Introduction

Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are both standard endoscopic treatments for early-stage gastrointestinal tumors. Submucosal fluid injection is an important part of endoscopic procedure, increasing the space between the lesion and the muscle layer and enabling easy and safe resection. Recently, PuraLift^TM (3-D Matrix Ltd, Tokyo, Japan), a novel submucosal injection solution made from self-assembling peptide hydrogel (SAP) was developed in Japan. SAP is fully synthetic and consists only of amino acids present in the human body, giving it the advantages of biodegradability and biocompatibility over conventional solutions. In addition, the 3D structure of the hydrogel supports cell proliferation in vitro, and self-assembling peptide hydrogel (SAPH) may promote wound healing. However, there are no reports on the effect of SAPH on ulcer healing after endoscopic resection.

Aims & Methods

The aim of this study was to assess the effect of SAPH on wound healing after endoscopic resection. EMR procedures were performed in the stomach of 4 living pigs with 3 patters of submucosal injection solution; normal saline injection group (NS); sodium alginate injection group (SA); PuraLift^TM injection group (SAPH). Each pig received 3 separate submucosal injections with 3 mL of the different solutions and then EMR was performed using a 15mm diameter snare. Immediately after EMR (W0) and on week 1(W1) and week 2(W2), we measured the ulcer diameter endoscopically using a measuring device. On week 3(W3) after EMR, all pigs were sacrificed and necropsied by en-bloc gastrectomy, followed by macroscopic measurement of ulcer diameter. All wound sites of the resected specimens were examined histopathologically by haematoxylin and eosin (HE) and Masson's trichrome (MT) and immunohistochemistry staining (αSMA, CD3, CD 31, CD107a). The ulcer reduction rate was calculated as follows : [(ulcer diameter at W0) -(ulcer diameter at week X)] / (ulcer diameter at W0) x 100(%). Ulcer epithelialisation and submucosal foreign bodies were assessed by HE staining, tissue damage in the muscle layer and the thickness of the fibrotic layer by MT staining. Five random fields at each wound site were photographed, and the average rate of positive areas by immunostaining in each injection solution group was calculated.

Results

Ulcer reduction rate at W1 was higher in SAPH group and SA group than NS group (24.1±13.5%; 24.6±17.9%; -6.9±7.6%; p<0.05), b but there were no significant differences at W2 and W3 among three groups. Complete epithelialisation of the ulcer occurred in all except one case of NS group. In SA group, all four cases showed residual injection solution in the submucosal layer with foreign body giant cell reaction and fibrous tissue growth. In contrast, in SAPH group, only one case showed a focal foreign body giant cell reaction without residual injection solution. The thickness of the fibrotic layer is greater in SA group than SAPH and NS groups (SA: 4.2±0.8mm, SAPH: 1.6±0.4mm, NS: 2.0±1.2mm, p<0.05). Tissue damage was not observed in either group. There were no differences in the rates or positive area of αSMA, CD3 and CD31 staining between groups. In contrast, the rates of positive area of CD107a staining were significantly higher in SA group than SAPH and NS group(SA: 13.9±1.0%, SAPH: 5.7±2.2%, NS:1.2±2.1%, p<0.001), indicating a high degree of macrophage accumulation.

Conclusion

SAPH induced good healing after EMR and was more biodegradable and biocompatible than sodium alginate.

Introduction

Linked color imaging (LCI), a unique image-enhanced endoscopy technique, expands the color range to enhance the recognition of subtle mucosal differences, facilitating early lesion detection. Recently, the advantage of LCI in cancer visibility and detection has been reported especially in Helicobacter pylori (H. pylori)-negative gastric cancer including cases post-eradication.¹ However, the correlations between the color of LCI’s visualized mucosa and histological findings have not been thoroughly investigated.

