Faculty Bibliography

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:Intraductal papillary mucinous neoplasms (IPMNs) are precursor lesions of pancreatic cancer with highly variable malignant potential. Current understanding of their biology remains incomplete, limiting accurate risk stratification and targeted interventions. OBJECTIVE:This study aimed to characterise the molecular and immune features of IPMN across different dysplasia grades and histological subtypes, with a focus on IPMN-associated invasive carcinoma (IPMN-IC). DESIGN/METHODS:Spatial whole-transcriptome profiling using Digital Spatial Profiling was conducted on 12 patients, capturing the full histological and dysplastic spectrum of IPMN and conventional pancreatic ductal adenocarcinoma. A total of 117 epithelial, immune and stromal areas of interest were analysed. An expanded cohort of 43 patients with IPMN was used to validate selected key markers. RESULTS:Transcriptomic analysis unveiled stage-specific molecular alterations and identified two distinct subsets of high-grade (HG) IPMN lesions: one resembling indolent lesions (HG) and the other IC (HG+). Key markers associated with divergent biological behaviours were identified, including MUC5AC and TFF1 in indolent lesions, and Claudin-1 in lesions with invasive potential. Immune profiling revealed a trajectory from activation to suppression during IPMN progression. Several characteristic immune checkpoint molecules, including CEACAM1 and CD44, were identified in IPMN-IC. CONCLUSION/CONCLUSIONS:This study provides a spatially resolved molecular map of IPMN progression, delineating key transcriptomic and immune signatures. These findings advance the understanding of IPMN biology and highlight potential biomarkers for risk stratification and therapeutic strategies.

BACKGROUND:Poor outcomes in pancreatic ductal adenocarcinoma (PDAC) are associated with delayed diagnosis and early systemic spread of disease. Development of liquid biopsies for screening could help detect low-stage disease in asymptomatic patients. We aimed to evaluate the association between incidental diagnosis on outcomes and assess the potential role of liquid biopsies. STUDY DESIGN/METHODS:An institutional registry was used to identify patients undergoing resection for PDAC at between 2010 and 2015. Patients were stratified based on presenting symptoms, and outcomes were analyzed. Preoperatively collected plasma that was available on these patients was analyzed using a multianalyte screening test based on ctDNA and proteins. RESULTS:Seventy-nine (9.6%) of 823 patients were diagnosed incidentally (asymptomatic at diagnosis). Incidental diagnosis was associated with type of surgery, and absence of nodal disease and lymphovascular invasion (all P<0.05). On multivariable analysis incidental diagnosis (HR, 0.561; 95%CI, 0.406-0.775; P<0.001) was independently associated with improved overall survival (OS), while tumor size ≥4cm (HR, 1.617; 95%CI, 1.201-2.176; P=0.002), nodal disease (HR, 1.259; 95%CI, 1.018-1.558; P=0.034), perineural invasion (HR,1.338; 95%CI, 1.030-1.739; P=0.029), and positive margins (HR,1.302; 95%CI, 1.058-1.602; P=0.013) were associated with poorer OS. Asymptomatic patients had a significantly longer OS (median-OS: 38 vs. 19 months (P<0.001). The rate of multianalyte test positivity was 75% (6/8) in asymptomatic patients compared to 73% (59/81) in symptomatic patients (P=0.895). CONCLUSION/CONCLUSIONS:Approximately 10% of patients with PDAC are diagnosed incidentally. In resected PDAC, incidental diagnosis is independently associated with improved OS. Multianalyte screening tests perform equally well in asymptomatic and symptomatic patients. These findings further reinforce the need for development of screening tools that can increase the rate of diagnosis at an asymptomatic stage and improve survival.

BACKGROUND:Indocyanine green fluorescence imaging can be used for intraoperative assessment of pancreatic stump perfusion with the aim to guide strategies to prevent postoperative pancreatic fistula in pancreatic surgery. The impact of indocyanine green in this setting is unknown since a systematic review is lacking. This review aimed to assess the relationship between indocyanine green fluorescence imaging of pancreatic stump perfusion and the risk of clinically relevant postoperative pancreatic fistula after pancreatic surgery. METHODS:A systematic literature search and meta-analysis were conducted, including studies published up to June 2025 that reported postoperative pancreatic fistula rate after pancreatic resection in relation to intraoperative pancreatic stump perfusion assessed by intraoperative indocyanine green fluorescence imaging. Hypoperfusion was defined as a heterogeneous or completely absent signal. Primary outcome was postoperative pancreatic fistula of which only grade B/C were included. Secondary outcome was postpancreatectomy acute pancreatitis. RESULTS:All 3 studies included analyzed patients who underwent pancreatoduodenectomy, comprising a total of 100 patients, with 18 (18%) presenting pancreatic stump hypoperfusion. No studies analyzing left pancreatectomy were identified, whereas only 1 paper analyzed the association between pancreatic hypoperfusion and postpancreatectomy acute pancreatitis. In that study, no patients developed postpancreatectomy acute pancreatitis after revision of the transection line initially found to be hypoperfused. The overall rate of postoperative pancreatic fistula was 13%. After robotic pancreatoduodenectomy (n = 27), stump hypoperfusion was associated with postoperative pancreatic fistula (67% vs 17%; P = .026), compared to the normally perfused group. No significant association of hypoperfusion and postoperative pancreatic fistula was observed after open pancreatoduodenectomy (n = 73). Meta-analysis confirmed the association of stump hypoperfusion with postoperative pancreatic fistula (odds ratio, 8.83; 95% confidence interval, 2.21-35.23; P = .005). CONCLUSION/CONCLUSIONS:A hypoperfused pancreatic stump, assessed intraoperatively using indocyanine green fluorescence imaging, appears to be associated with postoperative pancreatic fistula after pancreatoduodenectomy. Further research is needed to confirm these results in left pancreatectomy and develop a standardized indocyanine green protocol for pancreatic surgery.

