Since 2020, multiple large-scale studies (CODE BLUE-J) in Japan have accelerated the accumulation of evidence on colonic diverticular bleeding (CDB). This review summarizes the latest findings regarding CDB epidemiology and endoscopic hemostasis. Recent data show that CDB has become the most common cause of lower gastrointestinal bleeding in Japan, driven by an aging population and the increased use of antithrombotic medications. Although 70%-90% of patients achieve spontaneous hemostasis, rebleeding occurs in up to 35% of cases within 1 year. Despite an overall mortality rate of < 1%, patients with CDB can present with hypovolemic shock and may require urgent intervention. There are no effective pharmacological treatments for controlling CDB. Therefore, endoscopic therapy plays a crucial role in its management. Based on available evidence, both clipping and endoscopic band ligation are considered effective initial treatments. Recent studies indicate that direct clipping reduces early rebleeding compared with indirect clipping, while endoscopic band ligation achieves lower rebleeding rates (13%-15%) than clipping. The choice between direct clipping and endoscopic band ligation depends on the diverticulum location and the presence of active bleeding. Newer techniques, such as over-the-scope clip and self-assembling peptide application, have shown potential, but require further study. The detection of the bleeding source remains challenging because accurate identification is essential for successful hemostasis. Additional research is needed to refine the endoscopic diagnostic and therapeutic techniques, prevent rebleeding, and improve patient outcomes.

This study evaluates the effectiveness of PuraLift, a novel self-assembling peptide-based submucosal injection solution, in endoscopic submucosal dissection (ESD) procedures. We compared its performance to MucoUp in a variety of organ-spanning lesions (esophagus, stomach, and colon/rectum).

We included 40 consecutive ESD lesions from our hospital, with 19 treated using PuraLift and 21 using MucoUp. Special cases (such as those with ulcerative colitis, evident fibrosis due to post-treatment scars, and circumferential esophageal cases) and the cases that used device without waterjet function were excluded. Endoscopists assessed the satisfaction of submucosal lifting through needle injection on a 5-point scale. Firmness during local injection by the assistant for the PuraLift group was compared to MucoUp (MucoUp was set as a baseline score of 3) using a 5-point scale.

The firmness during local injection was significantly lower with PuraLift compared to MucoUp across all locations: esophagus (1 (1-2) vs. 3 (3-3), p = 0.018), stomach (1.5 (1-2) vs. 3 (3-3), p < 0.001), and colon/rectum (2 (1-2) vs. 3 (3-3), p < 0.001). However, there were no significant differences between PuraLift and MucoUp in terms of endoscopist satisfaction with lifting, amount of solution injected, glycerol used via jet function, or procedure time for any organ.

PuraLift, with its novel mechanism, offers comparable lifting satisfaction to MucoUp but with less firmness during injection. It presents a promising alternative as a local injection solution in ESD procedures.

Endoscopic submucosal dissection (ESD) is widely used to treat gastrointestinal mucosal and submucosal lesions. However, it may cause bleeding, perforation, and stricture. Although these complications can be avoided by introducing materials such as polyglycolic acid and carboxymethyl cellulose sheets, such approaches are expensive and time-consuming. Herein, we report a hydrogel prepared by combining a colloidal solution composed of konjac glucomannan (KGM) and sodium alginate (SA) and a fixative solution containing ε-poly-l-lysine (ε-PLL) and calcium chloride. The two solutions were mixed on the wound surface to form the KGM/SA/ε-PLL hydrogel through hydrogen bonds, coordination bonds, and electrostatic attraction. The effectiveness and convenience of applying the KGM/SA/ε-PLL hydrogel to promote wound healing in the esophagus and colon were assessed in vitro and in vivo. We found that the hydrogel stimulated epithelial proliferation, reduced inflammation, promoted recapillarization, and inhibited fibrosis in the esophagus and colon. Therefore, the KGM/SA/ε-PLL hydrogel is an effective and convenient agent that can promote post-ESD wound healing and is recommended for ulcer bed protection in daily clinical practice.

PuraStat (3-D Matrix, Tokyo, Japan) is an absorbent localized hemostatic agent that uses self-assembling peptide technology. In this multicenter pilot study, we evaluated the efficacy and safety of endoscopic hemostasis using PuraStat in patients with colonic diverticular bleeding (CDB).

This study involved patients who had CDB with stigmata of recent hemorrhage (SRH) and underwent endoscopic hemostasis with PuraStat monotherapy or combination therapy comprising PuraStat with endoscopic band ligation (EBL) or clipping (group A). Treatment outcomes and adverse events were assessed and compared with those of a previous cohort who underwent endoscopic hemostasis without PuraStat for CDB with SRH (group B). Factors associated with the reduction of recurrent bleeding were subsequently investigated.