Aims & Methods

This study aimed to investigate relationships between color values and histological findings visualized by LCI in H. pylori-negative gastric cancer.
Thirty-two patients with H. pylori-negative, differentiated-type intramucosal gastric cancer (≤20 mm) who underwent endoscopic submucosal dissection were retrospectively reviewed. Images captured with LCI and white light imaging (WLI) were analyzed using the CIE1976 (L^*a^*b^*) color space, as defined by the International Commission on Illumination (CIE).² Three regions of interest, each measuring 10 × 10 pixels, were set on the malignant tumor and adjacent mucosa to the border. The values of a^*(red-green) and b^* (yellow-blue) and the color difference (ΔE), which represents the overall difference between the two colors, were calculated. Histopathological evaluation using Hematoxylin-Eosin stained specimens was performed to highlight the demarcation between cancerous and noncancerous mucosa in a width of 1.0 mm inside and outside the lesion. Vascular density, glandular density, mucosal thickness, and the degrees of intestinal metaplasia (IM) were measured. Vascular density was calculated as the percentage of the occupied blood vessels in an area up to 200 μm from the surface. And the proportion of IM relative to the glands was measured and classified as the severe IM (≥60%), moderate IM (≥30% and <60%), or mild IM (<30%) groups.

Results

LCI significantly increased ΔE between the cancer and surrounding mucosa compared with WLI (P < 0.001); however, no significant differences in Δa^* and Δb^* were observed between LCI and WLI. Moderate correlations were observed between LCI a^* values and vascular density (ρ = 0.39, P < 0.001) and between LCI b^* values and the proportion of IM (ρ = −0.49, P < 0.001). Furthermore, the vascular density of cancer in the 0−100 μm depth showed a moderate correlation with the LCI a^* values (ρ = 0.41, P < 0.001). Severe IM significantly decreased the LCI b^* values compared with mild and moderate IM (P = 0.02, P < 0.001).

Conclusion

LCI quantitatively visualizes the superficial vascularity of cancer lesions and the presence of IM of the background mucosa in H. pylori-negative patients. It is a potential noninvasive tool for gastric cancer risk stratification and early detection.

References

1. Kato M, Ono S, Kawada K et al. Diagnostic performance of linked color imaging for gastric cancer by Helicobacter pylori infection status: a subanalysis of the large-scale, multicenter randomized controlled trial LCI-FIND. Helicobacter 2024; 29: e1308.
2. Kuehni RG. Color-tolerance data and the tentative CIE 1976 L a b formula. J Opt Soc Am 1976; 66: 497–500.

Disclosure

Shoko Ono has received lecture and/or consulting fees from Fujifilm.

Introduction

Endoscopic submucosal dissection (ESD) is widely accepted as the first-line treatment for early-stage EC, especially for endoscopic resection. However, stenosis is almost inevitable, when a circumferential mucosal defect involves over three-fourths of the esophageal circumference.¹ Multiple balloon dilation sessions are occasionally required, lowering patients’ quality of life.Local injection of corticosteroids, or oral corticosteroids administration are used to prevent strictures after ESD. Although these methods are effective, adverse events might occur. The application of polyglycolicacid (PGA) sheets combined with fibrin adhesive has also been reported to prevent stricture after esophageal ESD, but the effect of PGA alone is insufficient, steroids must be used in combination.² The administration of recombinant basic fibroblast growth factor (bFGF) to skin wounds can accelerate acute and chronic wound healing.³ However, its use in gastrointestinal tract treatment remains unreported, and its efficacy in preventing stricture after esophageal ESD is unknown.

Aims & Methods

This study aimed to evaluate the effectiveness of the combination of PGA sheets and bFGF through a comparative analysis. We resected a complete porcine esophagus circumference section by ESD. To investigate the preventive effect of bFGF on esophageal stricture formation after ESD, we endoscopically applied bFGF-soaked polyglycolic acid (PGA) sheets onto the wound bed after ESD and fixed them by spraying fibrin glue (PGA+bFGF group), PGA sheets alone onto the wound bed and fixed them by spraying fibrin glue (PGA group), or nothing (control group). sevaluated the mucosal constriction rate, and also performed several histological evaluations. We photographed five fields per section from each pig and measured the area stained with anti–α SMA antibody and anti–calponin-1 antibody per field of view (×200) with a digital image analyzer. To evaluate the state of tissue regeneration in the entire wound, we measured the thickness from the bottom edge of the area stained with Elastica–Masson staining to the surface layer of the wound.

