Risk factors of stent migration in esophageal cancer patients who underwent fully-covered self-expanding metal stents for malignant dysphagia or tracheoesophageal fistula.

BACKGROUND: More than 50% of esophageal cancer patients are diagnosed with advanced diseases and commonly experience dysphagia, some of whom even have tracheoesophageal fistula. Self-expandable metal stent (SEMS) is one of the recommended palliative methods, although complications such as chest pain and stent migration are not uncommon. The goal of this study was to examine the predictors of stent migration. METHODS: We conducted a retrospective cohort study to include patients with esophageal cancer and dysphagia/tracheoesophageal fistula. Clinicopathological information, stent characteristics and patient outcomes were collected for analysis, while side-effects of SEMS were recorded, potential predictors were examined, and patients' nutritional outcomes were compared in the migration and non-migration groups. RESULTS: A total of 54 patients with esophageal cancer who received fully covered SEMS between 2013 and 2022 were included. We found tumor across the esophagogastric junction (adjusted odds ratio (OR) = 32.64, P = 0.01) and the female sex (adjusted OR = 12.5, P = 0.02) were significant predictors for stent migration. There was a decreasing tendency in body mass index/body weight in migration and non-migration groups, but the former had a steeper downslope. CONCLUSION: Fully covered SEMS is a safe and effective strategy to palliate dysphagia or fistula. Tumor across esophagogastric junction and the female sex were higher risk predictors of stent migration. A careful patient selection would optimize the effects of SEMS placement, especially in those with short-expected lifespan.

Rescue therapy for refractory Helicobacter pylori infection: current status and future concepts.

Helicobacter pylori infection is an important issue worldwide, and several guidelines have been published for clinicians to achieve successful eradication. However, there are still some patients who remain infected with H. pylori after treatment. Clinicians should identify the reasons that caused treatment failure and find strategies to manage them. We have searched and organized the literature and developed methods to overcome factors that contribute to prior treatment failure, such as poor compliance, inadequate intragastric acid suppression, and antibiotic resistance. To improve compliance, telemedicine or smartphone applications might play a role in the modern world by increasing doctor-patient relationships, while concomitant probiotics could be administered to reduce adverse effects and enhance adherence. For better acid suppression, high-potency and high-dose proton-pump inhibitors or potassium-competitive acid blockers have preferable efficacy. To overcome antibiotic resistance, susceptibility tests either by culture or by genotyping are the most commonly used methods and have been suggested for antibiotic selection before rescue therapy, but empirical therapy according to detailed medical history could be an alternative. Eradication with a longer treatment period (14 days) has a better outcome than shorter period (7 or 10 days). Ultimately, clinicians should select antibiotics based on the patient's history of drug allergy, previous antibiotic exposure, local antibiotic resistance, available medications, and cost. In addition, identifying patients with a high risk of cancer and shared decision-making are also essential for those who have experienced eradication failure.

Real-World Evidence of Effectiveness and Safety of Vedolizumab for Inflammatory Bowel Disease in Taiwan: A Prospective Nationwide Registry (VIOLET) Study.

BACKGROUND: This nationwide prospective registry study investigated the real-world effectiveness, safety, and persistence of vedolizumab (VDZ) in inflammatory bowel disease (IBD) patients in Taiwan. Disease relapse rates after VDZ discontinuation due to reimbursement restriction were assessed. METHODS: Data were collected prospectively (January 2018 to May 2020) from the Taiwan Society of IBD registry. RESULTS: Overall, 274 patients (147 ulcerative colitis [UC] patients, 127 Crohn's disease [CD] patients) were included. Among them, 70.7% with UC and 50.4% with CD were biologic-naïve. At 1 year, 76.0%, 58.0%, 35.0%, and 62.2% of UC patients and 57.1%, 71.4%, 33.3%, and 30.0% of CD patients achieved clinical response, clinical remission, steroid-free remission, and mucosal healing, respectively. All patients underwent hepatitis B and tuberculosis screening before initiating biologics, and prophylaxis was recommended when necessary. One hepatitis B carrier, without antiviral prophylaxis due to economic barriers, had hepatitis B reactivation during steroid tapering and increasing azathioprine dosage, which was controlled with an antiviral agent. No tuberculosis reactivation was noted. At 12 months, non-reimbursement-related treatment persistence rates were 94.0% and 82.5% in UC and CD patients, respectively. Moreover, 75.3% of IBD patients discontinued VDZ due to mandatory drug holiday. Relapse rates after VDZ discontinuation at 6 and 12 months were 36.7% and 64.3% in CD patients and 42.9% and 52.4% in UC patients, respectively. CONCLUSIONS: The findings demonstrated VDZ effectiveness in IBD patients in Taiwan, with high treatment persistence rates and favorable safety profiles. A substantial IBD relapse rate was observed in patients who had mandatory drug holiday.

