Introduction

Oesophageal stent placement is a nonsurgical alternative for palliation of malignant obstruction. It is now established as a major treatment for dysphagia resulting from inoperable oesophageal cancer.

Aims & Methods

A retrospective study of all patients undergone oesophageal stent insertion at a single endoscopy unit under fluoroscopy from July 2015 to Nov 2022 was undertaken.
Aim: Evidence of immediate or late complications, repeat interventions, and for survival statistics after stent insertion.

Results

95 oesophageal stents were placed in 7 years. There were 28% Female (28/95) and 69% Males (68/95), mean age 73 (Range 47-91). The mean Indication dysphagia due to oesophageal stricture. Histology revealed: 64 adenocarcinoma, 22 squamous cell carcinoma, 5 high grade dysplasia. Location of malignancy:81 distal oesophagus, 6 proximal oesophagus, 5 Gastro-oesophageal junction and 3 Mid oesophagus. Types of stent used: 84 Fully Covered, 2 Uncovered.
No immediate complications reported apart from 2 stents moved on reintubation or extubation. The endoscopy was repeated in 43 patients.
Late complications 13% (13/95): 6 patients had Tumour overgrowth, 6 patients had Stent migration and one patient had a Food bolus. The 30 days mortality is 13%.

Conclusion

Palliative Oesophageal stent insertion in our hospital proved to be an effective treatment for patients with malignant dysphagia.
Outcomes compare favourably with published data in terms of complications and mortality.
It is a relatively safe procedure with no immediate complications and a low rate of serious acute complications.
Steps to improve post-procedure monitoring with prospective collection of data could be useful in future service development.

References

Esophageal stenting for benign and malignant disease: European Society of Gastrointestinal Endoscopy (ESGE) Guideline – Update 2021

Introduction

Crohn's disease (CD) is a chronic inflammatory bowel disease of unknown etiology with no cure. Reliable tools for the early identification of patients at risk, especially for long-term prediction, remain to be defined.

Aims & Methods

This study aimed to employ machine learning to develop proteomics-based models to predict future CD onset. We utilized data from 39,634 participants without baseline CD from the UK Biobank (UKB) as the training cohort. Feature selection involved Cox regression to identify proteins associated with incident CD, followed by automated machine learning-based importance ranking using five-fold cross-validation (10 repeats). Four machine learning algorithms were applied to construct predictive models. Independent validation was conducted in a geographically distinct UKB cohort (n = 13,262) and an external Southern China cohort (n =74).

Results

Among 2,736 proteins, Cox regression identified 44 proteins significantly associated with incident CD. CD274, CHI3L1, REG1B, ITGAV, PRSS8, ITGA11, GDF15, DEFA1_DEFA1B, and IL6 were ranked the top 9 in protein importance ordering. Machine learning models using four algorithms were constructed based on these proteins, with XGBoost demonstrating the best performance. In the geographically distinct UKB cohort, the protein model (area under the curve [AUC] 0.76) outperformed clinical risk models (highest AUC 0.67, P < 0.05) and was externally validated in the Southern China cohort (AUC 0.79). Combining these proteins with clinical data enabled desirable predictions up to 16 years pre-diagnosis (AUC 0.78). Our model performed better than existing PREDICTS model (AUC 0.68, P < 0.05) when applied to the UK Biobank population. Individuals in the high-risk group stratified by the protein model were 4.23 times more likely to develop CD.

Conclusion

Our findings suggest that proteomics-based models could be used to predict individuals who will develop CD up to 16 years in advance. The novel approach has important implications in identifying individuals at high-risk for evaluation of early intervention.

Introduction

Early identification of factors that predict disease course in ulcerative colitis (UC) is essential to guide therapeutic decisions and improve patient outcomes. Recognizing patients at higher risk of unfavorable evolution allows for more intensive monitoring and timely escalation of therapy. Clinical severity, disease extent, histological activity, and concomitant infections may all influence prognosis. Among these, Clostridioides difficile infection (CDI) is increasingly recognized in UC patients, but its independent impact on disease evolution remains uncertain. The objective of our study was to assess various baseline severity markers, including histological activity, and concomitant CDI at the time of UC diagnosis as potential predictors of disease-related morbidity during the first year following UC diagnosis.

Aims & Methods

We conducted a retrospective study on a cohort of 125 patients newly diagnosed with UC and followed for at least 12 months. Data collected included demographic characteristics, clinical presentation, biochemical markers, endoscopic findings, histologic disease activity (assessed using the Nancy Histological Index – NHI), and the presence of CDI at diagnosis. Disease-related morbidity was defined as any UC-related hospitalization occurring in the first year after diagnosis, excluding the initial admission for diagnostic purposes. Statistical analysis involved bivariate comparisons and multivariate logistic regression to identify independent predictors of hospitalization.

