Endoscopic submucosal dissection (ESD) for the treatment of esophageal mucosal lesions often leads to postoperative stenosis, causing difficulty in swallowing, known as dysphagia. In this study, we developed an in situ cross-linkable powder composed of alginate, gelatin, transglutaminase (TG), and calcium chloride ions (Ca2+), which can be administered through a 1.5 m-long and 3.2 mm-diameter endoscopic instrument channel. The powdered mixture of alginate and gelatin quickly formed a hydrogel by absorbing body fluids and was cross-linked by TG and Ca2+, which adhered ex vivo to porcine submucosal layers for over 2 weeks. In addition, we developed a new submucosal exfoliation model in rats that induced severe stenosis, similar to the ESD-induced stenosis models in clinical practice. When administered to the new rat model, the powder system effectively reduced the severity of esophageal stenosis based on body weight change monitoring, anatomical findings, and histological analysis. The body weight of the rats was maintained at the initial weight on postoperative day 14 (POD14), and epithelialization on POD7 and 14 improved to almost 100%. Additionally, collagen accumulation and the number of α-SMA-positive cells decreased due to powder administration. Therefore, these findings indicate that the in situ cross-linkable powder can prevent esophageal stenosis after ESD.

Postoperative stricture and refractory stricture are severe adverse events which occur after expansive esophageal endoscopic submucosal dissection (ESD). The aim of this study was to assess the efficacy of steroid injection, polyglycolic acid (PGA) shielding, and of additional steroid injection thereafter for the prevention of refractory esophageal stricture.

This is a retrospective cohort study of 816 consecutive cases of esophageal ESD performed between 2002 and 2021 at the University of Tokyo Hospital. After 2013, all patients with a diagnosis of superficial esophageal carcinoma covering over 1/2 the esophageal circumference underwent preventive treatment immediately after ESD with either "PGA shielding", "steroid injection", or "steroid injection + PGA shielding". Additional steroid injection was performed for high-risk patients after 2019.

The risk of refractory stricture was especially high in the cervical esophagus (OR 24.77, p = 0.002) and after total circumferential resection (OR 894.04, p < 0.001). "Steroid injection + PGA shielding" was the only method significantly effective in preventing stricture occurrence (OR 0.36; 95% CI 0.15-0.83, p = 0.012). This method also decreased the risk of refractory stricture (OR 0.38; 95% CI 0.10-1.28, p = 0.096), but additional steroid injection was the only significantly effective method for prevention of refractory stricture (OR 0.42; 95% CI 0.14-0.98, p = 0.029).

Combining steroid injection and PGA shielding is effective for preventing post-ESD stricture and refractory stricture. Additional steroid injection is a viable option for patients at high-risk for refractory stricture.

Gastrointestinal (GI) perforations are one of the major adverse events of endoscopic procedures. Polyglycolic acid (PGA) sheets with fibrin glue have been reported to close GI perforations. However, its clinical outcome has not yet been fully investigated; thus, we conducted a multicenter retrospective observational study to assess the efficacy of PGA sheeting for GI perforation.

The medical records of patients who underwent PGA sheeting for endoscopic GI perforations between April 2013 and March 2018 in 18 Japanese institutions were retrospectively analyzed. PGA sheeting was applied when the clip closure was challenging or failed to use. Perforations were filled with one or several pieces of PGA sheets followed by fibrin glue application through an endoscopic catheter. Nasal or percutaneous drainage and endoscopic clipping were applied as appropriate. Clinical outcomes after PGA sheeting for intraoperative or delayed perforations were separately evaluated.

There were 66 intraoperative and 24 delayed perforation cases. In intraoperative cases, successful closure was attained in 60 cases (91%). The median period from the first sheeting to diet resumption was 6 days (interquartile range [IQR], 4-8.8 days). Large perforation size (≥ 10 mm) and duodenal location showed marginal significant relationship to higher closure failure of intraoperative perforations. In delayed perforation cases, all cases had successful closure. The median period from the first sheeting to diet resumption was 10 days (IQR, 6-37.8 days). No adverse events related to PGA sheeting occurred.

