Introduction

Acute severe colitis (ASC) is an important cause of morbidity and mortality in Ulcerative Colitis (UC), requiring hospitalisation and, frequently, colectomy. Intravenous corticosteroids (CS) remain the first-line medical treatment. Approximately 40% of episodes of ASC do not respond to this treatment and require rescue therapy with ciclosporin (CIC) or infliximab (IFX)¹. In the past decades, these treatments and protocol-driven management algorithms led to reduced mortality and colectomy rates. A simple clinical scoring system (the Admission Model for the Intensification of Therapy in Acute Severe Colitis (ADMIT-ASC))³, based on CRP, albumin, and the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) score, was recently developed to predict the steroid response on admission.

Aims & Methods

We aimed to retrospectively assess the steroid non-response during admission with ASC and the usefulness of the new prognostic clinical index ADMIT-ASC at admission to predict steroid response in a Belgian tertiary center. All patients admitted with ASC between 1^st January 2015 and 1^st April 2023 were identified from our inflammatory bowel disease database at Erasme University Hospital. Inclusion criteria were ASC patients admitted at the hospital, standard treatment with at least 3 days of intravenous CS and endoscopy evaluation upon admission. ASC was defined according to modified Truelove and Witts’ criteria as ≥6 bloody stools/day with one or more markers of systemic disturbance (tachycardia >90 beats/min, temperature >37.8°C, haemoglobin <105 g/L or CRP >30 mg/L). Steroid non-response was defined as the need for medical rescue therapy (CIC of IFX) or colectomy during the admission. ADMIT-ASC index consists of four points: CRP ≥100 mg/L (1 point), albumin ≤25 g/L (1 point) and UCEIS score ≥4 (1 point) or ≥7 (2 points).

Results

Table I Admission Demographics data (n= 84)	Steroid response (n=49)	Steroid non-response (n=35)	P value
Median disease duration (years) (IQR)	3.6 (0.3-0.9)	2.1 (0.8-5.5)	0.5
Montreal Classification	E1 : 5/49 (10%) E2 : 20/49 (41%) E3 : 24/49 (49%)	E1 : 0/35 E2 : 12/35 (34%) E3 : 23/35 (66%)	0.084
5-ASA, n (%)	22 (45%)	10 (29%)	0.13
Methotrexate or thiopurine, n (%)	6 (12%)	9 (26%)	0.11
Infliximab, n (%)	4 (8.2%)	8 (23%)	0.058
Vedolizumab, n (%)	7 (14%)	5 (14%)	>0.9
Tofacitinib, n (%)	2 (4.1%)	2 (5.7%)	>0.9
Readmission, n (%)	12 (24%)	10 (29%)	0.7
5-ASA, 5-aminosalicylate P values from Wilcoxon rank-sum test or Fisher’s exact test.

Out of 127 patients admitted with UC and treated with intravenous CS during three days, 84 (45% male, median age of 31 years old) were included in the study. Admission demographics and clinical characteristics are described in Table 1.
For 17 patients (20%), the admission was their index presentation of UC. Response to CS was seen in 49 patients (58%). Thirty-three patients (39%) received medical rescue therapy (17/33 IFX and 16/33 CIC). Colectomy rate during admission was 13% after a median duration of 18 days (IQR: 16-54). Admission C reactive protein (CRP) (p=0.036), albumin (p=0.026) and UCEIS scores (p=0.022) were significantly associated with steroid non-response. Patients scoring 0, 1, 2, 3 and 4 had steroid response rates of 90%,75%, 55%, 19% and 0%, respectively. Scoring of ≥3 was 75% (95% CI, 0.43 to 0.95) predictive of steroid failure (OR 5.08, 95%, CI 1.38 to 24.5).

Conclusion

In this tertiary referral cohort study, we confirmed that the ADMIT-ASC index is a simple clinical tool that can be used on the day of admission to predict steroid non-response in ASC with a threshold of ≥3 to identify patients who are unlikely to respond to intravenous CS and enabling timely treatment escalation or surgery.

