Introduction

The Montreal classification reflects the varying phenotypes of Crohn’s including location and behaviour, however the majority of trials to date, despite including Montreal classification in baseline characteristics, do not report treatment efficacy by disease location. Ileal disease is associated with a higher risk of progression to stricturing and penetrating complications.

Aims & Methods

To perform a systematic review summarising the evidence for different biologic and advanced therapies available for small bowel Crohn’s disease in adult patients.
Systematic search of MEDLINE and EMBASE was conducted. Articles were then screened, duplicates removed. Inclusion criteria included trials with efficacy outcomes stratified via disease location. Primary outcome was drug efficacy, measured via endoscopic response, healing, clinical remission or improvement of MRI severity scores.

Results

A total of 868 publications were screened and assessed for eligibility following database screening and removal of duplicates. 12 studies were included with 746 patients, with a total median follow up of 52 weeks(range 14-165). All studies were included in qualitative analysis; Infliximab (6 trials n=404) Adalimumab (4 trials n=204), Vedolizumab (2 trials n=50), Ustekinumab (1 trial n=28), Filgotinib (1 trial n=60).
Of the 6 infliximab studies (n=404), 3 reported on endoscopic response (ER) and 2 endoscopic healing (EH) via double balloon enteroscopy, 2 reported on clinical outcomes only and 1 reported on improvements in MRI outcomes, as detailed in the below table. Median follow up was 52 weeks.

First author	Year	N	Design	Drug	Outcome	Follow up
Huang	2025	110 64 28 18	R	IFX UST VEDO	EH 29.6% (19/64) ER 42.2% (27/64) UH 35.9% (23/64) EH 10.7%(3/28) ER 28.6% (8/28) UH 17.9% (5/28) EH 5.5% (1/18) ER 11.1% (2/18) UH 11.1% (2/18)	52 weeks
Wei	2024	111	R	IFX	ER 42.3% (47/111) MH 29.7% (33/111)	32 months
Han	2021	91	R	IFX	DR(CR+MH) 47.2% (42/91)	14 weeks
Chen	2021	79	R	IFX	CR 46.8% (37/79)	38 months
Zorzi	2012	44 34 (I) 28 (M)	O	IFX – Induction (I) Maintenance(M)	CR 74% (20/28)	54 weeks
Van Assche	2013	15	P	IFX	MRI improvement 40% (6/15)	26 weeks

IFX=Infliximab, ADA=Adalimumab, VEDO=Vedolizumab,
EH= Endoscopic healing(defined as a modified SES-CD <3 or 0 if jejunal/proximal ileum), ER=Endoscopic Response(defined as a reduction of SES-CD by more than 50% at both segmental and complete level), UH=Ulcer Healing (defined as no inflammation, ulcers or erosions), MH=mucosal healing(SES-CD=0), DR=Deep Remission, CR=Clinical Remission

There were 4 trials for adalimumab (n=204), 2 trial outcomes reported on EH(53.3%) and ER on capsule (42%). Two trials focused on clinical response rates; 64-66%[iii][iv]. Median follow up was 52 weeks (range 24-154).
Ustekinumab data (n=28) was available from Huang et al who reported EH in 10.7%(3/28), ER in 28.6% (8/28) and UH rates of 17.9% (5/28).
Two retrospective studies reported on Vedolizumab outcomes(n=50); reporting on EH 5.5% (1/18), ER 11.1% (2/18), UH 11.1% (2/18) [v] and another study (n=36) reported on CT and MRI outcomes for ileal Crohn’s reporting a 22% (7/32) imaging response based on EMBARK scoring[vi]. Both studies had 52 week follow up.
One RCT involving two doses of Filgotinib reported rates of clinical remission (based on CDAI<150 at week 24) of 25% in both groups[vii] and secondary outcomes of MRI remission (based on MaRIAseg<7) in 6.3%(2/32) of 100mg arm and 8%(2/25) of the 200mg arm.

Conclusion

Robust retrospective data exists for small bowel mucosal healing with anti-TNF therapy. Data is lacking for vedolizumab, ustekinemab and newer smaller molecule therapies. Dedicated clinical trials are needed to specifically investigate the effectiveness of therapies in isolated ileal Crohn’s disease patients to optimise their management.

