Novel endoscopic duodenal observation protocol based on Seven Pictures Rule for detecting duodenal neoplasms during esophagogastroduodenoscopy: Prospective observational study.

OBJECTIVES: No protocol for esophagogastroduodenoscopic examination of the duodenum has been established. We examined the feasibility and ability to detect neoplasms of a novel duodenal examination protocol. METHODS: This was a two-facility, prospective, observational study. Our protocol, the Seven Pictures Rule (7PR), requires pictures of the following seven locations: anterior and posterior to the bulb, area of and contralateral to the superior duodenal angle, area of and contralateral to the ampulla, and the transverse duodenum. The primary outcome was rate of completion of 7PR. Secondary outcomes were overall rates of detecting neoplasms, rates of detecting neoplasms for each location, examination time, and completion rates for standard or ultrathin endoscopes. RESULTS: There were 1549 participants. The 7PR completion rate was 81.1% and the detection rates of overall neoplasms, adenomas, and carcinomas were 0.84%, 0.71%, and 0.06%, respectively. The area in which most neoplasms was detected was contralateral to the ampulla (69.2%), and the fewest the transverse duodenum (0%). Mean duration of duodenal examination was 53.1 s. Completion rates for standard vs. ultrathin were 84.4% (1077/1276) vs. 65.6% (179/273) (P < 0.01), respectively. CONCLUSIONS: Seven Pictures Rule is acceptable for duodenal examination and a potential quality indicator.

Role of Mir-452-5p Overexpression in Epithelial-Mesenchymal Transition (EMT) in Early-stage Colorectal Cancer.

BACKGROUND/AIM: The microRNA miR-452-5p holds a critical role in the progression of multiple tumor formations, but there is limited understanding regarding the epithelial-mesenchymal transition (EMT) progression and its underlying mechanisms in the early-stage colorectal cancer (CRC). We aimed to explore the change in miRNA expression in early-stage CRC and examine the role of these miRNAs in CRC. MATERIALS AND METHODS: The expression levels of miR-452-5p in tissues and cells of early-stage CRC were determined by real-time quantitative polymerase chain reaction. Additionally, the biological effects of miR-452-5p on CRC were investigated by in vitro functional experiments. RESULTS: The expression levels of miR-452-5p were found increased in early-stage CRC tissue. We found that miR-452-5p promoted CRC cell proliferation but inhibited epithelial-mesenchymal transition. Furthermore, miR-452-5p promoted cell proliferation through activation of the extracellular signal-regulated kinase pathway, and inhibited cell invasion through suppression of Slug (Snail2) expression and up-regulation of E-cadherin expression. CONCLUSION: The expression of miR-452-5p is up-regulated in early CRC and suppresses epithelial-mesenchymal transition in CRC. These discoveries suggest that miR-452-5p has the potential to serve as a viable therapeutic target for CRC.

Current Status of Endoscopic Full-Thickness Resection for Gastric Subepithelial Tumors: A Literature Review Over Two Decades.

BACKGROUND: With the development of endoscopic technology and devices, endoscopic full-thickness resection (EFTR) has been challengingly introduced for gastric subepithelial tumors (SETs). The resection and closure strategies are under investigation. This systematic review was performed to assess the current status and limitations of EFTR for gastric SETs. SUMMARY: MEDLINE was searched using the keywords "endoscopic full-thickness resection" or "gastric endoscopic full-thickness closure" AND "gastric" or "stomach" from January 2001 to July 2022. The outcome variables were the complete resection rate, major adverse event (AE) rate including delayed bleeding and delayed perforation, and closure-associated outcomes. Among 288 studies, 27 eligible studies involving 1,234 patients were included in this review. The complete resection rate was 99.7% (1,231/1,234). The major AE rate was 1.13% (14/1,234), with delayed bleeding in two (0.16%) patients, delayed perforation in one (0.08%), panperitonitis or abdominal abscess in three (0.24%), and other AEs in eight (0.64%). Surgical interventions were required intraoperatively or postoperatively in 7 patients (0.56%). Three patients underwent intraoperative conversion to surgery, due to intraoperative massive bleeding, technical difficulty of closure, and retrieval of falling tumor in the peritoneal cavity. Postoperative surgical rescues for AEs were required in four (0.32%). Subgroup analysis of AE outcomes showed no significant differences among closure techniques consisting of endoclips, purse-string suturing, and over-the-scope clips. KEY MESSAGES: This systematic review demonstrated acceptable outcomes of EFTR and closure for gastric SETs, indicating that EFTR is a promising forthcoming procedure.