PuraStat was used in 25 patients with CDB. The mean patient age was 70.8 years, 13 (52.0%) were men, and the most frequent bleeding sites were in the ascending colon (15 patients [60.0%]). The success rate of endoscopic hemostasis was 100% (25/25); 2 patients were treated with PuraStat monotherapy and 23 with combination therapy (EBL, 13 patients; clipping, 10 patients). The success rates were comparable between groups A and B (100% vs 96.4%, P = 1.000). The rate of recurrent bleeding within 30 days was significantly lower in group A than in group B (4.0% vs 20.9%, P = .047). Multivariate analyses revealed that the addition of PuraStat was associated with the reduced risk of recurrent bleeding (odds ratio, .11; 95% confidence interval, .01-.95; P = .045).

PuraStat can be easily added to conventional hemostatic methods for CDB, which could lower the risk of recurrent bleeding. (Clinical trial registration number: UMIN000053065.).

Although a novel submucosal injection material consisting of a fully synthetic, self-assembling peptide solution, PuraLift, has recently become commercially available in Japan, there are a few reports regarding the usefulness of this solution. The aim of this study was to investigate the feasibility of PuraLift for conventional endoscopic mucosal resection (EMR) in clinical practice.

This multicenter retrospective study was conducted at the endoscopy units of five institutions from January 2023 to May 2023. Consecutive patients who underwent EMR with PuraLift for 5-20-mm colorectal lesions were included in the introduction of this solution at each institute. The primary endpoint was the "effective resection" rate, defined as pathological complete resection, with "effective injection" defined as requiring no more than one additional injection due to adequate maintenance of mucosal lifting during EMR.

In total, 110 lesions in 70 patients were treated by conventional EMR using PuraLift. En-bloc resection was performed for 109 (99%) lesions, and complete resection was performed for 102 (93%) lesions. More than 95% of the lesions were neoplastic. Additional injections were required in only two lesions. Both were single additional injections, and the median overall injection volume was 1.5 mL. Therefore, the effective injection rate was 93% (95% confidence interval, 86%-96%). No adverse events occurred during the study period.

Although direct comparison with other materials is required, PuraLift seems feasible as an injection material for EMR.

Mallory-Weiss syndrome (MWS) is a common cause of gastroesophageal bleeding. Vomiting increases intra-abdominal and intra-esophageal pressures, causing hyperextension of the esophagogastric junction and laceration. Most affected patients respond well to conservative treatment; however, those with active bleeding require endoscopic intervention. Upon contacting blood, PuraStat gels and coats the bleeding point to achieve hemostasis. PuraStat is reportedly effective for non-variceal bleeding and bleeding associated with endoscopic procedures. However, there have been no reports on the use of PuraStat in MWS. Here we report a case in which PuraStat was useful for achieving hemostasis in a patient with MWS and difficult-to-achieve hemostasis. The patient was a 67-year-old man who had undergone coronary artery bypass grafting 1 month earlier and was taking an antithrombotic drug. He visited our hospital with bloody vomiting and melena in the evening and was diagnosed with upper gastrointestinal bleeding for which he underwent endoscopy. MWS with active bleeding was observed in the lower esophagus extending to the esophagogastric junction. We treated the patient with clipping; however, the oozing did not stop because of the large laceration. We applied PuraStat to the bleeding site and confirmed that the oozing had resolved; therefore, the procedure was terminated. The endoscope was reinserted the next day and confirmed the hemostasis. The patient was discharged without further deterioration. In patients with MWS with active bleeding, endoscopic hemostasis is commonly achieved using clips or endoscopic band ligation. However, PuraStat can achieve complete hemostasis when these techniques fail.

The use of radiotherapy has increased in recent years, especially for pelvic neoplasms, and this can result in long-term complications such as recurrent haemorrhagic radiation cystitis (RHC). A 73-year-old male patient presented to a hospital emergency department multiple times with visible haematuria and clots leading to urinary clot retention; he was finally diagnosed with RHC. During the last presentation, the bladder was irrigated continuously with saline using a three-way catheter. During hospitalisation, a cystourethroscopy was performed for bladder evaluation and clot evacuation. Multiple bleeding ulcers were recognised on the bladder wall, biopsies were taken for histopathology, and the ulcers cauterised. Packed red blood cell transfusions were required, and sodium hyaluronate (CystiStat®) bladder instillations were tried. There was no clinical improvement following any of these interventions. In light of the patient's deteriorating condition, cystoscopic application of PuraStat® 3ml was administered, which led to remission of the urinary bleeding in the short term. We continue to monitor the effects in the medium and long term. Based on current data, PuraStat® haemostatic agent therapy may be considered for RHC, when traditional treatments are ineffective or infeasible, potentially eliminating the need for more aggressive therapy such as cystectomy.

Delayed endoscopic sphincterotomy-related bleeding (ES bleeding) is an unavoidable adverse event (AE) that can have serious ramifications. Intraoperative ES bleeding, which stops spontaneously in most cases, is a known risk factor for delayed bleeding. This study aimed to examine the preventive effect of a novel self-assembling peptide (SAP) for delayed ES bleeding in patients who attained spontaneous hemostasis after intraoperative ES bleeding.

