post-ESD Ulcer Research Articles

A case of colon cancer implanted on endoscopic resection ulcer certified by cancer genomic testing

A 90 year-old man underwent endoscopic mucosal resection for lesions in the descending and sigmoid colons as well as endoscopic submucosal dissection (ESD) for a lesion in the rectal peritoneal reflection (Ra) 1 month before undergoing laparoscopic resection and D3 dissection for advanced cancer in the descending colon. One year later, he underwent a surveillance colonoscopy, and advanced colorectal cancer was detected on the ESD scar. The history suggested that this newly detected recurrent colorectal neoplasm on the ESD scar may have originated from cancer cells derived from the descending colon cancer that were implanted in the ESD ulcer, thereby initiating a new colorectal neoplasm. Cancer genomic testing further indicated that three of the four pathogenic variants detected in the recurrent colorectal neoplasm were consistent with pathogenic variants of descending colon cancer. This finding strongly supports our contention that cancer cells derived from the descending colon cancer were implanted in the post-ESD ulcer of the rectal Ra and proliferated, forming the recurrent colorectal neoplasm. This case report highlights the potential for tumor cell implantation on endoscopic resection ulcers and the utility of cancer genomic testing in validating this phenomenon.

Optimizing a self-solidifying hydrogel as an endoscopically deliverable hydrogel coating system: a proof-of-concept study on porcine endoscopic submucosal dissection-induced ulcers

Endoscopic submucosal dissection (ESD) benefits patients in the early stages of cancer, but it poses various risks of complication. Strategies involving the application of clinically approved products to cover ulcers caused by ESD can reduce these complications, but the fixed nature of their properties limit the understanding of their effects on ulcer healing. This study was focused on Tetra–PEG gel, an innovative hydrogel with controllable physical properties made from a sulfhydryl–maleimide pair. The use of biocompatible polyethylene glycol (PEG) in Tetra–PEG gel may allow for its application as a biomaterial. The aims of our study were to identify the characteristics of a self-solidifying hydrogel for endoscopic application and to develop a new ulcer coating agent for post-ESD treatment. We developed a specialized double-lumen catheter and determined the optimal application conditions of the hydrogel. We examined the hydrodynamic properties of the gelling solutions and elucidated the pressure drop that occurred during device operation. Finally, by considering previous experimental results, we successfully applied the hydrogel to post-ESD ulcers in porcine stomachs. We believed that by further optimizing hydrogels with effectively controlled properties and by continuing to investigate them through animal experiments, we could expand our understanding of the relationships among material and ulcer healing properties and apply this knowledge to clinical applications.

Using a novel hemostatic peptide solution to prevent bleeding after endoscopic submucosal dissection of a gastric tumor.

Endoscopic mucosal dissection has become the standard treatment for early gastric cancer. However, post-endoscopic submucosal dissection (ESD) ulcer occurs in 4.4% of patients. This study hypothesized whether applying PuraStat, a novel hemostatic peptide solution, prevents post-ESD bleeding. To investigate the preventive potential of PuraStat, a hemostatic formulation, against bleeding in post-ESD gastric ulcers. Between May 2022 and March 2023, 101 patients (Group P) underwent ESD for gastric diseases at our hospital and received PuraStat (2 mL) for post-ESD ulcers. We retrospectively compared this group with a control group (Group C) comprising 297 patients who underwent ESD for gastric diseases at our hospital between April 2017 and March 2021. P values < 0.05 on two-sided tests indicated significance. Post-ESD bleeding occurred in 6 (5.9%) (95%CI: 2.8-12.4) and 20 (6.7%) (95%CI: 4.4-10.2) patients in Groups P and C, respectively, with no significant between-group difference. The relative risk was 1.01 (95%CI: 0.95-1.07). The lesser curvature or anterior wall was the bleeding site in all 6 patients who experienced postoperative bleeding in Group P. In multivariate analysis, the odds ratios for resection diameter ≥ 50 mm and oral anticoagulant use were 6.63 (95%CI: 2.52-14.47; P = 0.0001) and 4.04 (1.26-0.69; P = 0.0164), respectively. The adjusted odds ratio of post-ESD bleeding and PuraStat was 1.28 (95%CI: 0.28-2.15). PuraStat application is not associated with post-ESD bleeding. However, the study suggests that gravitational forces may affect the effectiveness of applied PuraStat.

