Introduction

Endoscopic submucosal dissection (ESD) is the preferred treatment for superficial esophageal squamous cell carcinoma (ESCC). However, curative resection is not always achievable for all patients¹. Currently, the curability criteria was inconsistent among different societies^2-3 and may be overly stringent for suggesting additional treatments⁴, which causes dilemmas in clinical decision-making and potential overtreatments in some low-risk cases.

Aims & Methods

The research aim was to develop and validate a risk scoring system to assess curability after ESD for superficial ESCC. This study was based on a nationwide cohort, the China Early Esophageal Cancer Cohort, and all patients were follow-up at least for 3 years. Patients with superficial ESCC undergoing ESD were included, and those with positive horizontal margin, adjuvant chemoradiotherapy, and metachronous esophegeal cance after ESD were excluded. The primary outcome was noncurative resection, defined as either (1) pathological confirmation of residual tumor or lymph node metastasis (LNM) after additional surgery, or (2) identification of local recurrence, LNM, or distant metastasis during follow-up. Data from South and North China were used to develop and validate the scoring system, respectively. Logistic regression analysis was used for model construction, and Kaplan-Meier survival estimates, the C-statistic, and decision curve analysis were employed for performance evaluation.

Results

A total of 1,273 patients with superficial ESCC were included, with 995 for model development and 278 for validation. Multivariable analysis identified 6 independent risk factors for noncurative resection: tumor size ≥30 mm, submucosa invasion, positive vertical margin, lymphatic invasion, vascular invasion, and poor differentiation. For the risk scoring system (ESCC-eCura), lymphatic invasion was assigned as 2 points, and others were assigned as 1 point. In the development cohort, the non-curative resection rates of the low- (≤1 point), intermediate- (2 to 3 points), and high-risk (≥4 points) groups was 4.5%, 16.3%, and 75.0%, respectively. The ESCC-eCura demonstrated a C-statistic of 0.75 (95% condifence interval [CI], 0.69 - 0.81). In the validation cohort, the C-statistic was 0.84 (95% CI, 0.73-0.95), and intermediate- or high-risk groups were significant predictors for subsequent recurrence (hazard ratio [HR] for intermediate-risk group 14.35, 95% CI 4.01-51.35, P<0.001; HR for high-risk group 28.16, 95% CI 4.90-161.83, P<0.001; all compared with the low-risk group). Decision curve analysis also showed acceptable clinical benefits and utility.

Conclusion

This ESCC-eCura scoring system can predict non-curative resection after ESD for superficial ESCC, which offers a practical tool for individualized management. Additiomal treatments should be recommended for patients in ESCC-eCura intermediate- or high-risk groups, while follow-up may be acceptable for the low-risk group.

References

1.Jiang, H., et al., Risk and Pathological Factors of Recurrence after Endoscopic Resection for Superficial Esophageal Squamous Cell Carcinoma: A Systematic Review and Meta-analysis. Gastrointest Endosc, 2024.
2. Kitagawa, Y., et al., Esophageal cancer practice guidelines 2022 edited by the Japan esophageal society: part 1. Esophagus, 2023. 20(3): p. 343-372.
3. Pimentel-Nunes, P., et al., Endoscopic submucosal dissection for superficial gastrointestinal lesions: European Society of Gastrointestinal Endoscopy (ESGE) Guideline - Update 2022. Endoscopy, 2022. 54(6): p. 591-622.
4.Liu, Z., et al., Additional Esophagectomy Following Noncurative Endoscopic Resection for Early Esophageal Squamous Cell Carcinoma: A Multicenter Retrospective Study. Ann Surg Oncol, 2021. 28(12): p. 7149-7159.

Disclosure

Nothing to disclose.

Introduction

Mirikizumab (miri), a humanized IgG4 monoclonal antibody that selectively binds to interleukin-23 subunit p19, is approved for the treatment of moderately to severely active ulcerative colitis and Crohn’s disease. In ulcerative colitis, maintenance treatment with 200 mg miri given as two 1-mL subcutaneous (SC) injections every 4 weeks was efficacious and safe in the phase 3 maintenance LUCENT-2 and long-term extension LUCENT-3 trials. As SC injections can be associated with pain/discomfort and thus poor patient experience, an investigational 2-mL single injection delivering the same miri dose has been developed.

