Introduction

Metal (MS) or plastic stents (PS) are used for preoperative biliary drainage (PBD) in patients with pancreatic ductal adenocarcinoma (PDAC) undergoing neoadjuvant chemotherapy (NAC) or chemoradiotherapy (NACRT). However, there are no large studies comparing postoperative adverse events(AEs) and postoperative long-term outcomes between patients who received MS and those who received PS for PBD.

Aims & Methods

This multicenter retrospective study compared the safety and efficacy of PBD using MS and PS, including surgery-related adverse events and other clinical outcomes.
This study enrolled patients with resectable or borderline resectable PDAC requiring NAC or NACRT who underwent PBD with MS or PS at 17 tertiary care hospitals in Japan between January 2016 and December 2021. Clinical outcomes, including the incidence of recurrent biliary obstruction (RBO), time to RBO, time from stent placement to surgery, postoperative hospital stay, incidence of postoperative adverse events, and postoperative overall survival, were retrospectively analyzed.

Results

Among the 308 patients with PDAC who received PBD before NAC or NACRT, 251 subsequently underwent pancreatic resection. Of these 251 patients, 122 (48.6%) had PBD with MS, while 129 (51.4%) had PBD with PS. Because there were significant differences in baseline characteristics between both groups, propensity score matching was performed, resulting in 84 matched pairs. RBO occurred significantly less frequently in the MS group than in the PS group (11.9% vs. 59.5%, p < 0.001). Time to RBO is significantly longer in the MS group than in the PS group (median 353 days vs. 74 days, p < 0.001). The MS group also showed significantly reduced time to surgery from stent placement (median 95 days vs. 112 days, p = 0.010) and shorter postoperative hospital stays (median 17 days vs. 20 days, p = 0.025). Although postoperative AEs occurred less often in the MS group (19.1% vs. 29.8%), the difference was not statistically significant (p = 0.106). In both univariate and multivariate models, RBO was identified as the sole independent factor associated with postoperative AEs (odds ratio: 2.36, p = 0.019). However, the type of stent used was not significantly associated with the occurrence of postoperative AEs. Notably, the incidence of postoperative pancreatic fistula was significantly higher in patients who developed RBO compared to those who did not (16.7% vs. 5.6%, p = 0.027).

Conclusion

For patients with PDAC undergoing NAC or NACRT, MS placement is preferable to PS placement for PBD. MS placement was associated with a lower incidence of RBO and need for re-intervention, as well as a shorter perioperative hospital stay. Given the reduced frequency of RBO, which is an established risk factor for postoperative AE, MS placement is recommended for PBD in this setting.

Introduction

The incidence of superficial non-ampullary duodenal epithelial tumors (SNADETs) has markedly increased in recent endoscopic practice [1, 2]. Nevertheless, the detection rate during esophagogastroduodenoscopy remains low, with 0.15% for adenomas and 0.05% for carcinomas [3]. Large SNADETs, akin to other gastrointestinal malignancies, should be resected en bloc via endoscopic submucosal dissection (ESD). However, the incidence of perforation associated with duodenal ESD is notably high (11.6–35.7%), often necessitating invasive interventions such as pancreatoduodenectomy [4–6]. Endoscopists must learn duodenal ESD procedures through on-the-job training, as no suitable animal or simulation model exists. Although cadaver surgical training (CST) has become prevalent in surgical practice, its application in gastrointestinal endoscopic treatment has been infrequently documented. CST may provide superior anatomical landmarks and tissue fidelity compared to animal or simulation training. This study investigated the potential application of CST as a training model for duodenal ESD.

Aims & Methods

Between July 2024 and February 2025, CST was conducted on four donors preserved using the Thiel method. Upper gastrointestinal examination (UGIE) and multiple duodenal ESD procedures were performed. Among the participants, three had prior experience with these procedures (Experience; Group E), while four did not have such experience (Non-Experience; Group NE). Both groups executed all procedures, and subsequent retrospective studies were conducted: 1) the feasibility of UGIE and the performance of the duodenal ESD procedure for each donor, and 2) questionnaires administered to the participants (n=7) to assess the feasibility of each procedure (marking, submucosal injection, circumferential incision, submucosal dissection), realism of the simulation, and psychological barriers, using a 5-point rating scale ("1: significantly more challenging–5: significantly easier" or "1: strongly disagree–5: strongly agree"). Each score was compiled and presented as the median score.