Results

Esophageal stricture was significantly suppressed in the PGA+bFGF group compared with that in the control group (control: 63.6%, PGA: 42.2%, PGA+bFGF: 36.7%, p<0.05 for PGA+bFGF group vs control group). Moreover, areas stained with anti–α SMA antibody were significantly less in the PGA+bFGF and PGA groups compared with those in the control group (PGA+bFGF: 16.7%, PGA: 15.5%, control: 24.0%, p<0.01 for PGA+bFGF and PGA groups vs control group). Significant suppression in areas stained with anti–calponin-1 antibody was also observed in the PGA+bFGF and PGA groups compared with those in the control group (PGA+bFGF: 24.4%, PGA: 19.8%, control: 32.9%, p<0.001 for PGA+bFGF and PGA groups vs control group). Regarding the thickness of the fibrous layer in the wound, the difference between the thinnest and thickest areas was smallest in the PGA+bFGF group compared with the PGA and control groups (PGA+bFGF: 467.3, PGA: 934.9, control:726.2 μm, p<0.05 for PGA+bFGF group vs control group).

Conclusion

Stenosis after esophageal ESD is related to fibrosis in the acute phase. Administration of PGA and bFGF suppresses myofibroblast activation in the acute phase, thereby preventing esophageal constriction in pigs.

References

1. Miwata T, Oka S, Tanaka S, Kagemoto K, Sanomura Y, Urabe Y, et al. Risk factors for esophageal stenosis after entire circumferential endoscopic submucosal dissection for superficial esophageal squamous cell carcinoma. Surg Endosc. 2016;30(9):4049-56.
2. Sakaguchi Y, Tsuji Y, Shinozaki T, Ohki D, Mizutani H, Minatsuki C, et al. Steroid injection and polyglycolic acid shielding to prevent stricture after esophageal endoscopic submucosal dissection: a retrospective comparative analysis (with video). Gastrointest Endosc. 2020;92(6):1176-86 e1.
3. Akita S, Akino K, Imaizumi T, Hirano A. Basic fibroblast growth factor accelerates and improves second-degree burn wound healing. Wound Repair Regen. 2008;16(5):635-41.

Introduction

Ethanol-induced gastric ulcers are common and the treatment options are limited. Escin, a extract from the horse chestnut plant, has been proven to have therapeutic effects in improving inflammation, edema, and vascular permeability. However, its effects and mechanisms on ethanol-induced gastric mucosal injury are not yet clear.

Aims & Methods

This study aims to explore the protective effect of Escin on ethanol-induced gastric mucosal injury and its potential mechanisms, providing a new drug choice for the treatment of ethanol-induced gastric ulcers. For this purpose, a control, ethanol, ethanol+Escin , and ethanol+omeprazole groups were established in male SD rats to compare and analyze the ulcer index and histopathological scores of each group. The network pharmacology approach was used to predict potential targets of Escin related to gastric ulcers. Apoptotic proteins, NF-κb inflammatory pathway proteins, inflammatory factors, and related mRNA expression were analyzed by methods such as Immunofluorescence (IF), Immunohistochemistry (IHC), Western Blot (WB), real-time quantitative fluorescence PCR (q-PCR), and enzyme-linked immunosorbent assay (Elisa). Furthermore, an ethanol-induced GES-1 cell injury model was established to evaluate the protective effect of Escin. Finally, Transcriptomic sequencing was performed to identify key regulatory genes.

Results

The study found that Escin significantly reduced the damage of ethanol to gastric mucosal tissues. Network pharmacology analysis predicted that Escin is closely related to inflammatory pathways such as NF-κb in the treatment of gastric ulcers. IHC and WB results showed that Escin reduced the loss of gastric mucosal surface markers MUC5AC, TFF2, and gastric mucosal barrier protein O-ccludin, inhibited the expression of inflammatory factors IL-1β, IL-6, TNF-α, and apoptosis-related proteins BAX, Caspase-3, and promoted the expression of anti-apoptotic protein BCL-2. IF further revealed that Escin prevented the nuclear translocation of NF-κb, thereby inhibiting the activation of the NF-κb pathway. Elisa results showed a decrease in inflammatory factor levels in the plasma of rats in the Escin group, while q-PCR results demonstrated that Escin downregulated the expression levels of inflammatory factor mRNA in gastric tissues. Cell proliferation experiments also confirmed the protective effect of Escin against ethanol-induced damage. Finally, Transcriptomic analysis revealed significant upregulation of 27 inflammation-related genes in ethanol-treated gastric tissues. Notably, nine genes—Birc3, Bcl3, SOCS1, SOCS3, Ccl2, Cx3cl1, Pim1, SGK1, and OSMR—were identified as positive regulators of the TNF-α/NF-κB signaling axis through functional annotation and pathway enrichment analysis.