Efficacy of prophylactic clip closure in reducing the risk of delayed bleeding after colorectal endoscopic submucosal dissection in patients on anticoagulant therapy: Multicenter prospective study.

The high rate of delayed bleeding after colorectal endoscopic submucosal dissection (ESD) in patients undergoing anticoagulant therapy remains a problem. Whether prophylactic clip closure reduces the rate of delayed bleeding in these patients is unclear. This study aimed to evaluate the efficacy of prophylactic clip closure in patients receiving anticoagulants. This multicenter prospective interventional trial was conducted at nine referral centers in Japan. Patients regularly taking anticoagulants, including warfarin potassium or direct oral anticoagulants, and undergoing ESD for colorectal neoplasms were enrolled. The discontinuation of anticoagulants was minimized according to recent guidelines. After the ESD, post-ESD ulcers were prophylactically closed using endoclips. The primary end-point was the incidence of delayed bleeding. The sample size was 45 lesions, and prophylactic clip closurewas considered effective when the upper limit of the 90% confidence interval (CI) for delayed bleeding did not exceed 20%. Forty-five lesions were used, and three were excluded. Complete closure was achieved in 41/42 lesions (97.6%). The overall delayed bleeding rate was low, at 4.9% (2/41; 90% [CI] 0.8-14.5), which was significantly lower than that at the prespecified threshold of 20% (P = 0.007). The median closure procedure time was 17 min, and the median number of clips was nine. No massive delayed bleeding requiring transfusion, interventional radiology, or surgery was observed, and no thromboembolic events were observed. Prophylactic clip closure may reduce the risk of delayed bleeding following colorectal ESD in patients receiving anticoagulants. UMIN Clinical Trial Registry (UMIN000036734).

Single-channel endoscopic closure of a mucosal defect after endoscopic submucosal dissection using a disposable endoloop and a retrievable clip.

Endoscopic submucosal dissection (ESD) is a treatment with high rate of en bloc resection. It has been suggested that mucosal suture of post-ESD ulcers may reduce the incidence of delayed accidents. Suturing method for the ulcers and deep tears that use a single-channel scope and a reusable endoloop (Olympus, Tokyo, Japan) and ones that use a double-channel scope have been reported. Notably, due to difficulties in using a a reusable loop, we devised a suturing method that uses a single-channel scope, a disposable endoloop, and a SureClip (Micro-tech Endoscopy, Nanjing, China). The SureClip was inserted into the forceps hole and withdrawn from the tip. The loop portion of the endoloop was grasped with the SureClip while the disposable endoloop was halfway out and then delivered into the lumen outside the endoscope. After reaching the target site, the SureClip was opened and secured to one of the mucosa ends. The first clip was placed as far away from the sheath as possible. The use of the SureClip was then continued, for fixation at multiple sites, and the endoloop was tightened and sutured. No complications, such as bleeding or perforation, were observed.

A novel tetra-PEG based hydrogel for prevention of esophageal stricture after ESD in a porcine model

Endoscopic submucosal dissection (ESD) is an accepted treatment for early esophageal cancer and precancerous lesions, but resection of a large mucosal area often leads to postoperative esophageal stricture. Biomaterials provide a new option for the treatment of post-ESD ulcers. In this study, we developed a well-defined ammonolysis-based tetra-armed poly (ethylene glycol) (Tetra-PEG) hydrogel and investigated its efficacy and related mechanisms for preventing esophageal ESD-induced stricture in a porcine model. In terms of material properties, Tetra-PEG hydrogel present great biocompatibility，great capability to retain moisture, strong tissue adhesion and high mechanical strength. Then, six domestic female pigs were randomly divided into PEG (n = 3) and control groups (n = 3). A 3/4 of the esophageal circumference ESD was performed in all pigs. In PEG group, Tetra-PEG hydrogel was easily delivered via endoscopy and adhered to the ulcer bed tightly. Compared to control group, Tetra-PEG hydrogel accelerated esophageal ulcer healing at an early stage with enhanced epithelium regeneration, milder inflammation and lesser fibrosis by regulating TGF-β/Smad2 signaling. Taken together, our findings reveal Tetra-PEG hydrogel is a promising and attractive candidate for preventing the formation of fibrotic stricture in the process of esophageal ESD-induced ulcer repair.

