Intraductal Papillary Mucinous Neoplasm-derived Pancreatic Cancer

Intraductal Papillary Mucinous Neoplasm (IPMN)-derived pancreatic ductal adenocarcinoma (PDAC) represents a distinct entity from pancreatic intraepithelial neoplasia (PanIN)-derived PDAC, necessitating specific clinical and research efforts. This is demonstrated by superior overall survival (OS) in IPMN-derived PDAC (median OS 43.1 months) compared to PanIN-derived PDAC (23.0 months, p<0.001), even after propensity-score matching, highlighting the need for tailored guidelines. This PhD thesis aims to bridge the knowledge gap by investigating IPMN-derived pancreatic cancer through multiple phases of care including: operative management, chemotherapy, and prognostication and staging.

In part II investigating operative management, an increased optimal lymph node yield (>20) appears to enhance survival and at least ten lymph nodes prevents nodal under staging. Regarding margin status in IPMN-derived pancreatic cancer, this thesis supports reresection of high-grade dysplasia or invasive cancer to improve outcomes, while low-grade dysplasia is similar to normal pancreatic parenchyma at the transected margin. Moreover, total pancreatectomy for multifocal IPMN in the setting of IPMN-derived pancreatic cancer only appears to benefit younger patients. Finally, a scoping review on intraoperative pancreatoscopy, supports its potential to detect skip lesions, thus refining surgical decision-making.

In part III, chemotherapy is explored. For neoadjuvant chemotherapy, CA19-9 and pathologic response score appear to be robust markers of biologic response. For chemotherapy in the adjuvant setting, high-risk patients with elevated CA19-9 and nodal disease appear to benefit while patients low-risk patients may not need further systemic treatment. Future trials are needed to validate these findings.

Part IV evaluates prognostication and staging. This thesis validates T1 sub-staging for improved prognostication, while also supporting the AJCC 8th edition nodal staging system. When considering different IPMN-derived pancreatic cancer subtypes (tubular, colloid, oncocytic), tubular has the worst prognosis, while oncocytic has superior survival. However, intraductal oncocytic papillary neoplasm-derived pancreatic cancer patients are still at risk for delayed recurrence secondary to indolent biology. Finally, nodal disease and elevated CA19-9 are noted to be risk factors for early and systemic recurrence indicating a high-risk population requiring close monitoring.

This work advances the understanding of IPMN-derived PDAC, advocating for its recognition as a distinct entity requiring customized management. By addressing surgical, chemotherapeutic, and prognostic aspects, it lays the foundation for improved patient outcomes and informs future clinical practice and research.