Introduction

Endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) is widely recognized as the preferred diagnostic method for pancreatic lesions, achieving diagnostic accuracy rates between 78% and 95%. Rapid on-site evaluation (ROSE) improves adequacy rates but remains unavailable in many centers. In this context, we evaluated a simplified method, Visual On-Site Evaluation (VOSE), based on macroscopic evaluation of the biopsy sample, to predict histo-cytological adequacy without needing ROSE.
Primary aim: assess the accuracy of VOSE in predicting sample adequacy.
Secondary aims: evaluate the diagnostic yield of FNB and the potential reduction in unnecessary needle passes.

Aims & Methods

This prospective single-center study enrolled patients undergoing EUS-FNB for pancreatic lesions between January 2020 and February 2024.
VOSE parameters included the presence of a macroscopic visible core (MVC), number of specimens, and specimen length. Associations between VOSE findings and final histo-cytological adequacy were analyzed using Fisher’s exact test and Student’s t-test. A p-value < 0.05 was considered statistically significant. Study conducted at a university hospital center.

Results

Fifty-nine patients (57.6% male; mean age 67.9 ± 9.8 years) were included, contributing to a total of 59 pancreatic lesions. Across 218 passes performed, the overall sample adequacy rate was 91.5%.
Adequacy was significantly higher when using 22-G needles compared to 25-G needles (95.7% vs. 86.2%, p = 0.018). VOSE criteria (presence of MVC, multiple fragments, and long specimen) demonstrated a sensitivity of 52.3%, a specificity of 61.1%, and a positive predictive value (PPV) of 93.1% for predicting sample adequacy. Applying VOSE led to a 45% reduction in unnecessary additional passes.

Conclusion

EUS-FNB provides excellent diagnostic adequacy for pancreatic lesions, particularly with 22-G needles. The use of VOSE, a simple and reproducible macroscopic evaluation method, can reliably predict histo-cytological adequacy and substantially reduce the number of passes, offering a practical alternative in centers without ROSE availability.

References

1. El Chafic AH, Loren DE, Siddiqui AA. EUS-guided fine-needle biopsy of pancreatic masses: new tools, new techniques. Endosc Ultrasound. 2023;12(1):3-10.
2. Crinò SF, Larghi A, Bernardoni L, et al. EUS-guided fine-needle biopsy with or without ROSE for pancreatic masses: A multicenter randomized trial. Gastrointest Endosc. 2023;98(2):225-234.e3.
3. Bang JY, Hebert-Magee S, Navaneethan U, Hasan MK, Hawes R, Varadarajulu S. EUS-guided fine-needle biopsy of pancreatic masses: a meta-analysis comparing FNA and FNB. Gastrointest Endosc. 2022;95(5):893-905.e2.

Introduction

Alcohol is a common cause of acute pancreatitis, and ongoing consumption increases the risk of recurrent episodes. There are no international guidelines to direct behavioural or pharmacological interventions to reduce recurrence of alcohol-associated acute pancreatitis (AAP). Studies exploring the role of addiction medicine in patients with AAP are limited.

Aims & Methods

This study describes the uptake and role of the Addiction Medicine Unit (AMU), a specialist consultative service, in patients admitted with AAP. We conducted a retrospective cohort study including all inpatients diagnosed with AAP at a large multisite tertiary health service in Melbourne, Australia between May 2022 to May 2024. Patient demographics, diagnosis of alcohol use disorder (AUD) and pharmacological and non-pharmacological interventions provided by the AMU were obtained from the patient’s medical records.

Results

A total of 231 patients with 314 admissions with AAP were identified. Most were males (77.9%) with a median age of 44 years (IQR 21), with median bedside index of severity in acute pancreatitis (BISAP) score of 1 (IQR 1). Of the patients, 35 (11.1%) had necrotising pancreatitis, 30 (9.6%) required admission to the intensive care unit (ICU), and 1 patient died from AAP. The prevalence of AUD was 82.3%. Referral to the AMU occurred in 56.7% of admissions, predominantly among those with AUD (87.6%). Patients referred to the AMU had a higher median number of standard drinks per week (70 standards, range 6-385 standards) compared to those who were not referred (49 standards, range 1-301 standards) (p=0.024). The AMU recommended outpatient services alone in 40.4%, both pharmacological and outpatient interventions in 37.6%, and medications alone in 21.9%. Outpatient services included either a service for community-based assessment and counselling (86.4%), residential rehabilitation programs and/or detox services (5.8%), follow up in the AMU outpatient clinic (3.9%) or a combination of these outpatient services (3.9%). There were 137 (43.6%) admissions in which patients were commenced on medications for AUD. Topiramate (42.6%), and naltrexone (42.6%) were the most prescribed pharmacological agents by the AMU, followed by baclofen (9.8%), acamprosate (4.1%) and disulfiram (0.8%). Over the 2-year period, 54 (23.4%) were readmitted with AAP. Most patients were not readmitted within 30 days of discharge (73.2%) however there were 33 (10.5%) patients readmitted for pancreatitis or pancreatitis-related complications including pain or infection, and 18 (5.7%) readmitted to hospital for non-pancreatitis related reasons. Patients who were older (median 49 years) were more likely to be readmitted with AAP compared to those who were younger (median age 43 years) across the study period (p=0.05). There were six patients re-admitted with AAP with their index admission deemed related to an alcoholic binge without suspected underlying AUD. Of these six patients, only two were referred and reviewed by the AMU, with the other four patients not referred.