Results

1) UGIE was feasible in all four cases, although one instance of duodenal perforation occurred due to duodenal stretching. Duodenal ESD was feasible in all four cases and was performed a total of seven times.
2) In UGIE, procedural scores, such as insertion and observation at each location, were predominantly rated 4 or 5, with a score of 3 exclusively noted for intragastric observation. In duodenal ESD, all procedural scores for tasks such as submucosal injection and dissection were consistently assigned a rating of 4. The questionnaire score for the item "Was the duodenal mural architecture preserved?" was 4.5. The scores for the items "Is there psychological stress associated with handling cadavers?" and "Is CST useful for learning duodenal ESD technique?" were 4 and 4.5, respectively. No significant differences were observed in the scores between the E and NE groups for any of the evaluations.

Conclusion

The mural architecture of the gastrointestinal tract in CST, when fixed using the Theil method, closely resembles that of a living organism. It was subsequently identified that CST could serve as an effective educational model for duodenal ESD, marking this as the inaugural report on the subject. This methodology is expected to have broader applications in the education of endoscopic treatments, particularly for rare and challenging procedures such as duodenal ESD, and to contribute to the advancement of endoscopic techniques in future research.

References

1. Legué LM, Bernards N, Gerritse SL, et al. Trends in incidence, treatment and survival of small bowel adenocarcinomas between 1999 and 2013: a population-based study in The Netherlands. Acta Oncol. 2016;55:1183-1189.
2. Yoshida M, Yabuuchi Y, Kakushima N, et al. The incidence of non-ampullary duodenal cancer in Japan: The first analysis of a national cancer registry. J Gastroenterol Hepatol. 2021;36:1216-1221.
3. Yoshimizu S, Hirasawa T, Horiuchi Y, et al. Differences in upper gastrointestinal neoplasm detection rates based on inspection time and esophagogastroduodenoscopy training. Endosc Int Open. 2018;06:E1190–E1197.
4. Hoteya S, Furuhata T, Takahito T, et al. Endoscopic Submucosal Dissection and Endoscopic Mucosal Resection for Non-Ampullary Superficial Duodenal Tumor. Digestion. 2017;95:36-42.
5. Jung JH, KD. C, JY. A, et al. Endoscopic submucosal dissection for sessile, nonampullary duodenal adenomas. Endoscopy. 2013;45:133-135.
6. Kato M, Takeuchi Y, Hoteya S, et al. Outcomes of endoscopic resection for superficial duodenal tumors: 10 years' experience in 18 Japanese high volume centers. Endoscopy. 2022;54:663-670.

Introduction

Prophylactic wound closure after Endoscopic Submucosal Dissection (ESD) is suggested in high-risk patients to reduce delayed AEs (e.g. bleeding). The closure of large wounds can be challenging with standard endoscopic devices (e.g. endoclips) and dedicated devices are needed. Endoscopic Hand-Suturing (EHS) can be a therapeutic option to close extensive gastrointestinal defects. The current study presents the EHS experience from two Italian centers, aiming to assess the feasibility and clinical effectiveness of the EHS technique.

Aims & Methods

Data from two high-volume endoscopic Italian centers were retrospectively collected. Patients with an ESD wound closed using the SutuArt (Olympus Medical Systems, Tokyo, Japan) device were enrolled in the study (Figure1). Demographics, technical data, success rate, suturing speed, and AEs were recorded

Results

Between June 2023 and August 2024 10 patients were enrolled in the study, demographics in Table 1. All patients were at high-risk for delayed bleeding after gastric or colorectal ESD (figure2). The mean lesion size was 34mm (range 15-45). In all cases SutuArt (Olympus Medical Systems, Tokyo, Japan) needle holder with V-LOC 180, size 3-0 threads (Medtronic) were used. All procedures were performed by two expert endoscopists. ESD-wound closure was successfully achieved in 90% of cases. The mean suturing time was 42 min (range: 25–65 min, SD=23.3 min) meanwhile the mean ESD time was 86 minutes (range: 15–185min, SD=38min). Suturing significantly increased the total procedure time (120min Vs 86min, p<0.001). In one case, the wound closure failed due to suture breakage, resulting in needle entrapment within the mesorectum, with the impossibility of retrieving it. No other AEs were reported.

Conclusion

ESD-defects closure with EHS is feasible and safe with promising outcomes. However, this technique is significantly time-consuming. Probably extended training may be required for endoscopists performing suturing, and further studies are needed to assess the real-life applicability and the cost-effectiveness of this technique.

Introduction

Artificial Intelligence (AI)-powered Computer-aided diagnosis (CADx) systems provide real-time polyp histology prediction during colonoscopy, potentially improving accuracy in clinical decision-making. We aimed to assess CADx performance and its impact on endoscopist optical diagnosis for sessile serrated polyps (SSPs), traditional serrated adenomas (TSAs), adenomas with advanced histology, and cancers in a pragmatic implementation study.

