Introduction

Acute severe ulcerative colitis (ASUC) is a medical emergency associated with a significant mortality rate. The literature amongst medium-term outcomes of ASUC remain limited.

Aims & Methods

This study aims to determine if early medical rescue therapy in patients with ASUC reduces the need for colectomy in the medium-term. This was a retrospective cohort study conducted in an Australian quaternary IBD centre. Adult UC patients admitted between January 2015 and December 2021 that fulfilled the Truelove and Witts’ criteria for ASUC were identified and included. Demographic and clinical data was collected including date of colectomy and IBD-related readmission at 6 months. Patients who did not receive Infliximab (IFX) as rescue therapy or following discharge were excluded. Medium term was defined as within 1-3 years. The primary outcome of this study was colectomy (within 1-3 years), secondary outcomes were UC-related hospital re-admissions at 6 months. Kaplan-Meier curves were utilised to investigate colectomy and readmission-free days from the initial flare to the commencement of biologics. Multivariate log binomial models were employed to explore the significant factors related to colectomy and six-month readmission. The study was approved by the Southern Adelaide Local Health Network Ethics Committee LNR/22/SAC/157.

Results

Baseline Characteristics Male / Female, n Age, y, median (IQR)	Patients (n = 32) 17/15 36 (28-48)
Colectomy, n (%)	11 (34.4)
Length of stay in hospital, days, median (IQR) Flare to IFX commencement, days, median (IQR) IFX commencement to colectomy, days, median (IQR)	10 (7.8-13.3) 5 (3-7.3) 9 (5-330)
D1 CRP, mg/L, median (IQR) D3 CRP, mg/L, median (IQR)	95 (37.6-157.7) 29.7 (15.1-98.4)
D1 Albumin, g/L, median (IQR) D3 Albumin, g/L, median (IQR)	29 (23.8-32) 22 (20.5-27)
Haemoglobin, g/L, median (IQR) Platelet, 10^9/L, median (IQR)	119.5 (110-129.5) 400 (306-492.75)
Statistical Analysis - Colectomy Female D1 CRP D3 CRP D1 Albumin D3 Albumin	Odds Ratio / p-value 6.59 / 0.2 1.02 / 0.3 0.98 / 0.3 2.09 / 0.074 0.24 / 0.05
Statistical Analysis - Re-admission Female D1 CRP D3 CRP D1 Albumin D3 Albumin	Odds Ratio / p-value 1.14 / > 0.9 1.0 / 0.7 1.0 / > 0.9 0.79 / 0.2 0.98 / > 0.9

Table 1. Baseline Characteristics

267 patients with UC flares were identified between the shortlisted timeframes. After exclusions, 32 patients remained (median age, 36 years (18-71); 56.3% male). The median time of admission to the commencement of IFX was 5 days (3-7.3). The overall colectomy rate was 34.4% (11/32); of these patients, 3 needed a colectomy during their index presentation and 8 within the subsequent 3 years. The median time from IFX commencement to colectomy was 9 days (5-330). 9 patients (28.1%) had a UC-related readmission within 6 months of discharge. Biochemical results (day 1 CRP, day 1 albumin) and demographics such as age and gender were analysed, however we could not find any statistically significant association with the need for colectomy or UC-related readmission. The overall trend and likelihood of undergoing colectomy and having a UC-related admission rose with longer durations between IFX initiation, however the results were not statistically significant.

Conclusion

The need for colectomy remains high in patients with ASUC. We were unable to demonstrate any statistically significant predictors of colectomy in the medium term due to the small sample size. Future larger prospective studies are warranted to obtain statistical significant findings for our current study.

Introduction

Despite the progress in advanced therapies (AT) for ulcerative colitis (UC), selecting a second-line treatment after failure remains challenging. Recent guidelines recommend Ustekinumab (UST), Tofacitinib (TOFA), or Upadacitinib (UPA) as high-efficacy options after prior AT failure. However, no real-world studies have compared all three therapies.

Aims & Methods

Retrospective multicenter study (8 centers) of UC patients who failed ≥1 advanced therapy. Patients were stratified into UST, TOFA, or UPA groups and assessed at 16 and 52 weeks. The primary outcome was steroid-free clinical remission (SFCR) based on the Patient Reported Outcomes-2. Secondary outcomes included biochemical remission (fecal calprotectin ≤ 250 µg/g) and endoscopic remission (Mayo Endoscopic Subscore=0). Time to remission was assessed using Cox regression analysis. A subanalysis was performed including only second-line use after anti-TNF failure. Multivariate analysis was performed, adjusted for duration of disease, extent and number of prior therapies.

