Pancreatic Cancer Patient-derived Organoids Can Predict Response to Neoadjuvant Chemotherapy.

OBJECTIVE: To evaluate if patient-derived organoids (PDOs) may predict response to neoadjuvant (NAT) chemotherapy in patients with pancreatic adenocarcinoma. BACKGROUND: PDOs have been explored as a biomarker of therapy response and for personalized therapeutics in patients with pancreatic cancer. METHODS: During 2017-2021, patients were enrolled into an IRB-approved protocol and PDO cultures were established. PDOs of interest were analyzed through a translational pipeline incorporating molecular profiling and drug sensitivity testing. RESULTS: One hundred thirty-six samples, including both surgical resections and fine needle aspiration/biopsy from 117 patients with pancreatic cancer were collected. This biobank included diversity in stage, sex, age, and race, with minority populations representing 1/3 of collected cases (16% Black, 9% Asian, 7% Hispanic/Latino). Among surgical specimens, PDO generation was successful in 71% (15 of 21) of patients who had received NAT prior to sample collection and in 76% (39 of 51) of patients who were untreated with chemotherapy or radiation at the time of collection. Pathological response to NAT correlated with PDO chemotherapy response, particularly oxaliplatin. We demonstrated the feasibility of a rapid PDO drug screen and generated data within 7 days of tissue resection. CONCLUSION: Herein we report a large single-institution organoid biobank, including ethnic minority samples. The ability to establish PDOs from chemotherapy-naive and post-NAT tissue enables longitudinal PDO generation to assess dynamic chemotherapy sensitivity profiling. PDOs can be rapidly screened and further development of rapid screening may aid in the initial stratification of patients to the most active NAT regimen.

Impact of postoperative pancreatic fistula on outcomes in pancreatoduodenectomy: a comprehensive analysis of American College of Surgeons National Surgical Quality Improvement Program data.

BACKGROUND: Pancreatoduodenectomy (PD) is a major surgical procedure associated with significant risks, particularly postoperative pancreatic fistula (POPF). Studies have highlighted the importance of certain risk factors for POPF, which are crucial for surgical decision-making and the management of high-risk patients undergoing PD. This study aimed to assess the surgical outcomes of patients undergoing PD who met the International Study Group of Pancreatic Surgery - Class D (ISGPS-D) criteria. METHODS: This study analyzed American College of Surgeons National Surgical Quality Improvement Program data (2014-2021) for patients undergoing ISGPS-D PD, classified as having a soft pancreatic texture and a pancreatic duct of ≤3 mm. This study focused on mortality rates and the correlation between several factors and POPF (ISGPS grade B/C). RESULTS: From 5964 patients who underwent PD and met the ISGPS-D criteria, the 30-day mortality rate was 1.98%. Males had a higher incidence of POPF than females (57.42% vs 47.35%, respectively; P < .001). Patients with POPF experienced significantly higher rates of major postoperative complications (Clavien-Dindo grade ≥ IIIa), including thrombosis, pneumonia, sepsis, delayed gastric emptying, wound disruption, infections, and acute renal failure. There was a marked increase in the 30-day readmission and mortality rates in patients with POPF (30.0% vs 17.6% and 3.2% vs 1.4%, respectively; all P < .001). Multivariate analysis highlighted female sex as a protective factor against mortality (odds ratio [OR], 0.47; P < .001) and extended hospital stay (>10 days) as a predictor of increased mortality risk (OR, 2.37; P < .001). CONCLUSION: This study underscored the significant association between POPF and increased postoperative morbidity and mortality rates. Future efforts should concentrate on refining surgical techniques and improving preoperative assessments to mitigate the risks associated with POPF in patients undergoing PD.