References

1. Travis S, Satsangi J, Lémann M. Predicting the need for colectomy in severe ulcerativecolitis: a critical appraisal of clinical parameters and currently available biomarkers. Gut 2011;60:3–9.
2. Travis SP, Farrant JM, Ricketts C, et al. Predicting outcome in severe ulcerative colitis.Gut 1996;38:905–10.
3. Adams A, Gupta V, Mohsen W, et al. Gut 2023;72:433–442.

Disclosure

VB has not disclosure.
CDT has not disclosure.
CM has not disclosure.
AC has received lecture fees from Galapagos, Abbvie, Janssen, celltrion, Pfizer, Takeda.
DF has received lecture fees from Abbvie, Astrazeneca, Dr.Falk Pharma, Ferring, Janssen, Mundipharma, MSD, Pfizer, Takeda, Amgen, and advisory board fees from Abbvie, Janssen,Takeda, Celltrion, Amgen.
CL has received consultancy fees from Janssen, Abbvie, Takeda and Galapago and speaker fees from Sandoz, Janssen, Abbvie

Introduction

Postoperative ileus, is one of the most common causes of prolonged hospital stays after abdominal surgery which cause from physiologic hypomotility of the gastrointestinal tract occurring immediately after abdominal surgery. Multi-modal approach to the resolution of postoperative ileus includes ERAS protocol such as opioid minimization, early ambulation, intake of prokinetic drug. Mosapride citrate (mosapride) is known to promote gastrointestinal motility. The objective of this study is to evaluate the effects of mosapride on postoperative ileus and postoperative gastrointestinal motility in patients undergoing elective open and laparoscopic colorectal surgery.

Aims & Methods

The study was approved by ethics committee of the Faculty of Medicine Ramathibodi Hospital Mahidol University (Ref. Number COA.MURA2021/328,ClinicalTrials.gov Identifier: NCT04905147). Forty-four colorectal cancer patients, undergoing open and laparoscopic colorectal surgery in Ramathibodi Hospital during July 2021-August 2022, were randomly assigned to a mosapride group or control group. The mosapride group received 15 mg of mosapride by enteric route with 50 ml of water three times a day, starting on postoperative day 1. The control group received 15 mg of placebo drug with 50 ml of water at the same time. Postoperative time to the first passage of flatus and the first bowel movement were evaluated by one investigator with triple blind study. Time to step diet, length of postoperative hospital stays, and adverse effects were also evaluated in secondary outcomes.

Results

All forty four patients were include, twenty-three in control group and twenty-one in mosapride group. There were no statistically significance differences between mean age and type of surgery (laparoscopic or open) in two group (P>0.05). Time to first bowel movement and time to passage of flatus after operation were significantly shorter in the mosapride group than the control group (26 vs 50 hours, P=0.004 and 40 vs 70 hours, P=0.003, respectively). Time to step diet (soft diet) was also shorter in the mosapride group (90 vs 132 hours, P=0.004). Time to defecate was less in mosapride group than control group (80 vs 120 hours, P <0.001). Length of hospital stay was significantly shorter in patients receiving mosapride (7 vs 10 days, P=0.004).

Conclusion

This study demonstrated the efficacy of mosapride when administered to patients who underwent elective colorectal surgery. Mosapride significantly enhance recovery of gastrointestinal motility and shorter length of hospital stay with no significant adverse effects.