Prevention and management of esophageal stricture after esophageal ESD: 10 years of experience in a single medical center.

BACKGROUND/PURPOSE: Endoscopic submucosal dissection (ESD) is a minimally invasive endoscopic procedure to deal with local early esophageal neoplasm, although post-ESD esophageal stricture is a major delayed complication of esophageal ESD greatly influencing the patient's quality of life. This retrospective study was conducted to analyze the esophageal stricture after esophageal ESD while determining further treatment and outcome of stricture management. METHODS: From 2009 to 2021, we reviewed all patients who underwent ESD for esophageal squamous cell neoplasia in Kaohsiung Medical University Hospital. RESULTS: Totally, 133 patients with esophageal squamous cell neoplasm were enrolled. Among these 133 patients, 108 patients had lesions less than three-fourths in circumferential and 25 patients had lesions in excess of three-fourths circumferentially. Totally, 18 patients (13.5%) had symptomatic esophageal stricture and 17 patients (94.4%) had stricture existing over the upper or middle esophagus. The most important risk factor of esophageal stricture was the extent of resection of esophageal circumference, especially whole circumferential resection. Although oral steroid prevention medication was prescribed for high-risk patients with lesions more than three-fourth circumferential ESD, the stricture rate was still up to 40% (10/25). Endoscopic/luminal management with balloon dilation, radial incision and self-bougination achieved 83% (15/18) symptom remission. Three patients received surgical intervention with esophagectomy or jejunostomy. CONCLUSION: Esophageal stricture is frequently encountered in esophageal ESD. Aggressive preventative strategy is warranted for the high-risk group. Endoscopy/luminal management has high efficacy for post-ESD esophageal stricture.

Targeting of Mcl-1 Expression by MiRNA-3614-5p Promotes Cell Apoptosis of Human Prostate Cancer Cells.

MicroRNA (miRNA) acts as a critical regulator of growth in various human malignancies. However, the role of miRNA-3614 in the progression of human prostate cancer remains unknown. In this study, our results demonstrated that miRNA-3614-5p exerts a significant inhibitory effect on cell viability and colony formation and induces sub-G1 cell cycle arrest and apoptosis in human prostate cancer cells. Myeloid cell leukemia-1 (Mcl-1) acts as a master regulator of cell survival. Using the miRNA databases, miRNA-3614-5p was found to regulate Mcl-1 expression by targeting positions of the Mcl-1-3' UTR. The reduction of Mcl-1 expression by miRNA-3614-5p was further confirmed using an immunoblotting assay. Pro-apoptotic caspase-3 and poly (ADP-ribose) polymerase (PARP) were significantly activated by miRNA-3614-5p to generate cleaved caspase-3 (active caspase-3) and cleaved PARP (active PARP), accompanied by the inhibited Mcl-1 expression. These findings were the first to demonstrate the anti-growth effects of miRNA-3614-5p through downregulating Mcl-1 expression in human prostate cancer cells.

Modulating the ERK1/2-MMP1 Axis through Corosolic Acid Inhibits Metastasis of Human Oral Squamous Cell Carcinoma Cells.

