Faculty Bibliography

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.

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.

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.