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LOW PHOSPHOLIPID-ASSOCIATED CHOLELITHIASIS (LPAC) SYNDROME AS A NOT UNCOMMON CAUSE OF BILIARY PROBLEMS AND HOSPITAL ADMISSIONS

Isabel Spigarelli 1, BEATRIZ PILLADO 2, David Vincent López 3, Joaquin Poza Cordón 2, Marta Abadía Barnó 2, Gloria Ruiz Fernández 2, Pilar Castillo Grau 2, Antonio Olveira Martín 2

Affiliations

1 Fundación Jiménez Díaz University Hospital, Madrid, Spain

2 La Paz University Hospital, Madrid, Spain

3 La Paz University Hospital Research Institute-IdiPAZ, Madrid, Spain

Summary

AI Generated

An ambispective study of 237 biliary admissions in Spain found LPAC syndrome in 2.5% overall and 16.7% of patients under 40 years, with all patients remaining asymptomatic after ursodeoxycholic acid treatment.

Among 237 patients admitted for biliary disease over nine months, six were diagnosed with LPAC syndrome, representing an incidence of 2.5% overall, 16.7% in those under 40 years, and 21% in women under 40 years.
Thirty-six enrolled LPAC patients had mean symptom onset at 27.5 years, 69% were female, 59% had family history of biliary disease, and 89% showed intrahepatic lithiasis on imaging.
Cholecystectomy was performed in 78% of patients, with 61% experiencing recurrence after surgery, and genetic confirmation of MDR3 mutations was obtained in 28% of all patients.
All patients remained asymptomatic with no hospital readmissions after initiating ursodeoxycholic acid treatment.
The authors conclude that LPAC may be more common than previously recognized in younger patients with biliary disease and that diagnosis could prevent unnecessary surgeries and admissions.

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Abstract

Introduction

Biliary diseases are an important source of morbimortality for patients, as well as a burden for the healthcare system. In Spain they represent the main cause of hospitalization (2018: 104551 admissions, 81400 cholecystectomies). The genetic syndrome LPAC (low phospholipid-associated cholelithiasis) is a poorly known and considered as infrequent condition,
that involves the development of hepatolithiasis due to mutations in the ABCB4 gene, which encodes the MDR3 protein that functions as a biliary transporter. Its treatment with bile salts avoids symptoms, admissions and the need for surgery. Our aim is to determine its incidence and characteristics in our center.

Aims & Methods

We conducted an ambispective study between February 2021 and September 2022. To be eligible, the patients had to fulfil at least two of the following: onset of biliary symptoms before the age of 40 years; recurrence of symptoms after cholecystectomy; image of intrahepatic macro- or microlithiasis (hyperechoic foci, comet-tail images, biliary sludge alongside intrahepatic bile ducts). Demographic, clinical, ultrasound and genetic characteristics (analysis of MDR3 gene mutations) were analyzed, as well as their incidence among hospital admissions.

Results

36 patients with LPAC were enrolled (Table 1). 6 of them were identified among 237 patients admitted to the for biliary causes in the last 9 months, which represents an incidence of 2.5% (95% CI: 1.17-5.41). By age subgroup, the incidence was 16.7% among those admitted <40 years and 9.1% among those <50 years. Considering only women, the incidence was 21%
among those admitted <40 years and 15.8% among those <50 years.
The ultrasound characteristics were also analyzed. A trend was found between macrolithiasis with acoustic shadowing and presence of MDR3 mutations (42.9% vs 14.3%), although the differences were not statistically significant.
All patients remained asymptomatic and with no need of hospital readmissions after treatment with ursodeoxycholic acid was initiated.

Mean age at first symptoms (years)	27.5
Female gender	69.44% (25)
Hispanic origin	33.33% (12)
History of biliary diseases in first-degree relatives	58.82% (20)
BMI at diagnosis (kg/m²)	22.2
Comorbidities - Hypertension - Hypercholesterolemia - Diabetes	0.03% (1) 13.89% (5) 0.03% (1)
Intrahepatic cholestasis of pregnancy in women with a history of pregnancy	14.29%(2)
Clinical and imaging features - Acute cholecystitis - Acute pancreatitis - Acute cholangitis - Gallbladder lithiasis - Common bile duct lithiasis - Intrahepatic lithiasis: · Hyperecoic foci · Comet-tail images · Intrahepatic lithiasis with acoustic shadow	19.44% (7) 22.22% (8) 0.03% (1) 80.56% (29) 25% (9) 88.89% (32) 38.9% (14) 27.8% (10) 22.2% (8)
Cholecystectomy Recurrence after cholecystectomy	77.78% (28) 60.71% (17)
Genetic confirmation - among the total number of patients - among those who fulfil 3/3 criteria	28% 40%

Table 1. Demographic, clinical, ultrasound and genetic characteristics of LPAC patients.

Conclusion

LPAC syndrome is not as uncommon as it might seem, especially among individuals younger than 40 years old admitted for biliary diseases, and mostly women. Its correct diagnosis based on simple criteria would avoid a large number of hospital admissions and unnecessary cholecystectomies.