A total of 1507 patients met the eligibility criteria for inclusion in this study. The rates of delayed ES bleeding and AE besides bleeding were compared between patients administered the SAP (SAP group) and those who were simply observed after spontaneous hemostasis of intraoperative ES bleeding (control group). Propensity score matching was performed to adjust for differences between the groups.

The rate of delayed ES bleeding was significantly lower in the SAP group than that in the control group (0.9% vs 3.8%, P = 0.044). The rates of AEs other than bleeding were 2.4% and 3.8% in the SAP and control groups, respectively, and the difference lacked statistical significance (P = 0.481). Multivariate analysis revealed that the use of SAP was significantly associated with a lower frequency of delayed ES bleeding (odds ratio, 0.35; 95% confidence interval, 0.13-0.98; P = 0.047).

Self-assembling peptide may be a simple, safe, and useful way to reduce the risk of delayed ES bleeding in patients who experienced intraoperative ES bleeding and obtained subsequent spontaneous hemostasis.

Tonsillectomy is a common surgical procedure but carries a high risk of readmission for secondary bleeding and pain. This study evaluated the feasibility and effectiveness of using the hemostatic self-assembling peptide hydrogel RADA16 (PuraBond, 3-D Matrix SAS; Caluire et Cuire, France) to control bleeding from the tonsillectomy wound bed. Readmission/re-operation rates were compared between a prospective case series of 21 primarily adult tonsillectomy patients treated with topical RADA16 and an untreated historical Control group of 164 patients who underwent tonsillectomy by 10 surgeons at a single tertiary hospital in the UK between March 2019 and June 2022. Cumulative readmission rates for any reason were 2-fold elevated in Control subjects (18.9%; n = 31/164 subjects) compared to patients treated intra-operatively with RADA16 hemostatic hydrogel (9.5%; n = 2/21) (p = 0.378). Readmission rates for postoperative bleeding were 3-fold higher in Controls (14.6%; n = 24/164 subjects) than in the RADA16-treated group (4.8%; n = 1/21) (p = 0.317). A similar rate of retreatment for pain was recorded in the Control (4.3%; n = 7/164) and RADA16 (4.8%; n = 1/21) groups (p = 0.999). Two Control subjects (1.2%) required re-operation for recalcitrant bleeding; no RADA16 subject (0.0%) required re-operation for any reason. No device-related adverse events occurred in the RADA16 group. Surgeons were pleased with the easy learning curve and technical feasibility associated with intra-operatively administering RADA16 hemostatic hydrogel. Intra-operative hemostasis using RADA16 peptide hydrogel was straightforward and was associated with a trend of 3-fold lower rates of readmission for postoperative bleeding events than untreated Control subjects.

Gastrointestinal bleeding is a significant and potentially lethal event. We aimed to review the efficiency and safety of self-assembling peptides for the treatment and prevention of gastrointestinal tract bleeding.

We conducted a systematic search for studies describing the endoscopic use of self-assembling peptides for treatment or prevention of bleeding in the gastrointestinal tract in a parallel, independent fashion. The primary outcomes were rates of successful initial hemostasis, delayed bleeding, and rebleeding. The secondary outcomes were adverse events and ease and volume of gel used.

Seventeen studies were analyzed. Overall success rate of self-assembling peptides in gastrointestinal bleeding was 87.7% (38%-100%), regardless of etiology or associated treatments. Rebleeding rate ranged from 0% to 16.2%, with a mean of 4.7%, and overall delayed bleeding rate was 5% (range, 0%-15.9%). Only three adverse events were reported in a pooled number of 815 patients. The volume of gel used varied (0.43 to 3.7 mL) according to indication and type of bleeding.

The limited available data on the use of self-assembling peptides in gastrointestinal endoscopy suggest a high efficiency and good safety profile.

Endoscopic submucosal dissection (ESD) is the current standard treatment for early-stage esophageal neoplasms. However, the postoperative esophageal stricture after extensive mucosal dissection remains a severe challenge with limited effective treatments available. In this study, we introduced a chitosan/gelatin (ChGel) sponge encapsulating the adipose mesenchymal stem cells (ADMSCs)-derived exosomes (ChGelMSC-Exo) for the prevention of esophageal stenosis after ESD in a porcine model.

Pigs were randomly assigned into (1) ChGelMSC-Exo treatment group, (2) ChGelPBS group, and (3) the controls. Exosome treatments were applied immediately on the day after ESD as well as on day 7. Exosome components crucial for wound healing were investigated by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and small RNA sequencing. ChGelMSC-Exo treatment significantly reduced mucosal contraction on day 21, with less fiber accumulation and inflammatory infiltration, and enhanced angiogenesis when compared with the control and ChGelPBS groups. The anti-fibrotic effects following MSC-Exo treatment were further found to be associated with the anti-inflammatory M2 polarization of the resident macrophages, especially within the M2b subset characterized by the reduced TGFβ1 secretion, which sufficiently inhibited inflammation and prevented the activation of myofibroblast with less collagen production at the early stage after ESD. Moreover, the abundant expression of exosomal MFGE8 was identified to be involved in the transition of the M2b-macrophage subset through the activation of MFGE8/STAT3/Arg1 axis.