Aims & Methods

We performed a secondary analysis of a large prospective cohort comprising patients undergoing diagnostic, screening, and surveillance colonoscopies. All patients and polyps with SSPs, TSAs, advanced adenomas and/or cancers detected, and prospectively documented CADx assisted or CADx unassisted optical diagnoses were included in the study. The primary outcome was the sensitivity of CADx assisted and unassisted optical diagnoses for SSP identification. Secondary outcomes included sensitivity for TSA, advanced adenoma, and cancer identification as well as the impact of CADx output on endoscopists’ optical diagnoses.

Results

Within a cohort of 2622 patients with 2456 eligible polyps there were 140 (5.7%) SSPs, 22 (0.9%) TSAs, 213 (8.7%) advanced adenomas, and 13 (0.5%) cancers. Sensitivity for SSP identification of CADx assisted and unassisted optical diagnosis was 53.2% (95% CI 42.3-63.8) and 37.8% (95% CI 24.1-53.9) respectively; p=0.12. In CADx assisted cases, endoscopists correctly identified SSPs more frequently when CADx classified these as non-neoplastic (56/79 cases) compared to neoplastic (23/79 cases), (66.1% [95% CI 53.0-77.1] vs 21.7% [95% CI 9.6-41.9]; p=0.0003). Sensitivity for TSA identification as neoplastic by CADx output was 61.6% (8/13), but CADx assisted and unassisted endoscopist optical diagnosis performed similarly, identifying TSAs as neoplastic in 83.3% and 66.7% of cases respectively; p=0.61. Sensitivity for advanced adenoma identification as adenoma/neoplastic did not differ between CADx assisted and unassisted cases (Table 1). Sensitivity for optical diagnosis of cancer was 50.0% and 42.9% for CADx assisted and unassisted optical diagnosis, with 3/6 and 4/7 of cancers misdiagnosed as adenomas, respectively.

Table 1. Diagnostic performance of CADx assisted and unassisted optical diagnosis

	SSP		TSA		Advanced adenomas*		Cancers
	CADx assisted	CADx unassisted	CADx assisted	CADx unassisted	CADx assisted	CADx unassisted	CADx assisted	CADx unassisted
Polyps, n	79	37	12	9	71	83	6	7
Sensitivity, % (95% CI)	53.2 (42.3-63.8)	37.8 (24.1-53.9)	83.3 (54.0-97.0)	66.7 (34.7-88.4)	100.0 (95.0-100)	96.4 (89.3-98.9)	50.0 (11.8-88.2)	42.9 (9.9-81.6)
PPV, %	27.8	20.0	-	-	-	-	23.1	33.3
Incorrect endoscopist diagnoses
Hyperplastic, n	17	4	1	2	0	0	0	0
Adenoma, n	20	19	-	-	-	-	3	4
SSP, n	-	-	1	1	0	0	0	0
Cancer, n	0	0	0	0	0	3	-	-

*Adenomas with villous component or high grade dysplasia

Conclusion

In our study, CADx use did neither harm nor improve optical diagnostic performance in polyps with SSP, TSA, advanced adenoma, or cancerous histology. Sensitivity for identification of these lesions trended universally higher with CADx assisted optical diagnosis, though statistical significance was not achieved at the present sample size. Whilst both CADx assisted and unassisted optical diagnosis reliably identified advanced adenomas as adenomas, optical diagnosis sensitivity to recognize SSPs and cancerous lesions was low.

Disclosure

Daniel von Renteln has received research funding from ERBE Elektromedizin GmbH, Ventage, Pendopharm, Fujifilm, and Pentax, and has received consultant or speaker fees from Boston Scientific Inc., ERBE Elektromedizin GmbH, and Pendopharm. The remaining authors declare that they have no conflict of interest.

Introduction

Training with silicone models in colonoscopy is limited by the lack of realistic texture and appearance of mucosal tissue. Artificial intelligence (AI) offers a novel solution by enabling simulation of realistic appearing mucosa, which can enhance the overall visual realism of silicone-based models for endoscopic training.

Aims & Methods

We developed, using 239,875 images from 3,452 colonoscopies recorded using five different endoscopic processors, a style transfer AI model capable of transforming endoscopic video footage from a silicone colon into a video that visually mimics real mucosal tissue. The model was applied to two representative clips recorded from a silicone colon model, covering lesions and normal mucosa. Both the original and AI-enhanced videos were shown to N = 12 gastroenterologists (board certified and in training), who provided quantitative evaluations using a 5-point Likert scale (1: Strongly disagree, 5: Strongly agree) and free-text qualitative feedback. We conducted the statistical analysis using Wilcoxon signed-rank tests with Pratt adjustment for zero differences and analyzed the qualitative feedback with an inductive content analysis after Mayring.