Corosolic acid (CA; 2α-hydroxyursolic acid) is a natural pentacyclic triterpenoid with antioxidant, antitumour and antimetastatic activities against various tumour cells during tumourigenesis. However, CA's antitumour effect and functional roles on human oral squamous cell carcinoma (OSCC) cells are utterly unknown. In this study, our results demonstrated that CA significantly exerted an inhibitory effect on matrix metalloproteinase (MMP)1 expression, cell migration and invasion without influencing cell growth or the cell cycle of human OSCC cells. The critical role of MMP1 was confirmed using the GEPIA database and showed that patients have a high expression of MMP1 and have a shorter overall survival rate, confirmed on the Kaplan-Meier curve assay. In the synergistic inhibitory analysis, CA and siMMP1 co-treatment showed a synergically inhibitory influence on MMP1 expression and invasion of human OSCC cells. The ERK1/2 pathway plays an essential role in mediating tumour progression. We found that CA significantly inhibits the phosphorylation of ERK1/2 dose-dependently. The ERK1/2 pathway played an essential role in the CA-mediated downregulation of MMP1 expression and in invasive motility in human OSCC cells. These findings first demonstrated the inhibitory effects of CA on OSCC cells' progression through inhibition of the ERK1/2-MMP1 axis. Therefore, CA might represent a novel strategy for treating OSCC.

Comparison of Endoscopic Submucosal Dissection Application on Mucosal Tumor and Subepithelial Tumor in stomach.

Background: Endoscopic submucosal dissection is minimal invasive endoscopic procedure to deal with gastric tumor. Initially, it was developed to resect mucosal neoplasm since 2000 and extended its application to submucosal tumor in the following years. Although the basic ESD skills are similar in gastric mucosal tumor and subepithelial tumor, the success rate, complication may be different between the two types of gastric tumor resection. This retrospective study is conducted to analyze the ESD procedure in gastric mucosal tumor and subepithelial tumor. Methods: From 2007 to 2016, we reviewed all patients who underwent endoscopic submucosal dissection for gastric mucosal tumor and subepithelial tumor in Kaohsiung Medical University Hospital. Results: Totally, 35 patients with gastric subepithelial tumor and 41 patients with gastric mucosal tumor received endoscopic submucosal dissection are enrolled. Among 35 patients with subepithelial tumor, 32 (91.4%) patients achieved curative treatment. 1 patient received emergent operation and 2 patients received salvage operation to complete tumor resection. 8 patients (22.9%) occurred perforation and no delay bleeding was found. Among 41 patients with mucosal neoplasm, 30 (71.4%) patients achieved curative treatment. 2 patients received emergent operation and 9 patients received salvage operation to complete tumor resection. 9 patients (21.9%) occurred complication, 6 patients occurred delay bleeding and 3 patients had perforation. Conclusions: Comparing ESD between gastric mucosal tumor and subepithelial tumor, ESD had similar efficiency in curative treatment. However, ESD in subepethelial tumor encountered higher perforation and lesser delay bleeding.

Prognostic Value of EGFR Expression for Patients With Stage III Colorectal Cancer Receiving Fluoropyrimidine Metronomic Maintenance Therapy After Radical Resection and Adjuvant Oxaliplatin-Based Chemotherapy.

This study evaluated the survival effects of metronomic maintenance therapy with oral fluoropyrimidine in patients with stage III colorectal cancer (CRC) according to epidermal growth factor receptor (EGFR) expression. We enrolled 197 patients with stage III CRC who had undergone radical resection and FOLFOX regimen adjuvant chemotherapy. The clinicopathological features and effects of metronomic maintenance therapy with oral capecitabine (daily dose of 850 mg/m², twice daily, on days 114 every 3 weeks for 6 months) on survival according to treatment group and EGFR expression were analyzed. By conducting an in vitro cell line study and in vivo study through knockout of the EGFR gene, we analyzed the capacities of cell proliferation and migration. Relapse and survival were significantly more common in the FOLFOX group. Metronomic maintenance therapy was a significantly independent associated factor of relapse and survival as well as a prognostic factor of disease-free survival and overall survival. Significant intergroup differences in survival were only observed in patients with positive EGFR expression. Thus, our findings suggest EGFR expression is a prognostic factor in patients with stage III CRC receiving metronomic maintenance therapy. Analysis of EGFR expression in these patients helps identify potential candidates who may receive the optimal survival benefit from metronomic maintenance therapy.