Our study demonstrates that exosomal MFGE8 significantly promotes the polarization of the M2b-macrophage subset, consequently reducing collagen deposition. These findings suggest a promising potential for MSC-Exo therapy in preventing the development of esophageal stricture after near-circumferential ESD.

Precut fistulotomy is of interest as one of the salvage techniques for selective bile duct cannulation using endoscopic retrograde cholangiopancreatography. Of the various endoscopic treatments reported to date for bleeding associated with papillotomy incision, endoscopic hemostasis treatment with a novel self-assembling peptide (SAP) matrix-forming gel (TDM-621) (3-D Matrix Ltd., Tokyo, Japan) remains only insufficiently reported in the literature.

We herein report 6 cases of precut fistulotomy-related bleeding successfully treated with endoscopic hemostasis treatment with TDM-621, i.e., 5 and 1 cases during and after precut fistulotomy, respectively, in 2 males and 4 females aged 68-96 years (mean age, 85 years), 3 of whom had been on antithrombotic drugs. Types of bleeding treated included oozing bleeding (n = 5) and oozing bleeding from a visible vessel (n = 1). In all cases, complete hemostasis was achieved with TDM-621 without causing rebleeding.

Endoscopic hemostasis with TDM-621 may prove effective for precut fistulotomy-related bleeding and represent a potential modality of first choice in hemostasis. In addition, endoscopic hemostasis with combined modality therapy using TDM-621 and endoscopic hemoclips may prove effective for bleeding from visible vessels.

A hemostatic gel, PuraStat (3-D Matrix, Tokyo, Japan), is used for various gastrointestinal hemostasis. In this study, we analyzed the efficacy of PuraStat for perioperative bleeding (POB) and prevention of delayed bleeding (DB) to colorectal cold snare polypectomy (CSP) with continuous anticoagulant.

This was a single-center, retrospective study. Subjects were lesions of 2-9 mm under continuous anticoagulant from 2021 to 2023 and treated with PuraStat for POB. The definition of POB was bleeding which did not stop spontaneously by 1.0-1.5 min after resection and needed hemostasis. Successful hemostasis was defined as cessation of bleeding within 1.0-1.5 min after spraying PuraStat and the rate of it and risk factors of POB were analyzed. For comparison, cases receiving previous CSP without PuraStat were extracted from all cases with CSP (2018-2021), and POB and DB rate (DBR) were analyzed after propensity score matching.

One hundred twenty-two lesions (91: direct oral anticoagulant (DOAC), 31: warfarin) with anticoagulant were analyzed and the rate of successful hemostasis with PuraStat was 92.6% (DOAC/warfarin: 93.4%/80.6%, P = 0.01). The rate of DB was 0.0%. Multivariate analysis showed that significant risk factors about unsuccessful hemostasis for POB with PuraStat were lesion size 8-9 mm (P < 0.01), warfarin (P = 0.01), and combination of antiplatelet (P = 0.01). Regarding the comparison about CSP with/without PuraStat, the clipping rate and DBR were 8.5%/94.9% (P < 0.01) and 0%/1.7% (P = 1.0).

The effects of PuraStat for POB and DB in colorectal CSP with continuous anticoagulant were acceptable.

The demand for nonbiological hemostatic materials has increased in surgical practice; however, few have sufficient hemostatic efficacy. This study investigated whether optimizing the composition of sodium calcium alginate, which forms a stable gel, improves hemostatic efficacy.

The sodium calcium alginate was changed for each composition, including powder size, calcium substitution rate, molecular weight, and mannuronic/guluronic acid ratio. The hemostasis in liver punch-out injury and bleeding was evaluated using swine. For the study, sodium calcium alginate with different compositions was randomly applied to bleeding sites. Previous hemostatic materials, including cellulose and sodium alginate, were used as a control. We investigated hemostasis at 2 and 5 minutes after application.

Each powder size (53-150 μm, 150-250 μm, 53-250 μm) had a similar hemostatic effect. However, the hemostatic rate was significantly higher in sodium calcium alginate than in previous hemostatic materials (P value < .01). A 74.1% calcium substitution rate had the highest hemostasis at 2 and 5 minutes after application (2 minutes: 100%, 5 minutes: 95.2%). Regarding molecular weight, the hemostatic rate was significantly higher in 333,000 than in 50,000 (2 minutes: 95% vs 70%, 5 minutes: 95% vs 70%, P = .038). Moreover, a 1.9 mannuronic/guluronic acid ratio had the highest hemostasis compared with the 0.4 mannuronic/guluronic acid ratio (2 minutes: 58.8% vs 11.8%, 5 minutes: 58.8% vs 0%, P = .033) CONCLUSION: The composition of sodium calcium alginate with a high hemostatic effect was optimized. This new hemostatic material demonstrated potential usefulness for bleeding during surgery.

