Intracystic injection of large surface area microparticle paclitaxel for chemoablation of intraductal papillary mucinous neoplasms: Insights from an expanded access protocol.

Autor: Krishna SG; Division of Gastroenterology, Hepatology and Nutrition, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA. Electronic address: Somashekar.krishna@osumc.edu., Ardeshna DR; Division of Gastroenterology, Hepatology and Nutrition, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA., Shah ZK; Department of Radiology, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA., Hart PA; Division of Gastroenterology, Hepatology and Nutrition, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA., Culp S; Department of Biomedical Informatics, The Ohio State University College of Medicine, Columbus, OH, 43210, USA., Jones D; James Molecular Laboratory, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA; Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA., Chen W; Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA., Papachristou GI; Division of Gastroenterology, Hepatology and Nutrition, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA., Han S; Division of Gastroenterology, Hepatology and Nutrition, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA., Lee PJ; Division of Gastroenterology, Hepatology and Nutrition, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA., Shah H; Division of Gastroenterology, Hepatology and Nutrition, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA., Pawlik TM; Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA., Dillhoff M; Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA., Manilchuk A; Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA., Cloyd J JM; Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA., Ejaz A; Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA., Fry M; Division of Gastroenterology, Hepatology and Nutrition, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA., Noonan AM; Division of Medical Oncology, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA.
Jazyk: angličtina
Zdroj: Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] [Pancreatology] 2024 Mar; Vol. 24 (2), pp. 289-297. Date of Electronic Publication: 2024 Jan 11.
DOI: 10.1016/j.pan.2023.12.014
Abstrakt: Aims: A novel large surface area microparticle paclitaxel (LSAM-PTX) has unique properties of long retention in cystic spaces while maintaining high drug concentration. We prospectively evaluated the safety and response of EUS-guided fine needle injection (EUS-FNI) of LSAM-PTX to chemoablate branch duct (BD)-IPMNs.
Methods: Subjects diagnosed with BD-IPMNs exhibiting at least one worrisome criteria and considered non-surgical were enrolled in a multicenter clinical trial (NCT03188991) and subsequently included in an Expanded Access Protocol (EAP) where they received EUS-FNI of LSAM-PTX (15 mg/mL).
Results: Six BD-IPMNs measuring (mean ± SD) 3.18 ± 0.76 cm in diameter among 5 subjects (mean age: 66 years) were treated by EUS-FNI of LSAM-PTX. A mean of 4 doses of LSAM-PTX (mean dose/cyst: 73 ± 31 mg) were administered, and subjects were followed for up to 32 months. The mean volume reduction/cyst ranged from 42 to 89% (9.58 ± 5.1 ml to 2.2 ± 1.1 ml (p = 0.016)). The mean surface area reduction ranged from 31 to 83% (21.9 ± 8.7 cm 2 to 5.7 ± 2.5 cm 2 (p = 0.009)). Higher dosing-frequency of EUS-FNI of LSAM-PTX significantly correlated with a reduction in cyst volume (R 2  = 0.87, p = 0.03) and surface area (R 2  = 0.83, p = 0.04). Comparing pre- and post-ablation samples, molecular analysis of the cyst fluid revealed a loss of IPMN-associated mutations in 5 cases (83.3%), while reemergence was observed in 1 case and persistence in 1 case. Intracystic changes (fibrosis/calcification) were observed in 83.3% (n = 5). One subject developed mild acute pancreatitis (1 of 22 EUS-FNIs of LSAM-PTX).
Conclusion: In this EAP, EUS-FNI of LSAM-PTX into BD-IPMNs was safe and resulted in volume and surface area reduction, morphological changes, and loss of pathogenic mutations.
(Copyright © 2024 IAP and EPC. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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