References

[i] ‘Mucosal Healing and Clinical Efficacy of Adalimumab in Small Intestinal Crohn’s Disease (SIMCHA Study): Final Results From a Prospective, Open-Label, Single-Arm Study’, The Turkish Journal of Gastroenterology 34, no. 6 (9 June 2023): 603–10, https://doi.org/10.5152/tjg.2023.22527.
[ii] Barry Hall et al., ‘A Prospective 52week Mucosal Healing Assessment of Small Bowel Crohn’s Disease as Detected by Capsule Endoscopy’, Journal of Crohn’s and Colitis 8, no. 12 (December 2014): 1601–9, https://doi.org/10.1016/j.crohns.2014.09.005.
[iii] Yoram Bouhnik et al., ‘Efficacy of Adalimumab in Patients with Crohn’s Disease and Symptomatic Small Bowel Stricture: A Multicentre, Prospective, Observational Cohort (CREOLE) Study’, https://doi.org/10.1136/gutjnl-2016-312581.
[iv] F. Zorzi et al., ‘Efficacy and Safety of Infliximab and Adalimumab in C Rohn’s Disease: A Single Centre Study’, https://doi.org/10.1111/j.1365-2036.2012.05100.x.
[v] Zi-Cheng Huang et al., ‘Effectiveness of Biologics for Endoscopic Healing in Patients with Isolated Proximal Small Bowel Crohn’s Disease’, https://doi.org/10.3748/wjg.v31.i7.98448.
[vi] Lukasz Kwapisz et al., ‘CT or MR Enterography to Assess Response During Vedolizumab Therapy for Small Bowel Crohn’s Disease’, https://doi.org/10.1093/crocol/otac003.
[vii] Geert R. D’Haens et al., ‘Filgotinib for the Treatment of Small Bowel Crohn’s Disease: The DIVERGENCE 1 Trial’, https://doi.org/10.1053/j.gastro.2023.03.234.

Introduction

Pancreatic exocrine insufficiency (PEI) is a condition characterized by inadequate secretion or activity of pancreatic enzymes, resulting in the maldigestion and malabsorption of nutrients. While PEI is most commonly associated with chronic pancreatitis and cystic fibrosis, it also occurs frequently in the context of pancreatic and peri-pancreatic malignancies. In patients with pancreatic cancer PEI arises due to direct tumor infiltration, ductal obstruction, parenchymal destruction, or as a consequence of surgical resection. Other gastrointestinal malignancies, such as ampullary or biliary tree cancers, may also contribute to PEI through similar mechanisms. Importantly, PEI in cancer patients is often under-recognized, despite its significant impact on nutritional status, quality of life, and overall prognosis. Timely identification and management of PEI in malignancy-associated cases is crucial to optimize clinical outcomes and support ongoing cancer therapies.

Aims & Methods

The objective of this study is to assess the incidence of PEI in patients with biliopancreatic and ampullary tumors, to explore potential differences in PEI occurrence based on tumor location and to investigate possible associations between PEI and relevant biomarkers.
We conducted a retrospective observational analysis of a consecutively recruited patient cohort including patients diagnosed with biliopancreatic and ampullary tumors at a tertiary care hospital between 2016 and 2024.
PEI was defined as fecal elastase-1 (FE-1) levels below 100 µg/g.
At the time of diagnosis, we collected data on demographic characteristics, tumor-related variables, the incidence of PEI, and serum nutritional markers.

Results

We included 408 patients with malignancies potentially associated with PEI. Of these, 54.2% were male, with a mean age of 72 years (range: 38–101) and a mean body mass index (BMI) of 25.45 (SD ± 4.28).
The types of malignancies included were pancreatic ductal adenocarcinoma (PDAC) in 63.5% of patients, cholangiocarcinoma (CCA) in 23.8%, ampullary tumors in 9.8%, and gallbladder tumors in 2.9%. The overall incidence of PEI at the time of diagnosis was 38.2%. Among subgroups, the incidence was 51.4% in PDAC patients, 13.4% in those with CCA, and 25% in those with ampullary tumors. PEI incidence was significantly associated with elevated HbA1c (>5.8%, p<0.01) and Ca 19-9 levels (>37 U/mL, p<0.01).
In PDAC, tumors located in the pancreatic head were associated with a significantly higher incidence of PEI (58.8%) compared to tumors in the body (27.8%) and tail (21.7%) (p<0.01). In this subgroup, PEI was significantly associated with elevated HbA1c (>5.8%, p=0.03), elevated Ca 19-9 (>37 U/mL, p=0.04), and elevated bilirubin (>1.2 mg/dL, p<0.01).
In contrast, among CCA patients, no significant differences in PEI incidence were observed based on tumor location, and no significant associations were found between PEI and the clinical or laboratory variables analyzed .