Postoperative non variceal upper gastrointestinal haemorrhage may occur early or late and affect a variable percentage of patients-up to about 2%. Most cases of intraluminal bleeding are an indication for urgent Esophagogastroduodenoscopy (EGD) and require endoscopic haemostatic treatment. In addition to the approach usually adopted in non-variceal upper haemorrhages, these cases may be burdened with difficulties in terms of anastomotic tissue, angled positions, and the risk of further complications. There is also extreme variability related to the type of surgery performed, in the context of oncological disease or bariatric surgery. At the same time, the world of haemostatic devices available in digestive endoscopy is increasing, meeting high efficacy rates and attempting to treat even the most complex cases. Our narrative review summarises the current evidence in terms of different approaches to endoscopic haemostasis in upper bleeding in altered anatomy after surgery, proposing an up-to-date guidance for endoscopic clinicians and at the same time, highlighting areas of future scientific research.

RADA16 is a peptide-based biomaterial whose acidic aqueous solution spontaneously forms an extracellular matrix-like 3D structure within seconds upon contact with physiological pH body fluids. Meanwhile, its good biocompatibility, low immunogenicity, nontoxic degradation products and ease of modification make it an ideal scaffold for tissue engineering. RADA16 is a good delivery vehicle for cells, drugs and factors. Its shear thinning and thixotropic properties allow it to fill tissue voids by injection and not to swell. However, the weaker mechanical properties and poor hydrophilicity are troubling limitations of RADA16. To compensate for this limitation, various functional groups and polymers have been designed to modify RADA16, thus contributing to its scope and progress in the field of tissue engineering.

Short designer self-assembling peptide (dSAP) biomaterials are a new addition to the hemostat group. It may provide a diverse and robust toolbox for surgeons to integrate wound microenvironment with much safer and stronger hemostatic capacity than conventional materials and hemostatic agents. Especially in noncompressible torso hemorrhage (NCTH), diffuse mucosal surface bleeding, and internal medical bleeding (IMB), with respect to the optimal hemostatic formulation, dSAP biomaterials are the ingenious nanofiber alternatives to make bioactive neural scaffold, nasal packing, large mucosal surface coverage in gastrointestinal surgery (esophagus, gastric lesion, duodenum, and lower digestive tract), epicardiac cell-delivery carrier, transparent matrix barrier, and so on. Herein, in multiple surgical specialties, dSAP-biomaterial-based nano-hemostats achieve safe, effective, and immediate hemostasis, facile wound healing, and potentially reduce the risks in delayed bleeding, rebleeding, post-operative bleeding, or related complications. The biosafety in vivo, bleeding indications, tissue-sealing quality, surgical feasibility, and local usability are addressed comprehensively and sequentially and pursued to develop useful surgical techniques with better hemostatic performance. Here, the state of the art and all-round advancements of nano-hemostatic approaches in surgery are provided. Relevant critical insights will inspire exciting investigations on peptide nanotechnology, next-generation biomaterials, and better promising prospects in clinics.

Gastrointestinal bleeding (GIB) is a common and potentially fatal condition with all-cause mortality ranging from 3 to 10%. Endoscopic therapy traditionally involves mechanical, thermal, and injection therapies. Recently, self-assembling peptide (SAP) has become increasingly available in the United States. When applied to an affected area, this gel forms an extracellular matrix-type structure allowing for hemostasis. This is the first systematic review and meta-analysis to assess the safety and efficacy of this modality in GIB.

We performed a comprehensive literature search of major databases from inception to Nov 2022. The primary outcomes assessed were the success of hemostasis, rebleeding rates, and adverse events. The secondary outcomes assessed were successful hemostasis with monotherapy with SAP and combined therapy, which may include mechanical, injection, and thermal therapies. Pooled estimates were calculated using random-effects models with a 95% confidence interval (CI).

The analysis included 7 studies with 427 patients. 34% of the patients were on anticoagulation or antiplatelet agents. SAP application was technically successful in all patients. The calculated pooled rate of successful hemostasis was 93.1% (95% confidence interval (CI) 84.7-97.0, I2 = 73.6), and rebleeding rates were 8.9% (95% CI 5.3-14.4, I2 = 55.8). The pooled rates of hemostasis with SAP monotherapy and combined therapy were similar. No adverse events were noted related to SAP.

SAP appears to be a safe and effective treatment modality for patients with GIB. This modality provides an added advantage of improved visualization over the novel spray-based modalities. Further, prospective, or randomized controlled trials are needed to validate our findings.

