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.

Improved fluoroscopy-guided biopsies in the diagnosis of indeterminate biliary strictures: a multi-center retrospective study.

To evaluate the diagnostic accuracy of improved fluoroscopy-guided biopsies for indeterminate biliary strictures (IBDS). A multi-center retrospective study was performed. Patients with IBDS who underwent digital single-operator cholangioscopy (DSOC) and improved fluoroscopy-guided biopsies procedures were included. The individual sensitivity, specificity, and accuracy were analyzed. A total of 67 patients were enrolled in this multi-center retrospective study. The DSOC and improved fluoroscopy-guided biopsies procedures were successfully performed in all cases (100%). The sensitivity, specificity, and accuracy values were 83.3%, 89.5%, and 85.1% for DSOC visual impression; 95.8%, 94.7%, and 95.5% for improved fluoroscopy-guided biopsies procedures, respectively. The sensitivity and accuracy of improved fluoroscopy-guided biopsies were significantly higher compared with DSOC visual impression. Four patients (6.0%, 4/67) occurred adverse events after the procedures. Improved fluoroscopy-guided biopsies had a high diagnostic accuracy of IBDS diagnosis.

Modified Peroral Endoscopic Myotomy Technique for Type II Achalasia: A Multicenter Retrospective Study.

Aim: This retrospective study is aimed at evaluating the outcomes of a modified peroral endoscopic myotomy (POEM) technique in patients with type II achalasia. Methods: We performed a modified POEM procedure, which involved a shorter (total myotomy length = 4 cm), full-thickness myotomy, on 31 patients with type II achalasia. Clinical success rates, technical success rates, pre- and postoperative esophageal manometry results, complications, and reflux-related adverse events were evaluated. Results: The clinical success (Eckardt score ≤ 3) rates were 100% and 88.9% within 2 years and beyond 2 years postoperatively, respectively. The median lower esophageal sphincter pressures (LESP) decreased from 31.6 (26.7-49.7) mmHg preoperatively to 13.4 (10.5-21.6) and 11.8 (7.4-16.7) mmHg (P < 0.001) at 6 and 12 months postoperatively, respectively. The median integrated relaxation pressure (IRP) decreased from 27.8 (20.6-37.5) mmHg preoperatively to 12.9 (11.3-23.4) and 11.6 (9.6-16.8) mmHg (P < 0.001) at 6 and 12 months after POEM, respectively. Only one case (3.2%) of mucosal injury, four (12.9%) cases of reflux esophagitis, and two (6.5%) cases of gastroesophageal reflux symptoms were reported. Conclusions: The modified POEM technique showed excellent outcomes in patients with type II achalasia.

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.

Long non­coding RNA BANCR mediates esophageal squamous cell carcinoma progression by regulating the IGF1R/Raf/MEK/ERK pathway via miR­338­3p.

Esophageal squamous cell carcinoma (ESCC) is a type of digestive tract malignant tumor that severely threatens human health. The long non­coding RNA BRAF activated non­coding RNA (BANCR) and insulin­like growth factor 1 receptor (IGF1R) are associated with various types of cancer; however, it remains unclear whether BANCR can regulate IGF1R expression in ESCC. In the present study, the expression levels of BANCR, IGF1R mRNA and microRNA­338­3p (miRNA/miR­338­3p) in ESCC tissues or cells were detected by reverse transcription­quantitative polymerase chain reaction (RT­qPCR). The levels of IGF1R, E­cadherin, N­cadherin, Vimentin, p­Raf­1, p­MEK1/2 and p­ERK1/2 were measured by western blot analysis. The proliferation, migration and invasion of ESCC cells were determined by 3­(4,5­dimethylthiazol­2­yl)­2,5­diphenyltetrazolium bromide (MTT) or Transwell assays. The relationship between miR­338­3p and BANCR or IGF1R was predicted using starBase2.0 and confirmed by dual­luciferase reporter assay. The role of BANCR in ESCC in vivo was confirmed through a tumor xenograft assay. It was found that BANCR and IGF1R were upregulated, while miR­338­3p was downregulated in ESCC tissues and cells. Both BANCR and IGF1R knockdown suppressed the proliferation, migration, invasion and epithelial­mesenchymal transition (EMT) of ESCC cells. IGF1R enhancement reversed BANCR knockdown­mediated effects on the proliferation, migration, invasion and EMT of ESCC cells. BANCR regulated the Raf/MEK/ERK pathway by regulating IGF1R expression. Notably, BANCR regulated IGF1R expression by sponging miR­338­3p. Moreover, BANCR silencing inhibited tumor growth in vivo. On the whole, the findings of the present study demonstrate that BANCR inhibition blocks ESCC progression by inactivating the IGF1R/Raf/MEK/ERK pathway by sponging miR­338­3p.

Thermoresponsive aerification and tissue vacuolization for facilitating endoscopic submucosal resection.