Conclusion

• PEI is observed not only in patients with PDAC but also in those with CCA and ampullary tumors at the time of diagnosis.
• Given the high incidence of PEI in tumors located in the pancreatic head, empirical pancreatic enzyme replacement therapy should be considered in this subgroup.
• In PDAC patients, the presence of PEI is significantly associated with endocrine dysfunction, hyperbilirubinemia secondary to biliary obstruction and elevated Ca 19-9 levels.

Introduction

Colorectal cancer (CRC) is the second leading cause of cancer-related death worldwide^1,2. Liquid–liquid phase separation (LLPS) describes a reversible and dynamic process in which intracellular biomacromolecules condense into liquid-like biomolecular assemblies through multivalent interactions³. Emerging evidence indicates that dysregulated phase separation may play a pivotal role in cancer initiation and progression^4-6. However, the specific role and regulatory mechanisms of LLPS in the progression and metastasis of CRC remain largely unexplored.

Aims & Methods

Magnifying endoscopy combined with narrow-band imaging (ME-NBI) was used to perform targeted biopsies of distinct colorectal tissue subpopulations. Adjacent normal tissues, non-invasive cancer, and invasive colorectal cancer samples were separately collected for ATAC-seq and RNA-seq to identify core transcription factor (TF) involved in the progression of CRC. Then, the TF was purified in vitro and over-expressed in vivo separately to observe the phase separation phenomenon. Besides, phase separation-deficient mutants were identified and characterized to determine their biophysical properties. Finally, we evaluated its effects on CRC invasion and metastasis both in vitro and in vivo by using transwell migration and invasion assays, wound healing assays, and a lung metastasis model in nude mice.

Results

Multi-omics analysis identified ETV4 as a key driver of CRC progression. qRT-PCR and Western blot revealed that ETV4 were significantly elevated in CRC tissues compared to adjacent normal tissues. Correlation analysis based on data from The Cancer Genome Atlas (TCGA) further demonstrated that high ETV4 expression was positively associated with distant metastasis and advanced tumor stage in CRC. Meanwhile, the purified ETV4 readily formed droplet-like condensates in vitro. Transfection of HEK-293T and CRC cell lines with ETV4-GFP plasmids similarly resulted in the formation of distinct intracellular droplet-like condensates. Besides, fluorescence recovery after photobleaching (FRAP) assays using confocal laser microscopy demonstrated that fluorescence signals in the bleached regions of ETV4 condensates gradually recovered over time, indicating that these condensates exhibit dynamic liquid-like properties.
Based on the intrinsically disordered regions (IDRs) of ETV4, a series of truncated mutants (ΔIDR1, ΔIDR2, and ΔIDR3) were constructed. When these mutant plasmids were transfected into HEK-293 cells, only deletion of the IDR1 region (ΔIDR1) abrogated the formation of droplet-like condensates. Notably, expression of the IDR1 region alone was sufficient to restore condensate formation within cells, indicating that IDR1 is essential and sufficient for ETV4-mediated phase separation. Furthermore, in vitro experiments demonstrated that ETV4 overexpression significantly enhanced the migratory and invasive capacities of colon cancer cells, whereas ETV4 knockdown markedly suppressed these malignant phenotypes compared to control groups. Additionally, mice injected with ETV4 wild-type (ETV4-FL) cells developed significantly more lung metastases compared to controls, whereas those injected with the phase separation-deficient mutant (ETV4-ΔIDR1) failed to enhance metastatic dissemination.

Conclusion

This study identifies ETV4 as a pivotal transcriptional regulator that drives CRC progression and metastasis. Besides, ETV4 undergoes LLPS both in vitro and in vivo, with this process being specifically mediated by its first IDR1. Importantly, the pro-metastatic function of ETV4 is mechanistically dependent on its LLPS capability.

References

• 1. Bray, F. et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 74, 229–263 (2024).
• 2. Biller, L. H. & Schrag, D. Diagnosis and Treatment of Metastatic Colorectal Cancer: A Review. JAMA 325, 669–685 (2021).
• 3. Mehta, S. & Zhang, J. Liquid-liquid phase separation drives cellular function and dysfunction in cancer. Nat Rev Cancer 22, 239–252 (2022).
• 4. Zong, Z. et al. Alanyl-tRNA synthetase, AARS1, is a lactate sensor and lactyltransferase that lactylates p53 and contributes to tumorigenesis. Cell 187, 2375-2392.e33 (2024).
• 5. Liu, Q. et al. Glycogen accumulation and phase separation drives liver tumor initiation. Cell 184, 5559-5576.e19 (2021).
• 6. Ahn, J. H. et al. Phase separation drives aberrant chromatin looping and cancer development. Nature 595, 591–595 (2021).