References

1. Observatorio de resultados - Portal de Salud de la Comunidad de Madrid. Índice de colecistectomía laparoscópica. Sanidadmadrid.org [Internet, citado a 22 de febrero de 2023].
2. Subdirección General de Información Sanitaria, Ministerio de Sanidad. Registro de Actividad Sanitaria Especializada (RAE-CMBD): Actividad y resultados de la hospitalización en el Sistema Nacional de Salud Año 2018. 2021 feb.
3. Dong C, et al. Low-phospholipid-associated cholelithiasis syndrome: Prevalence, clinical features, and comorbidities. JHEP Rep. 2020 Nov 6;3(2):100201.
4. Goubault P, et al. Low-Phospholipid Associated Cholelithiasis (LPAC) syndrome: A synthetic review. J Visc Surg. 2019 Sep;156(4):319-328
5. Su S, Trinh A, Metz AJ, Speer T, Simkin P, Buchanan D, Boussioutas A, Gibson R. Targeted liver ultrasound performed by an expert is the pivotal imaging examination for low phospholipid-associated cholelithiasis. Eur J Gastroenterol Hepatol. 2023 Mar 1;35(3):327-332
6. Biyoukar M, Corpechot C, El Mouhadi S, Chambenois E, Vanderbecq Q, Barbu V, Dong C, Lemoinne S, Tordjman M, Jomaah R, Chazouilleres O, Arrivé L. ABCB4 variant is associated with hepatobiliary MR abnormalities in people with low-phospholipid-associated cholelithiasis syndrome. JHEP Rep. 2022 Sep 21;4(11):100590

Conference

UEG Week Copenhagen 2023

Topics

Hepatobiliary

Submission format

Abstract

Session

PP 07 Liver & biliary (Posters)

Citation

United European Gastroenterology Journal 2023; 11 (Supplement 8)

Published

2023

More Like This:

DUODENAL ASPIRATION BIOPSY WITH CEA-BASED THREE-ZONE RISK STRATIFICATION FOR PANCREATIC CYSTIC NEOPLASMS: A PROSPECTIVE MULTICENTER STUDY

Vitali Proutski

SHP2 REGULATES CAF ACTIVITY AND ADAPTIVE STROMAL REMODELING DURING VERTICAL RAS PATHWAY INHIBITION IN PANCREATIC CANCER

Dietrich Alexander Ruess

USE OF HIGH DOSE PROTON PUMP INHIBITORS INCREASES THE RISK OF DELAYED DEGRADATION OF BIODEGRADABLE BILIOPANCREATIC STENTS: A PROSPECTIVE REAL-WORLD EXPERIENCE FROM A TERTIARY REFERRAL CENTRE

Damien Meng Yew Tan

CIRCULATING PROTEIN PROFILES IN PANCREATIC DUCTAL ADENOCARCINOMA REVEAL DISTINCT EARLY-STAGE DISEASE-ASSOCIATED ALTERATIONS

Jurgita Skieceviciene

PREVALENCE AND NATURAL COURSE OF MRI-DIAGNOSED DILATED MAIN PANCREATIC DUCT: A LONGITUDINAL, POPULATION-BASED PROSPECTIVE COHORT STUDY WITH A TEN-YEAR FOLLOW-UP

Fabian Yazdi

CLINICAL IMPACT OF MULTIPLE EUS-FNA DURING PANCREATIC CYST SURVEILLANCE

Nadim Haddad

UEG Presentation

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DUODENAL ASPIRATION BIOPSY WITH CEA-BASED THREE-ZONE RISK STRATIFICATION FOR PANCREATIC CYSTIC NEOPLASMS: A PROSPECTIVE MULTICENTER STUDY

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DUODENAL ASPIRATION BIOPSY WITH CEA-BASED THREE-ZONE RISK STRATIFICATION FOR PANCREATIC CYSTIC NEOPLASMS: A PROSPECTIVE MULTICENTER STUDY

Aleksei Kashintsev 1,2, Anna Borovikova 3, Nikolai Kokhanenko 3, Mikhail Dinikin 4, Yuriy Pelipas 4, Olga Vavilova 3, Vladimir Zagainov 5,6, Ok Sek 2, Mikhail Vasilchenko 7, Olga Kolokolnikova 7, Aleksandr Kolbasov 7, Nasipbek Naraliev 5,6, Vitali Proutski 8

Affiliations

1 Pandica LTD/ State Pediatric Medical University, London, United Kingdom

2 Medsi LTD, Saint-Petersburg, Russian Federation

3 State Pediatric Medical University, Saint-Petersburg, Russian Federation

4 Cities oncological hospital, Saint-Petersburg, Russian Federation

5 Privolzhskiy research medical university, Nizhniy Novgorod, Russian Federation

6 Oncology research institute, Nizhniy Novgorod, Russian Federation

7 Medsi, Krasnogorsk, Russian Federation

8 Pandica LTD, London, United Kingdom

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Abstract

Introduction

Pancreatic cystic neoplasms (PCNs), particularly intraductal papillary mucinous neoplasms (IPMNs), carry a significant risk of malignant transformation and require accurate risk stratification. Current diagnostic approaches — cross-sectional imaging and endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) — have variable diagnostic yield, and EUS-FNA carries a complication rate of up to 3%. Pancreatic juice contains highly informative biomarkers (carcinoembryonic antigen [CEA], atypical cells, oncogenic mutations); however, reliable and uncontaminated collection of this material remains a significant technical challenge.