Conclusion

Our study highlights the critical role of the AMU in managing AAP, particularly given the high prevalence of concurrent AUD in this population. Despite this, significant gaps remain in screening for AUD and initiating referrals, resulting in only half of AAP patients being referred. Considering the substantial morbidity and healthcare cost associated with alcohol, efforts to improve referral practices during index admissions may be key to reduce readmissions for AAP and improve patient outcomes.

Introduction

Acute pancreatitis (AP) is a major cause of digestive-related hospitalizations. Systemic inflammatory response syndrome (SIRS) is present in 20–60% of cases and is associated with severe AP, multiorgan failure (MOF), or in-hospital mortality. This study aims to assess the clinical impact of transient and persistent SIRS on mortality and MOF, compared with the BISAP score.

Aims & Methods

A retrospective study was conducted on a prospective cohort of patients admitted with AP to a tertiary hospital between March 2017 and June 2019. Blood tests were recorded at admission and at 48 hours. Severity was defined using the 2012 Atlanta classification. MOF was defined as dysfunction of two or more organ systems lasting over 48 hours. Transient SIRS was present only at admission, while persistent SIRS lasted >48h. Univariate analysis and ROC curves were conducted using SPSS. Fagan nomograms estimated post-test probabilities of mortality and MOF using pre-test prevalence from the cohort.

Results

A total of 467 patients were included; 84 (18.41%) had SIRS at admission, of whom 32 (37.52%) had persistent SIRS. ROC analysis showed similar AUCs for persistent SIRS and BISAP ≥2, while transient SIRS had poor predictive value. Fagan nomograms showed persistent SIRS had the highest positive and negative likelihood ratios, and greater post-test probability for mortality and MOF, compared to BISAP ≥2 and transient SIRS.

Conclusion

Persistent SIRS was associated with higher risk of mortality and MOF, while transient SIRS had limited prognostic value. Persistent SIRS and BISAP ≥2 had comparable ROC performance, but Fagan nomograms demonstrated the superior clinical predictive utility of persistent SIRS. It showed post-test probabilities up to 40%, compared to 12–13% for BISAP ≥2. These results highlight the importance of monitoring SIRS persistence in AP for better risk stratification and early intervention.

References

1. Crockett SD, Wani S, Gardner TB, Falck-Ytter Y, Barkun AN; American Gastroenterological Association Institute Clinical Guidelines Committee. American Gastroenterological Association Institute guideline on initial management of acute pancreatitis. Gastroenterology. 2018;154(4):1096–1101. doi:10.1053/j.gastro.2018.01.032.
2. Singh VK, Wu BU, Bollen TL, Repas K, Maurer R, Mortele KJ, et al. Early systemic inflammatory response syndrome is associated with severe acute pancreatitis. Clin Gastroenterol Hepatol. 2009;7(11):1247–1251. doi:10.1016/j.cgh.2009.08.012.

Introduction

Pancreatic fluid collections (PFCs) are significant local complications that can arise from acute pancreatitis, and its management often involves drainage, although the benefits of metal stents over plastic stents remain uncertain. This meta-analysis compared the efficacy and safety of metal stents versus plastic stents for endoscopic ultrasound (EUS)-guided drainage of PFCs.

Aims & Methods

We searched PubMed, Embase, and Cochrane Library for randomized controlled trials (RCTs) comparing metal with plastic stents for drainage of PFCs. The odds ratio (OR) was used for binary outcomes and the mean difference (MD) for continuous outcomes with their respective 95% confidence interval (CI).

Results

This study included eight RCTs and over 500 patients. Procedure duration was shorter in the metal stent arm compared with the plastic stent arm (MD -10.63; 95%CI -16.12 to -5.15, p<0.001). However, there was no statistically significant difference between metal and plastic stents in clinical success (p=0.78), technical success (p=0.65), overall mortality (p=0.48), recurrence (p=0.23), number of interventions (p=0.85), need of necrosectomy (p=0.35), need of surgery (p=0.35), length of hospitalization (p=0.86), exocrine insufficiency (p=0.54), endocrine insufficiency (p=0.77), and AEs (p=0.36).

Conclusion

Metal stents for EUS-guided drainage of PFCs are associated with a shorter procedure duration. Besides that, it did not improve other clinically relevant outcomes in comparison with plastic stents.

