Novel sulfate tablet PBK-1701TC versus oral sulfate solution for colon cleansing: A randomized phase 3 trial.

BACKGROUND AND AIM: PBK-1701TC is a novel sulfate tablet-based that contains 320 mg of simethicone and delivers 90% of the salt and water delivered by oral sulfate solution (OSS) preparation. This study evaluated the efficacy, safety, and tolerability of PBK-1701TC compared with OSS in bowel preparation for colonoscopy. METHODS: This randomized, multicenter, phase 3 non-inferiority trial included adults aged 19 years or older with a body mass index of 19-30 kg/m2 undergoing colonoscopy at five university hospitals in Korea. The primary efficacy endpoint was successful bowel-cleansing rate, defined as Harefield Cleansing Scale grade A or B as evaluated by blinded central readers. Secondary endpoints included the presence of residual air bubbles. Adverse events and laboratory evaluations were monitored to assess safety. Tolerability was assessed via participant interview. RESULTS: Overall, 235 participants were randomized, and 224 were included in the per-protocol analysis (PBK, 112; OSS, 112). Successful bowel cleansing was achieved for 95.5% (107/112) in the PBK group, which was non-inferior to the OSS group (98.2%, 110/112) with a difference of -2.7% (one sided 97.5% confidence limit, -8.1%). The participants in the PBK group had fewer intraluminal bubbles (0.9% vs 81.3%, P < 0.001) and reported a lower incidence of nausea and vomiting, with better acceptance, taste, and willingness to repeat the regimen than those in the OSS group (all P < 0.05). CONCLUSION: The novel sulfate tablet, PBK-1701TC, was non-inferior to OSS with respect to bowel-cleansing efficacy and exhibited better safety and tolerability in adults undergoing colonoscopy.

Endoscopic versus surgical resection of GI stromal tumors in the upper GI tract.

BACKGROUND AND AIMS: Endoscopic resection has been performed for treatment of GI stromal tumors (GISTs) in the upper GI tract. However, the therapeutic roles of the endoscopic procedure remain debatable. We aimed in this retrospective study to evaluate the feasibility and long-term follow-up results of endoscopic resection of GISTs in the upper GI tract, compared with surgery. METHODS: Between March 2005 and August 2014, 130 cases of GIST in the upper GI tract were resected. We compared baseline characteristics and clinical outcomes including R0 resection rate and recurrence rate between the endoscopy group (n = 90) and surgery group (n = 40). RESULTS: The most common location of GIST was the stomach body in the endoscopy group, whereas it was the duodenum in the surgery group (P = .001). Tumor size was significantly smaller (2.3 vs 5.1 cm; P < .001), and procedure time (51.8 ± 36.2 vs 124.6 ± 74.7 minutes; P < .001) and hospital stay (3.3 ± 2.4 vs 8.3 ± 5.4 days; P < .001) were significantly shorter in the endoscopy group than in the surgery group. The R0 resection rate was 25.6% in the endoscopy group, whereas it was 85.0% in the surgery group (P = .001), and 50.0% of resected tumors belonged to a very low-risk group in the endoscopy group, whereas 35.0% and 30.0% belonged to low-risk and high-risk in the surgery group (P = .001). However, during 45.5 months of follow-up, the recurrence rate was not significantly different between the 2 groups (2.2% vs 5.0%; P = .586). CONCLUSIONS: Endoscopic resection might be an alternative therapeutic modality for GISTs in the upper GI tract in selective cases.

Characteristics of proximal early gastric cancer differentiating distal early gastric cancer.

Previous studies reported substantial differences between proximal and distal gastric cancer, however, most of the cases included in these studies were advanced gastric cancers (AGCs). The aim of this study was to investigate the unique characteristics of proximal early gastric cancer (EGC) by comparing with distal EGC. From March 2007 to March 2016, proximal and distal EGC patients who underwent endoscopic or surgical resection at our institution were matched 1:3 according to age and sex. We retrospectively analyzed the clinical and histopathological information. A total of 368 patients were enrolled including 92 (25%) in the proximal and 276 (75%) in the distal group. The proportion of patients who underwent surgery (56.5 vs. 20.3%, p<0.001), undifferentiated type (38.0 vs. 19.6%, p<0.001), tumor size (29.5 ±19.4 vs. 20.3 ±16.8 mm, p<0.001) and submucosal (SM) invasion (60.9 vs. 25.7%, p<0.001) were significantly higher in the proximal group than in the distal group. In multivariate analysis, the proximal location of EGC was a significant risk factor for SM invasion in the total population (odds ratio [OR], 3.541; 95% confidence interval [CI], 2.053-6.110; p<0.001), and in subgroup with EGC < 30mm (n = 279) (OR, 5.940; 95% CI, 2.974-11.862; p<0.001). In conclusion, careful therapeutic decision of proximal EGC is essential due to the different histopathological characteristics such as large tumor size and higher potential for SM invasion.

Inhibition of STAT3 in gastric cancer: role of pantoprazole as SHP-1 inducer.

BACKGROUND: We investigated the inhibitory effect of pantoprazole on signal transducer and activator of transcription 3 (STAT3) activity and invasiveness of gastric adenocarcinoma cells, and the role of SH2-containing protein tyrosine phosphatase 1 (SHP-1) in mediating role. METHODS: We used AGS and MKN-28 cells because of reduced SHP-1 and preserved p-STAT3 expression. Western blot, wound closure assay, Matrigel invasion assay and 3-D culture invasion assay were performed. Pharmacologic inhibitor of SHP-1 and siRNA were used for validation of the role of SHP-1. RESULTS: We observed that pantoprazole at 40, 80, and 160 µg/ml upregulated SHP-1 and downregulated p-STAT3 expression in a dose-dependent manner in AGS and MKN-28 cells. Furthermore, pantoprazole significantly downregulated mesenchymal markers (Snail1 and vimentin), upregulated epithelial marker (E-cadherin), and inhibited migration and invasion of AGS and MKN-28 cells. To validate the role of SHP-1 in inhibition of STAT3 activity by pantoprazole in gastric cancer cells, we performed pharmacologic inhibition (pervanadate) or knockdown of SHP-1 before pantoprazole treatment, which significantly attenuated the suppression of p-STAT3 and anti-migration and invasion effect by pantoprazole in AGS cells. In xenograft tumor model, tumor volume was significantly reduced by intraperitoneal injection of pantoprazole, with upregulation of SHP-1 and downregulation of p-STAT3, which were attenuated by concomitant injection of pervanadate. CONCLUSION: Our data suggest that the inhibitory effect of pantoprazole on cellular migration and invasion might be through inducing SHP-1 in gastric cancer cells.