Giampaolo Perri

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 role of age in pancreatic intraductal papillary mucinous neoplasms of the pancreas: Same risk of death but different implications for management

BACKGROUND Current guidelines do not address the role of age in the management of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. AIM To evaluate whether clinical features and risk for malignancy are affected by patients age at diagnosis. METHODS In total, 2189 IPMNs, both surgically resected or surveilled, were dichotomized according to a 50-year-old cutoff and compared in terms of pathological features, cumulative risk of developing high-risk stigmata (HRS), overall survival (OS) and disease-specific survival (DSS). RESULTS Patients <50 years had more frequent abdominal pain (38.5 vs. 22.4%; p < 0.01) and acute pancreatitis (20.4 vs. 9.3%; p < 0.01) at presentation. Patients ≥50 years old had more multifocal IPMNs (50 vs. 36.9%; p < 0.01), HRS (8.5% vs. 4.3%; p = 0.04) and invasive IPMNs (26.6% vs. 17.3%; p = 0.03) when resected. Moreover, patients ≥50 years old had a significantly higher cumulative risk of developing HRS over time, and a significantly lower OS, but similar DSS when compared with those <50 years old. CONCLUSIONS IPMNs diagnosed in older patients are more likely to progress to HRS despite the fact that cancer-related death is not affected by age. The follow-up schedule should not be adjusted according to age, but one should take into account that IPMNs in younger individuals have more time to progress toward malignancy.

Vanishing Pancreatic Cysts during Follow-Up: Another Step Towards De-Emphasizing Cyst Size as a Major Clinical Predictor of Malignancy

Introduction: In the management of pancreatic cystic neoplasms (PCN), size plays a crucial role as the expression of disease progression. While many evidences regarding the natural history of growing pancreatic cysts exist, almost no data are available regarding cysts with a reduction in size. Methods: Radiological and clinical data from patients of the dedicated pancreatic cysts outpatient clinic of the Department of General and Pancreatic Surgery, University of Verona Hospital were retrospectively reviewed. Patients diagnosed with PCNs reducing in size during follow-up were reviewed. Results: From a total of 3,146 patients, we identified 12 (0.38%) vanishing/reducing cysts without a history of pancreatitis. Most of them were presumed IPMN (66.6%). The median follow-up was 69 months and the median cyst’s size 30 mm (range 10–49). Most of the patients (75%) experienced a reduction in cyst size (median reduction of 8 mm, range 6–22) after a median time of 12 months (range 6–63), 3 patients experienced a complete disappearance of the cyst. Conclusion: Cyst size reduction during follow-up is a rare phenomenon of unknown explanation. It adds to the debate regarding the role of size as a clinical predictor whenever a definite diagnosis of a PCN cannot be reached.

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.

Does the surgical waiting list affect pathological and survival outcome in resectable pancreatic ductal adenocarcinoma

BACKGROUND High-volume centers have to deal with long surgical waiting-lists leading to a potential delay in treatment. This study assessed whether a longer time from diagnosis to surgery worsened pathological and survival outcomes in resectable pancreatic ductal adenocarcinoma (PDAC). METHODS A retrospective analysis of patients treated for resectable PDAC. Difference in size between preoperative CT-scan and specimen, pathological features, the rate of vascular and R1 resections as well as recurrence and survival were analyzed depending on the waiting time using a 30-day cut-off. RESULTS Waiting more than 30 days for surgery was associated with an increase in tumor size on specimen when compared with CT-scan (+3 vs. +1 mm, p = 0.04). T and N status, rate of vascular resection, grading, perineural and lymphovascular infiltration, and R1 rates did not differ between groups, as well as tumor recurrence (48.8% vs. 48.9%, p = 0.5) and survival (31 vs. 29 months, p = 0.7). For PDAC < 20 mm, waiting less than 30 days improved overall survival (p = 0.02). CONCLUSION The duration of the surgical waiting-list did not affect pathological features and survival. Delayed surgery was associated with increased cancer size on the specimen. However, surgery should not be delayed for PDACs < 20 mm as this may negatively affect the prognosis.