Natural history of pancreatic cystic lesions: A multicenter prospective observational study for evaluating the risk of pancreatic cancer

Abstract

Background and Aim: The aim of this study is to elucidate the natural history of pancreatic cystic lesions (PCLs), including branch duct-type intraductal papillary mucinous neoplasm (BD-IPMN), via midterm follow-up analysis of a multicenter prospective observational study (NSPINAL study). Methods: From July 2011 to October 2016, 881 patients with PCLs were enrolled in NSPINAL study, and 664 patients with > 12 months of follow up were analyzed. Every patient was asymptomatic, and endoscopic ultrasound was performed at the initial diagnosis to exclude high-risk individuals. Follow up included endoscopic ultrasound, computed tomography, or magnetic resonance imaging at least once a year. Serial morphological changes and the pancreatic cancer (PC) incidence, including malignant progression of PCLs, were evaluated. Results: The 664 patients (358 men) were followed for a median of 33.5 months (interquartile range 29). The cyst and main pancreatic duct sizes were 16.6 ± 9.3 and 2.3 ± 1.0 mm, respectively. Morphologically, 518 cases were multilocular, 137 were unilocular, and 9 had a honeycomb pattern; 269 cases involved multifocal lesions. Ninety-six patients (14.5%) showed worsening progression on imaging. There were two resectable and four unresectable cases of pancreatic ductal adenocarcinoma and three cases of malignant BD-IPMN. The 3-year risk of developing PC was 1.2%. The standardized incidence ratio for PC among PCLs was 10.0 (95% confidence interval 3.5-16.5), and the standardized incidence ratio among BD-IPMN was 16.6 (95% confidence interval 5.1-28.1). Multivariate analysis showed that development of symptoms and worsening progression were significant predictors of PC. Conclusions: Malignant progression of PCLs, including PC development, is not uncommon. Patients with PCLs should be carefully monitored to detect pancreatic ductal adenocarcinoma at early stages.

Surveillance of Cystic Lesions of the Pancreas: Whom and How to Survey

“…Again, the authors acknowledge the possibility of a safe surveillance for indolent BD-IPMN without WF or HRS. The mid-term analysis of the NSPINAL study group showed how the 3-year risk of developing PC was 1.2% and the standardized incidence ratio was 16.6 per 100,000 in BD-IPMN [22]. A previous review and meta-analysis that included studies published before 2016 showed similar results [29].…”

“…Only recently, several large observational series [17,18,19,20,21,22] including both surgically treated and surveilled patients allowed to gain a wider point of view with promising evidence available to better define the population that could be safely kept under surveillance.…”

Pancreatic fat content may increase the risk of imaging progression in low‐risk branch duct intraductal papillary mucinous neoplasm

“…Revisions to the Fukuoka guidelines recommend that low‐risk BD‐IPMN should be followed up by CT, MRI, and/or EUS at appropriate intervals, based on the size of each initial cyst. The main concern is the development of malignancy in the cyst and many studies have reported the natural history of malignant progression of low‐risk BD‐IPMN . However, the majority of incidental IPMN in clinical setting are small in size and lack currently defined high‐risk features.…”

“…It is also essential to identify factors associated with disease progression to malignancy in BD‐IPMN. Several studies have reported that those factors included cystic features (cyst size, the presence of a mural nodule, MPD dilatation, and growth rate in size) and patient's factors (symptoms, diabetes mellitus, smoking, or obesity). However, few data are available on risk factors of imaging progression in low‐risk BD‐IPMN .…”

“…For the patients having BD‐IPMN but without high‐risk stigmata or worrisome features (low‐risk BD‐IPMN), who comprise most cases of IPMN, management may depend on the initial cyst size. Several studies have reported factors that are associated with malignant IPMN, which include features of the cyst (size >3 cm, the presence of a mural nodule, main pancreatic duct dilatation, and growth rate in size) as well as patients' factors (symptoms, presence of diabetes mellitus, or smoking status). Although the main concern of IPMN is the onset of malignancy, Crippa et al recently reported that 52% of the 281 patients, including 159 with BD‐IPMN and high‐risk stigmata or worrisome features, had imaging progression such as an increase in cyst size, main pancreatic duct (MPD) dilatation, new nodules, or presence of new or recurrent symptoms during a median follow‐up period of 51 months.…”