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.

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.

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

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: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.

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.