Conclusion

Escin exerts a protective effect on ethanol-induced gastric mucosal damage by inhibiting the TNF-α/NF-κB pathway, reducing the expression of inflammatory factors and the level of cell apoptosis. Escin, as a novel therapeutic drug for ethanol-induced gastric ulcers, has certain clinical translational application value, but further clinical trials are needed to confirm the results.

Introduction

Treatment of gastrojejunal anastomotic ulcers, also known as marginal ulcers, is challenging, especially when established techniques such as proton pump inhibitor have failed.

Pura Stat, is a biocompatible transparent synthetic peptide hemostatic gel that is indicated for hemostatis of bleeding in small blood vessels or capillaries of the GI tract and vascular anastomoses. Our aim was to evaluate the feasibility of PuraStat in the setting of non-healing marginal ulcers when used in addition to proton pump inhibitor (PPI) therapy after failed standard therapies

Aims & Methods

We conducted a multi-center prospective case study of adult patients that underwent PuraStat application (3 ml) for marginal ulcers after failing multiple initial therapies with proton pump inhibitors for at least 8 weeks

Results

A total of 10 patients were included in the study. Patients who had an initial presentation of pain, nausea, anemia, with confirmed anastomotic ulceration seen on endoscopy were included. A total of 3mL of Purastat was applied on each of these patients’ ulcers, and a repeat endoscopy was performed to evaluate ulcers at ~3months. 9 out of 10 patients showed healing of marginal ulcer on repeat endoscopy in 3 months, while one patient did not present for repeat endoscopy. 9 out of 10 patients showed clinical improvement in their symptoms (90%), and one patient did not show improvement in their symptoms.

Conclusion

PuraStat is an important useful addition to the therapeutic toolbox for the treatment of anastomotic ulcers. Our small prospective case series shows effectiveness in symptom relief as well as clinical healing of anastomotic ulcers. Larger randomized clinical trials are needed.

References

1. Branchi F, Klingenberg-Noftz R, Friedrich K, Bürgel N, Daum S, Buchkremer J, Sonnenberg E, Schumann M, Treese C, Tröger H, Lissner D. PuraStat in gastrointestinal bleeding: results of a prospective multicentre observational pilot study. Surgical Endoscopy. 2022 May;36(5):2954-61
2. Tian Y, Rogers AM. Marginal ulcer: diagnosis and treatment. Clinical Algorithms in General Surgery: A Practical Guide. 2019:827-9.

Introduction

Endoscopic submucosal dissection (ESD) is a widely used treatment for early gastric tumors, but delayed bleeding remains a significant complication, especially in patients receiving antithrombotic therapy. As the population ages, the need for effective preventive strategies is growing.
Although various methods such as PGA sheets and fibrin glue have been explored, no definitive approach has been established. Moreover, a reliable animal model to evaluate strategies for preventing delayed bleeding does not currently exist.
To address this issue, Taguchi et al. developed a novel endoscopically sprayable wound dressing composed of hydrophobized gelatin microparticles (hMPs), which exhibit strong tissue adhesion. In preclinical studies using miniature swine, hMPs have shown various therapeutic effects on post-ESD ulcers, including anti-inflammatory and anti-fibrotic effects, as well as promotion of perforation closure.