Aims & Methods

To evaluate the feasibility, safety and diagnostic accuracy of duodenal aspiration biopsy (DAB) — a novel method of atraumatic mixed pancreatic juice and bile collection — for CEA measurement and cytological analysis in patients with PCNs, and to compare results with EUS-FNA data.
Prospective multicenter registry (4 centers, 2 cities; 2023–2025). 42 patients (16M/26F; mean age 59.8±13.3 years) with radiologically confirmed PCNs were enrolled. All underwent standard workup (CT, MRI/MRCP, EUS). DAB was performed using a purpose-designed triple-lumen catheter developed by our group, which isolates the descending duodenum around the major duodenal papilla under controlled negative pressure, enabling uncontaminated collection of pancreaticobiliary secretion. A key functional advantage of the device is its built-in shunting effect: the isolated duodenal segment is bypassed, allowing the patient to receive liquid nutrition during the procedure. This triggers neurohumoral stimulation of exocrine pancreatic secretion, yielding a physiological, undiluted aspirate of sufficient volume. CEA was measured in the supernatant (cutoff >192 ng/mL); cytological smears prepared from sediment (Papanicolaou stain). Clinical management determined by multidisciplinary boards per 2024 Kyoto Guidelines.

Results

DAB yielded diagnostic material in 42/42 patients (100%). Mean CEA levels differed significantly across groups: chronic pancreatitis 52.7 ng/mL; low-grade IPMN (grade I) 39.9 ng/mL; moderate-risk PCNs 142.8 ng/mL; high-grade IPMN/PDAC 434.0 ng/mL (p<0.001 vs. all groups). A three-zone risk model was derived: Zone I (CEA <100 ng/mL — benign disease); Zone II (100–192 ng/mL — active surveillance); Zone III (>192 ng/mL — high malignancy risk). At the >192 ng/mL threshold: sensitivity 92.0%, specificity 95.2% (AUC=0.971). In comparison, EUS-FNA enabled CEA measurement in only 11/42 patients (26.2%) due to insufficient aspirate volume. Surgery was performed in 5 patients; PDAC was confirmed histologically in 3. Atypical cells on DAB cytology were identified in 2/3 cancer cases. No DAB-related complications were recorded, whereas EUS-FNA complications occurred in 3/25 procedures (12%): 1 intracystic haemorrhage and 2 cyst infections.

Conclusion

DAB using a purpose-designed triple-lumen catheter with neurohumoral stimulation is a safe, technically straightforward and reproducible method for obtaining diagnostically informative pancreatic juice in patients with PCNs. CEA measurement combined with the three-zone risk stratification model provides high diagnostic accuracy for malignant transformation (AUC=0.971) and may complement or replace EUS-FNA in selected cases. Further prospective validation on larger cohorts is warranted.

References

1. Ohtsuka T, et al. International evidence-based Kyoto guidelines for the management of intraductal papillary mucinous neoplasm of the pancreas. Pancreatology. 2024;24(2):255–270.
2. Schweber AB, et al. Prevalence, incidence, and risk of progression of asymptomatic pancreatic cysts in large sample real-world data. Pancreas. 2021;50(9):1287–1292.
3. Brugge WR, et al. Diagnosis of pancreatic cystic neoplasms: a report of the cooperative pancreatic cyst study. Gastroenterology. 2004;126(5):1330–1336.

Event

UEG Week Barcelona 2026

Topics

Surgery Pancreas Mechanisms & Personalised Medicine Digestive Oncology

Submission format

Abstract

Session

Pancreatic cyst: Beyond the incidental findings

Citation

2026: United European Gastroenterology Journal 2026; 14 (S1)

Published

2026

More Like This:

DUODENAL ASPIRATION BIOPSY WITH CEA-BASED THREE-ZONE RISK STRATIFICATION FOR PANCREATIC CYSTIC NEOPLASMS: A PROSPECTIVE MULTICENTER STUDY

Vitali Proutski

SHP2 REGULATES CAF ACTIVITY AND ADAPTIVE STROMAL REMODELING DURING VERTICAL RAS PATHWAY INHIBITION IN PANCREATIC CANCER

Dietrich Alexander Ruess

USE OF HIGH DOSE PROTON PUMP INHIBITORS INCREASES THE RISK OF DELAYED DEGRADATION OF BIODEGRADABLE BILIOPANCREATIC STENTS: A PROSPECTIVE REAL-WORLD EXPERIENCE FROM A TERTIARY REFERRAL CENTRE

Damien Meng Yew Tan

CIRCULATING PROTEIN PROFILES IN PANCREATIC DUCTAL ADENOCARCINOMA REVEAL DISTINCT EARLY-STAGE DISEASE-ASSOCIATED ALTERATIONS

Jurgita Skieceviciene

PREVALENCE AND NATURAL COURSE OF MRI-DIAGNOSED DILATED MAIN PANCREATIC DUCT: A LONGITUDINAL, POPULATION-BASED PROSPECTIVE COHORT STUDY WITH A TEN-YEAR FOLLOW-UP

Fabian Yazdi

CLINICAL IMPACT OF MULTIPLE EUS-FNA DURING PANCREATIC CYST SURVEILLANCE

Nadim Haddad

UEG Presentation

New

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SHP2 REGULATES CAF ACTIVITY AND ADAPTIVE STROMAL REMODELING DURING VERTICAL RAS PATHWAY INHIBITION IN PANCREATIC CANCER

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SHP2 REGULATES CAF ACTIVITY AND ADAPTIVE STROMAL REMODELING DURING VERTICAL RAS PATHWAY INHIBITION IN PANCREATIC CANCER

