Diagnostic Efficacy and Decision-Making Role of Preoperative Endoscopic Ultrasonography in Early Gastric Cancer.

Objectives: Endoscopic ultrasonography (EUS) is the most commonly used method for T staging of early gastric cancer (EGC). However, the studies pertaining to EUS for staging EGC reported widely varied sensitivities and specificities. This study aimed to estimate the overall diagnostic accuracy of EUS for staging the depth of EGCs and to explore the influential factors. Methods: We retrospectively reviewed data from 208 consecutive patients with EGC, and all patients underwent EUS for estimating tumor invasion depth, followed by either curative surgery or endoscopic submucosal dissection (ESD). The diagnostic accuracy of EUS was evaluated by comparing the final histologic results of resected specimens. The correlation between accuracy of EUS and characteristics of EGC lesion was analyzed. Results: A total of 211 EGC lesions in 208 patients were included. The overall diagnostic accuracy of EUS in assessing the tumor invasion depth of EGC was 55.9%. Multivariate analysis showed that submucosal invasion (OR 2.615; 95% CI 1.203-5.684, P = 0.015) was independently associated with misdiagnosis of the depth of EGC and 0-III type lesions (OR 31.495; 95% CI 2.083-476.256, P = 0.013) were an independent risk factor for over-diagnosis of invasion depth by EUS. However, EUS was only suitable for lesions within absolute indications for endoscopic resection. Conclusions: The overall accuracy of EUS in diagnosing invasion depth of EGC was relatively low. Thus, EUS is not necessary routinely for determining the therapeutic strategy for EGC.

Construction of a novel predictive nomogram for difficult procedure of endoscopic submucosal dissection for colorectal neoplasms.

OBJECTIVES: To determine the predictors of difficult colorectal endoscopic submucosal dissection (ESD) and to develop a preoperative predictive model for difficult colorectal ESD procedures. METHODS: Colorectal neoplasms intended to be resected by ESD in our center between August 2013 and February 2019 were retrospectively enrolled. An ESD procedure which took more than 30 min, failed to remove the lesions en bloc or converted to surgery was defined as difficulty. Logistic regression analysis was conducted to find out the predictors of difficult ESD. A nomogram integrating independent predictors was developed and validated with respect to its discrimination, calibration and clinical application, using the receiver operating characteristic (ROC) curve, calibration plot and decision curve analysis (DCA), respectively. RESULTS: A total of 368 colorectal neoplasms in 355 patients were included. The independent predictors for difficult colorectal ESD were size ≥2 cm (odds ratio [OR] = 6.102, p < .001), positive non-lifting sign (OR = 6.569, p = .005), lesions located in left colon (OR = 2.475, p = .036) or rectum (OR = 2.183, p = .048), laterally spreading tumors (LSTs) (OR = 2.501, p = .008) and less colorectal ESD experience (≤20 cases) (OR = 2.3091, p = .028). The nomogram model incorporating the above predictors performed well in both of the training and validation sets (area under the cure [AUC] = 0.786 and 0.784, respectively). DCA demonstrated the clinical benefit of the nomogram was superior to that of each independent predictor alone. CONCLUSIONS: The nomogram incorporating tumor size, location, morphology, non-lifting sign and ESD experience of operator can be conveniently used to facilitate the preoperative prediction of difficult colorectal ESD.

Peroral endoscopic myotomy compared with pneumatic dilation for newly diagnosed achalasia.

BACKGROUND: This study retrospectively compared the safety and efficacy of two endoscopic techniques for treating newly diagnosed achalasia, pneumatic dilation (PD), and peroral endoscopic myotomy (POEM). METHODS: Demographics, clinical and manometric data, and outcomes were collected from the medical records of patients who received POEM or PD as the primary therapy for achalasia at our hospital from January 2012 to August 2015. RESULTS: Of 72 patients, 32 and 40 received POEM and PD, respectively. The two groups had similar preoperative features. On short-term follow-up, improvements in high-resolution esophageal manometry and barium esophagogram parameters were similar. For PD, the success rates at 3, 6, 12, 24, and 36 months were 95, 88, 75, 72, and 60%, respectively. For POEM, these were 96, 96, 96, 93, and 93% (P = 0.013, log-rank test). On subgroup analysis, the success rate was higher with POEM than that with PD in all 3 manometric subtypes, but only that of type III was statistically significant. POEM required significantly longer operative time and hospitalization than did PD (P < 0.001). Four POEM patients experienced subcutaneous emphysema. The rate of gastroesophageal reflux was higher in patients treated by POEM (18.8%) than that in PD (10%; P = 0.286). CONCLUSIONS: In the intermediate term, the remission rate of symptoms associated with POEM therapy was better than that with PD for newly diagnosed achalasia, especially in patients with type III achalasia. The short-term outcomes of the two therapies were similar.

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.