Aims & Methods

This study aimed (1) to establish an animal model of delayed bleeding after gastric mucosal injury, and (2) to evaluate the preventive effect of hMPs using this model.
(1) A delayed bleeding model was created by producing mucosal defects in the stomach using endoscopic mucosal resection with ligation (EMR-L), followed by continuous heparin infusion to maintain an activated clotting time (ACT) ≥220 seconds, which consistently induced delayed bleeding.
(2) Using this model in three miniature swine, we evaluated the preventive effect of hMPs by endoscopically spraying hMPs onto a total of 36 ulcers (12 per animal). We assessed delayed bleeding, as well as the retention and coverage of hMPs at the ulcer base.

Results

(1) In the heparin-treated group, delayed bleeding was observed in 3 of 4 animals (75%). All three animals whose maximum ACT before the start of continuous heparin infusion exceeded 220 seconds developed delayed bleeding. In contrast, no ACT prolongation or delayed bleeding was observed in the non-heparin-treated group (n = 3) at 24 hours.
(2) In the hMPs spray group (n = 3), all animals had ACT ≥220 seconds, and hMPs were sprayed onto 12 mucosal defects per animal (total 36 lesions). No delayed bleeding occurred in any animal. hMPs were retained at all ulcer sites, yielding a 100% retention rate. The ulcer base coverage by hMPs was as follows: 100% in 55.6% of sites (20/36), 75–99% in 19.4% (7/36), and 50–74% in 25.0% (9/36). No sites had coverage below 50%.
Exposed vessel-like structures were identified in 36.1% of the ulcers (13/36), and hMPs were found to adhere to all of these sites.

Conclusion

An animal model of delayed bleeding after endoscopic resection of the gastric mucosa was successfully established by maintaining an ACT ≥220 seconds through continuous heparin infusion. In this model, hMPs remained well on the ulcer base and provided broad coverage of mucosal defects. These findings suggest that hMPs may be effective in preventing post-endoscopic bleeding, particularly in patients receiving antithrombotic therapy.

Introduction

Endoscopic submucosal dissection (ESD) is the technique of choice for treating early gastric cancer deemed to have very low risk of lymph node metastasis based on endoscopic evaluation. However, currently, up to 20% of ressected lesions do not meet curative criteria, underlining the importance of patient selection.

Aims & Methods

We aimed to evaluate predictive factors for non curative ressection. We conducted a retrospective cohort study including consecutive gastric epithelial lesions removed by ESD between January of 2005 and June of 2024. Incomplete ESD were excluded. Non curative resection was defined using the high-risk resection criteria from the European Society of Gastrointestinal Endoscopy guidelines. Univariate and multivariate analysis were used to identify predictive factors.

Results

From 990 ESD, 974 were included in the final analysis: median size of lesion 19mm (P25-P75: 15-25), presence of ulceration in 25 (2.8%), deep submucosal invasion in 74 (7.6%), en bloc resection in 944 (96.9%), R0 resection in 901 (92.5%) and non curative resection in 116 (11.9%). In this sample, the following independent predictive factors for non curative resection were identified: location on the superior third of the stomach [adjusted Odds Ratio (aOR) 2.275; IC95% 1.248-4.148], lesion size > 20mm (aOR 4.212; IC95% 2.618-6.775), depressed/ulcerated lesion (aOR 2.394; IC95% 1.328-4.315) or sessile/pedunculated lesion (aOR 4.186; IC95% 2.083-8.411), presence of high-grade dysplasia (aOR 4.372; IC95% 2.139-8.939) or carcinoma (aOR 12.484; IC95% 5.995-25.998) in previous biopsies.

Conclusion

Location, size and morphology of lesion, as well as previous biopsy results are predictive factors for non curative resection, and may assist in decision-making regarding treatment alocation of gastric superficial lesions.

References

Dinis-Ribeiro M, et al. Management of epithelial precancerous conditions and early neoplasia of the stomach (MAPS III): European Society of Gastrointestinal Endoscopy (ESGE), European Helicobacter and Microbiota Study Group (EHMSG) and European Society of Pathology (ESP) Guideline update 2025. Endoscopy, 2025 May;57(5):504-554. doi: 10.1055/a-2529-5025.
Vasconcelos AC, et al. Endoscopic Resection of Early Gastric Cancer and Pre-malignant Gastric Lesions. Cancers, 2023 Jun 7;15(12):3084. doi: 10.3390/cancers15123084.