Effective and Secure Closure after Duodenal Endoscopic Submucosal Dissection: Combination of Endoscopic Ligation with O-Ring Closure and Over-the-Scope Clip.

Duodenal endoscopic submucosal dissection (ESD) is associated with high incidences of intraoperative complications and delayed adverse events (AEs). Delayed AEs can be reduced by closing the post-ESD defects. We developed a new method of closure after duodenal ESD, combining endoscopic ligation with O-ring closure (E-LOC) with an over-the-scope clip (OTSC) (Band OTSC; B-OTSC). Here, we conducted a single-center, retrospective, observational study to investigate the efficacy and safety of the B-OTSC method for preventing delayed AEs in patients undergoing duodenal ESD. The study included nine patients with superficial nonpapillary duodenal epithelial tumors who underwent ESD and were closed with B-OTSC from February 2021 to February 2023. There were no delayed AEs (0%), the mean (± standard deviation) closure time was 53 ± 21.6 min, the complete closure rate was 100%, and the mean hospital stay was 7.8 ± 1.8 days. The sustained closure rates at postoperative days 3 and 7 were 88.9% and 88.9%, respectively. The historical analysis indicated a significant difference in cost between B-OTSC and conventional OTSC (p < 0.01). In conclusion, B-OTSC was a safe, secure, and cost-effective method of closure after duodenal ESD, even in patients with post-ESD defects of more than half the circumference.

Antitumor Effect of Galectin-9 on Cell Proliferation and Tumor Growth of Human Duodenal Adenocarcinoma Cells.

BACKGROUND/AIM: Galectin-9 (Gal-9) induces tumor cell apoptosis in lymphoma and other malignant cell types. Duodenal adenocarcinoma is a rare malignancy, and there are insufficient data to determine a standard therapeutic approach. Here, we investigated the antitumor effect of Gal-9 in HuTu-80 duodenal adenocarcinoma cells. MATERIALS AND METHODS: Cell proliferation was examined in HuTu-80 cells using a Cell Counting Kit-8 assay. Cell cycle analysis, apoptosis array, and microRNA expression analysis were performed to identify the effect of Gal-9 on HuTu-80 cells. The antitumor effect of Gal-9 was also examined using xenograft mouse models. RESULTS: Gal-9 suppressed the proliferation of HuTu-80 via blockade of the G0 to G1 cell cycle transition. This blockade was accompanied by a strong decrease in cyclin D1 and phosphorylated Rb, suggesting a G1 arrest. Additionally, Gal-9 induced apoptosis, and the expression of cleaved caspase-3 was increased in Gal-9-treated HuTu-80 cells according to the apoptosis array. MiRNA microarrays revealed that Gal-9 altered the expression of miRNAs in HuTu-80 cells. CONCLUSION: These data demonstrate the therapeutic potential of Gal-9 and provide molecular mechanistic insights into its antitumor effect in HuTu-80 cells.

Does an Extraoral Suction Device Reduce Aerosol Generation and Prevent Droplet Exposure to the Examiner during Esophagogastroduodenoscopy?

Esophagogastroduodenoscopy (EGD) is an aerosol-generating procedure. A major challenge in the COVID-19 era is how to prevent the spread of aerosols and droplets in endoscopic units. We evaluated the effectiveness of an extraoral suction device in preventing indoor aerosol diffusion and droplet exposure for examiners. The study involved 61 patients who underwent EGD at our institution from 1 February to 31 March 2022. To determine whether aerosol spread increases before or after EGD examination with an extraoral suction device located in front of the patient's mouth, aerosols of 0.3, 0.5, 1, 3, 5, and 10 µm were measured with a handheld particle counter. The degree of contamination of the plastic gowns on the examiners was assessed using the rapid adenosine triphosphate test. The extraoral suction device significantly reduced the diffusion of large particles (3, 5, and 10 µm) after finishing the EGD examination. However, the diffusion of small particles (0.3 and 0.5 µm) was significantly increased. This extraoral suction device was effective in reducing large particle diffusion during EGD examination but was limited for minimizing small particle diffusion or droplet exposure to the examiner.