Aims & Methods

This phase 1 study (NCT06475729) aimed to assess the pharmacokinetic (PK) bioequivalence and safety of miri solution administered as one 2-ml injection compared with the commercially available two 1-ml injections. Healthy participants were stratified into weight categories (<75 kg, 75–85 kg, and >85 kg) and randomized (1:1) to receive one dose of 200 mg of SC citrate-free miri as either one (200 mg/2 mL) or two injections (each of 100 mg/1 mL) delivered by an autoinjector. Participants were sub-randomized (1:1:1) by injection site (arm, thigh, and abdomen). Blood samples were collected at pre-defined intervals up to 10 weeks post-dosing. The primary endpoint was PK, assessed by the maximum observed concentration (C_max), area under the concentration–time curve (AUC) from time zero to infinity (AUC_0–∞), and AUC from time zero to the last timepoint with measurable concentration (AUC_0–t). PK parameters were estimated using non-compartmental analysis. The secondary endpoint was safety, assessed by the incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) among participants exposed to miri. Evaluating the impact of injection site location on PK was an exploratory endpoint.

Results

A total of 244 participants (mean age: 42.4 years; 55.3% female) received one 200 mg/2 ml injection and 240 (mean age: 42.7 years; 53.3% male) received two 100 mg/1 ml injections. Baseline characteristics were similar in both groups. The three primary PK parameters all fell within the bioequivalence range (geometric least-squares mean [GM] ratio: 0.800–1.250; see table). Results were generally consistent across injection site locations with no significant differences between them. TEAEs were reported in 48 participants with one injection (19.7%) and 55 with two injections (22.9%). Most TEAEs were mild (62/74 events with one injection [83.8%] vs 85/100 with two injections [85.0%]). Injection-site reactions occurred in 5/244 [2.0%] of participants with one injection and 4/240 [1.7%] with two injections. No SAEs were reported in either group.

Conclusion

Miri 200 mg administered as one 2-ml SC injection was bioequivalent to two 1-ml injections, and most TEAEs were mild. In clinical practice, reducing the number of injections may improve patient experience and treatment adherence.

Disclosure

YO, CDP, AUK, KT, PP, XZ: Employees and shareholders of Eli Lilly and Company.
EVL Jr: Consulted for Abivax, AbbVie, Astellas, Avalo, Biocon, Bristol-Myers Squibb, Celltrion, Eli Lilly, Fresenius Kabi, Genentech, Gilead, Iota Biosciences, Iterative Health, Janssen, Merck, Morphic, Ono Pharma, Takeda, and TR1X Bio; received research support from AbbVie, Genentech, Gilead, Janssen, Merck, and Takeda; shareholder of Exact Sciences and Moderna.
GDH: Adviser and/or speaker for Abbvie, Alimentiv, Bristol Meiers Squibb, Boehringer Ingelheim, Celltrion, Eli Lilly, Galapagos, Glaxo Smith Kline, Immunic, Index Pharmaceuticals, Johnson and Johnson, Merck, Polpharm, Prometheus biosciences, Prometheus Laboratories, Procise diagnostics, Protagonist, Sandoz, Takeda, Tillotts, and Ventyx.
SBH: Received advisory board and/or consulting fees from Abbvie, Takeda, Janssen, Celltrion, Pfizer, GSK, Ferring, Novartis, Roche, Gilead, NeoPharm, Predicta Med, Galmed, Medial Earlysign, and Eli Lilly; stocks/options in Galmed, Evinature, PredictaMed and Alma Therapeutics; and research support from Abbvie, Takeda, Janssen, Celltrion, Pfizer, Medtronic & Galmed.

Introduction

Acute severe ulcerative colitis (ASUC) is a potentially life-threatening emergency that requires timely management. Intravenous corticosteroids are the first line therapy, but around 30% of patients fail to respond. Rescue therapy is effective in reducing short-term colectomy rates but its impact on disease course in the medium/long-term is not well characterized.

Aims & Methods

We aimed to assess if non-response to corticoids (and subsequent need for rescue therapy) in patients admitted with a first episode of ASUC is associated with worse disease-related outcomes in the long-term.
We conducted a retrospective study of all patients admitted with ASUC in the Gastroenterology department of a Portuguese tertiary center between 2018-2024. ASUC diagnosis was established according to Truelove and Witts’ criteria. Response to intravenous corticoids was defined as discharge without need for rescue therapy and/or colectomy. Patients with a previous admission for ASUC before the study period were excluded.
Patient files were reviewed and demographic, clinical, laboratory and endoscopic data was collected regarding the admission for ASUC and subsequent follow-up. Considered disease-related outcomes were need for switch of maintenance therapy, need for readmission and need for colectomy. Subanalyses were performed according to response to corticoid therapy. Statistical analysis was done using Stata version 12.1.

