Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Multicenter Study
. 2025 Jul;13(6):971-981.
doi: 10.1002/ueg2.70043. Epub 2025 Jun 18.

Small and Stable Pancreatic Cysts Are Reassuring During Surveillance: Results From the PACYFIC Trial

Iris J M Levink  1 , Marloes L J A Sprij  1   2 , Brechtje D M Koopmann  1   2 , Jihane Meziani  1 , Sanne Jaarsma  1 , Priscilla A van Riet  1 , Kasper A Overbeek  1 , Myrte Gorris  3 , Rogier P Voermans  3 , Jeanin E van Hooft  4 , Riccardo Casadei  5 , Mariacristina Di Marco  5 , Michael B Wallace  6 , Sanne A Hoogenboom  3   6 , Neville Azopardi  7 , Reea Ahola  8 , Marcin Polkowski  9   10 , Pieter Honkoop  11 , Silvia Carrara  12 , Erik J Schoon  13 , Niels G Venneman  14 , Laurens A van der Waaij  15 , Anne-Marie van Berkel  16 , Gemma Rossi  17   18   19 , Jilling F Bergmann  20 , Elizabeth Pando  21 , Georg Beyer  22 , Matthijs P Schwartz  23 , Frederike G I van Vilsteren  24 , Chantal Hoge  25 , Marianne E Smits  26 , Rutger Quispel  27 , Ellert J van Soest  28 , Patrick M Vos  29 , Robert C Verdonk  30 , Toon Steinhauser  31 , Eva Kouw  32 , Adriaan C I T L Tan  33 , Laszlo Czako  34 , Marco J Bruno  1 , Djuna L Cahen  1   35 ; PACYFIC‐Study Work Group
Affiliations
Multicenter Study

Small and Stable Pancreatic Cysts Are Reassuring During Surveillance: Results From the PACYFIC Trial

Iris J M Levink et al. United European Gastroenterol J. 2025 Jul.

Abstract

Background: Pancreatic cysts are increasingly discovered on imaging studies performed for unrelated conditions. Currently, surveillance of these lesions poses a substantial burden on patients, and health care recourses. We hypothesized that individuals with small and stable cysts have a diminutive risk of progressing to high-grade dysplasia (HGD) or pancreatic cancer (PC) that is similar to that in the general population.

Methods: This nested PACYFIC-study is a collaboration among 44 centers in Europe and Northern-America, and investigates the risk of HGD and PC for different cyst sizes and growth rates in participants without baseline worrisome features (WF) or high-risk stigmata (HRS).

Results: Of the 2369 PACYFIC participants, 975 met the inclusion criteria, with a mean age of 67 years (SD 13) and 65% being female. Of these, 438 individuals (45%) had a baseline small cyst size (< 15 mm), and 885 (91%) individuals had a slow growth rate (< 2.5 mm/year). During a median follow-up of 45 months (IQR 27), 20 individuals (2.1%) developed HGD, or PC. Individuals with small cysts had a 1.5-fold lower risk of developing WF or HRS (hazard ratio [HR] 0.7 [0.5-1.0], p = 0.03) than those with larger cysts but a similar risk of developing HGD or PC (p > 0.05). Slow growth was protective against the development of WF or HRS (HR 0.4 [0.2-0.6], p < 0.001) and HGD or PC (HR 0.04 [95% CI 0.02-0.12], p < 0.001). Individuals with small, stable sized cysts without baseline WF or HRS did not have a higher risk of HGD or PC than the general population (standardized incidence ratio [SIR] 1.13 [95% CI 0.01-6.30]).

Conclusion: Cyst size < 15 mm and growth rate < 2.5 mm/year appear to be "reassuring" features associated with a negligible risk of developing WF or HRS and HGD or PC. For cysts with these characteristics-and without baseline WF or HRS-less intensive surveillance (than currently recommended) or even cessation may be appropriate.

Keywords: cyst size; high‐grade dysplasia; intraductal papillary mucinous neoplasm (IPMN); pancreatic cancer; pancreatic cyst; stable cyst growth; surveillance.