Comparison of endoscopic closure versus non-closure for post-gastric endoscopic submucosal dissection artificial floor in antithrombotic therapy: a propensity score-matched analysis.

Background: The management of delayed bleeding after gastric endoscopic submucosal dissection (ESD) is currently an important issue because of recent increases in the number of patients on antithrombotic therapy. Artificial ulcer closure has been shown to prevent delayed complications in the duodenum and colon. However, its effectiveness in cases involving the stomach remains unclear. In this study, we aimed to determine whether endoscopic closure reduces post-ESD bleeding in patients undergoing antithrombotic therapy. Methods: We retrospectively analyzed 114 patients who had undergone gastric ESD while on antithrombotic therapy. The patients were allocated to one of 2 groups: a closure group (n=44) and a non-closure group (n=70). Endoscopic closure had been performed using multiple hemoclips or using the endoscopic ligation with O-ring closure method after coagulation of exposed vessels on the artificial floor. Propensity score matching resulted in 32 pairs of patients (closure vs. non-closure 32:32). The primary outcome was post-ESD bleeding. Results: The post-ESD bleeding rate was significantly lower in the closure group (0%) than in the non-closure group (15.6%) (P=0.0264). There were no significant differences between the 2 groups regarding white blood cell count, C-reactive protein, maximum body temperature, or scores on a verbal rating scale that assesses the degree of abdominal pain. Conclusion: Endoscopic closure may contribute to decreasing the incidence of post-ESD gastric bleeding in patients undergoing antithrombotic therapy.

Comparison of Needle Knife versus Scissors Forceps for Colorectal Endoscopic Submucosal Dissection: A Prospective Randomized Study.

BACKGROUND AND AIM: To evaluate the efficacy and safety of a grasping-type knife, called Clutch Cutter (CC), for colorectal endoscopic submucosal dissection (C-ESD). METHODS: This was a randomized prospective study. Patients who underwent C-ESD for colorectal neoplasms >20 mm and <50 mm in size were enrolled, dividing into two groups: ESD using needle type of dual knife alone (D-group) and circumferential incision using dual knife followed by submucosal dissection using CC (CC-group). The primary outcome was the self-completion rate. The secondary outcomes were intraoperative complication rate, procedure time, and en bloc resection rate. RESULTS: A total of 45 patients were allocated to the D-group and 43 to the CC-group were allocated. The self-completion rate was higher in the CC-group (87% [39/45] vs. 98% [42/43]). All of the six patients with an incomplete procedure in the D-group were completely resected with CC use. The intraoperative complication rate was not significant in either group (D vs. CC: 2% vs. 0%). The mean procedure time was significantly shorter in the D-group than that in the CC-group (62.0 vs. 81.1 min; p = 0.0036). The en bloc resection rate was 100% in the D-group and 98% in the CC-group. CONCLUSIONS: While dual knife use is superior to CC in terms of time efficiency, the use of CC may be a safe and efficacious option for achieving complete C-ESD.

Endoscopic Ligation with O-Ring Closure for Mucosal Defects after Rectal Endoscopic Submucosal Dissection: A Feasibility Study (with Video).

INTRODUCTION: Mucosal defect closure after colorectal endoscopic submucosal dissection (ESD) may prevent post-ESD adverse events. Delayed bleeding is a particular concern in the rectum due to the presence of numerous blood vessels. However, rectal defect closure often fails due to the thick rectal wall. This study aimed to examine the feasibility of our newly developed endoscopic ligation with O-ring closure (E-LOC) for defects after rectal ESD. METHODS: This was a prospective observational study conducted at a single institution. After excluding 2 patients with tumors mostly extending into the anal canal, the study cohort comprised 30 consecutive patients who underwent ESD of rectal neoplasms between July 2020 and July 2021. E-LOC using an endoscopic variceal ligation device was performed for closing mucosal defects after rectal ESD. The primary outcome was the complete closure rate. The secondary outcomes were the delayed bleeding rate, E-LOC procedure time, sustained closure rates on postoperative day (POD) 3, and E-LOC-associated complications. RESULTS: Complete closure of the defect (median defect size 29.0 mm) was successfully achieved in 24 cases (80%). Delayed bleeding occurred in one case with incomplete closure (3.3%). The median E-LOC procedure time was 25.5 min (interquartile range, 20.0-30.0 min). The sustained closure rates were 83.3% (20/24) on POD 3 in the 24 cases with complete closure. No E-LOC-associated complications occurred. DISCUSSION/CONCLUSIONS: E-LOC was feasible for defect closure after rectal ESD, and probably led to a decreased incidence of delayed bleeding.

