Precursor Epithelial Subtypes of Adenocarcinoma Arising from Intraductal Papillary Mucinous Neoplasms (A-IPMN): Clinicopathological Features, Recurrence and Response to Adjuvant Chemotherapy
Authors: Lucocq James , Haugk Beate , Parkinson Daniel , Darne Antony , Joseph Nejo , Hawkyard Jake , White Steve , Mownah Omar , Menon Krishna , Furukawa Takaki , Inoue Yosuke , Hirose Yuki , Sasahira Naoki , Mittal Anubhav , Samra Jas , Sheen Amy , Feretis Michael , Balakrishnan Anita , Ceresa Carlo , Davidson Brian , Pande Rupaly , Dasari Bobby V. M. , Tanno Lulu , Karavias Dimitrios , Helliwell Jack , Young Alistair , Nunes Quentin , Urbonas Tomas , Silva Michael , Gordon-Weeks Alex , Barrie Jenifer , Gomez Dhanny , van Laarhoven Stijn , Nawara Hossam , Doyle Joseph , Bhogal Ricky , Harrison Ewen , Roalso Marcus , Ciprani Deborah , Aroori Somaiah , Ratnayake Bathiya , Koea Jonathan , Capurso Gabriele , Bellotti Ruben , Stättner Stefan , Alsaoudi Tareq , Bhardwaj Neil , Jeffery Fraser , Connor Saxon , Cameron Andrew , Jamieson Nigel , Roberts Keith , Soreide Kjetil , Gill Anthony J. , Pandanaboyana Sanjay 
Published: July 2024

Abstract
Background
The clinico-oncological outcomes of precursor epithelial subtypes of adenocarcinoma arising from intraductal papillary mucinous neoplasms (A-IPMN) are limited to small cohort studies. Differences in recurrence patterns and response to adjuvant chemotherapy between A-IPMN subtypes are unknown.

Methods
Clincopathological features, recurrence patterns and long-term outcomes of patients undergoing pancreatic resection (2010–2020) for A-IPMN were reported from 18 academic pancreatic centres worldwide. Precursor epithelial subtype groups were compared using uni- and multivariate analysis.

Results
In total, 297 patients were included (median age, 70 years; male, 78.9%), including 54 (18.2%) gastric, 111 (37.3%) pancreatobiliary, 80 (26.9%) intestinal and 52 (17.5%) mixed subtypes. Gastric, pancreaticobiliary and mixed subtypes had comparable clinicopathological features, yet the outcomes were significantly less favourable than the intestinal subtype. The median time to recurrence in gastric, pancreatobiliary, intestinal and mixed subtypes were 32, 30, 61 and 33 months. Gastric and pancreatobiliary subtypes had worse overall recurrence (p = 0.048 and p = 0.049, respectively) compared with the intestinal subtype but gastric and pancreatobiliary subtypes had comparable outcomes. Adjuvant chemotherapy was associated with improved survival in the pancreatobiliary subtype (p = 0.049) but not gastric (p = 0.992), intestinal (p = 0.852) or mixed subtypes (p = 0.723). In multivariate survival analysis, adjuvant chemotherapy was associated with a lower likelihood of death in pancreatobiliary subtype, albeit with borderline significance [hazard ratio (HR) 0.56; 95% confidence interval (CI) 0.31–1.01; p = 0.058].

Conclusions
Gastric, pancreatobiliary and mixed subtypes have comparable recurrence and survival outcomes, which are inferior to the more indolent intestinal subtype. Pancreatobiliary subtype may respond to adjuvant chemotherapy and further research is warranted to determine the most appropriate adjuvant chemotherapy regimens for each subtype.