Results

A total of 35 patients hospitalized with a first episode of ASUC were included, 51.4% (n=18) male, median age at admission was 38 years [IQR 27-51]. Roughly half the patients had pancolitis at diagnosis (51.4%, n=18). Median disease duration was 9 months [IQR 0-26] and 22.9% (n=8) had previous exposure to biologic therapy. In 34.3% (n=12), ASUC was the initial presentation of UC. Median follow-up was 30 months [IQR 12-51].
Response to corticosteroid therapy was observed in 57.1% (20/35). All the steroid-refractory patients (15/35, 42,9%) responded to rescue therapy (Infliximab n=11; Tacrolimus n=3; Tofacitinib n=1) and avoided colectomy during the hospitalization.
Baseline characteristics were identical between steroid-responsive and steroid-refractory patients, except for a lower median age in corticoid refractory patients (29 years vs 48 years, p=0.02).
Survival analysis was performed and no differences between steroid-responsive and steroid-refractory patients were observed in need for switch of maintenance therapy [during first year (p=0,28) and during complete follow-up (p=0,54)] , need for readmission [during first year (p=0,55) and during complete follow-up (p=0,54)] or need for colectomy [during first year (p=0,09) and during complete follow-up (p=0,79)].

Conclusion

In our cohort of patients with a first episode of ASUC, with the current therapeutic paradigm, patients with steroid refractoriness had similar outcomes as corticosteroid responders. These results suggest that effective and timely therapy can change the natural history of ASUC.

References

1. Festa S, Scribano ML, Pugliese D, Bezzio C, Principi M, Ribaldone DG, Allocca M, Mocci G, Bodini G, Spagnuolo R, Vernia P, Mazzuoli S, Costa F, Barberio B, Cosintino R, Zerboni G, Aratari A, Armuzzi A, Papi C. Long-term outcomes of acute severe ulcerative colitis in the rescue therapy era: A multicentre cohort study. United European Gastroenterol J. 2021 May;9(4):507-516. doi: 10.1177/2050640620977405. Epub 2021 Feb 16. PMID: 33259773; PMCID: PMC8259429.
2. Zafer M, Zhang H, Dwadasi S, Goens D, Paknikar R, Dalal S, Cohen RD, Pekow J, Rubin DT, Sakuraba A, Micic D. A Clinical Predictive Model for One-year Colectomy in Adults Hospitalized for Severe Ulcerative Colitis. Crohns Colitis 360. 2021 Dec 21;4(1):otab082. doi: 10.1093/crocol/otab082. PMID: 36777555; PMCID: PMC9802419.

Introduction

IBS is a a condition which is highly denigratory to patients' quality of life, is often under-diagnosed and is managed through a mixture of diet/lifestyle modifications, treatments and psychological interventions. The following piece of research aims to understand the management patterns and emotional impact of the condition in the IBS population.

Aims & Methods

Surveys were deployed in ten countries (n=1,250 per country, total n=12,500). People were invited to complete the survey if they were aged 18-75, suffering from at least one of the following; constipation, diarrhoea, wind/bloating, abdominal pain, irregular bowel movements or ‘IBS’. With at least one incident in the past month.

Results

9% of the surveyed population reported IBS, with 78% of this group having a diagnosis from a healthcare professional. Key triggers of symptoms were; stress (48%), food allergy/intolerance/sensitivity (20%), poor sleep (19%), infection (18%).
37% used medication, 31% used biotics, 22% diet and home remedies, 18% used supplements. Dissatisfaction with regular treatment were that most treatment options only treat the symptom but not the underlying cause, with females managing their symptoms through diet/lifestyle changes more than males.
The emotional impact in the IBS is very high in prevalence and broad in scope. 71% of IBS sufferers felt worried, anxious or stressed about their symptoms. 62% felt frustrated and fed up. 39% felt embarrassment and negative impact to their confidence. Only 5% were not bothered by their symptoms.

Conclusion

The survey gave insight into management patterns of IBS patients, demonstrating a variety of treatments used. Surprisingly, a high number of IBS patients use biotics despite low quality of evidence. It was evident that IBS is a condition with a high emotional toll. Further qualitative research should delve further into these insights to further understand the patient population.

References

Quantitative U&A 2025- Lower GI - IBS deep dive

Disclosure

This survey was funded by Reckitt. Authors are Reckitt employees.

