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Background/Aims: The natural history of spontaneous decrease in the size of pancreatic cystic lesions (PCLs) without high-risk stigmata is under investigation. This study aimed to investigate the timing of spontaneous decrease in the size of PCLs without high-risk stigmata and to identify the characteristics associated with their complete resolution. Methods: From 2000 to 2016, patients with spontaneous decreases in PCL size on computed tomography (CT) and/or magnetic resonance imaging (MRI) who had at least 1 year of follow-up were evaluated retrospectively. Results: A total of 78 patients underwent follow-up for an average of 55.7 months. Most patients were asymptomatic, and 35 (37.2%) showed complete resolution. The initial mean PCL size was 1.6±0.9 cm (range, 0.5 to 5.6 cm). The average time to initial decrease in size and complete resolution of PCLs were 32.1 and 41.5 months, respectively. Compared with PCLs that completely resolved, presence of underlying malignancy was associated with partial resolution of PCLs in multivariable analysis (hazard ratio, 0.51; 95% confidence interval, 0.32 to 0.81; p=0.005). Endoscopic ultrasound (EUS) identified detailed findings, especially the presence of septum (p<0.001), calcification (p=0.015) and lobulation (p=0.001) that were not found on CT/MRI. Conclusions: Asymptomatic small PCLs without high-risk stigmata can naturally decrease in size at approximately 3 years, and complete resolution can be expected in the absence of underlying malignancy. Regular follow-up of approximately 3 years with EUS may be a reasonable and safe alternative when planning the initial treatment of small PCLs without high-risk stigmata.

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