Introduction

Patients with suspected main-duct intraductal papillary mucinous neoplasms (MD-IPMN) are frequently referred for surgery due to the high risk of malignancy (as high as 40% to 60% in the literature). However, many present with significant comorbidities or concurrent malignancies, complicating the surgical risk-benefit assessment. In such cases, advanced endoscopic procedures may assist in guiding clinical decision-making.

Aims & Methods

This study aimed to evaluate the role of EUS-guided fine-needle biopsy (EUS-FNB) and pancreatoscopy in individualized risk stratification and management decisions for patients with suspected MD-IPMN. We retrospectively analyzed eight patients treated at our center between March 2020 and March 2025. All patients presented with significant comorbidities or active oncologic disease. Data collected included endoscopic findings, biopsy results, complications, and final management decisions.

Results

Eight patients with suspected main-duct IPMN were included (mean age: 67.6 years; 3 females, 37.5%). The mean main pancreatic duct (MPD) diameter was 9.1 mm. All patients were evaluated in a multidisciplinary setting due to clinical complexity, including comorbidities or concurrent malignancies. EUS-guided fine-needle biopsy (EUS-FNB) was performed in 3 patients, and pancreatoscopy in 5. All procedures were technically successful. Biopsy samples were diagnostic in 2 of 3 EUS-FNB cases and 5 of 5 pancreatoscopy cases and contributed directly to management decisions. In 1 EUS-FNB case, the sample was non-diagnostic. Pancreatoscopy revealed mucin extrusion in 4/5 patients, papillary or villous projections in 3/5, and a 'fish egg' appearance in 2/5. These features supported risk assessment and, in several cases, justified a conservative approach in high-risk patients. Three patients underwent surgery following multidisciplinary review. One had concordant findings (high-grade dysplasia), while two had discordant outcomes: one with low-risk pancreatoscopy findings had invasive adenocarcinoma, and one with EUS-FNB showing low-grade atypia had high-grade dysplasia on final pathology. Five patients were managed with active surveillance. One case of mild post-ERCP pancreatitis occurred; no other complications were reported. Endoscopic findings influenced management in 5 of 8 patients (62.5%).

Conclusion

In this real-world case series, EUS-FNB and pancreatoscopy contributed meaningfully to individualized decision-making in patients with suspected MD-IPMN. However, discordance between endoscopic impressions and final pathology in two cases highlights the limitations of visual and cytologic assessment. These findings reinforce the need for integrating endoscopic data with imaging, clinical context, and multidisciplinary input when evaluating main-duct IPMN.

References

1. Salvia R, Fernández-del Castillo C, Bassi C, Thayer SP, Falconi M, Mantovani W, Pederzoli P, Warshaw AL. Main-duct intraductal papillary mucinous neoplasms of the pancreas: clinical predictors of malignancy and long-term survival following resection. Ann Surg. 2004 May;239(5):678-85; discussion 685-7. doi: 10.1097/01.sla.0000124386.54496.15. PMID: 15082972; PMCID: PMC1356276.
2. Sohn TA, Yeo CJ, Cameron JL, Hruban RH, Fukushima N, Campbell KA, Lillemoe KD. Intraductal papillary mucinous neoplasms of the pancreas: an updated experience. Ann Surg. 2004 Jun;239(6):788-97; discussion 797-9. doi: 10.1097/01.sla.0000128306.90650.aa. PMID: 15166958; PMCID: PMC1356287.

Introduction

Pancreatic calcification is the most frequent structural change in chronic pancreatitis (CP), but the factors associated with its development are not well understood.

Aims & Methods

We aimed to investigate the risk factors of calcification development in patients with chronic pancreatitis. The study protocol was registered on PROSPERO (CRD42024591837). On September 18, 2024, we conducted a systematic search across three databases (PubMed, EMBASE, and CENTRAL) for studies reporting factors associated with calcification in chronic pancreatitis (CP). Pooled proportions and odds ratios (OR) with 95% confidence intervals (CI) were calculated using a random effects model.