Endoscopic PGA sheeting could be a therapeutic option for GI perforations related to GI endoscopic procedures.

The management of postoperative bleeding, after gastric endoscopic submucosal dissection (ESD), has become particularly important because of the recent increase in antithrombotic use. Endoscopic shielding with polyglycolic acid (PGA) sheets has been shown to be effective. However, shrinkage and early displacement of the sheet remain challenges. This study aimed to determine the efficacy and safety of our developed method, named wafer paper and ring-mounted PGA sheet (WaRP).

Twenty-four patients with antithrombotic uptake who underwent the WaRP method following gastric ESD were retrospectively examined. This involved the delivery of a PGA sheet wrapped in wafer paper with ring-thread, and its fixation on the gastric floor using hemoclips. The primary outcome was the technical success rate of the WaRP, and several secondary outcomes were evaluated.

The technical success rate of WaRP was 100%. The procedure lasted a mean of 10.5 min (SD 6.7 min). The prevalence of complete retention at follow-up endoscopy was 83.3% (20/24). There were no WaRP-associated complications, but post-ESD hemorrhage occurred in two patients undergoing hemodialysis (8.3%).

The WaRP method is a simple and reliable means of PGA sheet delivery and placement that reduces the incidence of post-ESD hemorrhage.

Endoscopic resection has been the standard treatment for intramucosal esophageal cancers (ECs) because of the low risk of lymph node metastases in the lesions. In recent years, endoscopic submucosal dissection (ESD), which can resect large ECs, has been performed. However, the risk of esophageal stricture after ESD is high when the mucosal defect caused by the treatment exceeds 3/4 of the circumference of the lumen. Despite the subsequent high risk of luminal stricture, ESD has been performed even in cases of circumferential EC. In such cases, it is necessary to take measures to prevent stricture. Therefore, in this review, we aimed to clarify the current status of stricture prevention methods after esophageal ESD based on previous literature. Although various prophylactic methods have been reported to have stricture-preventing effects, steroid injection therapy and oral steroid administration are mainstream. However, in cases of circumferential EC, both steroid injection therapy and oral steroid administration cannot effectively prevent luminal stricture. To solve this issue, clinical applications, such as tissue shielding methods with polyglycolic acid sheet, autologous oral mucosal epithelial sheet transplantation, and stent placement, have been developed. However, effective prophylaxis of post-ESD mucosal defects of the esophagus is still unclear. Therefore, further studies in this research field are needed.

Background and study aims  Delayed bleeding is one of the most serious adverse events of gastric endoscopic submucosal dissection (ESD), especially in patients taking antithrombotic therapy. This study aimed to evaluate the utility and safety of a shielding method with autologous fibrin glue and polyglycolic acid (PGA) sheets for patients undergoing gastric ESD who are receiving antithrombotic therapy. Patients and methods  One hundred twenty-three patients who were treated with gastric ESD while receiving antithrombotic therapy between December 2014 and September 2017 were enrolled in this study. Patients who received the shielding method were classified into the shielding group. Others were classified into the conventional group. Various clinico-pathological factors were retrospectively compared between the two groups. Results  The shielding group consisted of 38 patients, and the conventional group consisted of the remaining 85 patients. In the shielding group, the rate of continuation of antithrombotic therapy was significantly higher (68.4 % vs 41.2 %). Incidence of delayed bleeding was lower in the shielding group (2.6 %, 1/38) than in the conventional group (14.1 %, 12/85). In the propensity score-adjusted logistic regression analysis, the delayed bleeding rate in the shielding group tended to be lower than in the conventional group ( P  = 0.070). Allogeneic transfusion was performed in eight patients (8/85, 9.4 %) in the conventional group and none in the shielding group ( P  = 0.047). No adverse event associated with endoscopic shielding were observed in the shielding group. Conclusions  This study suggests that a shielding method with autologous fibrin glue and PGA sheet effectively prevents delayed bleeding after gastric ESD in patients receiving antithrombotic therapy.

