Clinical Application of Self-Expanding Metal Stents in the Treatment of Obstructive Colorectal Cancer.

Objective: To investigate the safety and efficacy of self-expanding metal stent placement in treating obstructive colorectal cancer. Methods: A retrospective analysis was conducted on 33 patients with self-expanding metal stents. The technical success rate, clinical success rate, and stent-related complications were observed. Results: The success rate of self-expanding metal stent placement in this study was 100% (33/33), indicating that the procedure was technically successful in all cases. The clinical remission rate was 90.9% (30/33), indicating that the stent placement was effective in most cases in relieving obstructive colorectal cancer symptoms. However, the overall incidence of complications related to self-expanding metal stent placement was 12.1% (4/33), with stent displacement and detachment occurring in 3.0% (1/33) of cases each, and gastrointestinal perforation occurring in 6.1% (2/33) of cases. Conclusion: These findings suggest that stent placement is safe and effective, but there is a risk of complications that should be considered. It can serve as a transitional treatment or relieve symptoms in advanced cancer and improve quality of life.

Sarcoma protein kinase inhibition alleviates liver fibrosis by promoting hepatic stellate cells ferroptosis.

Liver fibrosis is a type of chronic pathological liver damage involving liver tissue hypoxia and abnormal extracellular matrix deposits. Hepatic stellate cells (HSCs) activation is critical for liver fibrosis. Currently, inhibiting HSCs activation or inducing HSCs ferroptosis is considered an effective strategy for the treatment of liver fibrosis. Sarcoma protein kinase (Src) is an important member of the tyrosine protein kinase family. Hypoxia causes Src phosphorylation at tyrosine 416 (Tyr 416), and inhibiting Src activation can alleviate liver fibrosis. There is currently little research on the relationship between Src activation and ferroptosis in liver fibrosis. 1-(1,1-Dimethylethyl)-1-(4-methylphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (PP1) is an inhibitor of Src activation at Tyr 416. Therefore, in this study we treated HSC-T6 cells with PP1 under normoxic and hypoxic culture conditions; moreover, PP1 was also used to treat a carbon tetrachloride-induced mouse liver fibrosis model. We explored whether inhibiting Src activation could alleviate liver fibrosis by promoting HSCs ferroptosis in vitro and in vivo. In vitro experiments showed that inhibiting Src activation in HSC-T6 cells significantly reduced hypoxia-inducible factor-1α (HIF-1α) expression and HSC-T6 cells activation, and ferroptosis was significantly increased. In vivo experiments revealed that inhibiting Src activation in fibrotic livers reduced HIF-1α expression; meanwhile, ferroptosis was promoted, and liver fibrosis was alleviated. Therefore, inhibiting Src activation, which increases HSCs ferroptosis, can alleviate liver fibrosis.

LncRNA KLK8 modulates stem cell characteristics in colon cancer.

BACKGROUND: Colon cancer, one of the most common and aggressive human malignancies, is the third leading cause of cancer-related death worldwide. Despite advances in systemic therapy, the 5-year survival rate of colon cancer patients remains at 30 % due to recurrence and metastasis. The poor prognosis is related to the presence of cancer stem cells (CSCs), and long non-coding RNAs (lncRNAs) play a significant role in CSCs. Thus, understanding of the correlation between CSCs and lncRNA in colon cancer is of it is of great clinical significance. METHOD: The expression of KLK8 expression in colon cancer tissues was determined by qRT-PCR. Colon cancer-derived CSCs could form sphere-like cell aggregates after 10 days of culturing in a serum-free medium. In addition, qRT-PCR and Western blotting were performed to assess the expression of CD44, Sox2, Oct4, and Nanog. RESULTS: KLK8 was markedly upregulated in colon cancer tissues in comparison with normal tissues, and its expression was related to tumor size, TNM stage, and metastasis, and positively correlated with the expression of CSCs-related genes in colon cancer tissues. CONCLUSIONS: Thus, KLK8 may serve as a potential prognostic and diagnostic biomarker in colon cancer patients.

Modified prophylactic 5-fr pancreatic duct stent enhances the rate of spontaneous dislodgement: A multicenter randomized controlled trial.

