Alex Borin

Observational study of the incidence of pancreatic and extrapancreatic malignancies during surveillance of patients with branch-duct intraductal papillary mucinous neoplasm

OBJECTIVE This observational analysis assessed the incidence of pancreatic and extrapancreatic malignancies in BD-IPMN patients. BACKGROUND Previous studies showed that progression to malignancy of pancreatic branch-duct (BD) intraductal papillary mucinous neoplasm (IPMN) is infrequent and that extrapancreatic malignancies (EPMs) occur with unusual frequency in IPMN patients. METHODS Patients observed from 2000 to 2012 and enrolled in a surveillance protocol according to the current guidelines were considered eligible for the study. Only patients with follow-up of more than 12 months were evaluated. The incidence of EPM was calculated only in patients who were free of them at the time of IPMN diagnosis. Data were compared with Italian cancer statistics. The standardized incidence ratios (SIRs) and the 5- and 10-year incidence rates were estimated. RESULTS The study population consisted of 569 patients. At a median follow-up of 56 months, 9 patients developed a pancreatic malignancy. Of these, 5 were unresectable. The SIR was 9.21 [95% confidence interval (CI), 1.85-26.91] in males, and 11.94 (95% CI, 4.36-26.0) in females, with a 5-year cumulative incidence of 1.4%. The EPM incidence analysis was performed in 456 patients. Thirty EPMs developed during the follow-up. The SIR was 1.40 (95% CI, 0.72-2.45) in males and 1.37 (95% CI, 0.81-2.16) in females. The 5-year rate of developing any EPM was 5.7%. CONCLUSIONS BD-IPMN patients are at risk of pancreatic carcinogenesis. Although the 5-year incidence rate was as low as 1.4%, the surveillance protocol based on the current guidelines failed to identify a small subset of patients who progressed to advanced disease. Patients with BD-IPMN are not at risk of extrapancreatic carcinogenesis.

Association Between Pancreatic Intraductal Papillary Mucinous Neoplasms and Extrapancreatic Malignancies

BACKGROUND & AIMS The association between pancreatic intraductal papillary mucinous neoplasms (IPMNs) and extrapancreatic neoplasms (EPNs) is controversial. We performed a multicenter observational study to assess the incidence of EPNs after an IPMN diagnosis. METHODS 1340 patients with IPMNs were evaluated from 2000 through 2013 at 4 academic institutions in Europe for development of EPN. To estimate the actual incidence of EPN, we excluded patients with an EPN previous or synchronous to the IPMN, and patients who had been followed for less than 12 months, resulting in a study population of 816 patients. The incidence of EPN was compared with sex-specific, age-adjusted European cancer statistics; the standardized incidence ratio (SIR), and the 5- and 10-year cumulative incidence rates were calculated. RESULTS A total of 290/1340 patients had a history of EPN (prevalence of 21.6%). In this subgroup of patients, the IPMN was discovered incidentally in 241. Among the 816 patients included in the incidence analysis, 50 developed an EPN after a median time of 46 months from study enrollment. The incidence of any EPN was not greater in patients with than without IPMN with a SIR of 1.48 (95% confidence interval, 0.94-2.22) in males and of 1.39 (95% CI 0.90-2.05) in females. The 5- and 10-year cumulative incidence rates for development of EPN in patients with IPMN were 7.9% and 16.6% in men, and 3.4% and 23.1% in women. CONCLUSIONS Patients with IPMN do not have a significantly higher incidence of EPNs than the general European population. It might not be necessary to screen patients with IPMN for EPN.

Systematic review, meta-analysis, and a high-volume center experience supporting the new role of mural nodules proposed by the updated 2017 international guidelines on IPMN of the pancreas

