Introduction

Acute Upper GI bleeds (AUGIB) are common and are associated with significant mortality (1). Quick recognition, resuscitation and endoscopy improves patient outcomes (2). Care bundles are known to improve care. The BSG 2018 AUGIB bundle was designed to standardise care. We aimed to audit management of AUGIB in two sites in North East England.

Aims & Methods

We retrospectively analysed patients who underwent endoscopy for AUGIB from May-October 2023. We surveyed junior doctors to assess knowledge and confidence in managing AUGIB.

Results

98 patients were identified across 2 sites, the mean age was 66, and 58% were male. The AUGIB bundle was used in 10% cases.
Recognition: 83% presented to A+E with AUGIB with the remainder already inpatients. 78% presented with melaena, and 24% were suspected variceal bleeds.

Resuscitation: 100% had EWS scores, 87% received IV fluids, and 93% patients with Hb<70 received RBC transfusion.

Risk Assessment: Mean Glasgow-Blatchford score (GBS) was 9 for both sites. Site 1 had calculated a GBS in 65% cases, and site 2 in 88%.

Table 1: Summary of treatment

	Site 1	Site 2	Overall
Variceal bleeds receiving antibiotics and terlipressin	50% (n=5)	69% (n=9)	61% (n=14)
Aspirin continued	60% (n=3)	66% (n=6)	64% (n=9)
Other antithrombotics held	100% (n=17)	91% (n=20)	95% (n=37)

Refer: of the 98 patients 70% discussed with endoscopist within 24hours, 47% had an OGD within 24 hours, and 30% required endoscopic intervention.

Review: 84% (site1) and 63% (site 2) had PPI plan, 50% (site 1) and 36% (site 2) had antithrombotic plan.

Of the small number of patients in which the bundle was used, all received appropriate resuscitation, all had GBS completed and all had OGD within 24hours of presentation.

200 surveys were sent across sites, 61 junior doctors responded. 73% felt confident in recognising AUGIB, and 65% felt confident in management. Only 32% knew appropriate initial variceal management. 40% were unsure when to call OOH endoscopist, and only 36% knew aspirin should continue.

Conclusion

Whilst recognition of AUGIB and fluid resuscitation is good, improvement is needed for risk assessment with GBS, management of suspected variceal bleeds, and timely referral for endoscopy. More detailed endoscopy reports are needed regarding PPI and antithrombotic plans.
More education with junior doctors is needed regarding management of AUGIB, and particularly when to call endoscopist and antithrombotic decisions. It would be helpful to educate staff to improve management. A reaudit of clinical management and the junior doctor survey is planned.

References

(1) Button LA, Roberts SE, Evans PA, Goldacre MJ, Akbari A, et al. (2011) Hospitalized incidence and case fatality for upper gastrointestinal bleeding from 1999 to 2007: a record linkage study. Aliment Pharmacol Ther 33: 64–76.
(2) McPherson SJ et al, National confidential enquiry into patient outcomes and deaths, Gatrointestinal haemorrhage, time to get control? 2015

Disclosure

Abstract submitted to BSG Live 24

Introduction

Immunohistochemistry (IHC) is a critical tool for tumor diagnosis and treatment. However, IHC is time consuming and costly, relies on the pathologists’ subjective interpretation. Deep learning has gained ground for predicting the biomarker expression on hematoxylin and eosin (H&E) staining images. In this study, we aim to create an automatic pipeline for the construction of deep learning models to generate virtual IHC output using H&E whole slide images and validate its clinical applicability by reader study.

Aims & Methods

We obtained 134 whole-slide images (WSIs) from 73 patients at Renmin Hospital of Wuhan University and extracted 415,463 patches from H&E-stained WSIs. Our study focused on five widely used biomarkers in pathology reports, namely anti-P40, CK-pan, Desmin, P53, and Ki-67, as recommended by the NCCN guidelines. We validated these models by using independent whole-slide images (WSIs). The number of WSIs used for each model were as follows: model-P40 (6 WSIs, 38389 Patches), model-PCK (9 WSIs, 72443 Patches), model-Ki67 (7 WSIs, 53162 Patches), model-Desmin (5 WSIs, 23974 Patches), and model-P53 (5 WSIs, 36822 Patches). We aimed to predict these biomarkers expression in H&E WSIs and quantify the percentage of Ki-67. There are three main steps: Firstly, we employed HEMnet neural network to align the corresponding IHC and H&E WSIs, transfering the molecular labels from IHC to H&E images. Secondly, pathologists reviewed the annotations made by HEMnet and corrected HE-IHC mismatched tiles using VIA labelling platform. Lastly, the deep learning models were trained to predict positive tiles. The performance of models was assessed by sensitivity, specificity, accuracy, and the area under the receiver operating characteristic curve (AUC). To assess the applicability of models, we randomly selected 30 cases including H&E and IHC WSIs for three pathologists to write the reports in the reader study by reading the interpretation of real IHC and AI-generated IHC.