Results

Independent predictors of UC-related hospitalization were Mayo clinical score (OR = 1.32; p = 0.016), pancolitis (OR = 2.82; p = 0.024), and histological activity (NHI; OR = 1.97; p = 0.014). CDI was identified in 20% of patients and was associated with significantly higher histological activity (median NHI = 3.5 vs. 3.0; p = 0.036), but did not independently predict hospitalization (OR = 1.84; p = 0.265).

Conclusion

Clinical activity, disease extent, and histological severity, at the time of diagnosis are strong, independent predictors of UC-related morbidity within the first year, underscoring their prognostic value beyond the initial presentation. These parameters retain their significance over the medium-term disease course, supporting early risk stratification and individualized treatment planning. Although CDI is associated with greater histologic inflammation at baseline, it does not independently influence outcomes during the first year. Notably, the identification of UC in 20% of patients during a CDI episode suggests that acute infection may unmask previously subclinical disease. These findings highlight the need for comprehensive and careful diagnostic evaluation - including clinical, endoscopic, and histologic assessment, in all patients with newly diagnosed UC.

Introduction

Bowel urgency (BU) is a bothersome symptom experienced by patients with ulcerative colitis (UC) and is associated with high clinical and quality-of-life burdens. Mirikizumab (MIRI), an anti-IL-23 antibody approved for the treatment of moderately-to-severely active UC, significantly reduced BU severity compared with placebo (PBO), and these improvements were associated with better clinical outcomes.¹ We evaluated the association between incremental improvement in BU severity at Week (W)12 and W52 with other patient-reported outcomes for MIRI-treated patients.

Aims & Methods

In LUCENT-1 (induction), patients were randomized 3:1 to intravenous MIRI 300 mg or PBO every 4 weeks (Q4W) for 12W. MIRI responders during induction were re-randomized 2:1 to subcutaneous MIRI 200 mg or PBO Q4W for 40W in LUCENT-2 (52W of continuous treatment). BU severity was measured using the Urgency Numeric Rating Scale ([UNRS] 0–10). Incremental improvement of BU severity was assessed as reduction of each single point of UNRS score from baseline (BL). The reduction of >7 points was pooled into one category due to sample size. The accumulative benefit of reducing 1 additional point of UNRS score was evaluated at W12 and W52 and was assessed for its association with mean percent improvement in inflammatory bowel disease questionnaire (IBDQ) total score, fatigue NRS, short-form (SF)-36 mental component score (MCS) and physical component score (PCS), and work productivity activity impairment (WPAI) productivity loss.

Results

Significantly greater proportions of patients receiving MIRI achieved UNRS score reduction at certain points versus PBO at W12 and W52. The reduction of each single point of UNRS score was associated with improvement in patient’s physical and mental health, fatigue, work productivity, and quality of life. At W12, fatigue and IBDQ showed greater percent improvements among all the PRO outcomes studied for each 1-point reduction of UNRS. Similar results were observed at W52 (Table 1).

Week 12 (N=868)	UNRS reduction	Fatigue NRS	IBDQ Total Score	MCS	PCS	WPAIa	Week 52 (N=365)	UNRS reduction	Fatigue NRS	IBDQ Total Score	MCS	PCS	WPAIb
	≤0	-11.9	16.0	6.6	9.4	4.9		≤0	8.9	35.9	18.5	21.2	23.9
	1	15.4	25.9	14.6	11.3	16.9		1	5.8	30.6	13.4	12.7	11.2
	2	28.7	31.1	13.7	14.0	20.1		2	32.4	37.5	18.8	18.6	30.1
	3	43.5	35.8	17.9	16.9	24.1		3	59.5	33.9	10.8	20.4	27.5
	4	49.8	49.1	19.7	23.5	24.2		4	62.4	55.6	17.9	33.7	42.1
	5	54.5	43.3	13.1	22.9	28.8		5	52.2	54.0	21.7	27.7	38.2
	6	59.3	55.2	22.1	24.0	36.4		6	68.9	63.0	26.0	26.5	41.9
	7	81.2	64.6	25.9	30.1	29.8		7	83.8	67.3	30.1	30.1	50.6
	>7	73.6	75.4	29.7	39.1	38.5		>7	88.1	87.6	35.0	45.4	54.8

^a Note: N=532, population was restricted to patients with baseline employment status = Yes.
^b Note: N=224, population was restricted to patients with baseline employment status = Yes.
Abbreviations: IBDQ = inflammatory bowel disease questionnaire; MCS = short-form-36 mental component score; N = number of patients in the analysis population; n = number of patients in the specified category; NRS= numeric rating scale; PBO = placebo; PCS = short-form-36 physical component score; UNRS = urgency numeric rating scale; WPAI= work productivity activity impairment productivity loss.
UNRS score was averaged from daily diary entries for a 7-day period. Data were considered as missing for that week if less than 4 days were available.