References

1. Collins TC, Daley J, Henderson WH, Khuri SF. Risk factors for prolonged length of stay after major elective surgery. Ann Surg 1999;230:251–9
2. Vather R, O'Grady G, Bissett IP, Dinning PG. Postoperative ileus: mechanisms and future directions for research. Clin Exp Pharmacol Physiol. 2014;41(5):358-370.
3. Goldstein JL, Matuszewski KA, Delaney C, Senagore A, Chiao E, Shah M, et al. Inpatient economic burden of postoperative ileus associated with abdominal surgery in the United States. P AND T.2007;32(2):82.
4. Venara A, Neunlist M, Slim K, Barbieux J, Colas PA, Hamy A, et al. Postoperative ileus: Pathophysiology, incidence, and prevention. J Visc Surg 2016;153:439-46.
5. Luckey A, Livingston E, Taché Y. Mechanisms and Treatment of Postoperative Ileus. Arch Surg. 2003;138(2):206–214.
6. Georgiadis, G & Markantonis, Sophia & Triantafillidis, John. (2000). Prokinetic agents: Current aspects with focus on cisapride. Annals of Gastroenterology. 13.
7. Reynolds, J.C. & Putman, P.E. (1992) Prokinetic Agents, Gastroenterol Clin of North Am, Vol.21, pp.567-596.
8. Taniyama, K., Makimoto, N., Furuichi, A. et al. Functions of peripheral 5-hydroxytryptamine receptors, especially 5-hydroxytryptamine₄ receptor, in gastrointestinal motility. J Gastroenterol 35, 575–582 (2000).

Introduction

Inflammatory bowel disease (IBD) is characterized by chronic inflammation due to an uncontrolled immune response orchestrated through, i.e. neutrophils. The basement membrane acts as a front-line defense promoting tissue integrity, where the α-3 chain of type IV collagen is solely expressed on the outermost layer of the mucosa. Detection of subclinical ulceration is crucial since early-stage IBD presents a unique window of opportunity for intervention, as the disease might become a self-sustaining process once deep inflammation becomes established. We therefore, wanted to develop a biomarker reflecting early tissue injury, aiding in the implementation of prompt treatment.

Aims & Methods

A competitive enzyme-linked immunosorbent assay quantifying a human neutrophil elastase (HNE) degraded fragment of type IV collagen α-3 chain was developed (C4A3-HNE). Dilution- and spiking recovery, inter- and intra-variability, and interference were evaluated. Acceptance criteria for technical validation were a recovery of 100% ±25 and an inter-intra variability of <15%. Commercial serum samples were purchased from ProteoGenex. Biological relevance was validated in an observational study from Odense University Hospital (OUH) and healthy controls. Groups were compared using Kruskal Wallis (Dunn‘s corrected).

Results

The technical validation of the C4A3-HNE assay demonstrated acceptable results for recovery, variation, and interference. Biological relevance was assessed in commercial IBD samples and healthy donors. C4A3-HNE was elevated in both CD and UC compared to healthy (p=0.001 and <0.0001)(AUC [95% CI]: 0.820 [0.669-0.971]; 0.875 [0.775-1.000]). The results were validated in an independent cohort of IBD patients (both p<0.0001). For UC, analysis showed that compared to patients in endoscopic remission, C4A3-HNE is elevated in patients with mild endoscopic activity, decreasing dose-dependently for moderate and severe disease (T1). Fecal calprotectin and CRP levels were also lower in IBD patients with high levels of C4A3-HNE (T1). With a cut-off value of 54.1 ng/ml, C4A3-HNE could significantly discriminate between mild and severe endoscopic disease (T1).

	Median conc. (ng/ml)	[IQR]	Patients (n)
Remission Mild Moderate Severe	61.16 71.77 56.07 40.52	49.74, 65.52 53.96, 79.17 39.21, 68.71 25.65, 69.01	10 18 19 10
	Low C4A3-HNE	High C4A3-HNE	Δ %
CD: Fecal Calprotectin (µg/g) UC: Fecal Calprotectin (µg/g) CD: CRP (mg/L) UC: CRP (mg/L)	721.8 840.0 8.4 7.4	365.7 491.6 6.5 5.0	67.7 52.3 26.5 38.5
	AUC [95% CI]	Cut-off value	Sens./Spec. (%)	OR
Remission vs. mild Mild vs. moderate Mild vs. severe	0.68 [0.48–0.85] 0.68 [0.51–0.83] 0.74 (*) [0.54–0.89]	68.8 59.9 54.1	61.1/90.0 72.2/73.3 77.8/70.0	14.1 (*) [1.7–166.6] 6.9 (*) [1.8–31.1] 6.4 (*) [1.2–33.5]

Conclusion

Our study demonstrates the biological and possible clinical relevance of the novel C4A3-HNE biomarker. The biomarker is elevated in patients with IBD compared with healthy, and high levels may reflect early mucosal damage in patients with UC. Furthermore, inflammatory markers were lower in IBD patients with high levels of C4A3-HNE, pointing towards high levels being indicative of early disease. C4A3-HNE may provide early detection of mucosal damage or prediction of relapse; however, further studies are required to assess the clinical validity of this biomarker.