Introduction

Ulcerative proctitis (UP) is associated with disabling symptoms such as diarrhea, hematochezia and bowel urgency¹. Adequate therapy is crucial for symptom control and may reduce the risk of proximal disease extension. Although prior studies have explored risk factors for disease progression, they are limited by small sample sizes and have conflicting results^2,3.

Aims & Methods

We aimed to (1) assess the incidence and (2) identify risk factors for disease progression in newly diagnosed UP patients. We included all patients diagnosed with UP (inflammation ≤15 cm beyond the anal verge) between January 2000 and January 2024 in a large, non-academic hospital in the Netherlands. Data were collected from diagnosis until the end of follow-up. Disease progression was defined as endoscopic extension of UP (Montreal E1) to either left-sided (E2) or pancolitis (E3). To avoid overestimating the risk of disease progression, we used a Fine & Gray (F&G) regression model to account for patients in long-term remission who had no in-hospital follow-up. Patients who were referred back to primary care and/or had no in-hospital follow-up for ≥2 years were considered in long-term remission, which was used as a competing event in the F&G model. The cumulative incidence of disease progression was calculated at 1-, 5- and 10-years follow-up and compared to the progression rates of traditional Kaplan-Meier survival estimates.

Results

In total, 486 UP patients were included; 283 (58%) were female and median age at diagnosis was 39 years (IQR 29-53). 371 (76%) patients were in clinical remission at last follow-up. Of those, 291 (78%) were treated with topical and/or oral 5-aminosalicylates (5-ASA) and/or topical steroids; 202 (54%) required only topical and/or oral 5-ASA. 50 (10%) patients had refractory UP and required treatment with immunosuppressants or advanced therapies. During a median follow-up of 6.2 years (IQR 2.1-12.2), disease progression occurred in 112 patients (23%), of whom 80 (16%) progressed to E2 and 32 (6.6%) to E3. Median time to progression was 57 months (IQR 22-103). The cumulative incidence of disease progression was 2.8% (95% CI 1.4-4.4%) at 1 year, 13.2% (95% CI 9.9-16.4%) at 5 years and 23.9% (95% CI 19.4-28.4%) at 10 years after diagnosis and would have been overestimated with traditional Kaplan-Meier analysis (5.1% [95% CI 1.9-8.1%] at 1 year, 24.6% [95% CI 14.9-33.3%] at 5 years and 46.3% [95% CI 30.3-58.6%] at 10 years). F&G analyses demonstrated that age <18 years at diagnosis (HR 2.61, p=0.009) and the absence of steroid-free remission at 3 months (HR 1.97, p=0.005) were significant predictors for disease progression (Table 1).

Conclusion

In this large cohort of newly diagnosed UP patients, the 10-year cumulative incidence of disease progression was 23.9%. Most patients responded well to conventional treatment, as 60% reached clinical remission with only topical and/or oral 5-ASA and/or topical steroids. Absence of steroid-free remission at 3 months and age <18 at diagnosis were significant predictors for disease progression. Better prediction of disease progression could help identify high-risk patients who may benefit from tailored monitoring strategies, as well as low-risk patients that may be suitable for referral back to primary care.

References

1. Meucci G, Vecchi M, Astegiano M, et al. The natural history of ulcerative proctitis: a multicenter, retrospective study. Gruppo di Studio per le Malattie Infiammatorie Intestinali (GSMII). Am J Gastroenterol. 2000;95(2):469-473
2. Huguet JM, Ferrer-Barceló L, Suárez P, et al. Endoscopic progression of ulcerative proctitis to proximal disease. Can we identify predictors of progression?. Scand J Gastroenterol. 2018;53(10-11):1286-1290.
3. Walsh E, Chah YW, Chin SM, et al. Clinical Predictors and Natural History of Disease Extension in Patients with Ulcerative Proctitis. Inflamm Bowel Dis. 2017;23(11):2035-2041.
4. Andersen PK, Geskus RB, de Witte T, Putter H. Competing risks in epidemiology: possibilities and pitfalls. Int J Epidemiol. 2012;41(3):861-870.

Disclosure

RJBP, JH, RAJP, REAvD and AGLB have nothing to disclose. LAAPD has served on advisory boards for Abbvie, Janssen, Galapagos, and Pfizer, and has received independent research funding from Pfizer. ACdV has has served on advisory boards for Takeda, Janssen, Bristol Myers Squibb, Abbvie, Pfizer, and Galapagos and has received unrestricted research grants from Takeda, Janssen, and Pfizer.