Introduction
The rising number of patients with intraductal papillary mucinous neoplasms (IPMNs) in countries with aging populations in the near future is predictable considering that the incidence of pancreatic cystic tumors is positively correlated with patient age and that IPMNs occur most frequently among multifocal pancreatic cystic tumors. Although the majority of IPMNs detected incidentally through various imaging tests have a tumor diameter ≤10 mm and are thus deemed low-risk for carcinogenesis, the possibility of malignant transformation persists. Thus, such IPMNs are subject to periodic follow-up diagnostic imaging. Therefore, an appropriate surveillance system must be established to effectively and efficiently identify cases of IPMN-related malignant transformation, which develops only in few IPMN cases, under the constraints of limited national healthcare funding.
Aims & Methods
In the current study, we analyzed the clinical background observed at initial patient presentation that affect long-term prognosis and tried to narrow the population for whom continued evaluation is inevitable. The study included 1645 patients with IPMNs (776 men and 869 women) treated at our hospital since 2010. We examined the types and timing of medical intervention (surgical resection or pancreatic carcinogenesis) selected mainly in terms of worrisome features (WF) as advocated by the international guidelines (Pancreatology, 2024:24;255–70) for IPMN treatment. Statistical analysis was performed using the chi-square test, log-rank test, and Cox proportional hazards model, with statistical significance set at α = 0.05.
Results
During the entire observation period, 123 patients (7.5%) had IPMN-derived carcinoma (IPMN-DC), whereas 41 patients (2.5%) had concomitant pancreatic ductal adenocarcinoma (PDAC), which required medical intervention. The proportion of cases with c-Stage I, II, III, and IV (UICC 8th edition) at the time of diagnosis were 52.0%, 43.9%, 0.8%, and 3.3%, respectively, for IPMN-DC and 39.0%, 31.7%, 9.8%, and 19.5%, respectively for PDAC. A significantly higher proportion of PDAC cases were diagnosed with an advanced disease stage that developed earlier in time. Factors with significantly shorter time for IPMN-DC medical intervention were: maximum cyst diameter ≥30 mm, non-branched type, main pancreatic duct diameter ≥5 mm, and septal nodal structure for IPMN-DC. For PDAC, these factors were maximum cyst diameter ≥30 mm, main duct type, main pancreatic duct diameter ≥5 mm, septal nodal structure, cyst enlargement (≥2.5 mm/year), and abnormally high levels of CA19-9. Both groups could be significantly stratified by the number of WFs. However, the difference was more distinct in IPMN-DC, whereas <1% (9/1190) medical intervention from the group with 0 WFs was noted in PDAC. Relative risk (hazard ratio, HR) analysis of WF in which proportional hazard was maintained revealed that the presence of septal nodular structure (HR 5.2), maximum cyst diameter ≥30 mm (HR 3.3), and main pancreatic duct diameter ≥5 mm (HR 2.6) were significant factors for IPMN-DC, whereas abnormally high CA19-9 levels (HR 5.0) and septal nodular structure (HR 4.8) were significant for PDAC. Conversely, a significantly higher percentage of patients who exhibited these factors at initial presentation also later developed IPMN-DC or PDAC.
Conclusion
Ten percent of IPMN cases will develop IPMN-DC or PDAC, thereby requiring careful follow-up, especially in cases with septal nodules, abnormally high CA19-9 levels, and cysts with a maximum diameter of ≥30 mm.
