Faculty Bibliography

BACKGROUND:Soft tissue sarcoma (STS) is a rare and heterogeneous malignancy with more than 100 histologic subtypes that can arise in virtually any part of the body. Although surgical resection is the standard of care, complete surgical resection is often limited by involvement of critical anatomy, and most subtypes are resistant to systemic therapies. Histotripsy uses microsecond length, high-pressure ultrasound (US) pulses delivered externally to generate cavitation inside the target tumor to mechanically liquefy tissue to acellular homogenate. This study tested the effect of histotripsy in a variety of soft tissue tumors (STTs) including benign tumors and sarcomas. METHODS:Histotripsy was delivered to 45 surgically excised ex vivo human samples with a custom 1 MHz 8-element US transducer guided by US imaging. RESULTS:Histotripsy was successful in creating an identifiable treatment effect across all subtypes including adipocytic tumors, benign myxoid and nerve sheath tumors, aggressive fibrous sarcomas, and high-grade sarcomas. Immediately after histotripsy, B-mode and shear-wave elastography US imaging was shown to effectively evaluate the treatment. Tissue structure heterogeneity among the tumor subtypes dictated the variation in histologic treatment effects. CONCLUSIONS:The data demonstrate effective US-guided histotripsy ablation on a robust cohort of ex vivo STTs. The variable treatment effects observed across tumor subtypes highlight the need for histotripsy parameter optimization, with support for its potential as a promising non-invasive treatment modality for sarcoma patients who currently have limited therapeutic options.

BACKGROUND:Although main duct (MD) and branch duct (BD) IPMNs differ in preoperative risk of malignant transformation, it remains unclear whether ductal subtype influences outcomes once invasive carcinoma develops and is resected. We compared recurrence and survival outcomes between these subtypes. METHODS:We identified patients with resected IPMN-derived pancreatic ductal adenocarcinoma (PDAC) from three institutions. Overall survival (OS) and recurrence-free survival (RFS) were estimated using Kaplan-Meier methods and compared with log-rank tests. Multivariable Cox regression models adjusted for age, T-stage, N-stage, histologic subtype, and adjuvant chemotherapy. RESULTS:Among 136 patients, 106 (78%) had MD-derived and 30 (22%) had BD-derived IPMN-associated PDAC. Median OS was 36.6 months and did not differ by subtype on log-rank (p = 0.472) or multivariable analysis (HR 0.45, 95% CI 0.15-1.31; p = 0.143). Median RFS was 41.8 months without significant difference by subtype on log-rank (p = 0.362) or adjusted analysis (HR 0.56, 95% CI 0.21-1.46; p = 0.234). CONCLUSIONS:In patients with resected IPMN-derived PDAC, ductal subtype was not significantly associated with OS. While clinically meaningful differences in RFS cannot be excluded, these findings suggest that once invasive cancer arises and is resected, ductal subtype alone may not provide additional prognostic information.

BACKGROUND:Some centres advocate preoperative radiotherapy in patients with pancreatic cancer and arterial involvement despite a lack of Level 1 evidence on survival benefit. Although it has been suggested that preoperative radiotherapy may increase the risk of postpancreatectomy haemorrhage (PPH) and morbidity, evidence is again lacking. This study investigated the association between preoperative radiotherapy and both PPH and major morbidity following arterial divestment/resection during pancreatic adenocarcinoma resection after chemotherapy. METHODS:Consecutive patients diagnosed with pancreatic adenocarcinoma and > 180° arterial involvement who were treated with preoperative chemotherapy with or without radiotherapy followed by pancreatic resection with arterial divestment/resection were included in the study. Logistic regression analyses including propensity score-based overlap weighting were performed to investigate associations between radiotherapy and in-hospital PPH grade B/C and major morbidity, expressed as adjusted risk differences (aRDs). RESULTS:Overall, 246 patients undergoing pancreatic resection with arterial resection (169, 69%) or divestment (77, 31%) were included. Radiotherapy was not associated with PPH (aRD 6%; 95% confidence interval (c.i.) -3 to 14), regardless of arterial divestment (aRD 3%; 95% c.i. -5 to 11) or arterial resection (aRD 12%; 95% c.i. 1 to 23; Pinteraction = 0.189). Radiotherapy was associated with a 14% (95% c.i. 2 to 25) higher risk of major morbidity, especially after arterial resection (aRD 27%; 95% c.i. 11 to 43) compared with arterial divestment (aRD -12%; 95% c.i. -35 to 11; Pinteraction = 0.006) and after external beam radiotherapy (aRD 21%; 95% c.i. 8 to 32) compared with stereotactic body radiotherapy (aRD -12%; 95% c.i. -27 to 6; Pinteraction = 0.0001). Ninety-day mortality was increased, albeit not significantly, after preoperative radiotherapy (10 (8%) versus 3 (3%) deaths with versus without preoperative radiotherapy, respectively; P = 0.067). CONCLUSIONS:Radiotherapy before resection of pancreatic cancer with > 180° arterial involvement was associated with an increased risk of postoperative major morbidity when arterial resection, but not arterial divestment, was performed. This risk should be taken into account when considering preoperative radiotherapy in patients who may require arterial resection.

