Faculty Bibliography

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.

Currently, no consensus exists regarding the definition of oligometastatic pancreatic ductal adenocarcinoma, its necessary diagnostic measures, and potential treatment approaches. To address these knowledge gaps, the OligoPanc project brought together an interdisciplinary group of experts to establish consensus using a modified Delphi process and clinical vignettes. Participants agreed that the number of metastatic lesions and the number of affected organs are key elements in defining oligometastatic pancreatic ductal adenocarcinoma. Specifically, up to three lesions in a single organ, either the liver or the lung, define oligometastatic pancreatic ductal adenocarcinoma and could be either synchronous or metachronous. Necessary diagnostics include a triple-phase contrast-enhanced CT scan of the chest and abdomen and MRI of the liver with a hepatocyte-specific contrast agent. In unclear cases, [¹⁸F]fluorodeoxyglucose-PET CT or MRI can be considered. A multidisciplinary tumour board is essential. Patient-intrinsic factors, including age, do not define oligometastatic disease but should be considered for any treatment decision. Systemic treatment before any local consolidative treatment, including surgery, stereotactic ablative radiotherapy, or other locally ablative techniques, is mandatory. The proposed definition should be incorporated into future trials to improve comparability and enable validation.

OBJECTIVE:The International Study Group of Pancreatic Surgery (ISGPS) aimed to uniform the definition and classification of mortality following pancreatic resections, to guide strategies for reducing preventable deaths and standardize reporting. BACKGROUND:Reported rates of mortality after pancreatic surgery vary widely depending on patient comorbidities, case mix, and institutional expertise and resources. Conventional reporting lacks granularity and fails to capture the mechanisms leading to death. A standardized classification rooted in causal analysis may provide a more meaningful framework to appraise outcomes and design targeted interventions. METHODS:A systematic review of the literature, focusing on mortality rates, causes of death, and existing classification systems after pancreatectomy was conducted. A consensus definition and tripartite classification were developed through iterative discussions, revisions, and final approval by the ISGPS board members. RESULTS:Postpancreatectomy mortality (PPM) was defined as death occurring within 90 days of any pancreatic resection, directly or indirectly attributable to a surgical complication and retrospectively linked to it through root-cause analysis. Three categories were established: PPM 1, vascular/technical complexity-related mortality (15-30%); PPM 2, pancreatectomy-specific complication-related deaths, mainly due to postoperative pancreatic fistula (POPF) and secondary systemic deterioration (45-65%); and PPM 3, cardiopulmonary and cerebrovascular deaths (10-25%). Each category reflects distinct mechanisms, timing of onset, intervention windows, and opportunities for rescue. DISCUSSION/CONCLUSIONS:The proposed ISGPS classification of mortality enables the development of targeted strategies to reduce potentially preventable deaths and provides a more robust framework for the appraisal and benchmarking of surgical outcomes. Prospective validation is warranted to standardize this newly defined quality metric, ensuring its consistent use in future reporting and ultimately enhancing surgical quality and patient safety on a global scale.

OBJECTIVE:We aimed to better understand patients' treatment preferences and quantify the level of cancer risk at which treatment preferences change (risk threshold) to inform better counseling of patients with intraductal papillary mucinous neoplasms (IPMNs). SUMMARY BACKGROUND DATA/BACKGROUND:The complexity of IPMN management provides an opportunity to align treatment with individual preference. METHODS:We surveyed a sample of healthy volunteers simulating a common scenario: undergoing an imaging study that incidentally identifies an IPMN. In the scenario, the estimated risk of cancer in the IPMN was 5%. Patients were asked their treatment preference (surgery or surveillance), to quantify the level of cancer risk in the IPMN at which their treatment preference would change (i.e. risk threshold), and their level of cancer anxiety as measured on a 5-point Likert scale. We examined associations between participant characteristics, treatment preferences, and risk threshold using multivariable linear regression. RESULTS:The median risk threshold among the 520 participants was 25% (IQR 2.3-50%). The risk threshold had a bimodal distribution: 40% of participants had a risk threshold between 0-10% and 47% had a risk threshold above 30%. When informed that the risk of cancer was 5%, 62% of participants (n=323) preferred surveillance, and the remaining 38% (n=197) preferred surgery. After adjusting for potential confounders, participants who expressed "worry" or "extreme worry" about the malignancy risk of IPMN had significantly lower risk thresholds than participants who were "not at all worried" (Coefficient -12, 95%CI -21 to -2, P=0.015 and Coefficient -18, 95%CI -29 to -8, P<0.001, respectively). CONCLUSIONS:Participants varied in treatment preference and risk threshold of incidentally identified IPMNs. Given the uncertainty in estimating the true malignant potential of IPMNs, a better understanding of a patient's risk threshold, as influenced by patient concern about malignancy, will help inform the shared decision-making process.

