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.

With a rising annual incidence, pancreatic cancer is now the third leading cause of cancer-related mortality in American men and women [...].

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: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.

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.

AI is now a cornerstone of modern dataset analysis. In many real world applications, practitioners are concerned with controlling specific kinds of errors, rather than minimizing the overall number of errors. For example, biomedical screening assays may primarily be concerned with mitigating the number of false positives rather than false negatives. Quantifying uncertainty in AI-based predictions, and in particular those controlling specific kinds of errors, remains theoretically and practically challenging. We develop a strategy called multidimensional informed generalized hypothesis testing (MIGHT) which we prove accurately quantifies uncertainty and confidence given sufficient data, and concomitantly controls for particular error types. Our key insight was that it is possible to integrate canonical cross-validation and parametric calibration procedures within a nonparametric ensemble method. Simulations demonstrate that while typical AI based-approaches cannot be trusted to obtain the truth, MIGHT can be. We apply MIGHT to answer an open question in liquid biopsies using circulating cell-free DNA (ccfDNA) in individuals with or without cancer: Which biomarkers, or combinations thereof, can we trust? Performance estimates produced by MIGHT on ccfDNA data have coefficients of variation that are often orders of magnitude lower than other state of the art algorithms such as support vector machines, random forests, and Transformers, while often also achieving higher sensitivity. We find that combinations of variable sets often decrease rather than increase sensitivity over the optimal single variable set because some variable sets add more noise than signal. This work demonstrates the importance of quantifying uncertainty and confidence-with theoretical guarantees-for the interpretation of real-world data.

BACKGROUND:Pancreatic adenosquamous carcinoma has historically poor overall survival, and the impact of perioperative chemotherapy remains unclear. We aimed to evaluate the impact of various chemotherapy regimens in patients with resected adenosquamous carcinoma. METHODS:Patients with resected adenosquamous carcinoma were identified from 3 high-volume programs between 2001 and 2022. We analyzed their clinicopathologic data and used Kaplan-Meier survival curves to assess the median overall survival and recurrence-free survival with 95% confidence intervals. Prognostic factors were assessed with a multivariable Cox-regression model adjusting for resectability status and Clavien-Dindo complications. RESULTS:Among 168 patients, cohorts of neoadjuvant chemotherapy (41, 24%) and upfront surgery (127, 76%) showed similar demographics and TNM staging. The median overall survival was shorter in the neoadjuvant chemotherapy cohort compared with the upfront surgery cohort (13 vs 21 months, P = .133). Median overall survival by treatment approach was no chemotherapy (4 months), only neoadjuvant chemotherapy (8 months), only adjuvant therapy (24 months), and both neoadjuvant chemotherapy and adjuvant therapy (17 months). Recurrence-free survival data (69 patients) showed upfront surgery had significantly longer recurrence-free survival compared with neoadjuvant chemotherapy (18 months vs 5 months, P = .046). Multivariable analysis showed adjuvant therapy was associated with improved overall survival (hazard ratio, 0.27; P < .001), whereas age ≥65 (hazard ratio, 1.79, P = .030) was associated with worse overall survival. CONCLUSION/CONCLUSIONS:The outcomes of resected adenosquamous carcinoma remain poor. Patients receiving neoadjuvant chemotherapy exhibited shorter recurrence-free survival and median overall survival, suggesting minimal benefit of neoadjuvant chemotherapy in treating this aggressive cancer. Meanwhile, adjuvant therapy appears to be protective but requires further investigation.