were used to attempt closure of the perforation but failed because of the long diameter of the injury. Therefore, an endoscopic purse-string suture, using endoloops with endoclips, was employed with an Olympus double-lumen endoscope. The perforation was successfully closed. At the 2-month follow-up visit, the patient had no complaints or symptoms. Our case once again proved its feasibility and safety and provided a new perspective for surgeons.