Steffen Keller 1, Xun Chen 1, Tonmoy Das 2, Xiao-En Li 1, Hanna Scheffold 1, Philipp Hafner 1, Asma Alrawashdeh 1, Huda Jumaa 1, Dominik von Elverfeldt 1, Wilfried Reichardt 1, Geoffroy Andrieux 2, Melanie Boerries 2,3, Stefan Fichtner-Feigl 1, Dietrich Alexander Ruess 1,3

Affiliations

1 University Medical Center Freiburg, Freiburg, Germany

2 Institute of Medical Bioinformatics and Systems Medicine, University of Freiburg, Freiburg, Germany

3 German Cancer Consortium (DKTK), Freiburg, Germany

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Abstract

Introduction

Mutations in KRAS occur in over 90% of pancreatic ductal adenocarcinoma (PDAC) cases, driving oncogenic signaling through the RAF-MEK-ERK (MAPK) cascade. Vertical RAS pathway inhibition through allosteric inhibition of Src-homology 2 domain-containing phosphatase 2 (SHP2) in combination with MEK or RAS inhibitors has demonstrated synergistic antitumor activity and delayed resistance onset in preclinical studies. PDAC is further characterized by a dense, immunosuppressive desmoplastic stroma dominated by heterogeneous cancer-associated fibroblasts (CAFs), which critically regulate tumor progression and therapy response.

Aims & Methods

We investigated how combined SHP2 and MEK/RAS inhibition affects CAF subtype composition and stromal remodeling using a comprehensive platform including murine and human primary fibroblasts, tumor-fibroblast co-cultures, and autochthonous KPC and KPF tumor models, applying in vitro assays, flow cytometry, multiplex immunohistochemistry, and scRNA analysis.

Results

SHP2 inhibition, in contrast to MEK or RAS inhibition alone, impaired CAF homeostasis, markedly reducing fibroblast viability and matrix-contractile function in vitro, accompanied by compensatory PI3K-AKT signaling activation. In vivo, dual SHP2/MEK inhibition induced dynamic remodeling of the tumor microenvironment, characterized by transient expansion of inflammatory CAFs (iCAFs) and alterations in extracellular matrix organization, followed by re-establishment of myofibroblastic CAF states under prolonged treatment and emerging adaptive treatment resistance.

Conclusion

Our preliminary findings reveal that vertical RAS pathway blockade and SHP2 inhibition in particular not only affects tumor cell-intrinsic signaling but also reshapes stromal architecture through CAF plasticity. These results highlight the importance of understanding and targeting tumor-stroma crosstalk to enhance therapeutic efficacy of RAS inhibition strategies in PDAC and support further evaluation of SHP2-based combination strategies to prevent stromal-mediated resistance.

Event

UEG Week Barcelona 2026

Topics

Mechanisms & Personalised Medicine Pancreas Digestive Oncology

Submission format

Abstract

Session

Pancreatic cancer: From bench to bedside

Citation

2026: United European Gastroenterology Journal 2026; 14 (S1)

Published

2026

More Like This:

DUODENAL ASPIRATION BIOPSY WITH CEA-BASED THREE-ZONE RISK STRATIFICATION FOR PANCREATIC CYSTIC NEOPLASMS: A PROSPECTIVE MULTICENTER STUDY

Vitali Proutski

SHP2 REGULATES CAF ACTIVITY AND ADAPTIVE STROMAL REMODELING DURING VERTICAL RAS PATHWAY INHIBITION IN PANCREATIC CANCER

Dietrich Alexander Ruess

USE OF HIGH DOSE PROTON PUMP INHIBITORS INCREASES THE RISK OF DELAYED DEGRADATION OF BIODEGRADABLE BILIOPANCREATIC STENTS: A PROSPECTIVE REAL-WORLD EXPERIENCE FROM A TERTIARY REFERRAL CENTRE

Damien Meng Yew Tan

CIRCULATING PROTEIN PROFILES IN PANCREATIC DUCTAL ADENOCARCINOMA REVEAL DISTINCT EARLY-STAGE DISEASE-ASSOCIATED ALTERATIONS

Jurgita Skieceviciene

PREVALENCE AND NATURAL COURSE OF MRI-DIAGNOSED DILATED MAIN PANCREATIC DUCT: A LONGITUDINAL, POPULATION-BASED PROSPECTIVE COHORT STUDY WITH A TEN-YEAR FOLLOW-UP

Fabian Yazdi

CLINICAL IMPACT OF MULTIPLE EUS-FNA DURING PANCREATIC CYST SURVEILLANCE

Nadim Haddad

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USE OF HIGH DOSE PROTON PUMP INHIBITORS INCREASES THE RISK OF DELAYED DEGRADATION OF BIODEGRADABLE BILIOPANCREATIC STENTS: A PROSPECTIVE REAL-WORLD EXPERIENCE FROM A TERTIARY REFERRAL CENTRE

Samuel Jun Ming Lim 1, Clement Wu 1, Christopher Jen Lock Khor 1, Damien Meng Yew Tan 1

Affiliations

1 Singapore General Hospital, Singapore, Singapore

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Abstract

Introduction

Biodegradable biliopancreatic stents reduce the need for follow up visits or repeat endoscopy after endoscopic retrograde cholangiopancreatography (ERCP). Stent degradation occurs primarily by hydrolysis, and in vivo, the flow of pancreatic juice and bile across the stent is stimulated by acidic chyme within the duodenum, which is affected by use of proton pump inhibitors (PPI). We present a prospective study examining delayed stent degradation and late adverse events after ERCP.