Although there have been several reports of treating large post-endoscopic submucosal dissection (ESD) ulcers by covering them with a polyglycolic acid sheet (PGAs), this approach presents problems regarding PGAs delivery. This study assessed the usefulness of a device delivery station system (DDSS) to evaluate the appropriate and rapid PGAs coating method with DDSS.

Thirty-nine of 41 patients who were diagnosed with early gastric cancer over 20 mm in diameter and pathologically diagnosed with well-differentiated adenocarcinoma were randomly allocated to the following two groups according to delivery method: the conventional PGAs delivery group (C group) (n = 19) and the new DDSS group (DDSS group) (n = 20). The primary outcome was the coating area per minute in the C group and DDSS group (cm²/min).

There were significant differences in the coating time (min), with values of 34.1 (15.0-60.7) vs. 16.85 (11.5-27.2) min for the C group and DDSS group, respectively (p = 0.001). There was also a significant difference in coating area per minute, with values of 0.261 (0.02-1.00) and 0.96 (0.173-2.06) cm²/min for the C group and DDSS group, respectively (p = 0.001). There were four cases of post-ESD bleeding (1-7 days after ESD) in the C group compared with 0 in the DDSS group, which represented a significant difference (p = 0.030).

The DDSS was very useful for rapidly delivering and tightly attaching a PGAs to control post-ESD bleeding.

University Hospital Medical Network (UMIN) 000026377.

There have been several reports that steroid administration is effective at preventing strictures after endoscopic submucosal dissection (ESD). However, adverse events after steroid use are of great concern. We have reported that shielding with a polyglycolic acid (PGA) sheet and fibrin glue can be useful for prevention of stricture after ESD. We conducted a retrospective analysis of efficiency of shielding with a PGA sheet and fibrin glue for prevention of esophageal stricture compared with intralesional steroid injection. ESD was performed on a total of 489 lesions in 400 patients for superficial esophageal cancer from January 2012 to July 2016. Of these, 39 lesions were enrolled in the study group (PGA sheet and fibrin glue) and 31 lesions were enrolled in the control group. The incidence of postoperative stricture at 6 weeks and the number of sessions of endoscopic balloon dilatation (EBD) required to resolve any strictures were evaluated. The post-ESD stricture rate was 9.1% in the study group (3/33 patients), which was not significantly lower than the stricture rate of 10.3% in the historical control group (3/29 patients; p = 1.00). The mean number of EBD was 0.057 ± 0.24 in the study group and 1.9 ± 5.1 in the control group, which was not significant (P = 0.95). PGA sheet and fibrin glue appear to be a promising option for the prevention of esophageal stricture similar to the effect of intralesional steroid injection.

In Japan, endoscopic resection (ER), including endoscopic mucosal resection and endoscopic submucosal dissection, is widely performed for superficial esophageal neoplasms and accepted as a minimally invasive treatment. Perforation is a major complication of ER, with an incidence rate of 1-5%. While conservative treatment has become a more common choice, surgical treatment of perforations is sometimes required, especially for large perforations. Of 1408 cases of esophageal ER that have been performed, 17 cases of perforation occurred at the Cancer Institute Hospital between 2005 and 2016. Most cases were treated with endoscopic clipping and managed conservatively; however, 2 cases were not eligible for endoscopic closure. We report two cases of large perforations of 15 and 20 mm, respectively. Both cases were treated conservatively with endoscopic tissue shielding, in which the perforations were covered with a large polyglycolic acid (PGA) sheet that was affixed with fibrin glue. Neither of the cases required open surgery. In both cases, feeding started three weeks after the procedure (19 and 21 days), and both were discharged within a month (29 and 30 days). In conclusion, tissue shielding with PGA sheets in large perforations after esophageal ER is a good choice to safely proceed with conservative treatment. On the other hand, endoscopic clipping is effective and reasonable for small perforations.