Vonoprazan - a new drug for inhibiting gastric acid secretion

Introduction and purpose &#x0D; Vonoprazan is a potassium-competent acid blocker (P-CAB). It has the potential to be an alternative to proton pump inhibitors (PPIs) as it inhibits hydrochloric acid secretion. The mechanism of action is different than PPIs - vonoprazan reversibly inhibits gastric H+, K+-ATPase, while PPIs irreversibly. Vonoprazan is approved for use in Japan and the US. The aim of the study was to review articles on the use of vonoprazan instead of PPIs in the treatment of acid-related gastrological diseases and to present the results obtained. &#x0D; &#x0D; A brief description of the state of knowledge &#x0D; Vonoprazan is used in the treatment of acid-related gastrological diseases. The 20 mg dose is suitable for most diseases, such as treatment of ulcers during low-dose aspirin treatment, post-endoscopic submucosal dissection (post-ESD) ulcers, erosive esophagitis (EE) in gastroesophageal reflux disease (GERD), and Helicobacter pylori eradication. &#x0D; &#x0D; Summary &#x0D; Researches suggest that the drug is an alternative for PPIs and can be used instead of them. The main advantage of this drug over PPIs is that it works faster, more potent and long-lasting. Studies suggest that vonoprazan can be use to treatment of the acid-related diseases and may be a better choice than PPIs. Vonoprazan may have a particular use in the treatment of PPI-refractory GERD. In post-ESD ulcers, a significant benefit in treatment effects of vonoprazan over PPIs cannot be clearly concluded.

Propensity score matching analysis to evaluate efficacy of polyethylene oxide adhesive on preventing delayed bleeding after gastric endoscopic submucosal dissection

Regardless of technical advancements, delayed bleeding is still a common adverse event after gastric endoscopic submucosal dissection (ESD), often occurring in the early postoperative phase. This study aimed to evaluate the efficacy of a newly designed polyethylene oxide (PEO) adhesive for preventing delayed gastric bleeding. Patients who underwent gastric ESD between December 2017 and December 2020 at three Chinese institutions were retrospectively reviewed. Patients receiving PEO application on gastric post-ESD ulcers were included in the PEO group, and patients without this procedure were included in the control group. To minimize potential bias, propensity score matching was performed, and sex, age, lesion size, lesion morphology, ulceration, localization, procedure time, frequency of major intraoperative bleeding, resected specimen size, lesion histopathology, submucosal invasion and the taking of antithrombotic drugs were included as matching factors. The incidence of delayed bleeding and time to bleeding were compared between both groups. After propensity score matching, 270 patients (135 per group) were included in the analysis. The delayed bleeding rate in the PEO group was significantly lower than that in the control group (1.5%, 2/135 vs. 8.9%, 12/135, P = 0.006). The median time (range) to bleeding was 4.5 (4–5) days in the PEO group and 2 (1–15) days in the control group, with no significant difference (P = 0. 198). PEO demonstrated a significant effect in reducing the rate of delayed bleeding. Further study is warranted to confirm the efficacy of PEO for bleeding that occurs in the early phase after gastric ESD.

