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Background <p>Managing branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) remains challenging, as guideline criteria (worrisome features/high-risk stigmata) and nomograms often leave uncertainty. Next-generation sequencing (NGS) may provide actionable molecular information that influences clinical decision-making.</p> Methods <p>We conducted a national, vignette-based decision-impact study involving 132 clinicians (gastroenterologists and surgeons). Four complex BD-IPMN vignettes (each with two to four worrisome features) were evaluated twice: pre-NGS and post-NGS after disclosure of either a high-risk mutation (positive) or its absence (negative). The primary endpoint was the within-physician change in management in the NGS-concordant direction (NGS+ surveillance to surgery; NGS− surgery to surveillance) assessed using McNemar’s test and mixed-effects logistic regression. Secondary endpoints included change in decision confidence, inter-physician agreement (Fleiss’ κappa), and practitioner factors.</p> Results <p>NGS significantly changed management in all vignettes (all <i>p</i> &lt; 0.001): with NGS−, surgical plans shifted to surveillance (43% in distal pancreatectomy; 61% in pancreatoduodenectomy scenarios); with NGS+, surveillance shifted to surgery (90% and 72%, respectively; both <i>p</i> &lt; 0.001). In mixed-model, post-NGS reduced surgery in NGS− cases (odd ratio [OR] 0.30, 95%confidence interval [CI] 0.16–0.57) and the post-NGS effect was strongly amplified in NGS+ cases (interaction OR 76.51, 95%CI 26.47–221.13). Population-averaged probabilities of choosing surgery shifted from 20% to 7% (NGS−) and 42% to 94% (NGS+). Decision confidence increased (proportional-odds OR 4.66, 95%CI 3.62–6.02, <i>p</i> &lt; 0.0001). Inter-physician agreement rose from <i>κ</i> = 0.044 (95%CI 0.033–0.055) pre-NGS to <i>κ</i> = 0.590 (95%CI 0.580–0.601) post-NGS (<i>p</i> &lt; 2×10<sup>−16</sup>). After NGS, practitioner characteristics no longer explained decision patterns.</p> Conclusions <p>In complex BD-IPMN scenarios, NGS significantly influences clinician decision-making and reduces inter-physician variability. These findings support its role as a decision-support tool.</p>

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Impact of Next-Generation Sequencing on Surgical Decision-Making in Branch-Duct IPMN

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月24日

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  • Maxime Remy,
  • Jeremie Albouys,
  • David Jérémie Birnbaum,
  • Sebastien Gaujoux,
  • Anne Laure Védie,
  • Clémence Descourvières,
  • Jean Michel Gonzalez,
  • Diane Lorenzo

摘要

Background

Managing branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) remains challenging, as guideline criteria (worrisome features/high-risk stigmata) and nomograms often leave uncertainty. Next-generation sequencing (NGS) may provide actionable molecular information that influences clinical decision-making.

Methods

We conducted a national, vignette-based decision-impact study involving 132 clinicians (gastroenterologists and surgeons). Four complex BD-IPMN vignettes (each with two to four worrisome features) were evaluated twice: pre-NGS and post-NGS after disclosure of either a high-risk mutation (positive) or its absence (negative). The primary endpoint was the within-physician change in management in the NGS-concordant direction (NGS+ surveillance to surgery; NGS− surgery to surveillance) assessed using McNemar’s test and mixed-effects logistic regression. Secondary endpoints included change in decision confidence, inter-physician agreement (Fleiss’ κappa), and practitioner factors.

Results

NGS significantly changed management in all vignettes (all p < 0.001): with NGS−, surgical plans shifted to surveillance (43% in distal pancreatectomy; 61% in pancreatoduodenectomy scenarios); with NGS+, surveillance shifted to surgery (90% and 72%, respectively; both p < 0.001). In mixed-model, post-NGS reduced surgery in NGS− cases (odd ratio [OR] 0.30, 95%confidence interval [CI] 0.16–0.57) and the post-NGS effect was strongly amplified in NGS+ cases (interaction OR 76.51, 95%CI 26.47–221.13). Population-averaged probabilities of choosing surgery shifted from 20% to 7% (NGS−) and 42% to 94% (NGS+). Decision confidence increased (proportional-odds OR 4.66, 95%CI 3.62–6.02, p < 0.0001). Inter-physician agreement rose from κ = 0.044 (95%CI 0.033–0.055) pre-NGS to κ = 0.590 (95%CI 0.580–0.601) post-NGS (p < 2×10−16). After NGS, practitioner characteristics no longer explained decision patterns.

Conclusions

In complex BD-IPMN scenarios, NGS significantly influences clinician decision-making and reduces inter-physician variability. These findings support its role as a decision-support tool.