Introduction

Cytotoxic agents have long been used in the treatment of malignant tumors and continue to play a central role. Chemotherapy-induced cell death has been proposed to enhance the efficacy of immunotherapy through mechanisms such as immunogenic cell death or antigen spreading. However, these immunological processes remain underutilized in the clinical management of pancreatic ductal adenocarcinoma (PDAC). Oncogenic KRAS is known to promote an inflammatory tumor microenvironment, a process that can be further amplified by cytotoxic chemotherapy—a phenomenon we previously described as a "chemotherapy-derived inflammatory response" (Takeuchi et al., Cancer Research, 2015). In the context of heterogeneous human PDAC, it remains unclear whether this response is primarily driven by the administered chemotherapeutic agents or by the intrinsic properties of cancer cells. Elucidating the determinants of this response is essential for optimizing treatment strategies.

Aims & Methods

To investigate the determinants of chemotherapy-derived inflammatory responses in PDAC, we conducted in vitro assays using a panel of PDAC cell lines and clinically relevant cytotoxic agents, including gemcitabine (GEM), 5-fluorouracil (5-FU), oxaliplatin, irinotecan, and paclitaxel. PDAC cell lines were classified according to their molecular subtypes (classical or basal). Each drug was administered at its IC50 concentration, and inflammatory cytokine responses were assessed by quantitative PCR, ELISA, and microarray analysis. Gene expression and cytokine secretion levels were compared across cell lines and treatment conditions. Granulocyte-macrophage colony-stimulating factor (GM-CSF) was used as a surrogate marker of the chemotherapy-induced inflammatory response.

Results

Using multiple assays, we found that the molecular subtype of PDAC (classical or basal) was not a major determinant of the chemotherapy-derived inflammatory response. Instead, gene expression patterns following drug-induced cell death varied significantly depending on the specific chemotherapeutic agent used. Notably, GEM strongly enhanced the expression of inflammatory cytokines through NF-κB activation, whereas 5-FU, despite inducing a comparable level of cell death, did not elicit such an inflammatory response. Gene set enrichment analysis based on microarray data further demonstrated that GEM and 5-FU induced distinct transcriptional profiles following cell death. These differences were also recapitulated in vivo using mouse tumor models.

Conclusion

Our findings suggest that chemotherapy-derived inflammatory responses are drug-specific. In particular, GEM may promote a suppressive tumor microenvironment by amplifying inflammation, potentially hindering anti-tumor immunity. To enhance the effectiveness of immunochemotherapy for PDAC, it will be crucial to elucidate the drug-specific mechanisms of cell death and to identify key regulatory molecules that can shift the response toward an immunogenic phenotype.

References

Takeuchi, S. Baghdadi, M. Tsuchikawa, T. Wada, H. Nakamura, T. Abe, H. Nakanishi, S. Usui, Y.Higuchi, K. Takahashi, M. Inoko, K. Sato, S. Takano, H. Shichinohe, T. Seino, K. Hirano, S. et al. Chemotherapy-Derived Inflammatory Responses Accelerate the Formation of Immunosuppressive Myeloid Cells in the Tissue Microenvironment of Human Pancreatic Cancer. Cancer Res. 75, 2629-2640 (2015).

Clinical Case Summary

We present a rare case of Heparin-Induced Thrombocytopenia (HIT) in a 58-year-old male with cirrhosis due to Hepatitis C, complicated by recurrent thrombosis of a Transjugular Intrahepatic Portosystemic Shunt (TIPS). The patient initially received intravenous heparin and mechanical thrombectomy for TIPS thrombosis. Upon switching to Low Molecular Weight Heparin (LMWH), his platelet count dropped from 120,000/µL to 70,000/µL, raising suspicion for HIT.
A positive anti-PF4/heparin antibody test confirmed the diagnosis [1]. Heparin was discontinued, and Argatroban, a direct thrombin inhibitor, was initiated to maintain anticoagulation. His platelet count recovered within 24 hours, and subsequent TIPS revision restored blood flow, improving his ascites and symptoms.
This case highlights the diagnostic complexity and therapeutic considerations of HIT in patients with severe liver disease and recurrent thrombotic events. Given the challenges of anticoagulation in cirrhotic patients, Argatroban was chosen due to its hepatic metabolism and adjustable dosing [2].
Our case underscores the importance of early HIT recognition, interdisciplinary collaboration, and careful anticoagulation selection in patients with TIPS thrombosis [3].
Illustrative Material (References to be used in the poster):

• Doppler Ultrasound: Confirming absent flow within the TIPS.
• CT Abdomen: Demonstrating ascites and portal hypertension.
• Platelet Trend Graph: Showing the decline and recovery post-heparin discontinuation.