Results

The sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve (AUC) of the models for classifying positive pixels of each biomarker was: P40 (91.64%, 87.39%, 88.66%, AUC: 0.95), PAN-CK (92.40%, 89.35%, 90.81%, AUC: 0.96), Ki67 (89.63%, 86.04%, 86.77%, AUC: 0.95), Desmin (91.44%, 88.11%, 89.17%, AUC: 0.96), and P53 (75.44%,86.52%,83.04%, AUC: 0.90). The predicted Ki-67 percentage was comparable to the assessments made by expert pathologists, with a difference ranging from 7.00%±3.69%. In the reader study, compared with real-IHC pathology report, the accuracy of AI-IHC pathology report of each biomarker was: Desmin(100%,66/66), Pan-CK(98.3% , 59/60), P53(98.3% ,59/60), T-stage(84.8% .56/66), P40(96.7% ,29/30). and there is no significant difference between the quatification of Ki-67 score(t= 0.253 ,P= 0.800).
​

The result of Reader Study
Items	Pathology report's accuracy of AI-IHC compared with Real-IHC					T test of Ki-67
	Desmin	Pan-CK	P53	T-stage	P40
Pathologist 1	100.0% (22/22)	100.0% (20/20)	70.0% (21/30)	68.2% (15/22)	100.0% (10/10)	t= 0.475 (P= 0.637)
Pathologist 2	100.0% (22/22)	95.0% (19/20)	66.7% (20/30)	95.5% (21/22)	100.0% (10/10)	t= - 0.775 (P= 0.443)
Pathologist 3	100.0% (22/22)	100.0% (20/20)	60.0% (18/30)	90.9% (20/22)	90.0% (9/10)	t= - 0.510 (P= 0.613)
Average	100.0% (66/66)	98.3% (59/60)	98.3% (59/60)	84.8% (56/66)	96.7% (29/30)	t= 0.253 (P= 0.800)

Conclusion

Our deep learning models have demonstrated promising performance in predicting gastrointestinal tumor biomarkers based on H&E slides. The utilization of these models can alleviate the burden of IHC staining and clinicopathological assessments. Furthermore, these models have the potential to aid in patient grading, facilitate informed treatment decisions, and provide valuable prognostic assessments.

Disclosure

There is no conflict of interest in this abstract.

Introduction

Decreased vagus nerve activity and increased inflammatory immune cells are observed in ulcerative colitis (UC) (1, 2). Due to its anti-inflammatory and protective properties, vagus nerve stimulation (VNS) has garnered attention for UC therapy (3). Non-invasive transcutaneous auricular vagus nerve stimulation (NitaVNS), devoid of the side effects associated with invasive techniques, demonstrates protective anti-inflammatory effects in our mouse UC-like model of colitis (4), although the specific cellular mechanisms remain unclear.

Aims & Methods

To evaluate the effects of NitaVNS on the distribution of granulocytes, macrophages, natural killer (NK) cells, and CD4⁺ and CD8⁺ T cells in the colon tissue, spleen, and mesenteric lymph nodes of a UC-like colitis mouse model, NitaVNS was administered to C57BL/6 male mice daily for 10 min, beginning one day before colitis induction with 5% dextran sulfate sodium for 5 days in water (the control group received regular water). This continued until the end of the study, with no stimulation in sham mice. The daily disease activity index (DAI) was evaluated along with distal macroscopic scores at the time of sacrifice. The frequencies of granulocytes (Ly6G), macrophages (F4/80), NK cells (NK1.1), CD4⁺ T cells (CD3, CD4), and CD8⁺ T cells (CD3, CD8) were analyzed in the cecum, proximal, mid and distal colon, spleen, and mesenteric lymph nodes (MLNs) using flow cytometry.