Disclosure

MA, MP, MK, and JM are employees of Nordic Bioscience A/S. MK owns stocks in Nordic Bioscience A/S.

Introduction

Tofacitinib is indicated for the treatment of adult patients with moderately to severely active ulcerative colitis (UC). The recommended induction scheme is 10 mg twice daily (BID) for at least 8 weeks followed by a maintenance dose of 5 mg BID. However, some patients require 10mg bid, for 16 weeks at the induction phase. Our study aimed to assess the demographics and disease characteristics of such patients and their outcome at 24 weeks.

Aims & Methods

This was a multicenter, retrospective, observational study which included patients with moderate to severe UC, who received induction therapy with Tofacitinib 10mg bid for a 16-week period. Data were collected between July 2018 and November 2022. The primary objective was disease outcome, defined as clinical remission and/or the need of steroids. Secondary outcomes were treatment withdrawal, treatment de-escalation and adverse events.

Results

In total 31 patients, are currently enrolled in our study, from 10 IBD centres [males: 51.6%, mean age at study entry: 40.0 years, median disease duration: 7 years]. Patient demographic and clinical characteristics at baseline are shown in table 1. Four patients (12.9%) discontinued treatment before week 24, due to inadequate response. De-escalation of dosing to 5mg bid tofacitinib was attempted in 13 of 27 patients (48.1%) and was successful in 7 patients (53.8%) who maintained clinical response until week 24 of the study. Of the other 6 out of 13 patients, 6 patients received again the higher dose (10 mg bid) and regained response and only one patient discontinued treatment. Overall, 85.7% (6/7) of the patients who received tofacitinib 5mg bid and 66.7% (14/21) who received 10mg bid at 24 weeks, had received more than one biologic prior to tofacitinib (P=0.34). At week 24, the partial Mayo score was available in 26 patients; 13 patients were in steroid-free clinical remission (pMayo <2). Twelve patients had mild active disease (pMayo 2-4) and 9 of them had stopped steroids. No major adverse events were observed during the entire observation period.

Table 1. Demographic and clinical characteristics of patients (N=31)
Age [years; mean (±SD)]		41.0 (±13.6)
Sex [N (%)]	Male	16 (51.6)
BMI [kg/m2; median (IQR)]		26.8 (23.7 – 28.6)
Smokers [N (%)]	Never/Current/Prior	23 (74.2)/ 3 (9.7)/ 5 (16.1)
Previous treatment [N (%)]	Systemic corticosteroids	25 (80.6)
	Thiopurines/ Methotrexate	16 (51.6)/ 2 (6.5)
	Biologics	26 (83.9)
pMayo score [N (%)]	2-4/ 5-7/ >7	9 (29.0)/ 14 (45.2)/ 8 (25.8)
EndoMayo score [Ν (%)]	2/3	10 (32.3) / 18 (58.1)

Conclusion

In a real-world setting, a 24-week treatment with tofacitinib 10mg BID is safe and the majority of patients achieve clinical remission and manage to stop steroids. De-escalation at 5mg bid is successful in more than half of them. We prospectively follow up our cohort to investigate whether these preliminary results will be confirmed for a longer period.

Introduction

Rigid surgical instruments used for conventional laparoscopic surgery provide limited movement, and it is difficult to perform skillful surgery due to their long, jointless straight features. Articulated instruments could have the same advantages seen in robotic surgery, such as excellent control in smaller spaces, restoration of more intuitive and ergonomic movements, and the ability to overcome obstacles on a direct visual line. The aim of this study was to evaluate the surgical performance and clinical outcomes of patients following laparoscopic colorectal surgery with multijoint laparoscopic instruments, ArtiSential® (LivsMed, Seongnam, Korea), compared with those using conventional instruments.

