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Optimizing branch-duct intraductal papillary mucinous neoplasms surveillance: Data-driven dimensional grouping for risk stratification and cost-effectiveness
Stefano Kayali, Simone Dibitetto, Alberto Busatto, Federica Gaiani, Andrea Pasta, Francesco Calabrese, Stefano Fantasia, Simone Caprioli, Andrea P Luzzi, Claudio G De Angelis, Edoardo V Savarino, Luigi Laghi, Edoardo G Giannini, Elisa Marabotto
Stefano Kayali, Federica Gaiani, Stefano Fantasia, Luigi Laghi, Department of Medicine and Surgery, University of Parma, Parma 43121, Emilia-Romagna, Italy
Stefano Kayali, Federica Gaiani, Luigi Laghi, Gastroenterology and Endoscopy Unit, University Hospital of Parma, Parma 43126, Emilia-Romagna, Italy
Simone Dibitetto, Claudio G De Angelis, University Division of Gastroenterology, City of Health and Science University Hospital, Turin 10126, Piedmont, Italy
Alberto Busatto, Edoardo V Savarino, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padua, Padova 35128, Veneto, Italy
Andrea Pasta, Francesco Calabrese, Edoardo G Giannini, Elisa Marabotto, Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS‐Ospedale Policlinico San Martino, Genoa 16132, Liguria, Italy
Simone Caprioli, Andrea P Luzzi, Department of Internal Medicine, University of Genoa, IRCCS‐Ospedale Policlinico San Martino, Genoa 16132, Liguria, Italy
Author contributions: Kayali S, Giannini EG and Marabotto E conceptualized the study; Kayali S performed the formal analysis, developed the methodology, administered the project, wrote the original draft and led the review and editing process; Dibitetto S, Busatto A and Fantasia S curated the data; Gaiani F, Pasta A and Calabrese F contributed equally to review and editing; Caprioli S and Luzzi AP provided supervision; De Angelis CG, Savarino EV and Laghi L contributed equally to supervision and to writing, review and editing; Giannini EG and Marabotto E supervised the study and contributed to writing, review and editing; all authors reviewed and approved the final manuscript.
Supported by the Project ROTI 2022 ALTRIMIN POS “Chemogenomica Funzionale Per Il Futuro Delle Terapie Personalizzate Nelle Neoplasie Maligne” (codice T3-AN-05), No. CUP: D93C22000610001.
Institutional review board statement: All data were retrospectively evaluated, preserving patients’ anonymity. According to the Italian Medicines Agency det. 20/03/2008 on retrospective observational studies using anonymous data, approval by an ethics committee was not mandatory. The study complied with the Declaration of Helsinki (2024 revision).
Informed consent statement: According to the Italian Medicines Agency det. 20/03/2008 on retrospective observational studies using anonymous data, approval by an ethics committee was not mandatory, and informed consent was waived.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
STROBE statement: The authors have read the STROBE Statement—a checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-a checklist of items.
Data sharing statement: Study data used for the analyses are stored on secure institutional servers. They are available from the corresponding author upon reasonable request.
Corresponding author: Stefano Kayali, MD, PhD, Research Fellow, Department of Medicine and Surgery, University of Parma, Viale Gramsci, 14, Parma 43121, Emilia-Romagna, Italy.
stefano.kayali@unipr.it
Received: September 30, 2025
Revised: December 3, 2025
Accepted: March 4, 2026
Published online: May 28, 2026
Processing time: 232 Days and 17.5 Hours
BACKGROUND
The rising detection of branch-duct intraductal papillary mucinous neoplasms (BD-IPMN) has led to updated surveillance guidelines, yet the true malignant transformation rate and the cost-effectiveness of these strategies remain uncertain. Current protocols are based on expert opinion rather than validated data, leading to conflicting recommendations and significant healthcare costs. This study addresses the need for an evidence-based approach to optimize surveillance by identifying robust risk factors and creating a more efficient protocol.
AIM
To determine the rate of BD-IPMN malignant progression, identify independent risk factors, and develop a surveillance protocol optimized for both diagnostic accuracy and cost-efficiency.
METHODS
This is a multicentric retrospective cohort study using prospectively collected data from four Italian tertiary care centers. A total of 333 patients undergoing surveillance for BD-IPMN between January 2017 and August 2023 were included. Multivariate Cox regression and segmentation analysis identified predictors and derived novel size thresholds for malignancy risk stratification. We then compared the diagnostic accuracy and 3-year surveillance costs of a proposed protocol against the Fukuoka 2017 and Kyoto 2024 guidelines.
RESULTS
Among 333 patients (median follow-up, 4 years), malignant transformation occurred in 11 (3.3%). Independent risk factors for malignancy included high risk stigmata (HRS) [hazard ratio (HR) = 4.4, 95% confidence interval (CI): 1.1-17.8, P = 0.04], the development of ≥ 2 worrisome features (WFs) (HR = 5.8, 95%CI: 1.5-22.4, P = 0.01), and cyst size (HR = 2.0, 95%CI: 1.3-3.0, P < 0.001). Two new cut-offs (1.5 cm and 3.0 cm) defined dimensional categories with distinct malignant potential (HR = 6.6, 95%CI: 1.7-25.4, P = 0.007, HR = 9.8, 95%CI: 1.1-89.7, P = 0.04). A proposed surveillance protocol preserved diagnostic accuracy while reducing 3-year costs by 11% vs Fukuoka and 21.4% vs Kyoto (P < 0.001). Scenario analysis confirmed cost-effectiveness.
CONCLUSION
IPMN degeneration is rare. HRS and at least two WFs may independently predict malignancy. Our surveillance protocol based on data-driven size cut-offs (1.5 cm and 3 cm) may enhance cost-effectiveness over current guidelines while maintaining diagnostic precision.
Core Tip: Malignant degeneration of branch-duct intraductal papillary mucinous neoplasms is rare. Surveillance strategies can be optimized for both safety and cost-effectiveness. This study identifies data-driven cyst size thresholds of 1.5 cm and 3.0 cm and finds that the presence of at least two worrisome features, not just one, is an independent predictor of malignancy. A new surveillance protocol based on these findings maintains diagnostic accuracy while reducing 3-year costs by up to 21.4% compared to current international guidelines, particularly by safely extending follow-up intervals for the majority of patients with small cysts.