Conclusion

Incremental improvement in bowel urgency corresponded to improvements in outcomes important to patients, underscoring the importance of managing BU symptoms in improving the quality of life for patients with UC.

References

1. Dubinsky MC, et al. Crohns Colitis 360 2023;5(1):otac044.

Disclosure

MD reports consultancy fees from AbbVie, Arena Pharmaceuticals, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Gilead Sciences, Janssen, Pfizer, Takeda, and UCB.
ST reports grants and/or research support from AbbVie, Buhlmann Diagnostics, Celgene, Eli Lilly and Company, the International Organization for the Study of Inflammatory Bowel Disease, Janssen, the Norman Collisson Foundation, Takeda, UCB, and Vifor Pharma; consulting fees from Abacus Pharmaceuticals, AbbVie, Actial, ai4gi, Alcimed, Allergan, Amgen, Arena Pharmaceuticals, Asahi Kasei Pharma, Astellas Pharma, AstraZeneca, Atlantic Pharmaceuticals, Barco, Biocare Pharma, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Buhlmann Diagnostics, Calcico, Celgene, Cellerix, Celsius Healthcare, Cerimon Pharmaceuticals, ChemoCentryx, Cisbio, Coronado Biosciences, Cosmo Pharmaceuticals, Ducentis BioTherapeutics, Dynavax, Elan Corporation, Eli Lilly and Company, Enterome, Falk Foundation, Ferring Pharmaceuticals, FPRT Bio, Giuliani, Genentech, Genzyme, GlaxoSmithKline, Glenmark Pharmaceuticals, Grünenthal, GW Pharmaceuticals, Immunocore, Immunometabolism, Indigo Biosciences, Janssen, Lexicon Pharmaceuticals, Medarex, Merck, MSD, Neovacs, Netbiotix, Novartis, Novo Nordisk, NPS Pharma, Ocera Therapeutics, Otsuka, Palau Pharma, Pentax Medical, Pfizer, Philips, Procter & Gamble, Pronota, Proximagen, Ptima Pharma, Receptos, Resolute, Robarts Pharmaceutical, Roche, Sandoz, Santarus, Sensyne Health, Shire, Sigmoid Pharma, SynDermix, Synthon, Takeda, Theravance Biopharma, TiGenix, Tillotts Pharma, TopiVert, TxCell, UCB, Vertex, VHsquared, Vifor Pharma, Warner Chilcott, and Zeria Pharmaceutical; and speaker fees from AbbVie, Amgen, Biogen, Falk Foundation, Ferring Pharmaceuticals, GlaxoSmithKline, Janssen, Shire, Takeda, and Zeria Pharmaceutical.
TK has served as a speaker, a consultant or an advisory board member for AbbVie, Ajinomoto Pharma, Asahi Kasei Medical, Astellas, Alfresa Pharma, Celltrion, Covidien, EA Pharma, Eisai, Eli Lilly, Ferring Pharmaceuticals, Gilead Sciences, Janssen, JIMRO, Kyorin Pharmaceutical, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, Nippon Kayaku, Pfizer, Takeda Pharmaceutical, Thermo Scientific, Zeria Pharmaceutical, and received research funding from AbbVie, Alfresa Pharma, Asahi Kasei Medical, EA Pharma, Kyorin Pharmaceutical, Mochida Pharmaceutical, Nippon Kayaku, Otsuka Holdings, Sekisui Medical, Thermo Fisher Scientific, Zeria Pharmaceutical.
BA-B has served on advisory board for Bristol Myers Squibb, Pfizer; and reports speaker fees from AbbVie, Takeda, Bristol Myers Squibb, Janssen Pharmaceuticals.
JW, BZ, HQ, CM, SF are employees and minor shareholders of Eli Lilly and Company.
DR reports grant support from Takeda and has served as a consultant for AbbVie, AltruBio, Arena Pharmaceuticals, Bristol Myers Squibb, Eli Lilly and Company, Genentech, Gilead Sciences, Iterative Scopes, Janssen, Pfizer, Prometheus Biosciences, Roche, Takeda, and Techlab.