Introduction

Pre-neoplastic lesions such as spasmolytic polypeptide-expressing metaplasia (SPEM) are early hallmarks of gastric carcinogenesis, arising in response to epithelial injury, inflammation, and extracellular matrix (ECM) remodeling¹. The ECM glycoprotein EMILIN-1 exerts a protective function in the gastric environment through its gC1q domain, which modulates epithelial–stromal signaling and immune homeostasis, by binding to α4β1/α9β1 integrins^2–4. This domain is specifically targeted and cleaved by neutrophil elastase (NE), resulting in functional inactivation of EMILIN-1⁵.

Aims & Methods

The aim of this study is to investigate the role of EMILIN-1 in preventing gastric pre-neoplastic lesions and to elucidate the biological consequences of its genetic or enzymatic inactivation.
We employed in vivo mouse models including wild-type (WT) mice expressing normal levels of EMILIN-1, EMILIN-1 knock out (KO) mice and transgenic mice carrying a point mutation (E955A) that renders the gC1q domain non-functional. Mice were treated either with Tamoxifen, which induces parietal cell loss, or with DMP-777, a selective NE inhibitor that induces gastric pre-neoplastic lesions and serves as a chemical model to prevent EMILIN-1 inactivation. Histological analyses were conducted to assess the severity and incidence of gastric lesions.

Results

Tamoxifen treatment induced SPEM in all genotypes. Although not statistically significant, lesion severity was greater in KO and E955A mice compared to WT mice, suggesting increased vulnerability in the absence of functional EMILIN-1. Similarly, DMP-777 treatment led to more pronounced pre-neoplastic alterations in EMILIN-1-deficient and mutant mice, whereas WT mice displayed milder changes, confirming the protective function of intact EMILIN-1.

Conclusion

Collectively, these findings demonstrate that EMILIN-1 actively suppresses gastric pre-neoplastic progression and that NE-mediated inactivation of EMILIN-1 is a critical pathogenic event. Pharmacological targeting of this axis with selective inhibitors may represent a novel preventive strategy in early gastric carcinogenesis.

References

1. Capuano A, Vescovo M, Canesi S, Pivetta E, Doliana R, Nadin MG, et al. The extracellular matrix protein EMILIN-1 impacts on the microenvironment by hampering gastric cancer development and progression. Gastric Cancer. 2024;27(5):1016–30.
2. Danussi C, Petrucco A, Wassermann B, Pivetta E, Modica TM, Del Bel Belluz L, et al. EMILIN1-α4/α9 integrin interaction inhibits dermal fibroblast and keratinocyte proliferation. JCell Biol. 3 ottobre 2011;195(1540-8140 (Electronic)):131–45.
3. Capuano A, Pivetta E, Sartori G, Bosisio G, Favero A, Cover E, et al. Abrogation of EMILIN1-β1 integrin interaction promotes experimental colitis and colon carcinogenesis. Matrix Biol. ottobre 2019;83:97–115.
4. Pivetta E, Capuano A, Vescovo M, Scanziani E, Cappelleri A, Rampioni Vinciguerra GL, et al. EMILIN-1 deficiency promotes chronic inflammatory disease through TGFβ signaling alteration and impairment of the gC1q/α4β1 integrin interaction. Matrix Biol. agosto 2022;111:133–52.
5. Maiorani O, Pivetta E, Capuano A, Modica TM, Wassermann B, Bucciotti F, et al. Neutrophil elastase cleavage of the gC1q domain impairs the EMILIN1-alpha4beta1 integrin interaction, cell adhesion and anti-proliferative activity. SciRep. 11 gennaio 2017;7(2045-2322 (Electronic)):39974.