Vonoprazan versus proton pump inhibitors for postendoscopic submucosal dissection bleeding in the stomach: a multicenter population-based comparative study

The effectiveness of vonoprazan relative to that of proton pump inhibitors (PPIs) after gastric endoscopic submucosal dissection (ESD) is unclear. Although previous studies used post-ESD ulcer healing as the outcome measure, post-ESD bleeding rate is the most objective and appropriate outcome measure because it has less ascertainment bias. We aimed to compare the post-ESD bleeding rates between vonoprazan and PPIs. This nationwide population-based retrospective cohort study was conducted between 2014 and 2018 and involved 9 hospitals. After 2 days of intravenous PPI administration, either vonoprazan or PPI was administrated from postoperative day 2 to30. Overall, data of 1715 patients (627 patient pairs) were analyzed through propensity score matching. The vonoprazan group had significantly lower post-ESD bleeding rates than the PPI group (overall, 11.9% vs 17.2%, P= .008; bleeding between days 2 and 30, 7.8% vs 11.8%, P= .015). The readmission rate because of post-ESD bleeding was lower in the vonoprazan group (2.4% vs 4.1%, P= .081). Blood transfusion (2.1% vs 3.0%, P= .15) and additional surgery because of delayed perforation (.5% vs 1.0%, P= .32) were not significantly different between the 2 groups. No deaths within 30 days occurred in both groups. On Cox regression analysis, vonoprazan use, lesion location (antrum), aspirin use, direct oral anticoagulant use, and Charlson Comorbidity Index (≥2) were associated with an increased risk of post-ESD bleeding within 30 days. Vonoprazan has a lower post-ESD bleeding rate than PPIs. Further prospective studies are required to confirm these results.

Second-look endoscopy findings after endoscopic submucosal dissection for colorectal epithelial neoplasms.

Background/AimsAlthough second-look endoscopy (SLE) is frequently performed after gastric endoscopic submucosal dissection (ESD) to prevent bleeding, no studies have reported SLE findings after colorectal ESD. This study aimed to investigate SLE findings and their role in preventing delayed bleeding after colorectal ESD.MethodsPost-ESD ulcer appearances were divided into coagulation (with or without remnant minor vessels) and clip closure groups. SLE findings were categorized according to the Forrest classification (high-risk ulcer stigma [type I and IIa] and low-risk ulcer stigma [type IIb, IIc, III, or clip closure]), and risk factors for high-risk ulcer stigma were analyzed.ResultsAmong the 375 cases investigated, SLEs were performed in 171 (45.6%) patients. The incidences of high-risk ulcer stigma and low-risk stigma were 5.3% (9/171) and 94.7% (162/171), respectively. During SLE, endoscopic hemostasis was performed more frequently in the high-risk ulcer stigma group than in the low-risk ulcer stigma group (44.4% [4/9] vs. 1.9% [3/162], respectively; p < 0.001), but most of the endoscopic hemostasis in the high-risk ulcer stigma group (3/4, 75.0%) were prophylactic hemostasis. Post-ESD delayed bleeding occurred in three (0.8%) patients belonging to the SLE group, of which, one patient was from the high-risk stigma group and two were from the low-risk stigma group.ConclusionsThe incidence of high-risk ulcer stigma during SLE was low, and delayed bleeding occurred in, both, high-risk and low-risk groups of SLE. SLEs performed after colorectal ESD may not be effective in preventing delayed bleeding, and further prospective studies are needed to evaluate the efficacy of SLE in post-colorectal ESD.

LGR5-Expressing Cells in the Healing Process of Post-ESD Ulcers in Gastric Corpus.