Clinical Case Summary

Case presentation: An 18-year-old male with a four-year history of recurrent nausea, vomiting, and upper abdominal pain, worsened after meals, was diagnosed with Superior Mesenteric Artery Compression Syndrome (SMAS).
Diagnosis and treatment: The diagnosis of SMAS was confirmed by CT and CTA, which revealed a reduced aortomesenteric angle and duodenal compression, excluding other gastrointestinal conditions like peptic ulcers and pancreatitis. An upper GI contrast study showed delayed gastric transit, and endoscopy revealed mild mucosal edema without obstruction. Blood tests showed elevated WBC (14.99 × 10⁹/L) and low albumin (61.5 g/L), indicating inflammation and malnutrition.
Given the failure of conservative treatment, the patient underwent laparoscopic duodenojejunostomy on March 14, 2025. The surgery was successful with minimal blood loss. Postoperatively, the patient received somatostatin, antibiotics, and nutritional support, with gradual transition from parenteral to enteral feeding. Follow-up imaging confirmed a successful anastomosis, and the patient experienced significant symptom relief and improved nutritional status.
Outcome and discussion: The patient was discharged after 38 days with substantial improvement in symptoms and quality of life. This case highlights the importance of considering SMAS in young patients with persistent postprandial symptoms. Early surgical intervention, such as duodenojejunostomy, is effective for relieving duodenal compression and improving outcomes, particularly when conservative treatment fails.The poster will include the patient's abdominal enhanced CT scan, 3D reconstruction images, pathological images, and postoperative drainage volume changes.

Introduction

Diagnosing the extent of early gastric cancer (EGC) using narrow-band imaging with magnification (NBI-M) can be challenging in cases with large lesions or severe surrounding gastritis. Moreover, if the endoscope tip contacts the lesion and causes bleeding, the quality of the diagnosis of EGC by NBI-M is degraded. The NBI-M method requires the endoscopist's skill because of the delicate manipulation of the endoscopic scope. In contrast, the acetic acid with indigocarmine (AIM) method is a simpler technique that facilitates extent diagnosis regardless of expertise. However, AIM does not yield effective results in all EGC cases.

Aims & Methods

The study aimed to determine the optimal method for delineating EGC extent during endoscopic submucosal dissection (ESD) marking. Informed consent was obtained from 107 patients scheduled for gastric ESD at our institution. The extent of EGC was assessed first with NBI-M, followed by thorough rinsing and spraying with 2% AIM. One minute after spraying AIM, visibility of the lesion extent was graded on a four-point scale: 0= not identifiable, 1= unclear, 2= approximately clear, 3= clear. Resected specimens were immunohistochemically stained for MUC5AC, MUC6, MUC2, and CD10. The immunohistochemical score for each staining was determined as follows: 0= no staining, 1= ≤1/3, 2= 1/3–2/3, 3= ≥2/3 of cancer stained. We examined the relationship between the extent of each staining and the clarity of extent diagnosis of EGC using the AIM method. In addition, a logistic analysis was performed on the factors involved in the cases in which AIM method was superior to NBI-M for extent diagnosis of EGCs.

Results

Of the initial 107 patients, 102 with 102 lesions were analyzed after excluding two cases of signet ring cell carcinomas, one case of gastric carcinoma with fundic gland type, and two cases with consent withdrawal. There were no significant differences in the degree of staining with AIM for gender, infection of Helicobacter pylori, degree of atrophy, lesion size or histological type. Regarding lesion location, EGCs located in the upper third of the stomach showed significantly clearer staining with the AIM method (p=0.0018): 10 lesions (76.9%) were clearly stained, 2 lesions (15.3%) were approximately clear, and 1 lesion (7.6%) was not identifiable. As for the relationship between AIM staining and mucin phenotype expression, only CD10 expression was significantly more frequent in EGCs that showed clear staining with AIM (p=0.019). In the diagnosis of the extent of gastric cancer, AIM was superior in 37 cases, NBI-M was superior in 41 cases, and equivalent in 24 cases. The factors involved in cases with superior AIM method were CD10 (p=0.097, OR 1.14) and upper third of stomach (p=0.042, OR 9.33) in univariate analysis and only upper third of stomach (p=0.027, OR 12.18) in multivariate analysis.

Conclusion

The proposed strategy for determining the extent of EGCs is to prioritize the AIM method for lesions with high CD10 expression and located in the upper third of the stomach.