Comparison of purse-string suture versus over-the-scope clip for gastric endoscopic full-thickness closure: traction and leak pressure testing in ex vivo porcine model.

BACKGROUND: The recently developed endoscopic full-thickness resection technique requires reliable closure. The main closure methods are the purse-string suture (PSS) technique and over-the-scope clip (OTSC) technique; however, basic data on the closure strength of each technique are lacking. This study was performed to compare the closure strengths of these two methods in an ex vivo porcine model. METHODS: In the traction test, a virtual 5-cm full-thickness closure line was closed by the following six methods three times each: conventional hemoclips, mucosal PSS, seromuscular PSS, mucosal OTSC, seromuscular OTSC, and surgical suture. The primary endpoint was the tension at the starting point of dehiscence, measured in Newtons (N) by an automatic traction machine. In the leak test, a 15-mm gastric full-thickness defect was closed by PSS or OTSC six times each, and the closed stomach was then pressurized in a water container. The primary endpoint was the leak pressure when air bubbles appeared. The secondary endpoints were the procedure time and presence of complete inverted closure. RESULTS: The mean tension was 2.16, 3.68, 5.15, 18.30, 19.30, and 62.40 N for conventional hemoclips, mucosal PSS, seromuscular PSS, mucosal OTSC, seromuscular OTSC, and surgical suture, respectively. Complete inverted closure was observed for seromuscular PSS, seromuscular OTSC, and surgical suture. The mean leak pressure was 13.7 and 24.8 mmHg in the PSS and OTSC group, respectively (P < 0.01). The mean procedure time was 541 and 169 s in the PSS and OTSC group, respectively (P < 0.01). Complete inverted closure was observed in OTSC alone. CONCLUSION: The OTSC, which allows complete inverted closure, showed greater closure strength than PSS. Considering the size limitation suitable for single OTSC, a therapeutic strategy for closing the larger size is further warranted.

Clinical and technical outcomes of endoscopic closure of postendoscopic submucosal dissection defects: Literature review over one decade.

Endoscopic submucosal dissection (ESD), which enables curative en bloc resection of early gastrointestinal neoplasms, has been an attractive minimally invasive surgery during the past two decades. Large post-ESD defects must be carefully managed to prevent adverse events (AEs). The major AEs comprise delayed bleeding (DB) and delayed perforation (DP), and overall AEs comprise DB plus DP. This review aimed to clarify the clinical efficacy and technical outcomes of endoscopic prophylactic closure for post-ESD defects. We identified studies involving ≥10 patients up to March 2022 in which endoscopic closure was applied for gastric, duodenal, and colorectal post-ESD defects. In the stomach, total rates of overall AEs and DB were significantly lower in the closure than non-closure group. In the duodenum, total rates of overall AEs, DB, and DP were significantly lower in the closure group. In the colorectum, total rates of overall AEs and DB were significantly lower in the closure group. Closure techniques, categorized into three groups (clip-based techniques, mechanical clipping, and surgical stitch-based techniques), were illustrated. Endoscopic closure demonstrated a certain ability to reduce DB after gastric, duodenal, and colorectal ESD as well as DP after duodenal ESD. Considering closure-associated costs, the indications and limitations of closure techniques should be further investigated.

MicroRNA profiles following telmisartan treatment in pancreatic ductal adenocarcinoma cells.