Supplemental home parenteral nutrition improved nutrition status with comparable quality of life in malnourished unresectable/metastatic gastric cancer receiving salvage chemotherapy.

BACKGROUND: Even with significant advances in surgical techniques and treatment, salvage chemotherapy remains the major treatment strategy for patients with unresectable or metastatic gastric cancer (GC). Practical and technical advances have simplified safe and convenient use of supplemental home parenteral nutrition (HPN). We aimed to clarify the role of HPN in patients with incurable GC undergoing salvage chemotherapy. METHODS: We enrolled 25 patients with GC with a nutritional risk index (NRI) of ≦ 97.5 undergoing HPN. Their nutritional status, laboratory data, and quality of life (QoL) were analyzed using the Research and Treatment of Cancer quality of life questionnaire-C30 before and after HPN administration at 0.5, 1, 2, and 3 months. We enrolled 25 patients with an NRI of > 97.5 not undergoing HPN as the control group. RESULTS: Total protein (P = 0.008), prealbumin (P < 0.001), and total cholesterol (P = 0.023) levels improved significantly after 0.5 months of HPN administration. The study group also demonstrated a marked improvement in nitrogen balance (P = 0.004) and prealbumin levels (P < 0.012) after 1 month. Gains in body weight after 1 month and body mass index after 2 months of HPN administration remained comparable with those of the control group. Global QoL scores were maintained and comparable with those of the control group. CONCLUSIONS: Supplemental HPN therapy for malnourished patients with unresectable or metastatic GC undergoing salvage chemotherapy is feasible and revealed marked improvement in nutritional status. Early HPN intervention should be considered an important part of palliative treatment for advanced GC.

Observational Study Comparing Efficacy and Safety between Neoadjuvant Concurrent Chemoradiotherapy and Chemotherapy for Patients with Unresectable Locally Advanced or Metastatic Gastric Cancer.

OBJECTIVE: Dismal outcomes in patients with locally advanced or metastatic gastric cancer (GC) highlight the need for effective systemic neoadjuvant treatment strategies to improve clinical results. Neoadjuvant multimodality strategies vary widely. This study compared the efficacy, safety, and clinical outcomes of neoadjuvant CCRT and chemotherapy for such patients. MATERIALS AND METHODS: Sixty-five patients with histologically confirmed locally advanced or metastatic GC following neoadjuvant CCRT or computed tomography (CT) were retrospectively enrolled between January 2010 and April 2019. Clinical outcomes included response, progression-free survival (PFS), and overall survival (OS), and toxicity was compared between the two groups. RESULTS: Of the 65 patients, 18 (27.7%) were in the response group (2 patients with a complete response and 16 with a partial response) and 47 (72.3%) in the nonresponse group (29 patients with a stable disease and 18 with a progressive disease). Multivariate analysis revealed no independent response predictor between CCRT and chemotherapy groups (all P > 0.05). Furthermore, results revealed no statistical differences in toxicity between the two groups (all P > 0.05). With a follow-up median of 12 months (ranging 6-48 months), 12-month OS and PFS were 39.7% and 20.4% in the CCRT group and 30.3% and 13.2% in the chemotherapy group, respectively. The median OS and PFS were 14.0 months (95% CI 9.661-18.339) and 9.0 months (95% CI 6.805-11.195) in the CCRT group and 10.0 months (95% CI 6.523-13.477) and 8.0 months (95% CI 6.927-9.073) in the chemotherapy group, respectively. Both OS (P=0.011) and PFS (P=0.008) in patients with CCRT were significantly better than those in patients with chemotherapy alone. CONCLUSION: Neoadjuvant CCRT achieved more favorable OS and PFS than did neoadjuvant chemotherapy alone, without significant increases of toxicity in patients. However, prospective randomized trials comparing treatment modalities are necessary to confirm the potential advantages of neoadjuvant CCRT.