Specialized clinical artificial intelligence (AI) tools are entering medical practice despite scarce independent evaluation. We quantitatively evaluate two clinical AI tools, OpenEvidence and UpToDate Expert AI, built on large language models (LLMs) against three frontier LLMs: GPT-5.2, Gemini 3.1 Pro and Claude Opus 4.6. Our evaluation has three stages: (1) 500 MedQA questions testing medical knowledge, (2) 500 HealthBench items measuring alignment with clinicians and (3) the real clinical queries (RCQ) benchmark, built from 100 de-identified queries from physicians to a general-purpose language model in a live clinical environment. For the RCQ benchmark, 12 US clinicians performed randomized, blinded review of model outputs, producing 1,800 model-question annotations. Frontier LLMs outperformed clinical AI tools in all three evaluations. Clinical AI tools performed comparably to auto-enabled Google Search AI Overview on the RCQ. These findings highlight the need for independent, real-world evaluation of AI tools before they enter clinical settings.

BACKGROUND:Robotic pancreaticoduodenectomy (RPD) is increasingly performed in the United States. Understanding factors associated with safe adoption of RPD is critical to reducing perioperative mortality during the learning curve. METHODS:Using the Epic Cosmos database, the study identified adult patients (age ≥18 years) who underwent pancreaticoduodenectomy (PD) between 2019 and 2025. Modified Poisson regression was used to assess factors associated with 30-day mortality using adjustment for age, sex, race, ethnicity, insurance, marital status, rural/urban residence, socioeconomic status, and diagnosis. Among surgeons performing two or more RPDs, mortality trends were analyzed across case-number thresholds. Mortality risk was assessed by cumulative RPD and open PD (OPD) experience, with adjustment for age and diagnosis. RESULTS:Among 23,995 patients with a median age of 69 years (interquartile range [IQR], 62-75 years), 1578 (6.6 %) underwent RPD. Use of RPD increased from 4% of PD in 2019 to 10% in 2025. The 30-day mortality was higher for RPD than for OPD (2.7 % vs 2.0 %; adjusted relative risks [aRR], 1.43 (IQR, 1.02-1.95; p = 0.029). In RPD, mortality decreased with increasing surgeon prior experience: 3.9 % (Q1: 0-1 cases), 3.9 % (Q2: 2-4 cases), 2.22 % (Q3: 5-8 cases), 2.67 % (Q4: 9-18 cases), 0.92 % (Q5: 19-71 cases). Increased RPD experience was associated with decreased mortality (per doubling RPD experience: aRR, 0.78 (95 % confidence interval [CI], 0.63-0.96; p = 0.02). The patients who underwent PD between 2023 and 2025 showed no adjusted increase in mortality with robotic technique (aRR, 1.04; 95 % CI, 0.61-1.65; p = 0.85). CONCLUSIONS:Nationwide, adoption of RPD is associated with increased 30-day mortality, which decreases substantially with increasing surgeon RPD experience. These findings suggest that structured, competency-based training pathways are needed to ensure safe dissemination of novel technology, including RPD.