Aims & Methods

We recruited consecutive patients who underwent ERCP with insertion of biodegradable biliopancreatic stents at our unit between June 2022 and September 2025. We performed analysis on demographic, clinical and stent-related factors. The primary outcome was the incidence of delayed stent degradation, defined by an intact stent or stent fragments seen in-situ on routine follow-up imaging after the expected degradation time. The secondary outcome was the rate of late adverse events occurring >14 days after ERCP.

Results

36 patients (58.3% female, median age 75 years) underwent ERCP with insertion of biodegradable biliopancreatic stents. Pancreatic and biliary stents were inserted in 86.1% and 13.9% of patients respectively. Pancreatic stents were 6Fr in diameter with a fast (12 days) degradation profile. Biliary stents were 10Fr in diameter with either a medium (20 days) or slow (11 weeks) degradation profile. All stents were inserted singly with a 100% technical success rate. 5 (13.9%) patients had delayed stent degradation, 4 of whom were on high dose PPI, defined as a daily dose of omeprazole 40mg and higher or its equivalent. 2 (5.6%) patients had late adverse events (pancreatitis 18 days after ERCP and cholangitis 8 months after ERCP), both of whom had delayed stent degradation.
On univariate analysis, a larger stent diameter (relative risk (RR) 21.75, 95% confidence interval (CI) 2.20-215.26, p=0.01) and use of high dose PPI (RR 37.33, 95% CI 3.08-452.04, p<0.01) were associated with delayed stent degradation. Stent length and use of low dose PPI were not associated with delayed stent degradation. On multivariable analysis, only the use of high dose PPI was significantly associated with delayed stent degradation (odds ratio 14.49, 95% CI 1.12-200.00, p=0.040).
Use of high dose PPI (RR 6.80, 95% CI 3.03-15.38, p=0.03) and delayed stent degradation (RR 11.36, 95% CI 3.85-33.33, p=0.02) were associated with late adverse events. Age, gender, stent diameter, stent length, and use of low dose PPI were not associated with late adverse events.

	Delayed stent degradation (n=5)	No delayed degradation (n=31)	Relative risk (95% CI)	p-value
Age ≥75 years (n=19) <75 years (n=17)	2 (10.5%) 3 (17.6%)	17 (89.5%) 14 (82.4%)	0.55 (0.08-3.76)	0.65
Gender Male (n=15) Female (n=21)	3 (20.0%) 2 (9.5%)	12 (80.0%) 19 (90.5%)	2.38 (0.35-16.36)	0.63
Indication of ERCP Biliary stricture (n=18) Choledocholithiasis (n=18)	2 (11.1%) 3 (16.7%)	16 (88.9%) 15 (83.3%)	0.63 (0.09-4.28)	1.00
Stent diameter 10Fr (n=5) 6Fr (n=31)	3 (60.0%) 2 (6.5%)	2 (40.0%) 29 (93.5%)	21.75 (2.20-215.26)	0.01
Stent length 8-10cm (n=27) 4-6cm (n=9)	5 (18.5%) 0 (0.0%)	22 (81.5%) 9 (100.0%)	1.40 (1.12-1.76)	0.30
Any PPI use Yes (n=15) No (n=21)	4 (26.7%) 1 (4.8%)	11 (73.3%) 20 (95.2%)	7.27 (0.72-73.38)	0.14
Low dose PPI Yes (n=8) No (n=28)	0 (0.0%) 5 (17.9%)	8 (100.0%) 23 (82.1%)	0.74 (0.60-0.91)	0.57
High dose PPI Yes (n=7) No (n=29)	4 (57.1%) 1 (3.4%)	3 (42.9%) 28 (96.6%)	37.33 (3.08-452.04)	<0.01

Conclusion

The use of high dose PPI may contribute to delayed degradation of biodegradable biliopancreatic stents. Large multi-center prospective studies are required to confirm these findings and evaluate the clinical impact of delayed stent degradation.

References

Anderloni A, Fugazza A, Maroni L, Ormando V, Maselli R, Carrara S, et al. New biliary and pancreatic biodegradable stent placement: a single-center, prospective, pilot study (with video). Gastrointest Endosc. 2020 Aug;92(2):405-411.
Pérez-Cuadrado Robles E, Lakhtakia S, Othman H, Tewethia HV, Yaacob N, Jarmin R, et al. A new biodegradable stent in bilio-pancreatic diseases: a prospective multi-center feasibility study. Rev Esp Enferm Dig. 2022 Sep;114(9):529-533.
Maieron A, Erhart L, Pramhofer P, Schöfl R, Spaun G, Steiner E, et al. Biodegradable biliopancreatic stents could help conserve health care resources during the COVID-19 pandemic: An observational multicenter study. Dig Liver Dis. 2023 Mar;55(3):310-315.

