Faculty Bibliography

Pancreatic ductal adenocarcinoma (PDAC) with extensive peripancreatic vessel involvement is classified as locally advanced pancreatic cancer (LAPC). For this group of patients, the current standard of care does not include considering a potentially curative oncologic resection. However, recent advances in multiagent chemotherapy and surgical techniques are challenging this paradigm. Moreover, the current determination of anatomic resectability is vague and unreliable. Here we propose a definition of local resectability, based on pre- and intra-operative assessment. This anatomic definition of resectability assumes careful patient selection based on tumor biology and patient condition. The pre-operative evaluation of vascular anatomy and tumor involvement is conducted using 3D-rendering of pancreas-protocol computed tomography. Identifying a disease-free arterial or venous segment above and below the tumor involvement ("suitable target") is the single critical factor that determines anatomic resectability. Intraoperative isolation of these target vessels confirms the feasibility of vascular reconstruction before resection. This approach, which focuses on identifying target vessels rather than circumferential involvement, offers a more straightforward and clinically relevant method for assessing surgical eligibility in LAPC patients at centers of excellence. In summary, reconstructability-based on surgical expertise and guided by tumor biology-now defines the modern paradigm of resectability in LAPC.

BACKGROUND:Accurate preoperative malignancy risk assessment in intraductal papillary mucinous neoplasm (IPMN) is essential to balance timely intervention for high-grade dysplasia or invasive cancer (HGD/IC) against avoiding unnecessary or premature surgery in low-grade IPMN. This study aimed to externally validate the 2023 International Association of Pancreatology (IAP)/Kyoto guidelines and develop a combined prediction model incorporating routinely collected clinical data and laboratory parameters. METHODS:We conducted a retrospective cohort study of 194 patients who underwent resection for IPMN between 2012 and 2024. We evaluated the predictive performance of the current IAP/Kyoto criteria ("Kyoto model"), developed a clinical model using routinely available laboratory and clinical variables, and integrated both into a combined model. Model performance was assessed using discrimination and calibration metrics, with internal validation via bootstrapping and five-fold cross-validation. RESULTS:The Kyoto model demonstrated modest discrimination (AUC 0.62). The clinical model, incorporating neutrophil-to-lymphocyte ratio (NLR), smoking history, blood glucose, CA19-9, and alkaline phosphatase, achieved an optimism-corrected AUC of 0.76. Compared to the Kyoto model, the combined model (AUC 0.77) significantly improved discrimination and calibration (p < 0.001). At a predicted probability threshold of >0.75, the combined model achieved a 90% specificity and 91% positive predictive value for HGD/IC, identifying a high-risk subgroup suitable for surgical intervention. CONCLUSIONS:Integrating routinely collected clinical and laboratory parameters with guideline-based imaging features shows promise to enhance preoperative identification of high-risk IPMN in patients already being considered for surgical resection. The combined model offers a practical, high-specificity tool to support surgical decision-making in this selected population, though its performance metrics should not be extrapolated to unselected surveillance cohorts. External validation is required before broader clinical implementation.

BACKGROUND:Risk calculators (RCs) support clinicians estimating the likelihood that a pancreatic intraductal papillary mucinous neoplasm (IPMN) would progress so that surveillance might be discontinued for low-risk lesions. We tested the effect of an RC on clinicians' judgment and decision-making and identified their cancer risk threshold for changing their decision. PATIENTS AND METHODS/METHODS:We presented clinicians with three vignettes (V1, V2, and V3) of patients with low-risk IPMNs and asked them to assess the likelihood that the IPMN would progress to develop high-risk features and whether they would recommend continuing surveillance imaging. Clinicians were randomly assigned to the clinical vignettes alone (n = 35) or supplemented by data from the Dutch-American Risk Stratification Tool (DART-1 RC: n = 37). We compared clinicians' judgments and decisions between groups and assessed their cancer risk threshold (level of risk at which recommendation would change). RESULTS:Across all vignettes, the RC resulted in no change in clinicians' judged likelihood of IPMN progression (V1 8.49 vs. 8.41%, p = 0.09; V2 4.39 vs. 6.75%, p = 0.99; V3 13.61 vs. 13.29%, p = 0.27) or recommendation to continue surveillance (V1 57 vs. 41%, p = 0.78; V2 41 vs. 59%, p = 0.55; V3 66 vs. 34%, p = 0.31). Clinicians varied in their reported risk threshold (V1 9%, interquartile range [IQR] 2, 13%; V2 9% [IQR 1, 15%], V3 8% [IQR 3, 20%]). CONCLUSIONS:An RC did not significantly influence clinicians' risk perception or decision to continue surveillance, although the study was limited by low sample size. The cancer risk threshold at which clinicians would change their recommendation varies widely. Future work is needed to understand why RCs do not appear to alter decision-making.