LGR5 is a promising stem cell marker in gastric pylorus, but there are few reports on its expression in human gastric corpus. To investigate the involvement of LGR5 expression in gastric corpus ulcer regeneration in humans. LGR5 expression was analyzed in five post-ESD ulcers during the healing process of regenerating epithelial cells of the gastric corpus. LGR5 expression was detected by mRNA in situ hybridization using an RNA scope kit. Immunohistochemistry of MUC6, HIK1083, and pepsinogen 1 (PG1) was performed to identify cell differentiation. We defined MUC6+/HIK1083-/PG1-, MUC6+/HIK1083+/PG1-, MUC6+/HIK1083+/PG1+, MUC6+/HIK1083-/PG1+, and MUC6-/HIK1083-/PG1+cells as pseudopyloric mucosa (PPM) phase 1 (PPM1), PPM phase 2 (PPM2), PPM phase 3 (PPM3), immature chief cells (ICC), and mature chief cells (MCC) in order from the ulcer center, respectively. In the regenerated mucosa around post-ESD ulcers, LGR5 expression was observed throughout the gland in PPM1-PPM3, but it was limited to the bottom of the gland in ICC and MCC. Furthermore, LGR5 expression was not identified in the normal gastric corpus. The H-score of PPM2 was significantly higher than that of PPM3 (P = 0.0313). The H-score of PPM3 was significantly higher than that of ICC (P = 0.0313). The LGR5 H-score was higher at the immature stage, which decreased gradually with progression of the differentiation stage. LGR5 expression appears to contribute to mucosal regeneration in the human gastric corpus. The application of LGR5 expression analysis to mucosal regeneration and fundic gland-type gastric tumors is expected.

Allogeneic epithelial cell sheet transplantation for preventing esophageal stricture after circumferential ESD in a porcine model: preliminary results

Objectives Circumferential endoscopic submucosal dissection (ESD) for large lesions induces severe stricture, requiring subsequent treatment. We aimed to evaluate the efficacy of allogeneic epithelial cell sheet transplantation in preventing esophageal stricture after circumferential ESD in a porcine model. Materials and methods A total of 15 conventional pigs underwent a 4 cm long circumferential ESD in the mid-esophagus. Out of these animals, 11 were immediately subjected to allogeneic oral mucosal cell sheet transplantation at the resection site, whereas four pigs underwent circumferential ESD only. We performed upper endoscopy 1 and 2 weeks after ESD and assessed the degree of esophageal stricture and histologic characteristics. Results Dysphagia scores and weight change ratios recorded 1 and 2 weeks after ESD did not differ between the two groups. The stricture rate 2 weeks after ESD was 100% in the control group and 90.9% in the cell sheet group (p = 1.000). The median mucosal constriction rates of the control and cell sheet groups were 73.5% (range 63.0–80.0%) and 53.8% (37.5–73.3%, p = .018), respectively. With regard to microscopic measurements, the length of re-epithelialization was greater in the cell sheet group than in the control group (2,495 µm vs. 369 µm, p = .008). Median fibrosis thickness and degree of muscle damage were not significantly different between groups. Conclusions Although allogeneic epithelial cell sheet transplantation showed greater re-epithelialization and less mucosal constriction of post-ESD ulcers, it was not sufficiently effective in preventing post-ESD stricture.

Accelerating ESD-induced gastric ulcer healing using a pH-responsive polyurethane/small intestinal submucosa hydrogel delivered by endoscopic catheter.

Endoscopic submucosal dissection (ESD) is the standard treatment for early-stage gastric cancer, but the large post-operative ulcers caused by ESD often lead to serious side effects. Post-ESD mucosal repair materials provide a new option for the treatment of post-ESD ulcers. In this study, we developed a polyurethane/small intestinal submucosa (PU/SIS) hydrogel and investigated its efficacy for accelerating ESD-induced ulcer healing in a canine model. PU/SIS hydrogel possessed great biocompatibility and distinctive pH-sensitive swelling properties and protected GES-1 cells from acid attack through forming a dense film in acidic conditions in vitro. Besides, PU/SIS gels present a strong bio-adhesion to gastric tissues under acidic conditions, thus ensuring the retention time of PU/SIS gels in vivo. In a canine model, PU/SIS hydrogel was easily delivered via endoscopy and adhered to the ulcer sites. PU/SIS hydrogel accelerated gastric ulcer healing at an early stage with more epithelium regeneration and slight inflammation. Our findings reveal PU/SIS hydrogel is a promising and attractive candidate for ESD-induced ulcer repair.