Conference

UEG Week Barcelona 2026

Topics

Pancreas

Submission format

Abstract

Session

Interventional pancreatobiliary endoscopy: Drainage strategies, stent innovation, and real-world outcomes (Posters)

Citation

2026: United European Gastroenterology Journal 2026; 14 (S1)

Published

2026

More Like This:

DUODENAL ASPIRATION BIOPSY WITH CEA-BASED THREE-ZONE RISK STRATIFICATION FOR PANCREATIC CYSTIC NEOPLASMS: A PROSPECTIVE MULTICENTER STUDY

Vitali Proutski

SHP2 REGULATES CAF ACTIVITY AND ADAPTIVE STROMAL REMODELING DURING VERTICAL RAS PATHWAY INHIBITION IN PANCREATIC CANCER

Dietrich Alexander Ruess

USE OF HIGH DOSE PROTON PUMP INHIBITORS INCREASES THE RISK OF DELAYED DEGRADATION OF BIODEGRADABLE BILIOPANCREATIC STENTS: A PROSPECTIVE REAL-WORLD EXPERIENCE FROM A TERTIARY REFERRAL CENTRE

Damien Meng Yew Tan

CIRCULATING PROTEIN PROFILES IN PANCREATIC DUCTAL ADENOCARCINOMA REVEAL DISTINCT EARLY-STAGE DISEASE-ASSOCIATED ALTERATIONS

Jurgita Skieceviciene

PREVALENCE AND NATURAL COURSE OF MRI-DIAGNOSED DILATED MAIN PANCREATIC DUCT: A LONGITUDINAL, POPULATION-BASED PROSPECTIVE COHORT STUDY WITH A TEN-YEAR FOLLOW-UP

Fabian Yazdi

CLINICAL IMPACT OF MULTIPLE EUS-FNA DURING PANCREATIC CYST SURVEILLANCE

Nadim Haddad

UEG Presentation

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CIRCULATING PROTEIN PROFILES IN PANCREATIC DUCTAL ADENOCARCINOMA REVEAL DISTINCT EARLY-STAGE DISEASE-ASSOCIATED ALTERATIONS

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CIRCULATING PROTEIN PROFILES IN PANCREATIC DUCTAL ADENOCARCINOMA REVEAL DISTINCT EARLY-STAGE DISEASE-ASSOCIATED ALTERATIONS

Juozas Kupcinskas 1,2, Rūta Steponaitienė 2, Darja Nikitina 2, Egidijus Morkunas 1, Audrius Ivanauskas 1, Greta Gedgaudiene 2, Jurgita Skieceviciene 2

Affiliations

1 Lithuanian University of Health Sciences, Kaunas, Lithuania

2 Lithuanian University Of Health Sciences, Kaunas, Lithuania

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Abstract

Introduction

Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal malignancy due to late diagnosis and limited treatment options, underscoring the need for minimally invasive biomarkers enabling earlier detection. Circulating proteins reflecting systemic immune and inflammatory responses may capture tumor-associated alterations at early stages of disease development.

Aims & Methods

The objective of this study was to characterize circulating protein profiles in patients with pancreatic ductal adenocarcinoma compared to healthy controls and to identify disease-associated alterations, with a particular focus on early-stage disease and their potential utility as minimally invasive biomarkers for early detection.
Serum samples from 312 patients with PDAC across all stages (151 males/161 females; mean age 67.3 ± 10.8 years) and 172 healthy controls (84 males/88 females; mean age 62.7 ± 11.2 years) were analyzed using the Olink Immuno-Oncology panel. Protein levels were quantified using proximity extension assay technology. Differential protein abundance analysis was performed using the Limma framework with multiple testing correction. Subgroup analysis was conducted to evaluate protein level changes in early-stage PDAC. Additionally, a preliminary assessment of classification performance using leave-one-out cross-validation (LOOCV) AUC was conducted in this subgroup.

Results

A broad set of circulating immune-related proteins was significantly altered in PDAC patients compared to healthy controls, indicating systemic immune dysregulation associated with the disease. Subgroup analysis of early-stage PDAC (stage I–II) demonstrated the most pronounced differences among CD40-L, EGF, MCP-1, CSF-1, MCP-3, CAIX, TNFSF14, CCL20, MUC-16, IL-8 and ARG1, with all proteins showing significantly upregulated levels (adjusted p < 0.05, LOOCV AUC = 0.75, 95% CI: 0.62–0.88). The identified protein panel reflects systematic alterations in immune cell recruitment, inflammatory signaling and tumor–microenvironment interactions. Notably, a consistent pattern across these markers suggests that a coordinated systemic response may be detectable prior to advanced tumor progression.

Conclusion

Circulating immune-related proteins are significantly altered in PDAC, with particularly pronounced and consistent changes observed in early-stage disease. These findings highlight the presence of systemic immune alterations detectable in peripheral blood and support the potential diagnostic relevance of circulating protein profiles as minimally invasive biomarkers for PDAC detection. Further studies of larger scale early-stage PDAC cohorts are warranted to validate these findings and to assess their performance in early detection settings.

Event

UEG Week Barcelona 2026

Topics

Mechanisms & Personalised Medicine Pancreas Digestive Oncology

Submission format

Abstract

Session

Pancreatic cancer: From bench to bedside

Citation

2026: United European Gastroenterology Journal 2026; 14 (S1)

Published

2026

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Fabian Yazdi

CLINICAL IMPACT OF MULTIPLE EUS-FNA DURING PANCREATIC CYST SURVEILLANCE

Nadim Haddad

UEG Presentation

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PREVALENCE AND NATURAL COURSE OF MRI-DIAGNOSED DILATED MAIN PANCREATIC DUCT: A LONGITUDINAL, POPULATION-BASED PROSPECTIVE COHORT STUDY WITH A TEN-YEAR FOLLOW-UP

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PREVALENCE AND NATURAL COURSE OF MRI-DIAGNOSED DILATED MAIN PANCREATIC DUCT: A LONGITUDINAL, POPULATION-BASED PROSPECTIVE COHORT STUDY WITH A TEN-YEAR FOLLOW-UP

Daniel Schmitz 1, Ali Alexander Aghdassi 2, Mark Wielpütz 3, Henry Völzke 3, Robin Bülow 3, Fabian Yazdi 1

Affiliations

1 Medical School Hamburg-Helios Kliniken Schwerin, Schwerin, Germany

2 Medizin. Universität Greifswald, Greifswald, Germany

3 Universität Greifswald, Greifswald, Germany

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Abstract

Introduction

Pancreatic main duct dilation (PMDD) may indicate an increased risk of developing pancreatic cancer. Little is known about the prevalence and natural course of PMDD in the general population. Therefore, this study aimed to analyse PMDD using magnet resonance imaging (MRI).