		AIM staining (Degree of EGC extent)
		0:not identifiable	1:unclear	2:approximately clear	3:clear	p-value
% stained of CD10	0:0%	0	2	0	0	0.019
	1:<1/3	7	9	3	2
	2:1/3 to 2/3	6	12	6	12
	3:>2/3	5	7	10	21
Location	Upper	1	0	2	10	0.0018
	Middle	1	10	8	9
	Lower	16	20	9	16

Introduction

Providing people who have alcohol use disorder (AUD) with feedback about their liver (biofeedback using Fibroscan) may influence their drinking behaviour. It is unclear if and how having a Fibroscan may support behaviour change. There are also questions about how receiving a ‘normal’ result influences an individual’s feelings about their alcohol use.

Aims & Methods

This qualitative study aimed to explore people’s experiences of receiving different Fibroscan results and the impact they felt it had on them. Seventeen qualitative transcripts (11 recovery narratives, 6 post-trial interviews) from the KLIFAD trial (ISRCTN16922410) were analysed. An initial realist programme theory of a complex intervention was produced using the literature and other psychological theories of behaviour change to predict how the Fibroscan may influence behaviour change. A deductive qualitative analysis was conducted to find evidence for an initial programme theory of how the KLIFAD intervention may influence alcohol-related behaviour change. Initial ideas in the programme theory were amended based on qualitative insights.

Results

Of these participants, ten were ≥50 years of age, nine were male, 14 were white and three were of minority ethnicity, most were heavy drinkers. Fibroscan results ranged from normal (≤7 kPa=9), intermediate (8–14 kPa=4) to high (≥15 kPa=4). At follow-up ten reported abstinence and seven reduction in alcohol consumption, none reported increased consumption. Fibroscan was seen by some participants as an opportunity (or a privilege not all get to have) to find out about their health, and a chance to “see inside what is going on”. Those reflecting on receiving high scores described it as a shock, rock bottom, or an instant turning point. Most receiving normal results felt reassured and saw it as an opportunity to change their behaviour. Reducing the score by reducing alcohol use was described as a motivator for three participants. Not all participants (n=2) felt Fibroscan would help reduce alcohol use, often due to acute drinking, co-existing mental health diseases, hopelessness, or memory issues. Other factors influencing its impact included health priorities, loneliness, supportive relationships, age, symptoms such as pain, language barrier, stage of change, recognition of alcohol issues, and service engagement. One participant expressed guilt about self-inflicted harm when preparing for the test.

Conclusion

This study highlights the varied impact of Fibroscan biofeedback on alcohol-related behaviour change, influenced by individual circumstances such as mental health, readiness to change, and social support. High Fibroscan scores often prompted reflection and action, while normal scores reassured and motivated. Addressing barriers and stigma could enhance its effectiveness.

Clinical Case Summary

A 66-year-old female with a history of prior stroke presented with generalized weakness. She was disoriented and unable to provide a reliable history. She was febrile and tachycardic, and labs were notable for elevated direct bilirubin and liver enzymes. Physical exam was notable for right upper quadrant tenderness and well-healed scarring consistent with prior abdominal surgery. CT abdomen showed intrahepatic micro-abscesses and MRI revealed a cystic duct–duodenal fistula. Due to the patient’s clinical improvement with antibiotics, she was able to be discharged with a plan for outpatient ERCP. Due to issues with insurance coverage following discharge, the patient was lost to follow-up.
This is a rare presentation of a cysto-duodenal fistula that was the source of cholangitis and hepatic micro-abscesses resulting in sepsis. The incidence of cysto-duodenal fistulas is unknown, though fewer than 12 case reports of cystic duct-enteric fistulas have been published. The formation of a fistula can occur after cholecystectomy, involving a persistent cystic duct remnant that can become obstructed by calculi, leading to increased pressure and subsequent fistulization. It can present within days to years following cholecystectomy. This patient’s surgical history was unclear due to her altered mental status and a lack of records, though she had abdominal scarring and imaging findings that were consistent with prior cholecystectomy. It was confirmed that the patient did not have any recent abdominal procedure or cholecystectomy, making her presentation even rarer. Patients with a cysto-duodenal fistula typically present with signs of biliary sepsis, like in this case. ERCP is both a key diagnostic and therapeutic tool, as management of the fistula may involve interventions such as sphincterotomy and stenting to relieve obstruction. If endoscopic management is unsuccessful or if symptoms recur, surgical intervention may be necessary.

References

CT abdomen showed multiple small irregular hypodense lesions concerning for intrahepatic micro-abscesses. MRI was performed for further characterization and revealed inflammatory changes of the cystic duct stump with high suspicion for cystic duct–duodenal fistula and hepatic micro-abscesses (most notable in segment VII) with no drainable abscess.