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Patterns of Recurrence and Long-Term Outcomes in Patients Who Underwent Pancreatectomy for Intraductal Papillary Mucinous Neoplasms With High Grade Dysplasia: Implications for Surveillance
Aaron U. Blackham*1, Matthew Doepker1, Barbara A. Centeno2, Gregory Springett3, José M. Pimiento1, Mokenge P. Malafa1, Pamela J. Hodul1
1Surgical Oncology, Moffitt Cancer Center, Tampa, FL; 2Pathology, Moffitt Cancer Center, Tampa, FL; 3Medical Oncology, Moffitt Cancer Center, Tampa, FL

Introduction: Intraductal papillary mucinous neoplasms (IPMN) are considered non-invasive, pre-malignant lesions of the pancreatic duct. While IPMNs with high-grade dysplasia (HGD) are thought to represent high-risk lesions, the natural history of this disease following pancreatic resection is unknown.
Methods: Patients with IPMN treated with pancreatectomy were identified from a single institution database from January 1999 to May 2015. Pathology reports were reviewed to classify the degree of dysplasia and the presence of invasive disease. Patterns of recurrence and long-term outcomes were analyzed retrospectively.
Results: HGD was diagnosed in 93 out of 276 patients (33.7%) who underwent pancreatectomy for IPMN. Seventeen patients had predominately moderate dysplasia but had foci of HGD. Four patients had HGD with microinvasion. IPMN was classified as main duct, branch duct, or mixed in 23 (27.4%), 31 (36.9%) and 30 patients (35.7%), respectively. Total pancreatectomy was performed on 14 patients (15.1%) due to diffuse or multifocal disease. IPMN involved the pancreatic resection margin in 16 patients (17.2%) but the margin was positive for HGD in only 2 patients (2.2%). With a median follow-up of 32.0 months (range 1-170 months), 85 patients (91.4%) had stable residual disease or no evidence of recurrence in the remnant pancreas. No recurrence was seen in the 4 patients with microinvasion at the time of last follow-up (8.1, 32.0, 34.3 and 39.3 months). Four patients developed new or enlarging IPMN without high-risk features in the remnant pancreas and continued active surveillance. One patient who developed a second IPMN underwent completion pancreatectomy for HGD and subsequently presented with metastatic disease 31.7 months later. Three additional patients (3.2%) developed invasive adenocarcinoma in the remnant pancreas not associated with IPMN; one patient was treated with resection and the other two were treated with chemotherapy due to the presence of synchronous metastases in one and the other being medically unfit for surgery. Median time to recurrence of HGD or development of invasive adenocarcinoma was 24.0 months (range 6.7 to 72.0 months).
Conclusion: The prognosis of IPMN with HGD following resection is very good for most patients and the majority of patients with residual or recurrent IPMN have stable, low-risk disease. However, HGD IPMN may be a marker for developing IPMN recurrence or non-IPMN associated adenocarcinoma in a small subset of patients. As such, more intensive initial and long-term surveillance should be considered.

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