Aims & Methods

Longitudinal MRI combined with magnetic resonance cholangiopancreatography was performed between 2008 and 2021 as part of the prospective population-based Study of Health in Pomerania (SHIP), with 2,2 ± 0,6 MRI per participant on average performed within an average of 10,8 ± 1,2 yrs. PMDD was defined as ≥ 5 mm, and was correlated with clinical and epidemiological data.

Results

The prevalence of PMDD was 81/2985 individuals (2.7%). The mean age of these was 55.1 ± 13.2 yrs. Cumulative 5 yr-incidence of newly developed PMDD was 1.1% (22/1935) and 3.0% (15/ 496) after 10 yrs. Poisson regression analysis revealed strong associated factors of PMDD: active smoking (PR 2.93), diabetes (PR 2.58) and frequent alcohol abuse (PR 1.78) After a median follow-up period of 4.5 years, pancreatic cancer and chronic pancreatitis were diagnosed more frequently in the PMDD group: 2/81 (2.5%) vs. 24/2904 (0.8%) and 8/81 (9.9%) vs. 46/2904 (1.6%). Pancreatic cancerspecific survival was lower in cases of PMDD (HR = 4.96 (95% CI 1.31–18.84)).

Conclusion

A PMDD ≥5 mm is a frequent incidental MRI finding in the general population (2.7%). The risk of malignant transformation was higher with PMDD (2.5%) than without (0.8%). Chronic pancreatitis was diagnosed four times as often than pancreatic cancer in follow-up.

References

[1] Schmitz D, Stenzinger A, Grützmann R, et al. The differential diagnosis and management of pancreatic cystic neoplasms. Dtsch Arztebl Int 2025;122(22): 617–22.
[2] John U, Greiner B, Hensel E, et al. Study of health in Pomerania (SHIP): a health examination survey in an east German region: objectives and design. Sozial- Praventivmed € 2001;46(3):186–94.
[3] Aghdassi AA, Schauer B, Duscha D, et al. Comparability of size measurements of the pancreas in magnetic resonance imaging and transabdominal ultrasound. Clin Anat 2020;33(3):431–9.
[4] Volzke € H, Alte D, Schmidt CO, et al. Kohortenprofil: die Erforschung der Gesundheit in Pommern. Int J Epidemiol 2011;40(2):294–307.
[5] Hegenscheid K, Kühn JP, Volzke € H, Biffar R, Hosten N, Puls R. Whole-body magnetic resonance imaging of healthy volunteers: pilot study results from the population-based SHIP study. Rofo € 2009;181(8):748–59.
[6] Hosten N, Bülow R, Volzke € H, et al. SHIP-MR and radiology: 12 years of whole-body magnetic resonance imaging in a single center. Healthcare (Basel) 2021;10(1):33.
[7] Volzke € H, Schossow € J, Schmidt CO, et al. Cohort profile update: the study of health in Pomerania (SHIP). Int J Epidemiol 2022;51(6):e372–83.

Disclosure

All authors declare that they have no conflict of interest with regard to the content of the presented study

Event

UEG Week Barcelona 2026

Topics

Radiology & Imaging Pancreas Endoscopy Digestive Oncology

Submission format

Abstract

Session

Pancreatic cyst: From molecular insights to clinical care

Citation

2026: United European Gastroenterology Journal 2026; 14 (S1)

Published

2026

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SHP2 REGULATES CAF ACTIVITY AND ADAPTIVE STROMAL REMODELING DURING VERTICAL RAS PATHWAY INHIBITION IN PANCREATIC CANCER

Dietrich Alexander Ruess

USE OF HIGH DOSE PROTON PUMP INHIBITORS INCREASES THE RISK OF DELAYED DEGRADATION OF BIODEGRADABLE BILIOPANCREATIC STENTS: A PROSPECTIVE REAL-WORLD EXPERIENCE FROM A TERTIARY REFERRAL CENTRE

Damien Meng Yew Tan

CIRCULATING PROTEIN PROFILES IN PANCREATIC DUCTAL ADENOCARCINOMA REVEAL DISTINCT EARLY-STAGE DISEASE-ASSOCIATED ALTERATIONS

Jurgita Skieceviciene

PREVALENCE AND NATURAL COURSE OF MRI-DIAGNOSED DILATED MAIN PANCREATIC DUCT: A LONGITUDINAL, POPULATION-BASED PROSPECTIVE COHORT STUDY WITH A TEN-YEAR FOLLOW-UP

Fabian Yazdi

CLINICAL IMPACT OF MULTIPLE EUS-FNA DURING PANCREATIC CYST SURVEILLANCE

Nadim Haddad

UEG Presentation

New

Share via Email Share on Facebook Share on X Share on LinkedIn Share on Bluesky

CLINICAL IMPACT OF MULTIPLE EUS-FNA DURING PANCREATIC CYST SURVEILLANCE

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CLINICAL IMPACT OF MULTIPLE EUS-FNA DURING PANCREATIC CYST SURVEILLANCE