BACKGROUND/UNASSIGNED:Histotripsy is a novel, non-invasive, non-ionising, non-thermal method of mechanical tumour disruption that received US FDA approval in October 2023 for the treatment of liver tumours. This study aims to summarise and evaluate the safety and outcomes data following histotripsy of primary and secondary liver tumours. METHODS/UNASSIGNED:statistic and Cochran's Q test. Publication bias was assessed using funnel plot visual inspection and Egger's regression test. Finally, the histotripsy technology was assessed using the IDEAL framework to inform the design of future trials. This work was registered with PROSPERO (CRD420261299804). FINDINGS/UNASSIGNED:= 6.6%). No significant publication bias was detected for mortality and safety outcomes; however, formal assessment of publication bias was limited by the small number of studies for these and all outcomes. All radiological control outcomes showed substantial heterogeneity across studies. INTERPRETATION/UNASSIGNED:Although there is notable heterogeneity across studies, pooled results indicate that histotripsy has high rates of technical feasibility and local control with a favourable side effect profile. Interpretation of these findings is limited by the small number of available studies, variability in outcome definitions and imaging assessment methods, and short follow-up durations. These results underscore the need for larger, prospectively designed studies with standardised reporting frameworks and longer follow-up to more precisely characterise the clinical, radiologic, and quantitative imaging outcomes following histotripsy. FUNDING/UNASSIGNED:None.

BACKGROUND:Accurate preoperative malignancy risk assessment in intraductal papillary mucinous neoplasm (IPMN) is essential to balance timely intervention for high-grade dysplasia or invasive cancer (HGD/IC) against avoiding unnecessary or premature surgery in low-grade IPMN. This study aimed to externally validate the 2023 International Association of Pancreatology (IAP)/Kyoto guidelines and develop a combined prediction model incorporating routinely collected clinical data and laboratory parameters. METHODS:We conducted a retrospective cohort study of 194 patients who underwent resection for IPMN between 2012 and 2024. We evaluated the predictive performance of the current IAP/Kyoto criteria ("Kyoto model"), developed a clinical model using routinely available laboratory and clinical variables, and integrated both into a combined model. Model performance was assessed using discrimination and calibration metrics, with internal validation via bootstrapping and five-fold cross-validation. RESULTS:The Kyoto model demonstrated modest discrimination (AUC 0.62). The clinical model, incorporating neutrophil-to-lymphocyte ratio (NLR), smoking history, blood glucose, CA19-9, and alkaline phosphatase, achieved an optimism-corrected AUC of 0.76. Compared to the Kyoto model, the combined model (AUC 0.77) significantly improved discrimination and calibration (p < 0.001). At a predicted probability threshold of >0.75, the combined model achieved a 90% specificity and 91% positive predictive value for HGD/IC, identifying a high-risk subgroup suitable for surgical intervention. CONCLUSIONS:Integrating routinely collected clinical and laboratory parameters with guideline-based imaging features shows promise to enhance preoperative identification of high-risk IPMN in patients already being considered for surgical resection. The combined model offers a practical, high-specificity tool to support surgical decision-making in this selected population, though its performance metrics should not be extrapolated to unselected surveillance cohorts. External validation is required before broader clinical implementation.

BACKGROUND:Pancreatic cancer with early onset is increasing but comparisons with average onset cases have yielded mixed results (EOPC versus AOPC; age <50 versus ≥50). We compared clinicopathologic features, prognosis, and molecular traits of resected EOPC versus AOPC. METHODS:We retrospectively included patients with PDAC resected between 2010 and 2017 from The National Cancer Database (NCDB). Clinicopathologic data were compared across EOPC versus AOPC. Kaplan-Meier curves and cox-regression were used to perform survival analysis. Molecular features were compared using data from the cBioPortal. RESULTS:24,078 patients with resected PDAC were included, of whom 1698 (7.1 %) had EOPC. Poor prognostic factors, including high grade, advanced T-stage, and lymphovascular invasion, were less prevalent in EOPC (All p < 0.05). Patients with EOPC more frequently received neoadjuvant (28 % vs. 22 %; p < 0.001) and adjuvant chemotherapy (68 % vs. 58 %; p < 0.001) and experienced improved OS (median OS 29.5 vs 25.9 months, p = 0.023; 5-year OS: 26.9 % vs 20.8 %). No differences in the presence of key driver mutations were observed between the two groups but some distinct oncogenic mutations were observed in EOPC. CONCLUSION/CONCLUSIONS:EOPC and AOPC are clinically similar but some cases of EOPC may harbor divergent molecular changes. These patients may have only marginally improved survival.