Introduction

Pancreatic ductal adenocarcinoma (PDAC) ranks among the most aggressive malignancies, with a five-year survival rate below 10%. Its poor prognosis stems from late diagnosis, rapid disease progression, and marked resistance to conventional therapies, largely driven by frequent KRAS and TP53 mutations. These genetic alterations disrupt multiple cellular processes, including intracellular calcium (Ca²⁺) signaling, which plays a critical role in tumor progression. Plasma membrane calcium ATPase isoform 4 (PMCA4) is a major regulator of cytosolic Ca²⁺ levels, essential for maintaining cellular homeostasis. Elevated expression of PMCA4 in PDAC has been associated with enhanced cell migration, apoptosis resistance, and poor clinical outcomes. PMCA4 localizes at focal adhesions, supporting motility and metastatic potential. Paradoxically, PMCA4 dysfunction can lead to Ca²⁺ overload, activating oncogenic pathways that drive cell proliferation and survival. The cystic fibrosis transmembrane conductance regulator (CFTR), an epithelial chloride channel, also modulates calcium homeostasis. CFTR deficiency or dysfunction impairs PMCA4 activity, while paradoxically inducing its overexpression, likely as a compensatory mechanism in response to altered Ca²⁺ signaling. This functional interaction between CFTR and PMCA4 is particularly relevant in pancreatic ductal epithelial cells, where both proteins co-localize at the apical membrane. Their coordinated function is crucial for regulating calcium and chloride transport, and its disruption may contribute to PDAC progression.

Aims & Methods

This study aim to investigate whether CFTR deficiency contributes to PMCA4 overexpression in PDAC cells and whether pharmacological restoration of CFTR function using Trikafta can normalize calcium signaling and modulate tumor cell behavior. Therefore we utilized both human pancreatic ductal organoids (hPOs) and the Capan-1 PDAC cell line to assess calcium and chloride transport. Intracellular calcium levels were measured using FURA-2-AM, and chloride efflux was monitored with MQAE dye. Immunofluorescence staining was employed to analyze the expression and localization of CFTR, PMCA4, SOX9, Vimentin, and α-SMA.

Results

We successfully cultured human pancreatic organoids from adult pancreas-derived stem cells using standard 3D culture conditions. Following the establishment of primary organoids, we performed the first passage to expand the culture. The organoids were then dissociated into single cells and plated onto 24 mm cover glasses for further analysis. Our experiments confirmed the expression of ductal markers in 2D human pancreatic organoids (hPOs) with the lack of mesenchymal markers Vimentin, and α-SMA. Immunofluorescent staining was visualized using a Zeiss LSM880 confocal microscope. Functional assays revealed that Capan-1 cells exhibited significantly reduced Ca²⁺ and Cl⁻ efflux compared to hPOs, indicating impaired CFTR and PMCA acitivty. Notably, treatment with Trikafta, a clinically approved CFTR modulator, successfully restored CFTR and PMCA4 activity in Capan-1 cells.

Conclusion

Our findings indicate that CFTR dysfunction contributes to the increased PMCA expression in PDAC cells, which can be ameliorated by Trikafta treatment. This study highlights the critical interplay between CFTR dysfunction and calcium homeostasis in pancreatic ductal adenocarcinoma (PDAC). These results underscore the relevance of epithelial ion transport pathways in PDAC pathophysiology and support further investigation of adjunctive approach in PDAC treatment.

Introduction

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer that poses significant therapeutic challenges. In this regard, the identification of prognostic biomarkers is crucial to improve the prediction of clinical outcomes and guide therapeutic decisions. Tumour-associated autoantibodies (TAAbs) have been identified as prognostic biomarkers in several types of cancer, as they can be generated before the first clinically detectable signs of disease.

Aims & Methods

The aim of this study was to identify TAAbs that can be used as prognostic biomarkers in PDAC. 80 sera from patients with PDAC, divided into four groups according to disease stage, were included in the study: patients with premalignant lesions (n = 20), patients undergoing curative resection after diagnosis (CR) (n = 20), patients with unresectable advanced locoregional disease (LA) (n = 20) and patients with metastatic disease (MT) (n = 20). Sera from each group were analysed divided into 4 pools of 5 samples each using the HuProt Human Protreome microarray v4.0 (CDI Laboratories, Baltimore, MD). Candidate TAAbs with high specific reactivity in MT and/or LA samples were selected according to the following criteria: z-score ≥ 3 in at least 2/4 pools and fold-change > 1.2. The RNAseq data collected in the Human Protein Atlas were used to determine protein expression levels and prognostic value. The GSE15471, GSE28735 and GSE16515 databases were used to compare expression levels with those of healthy subjects without the disease.

Results

43 TAAbs demonstrated high levels of specific reactivity in samples from MT and/or LA patients. Of these highly recognised proteins, 15 were selected for showing notable levels of expression in tumour tissue from PDAC patients and prognostic capacity in some types of cancer. Of these 15, 2 proteins involved in tumour development were identified. Survival analyses showed that six of the 15 selected proteins were significantly associated with a worse prognosis in PDAC patients (p < 0.05). Finally, in the comparison with control tumour tissue, 5 proteins were identified with significantly higher expression in patients diagnosed with the disease (p < 0.05 in at least 2 of the cohorts used).

Conclusion

15 TAAbs have been identified as promising candidates for prognostic biomarkers in PDAC. Further validation studies are required to confirm their prognostic value and to develop a robust biomarker signature with potential for clinical application and market translation.