Results

All physicians prefer the AI-enhanced videos over the original silicone footage due to the more realistic representation of the colon. This can also be seen from the quantitative data, as the participants rated the AI-enhanced videos as significantly more visually realistic (M = 2.42 vs 4.17, Z = -3.22, p < .001), helpful for training (M = 3.67 vs 4.25, Z = -2.65, p = .016) and polyp characterization (M = 2.92 vs 3.75, Z = -2.38, p = .027), favored for usage (M = 2.92 vs 4.00, Z = -2.80, p = .005), and facilitating optical diagnoses (M = 3.58 vs 4.42, Z = -2.23, p = .039). Though, the participants rated the original silicone footage as significantly less mentally demanding than the AI-enhanced videos (M = 1.67 vs 2.42, Z = -2.61, p = .016). Open-ended feedback highlighted the more realistic AI generated mucosa as an enhancement (100 %) to the unrealistic silicone surface (92 %) while suggesting that further development should focus on integrating more realistic lesions (33 %) and increasing mucosal details (42 %).

Conclusion

AI-driven simulation of normal mucosa improves the realism, acceptance, and educational value of silicone colon models used in endoscopy training.

Introduction

Hot endoscopic mucosal resection (H-EMR) is the standard of care for large non-pedunculated colorectal polyps (LNPCPs) without suspicion of submucosal invasion, achieving low recurrence rates after en bloc resection or piecemeal resection with margin ablation in expert centers.^1,2 However, electrocautery is also responsible for complications which can lead to significant morbidity and necessitate additional invasive procedures.^3,4 Cold snare polypectomy (CSP) has proven to be preferable to H-EMR for adenomas ≤10mm and non-dysplastic sessile serrated lesions, providing comparable efficacy with improved safety, shorter procedural time and lower costs.⁵ These advantages have driven interest in expanding CSP to larger polyps.

Aims & Methods

This meta-analysis of randomized controlled trials (RCTs) aimed to compare the risk of recurrence and adverse events between cold snare polypectomy (CSP) and hot-endoscopic mucosal resection (H-EMR) for large non-pedunculated colorectal polyps (LNPCPs).
A systematic search of Medline, Embase and Cochrane Library databases was performed through August 2024 for studies comparing recurrence, bleeding and perforation rates between CSP and H-EMR for LNPCPs ≥15mm (PROSPERO ID: CRD42024568272). RCTs were included in the quantitative analysis. A random-effects meta-analysis, with heterogeneity measured with I², was conducted to generate pooled risk ratios (RR) with 95% confidence intervals.

Results

Four RCTs comprising 1516 LNPCPs (766 CSP and 750 H-EMR) in 1442 patients were included in the quantitative analysis. CSP demonstrated a higher recurrence risk at first surveillance colonoscopy than H-EMR in the pooled analysis (22.6% vs. 10.8%; RR=1.98; 95% CI: 1.22–3.21; p=0.02; moderate-certainty evidence), corresponding to a number needed to harm of 9. Regarding adverse events, CSP demonstrated a 67% reduced risk of delayed bleeding (1.2% vs. 3.9%; RR=0.33; 95% CI: 0.12-0.89; p=0.03; high-certainty evidence), corresponding to a number needed to treat of 37. Although CSP appeared to reduce the risk of intraprocedural bleeding (10.0% vs. 19.8%; RR=0.30, 95% CI: 0-52256.34, p=0.42), the wide confidence interval from the random-effects model included 1. There were no intraprocedural or delayed perforations in the CSP group.

Author	Study design	Number of patients		Age, mean (SD), years	Female, %	Number of LNPCPs		LNPCP size, mean/median (SD/IQR), mm	Right Location, %		Adenomatous histology, %
		CSP	H-EMR			CSP	H-EMR		CSP	H-EMR	CSP	H-EMR
O’ Sullivan T. et al., 2024	Single center, RCT	87	90	68.2 (10.0)	46.9	87	90	30 (25-35)	96.5	86.7	100	100
Steinbrück et al., 2024	Multicenter, RCT	184	192	65.9 (10.5)	48.2	193	203	30.1 (10.2)	88.1	86.2	60.7	68.5
Pohl H. et al., 2024	Multicenter, RCT	336	324	65.3 (10.2)	47.7	371	343	30 (25.4)	82.5	83.4	NR	NR
Nogales et al., 2023	Multicenter, RCT	115	114	67.9 (10.6)	43.3	115	114	25 (22-30)	80.0	78.1	71.9	77.2