Results

We evaluated 259 cases [54.4% (n=141) female; diagnostic age 32.3 ± 15.1 years] who initiated UST (n=105; 40.5%), UPA (n=87; 33.6%) or TOFA (n=67; 25.9%). The groups were similar in disease duration (UST: 11.6 ± 8.0; UPA: 9.8 ± 6.4; TOFA: 10.4 ± 5.4 years) and 49.8% (n=129) had failed ≥2 previous AT
At week 16, UPA showed higher SFCR compared to UST (OR 2.1; p=0.014) and TOFA (OR 2.1; p=0.040), with no difference at week 52. Biochemical remission was higher with UPA at week 16 vs UST (OR 2.3; p=0.015) and TOFA (OR 2.1; p=0.039) and at week 52 vs UST (OR 4.7; p=0.010) and TOFA (OR 4.6; p=0.013). At week 16, endoscopic remission was higher with UST (OR 3.5; p=0.036) and UPA (OR 3.1; p=0.041) compared to TOFA; and at week 52, UPA was associated with higher endoscopic remission vs UST (OR 3.6; p=0.036).
In Cox regression, UPA achieved earlier biochemical remission than UST (HR 1.9; p<0.001) and TOFA (HR 1.8; p=0.011). JAK inhibitors led to earlier endoscopic remission than UST (vs UPA: HR 3.2; p<0.001; vs TOFA: HR 1.4; p=0.002).
In the subanalysis, UPA as second-line therapy demonstrated higher SFCR than TOFA (OR 3.6; p=0.035) and higher endoscopic remission at week 52 than TOFA (OR 12.0; p=0.017), and trend-wise compared to UST (OR 4.5; p=0.090).

Conclusion

Even though all three medication demonstrated high efficacy in bio-exposed UC patients, UPA achieved better results in this real world study.

References

Singh, Siddharth, et al. "AGA living clinical practice guideline on pharmacological management of moderate-to-severe ulcerative colitis." Gastroenterology 167.7 (2024): 1307-1343.

Introduction

Piecemeal endoscopic mucosal resection (pEMR) is the preferred treatment for large non-pedunculated colorectal polyps (LNPCPs)[1,2]. A major limitation of pEMR is residual or recurrent adenoma (RRA), which was reported to in 15%-30% of cases at first surveillance colonoscopy (SC1)[3], performed 3-6 months after the index procedure, but is reduced to the range of 3%-5% by applying ablative measures to the post-EMR resection margin[4].

Aims & Methods

This study aimed to evaluate the effects of late SC1 on RRA.
This is an analysis of a prospectively collected cohort of adult patients referred for pEMR at two academic centers in Israel, from 2016 to 2023. We included all patients who underwent pEMR of LNCPCs and completed SC1.
We compared outcomes between patients who completed early SC1 at 3-6 months following the index procedure with patients who completed late SC1 later than 6 months. All procedures and surveillance colonoscopies were performed by experienced endoscopists trained in pEMR using high-definition scopes. EMR was followed by thermal ablation of the entire mucosal defect margin with snare soft tip coagulation, as previously described[4].
Scar evaluation at SC1 was performed with high-definition white light and chromoendoscopy. Our primary endpoint was RRA at SC1.
Analyses were performed per lesion. We compared baseline parameters and outcome rates between groups, and performed multivariate analysis to assess the adjusted association of months to SC1 with RRA.

Results

We analyzed 516 lesions that underwent index pEMR resection and subsequent SC1. Baseline parameters and recurrence rates are presented in Table 1. The early SC1 group (n=371) underwent SC1 at a mean of 5.1 months versus a mean of 11.1 months in the late SC1 group (p<0.01; Table 1). Polyp size in the early SC1 group was significantly larger than that in the late SC1 group (mean size 35.9 mm [SD 13.9] vs. 32.1 mm [SD 12.4], p<0.01; Table 1). The distribution of lesion location, granularity differed between the groups (Table 1). However, there were no significant differences in lesion Paris classification or rates of high grade dysplasia (Table 1).
We found no statistically significant difference in the rate of recurrence at SC1 between the two groups (6.3% in the standard group versus 4.8% in the delayed group, p=0.64). Additionally, a sub-analysis comparing the early SC1 group to patients with very late SC1 (>12 months – mean time to SC1 17.9 (SD [5.4] months) and did not reveal significant difference in recurrence at SC1 (6.2% in the early SC1 vs 6.3% in the very late group, p=1).
Multivariate analysis, adjusted for lesion size, location, and high-grade dysplasia, showed that time to SC1 was not significantly associated with RRA (odds ratio 1.05, 95% confidence interval 0.98-1.13).