Background: Mural nodules (MNs) have a predominant role in the 2016 revision of the international guidelines on intraductal papillary mucinous neoplasms (IPMN) of the pancreas. The aim of this study was to evaluate MNs as predictors of invasive cancer (iCa) or high‐grade dysplasia (HGD) in IPMNs and to investigate the role of MN size in risk prediction. Methods: A PRISMA‐compliant systematic review of the literature and meta‐analysis on selected studies were conducted. The random effect model was adopted, and the pooled SMD (standardized mean difference) obtained. The surgical series of IPMNs at a single high‐volume institution was reviewed. Results: This review included 70 studies and 2297 resected IPMNs. MNs have a positive predictive value for malignancy of 62.2%. The meta‐analysis suggested that MN size has a considerable effect on predicting IPMNs with both iCa or HGD with a mean SMD of 0.79. All studies included in the meta‐analysis used contrast‐enhanced endosonography (CE‐EUS) to assess MNs. Due to the heterogeneity of the proposed thresholds, no reliable MN size cut‐off was identified. Of 317 IPMNs resected at our institution, 102 (32.1%) had a preoperative diagnosis of MN. Multivariate analysis showed that MN is the only independent predictor of iCa and HGD for all types of IPMNs. Conclusion: MNs are reliable predictors of iCa and HGD in IPMNs as proposed by the 2016 IAP guidelines. CE‐EUS seems to be the best tool for characterizing size and has the best accuracy for predicting malignancy. Further studies should determine potential MN dimensional cut‐offs.

The Clinical Management of Main Duct Intraductal Papillary Mucinous Neoplasm of the Pancreas

Background: Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas comprise a heterogeneous group of intraductal mucin-producing neoplasms representing a typical adenoma-to-carcinoma sequence. The involvement of the main pancreatic duct (MPD) is a feature of paramount importance, directly related to a more aggressive biology and a higher malignancy rate. Method: We review and discuss the clinical management of IPMNs with a MPD involvement, recalling the different consensus guidelines and addressing recent controversies in literature, presenting the current clinical practice in Verona Pancreas Institute. Results: All the aspects of surgical management were discussed, from the indication for surgery to the intraoperative management and the follow-up strategies. Conclusion: The management of presumed IPMNs involving the MPD at our Institution is in line with the International Association of Pancreatology 2012 guidelines, revised in 2016. Surgical resection proposed should achieve the complete removal of the tumor with negative margins. Despite a good prognosis in terms of survival of overall resected main duct intraductal papillary mucinous neoplasms, follow-up should not be discontinued.

Cohort Study of the Incidence of Extrapancreatic Neoplasm During Clinical and Radiological Surveillance of Patients with Branch-Duct IPMN

Context In the latest years, there has been controversy about the relationship between intraductal papillary mucinous neoplasms (IPMN) and the development of extrapancreatic neoplasms. While a number of prevalence studies confirmed this association, the only cohort studies available did not. Objective This is a cohort study of patients with branch-duct IPMN and without a personal history of other non-pancreatic neoplasms who were enrolled in a radiological surveillance protocol. The objective was to assess the incidence of extrapancreatic neoplasms during the follow-up period in comparison with that of the Italian general population. Methods Patients with well-documented branch-duct IPMN on cross-sectional imaging (MRI) and devoid of malignancy concern (according to an institutional protocol from 2000 until 2005 and to the IAP guidelines from 2005 and onwards) were enrolled in a radiological surveillance protocol on a yearly basis. The occurrence of other non-pancreatic neoplasms was recorded in a prospective database and the incidence was compared with the Italian tumor registry (AIRTUM). In particular, number of expected cases was calculated, and the standardized incidence ratio (observed/expected cases) with 95% CI was obtained. Risk function for the development of extrapancreatic neoplasms was then plotted according to the method of Kaplan and Meier. For the purposes of this study, follow-up was stopped on July 2013. Results Study population consisted of 472 patients observed over a 12-year period (2000-2012). Median follow-up was 44 months. Fifty-nine patients (12.5%) developed at least an extrapancreatic malignant neoplasm, for a total of 61 neoplastic events. Median time-to-presentation was 34 months. The most frequent neoplasms were breast cancer (n=15), renal clear cell carcinoma (n=7), colorectal cancer (n=5), melanoma (n=5), lung cancer (n=5), prostate cancer (n=4), and thyroid cancer (n=4). The cumulate incidence of extrapancreatic neoplasms in the study population was significantly greater than the expected incidence in the Italian population, with a standardized incidence ratio of 1.75 (95% CI: 1.33-2.26). According to the plotted risk function, the risk of developing a non-pancreatic neoplasm increased over time (1 year: 2%; 2 years: 4%; 5 years: 8%). Conclusion Patients with branch-duct IPMN have a 1.75 fold increase of non-pancreatic neoplasms during the follow-up period. This warrants sub-analyses by sex, age, type of neoplasm, and possible revision of follow-up protocols, with targeted tumor screening.