Gastric juice-based PCR assay: An alternative testing method to aid in the management of previously treated Helicobacter pylori infection.

BACKGROUND: Culture of Helicobacter pylori with previous eradication failure has been emphasized in clinical guidelines. The current unmet need to manage previously treated H pylori is one tool with diagnostic accuracy and ability for antibiotics susceptibility. Gastric juice PCR can provide diagnosis and antibiotics susceptibility; however, whether treatment failure affects its accuracy remains uninvestigated. Our study aimed to investigate diagnostic accuracy and antibiotics susceptibility of juice PCR in previously treated H pylori and to compare with the current standard of culture. METHODS: We categorized all 547 patients into treatment-naïve, post-1st treatment, post-2nd treatment, and post-3rd treatment. Helicobacter pylori infection was confirmed using gold standards. Sensitivity, specificity, positive predictive value, negative predictive value, receiver operating characteristic (ROC) curve and area under ROC curve (AUC) of juice PCR and culture were calculated. Intra-gastric H pylori density was evaluated. Lastly, the antibiotics susceptibility results of gastric juice and culture were compared. RESULTS: Our findings demonstrated AUC was higher in juice PCR than culture in all patients (96.7% vs 91.3%, P < 0.0001). The superiority of juice PCR was statistically significant in previously treated patients (P < 0.0001) but not in treatment-naïve patients (P = 0.13). Antral H pylori density was less marked in previously treated patients (P = 0.014). The comparisons of PCR-RFLP and E-test for Clarithromycin resistance showed reliable AUC = 89.8%. CONCLUSION: Compared with the current standard of culture, the gastric juice PCR contains the strengths of performing the antibiotics susceptibility and overcomes the shortcomings of low accuracy. Consequently, gastric juice PCR suits the unmet need to manage previously treated H pylori.

Helicobacter pylori Infection-Induced Hepatoma-Derived Growth Factor Regulates the Differentiation of Human Mesenchymal Stem Cells to Myofibroblast-Like Cells.

Hepatoma-derived growth factor (HDGF) plays a critical role in tumor cell proliferation, anti-apoptosis, VEGF expression, lymph node metastasis and poor prognosis in human gastric cancer. Gastric cancer, as one of the most prevalent cancers worldwide, is the second leading cause of cancer-related mortality in the world for the prognosis of gastric cancer is generally poor, especially in patients with advanced stage. Helicobacter pylori (H. pylori) infection causes the chronic inflammation of stomach as well as the development of gastric cancer, with a three to six-fold increased risk of gastric cancer. Carcinoma-associated fibroblasts (CAFs) are myofibroblasts in tumor microenvironment, which possess various abilities to promote the progression of cancer by stimulating neoangiogenesis, proliferation, migration, invasion and therapy resistance of tumor cell. Mesenchymal stem cells (MSCs) are reported to promote tumor malignance through differentiation of MSCs toward CAFs. In the present study, we demonstrated that H. pylori infection promotes HDGF expression in human gastric cancer cells. HBMMSCs treated with HDGF assume properties of CAF-like myofibroblastic phenotypes, including expression of myofibroblast markers (α-smooth muscle actin (α-SMA), procollagen α1, tropomyoson I, desmin, fibroblast activation protein (FAP)), and fibroblast markers (prolyl-4-hydroxylase A1 (PHA1) and fibroblast specific protein-1 (FSP-1)/S100A4). HDGF recruits HBMMSCs, and then HBMMSCs further contributes to cell survival and invasive motility in human gastric cancer cells. Treatment of HDGF neutralizing antibody (HDGF-NAb) and serum significantly inhibit HDGF-regulated differentiation and recruitment of HBMMSCs. These findings suggest that HDGF might play a critical role in gastric cancer progress through stimulation of HBMMSCs differentiation to myofibroblast-like cells.

Peritoneal epithelioid angiosarcoma: A case report.