Inflammatory bowel diseases (IBDs) treatments have shifted from small-molecular therapeutics to the oncoming biologics. The first-line biologics against the moderate-to-severe IBDs are mainly involved in antibodies against integrins, cytokines and cell adhesion molecules. Besides, other biologics including growth factors, antioxidative enzyme, anti-inflammatory peptides, nucleic acids, stem cells and probiotics have also been explored at preclinical or clinical studies. Biologics with variety of origins have their unique potentials in attenuating immune inflammation or gut mucosa healing. Great advances in use of biologics for IBDs treatments have been archived in recent years. But delivering issues for biologic have also been confronted due to their liable nature. In this review, we will focus on biologics for IBDs treatments in the recent publications; summarize the current landscapes of biologics and their promise to control disease progress. Alternatively, the confronted challenges for delivering biologics will also be analyzed. To combat these drawbacks, some new delivering strategies are provided: firstly, designing the functional materials with high affinity toward biologics; secondly, the delivering vehicle systems to encapsulate the liable biologics; thirdly, the topical adhering delivery systems as enema. To our knowledge, this review is the first study to summarize the updated usage of the oncoming biologics for IBDs, their confronted challenges in term of delivery and the potential combating strategies.

Video 1Outline of how self-assembling peptide gel can be used ex vivo.

Esophageal varices are dilated submucosal esophageal veins that connect the portal and systemic circulations. Bleeding esophageal varices is a well-recognized complication of liver cirrhosis.It is known that in active variceal bleeding, treatment needs to be started promptly. Treatments comprise band ligation, sclerotherapy, removable stent placement, balloon tamponade, and transjugular intrahepatic portosystemic shunt (TIPS).We report a case in which hemodynamic stability can be maintained with the use of Purastat to control bleeding.

Complications of endoscopic sinus/nasal turbinate surgery include postoperative hemorrhage, synechiae formation, and poor wound healing. Our primary objectives were to evaluate whether a topical hydrogel based on self-assembling RADA16 peptides: i) reduces bleeding and synechiae formation, and ii) supports wound healing, using a sheep nasal surgery model.

Thirty sheep received endoscopic surgery-created bilateral nasal mucosal injuries on the middle turbinate/opposing septum. Injuries were randomly assigned RADA16, Gelatin-thrombin, or no treatment. Outcomes included intra-operative hemostasis, scar tissue/synechiae formation and wound healing at 2 weeks and the 6-week study terminus, and histopathology.

Intra-operative hemostasis time improved with RADA16 and Gelatin-thrombin versus Control wounds (139.7±56.2 s, 145.4±58.1 s, and 224.0±69.9 s, respectively; p < 0.0001 for both comparisons). Two-week synechiae scores (maximum 4 points) were similar in Controls (2.9±1.8 points) and Gelatin-thrombin (3.1±1.6 points) wounds (p > 0.05), but were reduced in RADA16 sites by 91% versus Controls and 92% versus Gelatin-thrombin treatment (0.3±0.6 points; p < 0.0001 for both comparisons). Six-week synechiae scores were similar in Control (1.1±1.7 points) and Gelatin-thrombin (1.7±2.0 points) wounds (p > 0.05), but reduced 100% in RADA16-treated wounds. Synechiae occurred in fewer RADA16-treated sites at 2 weeks (20%) versus Gelatin-thrombin (80%) and Controls (75%; p < 0.01) and at 6 weeks (0%, 50% and 35%, respectively; p < 0.01). RADA16 was associated with significantly lower 6-week histopathology scores, driven by reduced submucosal fibrosis and angiogenesis.

Although RADA16 and Gelatin-thrombin similarly accelerated hemostasis in this sheep endoscopic sinus surgery model, only RADA16 reduced postoperative synechiae formation at 2 weeks with an absence of synechiae at 6 weeks. Histology suggested RADA16 enhanced mucosal regeneration.

Background and Objectives: A novel synthetic self-assembling peptide, PuraStat, has been introduced as a hemostatic agent. This case series aimed to evaluate the clinical efficacy of PuraStat for gastrointestinal bleeding during emergency endoscopy. Cases: Twenty-five patients with gastrointestinal bleeding who had undergone emergency endoscopy with PuraStat between August 2021 and December 2022 were retrospectively examined. Six patients were receiving antithrombotic agents, and ten patients with refractory gastrointestinal bleeding had undergone at least one endoscopic hemostatic procedure. The breakdown of bleeding was gastroduodenal ulcer/erosion in 12 cases, bleeding after gastroduodenal or colorectal endoscopic resection in 4 cases, rectal ulcer in 2 cases, postoperative anastomotic ulcer in 2 cases, and gastric cancer, diffuse antral vascular ectasia, small intestinal ulcer, colonic diverticular bleeding, and radiation proctitis in each case. The method of hemostasis was only PuraStat application in six cases, and hemostasis in combination with high-frequency hemostatic forceps, hemostatic clip, argon plasma coagulation, and hemostatic agents (i.e., thrombin) in the remaining cases. Rebleeding was observed in three cases. Hemostatic efficiency was observed in 23 cases (92%). Conclusions: PuraStat has the expected hemostatic effect on gastrointestinal bleeding during emergency endoscopy. The use of PuraStat should be considered in emergency endoscopic hemostasis of gastrointestinal bleeding.

