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: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.

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.

INTRODUCTION/BACKGROUND:The influence of baseline health-related quality of life (HRQoL) on peri-operative outcomes in pancreatobiliary (PB) patients is not well established. This study investigated the impact of baseline HRQoL on peri-operative outcomes and the effect of surgery on HRQoL. METHODS:A secondary post-hoc analysis of a multicenter trial (2011-2016) assessed PB patients undergoing pancreatectomy. Pre-operative and 30-day post-operative FACT-G surveys were analyzed. Logistic regressions determined associations between baseline HRQoL scores and 60-day major complications. Subgroup analysis evaluated change in HRQoL (pre-operative to 30-day scores). RESULTS:Among 391 patients, higher baseline HRQoL (FACT-G overall OR 0.54,p ​= ​0.04) was associated with decreased likelihood of developing major complications. Surgery resulted in improvement in HRQoL for patients with chronic pancreatitis (10.2 points) compared to other pathologies (-7 to 3.9 points). CONCLUSION/CONCLUSIONS:Baseline HRQoL was associated with post-operative complications and HRQoL significantly improved for patients with chronic pancreatitis, highlighting the importance of HRQoL on patient-centered outcomes.

SUMMARY OF BACKGROUND DATA/BACKGROUND:Intraductal papillary mucinous neoplasm (IPMN)-derived pancreatic cancer is typically managed like pancreatic intraepithelial neoplasia (PanIN)-derived pancreatic cancer. However, in IPMN-derived pancreatic cancer, the role of chemotherapy remains controversial, particularly in the neoadjuvant setting (NAT). OBJECTIVE:To evaluate the role of neoadjuvant chemotherapy in IPMN-derived pancreatic cancer. METHODS:Patients with IPMN-derived pancreatic cancer treated with either upfront surgery (US) or NAT were identified from eight international centers (2000-2023). Clinicopathologic data were compared. Date of first treatment was used for Kaplan-Meier and log-rank tests to compare overall (OS) and recurrence free survival (RFS). Multivariable Cox-regression was performed in patients that underwent NAT. RESULTS:In 1,019 patients, 76 (7%) underwent NAT. Patients who received NAT had higher baseline CA19-9 levels (P<0.001). Of these 76 patients, 27 (36%), 20 (26%), and 29 (38%) had resectable, borderline resectable, or locally advanced pancreatic cancer at diagnosis, respectively. Advanced resectability stage was significantly more common in the NAT patients as compared to those who underwent US (P<0.001). OS for US patients was 38.0 months (95%CI: 33.7.1-44.3), which was not statistically different than those that received NAT [27.5 mo (95%CI: 23.1-46.7), P=0.121]. This was also valid for patients with resectable disease [US: 38.1 mo vs. NAT: 35.6 mo, P=0.920)]. Complete or marked pathological treatment response (P=0.046) and serological CA19-9 normalization after NAT (P=0.017) were associated with improved survival. On Cox-regression for OS, N2 disease [HR: 4.15 (95%CI: 1.71-10.10)], elevated CA19-9 [HR: 2.02 (95%CI:1.06-3.85)] and R1 margin [HR: 2.36 (95%CI:1.20-4.61)] was independently associated with OS after NAT, while resectability status was not. CONCLUSION/CONCLUSIONS:After NAT and resection, advanced resectability stage was not associated with worse OS indicating the value of this approach for borderline resectable and locally advanced IPMN-derived pancreatic cancer. The benefit of NAT in resectable disease is unclear and may require an individualized approach. Biological treatment effect can be assessed with CA19-9 and confirmed by pathologic response.