TABLE 1. Comparison of baseline variables and outcome between the early and late SC1.

	Early SC1 (n=371)	Late SC1 (n=145)	P value
Time to SC1, months	5.1 (1.1)	11.1 (5.6)	<0.01
Age, years	65.4 (10.4)	68.0 (10.2)	0.01
Female, n (%)	168 (45.4)	51 (35.2)	0.05
Lesion Size, mm	35.9 (13.9)	32.1 (12.4)	<0.01
Distal location, n (%)	111 (29.9)	29 (20.0)	0.03
Granular morphology, n (%)	230 (63.7)	74 (53.2)	0.04
Paris IIb/IIc/III, n (%)	39 (10.5)	15 (10.3)	1.00
High grade dysplasia, n (%)	97 (26.1)	33 (22.8)	0.49
Recurrence at SC1, n (%)	23 (6.2)	7 (4.8)	0.70

SC1, First surveillance colonoscopy

Conclusion

Late SC1 is not associated with an increased RRA. Hence, we suggest that high-quality pEMR with margin ablation may alleviate the need for early SC1, thereby reducing healthcare and patient burdens. Further interventional studies are required.

References

[1] Ferlitsch M, Moss A, Hassan C, et al. Colorectal polypectomy and endoscopic mucosal resection (EMR): European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline. Endoscopy 2017; 49: 270–297. doi:10.1055/S-0043-102569/ID/JR15335-1/BIB
[2] Shaukat A, Kaltenbach T, Dominitz JA, et al. Endoscopic Recognition and Management Strategies for Malignant Colorectal Polyps: Recommendations of the US Multi-Society Task Force on Colorectal Cancer. Gastroenterology 2020; 159: 1916-1934.e2. doi:10.1053/j.gastro.2020.08.050
[3] Belderbos TDG, Leenders M, Moons LMG, et al. Local recurrence after endoscopic mucosal resection of nonpedunculated colorectal lesions: Systematic review and meta-analysis. Endoscopy 2014; 46: 388–400. doi:10.1055/S-0034-1364970/ID/JR910-7/BIB
[4] Klein A, Tate DJ, Jayasekeran V, et al. Thermal Ablation of Mucosal Defect Margins Reduces Adenoma Recurrence After Colonic Endoscopic Mucosal Resection. Gastroenterology 2019; 156: 604-613.e3. doi:10.1053/j.gastro.2018.10.003

Disclosure

The authors report no conflict of interests

Introduction

The Maastricht V/ Florence Consensus has updated guidelines for the management of Helicobacter Pylori (HP) infection with special emphasis in high clarithromycin resistance settings as it is the case in our country. In line with the recommendations of the European Guidelines on surgery of severe obesity [1] and the recommendations of the American Society of Gastrointestinal Endoscopy on endoscopy of the bariatric patient [2) a policy of systematic HP screening and overtime updated eradication was implemented in obese patients undergoing Roux-en Y gastric bypass (RYGB) surgery.

Aims & Methods

Five year period (2020-2024) single center study. The aim was, in obese patients undergoing RYGB surgery, to assess the cumulative HP eradication rate by adopting, at first line, a 10 days bismuth quadruple therapy (BQT) - proton pump inhibitor (PPI) bid and three-in-one single capsule containing bismuth, metronidazole, and tetracycline qid - and, at second line, a 14 days levofloxacin based therapy ( LBT) – PPI bid, amoxicillin 1000 mg bid and levofloxacin 500mg bid. HP infection status was assessed, at baseline, by histology or urea breath test and post treatment, by urea breath test 4-6 weeks after the end of the therapy.

Results

One thousand four hundred and forty-nine consecutive HP‑positive patients completed BQT treatment: 1160 (80.1%) female, age 43.5 (±10.5) years, median age of 44 years), age range of 18-69 years. HP was eradicated in 1220 patients – 84.2% (95%CI: 82.2%-86.0%). In the remaining 229 patients, 87 patients withdrew and HP was eradicated in 118 patients out of 145 with LBT. The intention to treat (ITT) and per protocol (PP) cumulative eradication rates were, respectively, 92.3% (95%CI: 90.9%-93.6%). and 98.0% (95%CI: 97.1%-98.6%). Eradication rates were not significantly different by gender and age.

