New traction method (traction ring) for colorectal endoscopic submucosal dissection.

OBJECTIVES: Colorectal endoscopic submucosal dissection (ESD) is challenging because of the difficulty in adequately visualizing the submucosal layer. Many traction methods have been developed to facilitate submucosal dissection; however, they are not widely applied. Therefore, we designed a new traction device, a traction ring, and conducted this pilot study to evaluate its feasibility and safety for colorectal ESD. METHODS: Twenty patients with colorectal lesions who underwent traction ring-assisted ESD were retrospectively included. The main outcomes included en bloc resection rate, R0 resection rate, procedure time, resection time, and intraoperative and postoperative complications. RESULTS: The median procedure time was 74.5 min (range 35-269 min). The median resection time was 55 min (range 25-209 min). Application of the traction system accounted for only 2.7% of the entire procedure time. The en bloc resection rate was 95.0% (19/20), whereas the R0 resection rate was 90.0% (18/20). All traction rings were successfully set and retrieved. Significant intraoperative bleeding was not observed. One patient experienced perforation after treatment, but no further intervention was required. No delayed complications were observed within 1 month post-ESD. CONCLUSION: Traction ring is an effective and safe method for colorectal ESD and can be used at any location in the colorectum.

Endoscopic submucosal dissection for colorectal laterally spreading tumors: Clinical outcomes and predictors of technical difficulty.

OBJECTIVE: We aimed to investigate the clinical outcomes of endoscopic submucosal dissection (ESD) for the treatment of colorectal laterally spreading tumors (LSTs) and the factors related to technical difficulty. METHODS: Consecutive patients who underwent ESD for colorectal LSTs between June 2013 and January 2019 were retrospectively included. Factors associated with difficult ESD procedures (defined as conversion to piecemeal resection or discontinuation of endoscopic procedure), and dissection with a slow speed (<8 mm2 /min), were determined using the logistic regression analysis. RESULTS: A total of 325 patients with 342 colorectal LSTs (median size 20.0 mm) were enrolled. The proportions of granular (LST-G) and non-granular LST (LST-NG) were 62.9% and 37.1%, respectively. The overall en bloc and complete resection rates were 89.8% and 81.9%, respectively. The endoscopic procedure was discontinued in four lesions (1.2%), and 31 (9.1%) converted to piecemeal resection because of technical difficulty. Using multivariate analysis, positive non-lifting sign (odds ratio [OR] 19.9, P < 0.001), tumor size ≥20 mm (OR 10.0, P < 0.001), and less experienced endoscopists (OR 3.7, P = 0.005) were independent factors for technically difficult procedure. Positive non-lifting sign (OR 3.7, P = 0.004), lesion size <20 mm (OR 3.7, P < 0.001), LST-NG type (OR 1.8, P = 0.034), and less colorectal ESD experience (OR 1.9, P = 0.016) were independent factors of slow-speed dissection. CONCLUSIONS: ESD was feasible and safe for treating colorectal LSTs. Positive non-lifting sign and tumor ≥20 mm indicated difficult ESD procedures. Technical failure was more likely to occur in lesions resected by less-experienced endoscopists. Dissection speed might be improved with more experienced operators.

CacyBP/SIP nuclear translocation regulates p27Kip1 stability in gastric cancer cells.

AIM: To investigate the mechanism of calcyclin binding protein/Siah-1 interacting protein (CacyBP/SIP) nuclear translocation in promoting the proliferation of gastric cancer (GC) cells. METHODS: The effect of CacyBP/SIP nuclear translocation on cell cycle was investigated by cell cycle analysis. Western blot analysis was used to assess the change in expression of cell cycle regulatory proteins and proteasome-mediated degradation of p27Kip1. Co-immunoprecipitation (co-IP) analysis was performed to examine the binding of CacyBP/SIP with Skp1. A CacyBP/SIP truncation mutant which lacked the Skp1 binding site was constructed and fused to a fluorescent protein. Subsequently, the effect on Skp1 binding with the fusion protein was examined by co-IP, while localization of fluorescent fusion protein observed by confocal laser microscopy, and change in p27Kip1 protein expression assessed by Western blot analysis. RESULTS: CacyBP/SIP nuclear translocation induced by gastrin promoted progression of GC cells from G1 phase. However, while CacyBP/SIP nuclear translocation was inhibited using siRNA to suppress CacyBP/SIP expression, cell cycle was clearly inhibited. CacyBP/SIP nuclear translocation significantly decreased the level of cell cycle inhibitor p27Kip1, increased Cyclin E protein expression whereas the levels of Skp1, Skp2, and CDK2 were not affected. Upon inhibition of CacyBP/SIP nuclear translocation, there were no changes in protein levels of p27Kip1 and Cyclin E, while p27Kip1 decrease could be prevented by the proteasome inhibitor MG132. Moreover, CacyBP/SIP was found to bind to Skp1 by immunoprecipitation, an event that was abolished by mutant CacyBP/SIP, which also failed to stimulate p27Kip1 degradation, even though the mutant could still translocate into the nucleus. CONCLUSION: CacyBP/SIP nuclear translocation contributes to the proliferation of GC cells, and CacyBP/SIP exerts this effect, at least in part, by stimulating ubiquitin-mediated degradation of p27Kip1.

