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: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.

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.

BACKGROUND:Pancreatic cancer is a challenging malignancy with an aggressive biology and limited treatment options, contributing to low survival rates. Supportive and palliative care play a key role in improving the quality of life and psychological distress for patients and their families. However, appropriate delivery and effectiveness of these interventions may be influenced by social determinants of health (SDOH). These factors create significant barriers for patients, influencing their access to care and ability to make informed decisions. This review explores the role of SDOH in supportive and palliative care of pancreatic cancer patients and identifies areas for improvement to enhance this type of care for vulnerable populations. METHODS:A thorough narrative review was carried out to evaluate the influence of social determinants of health on supportive and palliative care in the management of pancreatic cancer, focusing on symptom management, psychosocial support, nutritional support, advance care planning, rehabilitation, functional support, and care coordination. RESULTS:This review demonstrates that disparities exist. Black and Asian patients receive less pain medications; those with lower level of education struggle to access psychological support; Hispanic and Black patients often do not receive needed nutritional care; and end-of-life planning is less common among non-White and less-educated patients. CONCLUSIONS:SDOH significantly affects the experience and delivery of supportive and palliative care in pancreatic cancer patients, exacerbating inequities across multiple domains of care. Addressing these disparities requires coordinated efforts at clinical, organizational, and policy levels to ensure equitable access to care for all patients in their final phase of life. Integrating attention to SODH into care delivery models can improve outcomes and enhance quality of life for these patients.

BACKGROUND:Intraductal papillary mucinous neoplasm (IPMN)-derived pancreatic cancer was previously categorized into tubular, colloid, and oncocytic subtypes. Intraductal oncocytic papillary neoplasms (IOPN) has long been associated with superior prognosis/indolent behavior, however, there is discordant emerging evidence. This study aimed to investigate this conflicting literature. METHODS:Patients with resected IOPN-derived and IPMN-derived pancreatic cancer were identified from six international centers. Log-rank tests compared time to (TtR) and survival after (SAR) recurrence and five-year overall survival (OS). A multivariable mixed model was used to determine hazard ratios (HR) with confidence intervals (95%CI) for five-year survival. RESULTS:Of 879 patients, 20 (2%) had IOPN-derived pancreatic cancer. Most patients had T1 (55%) or N0 (70%) disease. IOPN and colloid IPMN-derived pancreatic cancers had similar recurrence rates (25% vs. 24%), while recurrence was more common in tubular IPMN-derived pancreatic cancer (42%, p < 0.001). IOPN-derived pancreatic cancer displayed a longer TtR and SAR compared to colloid and tubular IPMN-derived pancreatic cancers. IOPN-derived and colloid IPMN-derived cancers demonstrated significantly lower 5-year mortality risks compared to tubular IPMN-derived cancers (74% and 27% risk reduction, respectively; p < 0.05). CONCLUSION/CONCLUSIONS:IOPN-derived pancreatic cancers have excellent OS. However, some patients have poor prognostic factors and are at risk for both local and systemic recurrence. Given more indolent disease progression given delayed TtR and prolonged SAR compared to colloid and tubular IPMN-derived pancreatic cancers, there may be a role for prolonged surveillance.

BACKGROUND:Antithrombotic therapy (AT) aims to strike a balance between preventing thromboembolic and hemorrhagic complications. However, evidence for AT management after pancreatectomy with vascular reconstruction is lacking. We aimed to provide an overview of the current use of AT for pancreatic surgery with vascular reconstructions. PATIENTS AND METHODS/METHODS:A web-based survey was distributed to 123 surgeons from high-volume pancreas centers (>50 pancreatic resections/year). AT management after different types of vascular reconstruction were investigated. An "aggressive" protocol was defined as the use of any AT protocol other than prophylactic heparin, aspirin, or their combination. RESULTS:The survey was completed by 80 surgeons (59% Europe, 30% USA, 11% Asia). In Europe/Asia, prophylactic heparin was the most commonly reported protocol after partial venous resection/end-to-end anastomosis/human graft (71%/65%/50%, respectively), and an "aggressive" protocol (86%) was the most frequently used after prosthetic graft reconstruction. Conversely, in the USA, prophylactic heparin + aspirin was the most commonly reported protocol after all types of venous reconstruction. Following arterial reconstruction, heparin + aspirin was the most commonly reported protocol, regardless of region. An "aggressive" protocol was more frequently used in Europe/Asia (odds ratio (OR) 1.28; p < 0.001) and following vein reconstruction with either human graft (OR 1.2; p = 0.007) or prosthetic graft (OR 1.56, p <0.001), while ultrasound (OR 1.65; p < 0.001) and arterial reconstruction (OR 1.64; p < 0.001) were significantly associated with antiplatelet use. CONCLUSIONS:In an international cohort of high-volume pancreas surgeons, significant variation in the use of AT following pancreatectomy with vascular reconstruction was observed. This variation was driven by geographical differences and the type of vascular reconstructions performed. In an international cohort of high-volume pancreas surgeons, this Worldwide Snapshot Survey analyzed the current use of antithrombotic therapy for pancreatic surgery with vascular reconstruction. A significant heterogeneity in antithrombotic practice was found and it was mainly driven by geographical differences and the type of vascular reconstructions performed.