Background and study aims  Advanced endoscopic resection techniques carry a risk of delayed bleeding (DB). A novel fully synthetic self-assembling peptide (SAP) has shown promising results in mitigating this risk. In this meta-analysis, we evaluated all available data and analyzed the effectiveness of SAP in reducing DB after advanced endoscopic resection of gastrointestinal luminal lesions. Patients and methods  Electronic databases (PubMed, Embase, and Cochrane Library) from January 2010 through October 2022 were searched for publications addressing the use of SAP solution in patients undergoing advanced endoscopic resection of gastrointestinal lesions. Pooled proportions were calculated using fixed (inverse variance) and random-effects (DerSimonian-Laird) models. Results  The initial search identified 277 studies, of which 63 relevant articles were reviewed. The final analysis included data from six studies comprising 307 patients that met inclusion criteria. The pooled rate of DB was 5.73 % (95 % confidence interval [CI] = 3.42-8.59). Mean patient age was 69.40 years ± 1.82. The weighted mean size of resected lesions was 36.20 mm (95 % CI = 33.37-39.02). Endoscopic submucosal dissection was used in 72.69 % (95 % CI = 67.62-77.48), while endoscopic mucosal resection was used in 26.42 % (95 % CI = 21.69-31.44) of the procedures. Among the 307 patients, 36 % were on antithrombotic medications. No adverse events (AEs) were attributable to using SAP, with a pooled rate of 0.00 % (95 % CI = 0.00-1.49). Conclusions  SAP solution appears promising in reducing post-procedural DB after advanced endoscopic resection of high-risk gastrointestinal lesions with no reported AEs.

Background and Objectives: Bleeding is one of the most feared and frequent adverse events in the case of EUS-guided drainage of WOPN using lumen-apposing metal stents (LAMSs) and of direct endoscopic necrosectomy (DEN). When it occurs, its management is still controversial. In the last few years, PuraStat, a novel hemostatic peptide gel has been introduced, expanding the toolbox of the endoscopic hemostatic agents. The aim of this case series was to evaluate the safety and efficacy of PuraStat in preventing and controlling bleeding of WOPN drainage using LAMSs. Materials and Methods: This is a multicenter, retrospective pilot study from three high-volume centers in Italy, including all consecutive patients treated with the novel hemostatic peptide gel after LAMSs placement for the drainage of symptomatic WOPN between 2019 and 2022. Results: A total of 10 patients were included. All patients underwent at least one session of DEN. Technical success of PuraStat was achieved in 100% of patients. In seven cases PuraStat was placed for post-DEN bleeding prevention, with one patient experiencing bleeding after DEN. In three cases, on the other hand, PuraStat was placed to manage active bleeding: two cases of oozing were successfully controlled with gel application, and a massive spurting from a retroperitoneal vessel required subsequent angiography. No re-bleeding occurred. No PuraStat-related adverse events were reported. Conclusions: This novel peptide gel could represent a promising hemostatic device, both in preventing and managing active bleeding after EUS-guided drainage of WON. Further prospective studies are needed to confirm its efficacy.

PuraStat is a newly developed self-assembling hemostatic gel which is expected to be applied to bleeding from various lesions of the gastrointestinal tract. Yamamoto and colleagues describe the practical use of this hemostatic gel for delayed bleeding after endoscopic papillectomy, with accompanying video.

ESGE suggests conventional endoscopic submucosal dissection (ESD; marking and mucosal incision followed by circumferential incision and stepwise submucosal dissection) for most esophageal and gastric lesions. ESGE suggests tunneling ESD for esophageal lesions involving more than two-thirds of the esophageal circumference. ESGE recommends the pocket-creation method for colorectal ESD, at least if traction devices are not used. The use of dedicated ESD knives with size adequate to the location/thickness of the gastrointestinal wall is recommended. It is suggested that isotonic saline or viscous solutions can be used for submucosal injection. ESGE recommends traction methods in esophageal and colorectal ESD and in selected gastric lesions. After gastric ESD, coagulation of visible vessels is recommended, and post-procedural high dose proton pump inhibitor (PPI) (or vonoprazan). ESGE recommends against routine closure of the ESD defect, except in duodenal ESD. ESGE recommends corticosteroids after resection of  > 50 % of the esophageal circumference. The use of carbon dioxide when performing ESD is recommended. ESGE recommends against the performance of second-look endoscopy after ESD. ESGE recommends endoscopy/colonoscopy in the case of significant bleeding (hemodynamic instability, drop in hemoglobin > 2 g/dL, severe ongoing bleeding) to perform endoscopic hemostasis with thermal methods or clipping; hemostatic powders represent rescue therapies. ESGE recommends closure of immediate perforations with clips (through-the-scope or cap-mounted, depending on the size and shape of the perforation), as soon as possible but ideally after securing a good plane for further dissection.