Lugol chromoendoscopic screening for esophageal dysplasia/early squamous cell carcinoma in patients with esophageal symptoms in low-risk region in China.

Detection of esophageal dysplasia/early esophageal squamous cell carcinoma (ESCC) is essential for improving 5-year survival. The aim of this prospective study was to evaluate whether Lugol chromoendoscopy improves the detection of esophageal dysplasia/early ESCC in patients with esophageal symptoms in a low-incidence region in China. Eligible patients were randomly assigned into two groups who received routine endoscopy or Lugol chromoendoscopy. During endoscopy, between one and five biopsies were taken from visible lesions for routine endoscopy, or unstained areas of >0.5 cm in diameter for Lugol chromoendoscopy. In total, 812 patients were enrolled, 395 for routine endoscopy and 417 for Lugol chromoendoscopy. The overall detection rate of esophageal dysplasia/early ESCC was 10.6% (86/812), the detection rates were 7.3% (29/395) and 13.7% (57/417) in routine and chromoendoscopy groups, respectively (χ2=8.58, P=0.003). The detection rates were 8.3% (48/580), 17.2% (17/99) and 16.5% (22/133), respectively, in patients with reflux, dysphagia and globus sensation symptoms. In the chromoendoscopy group, 213 patients had unstained lesions of >0.5 cm, the detection rates of dysplasia/early carcinoma were 5.3% (4/76) in those with lesions of 0.5-1.0 cm, and 37.2% (51/137) in those with lesions >1.0 cm (χ2=21.46, P<0.001). These results indicate that Lugol chromoendoscopy improves the detection rate of esophageal dysplasia/early carcinoma in patients with esophageal symptoms compared with routine endoscopy. We propose that Lugol chromoendoscopy must therefore be considered in addition to routine endoscopy in patients with esophageal symptoms.

Effects of cyclooxygenase-2 on human esophageal squamous cell carcinoma.

AIM: To study the relationship between the cyclooxygenase (COX)-2 gene and the proliferation and apoptosis of esophageal squamous carcinoma EC109 cells. METHODS: The techniques of RNA interference (RNAi) and cell transfection, as well as the levels of oncogenicity in nude mice, were used to study the role of COX-2 in the esophageal squamous carcinoma cell (ESCC) line EC109. Following RNAi and transfection, Western blotting analysis was used to determine the expression of the COX-2 protein. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) reduction assay was used to evaluate cell growth, and flow cytometry was used to detect cell apoptosis. RESULTS: Western blotting analysis demonstrated that COX-2 expression was significantly reduced in EC109 cells treated with COX-2-specific short interfering RNA (siRNA) but was increased in EC109 cells transfected with COX-2. Furthermore, COX-2 siRNA treatment inhibited cell proliferation (P < 0.01) and induced apoptosis in EC109 cells, as determined by an MTT assay and by flow cytometry, respectively. In contrast, transfected COX-2 led to increased cell proliferation (P < 0.05) and decreased apoptosis in EC109 cells. In addition, combination treatment of cells with COX-2 siRNA and aspirin had a synergistic effect (P < 0.01). For experiments measuring tumorigenicity, xenograft tumors of a greater volume and weight were found in the COX-2 group compared with other groups (P < 0.05). A large dose of aspirin inhibited tumor growth in nude mice effectively (P < 0.05), and the rate of tumor suppression was 51.8% in the high-dose aspirin group. CONCLUSION: COX-2 plays a very critical role in ESCC carcinogenesis, and COX-2 siRNA combined with aspirin has the potential to be an anticancer therapy for the treatment of ESCC.