Background: Pancreatic ductal adenocarcinoma (PDAC) is the most devastating of all cancers with an extremely poor prognosis. It has few effective and reliable therapeutic strategies. Telmisartan, a widely used antihypertensive drug, is an angiotensin II type 1 (AT1) receptor blocker (ARB). Telmisartan inhibits cancer cell proliferation, but the underlying mechanisms in PDAC, remain unknown. Material and Methods: In the present study, we evaluated the effects of telmisartan on human PDAC cell proliferation in vitro. We assessed the effects of telmisartan on human PDAC cells using the cell lines PK-1 and PANC-1. Results: Telmisartan inhibited the proliferation of these cells via blockade of the G0 to G1 cell cycle transition. This was accompanied by a strong decrease in cyclin D1. Telmisartan was also shown by receptor tyrosine kinase and angiogenesis arrays to reduce the phosphorylation of epidermal growth factor receptor (EGFR), and miRNA expression was markedly altered by telmisartan in PK-1 cells. Conclusion: In conclusion, telmisartan inhibits human PDAC cell proliferation by inducing cell cycle arrest. Furthermore, telmisartan significantly altered miRNA expression in vitro. Taken together, our study demonstrated the therapeutic potential of telmisartan and provides molecular mechanistic insights into its anti-tumor effect on PDAC cells.

Acceptability of Hybrid Endoscopic Submucosal Dissection Using Multifunctional Snare for Small-sized Gastric Neoplasms: A Prospective Observational Study.

BACKGROUND AND AIMS: The most suitable procedure for resecting small-sized gastric neoplasms remains unclear. Endoscopic mucosal resection leads to non-curative resection owing to slippage of the snare, and technically difficult endoscopic submucosal dissection (ESD) is instrumentally uneconomical. A novel, cost-effective, multifunctional snare called SOUTEN is available as a hybrid ESD (h-ESD) device developed for facilitating ESD. This study aimed to assess the acceptability of h-ESD using the SOUTEN for resecting small-sized gastric neoplasms. METHODS: This was a prospective observational study conducted at our single institution between March 2019 and March 2021. Fifty-seven consecutive patients who underwent h-ESD using SOUTEN for small-sized gastric neoplasms ≤15 mm involving adenoma and tubular-type mucosal carcinoma without ulceration were enrolled. The primary outcome was curative resection rate for h-ESD. Secondary outcomes were the rates of conversion to ESD, rate of total (h-ESD + ESD) curative resection, procedure time, rates of intra-and post- operative complications, and presence of additional knives excluding hemostatic forceps. RESULTS: The curative resection rate of h-ESD was 89.5% (51/57). The total (h-ESD + ESD) curative resection rate was 94.7% (54/57). The mean procedure time was 21.2 (±16.5) minutes. One case of delayed bleeding occurred. Additional knives were applied in two cases. CONCLUSIONS: The cost-efficient h-ESD using SOUTEN can be an acceptable procedure for resecting small- sized gastric neoplasms.

Effect of Lenvatinib treatment on the cell cycle and microRNA profile in hepatocellular carcinoma cells.

Lenvatinib is a tyrosine kinase receptor inhibitor used to treat unresectable hepatocellular carcinoma (HCC). In this study, we investigated the antitumor effects of Lenvatinib treatment on HCC cell lines. Proliferation was examined in four HCC cell lines (HuH-7, Hep3B, Li-7, and PLC/PRF/5) using Cell Counting Kit-8 assays. Xenograft mouse models were used to assess the effects of Lenvatinib in vivo. Cell cycle, western blotting, and microRNA (miRNA) expression analyses were performed to identify the antitumor inhibitory potential of Lenvatinib on HCC cells. Lenvatinib treatment suppressed proliferation of HuH-7 and Hep3B, but not Li-7 and PLC/PRF/5 cells and induced G0/G1 cell cycle arrest and cyclin D1 downregulation in Lenvatinib-sensitive cells. Lenvatinib treatment also reduced tumor growth in HuH-7 xenograft mouse models. miRNA microarrays revealed that Lenvatinib treatment altered the expression of miRNAs in HuH7 cells and exosomes. Our results demonstrated the therapeutic potential of Lenvatinib and provide molecular mechanistic insights into its antitumor effects for treating HCC.