Effects of vonoprazan on gastric PH and clinical course after gastric ESD: A retrospective and prospective study

BackgroundVonoprazan has been more widely used for artificial ulcers after endoscopic submucosal dissection (ESD) for early gastric cancer; however, no reports have examined intragastric pH during ESD. The present study aimed to measure gastric pH at the time of ESD and the clinical course afterwards for patients treated with vonoprazan the night before undergoing ESD. Materials and methodsWe examined medication status regarding gastric acid secretion and antithrombotic drugs, post-ESD bleeding as a perioperative complication, and the timing of upper gastrointestinal endoscopy after ESD and ulcer healing in 156 patients who underwent gastric ESD at our hospital from January 2014 to December 2019. The gastric pH was measured at the time of ESD after administration of 20 mg vonoprazan on the night before gastric ESD. ResultsThere were 14 cases of post-ESD bleeding in patients treated with proton-pump inhibitors (PPIs), including oozing during second-look endoscopy compared to only 1 case of bleeding with vonoprazan administration (p < 0.05). Vonoprazan was also associated with better post-ESD ulcer healing than PPIs. Gastric pH during ESD after vonoprazan administration on the night before gastric ESD was ≥6.96 in all 11 patients. ConclusionPost-ESD bleeding was reduced, and ulcer healing was improved in patients treated with vonoprazan the night before their procedure. Our results suggest high gastric pH during ESD due to vonoprazan administration may be beneficial for hemostasis and ulcer healing following ESD.

Covering Post-Endoscopic Submucosal Dissection Ulcers in Miniature Swine with Hexanoyl (Hx:C6) Group-Modified Alkaline-Treated Gelatin Porous Film (HAG) Induces Proper Healing by Decreasing Inflammation and Fibrosis

Background and Aims: Hexanoyl (Hx:C6) group-modified alkaline-treated gelatin porous film (HAG) is a newly developed degradable hydrogel characterized by strong adhesiveness and high affinity for vascular endothelial growth factor (VEGF). The aim of this study was to clarify the effect of HAG sheets on the healing process of post-endoscopic submucosal dissection (ESD) porcine gastric artificial ulcers. Methods: (1) To evaluate the adhesiveness of HAG sheets over time, we performed ESD to create 1 artificial ulcer and covered the lesion with 1 HAG sheet using 1 miniature swine. We observed 2 ulcers by endoscopic and microscopic examinations. (2) To examine the effect of HAG sheets on post-ESD ulcer healing, we performed ESD using 5 miniature swine. The artificial ulcers were covered with HAG sheets, or left uncovered after ESD (day 0), followed by macroscopic and microscopic examinations. On days 7 and 14, we observed 2 ulcers by endoscopic examinations. On day 14, the animals were sacrificed, and histological examination was performed on the 3 stomachs that could be extirpated. Results: (1) On day 7, adhesion of HAG sheets was observed. (2) Gastric ulcer area on day 7 was significantly larger in the covered ulcers than in the non-covered ulcers (p = 0.046). On day 14, although there was no significant difference in ulcer area irrespective of covering (p = 0.357), the covered ulcers tended to repair less fold convergence than non-covered ulcers. The covered ulcer sheets significantly decreased inflammatory cell infiltration (p = 0.011), but significantly increased the abundance of macrophages (p = 0.033), in submucosal layers. Also, the abundance of alpha-smooth muscle actin-positive cells in submucosal layers of the covered ulcers was significantly reduced (p = 0.044), leading to a decrease in collagen accumulation. In addition, fibrosis and atrophy of the muscularis propria were significantly lower for covered ulcers than for non-covered ulcers. Furthermore, microvessels and VEGF-positive cells were significantly more abundant in the submucosal layers of the covered ulcers (p < 0.001 and p = 0.024, respectively). Conclusions: HAG sheets induced post-ESD ulcer healing with less submucosal inflammation and muscularis propria injury and have the potential to decrease excess scarring.

Endoscopic Doppler probe ultrasonography for detecting blood flow at post-endoscopic submucosal dissection ulcers of the stomach.