BACKGROUND AND OBJECTIVES: Prophylactic pancreatic duct stent placement effectively reduces post-endoscopic retrograde cholangiopancreatography pancreatitis in high-risk patients, but the optimal stent remains unclear. We modified a 5-Fr, 3 cm pancreatic stent by removing the flange on the pancreatic side and compared the rate of spontaneous dislodgement and complications with the ordinary stent. METHODS: This was a randomized controlled trial at six tertiary endoscopic centers. Patients deemed high risk for post-endoscopic retrograde cholangiopancreatography pancreatitis randomly received modified or ordinary pancreatic stent. The primary outcome was spontaneous stent dislodgement at five days and 14 days. Secondary outcomes were the success rate of stent placement and complications. RESULTS: A total of 276 patients were randomly assigned to receive modified stents (mS group) and ordinary stents (oS group). The placement of a pancreatic stent was successful in all 276 patients. There were no significant differences between groups with respect to age, sex, major diagnosis, or indications for stenting. At five days the spontaneous dislodgement rate was 47.72% for the mS group and 15.67% for the oS group (p<0.001); at 14 days the rates were 84.21% and 42.65%, respectively (p < 0.001). Post-endoscopic retrograde cholangiopancreatography pancreatitis occurred in 6.52% of all patients. There were no significant differences regarding the incidences of post-endoscopic retrograde cholangiopancreatography pancreatitis, hemorrhage or fever. CONCLUSIONS: The modified short 5-Fr stent has a higher spontaneous dislodgement rate than ordinary pancreatic stent, thus obviating the need for endoscopic removal. The modified pancreatic stent does not increase the incidence of post-endoscopic retrograde cholangiopancreatography pancreatitis or other complications. The endoscopist can consider removing the flange on the pancreatic duct side for prophylactic pancreatic duct manipulation.

Establishing a rabbit model of malignant esophagostenosis using the endoscopic implantation technique for studies on stent innovation.

BACKGROUND: Stents are recommended in patients with dysphagia caused by esophageal stricture, but an ideal stent does not currently exist. Thus, studies on new esophageal stents are necessary, and suitable animal models are desperately needed for these studies. The aim of this study was to establish a model of malignant esophageal stricture in rabbit for studies on stent innovation. METHODS: A total of 38 New Zealand white rabbits were used in this study. Using the endoscopic submucosal injection technique, VX2 fragments were inoculated into the submucosal layer of the rabbit thoracic esophagus, and an endoscopic follow-up was subsequently performed to observe the tumor development and progression. The self-expandable metal stents were randomly deployed in rabbits with severe esophageal stricture to investigate the safety and feasibility of the animal models for stenting. RESULTS: An endoscopic implantation procedure for VX2 tumors was completed in 34/38 rabbits, and tumor development was confirmed in 30/34 animals. The success rate of the endoscopic implantation and tumor development were 89.4% (95% CI, 79.6% to 99.2%) and 88.2% (95% CI, 76.9% to 99.5%) respectively. During the endoscopic follow-up period, severe esophageal stricture occurred in 22/30 rabbits with a rate of 73.3% (95% CI, 57.5% to 89.1%), and 12/22 models received stent placement. During and after stent implantation, no severe stent-related complication or mortality occurred in the animal models. The rabbits that received stent placement survived longer than those without stent implantation (the mean survival time: 53.9 days versus 40.3 days, P = 0.016). CONCLUSION: The endoscopic method is a safe and effective method for establishing a malignant esophagostenosis model in rabbits. This model can simulate the human body environment for stent deployment and is an excellent tool for the study of stent innovation for the treatment of esophageal cancer.

Comparison of endoscopic submucosal implantation vs. surgical intramuscular implantation of VX2 fragments for establishing a rabbit esophageal tumor model for mimicking human esophageal squamous carcinoma.

PURPOSE: This study was undertaken to establish a rabbit esophageal tumor model for mimicking human esophageal squamous carcinoma (ESC) by endoscopic and surgical implantation of VX2 tumors. METHODS: Fragments of a VX2 tumour were endoscopically implanted in the submucosal layer of the thoracic esophagus of 32 New Zealand white rabbits, while 34 animals received surgical implantation into the muscular layer. Then, the animals were studied endoscopically and pathologically. The safety and efficiency of the two methods and the pathological features of the animal models were analyzed. RESULTS: Both the endoscopic and the surgical method had a relatively high success rate of tumor implantation [93.7% (30/32) vs. 97.1% (33/34)] and tumor growth [86.7% (26/30) vs. 81.8% (27/33)], and the variation in the results was not statistically significant (P>0.05). Compared with those produced by the surgical method, the models produced by the endoscopic method had a higher rate of severe esophageal stricture [61.5% (16/26) vs. 29.6% (8/27)] and of intra-luminal tumor growth [73.1% (19/26) vs. 37.0% (10/27)], and had a lower rate of tumor invasion of adjacent organs [53.8% (14/26) vs. 81.5% (22/27)]; all of these results were statistically significant (P<0.05). However, the difference in the survival time and the rates of tumor regional/distant metastasis [38.5% (10/26) vs. 51.8% (14/27)] between the two methods were not statistically significant (P>0.05). CONCLUSION: The endoscopic and surgical methods are both safe and effective for establishment of VX2 tumors in the rabbit esophagus. The models produced by the two methods have different pathologic features mimicking that of human ESC. We recommend the models for studies on surgical procedures and minimally invasive treatments.