Results

NitaVNS in colitic mice significantly improved the DAI and macroscopic scores related to rectal bleeding, colon bleeding, fecal consistency loss, and shortened colon length compared to sham-stimulated colitic mice. In contrast, no changes were observed in the non-colitic mice. While NitaVNS did not alter the frequency of Ly6G⁺ cells in the cecum, mid/distal colon, and MLNs, it significantly decreased the positivity of these cells in the proximal colon and spleen of mice with colitis without affecting non-colitic mice. NitaVNS significantly decreased the frequency of F4/80⁺ cells in the mid-colon but did not influence these cells in the cecum, proximal and distal colon, spleen, or MLNs. In colitic conditions, NitaVNS significantly increased NK cell frequency in the spleen without affecting non-colitic mice. Moreover, NitaVNS did not alter the frequency of NK cells in the colon or MLNs in colitic or non-colitic mice. Additionally, NitaVNS did not induce changes in CD4⁺ and CD8⁺ T cell distribution in the colon tissue, spleen, or mesenteric lymph nodes of colitic and non-colitic mice.

Conclusion

These results suggest that NitaVNS could potentially reduce inflammation in colitic mice, locally and systemically, by decreasing the frequency of granulocytes in the colon and spleen and colonic macrophages. Additionally, NitaVNS increased the number of splenic NK cells, potentially contributing to its systemic effects. These findings indicate promising therapeutic potential for NitaVNS.

References

1. Ghia JE, Blennerhassett P, Kumar-Ondiveeran H, Verdu EF, Collins SM. The vagus nerve: a tonic inhibitory influence associated with inflammatory bowel disease in a murine model. Gastroenterology. 2006;131(4):1122-30.
2. Wiese JJ, Manna S, Kühl AA, Fascì A, Elezkurtaj S, Sonnenberg E, Bubeck M, Atreya R, Becker C, Weixler B, Siegmund B, Patankar JV, Prüß MS, Schumann M. Myenteric Plexus Immune Cell Infiltrations and Neurotransmitter Expression in Crohn's Disease and Ulcerative Colitis. J Crohns Colitis. 2024 Jan 27;18(1):121-133.
3. Verma N, Mudge JD, Kasole M, Chen RC, Blanz SL, Trevathan JK, Lovett EG, Williams JC, Ludwig KA. Auricular Vagus Neuromodulation-A Systematic Review on Quality of Evidence and Clinical Effects. Front Neurosci. 2021 Apr 30;15:664740.
4. Hesampour F, Tshikudi D, Veysel Özden A, Bernstein CN, Ghia JE. A54 The impact of non-invasive transcutaneous auricular nerve stimulation (NitaVNS) on the development of experimental colitis in mice. J Can Assoc Gastroenterol. 2023 Mar 7;6(Suppl 1):30.

Disclosure

F. Hesampour: None Declared, D. Tshikudi: None Declared, A. Veysel Özden: The employee of the company providing the stimulator, C. N. Bernstein: None Declared, J-E. Ghia: None Declared.

Clinical Case Summary

Introduction: Endoscopic Full-thickness Resection (EFTR), full-layer resection and suture using a flexible endoscope alone, is less invasive than Laparoscopy and Endoscopy Cooperative Surgery (LECS) because it does not require stromal processing and does not involve vagotomy, and is attracting attention as a new treatment for submucosal tumors(SMT). However, suturing the gastrointestinal tract using a flexible endoscope alone is problematic because the equipment is expensive and the technique is difficult. On the other hand, Laparoscopic Intragastric Surgery (LIGS), developed by Ohashi et al. in 1995, is a highly safe procedure. Combining EFTR with suturing by LIGS (EFTR-LIGS) enables accurate resection and safe suturing, but this has not been reported.
Aim & Methods: LIGS is a procedure in which a single laparoscopic port is created directly into the stomach, the device is inserted, and surgery is performed from the lumen of the stomach as in conventional laparoscopic surgery. In this presentation, we will demonstrate the technique of EFTR-LIGS in two cases. First case was 76 years-old man who was admitted after endoscopic hemostasis for bleeding from GIST in the stomach. On Day 3 of admission, emergency surgery was necessary due to rebleeding. EFTR was selected, as the procedure, though full-layer resection was possible, suturing was not possible due to amount of clot, and the defect was sutured by LIGS. Second case was 75 years-old woman with gastric GIST. After full-layer resection by EFTR, a laceration of the pharynx occurred when retrieval through the pharynx, we performed LIGS to extract the tumor through the abdominal wall and suture the defect.
Results: The average suture time for LIGS is just 5 minutes. There were no complications and average postoperative length was 5days.
Conclusion: The collaboration of EFTR and LIGS is a minimally invasive treatment for that is safe, not difficult and inexpensive, and is very useful procedure for SMT in a stomach.