Background and study aims The rate of early rebleeding after endoscopic submucosal dissection (ESD) for early gastric cancer ranges from 5 % to 38 %, despite application of preventive methods. Post-ESD rebleeding may be caused by “invisible” vessels that may not be detectable using ultrasonographic techniques. Recently, Doppler probe ultrasonography (DOP) has been used in endoscopy. Because little is known about the usefulness of DOP for decreasing the post-ESD rebleeding rate, we performed a preliminary case series study. Patients and methods Twelve patients underwent DOP for post-ESD ulcer evaluation after visible vessel coagulation. In this study, the novel DOP system used in the vascular surgery department was used. DOP-positive invisible vessels were shown as a pulse wave on the monitor. Results No (0 %) cases of post-ESD rebleeding occurred. Twenty invisible vessels were detected, and 13 were subjected to additional coagulation up to a depth of 3 mm. Mean DOP procedure time was 11.6 minutes (range: 8–18 minutes). In these latter cases, disappearance of the Doppler pulse wave was confirmed. No early rebleeding or other adverse events were experienced. Conclusion DOP is a safe and feasible method for detecting invisible vessels in post-ESD ulcers. Further investigation of the clinical relevance is warranted.

Efficacy of the Envelope Method in Applying Polyglycolic Acid Sheets to Post-Endoscopic Submucosal Dissection Ulcers in Living Pigs.

Background/AimsApplication of polyglycolic acid (PGA) sheets using fibrin glue in post-endoscopic submucosal dissection (ESD) ulcers to prevent bleeding has been reported to be difficult with the conventional delivery method because of gravity. This study assessed the usefulness of the envelope-based delivery system with and against gravity in living pigs. MethodsPGA sheets were applied on post-ESD ulcers with and against gravity six times each using the conventional and envelope methods, respectively. The PGA sheet delivery time and the endoscopic and histological findings of the treated ulcer floors were compared. ResultsWith gravity, the median PGA sheet application time was 1.00 (0.68–1.30) min/cm2 and 0.32 (0.18–0.52) min/cm2 with the conventional and envelope techniques (p=0.002), respectively, and against gravity, it was 1.20 (1.13–1.63) min/cm2 and 0.50 (0.39–0.58) min/cm2 (p=0.002), respectively. Against gravity, the endoscopic and histological findings revealed that the conventional group had insufficient fixation of the PGA sheets, but the envelope groups had sufficient fixation. The results with gravity were similar between the groups. ConclusionsThe envelope method makes it possible to deliver PGA sheets to the stomach quickly and cover ulcers appropriately both with and against gravity in living pigs.

Clinical Outcomes of Vonoprazan-Treated Patients after Endoscopic Submucosal Dissection for Gastric Neoplasms: A Prospective Multicenter Observation Study

Background: Vonoprazan (VPZ) has the potential to prevent delayed bleeding and promote ulcer healing after endoscopic submucosal dissection (ESD) similar to proton pump inhibitors (PPIs). Objective: We aimed to evaluate the outcomes of VPZ-treated patients after ESD and compared the efficacy and feasibility in preventing a delayed bleeding and in healing an artificial ulcer after ESD between the VPZ and PPI therapies. Methods: This was a prospective, observation study in 11 Japanese medical institutions. We enrolled and evaluated 223 patients who underwent gastric ESD followed by VPZ treatment (VPZ group). We selected 385 patients who underwent gastric ESD followed by PPI treatment as historical controls (PPI group) to compare the outcomes between the VPZ and PPI groups using a propensity score matching analysis. Results: Among the 223 patients treated with VPZ, 173 were men and 50 were women with a median age of 72 years and with a median tumor size of 12.0 mm. Rates of en bloc resection and complete resection were 99.1 and 94.2%, respectively. Lymphovascular invasion was found in 6 (6.3%) cases. Intraoperative perforation and delayed bleeding occurred in 3 (1.3%) and 10 patients (4.5%), respectively. Scarring of artificial post-ESD ulcer was found in 153 patients (68.6%) at 6 weeks after ESD. The 205 pairs of propensity score-matched patients were comparable between the VPZ and PPI groups. The rate of delayed bleeding in the VPZ and PPI groups was 3.9 and 4.4%, respectively (difference, 0.5 percentage points; 95% confidence interval, −3.7 to 2.8%; non-inferiority, p = 0.01). Therefore, VPZ therapy demonstrated non-inferiority against PPI therapy in reducing the rate of delayed bleeding. The scar-stage ulcer at 6 weeks in the VPZ group and 8 weeks in the PPI group was 68.3 and 74.6%, respectively (p = 0.19). Conclusions: VPZ therapy showed an efficacy and feasibility in preventing a delayed bleeding after ESD similar to the PPI therapy. VPZ for 6 weeks and PPI for 8 weeks were similarly effective for an artificial ulcer healing after ESD.