BACKGROUND AND AIMS: Mucosal lifting and its persistence are critical for maintaining the operational space and preventing perforation in endoscopic operation. Although numerous agents have been investigated, optimization is still required for improving their clinical performance. In the present study, we proposed a novel concept of thermoresponsive aerification and tissue vacuolization for submucosal injection. METHODS: Lifting performance and operational condition were first evaluated in porcine stomachs in vitro and rabbits in vivo. Dodecafluoropentane (DDFP) injection dosage, lifting persistency and operational assistance were quantitatively recorded. Gross and histological pathology were also analyzed to identify DDFP acute toxicity and long-term safety. The endoscopic submucosal dissection (ESD) procedure with DDFP was carried out on pigs in vivo to confirm its operational feasibility, efficacy, and safety. RESULTS: Dodecafluoropentane aerification could achieve better mucosal lift with lower dosage (1% of normal saline dosage). Thermoresponsive DDFP aerification could provide continuous replenishment and longer persistence. Meanwhile, its tissue vacuolization effect significantly facilitated submucosal tissue dissection in in vitro study. Similar performance was verified in vivo. The particular vacuole-like submucosal structure was seen after DDFP onset, which also promoted reepithelization and wound healing. No tissue damage, gas embolism, biotoxicity, and physicochemical risk were observed. CONCLUSION: Bioinert DDFP was feasible, efficient, and safe as the novel submucosal lifting candidate.

Cap-assisted clip closure of large esophageal perforations caused by a duodenoscope during endoscopic retrograde cholangiopancreatography (with video).

BACKGROUND/AIMS: Esophageal perforation is a rare complication of endoscopic retrograde cholangiopancreatography and the perforation is usually too large to close with endoclips. We developed an endoscopic procedure for the perforations. METHODS: A gastroscope fitted with a cap was inserted into the esophagus to perform the clip closure. The closure procedure was divided in 3 steps: step 1 is large clip closure; step 2 is small clip closure; and step 3 is the nasogastric tube placement for drainage. RESULTS: A total of 4 patients underwent a cap-assisted clip closure and the procedures were completed successfully within 30 minutes. The cure was achieved in all the 4 patients after a relatively short period of hospital stay and no patient complained of closure-related complication. CONCLUSIONS: The cap-assisted clip closure procedure is effective, safe, and easy to carry out for the closure of large esophageal perforations. It may also be applied to perform the closure of large perforations at other sites of the digestive tract.

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.

[A meta-analysis of the effect and safety of angiotensin II receptor blockers in treatment of portal hypertension in cirrhotic patients].

OBJECTIVE: To evaluate the efficacy and safety of the angiotensin II receptor blockers (ARB) in reducing portal hypertension (PHT) in patients with cirrhosis. METHODS: PubMed, EMBASE, Web of Science, The Cochrane Central Register of Controlled Trials, Chinese Biomedical Database, Chinese Journals Full-text Database and WanFang Digital Journal Full-text database were searched. Statistical analysis was performed by meta-analysis using RevMan4.2 software. RESULTS: Among 8 randomized controlled trials (RCT) including 282 patients met the inclusion criteria, 4 trials were analyzed to compare the ARB with the placebo or no treatment and the other 4 trials were analyzed to compare the ARB with propranolol. Meta-analysis results were as follows. (1)The ARB resulted in more significant hepatic venous pressure gradient (HVPG) reduction as compared with the placebo or no treatment [WMD = 1.87 mm Hg (1 mm Hg = 0.133 kPa), 95%CI (0.86 - 2.87) mm Hg, P = 0.00003]. And the ARB were similar to propranolol in reducing HVPG [WMD = 0.92 mm Hg, 95%CI (-0.41 - 2.26) mm Hg, P = 0.17]. (2)The ARB led to more significant reduction in mean arterial pressure than the placebo or no treatment [WMD = 8.89 mm Hg, 95%CI (7.16 - 10.62) mm Hg, P < 0.000 01], but they were similar to propranolol in giving rise to mean arterial pressure reduction (WMD = 0.41, 95%CI -4.46 - 5.28, P = 0.87) which had no significant difference. And the ARB had no significant effect on the heart rate of the patients, which was similar to no treatment group (P > 0.05). Whereas, propranolol could greatly decrease heart rate of the patients (WMD = -21.25, 95%CI -25.83 - 16.68, P < 0.000 01). (3) No significant differences were found in serum bilirubin and creatinine levels between the ARB and the placebo or no treatment groups (P > 0.05). The rate of nonspecific adverse events was higher in the ARB groups than in the placebo or no treatment groups (P = 0.03), but it showed there was no difference between the ARB and propranolol groups (P = 0.72). CONCLUSION: The ARB is effective in reducing portal hypertension in patients with cirrhosis, which is similar to propranolol. Their effects on mean arterial pressure is similar to propranolol without significant effects on hear rate, liver function and kidney function, and with less nonspecific adverse events. The ARB could become a new choice for the treatment of portal hypertension.