INTRODUCTION: Peritoneal angiosarcoma is an extremely rare sarcoma (0.01287% incidence per 100,000) with an aggressive course and a poor prognosis. In this case, the manifestation of peritoneal angiosarcoma was ascites, which caused difficulty in early diagnosis and the diagnosis of peritoneal angiosarcoma, was made only after the surgery. PATIENT CONCERNS: A 61-year-old man working in Mainland China presented with a 1-month history of abdominal distension. A contrast-enhanced abdominal computed tomography (CT) scan revealed peritoneal carcinomatosis with massive ascites. However, his tuberculosis (TB) polymerase chain reaction was negative. The ascites cell block and cytology also revealed negative for malignant cells. The patient underwent intra-abdominal tumor excision. After the operation, the patient's blood pressure (BP) dropped. Due to the state of shock, he was transferred to an intensive care unit (ICU). DIAGNOSES: According to the pathology report, the neoplastic cells were positive for cytokeratin, cluster of differentiation 31 (CD31), cluster of differentiation 34 (CD34), and negative for cytokeratin 7 (CK7), cytokeratin 7 (CK20). Therefore, the diagnosis of epithelioid angiosarcoma was made. INTERVENTIONS: The patient took 400 mg of Pazopanib once a day. OUTCOMES: Even though vasopresser was used, the patient's BP was still low. Finally, he expired. LESSONS: Initialy, the patient presented with abdominal distension and large amount of ascites in the beginning. TB peritonitis was highly suspected after the abdominal CT scan. Therefore, surgical procedures would be essential in the identification of proper diagnosis. In the future, the diagnosis of peritoneal epithelioid angiosarcoma should also be taken into consideration for patients with abnormal ascites besides the common diagnoses of TB, liver cirrhosis, and infection.

Enteral nutrition and quality of life in patients undergoing chemoradiotherapy for esophageal carcinoma: a comparison of nasogastric tube, esophageal stent, and ostomy tube feeding.

BACKGROUND AND AIMS: This study prospectively recruited esophageal squamous cell carcinoma patients who received esophageal stent, nasogastric tube (NGT), or jejunostomy/gastrostomy feeding to compare the changes in nutritional status and quality of life during chemoradiation therapy (CRT). METHODS: In total, 81 patients were analyzed (stent, 7; surgical ostomy, 26; NGT, 19; oral intake, 29). An NGT was inserted when, despite medication, dysphagia or pain worsened with oral feeding during CRT. Serial body weight and daily narcotic demand were recorded. Changes in serum albumin level and quality of life were also assessed. In subgroup analysis comparing NGT and prophylactic surgical ostomy feeding, 5 patients with total occlusion in the ostomy group were excluded. RESULTS: Patients in all groups had similar decreases in mean body weight with an overall change of -6.41% ± 5.21% at the end of CRT. The stent group had significantly worse pain, decreased albumin (-1.03 ± .9 mg/dL), and decreased quality of life across CRT compared with the other groups. In subgroup analysis the stent group had significantly higher weight loss, whereas the NGT group had higher narcotic demand and slightly worse quality of life. Two patients (7.7%) had ileus days after jejunostomy creation. Five patients (23.8%) among those received prophylactic ostomy creation and scarcely used it. CONCLUSIONS: These preliminary results raise concerns that use of esophageal stents may be less suitable in patients undergoing CRT. Tube feeding by means of transnasal or percutaneous routes appear to be comparably effective during CRT, but both have advantages and disadvantages. We suggest a careful endoscopic evaluation to select the population more appropriate for NGT feeding on an as-needed basis during CRT.

Effects of alcohol consumption, cigarette smoking, and betel quid chewing on upper digestive diseases: a large cross-sectional study and meta-analysis.

