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Objectives <p>To investigate whether cyst shrinkage in intraductal papillary mucinous neoplasm (IPMN) is paradoxically associated with a higher risk of concomitant pancreatic ductal adenocarcinoma (PDAC).</p> Materials and methods <p>This retrospective cohort included 1103 patients with pathologically or cytologically confirmed branch-duct or mixed-type IPMN followed for ≥ 1 year. Patients were classified by annual cyst size change rate per the 2024 Kyoto guideline thresholds: shrinkage (&lt; 0 mm/year), stable (0 to &lt; 2.5 mm/year), and growth (≥ 2.5 mm/year). The primary outcome was concomitant PDAC, with IPMN-derived carcinoma as a competing event. Multivariable Fine-Gray regression compared shrinkage with a pre-specified merged non-shrinkage reference; cause-specific Cox regression served as sensitivity analysis.</p> Results <p>Of 1103 patients (541 men, 562 women; mean age, 67.3 ± 9.8 years), 282 (25.6%) showed shrinkage, 728 (66.0%) remained stable, and 93 (8.4%) showed growth. Concomitant PDAC was most frequent in shrinkage (6/282, 2.1%), followed by stable (8/728, 1.1%), with no events in growth (0/93). IPMN-derived carcinoma was most frequent in growth (9/93, 9.7%). Adjusted for age, sex, initial cyst size, and main pancreatic duct diameter, shrinkage was independently associated with concomitant PDAC (subdistribution hazard ratio 4.46; 95% CI 1.62–12.30; <i>p</i> = 0.004); cause-specific Cox regression yielded a concordant estimate (hazard ratio 4.54; 95% CI 1.52–13.50; <i>p</i> = 0.007).</p> Conclusion <p>In this single-center retrospective cohort, cyst shrinkage was associated with an increased incidence of concomitant PDAC, contrary to the prevailing assumption that shrinkage reflects a benign course. Given the modest number of concomitant PDAC events (<i>n</i> = 14), these findings are hypothesis-generating and exploratory; external validation in multicenter prospective cohorts is required before clinical surveillance practice is modified.</p> Key Points <p><Emphasis Type="BoldItalic">Question</Emphasis> <i>Cyst shrinkage during intraductal papillary mucinous neoplasm surveillance is considered reassuring, but its association with concomitant pancreatic cancer risk remains unclear.</i></p> <p><Emphasis Type="BoldItalic">Findings</Emphasis> <i>Shrinkage was paradoxically associated with higher concomitant pancreatic cancer risk (subdistribution hazard ratio 4.46); the growth group’s 0% rate reflected competing risks from IPMN-derived carcinoma.</i></p> <p><Emphasis Type="BoldItalic">Clinical relevance</Emphasis> <i>Radiologists should not reduce surveillance intensity for shrinking intraductal papillary mucinous neoplasm cysts, as these patients carry an elevated risk of concomitant pancreatic cancer developing independently of the monitored cyst.</i></p> Graphical Abstract <p></p>

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Shrinkage paradox in intraductal papillary mucinous neoplasms is associated with higher concomitant pancreatic cancer risk

  • 期刊论文

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  • 发表日期：

    2026年7月10日

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  • Hideyuki Fukui,
  • Teppei Yoshioka,
  • Katsuhiko Sato,
  • Yuki Makino,
  • Hiromitsu Onishi,
  • Atsushi Nakamoto,
  • Takashi Ota,
  • Toru Honda,
  • Feier Ding,
  • Yukihiro Enchi,
  • Daisaku Yamada,
  • Yasunari Fukuda,
  • Hidetoshi Eguchi,
  • Takahiro Kodama,
  • Noriyuki Tomiyama

摘要

Objectives

To investigate whether cyst shrinkage in intraductal papillary mucinous neoplasm (IPMN) is paradoxically associated with a higher risk of concomitant pancreatic ductal adenocarcinoma (PDAC).

Materials and methods

This retrospective cohort included 1103 patients with pathologically or cytologically confirmed branch-duct or mixed-type IPMN followed for ≥ 1 year. Patients were classified by annual cyst size change rate per the 2024 Kyoto guideline thresholds: shrinkage (< 0 mm/year), stable (0 to < 2.5 mm/year), and growth (≥ 2.5 mm/year). The primary outcome was concomitant PDAC, with IPMN-derived carcinoma as a competing event. Multivariable Fine-Gray regression compared shrinkage with a pre-specified merged non-shrinkage reference; cause-specific Cox regression served as sensitivity analysis.

Results

Of 1103 patients (541 men, 562 women; mean age, 67.3 ± 9.8 years), 282 (25.6%) showed shrinkage, 728 (66.0%) remained stable, and 93 (8.4%) showed growth. Concomitant PDAC was most frequent in shrinkage (6/282, 2.1%), followed by stable (8/728, 1.1%), with no events in growth (0/93). IPMN-derived carcinoma was most frequent in growth (9/93, 9.7%). Adjusted for age, sex, initial cyst size, and main pancreatic duct diameter, shrinkage was independently associated with concomitant PDAC (subdistribution hazard ratio 4.46; 95% CI 1.62–12.30; p = 0.004); cause-specific Cox regression yielded a concordant estimate (hazard ratio 4.54; 95% CI 1.52–13.50; p = 0.007).

Conclusion

In this single-center retrospective cohort, cyst shrinkage was associated with an increased incidence of concomitant PDAC, contrary to the prevailing assumption that shrinkage reflects a benign course. Given the modest number of concomitant PDAC events (n = 14), these findings are hypothesis-generating and exploratory; external validation in multicenter prospective cohorts is required before clinical surveillance practice is modified.

Key Points

Question Cyst shrinkage during intraductal papillary mucinous neoplasm surveillance is considered reassuring, but its association with concomitant pancreatic cancer risk remains unclear.

Findings Shrinkage was paradoxically associated with higher concomitant pancreatic cancer risk (subdistribution hazard ratio 4.46); the growth group’s 0% rate reflected competing risks from IPMN-derived carcinoma.

Clinical relevance Radiologists should not reduce surveillance intensity for shrinking intraductal papillary mucinous neoplasm cysts, as these patients carry an elevated risk of concomitant pancreatic cancer developing independently of the monitored cyst.

Graphical Abstract