Effect of Aspirin on G0/G1 Cell Cycle Arrest and microRNA Signatures in Pancreatic Adenocarcinoma Cells.

BACKGROUND/AIM: Anti-inflammatory drugs, such as aspirin, have attracted attention as anticancer agents that can be applied to standard chemotherapy for pancreatic cancer. This study aimed to examine the antitumour effects and possible fundamental mechanisms of aspirin in pancreatic cancer cells. MATERIALS AND METHODS: We appraised the antitumour effects of aspirin on cell proliferation and tumour growth, cell cycle distribution, apoptosis, signalling pathways, angiogenesis-related proteins, and phosphorylated receptor tyrosine kinases (p-RTKs) and identify miRNAs associated with its antitumour effects. RESULTS: Aspirin inhibited cell proliferation in pancreatic cancer cell lines and induced G0/G1 cell cycle arrest by decreasing the expression of cyclin D1. Aspirin inactivated glycogen synthase kinase (GSK)-3ß but had no effect on the p38 mitogen-activated protein kinase (MAPK) pathway, p-RTKs, or angiogenesis-related molecules. Aspirin treatment statistically increased the expression of 274 miRNAs in PANC-1 cells and 30 miRNAs in PK-8 cells and suppressed the expression of 294 miRNAs in PANC-1 cells and 13 miRNAs in PK-8 cells. CONCLUSION: Aspirin inhibited the proliferation of pancreatic cancer cells and induced cell cycle arrest. Aspirin also inactivated GSK-3ß but not the p38 MAPK pathway. Thus, aspirin may be used in combination with chemotherapeutic agents for pancreatic cancer.

Characterization of Cisplatin Effects in Lenvatinib-resistant Hepatocellular Carcinoma Cells.

BACKGROUND/AIM: Drug resistance to molecular targeted agents, such as lenvatinib, is an important issue. The aim of this study was to explore the mechanism of lenvatinib resistance and to investigate potential drugs that may improve the treatment of lenvatinib-resistant (LR) hepatocellular carcinoma (HCC). MATERIALS AND METHODS: LR cells were developed by long-term culture under lenvatinib exposure. We analyzed the biological characteristics of LR cells in vitro, and investigated the antitumor effects and endogenous mechanisms of cisplatin in LR cells. RESULTS: The proliferative potential of LR cells was enhanced by activation of ERK signaling and changes in several miRNAs. Cisplatin inhibited cell proliferation of LR cells and induced G2/M cell cycle arrest. Furthermore, cisplatin triggered the DNA damage response, via the ATM/ATR-Chk1/Chk2 signaling pathway. CONCLUSION: Proliferation of LR cells was induced upon ERK signaling activation. Cisplatin exerted antitumor effects in LR cells and was involved in the regulation of miRNAs associated with drug resistance.

Ipragliflozin attenuates non-alcoholic steatohepatitis development in an animal model.

Non-alcoholic steatohepatitis (NASH) is a common chronic liver disease with no decisive treatment. The sodium glucose cotransporter 2 (SGLT2) inhibitor ipragliflozin was developed as a new oral hypoglycemic drug, which can improve NASH via an insulin-independent glucose-lowering effect by inhibiting glucose reabsorption in the renal proximal tubules. However, ipragliflozin appears to modulate steatosis or inflammation via different pathways. To elucidate the new mechanism of ipragliflozin for the treatment of NASH, we evaluated its effects in a NASH mouse model (STAM mice) with beta cell depletion, and compared the expression of microRNAs (miRNAs) in STAM mice treated with or without ipragliflozin (16.7 µg/day for 5 weeks). Ipragliflozin reduced aspartate transaminase and alanine aminotransferase levels, along with reduced hepatic steatosis, hepatocyte ballooning, lobular inflammation, and liver fibrosis. In addition, ipragliflozin upregulated mitochondrial transport-related and antioxidant defensive system-related genes in the liver. Among 2555 mouse miRNA probes, miR-19b-3p was commonly differentially expressed with ipragliflozin treatment for 5 weeks in both the liver and serum but in different directions, with a decrease in the liver and increase in the serum. Therefore, ipragliflozin can improve NASH development likely through the antioxidative stress pathway and by regulating miR-19b-3p.