References

1. https://doi.org/10.1182/blood.V96.3.846
2. NHS Greater Glasgow and Clyde. (n.d.). Heparin-Induced Thrombocytopenia: Diagnosis and Treatment. Retrieved from https://www.nhsggc.org.uk/media/262742/heparin-induced-thrombocytopenia-diagnosis-and-treatment.pdf
3. Warkentin, T. E., & Greinacher, A. (2004). Heparin‐induced thrombocytopenia: recognition, treatment, and prevention: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. British Journal of Haematology, 123:565-576. https://doi.org/10.1046/j.1365-2141.2003.04334.x

Disclosure

The authors declares no conflicts of interest.

Introduction

Upper gastrointestinal bleeding(UGIB) is a common condition that entails morbidity and mortality. Therefore, an early prediction of negative outcomes would be clinically relevant selecting patients who might benefit from a closer follow up. In this way, several pre-endoscopic scoring systems have been developed for risk assessment in the emergency room(1).
One of the limitations of scoring systems is that sensitivity and specificity alone (usually combined in the receiver operator characteristic curve) may help comparing the accuracy of different systems but cannot be used to accurately estimate the probability for an individual patient. A more appropriate approach is to establish the post‐test probability considering the expected pre‐test probability of poor outcomes in the population(2).

Aims & Methods

Given the absence of previous similar studies in UGIB, we aim to investigate the role of the most common pre-endoscopy scoring systems in modifying the pre-test probability of adverse outcomes.
Retrospective analysis of a prospective registry of UGIB patients admitted to 'Virgen de las Nieves University Hospital' (2013-2024). The outcomes included were intervention (composite endpoint including need of transfusion, endoscopy therapy, interventional radiology or surgery) and in-hospital mortality.
Pre-endoscopy scores analyzed were MAPASH,ABC and GBS as they have demonstrated their utility in predicting adverse events. The thresholds used for the definition of low-risk patients(test negative) were ABC≤3,MAPASH≤2 and GBS≤1(3).
First, the prevalence of the main outcomes was calculated to obtain the pre‐test probability. Next, characteristics of different scoring systems were used to obtain the likelihood ratio(LR) and to estimate the post‐test probability using an online calculator (http://araw.mede.uic.edu/cgi-bin/testcalc.pl).

Results

1649 UGIB patients were included.
Prevalence of intervention(pre-test probability) was 75%.
The sensitivity and specificity of MAPASH were 71.4% and 78.4%,respectively. +LR and -LR 3.31 and 0.36,respectively. Post‐test probability was 91% when positive and 52% when negative.
The sensitivity and specificity of ABC were 68.1% and 66.8%,respectively. +LR and -LR 2.05 and 0.48,respectively. Post‐test probability was 86% when positive and 59% when negative.
The sensitivity and specificity of GBS were 98.8% and 8.7%,respectively. +LR and -LR 1.08 and 0.14,respectively. Post‐test probability was 76% when positive and 29% when negative.
Prevalence of in-hospital mortality(pre-test probability) was 11%.
The sensitivity and specificity of MAPASH were 90.1% and 44.8%, respectively. +LR and -LR 1.63 and 0.22,respectively. Post‐test probability was 17% when positive and 3% when negative.
The sensitivity and specificity of ABC were 95.9% and 44.8%,respectively. +LR and -LR 1.74 and 0.09,respectively. Post‐test probability was 18% when positive and 1% when negative.
The sensitivity and specificity of GBS were 99.4% and 3.6%,respectively. +LR and -LR 1.03 and 0.17, respectively. Post‐test probability was 11% when positive and 2% when negative.