Results

The systematic search resulted in 10,893 articles, from which 85 eligible studies were identified, covering a total of 34568 participants. The odds of calcification were 45% higher in alcoholic compared to idiopathic CP (OR=1.45, CI: 1.00–2.11). Alcohol consumption (OR=2.31, CI: 1.8–2.98) and smoking (OR=2.22, CI: 1.61–3.06) were associated with a two times higher risk of calcification in CP, when compared to non-smokers and non-drinkers. In contrast, the presence of CFTR mutations did not increase the risk of calcification in CP (OR=0.43, CI: 0.11–1.66) compared to patients without CFTR mutations.

Conclusion

Alcohol consumption and smoking were significantly associated with the presence of calcification in CP, making it essential to identify these risk factors and incorporate smoking cessation and alcohol reduction programs into standard care.

Introduction

The optimal management of small (≤2 cm) low-grade pancreatic neuroendocrine neoplasms (PNENs) remains a subject of ongoing debate. While surgical resection has traditionally been the standard treatment, its invasiveness and potential for long-term complications, such as pancreatic insufficiency, have driven interest in less invasive alternatives. Recently, endoscopic ultrasonography-guided ethanol injection (EUS-EI) has emerged as a promising treatment option, offering the potential for localized tumor control with minimal impact on surrounding pancreatic tissue.

Aims & Methods

This study was conducted at a single academic center between 2014 and 2024, and the data were retrospectively analyzed. Eligibility criteria included patients with pathologically confirmed grade 1 PNENs ≤2 cm who were either poor surgical candidates or declined surgery. The procedure was carefully planned to minimize complications and improve treatment outcomes. A 25-gauge needle was used to reduce the risk of ethanol leakage. Pure ethanol was injected under EUS guidance until hyperechoic bubbles fully surrounded the tumor margin. To ensure complete coverage while minimizing ethanol exposure, ethanol was injected from multiple sites if needed. Importantly, the maximum ethanol volume per session was limited to 2 mL to prevent overexposure and reduce adverse events. To optimize treatment efficacy, contrast-enhanced computed tomography (CE-CT) was performed on postoperative day 3. If residual enhancement was detected, an additional ablation session was scheduled during the same hospitalization, allowing for planned, staged treatment.

Results

A total of 41 patients including four patients with insulinoma underwent EUS-EI, The median tumor size of 10 mm (range: 6–15 mm). The median ethanol volume in the initial session was 0.9 mL (range: 0.3–2.0 mL), and the total median volume was 1.0 mL (range: 0.3–3.2 mL), reflecting the effectiveness of carefully distributed, low-volume injections. Fifteen patients (37%) required an additional planned ablation session based on CE-CT findings. Mild pancreatitis occurred in 6 patients (14%), and the median hospital stay was 5 days (range: 4–8 days), suggesting a favorable safety profile. Complete ablation was confirmed in 37 patients (90%) at one month post-procedure. All patients with insulinomas experienced an improvement in hypoglycemia-related symptoms. During a median follow-up of 36 months, local recurrence was observed in only 2 patients (5%), occurring at 22 and 51 months, respectively. Notably, no cases of new-onset diabetes mellitus were reported.

Conclusion

Planned, staged EUS-guided ethanol injection using low per-session ethanol volumes is a safe and effective treatment strategy for patients with small, low-grade PNENs. This approach appears to reduce procedure-related complications while enhancing the rate of complete tumor ablation.

References

Matsumoto K, Kato H, Itoi T et al. Efficacy and safety of endoscopic ultrasonography-guided ethanol injections of small pancreatic neuroendocrine neoplasms: a prospective multicenter study. Endoscopy. 2025 Apr;57(4):321-329. doi: 10.1055/a-2452-4607. Epub 2024 Oct 25. PMID: 39454635; PMCID: PMC11997695.

Introduction

IgG4-related disease (IgG4-RD) is a chronic fibro-inflammatory multi-systemic disease. Pancreato-biliary involvement is reported in up to 60%, which can lead to exocrine and endocrine pancreatic insufficiency. Glucocorticoids can be used to control active inflammation but are associated with substantial toxicity. B-cell depletion with anti-CD20 chimeric Rituximab (RTX) and anti-CD19 humanised Inebilizumab (INEB) are steroid-sparing and used to control disease flares. INEB is the only FDA-approved medication for the treatment of IgG4-RD.