PubMed Disclaimer

Conflict of interest statement

Iris J.M. Levink, Marloes L.J.A. Sprij, Brechtje D.M. Koopmann, Sanne Jaarsma, Priscilla A. van Riet, Kasper A. Overbeek, Jihane Meziani, Myrte Gorris, Rogier P. Voermans, Riccardo Casadei, Mariacristina Di Marco, Sanne A. Hoogenboom, Neville Azopardi, Reea Ahola, Marcin Polkowski, Pieter Honkoop, Erik J. Schoon, Niels G. Venneman, Laurens A. van der Waaij, Anne‐Marie van Berkel, Gemma Rossi, Jilling F. Bergmann, Elizabeth Pando, Georg Beyer, Matthijs P. Schwartz, Frederike G.I. van Vilsteren, Chantal Hoge, Marianne E. Smits, Rutger Quispel, Ellert J. van Soest, Patrick M. Vos, Robert C. Verdonk, Toon Steinhauser, Eva Kouw, Adriaan C.I.T.L. Tan, Laszlo Czako, and Djuna L. Cahen have no conflicts of interest. Jeanin E. van Hooft: Boston Scientific (Lecture), Cook medical (Lecture), Fuji Film (Lecture), Olympus (Consultancy fee). Michael B. Wallace: Consulting: Verily, Boston Scientific, Endiatix, Fujifilm, Medtronic, Surgical Automations; Research grants: Fujifilm, Boston Scientific, Olympus, Medtronic, Ninepoint Medical, Cosmo/Aries Pharmaceuticals’ Stock/Stock Options:, Virgo Inc., Surgical Automations. Silvia Carrara: Olympus (lecture). Marco J. Bruno: Boston Scientific (Consultant, support for industry and investigator‐initiated studies), Cook Medical (Consultant, support for industry and investigator‐initiated studies), Pentax Medical (Consultant, support for investigator‐initiated studies), Mylan (Support for investigator‐initiated studies), ChiRoStim (Support for investigator‐initiated studies).

Figures

FIGURE 1
FIGURE 1
Flowchart showing the in‐ and exclusion of PACYFIC participants. Nine hundred seventy‐five participants were included in the cyst size cohort; this cohort was subdivided into a small cyst size group (< 15 mm) and a larger cyst size group (≥ 15 mm). For the cyst growth analysis, only those 951 participants who had more than 12 months of follow‐up were included. Cyst size or cyst growth were not included as worrisome features (WF) or high‐risk stigmata (HRS). FU = follow‐up, PC = pancreatic cancer.
FIGURE 2
FIGURE 2
Cox proportional hazard plots showing the risk of developing worrisome features (WFs) or high‐risk stigmata (HRS). (a, c, and d). The hazard ratio (HR; adjusted for age and sex) per cyst size (a) and cyst growth group (c, d). (b) The absolute risk per cyst size and growth group.
FIGURE 3
FIGURE 3
Cox proportional hazard plots showing the risk of developing high‐grade dysplasia (HGD) or pancreatic cancer (PC). (a) The absolute risk per cyst size and growth group. (b–d) The hazard ratio (HR; adjusted for age and sex) per cyst size (b) and cyst growth group (c, d).
See this image and copyright information in PMC

References

    1. Siegel R. L., Giaquinto A. N., and Jemal A., “Cancer Statistics, 2024,” CA: A Cancer Journal for Clinicians 74, no. 1 (2024): 12–49, 10.3322/caac.21820. - DOI - PubMed
    1. Kromrey M.‐L., Bülow R., Hübner J., et al., “Prospective Study on the Incidence, Prevalence and 5‐Year Pancreatic‐Related Mortality of Pancreatic Cysts in a Population‐Based Study,” Gut 67, no. 1 (2018): 138–145, 10.1136/gutjnl-2016-313127. - DOI - PubMed
    1. The European Study Group on Cystic Tumours of the Pancreas , “European Evidence‐Based Guidelines on Pancreatic Cystic Neoplasms,” Gut 67, no. 5 (2018): 789–804, 10.1136/gutjnl-2018-316027. - DOI - PMC - PubMed
    1. Ohtsuka T., Fernandez‐Del Castillo C., Furukawa T., et al., “International Evidence‐Based Kyoto Guidelines for the Management of Intraductal Papillary Mucinous Neoplasm of the Pancreas,” Pancreatology 24, no. 2 (2024): 255–270, 10.1016/j.pan.2023.12.009. - DOI - PubMed
    1. Konings I. C. A. W., Canto M. I., Almario J. A., et al., “Surveillance for Pancreatic Cancer in High‐Risk Individuals,” BJS Open 3, no. 5 (2019): 656–665, 10.1002/bjs5.50180. - DOI - PMC - PubMed

Publication types