Cigarette smoking is a well-known risk factor of upper digestive diseases. Findings on alcohol's effect on these diseases are inconsistent and with the exception of its association with esophageal cancer, little is known about betel quid chewing. This study investigated the association between use of these three substances and upper digestive diseases. We collected data from 9,275 patients receiving upper endoscopies between April 2008 and December 2013. Polynomial regressions were used to analyze the association between risk factors and diseases of the esophagus, stomach and duodenum. Meta-analysis for use of these substances and esophageal diseases was also performed. Participants who simultaneously consumed cigarettes, alcohol and betel quid had a 17.28-fold risk of esophageal cancer (95% CI = 7.59-39.33), 2.99-fold risk of Barrette's esophagus (95% CI = 2.40-4.39), 1.60-fold risk of grade A-B erosive esophagitis (95% CI = 1.29-2.00), 2.00-fold risk of gastric ulcer (95% CI = 1.52-2.63), 2.12-fold risk of duodenitis (95% CI = 1.55-2.89) and 1.29-fold risk of duodenal ulcer (95% CI = 1.01-1.65). Concurrent consumption of more substances was associated with significantly higher risk of developing these diseases. Meta-analysis also revealed use of the three substances came with a high risk of esophageal diseases. In conclusions, cigarette smoking, alcohol drinking and betel quid chewing were associated with upper digestive tract diseases.

A long-term risk-benefit analysis of low-dose aspirin in primary prevention.

BACKGROUND: The long-term risk-benefit effect of occasional and regular use of low-dose aspirin (≤ 100 mg per day) in primary prevention of vascular diseases and cancers was calculated. METHODS: One representative database of 1 000 000 participants from Taiwan's National Health Insurance scheme in 1997-2000 was used. The potential study subjects were those aged 30-95 years, were found not to have been prescribed aspirin before 1 January 2000, but to have first been prescribed low-dose aspirin (≤ 100 mg per day) after that date and were followed up to 31 December 2009. Participants prescribed low-dose aspirin < 20% during the study period were considered occasional users and those prescribed ≥ 80% regular users. After the propensity score matching, rate differences of haemorrhage, ischaemia and cancer between these users were calculated their net clinical risk. RESULTS: A total of 1720 pairs were analysed. During the study period, haemorrhage and ischaemia occurred in 25 (1·45%) and 67 participants (3·90%) in occasional users and 69 (4·01%) and 100 participants (5·81%) in regular users, whereas cancer occurred in 32 participants (1·86%) in occasional users and 26 participants (1·51%) in regular users. The crude and adjusted net clinical risks of low-dose aspirin use between the two frequency of users (≥ 80% vs. < 20%) were 4·12% (95% CI = 2·19%, 6·07%; P < 0·001) and 3·93% (95% CI = 2·01%, 5·84%; P < 0·001). CONCLUSIONS: A long-term regular use of low-dose aspirin might not be better than occasional use in the primary prevention against major vascular diseases and cancer.

Chemokine (C-C Motif) Ligand 5 is Involved in Tumor-Associated Dendritic Cell-Mediated Colon Cancer Progression Through Non-Coding RNA MALAT-1.

Tumor micro-environment is a critical factor in the development of cancer. The aim of this study was to investigate the inflammatory cytokines secreted by tumor-associated dendritic cells (TADCs) that contribute to enhanced migration, invasion, and epithelial-to-mesenchymal transition (EMT) in colon cancer. The administration of recombinant human chemokine (C-C motif) ligand 5 (CCL5), which is largely expressed by colon cancer surrounding TADCs, mimicked the stimulation of TADC-conditioned medium on migration, invasion, and EMT in colon cancer cells. Blocking CCL5 by neutralizing antibodies or siRNA transfection diminished the promotion of cancer progression by TADCs. Tumor-infiltrating CD11c(+) DCs in human colon cancer specimens were shown to produce CCL5. The stimulation of colon cancer progression by TADC-derived CCL5 was associated with the up-regulation of non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1), which subsequently increased the expression of Snail. Blocking MALAT-1 significantly decreased the TADC-conditioned medium and CCL5-mediated migration and invasion by decreasing the enhancement of Snail, suggesting that the MALAT-1/Snail pathway plays a critical role in TADC-mediated cancer progression. In conclusion, the inhibition of CCL5 or CCL5-related signaling may be an attractive therapeutic target in colon cancer patients.