Srikar Reddy 1, Carlos Guarner-Argente 2, Abdalla Khouqeer 1, Dimitrios Moris 1, Meggin Sabatino 1, Alexander Kroemer 1, Priyanka Kanth 1, Walid Chalhoub 1, Nadim Haddad 1

Affiliations

1 MedStar Georgetown University Hospital, Washington, United States

2 Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

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Abstract

Introduction

Pancreatic cystic lesions (PCLs) are increasingly detected incidentally. While endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) with cyst fluid analysis is central to diagnosis and risk stratification, the clinical utility of repeated EUS-FNA during long-term surveillance remains poorly defined. This study aimed to evaluate whether multiple EUS-FNA procedures during pancreatic cyst surveillance provide clinically meaningful information that influences diagnosis or management decisions.

Aims & Methods

We conducted a retrospective cohort study of patients who underwent at least two EUS-FNA procedures for pancreatic cyst diagnosis and surveillance at a tertiary academic center between January 2009 and December 2024. The primary outcome was change in cyst diagnosis and/or management resulting from multiple FNA procedures. Secondary outcomes included diagnostic accuracy, complication rates, and identification of predictive factors to benefit from repeat sampling. Cyst fluid biomarkers analyzed included carcinoembryonic antigen (CEA), amylase, glucose, and molecular markers (KRAS and GNAS mutations).

Results

A total of 151 patients (66.3±13.2 years, 63% female) underwent a median of 3 EUS-FNA procedures (IQR 2-4; range 2-11), with a median interval of 14 months (IQR 11-23), over a median follow-up of 89 months (IQR 52-122). A change in diagnosis occurred in 19 patients (12.6%), determined primarily by multiple EUS-FNA findings in 11 (7.3%). Multiple EUS-FNA resulted in a relative increase of CEA, KRAS, and GNAS sensitivity of 42.4, 71.8 and 90.1%, respectively, while maintaining a high specificity (Table).
Multiple FNA led to a change in diagnosis or management in 20 patients (13.2%) after a median of 61.5 months (IQR 23-92) and 2.5 FNAs (IQR 2-4). The characteristics of the cyst fluid that led to the change were only biochemical in 6 (CEA in 2, amylase in 1, glucose in 1, and a combination of factors in 2), only molecular in 9 (KRAS 7 and GNAS in 2), and a combination of biochemical and molecular in 5 (3 KRAS and 2 GNAS).
Factors independently associated to a lower benefit of repeating FNA were older age (OR 0.96 per year increase, 95% CI 0.91–1.00; p=0.036), initial positive GNAS and/or KRAS (OR 0.15, 95% CI 0.03–0.6; p<0.01), CEA <30 (OR 0.08, 95% CI 0.01–0.3; p<0.01), and amylase <36000 (OR 0.14, 95% CI 0.01–0.64; p<0.01). Most patients (62.9%) fulfilled at least one low-benefit criterion for multiple FNA, and only 5.6% of these patients derived benefit, compared with 25.5% of patients without such characteristics (OR 6.6, 95% CI 2.2–19.3; p<0.01).

Conclusion

Multiple EUS-FNA with biochemical and molecular testing during pancreatic cyst surveillance can provide clinically meaningful information that influences diagnosis and management. Repeating FNA is less valuable in older patients with diagnostically uncertain baseline findings, particularly those with CEA higher than 30, amylase lower than 36,000, and negative molecular markers. These findings support a selective approach to repeat EUS-FNA rather than routine repeated sampling in all patients under surveillance.

Event

UEG Week Barcelona 2026

Topics

Radiology & Imaging Pancreas Endoscopy Digestive Oncology

Submission format

Abstract

Session

Pancreatic cyst: From molecular insights to clinical care

Citation

2026: United European Gastroenterology Journal 2026; 14 (S1)

Published

2026

More Like This:

DUODENAL ASPIRATION BIOPSY WITH CEA-BASED THREE-ZONE RISK STRATIFICATION FOR PANCREATIC CYSTIC NEOPLASMS: A PROSPECTIVE MULTICENTER STUDY

Vitali Proutski

SHP2 REGULATES CAF ACTIVITY AND ADAPTIVE STROMAL REMODELING DURING VERTICAL RAS PATHWAY INHIBITION IN PANCREATIC CANCER

Dietrich Alexander Ruess

USE OF HIGH DOSE PROTON PUMP INHIBITORS INCREASES THE RISK OF DELAYED DEGRADATION OF BIODEGRADABLE BILIOPANCREATIC STENTS: A PROSPECTIVE REAL-WORLD EXPERIENCE FROM A TERTIARY REFERRAL CENTRE

Damien Meng Yew Tan

CIRCULATING PROTEIN PROFILES IN PANCREATIC DUCTAL ADENOCARCINOMA REVEAL DISTINCT EARLY-STAGE DISEASE-ASSOCIATED ALTERATIONS

Jurgita Skieceviciene

PREVALENCE AND NATURAL COURSE OF MRI-DIAGNOSED DILATED MAIN PANCREATIC DUCT: A LONGITUDINAL, POPULATION-BASED PROSPECTIVE COHORT STUDY WITH A TEN-YEAR FOLLOW-UP

Fabian Yazdi

CLINICAL IMPACT OF MULTIPLE EUS-FNA DURING PANCREATIC CYST SURVEILLANCE

Nadim Haddad