We read with great interest the recent study by Holmberg et al. on survival after pancreatic resection for intraductal papillary mucinous neoplasms (PMNs) 1. The authors report excellent short- and long-term survival following resection of IPMN without preoperative signs of malignancy, with comparable outcomes between low-grade dysplasia (LGD), high-grade dysplasia (HGD) and early invasive lesions. At the same time, the study highlights a high proportion of resections yielding LGD and a substantial number of upfront surgeries without prior surveillance, raising concerns about overtreatment. These findings are consistent with accumulating evidence 2, confirming that a considerable fraction of IPMN resections result in LGD with uncertain clinical benefit. We commend the authors for addressing a clinically relevant and timely issue. While they appropriately acknowledge limitations inherent to the retrospective and multicenter design, additional factors relevant to biological risk stratification were not explored. First, the study does not address the imbalance related to lesion location and surgical approach. The higher rate of distal pancreatectomy in patients with LGD is likely due to the lower morbidity and mortality compared to pancreatoduodenectomy. However, emerging data suggest that IPMNs arising from the ventral pancreas, involving the head and isthmus, may carry a higher biological risk of malignant progression 3. This creates a paradox in which lower risk lesions are more frequently resected because surgery is safer, while more aggressive lesions are approached more cautiously, supporting a shift from a surgery driven to a biology driven decision-making process. Second, it is unclear whether IPMN related pancreatitis was captured. Acute pancreatitis is a recognized relative indication for surgery and is associated with increased risk of HGD 4. Third, the role of the exposome is not considered. Environmental and lifestyle exposures are increasingly recognized as contributors to pancreatic carcinogenesis and may influence IPMN progression 5. Fourth, the role of endoscopic ultrasound (EUS) remains insufficiently explored. Its impact on clinical decision making during the pre-operative workup is not reported, despite evidence that it influences both under and overtreatment. Finally, the absence of IPMN epithelial subtype represents an additional limitation. Subtypes differ in biological behavior and malignant potential. Without this information, lesions with distinct morphological profiles are grouped together, limiting interpretation. In conclusion, while this study supports excellent outcomes after preventive IPMN resection, it also underscores the persistent challenge of overtreatment. Future efforts should integrate anatomical, clinical, imaging and molecular factors into a biologically driven, personalized risk stratification framework. The authors declare no conflicts of interest. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.
Capurso et al. (Wed,) studied this question.