Conclusion

While MAPASH and ABC effectively prioritize high-risk patients for intervention, their ability to rule out intervention in low-risk patients is limited. Additionally, they are more useful excluding mortality among low-risk patients than accurately predicting fatal outcomes. GBS,in contrast, are useful identifying low risk patients for intervention and mortality.
Given these findings, clinicians should interpret these scores with caution and incorporate additional clinical parameters into decision-making.

References

1. Boustany A, Alali AA, Almadi M, Martel M, Barkun AN. Pre-Endoscopic Scores Predicting Low-Risk Patients with Upper Gastrointestinal Bleeding: A Systematic Review and Meta-Analysis. J Clin Med. 9 de agosto de 2023;12(16).
2. Capurso G, Ponz de Leon Pisani R, Lauri G, Archibugi L, Hegyi P, Papachristou GI, et al. Clinical usefulness of scoring systems to predict severe acute pancreatitis: A systematic review and meta‐analysis with pre and post‐test probability assessment. United European Gastroenterol J. 27 de septiembre de 2023;11(9):825-36.
3. Jimenez-Rosales R, Lopez-Tobaruela JM, Lopez-Vico M, Ortega-Suazo EJ, Martinez-Cara JG, Redondo-Cerezo E. Performance of the New ABC and MAP(ASH) Scores in the Prediction of Relevant Outcomes in Upper Gastrointestinal Bleeding. J Clin Med. 30 de enero de 203;12(3):1085.

Introduction

Biliary strictures present a major diagnostic challenge as benign and malignant conditions often exhibit similar clinical and imaging findings. In cases of indeterminate strictures, obtaining a tissue sample is crucial since no laboratory test can definitively confirm malignancy. Notably, up to 25% of patients undergoing surgery for suspected cholangiocarcinoma (CCA) are ultimately diagnosed with benign disease, underscoring the difficulty of preoperative diagnosis. The low cellularity and desmoplastic nature of CCA further complicate cytological and histological assessments. Current ESGE guidelines recommend ERCP with tissue acquisition (TA) as the preferred diagnostic approach for perihilar strictures requiring drainage.

Aims & Methods

This study aims to evaluate the diagnostic accuracy of EUS-TA for both distal and perihilar biliary strictures in a high-volume bilio-pancreatic endoscopy referral center. A retrospective analysis was conducted on a prospectively maintained database of patients who underwent EUS-TA at San Raffaele Hospital between April 2021 and June 2024 due to obstructive jaundice or biliary strictures identified via CT or MRI. Patients with preexisting pancreatic lesions, extrinsic biliary compression, or choledocholithiasis without biliary abnormalities were excluded. EUS-guided tissue sampling was performed using 25–22-gauge FNA or FNB needles with Rapid On-Site Evaluation (ROSE) by cytotechnicians. The final diagnosis was established based on surgical pathology, imaging, or a minimum follow-up of six months. Sensitivity, specificity, and likelihood ratios (LLR+ and LLR−) were calculated using 2×2 contingency tables, with 95% confidence intervals estimated via the Clopper-Pearson method. Additionally, a Random Forest model was developed using an 80:20 stratified split of the dataset, preserving class distribution. The model achieved an accuracy of 83.33% on the test set.

Results

Of the 249 patients screened, 86 met the inclusion criteria. Among them, 47 (54.7%) had perihilar strictures, and 39 (45.3%) had distal strictures. Strictures presented as lesions in 65% of cases and as wall thickening in 35%. Malignancy was diagnosed in 76.7% of cases, while 23.2% were benign. Adequate tissue sampling was achieved in 94% of cases, with five false-negative results. EUS-TA demonstrated an overall sensitivity, specificity, and accuracy of 86.4%, 95%, and 88.4%, respectively. In perihilar strictures, sensitivity was 85.7%, specificity 100%, and accuracy 87.2%, with an NPV of 45.4% and negative LR of 0.14. Combining EUS-TA with ERCP-TA improved sensitivity to 89% and accuracy to 92%.The Random Forest model showed high diagnostic performance, with a precision of 0.88, recall of 0.94, and an F1-score of 0.91 for malignant lesions. Multivariate analysis identified male sex, jaundice, mass-like presentation, and vascular invasion as independent predictors of malignancy. No clinical or EUS factors were significantly associated with diagnostic accuracy prediction.