Aims & Methods

Patients aged 19–80 years undergoing elective laparoscopic surgery for colorectal disease between December 2021 and November 2022, were consecutively enrolled. The first 20 cases underwent conventional laparoscopic surgery, and the latter 50 cases underwent laparoscopic surgery using ArtiSential®. Unedited operative videos were submitted to the Crowd-Sourced Assessment of Technical Skills (C-SATS) platform for evaluation using the Global Operative Assessment of Laparoscopic Skills (GOALS), which is a validated tool for technical proficiency. Each of GOALS’ four domains (bimanual dexterity, depth perception, efficiency, and tissue handling) was scored on a Likert scale between 1 and 5, scoring anchor, with a total score ranging from 4 to 20. The learning curve analysis was performed using the cumulative sum control chart (CUSUM) for GOALS grades (Registration number: KCT0006798).

Results

There was no significant difference between group with regards to type of operation, hospital stay, and 30-day postoperative complication. The GOALS’ grades were similar between the two groups (15.7 ± 0.7 vs. 15.9 ± 0.5, P = 0.190), but the scores in two domains (depth perception and tissue handling) were significantly higher in the ArtiSential® group (3.9 ± 0.3 vs. 4.0 ± 0.2, P = 0.014 and 3.9 ± 0.2 vs. 4.1 ± 0.2, P = 0.048, respectively) compared with those in the conventional group. In addition, patients in the ArtiSential® group experienced a shorter operation time (122.3 ± 58.9 vs. 88.1 ± 35.1, P = 0.022) and less intraoperative blood loss (56.5 ± 69.9 vs. 29.8 ± 1.4, P = 0.002) than those in the conventional group. According to the CUSUM learning curve analysis, the first 10 cases using ArtiSential® were in the inexperienced phase, and the remaining 40 cases were in the experienced phase. The GOALS’ score in the experienced phase of ArtiSential® was improved compared with that in the conventional group (16.0 ± 0.5 vs. 15.7 ± 0.7, P = 0.037).

Conclusion

A plateau in the learning curve of laparoscopic colorectal surgery performed with an articulated instrument was observed in approximately 10 cases, and it can be expected that surgical proficiency in the experienced phase increases without deterioration of clinical outcome as compared to that in conventional surgery.

References

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Disclosure

This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grantnumber: HI20C2092).

Introduction

To evaluate the utility of the unroofing technique in the diagnosis of gastrointestinal subepithelial tumors (SETs), we performed a multicenter retrospective study.

Aims & Methods

This study was conducted in 10 hospitals and involved all eligible patients who underwent unroofing techniques to gain biopsy for gastrointestinal SETs between April 2015 and March 2021. The primary endpoint was the rate of correct diagnosis with the unroofing technique, and the secondary endpoints were the incidence of adverse events and the factors contributing to the correct diagnosis.

Results

The study included 61 patients with 61 gastrointestinal SETs, a median tumor size of 20 mm, and a median procedure time of 38 minutes with 82% successful tumor exposure. The rate of tissue acquisition was 98.4%, and the rate of pathological diagnosis was 72.1%. In 44 cases with a pathological diagnosis, two showed discrepancies with the postresection pathological diagnosis. No factors, including facility experience, organ, tumor size, or tumor exposure, significantly affected the correct diagnosis. No significant differences in the correct diagnosis rate were observed between less than ten experiences and more than ten experiences (74.1 vs. 70.6%). The correct diagnosis rates for tumors <20 mm and ≥20 mm were 76.9% and 65.7%, respectively. There was one case of delayed bleeding and two cases of perforations.

Conclusion

The diagnostic yield of the unroofing technique was acceptable. The unroofing technique was beneficial regardless of institutional experience, organ, tumor size, or actual tumor exposure.