Comparison of efficacy of pharmacological therapies for gastric endoscopic submucosal dissection-induced ulcers: a systematic review and network meta-analysis

ABSTRACTObjectives: This study aimed to compare the efficacy of various anti-ulcer medications in preventing delayed bleeding and promoting ulcer healing after ESD.Methods: Asystematic search was conducted for articles up to August2019. The treatments of iatrogenic ulcer were analyzed by Bayesian network meta-analysis.Results: The analysis included 28 studies. Six treatments were compared. For the prevention of delayed bleeding, potassium-competitive acid blocker (P-CAB) alone was superior to proton-pump inhibitor (PPI) alone [RR = 1.02, 95%CI (1.00, 1.05)]. Treatments based on P-CAB tended to be better than the non-P-CAB groups [RR = 1.05, 95%CI (1.03, 1.07)]. Concerning the ulcer healing rate at 4 weeks, the combined treatment of PPI and mucoprotective agent (MP) was superior to PPI alone [RR = 1.81, 95%CI (1.19, 2.76)] and P-CAB alone [RR = 2.75, 95%CI (1.02, 7.44)]. At 8 weeks, PPI+MP and P-CAB+MP tend to be superior to than the other four groups. The healing effect of MP-based therapies was better than that of non-MP groups at 4 weeks [RR = 1.63, 95%CI (1.32, 2.01)] and 8 weeks [RR = 1.06, 95%CI (1.02, 1.11)].Conclusion: P-CAB may prevent delayed bleeding, but not significantly. MP agents have the potential to heal post-ESD ulcers.

Feasibility of a new ligation using the double-loop clips technique without an adhesive agent for ulceration after endoscopic submucosal dissection of the colon (with video)

Several ligation techniques for ulceration after endoscopic submucosal dissection (ESD) have been reported, but none have been established for clinical use because of technical complexity and the need for expensive equipment. Therefore, the technical feasibility of a new ligation method using the double-loop clips (D-L clips) technique without an adhesive agent for ulceration after ESD of the colon was assessed. Among 35 patients who underwent ESD of the colon in Kushiro Rosai Hospital between April 2019 and September 2019, 26 patients who underwent ligation using the D-L clips technique for the post-ESD ulcer bed were included in this retrospective study. Continuation or cessation of antithrombotic agents was based on the Guidelines for Gastroenterological Endoscopy in Patients Undergoing Antithrombotic Treatment. The rate of en bloc R0 resection was 97.1%, the median length of the resected specimen was 3.2 cm (interquartile range [IQR], 2.8-3.8 cm), and the complete ligation rate was 88.5% (23 of 26). Excluding patients with lesion sites in the rectum below the peritoneal reflection, the complete ligation rate was 95.5% (21 of 22). The median duration of the ligation procedure was 20 minutes (IQR, 16-24 minutes). The only delayed procedural adverse event was post-ESD coagulation syndrome in 1 patient. Incomplete ligation was significantly more frequent in patients with lesion sites in the inferior rectal valve/anal verge area (P= .0269). Ligation using the D-L clips technique without an adhesive agent is feasible for closing ulceration after ESD of the colon, whereas other techniques may be necessary for lesions in the rectum below the peritoneal reflection.