Endoscopic submucosal dissection (ESD) has become widely accepted as a standard method of treatment for superficial gastrointestinal neoplasms because it enables en block resection even for large lesions or fibrotic lesions with minimal invasiveness, and decreases the local recurrence rate. Moreover, specimens resected in an en block fashion enable accurate histological assessment. Taking these factors into consideration, ESD seems to be more advantageous than conventional endoscopic mucosal resection (EMR), but the associated risks of perioperative adverse events are higher than in EMR. Bleeding after ESD is the most frequent among these adverse events. Although post-ESD bleeding can be controlled by endoscopic hemostasis in most cases, it may lead to serious conditions including hemorrhagic shock. Even with preventive methods including administration of acid secretion inhibitors and preventive hemostasis, post-ESD bleeding cannot be completely prevented. In addition high-risk cases for post-ESD bleeding, which include cases with the use of antithrombotic agents or which require large resection, are increasing. Although there have been many reports about associated risk factors and methods of preventing post-ESD bleeding, many issues remain unsolved. Therefore, in this review, we have overviewed risk factors and methods of preventing post-ESD bleeding from previous studies. Endoscopists should have sufficient knowledge of these risk factors and preventive methods when performing ESD.

Background and Study Aims. When performing endoscopic submucosal dissection (ESD) for patients on antithrombotic agents, the frequency of delayed bleeding is expected to increase. The endoscopic polyglycolic acid (PGA) felt and fibrin glue sealing method could be a new method for prevention of delayed bleeding. Patients and Methods. The safety and efficacy of the endoscopic tissue sealing method with PGA sheets and fibrin glue for the prevention of post-ESD bleeding were examined in 104 patients taking antithrombotic agents. During the study period, 70 patients taking antithrombotic agents did not undergo the sealing method, 36 patients discontinued antithrombotic agents, and 724 patients had not received antithrombotic therapy. Results. Delayed bleeding rates were 3.8% (4/104) in the sealing group, 12.9% (9/70) in the nonsealing group, 8.3% (3/36) in the discontinuation group, and 4.6% (33/724) in the nonantithrombotic therapy group. Thus, the delayed bleeding rate was significantly lower in the sealing group than in the nonsealing group and comparable to that in the nonantithrombotic therapy group. Conclusions. This PGA felt and fibrin glue sealing method might become a promising post-ESD bleeding prevention method in patients taking antithrombotic agents (UMIN000013990, UMIN000013993).

To prevent severe esophageal stenosis after aggressive endoscopic submucosal dissection (ESD), our group previously reported an efficient treatment using cell sheets that had been fabricated from patient cells. However, this transplantation procedure had not been easy for every endoscopist and needed to be improved to derive the full effect of epithelial cell sheets.

To develop an endoscopic device that enables easy and effective cell sheet transplantation and to evaluate its performance and clinical feasibility.

Animal study.

Animal experimentation laboratory.

Three pigs underwent circumferential esophageal ESD while under general anesthesia. A total of 12 cell sheets were endoscopically transplanted to the ESD site; 6 cell sheets were transplanted by using an endoscopic device that we developed, and 6 cell sheets were transplanted by using the conventional method.

Procedure time, transplanted area on the ESD site, transplantation success rate, and monitoring of adverse events or incidents.

The device allowed successful transplantation of all cell sheets with a shorter procedure time than with the conventional method (4.8 ± 0.8 minutes vs 13.3 ± 5.7 minutes, respectively) (P = .005) and onto a larger area (111.3 ± 56.3 mm(2) vs 41.8 ± 4.2 mm(2), respectively) (P = .023) with a higher success rate (100% vs 83%, respectively). No adverse incidents were monitored in each method.

Animal study, small sample.

A newly designed endoscopic cell sheet transplantation device would be useful.