Aims & Methods

Our aim was to compare B-cell depleting agents for the treatment of IgG4-RD. We searched PubMed, Cochrane Central Register of Clinical Trials and Embase databases for studies of maintenance therapy in IgG4-RD with a pre-defined strategy and performed a network meta-analysis to assess relapse at 12 months, occurrence of infections and infusion-related reactions.

Results

96 out of 2545 manuscripts underwent full text review after exclusions. Three studies met eligibility for the meta-analysis, two reporting the use of RTX and one of INEB (Table 1).

For the primary outcome of disease relapse at 12 months, INEB had a risk ratio (RR) of 5.8 (95% CI 0.29 - 115.02) and RTX had an RR of 2.29 (95% CI 0.19 - 28.21), with INEB being superior in preventing relapses. The RR for infections with INEB was 0.81 (95% CI 0.19 - 3.41) whilst with RTX was 0.62 (95% CI 0.13 - 3.04). The RR for infusion-related reactions with INEB was 1.27 (95% CI 0.09 - 18.76) and for RTX was 0.93 (95% CI 0.11 - 8.19). These must be interpreted in the context of study design; INEB in a phase 3 randomised trial following a stringent safety protocol for reporting of adverse events, and RTX in retrospective observational studies.

Conclusion

This Network Meta-analysis demonstrates that INEB is superior to RTX at preventing disease relapses in patients with IgG4-RD at 12 months. Adverse events, such as infection and infusion-related reactions, were comparable in lieu of the methodological differences between studies.

Disclosure

Emma L Culver has received speaker fees from Albireo/IPSEN, Advanz/Intercept, Dr Falk, Amgen, GSK, Mirum Pharma, Gilead, Chemomab, Zenus Bio, and Advisory/consultancy fees from Advanz/Intercept, IPSEN, Mirum, GSK, Dr Falk Pharma, Amgen, Zenus Bio, Sanofi, Moderna and Sail BioPharma. MC has received speaker fees from Albireo/IPSEN, Advanz/Intercept, Amgen, GSK, Mirum Pharma, Gilead, and Advisory/consultancy fees from Advanz/Intercept, Alphasigma, Albireo/IPSEN, Mirum, GSK, Dr Falk Pharma, Amgen, Mayoly, Echosens, Kowa, Moderna, Zydus.

Introduction

Differentiating mucinous (MPCLs) from non-mucinous pancreatic cystic lesions (NMPCLs) remains critical for appropriate therapeutic decisions. While carcinoembryonic antigen (CEA) levels >192 ng/mL have been the conventional benchmark, their limited sensitivity underscores the need for more accurate alternatives. Recent data suggest intracystic glucose levels may be a promising biomarker. This study prospectively evaluated the diagnostic performance of intracystic glucose compared to CEA in pancreatic cyst fluid obtained via EUS-guided fine needle aspiration (EUS-FNA).

Aims & Methods

From July 2018 to October 2024, 24 patients with pancreatic cystic lesions undergoing EUS-FNA using a 22G needle were included. Glucose and CEA concentrations were measured using standard biochemical protocols. Final diagnosis was based on surgical pathology (n=5), cytopathology (n=9), or consensus radiologic/endoscopic evaluation by two blinded expert pancreatologists (n=10). All procedures and analyses were performed in a tertiary academic gastroenterology center in Morocco.

Results

Mean patient age was 59.8 years. Diagnoses comprised 13 mucinous cysts (54.2%; including 9 IPMNs and 4 MCNs), 7 serous cystadenomas (29.2%), 2 cystic neuroendocrine tumors (8.3%), 1 pseudocyst, and 1 simple cyst.
The mean intracystic glucose level in MPCLs was 14.1 mg/dL (95% CI: 5.6–22.6), versus 90.3 mg/dL (95% CI: 82.1–98.6) in NMPCLs (p < 0.0001). A glucose threshold of ≤30 mg/dL yielded an AUC of 0.94 (95% CI: 0.84–0.99), with 92.3% sensitivity and 100% specificity.
For CEA ≥192 ng/mL, AUC was 0.71 (95% CI: 0.54–0.86), with 46.1% sensitivity and 100% specificity. No significant correlation was found between glucose levels and either CEA or cyst size.