Clinical Case Summary

Introduction: Cholecystoduodenal fistula (CDF) is a rare gallstone complication causing abnormal communication between the gallbladder and duodenum. Surgical treatment carries significant risks in elderly patients due to frequent comorbidities. We present a minimally invasive strategy combining enteral nutrition support and endoscopic duodenal stenting for CDF management in a high-risk patient.
Case summary: An 84-year-old woman presented with intermittent right upper quadrant pain and fever for two months. Her medical history included hypertension, type 2 diabetes, and myocardial infarction. Examination revealed right upper quadrant tenderness without peritonitis. Laboratory findings indicated markedly elevated C-reactive protein and mild leukocytosis. Contrast-enhanced abdominal CT identified gallstones and duodenal wall thickening, suggesting CDF. Gastroscopy revealed gallstones within the duodenal bulb; following stone removal, a fistulous opening was visualised and confirmed by contrast imaging. Initial conservative therapy (antibiotics, acid suppression, nasojejunal nutrition) failed, with follow-up CT at 20 days showing persistent fistula patency. Considering advanced age and comorbidities, a multidisciplinary team opted for endoscopic duodenal stenting. Gastroscopy identified pinpoint stenosis in the duodenal bulb, which was endoscopically dilated, enabling successful placement of a fully covered metallic stent.Postoperatively, the patient resumed oral liquids and was discharged shortly thereafter. Follow-up confirmed stable stent position, resolution of biliary pneumatosis, and complete symptom relief.
Conclusion: This case highlights the effectiveness of combining enteral nutrition and endoscopic duodenal stenting as a safe, minimally invasive alternative for elderly, high-risk patients with CDF, meriting further investigation.

Disclosure

Nothing to disclose.

Introduction

The biliary tract cancers (BTC) are among the most frequent differential diagnosis of the obstructive cholestasis. Accurate diagnosis remains challenging, as conventional tools such as brush cytology and CA 19-9 lack sufficient sensitivity and histological confirmation is often difficult. The subsequent management of this condition involves the use of biliary tract stenting via endoscopic retrograde cholangiography to facilitate optimal bile flow. We have recently reported that biliary stents are a potential source of molecular biomarkers, including the microbiome.

Aims & Methods

The aim of this study was to investigate the potential of biliary stent microbiome patterns as a biomarker for BTC. Patients diagnosed with obstructive cholestasis of various aetiologies, including malignant disease, BTC and non-malignant disease (NM) including inflammatory and postoperative stenosis, were prospectively enrolled. The study was conducted in 3 steps including discovery, confirmation and validation cohorts to ensure reliability and reproducibility. The discovery cohort comprised a total of 123 patients (28 with BTC, 54 other malignancies and 69 NM). The confirmation cohort comprised 54 patients (16 with BTC) with the inclusion of stents from alternative time points or independent stents as part of the multi-stenting management from the same time point. The validation cohort included stents from 38 independent patients (11 with BTC). The DNA was extracted and subsequently analysed using 16S rRNA gene sequencing. The diagnostic performance was assessed using a receiver operating characteristic (ROC) curve, and the area under the curve (AUC) was calculated.

Results

There were significant differences in the stent-derived microbiome between BTC and patients with other conditions. BTC was associated with a higher abundance of following taxa Bacillales, Peptoniphilaceae, Erysipelotrichaceae and Actinomyces while Fusobacteriaceae, Klebsiella, Dialister and Anaeroglobus was increased in the non-malignant cohort. The calculation of the microbiome-based prediction score was performed by utilising the abundance of the significantly different taxa and applying logarithmic normalisation. ROC analysis on the testing cohort, revealed an AUC of 0.82 (95%-CI: 0.73 to 0.90, p < 0.0001) in prediction of BTC based on the microbial score. To confirm the data, independent analyses were performed using the confirmation cohort revealing comparable results with the AUC of 0.85 (95%-CI: 0.74 to 0.97, p < 0.0001). In the subsequent phase, an independent validation cohort was used to confirm the robustness of the findings. ROC analysis yielded an AUC of 0.83 (95% CI: 0.71–0.96, p = 0.0014), demonstrating promising reproducibility of the microbiome-based score as a diagnostic tool.

Conclusion

Patients with biliary stenosis exhibit distinct biliary microbial alterations. Using stent-derived microbiome data analysis, we developed a novel microbiome-based score to estimate the probability of BTC in patients with cholestasis. Results from both validation and confirmatory cohorts strongly support the utility of this tool for predicting BTC in patients with biliary stenosis.

Introduction

Metastasis is the leading cause of poor prognosis and high mortality in colorectal cancer (CRC). Chemokines play multifaceted roles in cancer immunity and progression. CCL7 is upregulated in CRC, but how CCL7 regulates CRC metastasis at the molecular level remains unclear.

Aims & Methods

In this study, we investigate the regulatory mechanisms and clinical significance of CCL7-mediated CRC metastasis.Immunohistochemistry (IHC) assay was performed to detect the expression of CCL7 and SOX4 in CRC tissue, moreover, the correlation between their expression and tumor distant metastasis, survival, and prognosis was analyzed. To explore their impact on CRC migration, invasion and metastasis, functional experiments and animal experiments were performed in vitro and in vivo, respectively. Gene expression changes were studied by real-time quantitative PCR (qRT‒PCR), Western Blot (WB) and RNA-seq analysis. Chromatin Immunoprecipitation sequencing (ChIP-seq), luciferase reporter assay and Electrophoretic Mobility Shift assay (EMSA) were implemented to explore the mechanisms.