BACKGROUND:Prognostic factors in resected pancreatic ductal adenocarcinoma (PDAC) have been determined under the assumption that hazard ratios (HRs) remain static. However, PDAC is a dynamic disease with evolving conditional survival. The aim of this study was to determine if the impact of prognostic factors in PDAC is time-varying. METHODS:This was a multicenter, retrospective cohort study of the prospectively maintained Dutch Pancreatic Cancer Recurrence Database and New York University and Johns Hopkins Hospital Institutional Databases. Patients with complete macroscopic resection of histopathologically proven PDAC between 2014 and 2019 and available follow-up data were included. The time-varying impact of prognostic factors identified by univariable Cox regression was modeled using Aalen's Additive Regression Models (Aalen's models) and visualized as plots of cumulative hazard. RESULTS:In total, 3104 patients were included, of whom 938 (30.2%) received neoadjuvant therapy (NAT), whereas the rest underwent upfront surgery (US). A total of 201 (6.5%) patients achieved observed long-term survival (>5 years). Aalen's models showed that lymphovascular invasion, perineural invasion, and nodal disease were prognostic up to 2 years postoperatively. At varying points thereafter, these variables lost their impact in the NAT but not US patients. Similarly, during the fourth year of follow-up, American Society of Anesthesiology scores became impactful in the NAT but not in the US patients. CONCLUSION/CONCLUSIONS:The impact of prognostic factors in resected PDAC across NAT and US patients is time-varying. Our results suggest that aggressive disease drives early mortality but, after NAT, tumor-biological factors lose prognostic importance to frailty and comorbidities over time.

PURPOSE/OBJECTIVE:Histotripsy is a non-invasive ultrasound-based tumor ablation modality. This study aims to describe the preliminary safety and short-term imaging findings related to histotripsy of liver metastases. MATERIALS AND METHODS/METHODS:All patients who underwent histotripsy for liver metastases from February 2024 to January 2025 at a single center were retrospectively reviewed. Demographic, clinical, imaging, procedural, and adverse event data were collected via chart review. Immediate post-treatment ablation zones were measured on CT and compared to pretreatment tumor size and treatment cavity size on follow-up imaging. Untreated tumors were assessed using revised RECIST criteria to evaluate for off-target effects. RESULTS:Histotripsy was performed on 56 metastatic liver tumors (most common: 32% colorectal, 18% breast) in 26 patients (54% female, age 59.1 ± 15.6y). All patients were discharged within 36 h. Immediate post-procedural ablation zones (36.6 + 13.1 mm) were larger compared to pretreatment tumors (30.5 + 18.5 mm) (p = 0.0013). One-month ablation zones (31.5 + 16.7 mm) were smaller compared to immediate post-procedural ablation zones (p = 0.00064). Two patients experienced off-target effects in non-treated liver tumors following histotripsy while off cytotoxic therapy. One patient experienced a Grade 3 complication of bacteremia requiring prolonged inpatient admission. No deaths occurred within 30 days. CONCLUSION/CONCLUSIONS:Histotripsy demonstrates a favorable safety profile for liver metastases. Observed off-target effects in untreated lesions suggest systemic immunomodulatory responses. Further investigation is warranted to elucidate patient-specific factors (e.g., tumor biology, concurrent therapies) that optimize systemic immune activation. Larger prospective studies with longitudinal immune profiling are needed to validate histotripsy's potential dual role as a locoregional therapy and immune primer in metastatic liver disease. LEVEL OF EVIDENCE/METHODS:Level 2b, retrospective cohort study.

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.

This manuscript describes the evolution in the operative management of pancreatic cancer. Early attempts at pancreatic resection were met with daunting peri‑operative outcomes but were fine-tuned to yield today's established pancreatic resections. Advances in medical therapy, including neo-adjuvant therapy for borderline resectable pancreatic cancers and refined adjuvant regimens, have improved oncologic outcomes and are allowing surgeons to move beyond current anatomic distinctions of resectability. Venous, hepatic artery and celiac axis resection during pancreatectomy are now common vascular operations at specialty centers which have been associated with favorable oncologic outcomes. Recent efforts are addressing locally advanced pancreatic cancer with superior mesenteric artery and/or multivessel involvement using either arterial divestment or arterial resection and reconstruction. An additional consideration in the treatment of pancreatic cancer is the benefit and risks of neoadjuvant radiation in locally advanced cases which has been avoided thus far given concerns regarding the effect of radiation on the vasculature. Therefore, with these improvements in peri‑operative therapy and robust preoperative planning often with the aid of vascular and microvascular surgeons, several centers have been exploring new frontiers in the operative management of locally advanced pancreatic adenocarcinoma.