Conclusion

By adopting the Maastricht V/ Florence Consensus BQT first line therapy and second line LBT therapy, high ITT and PP cumulative HP eradication rates are achieved leaving only a residual number of obese patients undergoing RYGB in need of the culture and susceptibility testing prior to third line treatment.

References

1. Fried M, Hainer V, Basdevant A, et al. European Guidelines on surgery of severe obesity. . International Journal Of Obesity 2007;31:569-577.
2. ASGE Guidelines. Role of endoscopy in the bariatric patient. Gastrointest Endosc 2008; 68:1-10.

Disclosure

NO CONFLICT OF INTEREST

Introduction

Eosinophilic esophagitis (EoE) is a chronic inflammatory disease characterized by esophageal dysfunction and a peak eosinophil count of >15 cells per high power field (HPF). Recent studies suggest that mast cells play a key role in its pathophysiology. This study investigates the presence of mast cells in different groups of patients with EoE.

Aims & Methods

Biopsy samples from patients newly diagnosed with EoE were analyzed, and the Eosinophilic Esophagitis Histology Scoring System (EOEHSS) grade and stage scores were calculated. Biopsy samples were divided in two groups: t0 (before the starting of EoE therapy) and t1 (after EoE therapy). Mast cells were detected using tryptase immunohistochemistry, and the maximum number of mast cells counted in a high-power field (PMC), was recorded. Univariate correlation analysis were performed between PMC and peak eosinophil count (PEC), PMC and EOEHSS grade, PMC and EOEHSS stage, PMC and EREFS.

Results

12 patients affected by EoE were divided in group 1, treated with PPIs [Esomeprazole 40 mg, bis in die (bid)] and group 2, treated with BOT (budesonide oral tablets 1 mg, bid). Univariate correlation analysis were performed at t0 and t1. Results from Pearson’s R for analysis at t0 are showed a positive linear correlation in PEC-PMC (0,567, p=0,043) and EOEHSS grade-PMC (0,559, p=0,047). At t1, EREFS-PMC had a positive correlation (0,726, p 0,005), like also EOEHSS grade-PMC (0,74, p=0,002) and EOEHSS stage-PMC (0,818, p<0,001).

	R	p
EREFS-PMC (t0)	0.244	0.423
PEC-PMC (t0)	0.567	0.043
EOEHSS grade-PMC (t0)	0.559	0.047
EOEHSS stage-PMC (t0)	0.390	0.187
EREFS-PMC (t1)	0.726	0.005
PEC-PMC (t1)	0.340	0.256
EOEHSS grade-PMC (t1)	0.74	0.002
EOEHSS stage-PMC (t1)	0.818	<0.001

Conclusion

PCM positively correlates with PEC, EOEHSS grade, EOEHSS stage and EREFS in untreated samples, supporting their role in EoE and type-2 inflammation. In treated cases, PMC correlate with PEC, EOEHSS grade, EREFS. A highly statistically significant strong positive linear correlation was found between PMC and EOEHSS stage, as the latter is more likely to reflect the whole esophageal histologic changes.
Our study suggests that mast cell count, alongside eosinophil counts, could be an important factor in evaluating anti-inflammatory therapeutic interventions and it may be a useful adjunct to existing endoscopic and histologic markers in assessing EoE severity, supporting their role in EoE and type-2 inflammation. To confirm these findings, further longitudinal prospective studies are required.

References

N. de Bortoli, P. Visaggi, R. Penagini et al., The 1st EoETALY consensus on the diagnosis and management of eosinophilic esophagitis – Definition, clinical presentation and diagnosis, Digestive and Liver Disease
Collins MH, et al. Eosinophilic esophagitis histology remission score: significant relations to measures of disease activity and symptoms. J. Pediatr. Gastroenterol. Nutr. 2020;70(5):598–603
Kanamori A, et al. Esophageal mast cells may be associated with the perception of symptoms in patients with eosinophilic esophagitis. Esophagus. 2023 Apr;20(2):333-341
Bolton SM, et al. Mast Cell Infiltration Is Associated With Persistent Symptoms and Endoscopic Abnormalities Despite Resolution of Eosinophilia in Pediatric Eosinophilic Esophagitis. Am J Gastroenterol. 2020 Feb;115(2):224-233.