Results

Two clinical cohorts showed that CCL7 and SOX4 were upregulated in CRC tissues and correlated with lymphatic metastasis, distant metastasis, and poor prognosis. Functionally, CCL7 and SOX4 promoted CRC cell proliferation, invasion and metastasis in vitro and in vivo, respectively. Rescue assays revealed SOX4 as a downstream molecule involved in CCL7-mediated CRC metastasis. Through binding to the promoter region of CD44 directly, SOX4 activated its transcription and promotes CRC metastasis, which we proved via promoter analysis assays and analysis of the results of ChIP-seq and RNA-Seq. The Wnt/β-catenin signaling pathway contributed to the regulation of these processes.

Conclusion

The chemokine CCL7 induces elevated expression of SOX4, which subsequently promotes CRC metastasis by transcriptionally upregulating CD44. The CCL7-SOX4-CD44 axis could be applied as a potential target and strategy for preventing and treating CRC metastasis in clinical settings.

Clinical Case Summary

Introduction: Non-occlusive mesenteric ischemia (NOMI) is a rare but critical condition resulting from insufficient mesenteric blood flow without arterial occlusion. When complicated by portal venous thrombosis and small bowel obstruction, NOMI presents significant diagnostic and therapeutic challenges, requiring early recognition and multidisciplinary management to improve outcomes.
Methods: This study retrospectively analyzed a NOMI patient with portal venous thrombosis and small bowel obstruction, reviewing clinical history, imaging, treatment strategies, and outcomes. The effectiveness of catheter-directed thrombolysis with anticoagulation and surgical intervention for recurrent ischemia was assessed, including recurrence rates and treatment outcomes.
Results: A 60-year-old male with atrial fibrillation, presented with prolonged abdominal pain and bloating. Imaging showed mesenteric and portal venous thrombosis causing small bowel obstruction. He underwent catheter-directed thrombolysis with initial improvement. However, symptoms recurred one month later, necessitating small bowel resection due to chronic ischemia. Postoperatively, the patient recovered well with no further recurrence.
Conclusions: This study emphasizes the need for early diagnosis and multidisciplinary management in NOMI with portal venous thrombosis. Catheter-directed thrombolysis with anticoagulation effectively restores mesenteric blood flow, while surgical intervention is key for recurrent ischemia. Tailored, evidence-based approaches are crucial for optimizing outcomes.
The poster will include specimen images, immunohistochemical images, and abdominal CT images.

Clinical Case Summary

Celiac disease (CD), an autoimmune enteropathy triggered by gluten ingestion, commonly presents with gastrointestinal symptoms but can also manifest with various extra-intestinal symptoms, including cutaneous manifestations. Erythema nodosum (EN), a form of acute hypodermitis, is a rare extra-intestinal manifestation of CD and is often associated with other conditions such as infections and inflammatory enteropathies. We report the case of an 11-year-old girl who presented with erythema nodosum and was subsequently diagnosed with celiac disease. The patient exhibited deep, painful red nodules on the anterior surface of both legs and the dorsal surface of the feet, which persisted for a month prior to her referral. Laboratory testing revealed markers of celiac disease, and endoscopic evaluation revealed mosaic antritis and duodenitis with a characteristic fish-scale appearance. Duodenal biopsy confirmed a diagnosis of celiac disease (Marsh stage 3c class), with a significant intraepithelial lymphocytosis of 47%. After initiating a strict gluten-free diet, the patient showed complete resolution of the skin lesions within six weeks. This case underscores the importance of considering celiac disease in the differential diagnosis of erythema nodosum, particularly in patients with unexplained cutaneous manifestations. It also highlights the potential benefits of early screening for celiac disease in patients with EN, as a strict gluten-free diet can lead to both dermatological and gastrointestinal improvement. Further research is needed to establish a clear causal relationship between celiac disease and erythema nodosum.