Table 1. Patients, LNPCPs and procedure characteristics of the randomized controlled trials included in the quantitative analysis. (List of abbreviations: CSP, cold snare polypectomy; H-EMR, hot endoscopic mucosal resection; IQR, interquartile range; LNPCPs, large non-pedunculated colorectal polyps; NR, not reported; SD, standard deviation; RCT, randomized controlled trial)

Conclusion

CSP has nearly double the recurrence risk of H-EMR for LNPCPs. However, its superior safety profile may make it a preferable option for patients where procedural safety is prioritized over radicality, such as those with extensive comorbidities.

References

1. Ferlitsch M, Hassan C, Bisschops R et al. Colorectal polypectomy and endoscopic mucosal resection: European Society of Gastrointestinal Endoscopy (ESGE) Guideline - Update 2024. Endoscopy 2024; 56: 516-545. doi:10.1055/a-2304-3219
2. Kaltenbach T, Anderson JC, Burke CA et al. Endoscopic Removal of Colorectal Lesions: Recommendations by the US Multi-Society Task Force on Colorectal Cancer. Am J Gastroenterol 2020; 115: 435-464. doi:10.14309/ajg.0000000000000555
3. Sidhu M, Shahidi N, Gupta S et al. Outcomes of Thermal Ablation of the Mucosal Defect Margin After Endoscopic Mucosal Resection: A Prospective, International, Multicenter Trial of 1000 Large Nonpedunculated Colorectal Polyps. Gastroenterology 2021; 161: 163-170.e163. doi:10.1053/j.gastro.2021.03.044
4. Meulen LWT, Bogie RMM, Winkens B et al. Thermal ablation of mucosal defect margins to prevent local recurrence of large colorectal polyps: a systematic review and meta-analysis. Endosc Int Open 2022; 10: E1127-e1135. doi:10.1055/a-1869-2446
5. Rex DK, Anderson JC, Pohl H et al. Cold versus hot snare resection with or without submucosal injection of 6- to 15-mm colorectal polyps: a randomized controlled trial. Gastrointest Endosc 2022; 96: 330-338. doi:10.1016/j.gie.2022.03.006

Introduction

Acetaminophen (APAP) overdose is a primary cause of drug-induced liver injury (DILI). Although the inflammatory microenvironment plays a critical role in APAP-induced liver injury (AILI), its cellular interaction network and molecular regulatory mechanisms remain incompletely elucidated. Krüppel-like factor 4 (KLF4), a zinc finger transcription factor, is known to regulate monocyte differentiation, but its functional role in the AILI inflammatory microenvironment remains unclear. This study aims to investigate the regulatory effects of myeloid KLF4 deletion on the AILI microenvironment.

Aims & Methods

By integrating multidimensional omics analysis and a myeloid-specific Klf4 knockout mouse model, we dynamically dissected microenvironmental remodeling during AILI progression. Liver samples were collected for RNA sequencing, combined with single-cell transcriptomics, flow cytometry, and molecular interaction validation to clarify the KLF4-dependent cellular subpopulation interaction network. In vivo liver imaging, histology, biochemical assays, and molecular experiments were performed to validate KLF4-dependent intercellular interactions. Primary hepatocytes and hepatocyte cell lines were used for in vitro verification.

Results

Myeloid-specific KLF4 deletion led to an increase in CXCL2⁺CXCL3⁺CD24⁺ monocytes, which activated the NF-κB signaling pathway to secrete CXCL2/CXCL3 chemokines. These chemokines bound to the CXCR2 receptor on neutrophils, driving neutrophil infiltration and neutrophil extracellular traps (NETs) formation, while amplifying the TNF-α signaling pathway. Concurrently, myeloid KLF4 knockout induced enrichment of CXCL1⁺IL17RA⁺ endothelial cells. Neutrophil-derived NETs promoted endothelial phenotypic switching toward pro-inflammatory polarization, while endothelial-derived CXCL1 further recruited neutrophils, establishing a "monocyte-neutrophil-endothelial" cellular subpopulation interaction that perpetuated microenvironmental inflammation.

Conclusion

This study reveals the molecular mechanism by which KLF4 drives inflammatory cascades in the AILI microenvironment through regulation of the myeloid-endothelial interaction network. We propose therapeutic strategies targeting NETs formation or the CXCL2/CXCL3-CXCR2 axis, providing novel targets for precise intervention in AILI.