BACKGROUND:Most branch duct intraductal papillary mucinous neoplasms (BD-IPMNs) are indolent, but distinguishing those harboring high-grade dysplasia or invasive cancer remains difficult. This analysis focuses not on incidental small BD-IPMNs but on the subset whose cyst characteristics bring surgery into the decision-making discussion. Surgery prevents malignant progression but carries morbidity; surveillance avoids overtreatment but risks delayed cancer detection. Current guidelines rely on fixed thresholds that may not reflect individual variation. Our study compared immediate surgery and initial surveillance in patients with BD-IPMNs, using a decision-analytic model that incorporates patient-specific risk factors. METHODS:A Markov decision model compared immediate surgery with initial surveillance, incorporating age, comorbidities, and cyst location. Health states reflected progression from low-grade to high-grade dysplasia and invasive cancer, postoperative complications, recurrence, and quality-of-life decrements. Transition probabilities were derived from published studies and American College of Surgeons (ACS)-National Surgical Quality Improvement Program data. The primary outcome was quality-adjusted life-years (QALYs). RESULTS:For a 60-year-old patient with mild comorbidities and a pancreatic head BD-IPMN, immediate surgery provided 16.8 QALYs versus 16.3 with surveillance (incremental gain, 0.5 QALYs). Lifetime cancer probability was lower with surgery (24.5% vs 33.5%), as was cancer-related mortality (9.3% vs 20.3%), though surgery resulted in more resections for low-grade dysplasia (55.0% vs 15.3%). Age, baseline cancer probability, and perioperative mortality were the strongest determinants of the preferred strategy. CONCLUSIONS:Among patients with BD-IPMNs being considered for surgery, immediate resection offers a modest benefit for younger, healthier individuals, whereas surveillance remains appropriate for older or comorbid patients. These findings support individualized, risk-based management rather than universal application of guideline thresholds.

BACKGROUND:Management of intraductal papillary mucinous neoplasms (IPMNs) requires choosing between surgical resection and active surveillance, yet current diagnostic tools cannot reliably distinguish which lesions harbor high-grade dysplasia or invasive cancer. As a result, many patients undergo major pancreatic surgery for low-grade disease, while others are observed until progression emerges. This uncertainty contributes to substantial variation in surgeon risk estimates, intervention thresholds, and treatment recommendations. Patients likewise differ in their tolerance for cancer risk, views on surgical morbidity, perceived burden of ongoing surveillance, and desired role in decision-making, making IPMN a distinctly preference-sensitive clinical scenario. Although recent international guidelines acknowledge the importance of incorporating patient values into management decisions, practical frameworks for doing so remain underdeveloped. METHODS:We performed a narrative review of the literature examining sources of uncertainty in IPMN management, variation in surgeon and patient risk perception, and existing approaches to shared decision-making (SDM) in preference-sensitive surgical decisions. We also evaluated communication strategies and decision-support tools relevant to improving decision quality in the setting of uncertain malignant potential. RESULTS:Evidence demonstrates substantial heterogeneity in both clinician and patient interpretation of malignancy risk, operative morbidity, and acceptable thresholds for surgical intervention. Surgeons and patients often weigh competing risks diff erently, contributing to variation in management recommendations even when clinical characteristics are similar. SDM provides a structured approach to integrating individualized malignancy risk estimates, discussion of treatment trade-off s, and elicitation of patient values. Conceptual frameworks and emerging decision-support tools suggest that SDM may improve calibration of risk perception, reduce unwarranted variation in care, and enhance alignment between treatment decisions and patient preferences. CONCLUSIONS:IPMN management represents a high-stakes clinical decision made under conditions of incomplete information. SDM off ers a pragmatic strategy to integrate clinical evidence with patient values when choosing between resection and surveillance. Incorporating SDM into routine IPMN care may improve decision quality, promote transparency in risk communication, and support more patient-centered recommendations while preserving clinical judgment.

BACKGROUND:The 2024 Kyoto guidelines for the management of intraductal mucinous neoplasms (IPMNs) build on previous guidelines that consider worrisome features (WF) and high-risk stigmata (HRS) to recommend surveillance or resection. These new guidelines have not yet been validated. METHODS:Patients undergoing pancreatectomy for an IPMN at an academic medical center between 2012 and 2023 were included. IPMNs were categorized as low-grade dysplasia (LGD), high-grade dysplasia (HGD), or invasive carcinoma (IC). Preoperative imaging was used to determine HRS and WF in accordance with the 2024 Kyoto guidelines. We compared IPMNs with LGD to those with HGD or IC using univariate analyses and evaluated logistic regression models with c-statistics. RESULTS:Of 211 patients, 84 (40%) had LGD, 49 (23%) had HGD, and 78 (37%) had IC. Among HRS, obstructive jaundice (p = 0.004), pancreatic duct ≥ 10 mm (p < 0.001), and suspicious or positive cytology (p < 0.001) were significantly associated with HGD/IC. An increasing number of HRS were associated with higher rates of HGD/IC. Among WFs, an abrupt change in the caliber of pancreatic duct with distal pancreatic atrophy (p = 0.001) and cystic growth ≥ 2.5 mm/year (p = 0.033) were significantly associated with higher rates of HGD/IC. Increasing numbers of WFs were also associated with higher rates of HGD/IC. The 2024 Kyoto model showed improved discrimination (area under the curve [AUC] = 0.849) compared with the 2017 Fukuoka model (AUC=0.780, p = 0.06). CONCLUSION/CONCLUSIONS:The risk of HGD/IC in IPMNs increased in a stepwise fashion as the number of WFs increased. The 2024 guidelines represent an advancement over the 2017 guidelines, notably with the inclusion of suspicious cytology as an HRS.