Introduction

Inflammatory Bowel Disease (IBD) patients carry a high risk of malnutrition, independently of disease activity. Screening for malnutrition in IBD is currently recommended since malnutrition, as well as low Fat-Free Mass Index (FFMI), have been associated to poor disease outcomes. However, due to a non-universal definition of malnutrition, most Nutritional Screening Tools (NSTs) have been validated compared to different reference methods and do not consider patients’ body composition. Moreover, the ability of most NSTs to predict malnutrition over time has not been explored.

Aims & Methods

The aim of this study was to compare the efficacy of different NSTs to predict malnutrition, as defined by the ESPEN 2015 and GLIM criteria, and a low FFMI in a cohort of inactive/mildly active IBD patients.
This is a prospective, single center, cohort study enrolling Crohn’s disease (CD) and ulcerative colitis (UC) patients in clinical remission or with mildly active disease as defined by Harvey-Bradshaw Index and partial Mayo Score, respectively. MUST, MIRT, MNA, NRS-2002 and SaskIBD-NR questionnaires and Bioelectrical Impedance Analysis (BIA) were performed at baseline and after six months follow-up. A low FFMI was defined as <18 kg/m2 in males and <15 kg/m2 in females. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and the accuracy of the different NSTs for the detection of malnutrition and low FFMI at six months were calculated.

Results

Sixty-six (CD: 32; UC: 34) IBD patients were enrolled. Median age was 55.5 years (IQR 34-62.8), median disease duration was 10 years (IQR 6-17). At baseline, all CD and 30/34 (88%) UC patients were in clinical remission; median C-reactive protein was 0.8 mg/L (IQR 0-3.8), median fecal calprotectin was 55.2 mcg/g (IQR 12.9-326). Of the entire cohort, 6/66 (9%) and 17/66 (26%) patients were malnourished according to GLIM and ESPEN criteria, respectively, [(GLIM CD:3, UC: 3)(ESPEN: CD: 3; UC:14)] and 5/66 (8%) had low FFMI (CD:1; UC: 4). At 6 months follow-up, all CD and 31/34 (91%) UC patients were in clinical remission. Ten out of 66 (15%) and 32/66 (48%) patients were malnourished according to GLIM and ESPEN criteria, respectively [(GLIM CD:5, UC: 5)(ESPEN: CD: 15; UC:17)], 11/66 (17%) patients had low FFMI (CD: 3; UC: 8). Baseline MIRT showed the highest sensitivity for the diagnosis of both ESPEN and GLIM-defined malnutrition at 6 months (ESPEN: 40.5%; GLIM: 50%). For ESPEN, MIRT and NRS2002 were the most accurate NSTs (MIRT: 50%, NRS2002: 51.5%), while SaskIBD (75.8%) showed the highest accuracy in detecting GLIM-malnourished patients at 6 months follow up. Among all NSTs, baseline MIRT, MNA and NRS2002 had the highest sensitivity for the detection of low FFMI at six months (MIRT, MNA, NRS2002: 45.5%), while SaskIBD_NR was the most accurate (80.3%).

Conclusion

MIRT might be the NSTs of choice to predict defined malnutrition and low Fat-Free Mass Index at 6 months follow-up in a cohort of inactive/mildly active IBD patients.

References

Huang S, Niu Y, Liu X, Gu Z, Huang A, Wu J. Characteristics of malnutrition according to Global Leadership Initiative on Malnutrition criteria in non-surgical patients with inflammatory bowel disease. Nutrition. 2022;94:111514. doi:10.1016/j.nut.2021.111514

Jensen GL, Cederholm T, Correia MITD, et al. GLIM Criteria for the Diagnosis of Malnutrition: A Consensus Report From the Global Clinical Nutrition Community. JPEN J Parenter Enteral Nutr. 2019;43(1):32-40. doi:10.1002/jpen.1440

Cederholm T, Bosaeus I, Barazzoni R, et al. Diagnostic criteria for malnutrition - An ESPEN Consensus Statement. Clin Nutr. 2015;34(3):335-340. doi:10.1016/j.clnu.2015.03.001

van Bokhorst-de van der Schueren MA, Guaitoli PR, Jansma EP, de Vet HC. Nutrition screening tools: does one size fit all? A systematic review of screening tools for the hospital setting. Clin Nutr. 2014;33(1):39-58. doi:10.1016/j.clnu.2013.04.008

Ding NS, Tassone D, Al Bakir I, et al. Systematic Review: The Impact and Importance of Body Composition in Inflammatory Bowel Disease. J Crohns Colitis. 2022;16(9):1475-1492. doi:10.1093/ecco-jcc/jjac041