BACKGROUND/PURPOSE/OBJECTIVE:Intraductal papillary mucinous neoplasms (IPMNs) progress from low-grade dysplasia to high-grade dysplasia (HGD) or invasive carcinoma (IC). High diagnostic accuracy is critical for surgical decision-making. METHODS:We searched Medline, Embase, and Cochrane Library from January 1, 2015, to January 27, 2025. Eligible studies reported on resected IPMNs, assessing diagnostic features for HGD/IC. Two reviewers screened articles, extracted data, and assessed bias using the Newcastle-Ottawa scale. Descriptive statistics summarized outcomes. The performance of worrisome features (WFs) and high-risk stigmata (HRS) based on International Association of Pancreatology guidelines were evaluated. RESULTS:In the 53 studies, 12 953 patients were included. HRS including obstructive jaundice and enhancing mural nodules ≥5mm showed robust specificity for HGD/IC, while main pancreatic duct size ≥10mm showed variable diagnostic accuracy. WFs such as cyst size ≥3 cm performed poorly, while cyst growth rate >3.5 mm/year demonstrated higher sensitivity (88%) and specificity (91%). Although rare, abrupt caliber change with distal atrophy was a robust predictor of malignancy (median odds ratio: 3.01). Acute pancreatitis and lymphadenopathy displayed variable value. Incremental improvement in diagnostic accuracy was observed with additional HRS or WFs. CONCLUSIONS:Current diagnostic markers are valuable but provide limited guidance for surgical decision-making in IPMNs, highlighting the need for further refinement of diagnostic tools.

AIM/OBJECTIVE:To evaluate whether transitional circulating tumor cells (trCTCs) predict systemic recurrence of pancreatic ductal adenocarcinoma (PDAC) and assess their potential role in risk stratification for systemic treatment. BACKGROUND:The high metastatic potential of PDAC is believed to be associated with early dissemination after cancer cell reprogramming via an epithelial-to-mesenchymal transition. These cells are detectable in circulation as trCTCs and could serve as valuable biomarker capturing systemic disease involvement. METHODS:The prospective CLUSTER trial enrolled patients scheduled for PDAC resection (2016-2018). Pre- and postoperative CTCs were isolated with the Isolation-by-SizE-of-Tumor-Cells device and characterized by immunofluorescence. Cox regression with spline terms assessed associations between preoperative biomarkers and systemic recurrence, while multivariable subgroup analyses with interaction tests evaluated overall survival (OS) stratified by adjuvant chemotherapy. RESULTS:In preoperative samples, trCTCs were detected in 82 (67%) of 123 patients with a median number of two cells per ml (IQR 1-3). A linear association between preoperative trCTC counts and systemic recurrence (χ²=13.2, P=0.004) was observed, but no relevant correlation with CA19-9 levels was found (Pearson correlation=0.05, 95% CI:-0.13-0.23). Furthermore, trCTC-positivity after resection predicts recurrence and is associated with prolonged OS associated with adjuvant therapy (HR 0.21, 95%CI: 0.09-0.49) after adjustment for tumor stage and neoadjuvant chemotherapy. CONCLUSIONS:Preoperatively, higher trCTC counts are associated with increased risk of systemic recurrence, while postoperative presence reflects minimal residual disease. Integrating trCTC assessment alongside currently used biomarkers into the clinical pathway for patients with PDAC could enhance risk stratification and support more personalized treatment decisions.

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:Pancreatic cancer with early onset is increasing but comparisons with average onset cases have yielded mixed results (EOPC versus AOPC; age <50 versus ≥50). We compared clinicopathologic features, prognosis, and molecular traits of resected EOPC versus AOPC. METHODS:We retrospectively included patients with PDAC resected between 2010 and 2017 from The National Cancer Database (NCDB). Clinicopathologic data were compared across EOPC versus AOPC. Kaplan-Meier curves and cox-regression were used to perform survival analysis. Molecular features were compared using data from the cBioPortal. RESULTS:24,078 patients with resected PDAC were included, of whom 1698 (7.1 %) had EOPC. Poor prognostic factors, including high grade, advanced T-stage, and lymphovascular invasion, were less prevalent in EOPC (All p < 0.05). Patients with EOPC more frequently received neoadjuvant (28 % vs. 22 %; p < 0.001) and adjuvant chemotherapy (68 % vs. 58 %; p < 0.001) and experienced improved OS (median OS 29.5 vs 25.9 months, p = 0.023; 5-year OS: 26.9 % vs 20.8 %). No differences in the presence of key driver mutations were observed between the two groups but some distinct oncogenic mutations were observed in EOPC. CONCLUSION/CONCLUSIONS:EOPC and AOPC are clinically similar but some cases of EOPC may harbor divergent molecular changes. These patients may have only marginally improved survival.