Millions of individuals undergo gastrointestinal (GI) tract surgeries each year with common postoperative complications including bleeding, perforation, anastomotic leakage, and infection. Today, techniques such as suturing and stapling seal internal wounds, and electrocoagulation stops bleeding. These methods induce secondary damage to the tissue and can be technically difficult to perform depending on the wound site location. To overcome these challenges and to further advance wound closure, hydrogel adhesives are being investigated to specifically target GI tract wounds because of their atraumatic nature, fluid-tight sealing capability, favorable wound healing properties, and facile application. However, challenges remain that limit their use, such as weak underwater adhesive strength, slow gelation, and/or acidic degradation. In this review, we summarize recent advances in hydrogel adhesives to treat various GI tract wounds, with a focus on novel material designs and compositions to combat the environment-specific challenges of GI injury. We conclude with a discussion of potential opportunities from both research and clinical perspectives.

Peptide amphiphiles (PAs) are peptide-based molecules that contain a peptide sequence as a head group covalently conjugated to a hydrophobic segment, such as lipid tails. They can self-assemble into well-ordered supramolecular nanostructures such as micelles, vesicles, twisted ribbons and nanofibers. In addition, the diversity of natural amino acids gives the possibility to produce PAs with different sequences. These properties along with their biocompatibility, biodegradability and a high resemblance to native extracellular matrix (ECM) have resulted in PAs being considered as ideal scaffold materials for tissue engineering (TE) applications. This review introduces the 20 natural canonical amino acids as building blocks followed by highlighting the three categories of PAs: amphiphilic peptides, lipidated peptide amphiphiles and supramolecular peptide amphiphile conjugates, as well as their design rules that dictate the peptide self-assembly process. Furthermore, 3D bio-fabrication strategies of PAs hydrogels are discussed and the recent advances of PA-based scaffolds in TE with the emphasis on bone, cartilage and neural tissue regeneration both in vitro and in vivo are considered. Finally, future prospects and challenges are discussed.

To compare the effectiveness of the novel hemostatic peptide, TDM-621, with that of conventional hemostatic methods in treating intraoperative blood oozing during endoscopic submucosal dissection (ESD).

This multicenter, open-label, randomized controlled trial involved 227 patients with gastric and rectal epithelial tumors in whom ESD was indicated. Patients in whom the source of blood oozing was difficult to identify with waterjet washing during the procedure and required hemostasis with hemostatic forceps were randomly assigned to the TDM-621 and control groups. The TDM-621 group (in which hemostasis was achieved with TDM-621, followed by coagulation hemostasis with hemostatic forceps, as needed) was compared with the control group (in which hemostasis was achieved with hemostatic forceps). The primary end point was the mean number of coagulations with hemostatic forceps, determined by a blinded independent review committee. The secondary end points were the rate of achievement of hemostasis with only TDM-621, the dosage of TDM-621, and adverse events in the TDM-621 group.

The mean number of coagulations with hemostatic forceps was significantly reduced in the TDM-621 group (1.0 ± 1.4) compared with that in the control group (4.9 ± 5.2) ( P < 0.001). The rate of hemostasis achievement with only TDM-621 was 62.2%; the mean dosage of TDM-621 was 1.75 ± 2.14 mL. The rates of grade ≥3 adverse events were 6.2% and 5.0% in the TDM-621 and control groups, respectively.

TDM-621 is a useful, easily operable hemostatic peptide for treatment of blood oozing during gastric and rectal ESD, with no serious safety concerns.

New endoscopic approaches for the prevention of delayed bleeding (DB) after gastric endoscopic submucosal dissection (ESD) have been reported in recent years, and endoscopic delivery of biodegradable polymers for iatrogenic ulcer hemostasis and coverage has emerged as one of the most promising techniques for post-ESD management. However, the comparative efficacy of these techniques remains uncertain. We performed a systematic search of multiple databases up to May 2022 to identify studies reporting DB rates as outcomes in patients undergoing gastric ESD who were treated with subsequent endoscopic management, including endoscopic closure (clip-based methods and suturing), PGA sheet tissue shielding, and hemostatic powder/gel spray (including polymeric sealants and other adhesives). The risk ratios (RRs) of delayed bleeding in treatment groups and control groups were pooled, and the Bayesian framework was used to perform a network meta-analysis (NMA). Among these studies, 16 head-to-head comparisons that covered 2742 lesions were included in the NMA. Tissue shielding using PGA sheets significantly reduced the risk of DB by nearly two thirds in high-risk patients, while hemostatic spray systems, primarily polymer-based, reduced DB in low-risk patients nine-fold. Researchers should recognize the essential role of polymers in the management of ESD-induced ulcers, and develop and validate clinical application strategies for promising materials.