Conclusion

This study confirms the strong diagnostic performance of EUS-TA for biliary strictures, including perihilar cases. The combination of EUS-TA and ERCP-TA significantly improves diagnostic yield, particularly for perihilar strictures. These findings support the use of EUS-TA as a first-line diagnostic approach in high-expertise centers, with a same-session EUS-ERCP strategy optimizing procedural efficiency and reducing risks.

Introduction

Japan NBI Expert Team (JNET) classification is clinically useful for diagnosing colorectal cancer; however, the major challenge in its application is eliminating the differences in diagnosis among endoscopists. In the JNET classification, Type 1 corresponds to hyperplastic polyps and sessile serrated lesions (SSL); Type 2A, adenomas to Tis; Type 2B, Tis and T1a; and Type 3, T1b or deeper lesions. We believe that diagnostic support using artificial intelligence can contribute to the standardization of the JNET classification of NBI diagnosis. Therefore, we developed a computer-aided diagnosis (CADx) system to support the JNET diagnosis and evaluated diagnostic performance of the CADx.

Aims & Methods

We developed a CADx system that can perform full-screen image classification while providing more detailed segmentation results as an output. This structure uses a deep convolutional network with the backbone of ResNet34 as a feature extractor for the entire system, and a structure of two transformer encoder blocks to perform full-screen classification. Further, we used a single-layer convolutional structure with a convolutional kernel size of 1 as the segmentation head. We examined 111 lesions: hyperplastic polyp/SSL, 36 lesions; adenoma, 37 lesions; Tis/T1a, 15 lesions; and T1b or deeper, 23 lesions using Olympus CV-290 and CV-1500 processors and Olympus CF-HQ290ZI, CF-XZ1200DI, and CF-EZ1500DI endoscopes. Each lesion was identified according to the JNET classification: Hyperplastic polyp/SSL, Type 1; Adenoma, Type 2A; Tis/T1a, Type 2B; T1b or deeper, Type 3. The accuracy between the histopathological findings and diagnosis by CADx system was calculated.

Results

The accuracy between CADx system and the histopathological findings was 94.4% (34/36) for hyperplastic polyp/SSL, 81.1% (30/37) for adenoma, 60.0% (9/15) for Tis/T1a, and 74.0% (17/23) for T1b or deeper lesions.

Conclusion

We developed a multiclass CADx system for colorectal lesions that performs JNET classification for histopathological findings, which may assist in the NBI-based diagnosis of colorectal lesions in facilities where the NBI diagnosis with magnifying endoscopy is not widespread.

Introduction

Abdominal obesity is a major global health burden, driving risk for cardiovascular disease, type 2 diabetes, and cancer (1). Lifestyle interventions, particularly dietary modifications, are central to prevention. The Mediterranean Diet (MedDiet), recognized for its cardiometabolic benefits, emphasizes Extra-Virgin Olive Oil (EVOO) as a primary fat source. We previously validated the Chrono Med Diet Score (CMDS), a novel index integrating dietary quality and chrono-nutritional principles, and demonstrated its associations with visceral adiposity, cardiometabolic risk, and cancer incidence (2,3). Although EVOO is central to the MedDiet, its specific contributions to metabolic health remain incompletely defined. This study aimed to investigate the relationship between habitual EVOO intake frequency, MedDiet adherence (CMDS), and anthropometric outcomes.

Aims & Methods

We analyzed data from 16,273 adults (46.5% male; 94.1% of European origin) who completed the CMDS-based online survey (www.chronomeddiet.org) since April 2023. Data included age, sex, height, weight, waist circumference (WC), and dietary/lifestyle information. BMI was calculated from self-reported height and weight. EVOO intake frequency was categorized as: sporadic (<3 days/week), frequent (≥3 but <6 days/week), or regular (≥6 days/week), based on ~25g/day (~2 tablespoons). Visceral obesity was defined per IDF 2006 criteria for Europids. Statistical analyses included Student’s t-tests, ANOVA with Bonferroni correction, mediation analysis, and multivariable logistic regression adjusting for confounders.

