J. Enrique Domínguez-Muñoz

Background: Pancreatic exocrine insufficiency (PEI) is a maldigestion syndrome leading to symptoms and nutritional deficiencies. Prospective real‐world data on pancreatic enzyme replacement therapy (PERT) dose requirements across aetiologies are limited. Objective: To define PERT dose requirements and treatment outcomes across PEI aetiologies in specialist European practice. Methods: EURO‐PEI was a multicentre observational registry with predominantly prospective data collection conducted at eight pancreatic centres in five European countries between June 2021 and September 2025. Adults with clinician‐established PEI in whom PERT was initiated or actively optimised were included. The primary outcome was the optimised PERT dose associated with the achievement of a clinician‐assessed therapeutic goal: improvement or resolution of PEI‐related symptoms with normalisation or clinically relevant improvement of nutritional abnormalities. Results: Among 1015 patients, PEI was secondary to chronic pancreatitis in 496 (48.9%), pancreatectomy in 185 (18.2%), pancreatic cancer in 174 (17.1%), and acute pancreatitis in 95 (9.4%). Median total daily optimised doses were highest after pancreatectomy (240,000 PhU, IQR 175,000–375,000) and in pancreatic cancer (210,000 PhU, 175,000–325,000), compared with chronic pancreatitis (175,000 PhU, 120,000–210,000) and acute pancreatitis (100,000 PhU, 75,000–200,000). After optimisation, the therapeutic goal was achieved in 951 patients (93.7%); of these, 446 (46.9%) required enzyme doses exceeding commonly recommended starting doses. Related adverse events occurred in 38 patients (3.7%). Conclusions: PERT dose requirements vary substantially by PEI aetiology, supporting aetiology‐aware starting doses, early reassessment, and individualised optimisation in high‐risk groups.

Pancreatic exocrine insufficiency (PEI) is a potential but under-recognized complication after upper gastrointestinal (GI) surgery, contributing to malabsorption and nonspecific GI symptoms. This prospective cohort study included adult patients undergoing esophagectomy or gastrectomy at a single tertiary referral center between March 2022 and January 2024. A total of 51 patients were included, with 34 completing full follow-up. The primary outcome was the prevalence of PEI. A secondary outcome was the effect of pancreatic enzyme replacement therapy (PERT) in patients with PEI. Among 31 patients undergoing esophagectomy, one (3.2%) was diagnosed with PEI. In contrast, PEI was identified in five (25.0%) of 20 patients after total or subtotal gastrectomy. PERT was administered in all patients with PEI. At 12-months' follow-up, clinical improvement in PEI symptoms was observed in four of six patients, while in two patients, disease progression due to cancer prevented assessment of the PERT effect. PEI is a clinically significant postoperative complication after upper GI surgery. These findings support the inclusion of pancreatic exocrine function assessment in the postoperative follow-up of gastric surgery patients, particularly those presenting with nonspecific GI symptoms and malabsorption, to enable timely diagnosis and management.

Faecal elastase-1 testing is the most commonly used method for diagnosing pancreatic exocrine insufficiency (PEI), but has poor diagnostic precision and cannot guide titration of pancreatic enzyme replacement therapy (PERT). An alternative is ¹³C-mixed triglyceride breath test. We investigated concordance between breath test and faecal elastase-1, and response to bicarbonate-buffered enzymes. In this prospective study, adults with faecal elastase 13CO2 exhalation (substudy II). Baseline tests where performed in 25 participants. Thirteen participants had normal breath test, 11 agreed to pause PERT, but only five participants did not reinitiate treatment (substudy I). 12 participants were included in substudy II (mean age 65, all males). All had significant breath test improvements on lowest enzyme dose (24,000 IU) versus baseline (mean difference 21.5%, p < 0.001), yet higher enzyme doses did not improve results significantly. About half of participants previously categorised with PEI had normal ¹³C-mixed triglyceride breath test, questioning diagnosis. Most participants demonstrated normal breath test with lowest enzyme dose during standardised test meal. However, this finding may not generalise to habitual meals.

Background: Inflammatory bowel disease (IBD) develops from a dysregulated immune response influenced by environmental exposures. Radon, a radioactive gas, has known biological effects, but its role in IBD remains unexplored. Objectives: To examine the association between residential radon exposure and the risk and clinical course of IBD. Design: A case–control study with 1-year prospective follow-up of cases. Methods: We included 178 newly diagnosed IBD patients and 178 age- and sex-matched controls in Santiago de Compostela, Spain, from June 2020 to September 2023. Residential radon levels were measured using passive detectors for 3 months. Outcomes included IBD diagnosis, disease extent, hospitalizations, and flares. Logistic regression was used to estimate odds ratios adjusted for age and sex. Results: Median residential radon was 144.5 Bq/m ³ in IBD cases and 189.5 Bq/m ³ in controls. Higher radon levels were associated with reduced odds of IBD (OR 0.5 for 100–299 and >299 Bq/m ³ vs 0–99 Bq/m ³ ). No significant association was found between radon levels and hospitalizations or flares. Among ulcerative colitis patients, higher radon was linked to more extensive disease. Conclusion: Higher residential radon exposure might be inversely associated with IBD risk. However, it does not appear to influence disease progression. Further studies are needed to confirm these findings, since this is the first study on this topic, and chance or selection bias might be present.