Introduction

Data on using Intestinal Ultrasonography (IUS) for monitoring colonic lesions and treatment response in ulcerative colitis (UC) are still limited and most results are from single-center units usually performed in centers with a special expertise in IUS.

Aims & Methods

Our multicenter study aimed to identify predictive factors and monitor early response after different therapies in UC.
Methods: From July 2022 to Oct. 2023, we conducted a multicenter study at 5 IBD centers. UC pts starting biological therapies or small molecules were included, and underwent colonoscopy (CS), IUS, clinical assessments at baseline and at 12 weeks. All pts received standard of care therapy according to ECCO guidelines. Exclusion criteria were disease limited to the rectum, active infections, and inability or contraindication to perform CS and/or IUS within the time intervals established by the study. Colonic wall thickening (CWT), vascularization (CWF), Milan Ultrasound Criteria (MUC), Mayo endoscopic score (MES), total/partial Mayo score were evaluated.

Results

Eighty-four UC patients were enrolled and eligible for starting biological therapy or small molecules. Forty-nine out of 84 pts (58.4%) were male, 40 pts (47.6%) had extensive colitis and 44 pts (52.4%) had left colitis, with a disease duration of 20 months (1-336); 53 pts (63%) were steroid-dependent/refractory. Forty-one pts (48.9%) started anti-TNFs, 14 pts (16.6%) anti-IL12/23 or anti IL 23, 16 pts (19%) vedolizumab, and 13 pts (15.5%) JAKi. After 12 weeks, 39 out of 84 patients (46.4%) had partial Mayo score<2, 31 patients (36.9%) 2-4, 10 patients (11.9%) 5-7, and 4 patients (4.76%) >7. Forty-three out of 84 patients (51.2%) had MES=0-1, while 41 out of 84 patients (48.8%) had MES=2-3. Fifteen out of 84 patients (17.9%) had ultrasonographic response (defined as CWT<3mm) and 26 out of 84 patients (30.1%) had MUC<6.2 (1). Logistic regression was performed to evaluate the relationship between clinical/endoscopic and ultrasonographic characteristics and early IUS response at 3 months. Univariable analysis showed that active smoking ([RR], 1.9; 95% CI, 1.2–3.1, p<0.005), appendectomy ([RR], 2.5; 95% CI, 1.9–3.2, p<0.0001), partial Mayo score <2 ([RR], 2.18; 95% CI, 1.5–3, p<0.001) were associated with higher risk of response at 3 months. Inversely, severe endoscopic lesions (MES 3) (RR, 0.3; 95% CI, 0.2–0.6; p<0.0001), presence of lymph-nodes, mesenteric hypertrophy and vascularization (p<0.001, RR 0.36, 0.28, 0.45 respectively) were associated with a lower risk of response at 3 months. CWT was associated with a lower risk of response at 3 months (RR 0.66, 95% CI, 0.53-0.81, p<0.0001) and every increased mm was associated with a 34% reduction of IUS response. MUC was associated with a lower risk of response at 3 months (RR 0.78, 95% CI, 0.7-0.87) and every increased of one point was associated with a 22% reduction of IUS response. In the multivariable analysis, CWT and MUC were the only predictive factors associated with IUS response at 3 months (RR 0.70, 0.78 respectively, p<0.04). A CWT<5.5 mm showed a 2.5 risk of treatment response at 3 months.

Conclusion

Our multicenter study demonstrated that IUS allows close monitoring of treatment in UC. MUC, and in particular CWT, are valuable parameters to predict early response in UC.

References

1)Allocca M, et al. Predictive value of Milan ultrasound criteria in ulcerative colitis: a prospective observational cohort study. United European Gastroenterol J. 2022; 10:190-7.