Results

Significant sex differences were observed in age, BMI, WC, and CMDS. Participants with regular EVOO intake were significantly older (55.9±8.1 years) than sporadic (53.9±7.1) and frequent (54.1±7.7) consumers (p=0.0019), yet showed more favorable anthropometrics. Compared to sporadic intake, regular intake was associated with significantly lower BMI (24.7±3.0 vs 26.6±2.9, p<0.001) and WC (89.1±6.7 cm vs 99.4±9.1 cm, p<0.0001), with consistent results across sexes (p<0.0001 for both). Mediation analysis revealed that EVOO’s effect on WC was significantly mediated by CMDS (β = –0.83, p<0.0001), accounting for 61.9% of the total effect. A direct association also persisted after adjusting for CMDS (β = –0.59, p<0.0001). In logistic regression, non-regular EVOO intake (sporadic + frequent) was associated with substantially higher odds of abdominal obesity (OR 5.1; 95% CI: 3.3–6.8; p<0.0001).

Conclusion

In this large cohort, regular EVOO consumption is independently associated with lower BMI and WC, and with higher CMDS adherence. EVOO exerts a dual role in metabolic health, both mediating and independently enhancing the relationship between chrono-Mediterranean diet adherence and reduced abdominal obesity. Non-regular EVOO intake emerges as a strong risk factor for visceral adiposity, irrespective of overall diet quality.

References

1. Crudele L, Piccinin E, Moschetta A. Visceral Adiposity and Cancer: Role in Pathogenesis and Prognosis. Nutrients. 2021 Jun 19;13(6):2101.
2. De Matteis C, Crudele L, Battaglia S, Loconte T, Rotondo A, Ferrulli R, et al. Identification of a Novel Score for Adherence to the Mediterranean Diet That Is Inversely Associated with Visceral Adiposity and Cardiovascular Risk: The Chrono Med Diet Score (CMDS). Nutrients. 2023 Apr 15;15(8):1910.
3. De Matteis C, Crudele L, Gadaleta RM, Di Buduo E, Novielli F, Petruzzelli S, et al. Low Adherence to Mediterranean Diet Characterizes Metabolic Patients with Gastrointestinal Cancer. Nutrients. 2024 Feb 24;16(5):630.

Introduction

Management of acute cholecystitis in high-risk surgical candidates presents a clinical challenge. Percutaneous drainage via a cholecystostomy tube has been the preferred alternative in this cohort, with high rates of complications and low patient acceptability. Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) using lumen-apposing metal stents (LAMS) has been proposed as an alternative. Although several prospective studies and one randomised control trial have been published, it is not current standard of practice and there remains some concerns regarding its safety and efficacy.

Aims & Methods

This study evaluates the efficacy and safety of EUS-GBD for non-surgical candidates presenting with acute cholecystitis in the largest prospective cohort at a tertiary hospital within Australia and New Zealand. From July 2024, prospectively collected cases who underwent EUS-GBD using LAMS were entered into a secure database at our institution. Patients were followed for up to 180 days after index EUS-GBD procedure. Primary outcomes included technical and clinical success. Secondary outcomes include adverse events (AE), re-intervention rates and mortality.

Results

Twenty four patients (12 females, 12 males; mean age 75.5 years; range: 54–90) were included from July 2024 to April 2025. Patients were comorbid (mean Charlson Comorbidity Index 5.1), frail (mean Clinical Frailty Scale 4), and had high peri-operative risk (mean ASA score 3). EUS-GBD was technically and clinically successful in 100% of cases. Two (8.33%) patients experienced adverse events (stent occlusion requiring reinterventions). One (4.15%) patient developed atrial fibrillation driven by underlying sepsis necessitating admission to the high-dependency unit following EUS-GBD. There was one death occurring 23 days following EUS-GBD, deemed unrelated to the procedure. There were no procedure related mortality during the study period with an average follow up of 155 days.

Conclusion

Our study demonstrates that EUS-GBD is an effective and safe management option for gallbladder drainage in non-surgical candidates with acute cholecystitis. The high technical and clinical success rates, coupled with few procedure-related complications, support its use as the preferred option for drainage in otherwise poor surgical candidates due to significant medical comorbidities. However, larger studies are needed to validate these findings.

Disclosure

Drs Weilert, Chin and Prof. Fockens - consultants for Boston Scientific