Introduction: Pancreatic exocrine insufficiency (PEI) is seen in primary pancreatic disease but has also been seen in extrapancreatic conditions including celiac disease (CeD). The symptoms of PEI and CeD often overlap, which makes diagnostics challenging. In this systematic review and meta‐analysis, we aimed to investigate the prevalence of PEI in CeD. Methods: With the assistance of a professional librarian, we searched five databases: PubMed, Embase, Cochrane, Web of Science Core Collection, and Google Scholar, up until October 21, 2024. The pooled prevalence of PEI in biopsy‐confirmed CeD was estimated, and the quality of studies appraised. Results: We identified and screened the titles and abstracts of 1432 publications, of which 60 were reviewed in full text and 12 were included in the analyses. The overall pooled weighted prevalence of PEI in CeD was 13.5% (95% CI 7.2–21.0). The prevalence was similar among children (14.2%; 95% CI 2.0–32.8) and adults (12.8%; 95% CI 7.8–18.7) with CeD. The prevalence in studies that used secretory testing to define PEI was 13.1% (95% CI 6.4–21.3) and in those requiring digestive tests 17.1% (95% CI 5.8–32.1). The weighted prevalence of PEI was significantly higher among untreated CeD patients (18.2%) than patients on a gluten‐free diet (6.9%) ( p = 0.03), in both adults and children. Conclusion: One in eight individuals with CeD may suffer from PEI. The prevalence was particularly high in untreated CeD. PEI should be considered in patients who do not respond to a gluten‐free diet.

Background & Aims: Pancreatic ductal adenocarcinoma (PDAC) genetic susceptibility is partially identified. The complement system (CS) influences carcinogenesis and participates in immunological defense and homeostasis; however, its role in PDAC genetic susceptibility and prognosis is underexplored. Methods: The association of SNPs within 111 CS-related genes with PDAC risk was assessed in the PanGenEU study and validated in the UKBiobank. We investigated the association between the CS-related gene variation and PDAC risk, followed by an in-depth functional in-silico study using TCGA and ICGC data. We assessed whether CS-related genes were associated with prognosis at germline and somatic levels. We investigated the immune infiltration of PDAC tumors according to their transcriptomic profile. Results: Genetic variation in FCN1 and PLAT was significantly associated with PDAC risk. PDAC patients with elevated expression of IGHG3 , IGKC , IGHM , F2R , F2RL2 , CFI , A2M , and C4A displayed improved survival and higher infiltration of CD8 ⁺ , B cells, and Th1 cells. Individuals with high expression levels of FGA , SERPINE1 , FGG , and F3 had poorer survival, higher infiltration of Tregs, and lower infiltration of CD8+ cells. Conclusions: Results from this study suggest that CS-related genes play a role in PDAC genetic susceptibility and survival through specific immune cell infiltration.

Pancreatic exocrine insufficiency (PEI) is defined as a reduction in pancreatic exocrine secretion below the level that allows the normal digestion of nutrients. Pancreatic disease and surgery are the main causes of PEI. However, other conditions and upper gastrointestinal surgery can also affect the digestive function of the pancreas. PEI can cause symptoms of nutritional malabsorption and deficiencies, which affect the quality of life and increase morbidity and mortality. These guidelines were developed following the United European Gastroenterology framework for the development of high‐quality clinical guidelines. After a systematic literature review, the evidence was evaluated according to the Oxford Center for Evidence‐Based Medicine and the Grading of Recommendations Assessment, Development, and Evaluation methodology, as appropriate. Statements and comments were developed by the working groups and voted on using the Delphi method. The diagnosis of PEI should be based on a global assessment of symptoms, nutritional status, and a pancreatic secretion test. Pancreatic enzyme replacement therapy (PERT), together with dietary advice and support, are the cornerstones of PEI therapy. PERT is indicated in patients with PEI that is secondary to pancreatic disease, pancreatic surgery, or other metabolic or gastroenterological conditions. Specific recommendations concerning the management of PEI under various clinical conditions are provided based on evidence and expert opinions. This evidence‐based guideline summarizes the prevalence, clinical impact, and general diagnostic and therapeutic approaches for PEI, as well as the specifics of PEI in different clinical conditions. Finally, the unmet needs for future research are discussed.

Genetic susceptibility loci are associated with PDAC risk and survival, but the impact of germline HLA region variation remains largely unexplored. This study examined HLA I-II alleles within the PanGenEU study and validated our findings using external datasets (UK Biobank, TCGA, PAN-NGS trial, and Caris trial). HLA-A*02:01and HLA-B*49 alleles were linked to a decreased risk of PDAC, whereas HLA-B*39 , HLA-DPB1*04, and HLA-A*26:01 were directly associated with increased risk. PDAC patients carrying the HLA-A*02:01 allele also showed lower mortality rates, with the effect being more pronounced in those with KRAS ^G12V mutations, pointing to a host*tumor genetic interaction. This research highlights HLA-A*02:01 , found in 20% of Europeans, as a marker for reduced PDAC risk and mortality, especially in KRAS ^G12V mutated tumors. Results from this study could enhance personalized medicine for PDAC by identifying patients who may benefit from regular screenings through tailored risk assessments. Importantly, our findings are crucial for stratifying PDAC patients based on their genetic background and tumor mutational profile, which can guide treatment strategies.