Conclusion

Intracystic glucose represents a simple, cost-effective, and highly accurate marker for distinguishing mucinous from non-mucinous pancreatic cystic lesions. It demonstrates superior sensitivity compared to CEA and can be a valuable adjunct in the diagnostic algorithm of pancreatic cysts, particularly in resource-conscious settings.

References

 Carrara S, Ceriello A, Arcidiacono PG. Glucose in pancreatic cyst fluid: a reliable test for mucinous cysts? Endoscopy. 2022;54(1):63–70.
 Köker D, Tevethia H, Madhoun MF. Intracystic glucose: a promising low-cost tool in differentiating pancreatic cysts. Gastrointest Endosc. 2023;97(4):832–9.
 Alomari F, Hammad T, Khasawneh MA, et al. Diagnostic performance of EUS-FNA glucose vs CEA in pancreatic cysts. Pancreas. 2021;50(5):661–6.

Introduction

EUS-guided drainage using lumen-apposing metal stents (LAMSs) and direct endoscopic necrosectomy (DEN) are primary treatment modalities for symptomatic pseudocysts and walled-off pancreatic necrosis (WOPN). However, bleeding is a frequent and serious adverse event associated with these procedures, often requiring radiological or surgical interventions also due to the limitations of conventional endoscopic hemostatic techniques. PuraStat is a novel topical hemostatic agent that has demonstrated excellent results in managing gastrointestinal bleeding.

Aims & Methods

Our aim was to evaluate the efficacy and safety of PuraStat in managing bleeding secondary to EUS-guided drainage and DEN of pancreatic fluid collections (PFCs). In this multicenter, retrospective, observational study we described 27 patients who underwent PuraStat treatment because of active bleeding during or after EUS-guided drainage or DEN sessions of pseudocysts or WOPN between 2017 and 2024.

Results

38 bleeding episodes were recorded (10 patients with WOPN experienced multiple bleeding events). The bleeding type was oozing in 36 cases and spurting in 2 cases. PuraStat was successfully applied in 100% of patients and achieved successful hemostasis in 96.5% of cases. No re-bleeding occurred. No PuraStat-related adverse events were recorded.

Conclusion

PuraStat is a safe, effective, and easy-to-use hemostatic agent for managing oozing hemorrhages related to PFCs EUS-guided drainage or DEN. Prospective and comparative studies are needed to confirm these preliminary data.

Introduction

Chronic pancreatitis (CP) may have differences in causes, presentations and progression related to sex. There are few studies describing the sex related phenotype of CP.

Aims & Methods

We aimed to study sex differences in etiology, complications and treatment of CP in a large, North-European CP cohort. Data were extracted from the Scandinavian Baltic Pancreatic Club (SBPC) database. The collected data included sex, age, etiology, anthropometric measures, data for smoking and alcohol exposures and data on treatment and complications from CP. Differences between sexes were compared with multiple logistic regression models.

Results

We included 1922 patients in the analyses, of whom 1264 were men. Mean age of CP onset was 52.5 (SD 15.0) years in men and 51.5 (SD 16.4) years in women (p=0.2). In univariate analysis alcohol etiology and smoking was associated with male sex, whereas hereditary pancreatitis, efferent duct obstruction, autoimmune pancreatitis were associated to female sex. Numbers of men and women with non-alcoholic etiology were almost equal (461 and 422, respectively). In multivariate analysis including all etiologies, time with disease and age; alcohol etiology remained strongly associated to male sex (OR 2.92 (2.29-3.71), p<0.001), whereas duct obstruction etiology was associated with female sex (OR 0.62 (0.44-0.89), p=0.01).
Significantly more women were underweight (p<0.001), and more men were overweight (p<0.001). Concerning other complications, diabetes mellitus (DM) was strongly associated with men (OR 1.62 (1.27-2.07), p<0.001), whereas osteoporosis was strongly associated with women (OR 0.47 (0.32-0.70), p<0.001). Recurrent acute pancreatitis and exocrine insufficiency were equally distributed between the sexes. There were no differences between sexes for medical, endoscopic or surgical treatment options.

Conclusion

More men than women had alcohol induced CP, but there was almost no difference in absolute numbers of men and women with non-alcoholic CP. Among the CP patients, DM was associated with men, while osteoporosis was associated with women.