Tommaso Pollini

The Evolution of Surgical Strategies for Pancreatic Neuroendocrine Tumors (Pan-NENs)

Objective: The objective of the present analysis is 2-fold: first, to define the evolution of time trends on the surgical approach to pancreatic neuroendocrine neoplasms (Pan-NENs); second, to perform a complete analysis of the predictors of oncologic outcome. Background: Reflecting their rarity and heterogeneity, Pan-NENs represent a clinical dilemma. In particular, there is a scarcity of data regarding their long-term follow-up after surgical resection. Methods: From the Institutional Pan-NEN database, 587 resected cases from 1990 to 2015 were extracted. The time span was arbitrarily divided into 3 discrete clusters enabling a balanced comparison between patient groups. Analyses for predictors of recurrence and survival were performed, together with conditional survival analyses. Results: Among the 587 resected Pan-NENs, 75% were nonfunctioning tumors, and 5% were syndrome-associated tumors. The mean age was 54 years (±14 years), and 51% of the patients were female. The median tumor size was 20 mm (range 4 to 140), 62% were G1, 32% were G2, and 4% were G3 tumors. Time trends analysis revealed that the number of resected Pan-NENs constantly increased, while the size (from 25 to 20 mm) and G1 proportion (from 65% to 49%) decreased during the study period. After a mean follow-up of 75 months, recurrence analysis revealed that nonfunctioning tumors, tumor grade, N1 status, and vascular invasion were all independent predictors of recurrence. Regardless of size, G1 nonfunctioning tumors with no nodal involvement and vascular invasion had a negligible risk of recurrence at 5 years. Conclusions: Pan-NENs have been increasingly diagnosed and resected during the last 3 decades, revealing reliable predictors of outcome. Functioning and nodal status, tumor grade, and vascular invasion accurately predict survival and recurrence with resulting implications for patient follow-up.

Are Cystic Pancreatic Neuroendocrine Tumors an Indolent Entity? Results from a Single Center Surgical Series

Introduction: Cystic pancreatic neuroendocrine tumors (CPanNETs) represent an uncommon variant of pancreatic neuroendocrine tumors (PanNETs). Due to their rarity, there is a lack of knowledge with regard to clinical features and postoperative outcome. Methods: The prospectively maintained surgical database of a high-volume institution was queried, and 46 resected CPanNETs were detected from 1988 to 2015. Clinical, demographic, and pathological features and survival outcomes of CPanNETs were described and matched with a population of 92 solid PanNETs (SPanNETs) for comparison. Results: CPanNETs accounted for 7.8% of the overall number of resected PanNETs (46/587). CPanNETs were mostly sporadic (n = 42, 91%) and nonfunctioning (39%). Two functioning CPanNETs were detected (4.3%), and they were 2 gastrinomas. The median tumor diameter was 30 mm (range 10-120). All tumors were well differentiated, with 38 (82.6%) G1 and 8 (17.4%) G2 tumors. Overall, no CPanNET showed a Ki-67 >5%. A correct preoperative diagnosis of a CPanNET was made in half of the cases. After a median follow-up of >70 months, the 5- and 10-year overall survival of resected CPanNETs was 93.8 and 62.5%, respectively, compared to 92.7 and 84.6% for SPanNETs (p > 0.05). The 5- and 10-year disease-free survival rates were 94.5 and 88.2% for CPanNETs and 81.8 and 78.9% for SPanNETs, respectively (p > 0.05). Conclusion: In the setting of a surgical cohort, CPanNETs are rare, nonfunctional, and well-differentiated neoplasms. After surgical resection, they share the excellent outcome of their well-differentiated solid counterparts for both survival and recurrence.

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.

Pancreaticoduodenectomy in patients ≥ 75 years of age: Are there any differences with other age ranges in oncological and surgical outcomes? Results from a tertiary referral center

AIM To compare surgical and oncological outcomes after pancreaticoduodenectomy (PD) in patients ≥ 75 years of age with two younger cohorts of patients. METHODS The prospectively maintained Institutional database of pancreatic resection was queried for patients aged ≥ 75 years (late elderly, LE) submitted to PD for any disease from January 2010 to June 2015. We compared clinical, demographic and pathological features and survival outcomes of LE patients with 2 exact matched cohorts of younger patients [≥ 40 to 64 years of age (adults, A) and ≥ 65 to 74 years of age (young elderly, YE)] submitted to PD, according to selected variables. RESULTS The final LE population, as well as the control groups, were made of 96 subjects. Up to 71% of patients was operated on for a periampullary malignancy and pancreatic cancer (PDAC) accounted for 79% of them. Intraoperative data (estimated blood loss and duration of surgery) did not differ among the groups. The overall complication rate was 65.6%, 61.5% and 58.3% for LE, YE and A patients, respectively, P = NS). Reoperation and cardiovascular complications were significantly more frequent in LE than in YE and A groups (P = 0.003 and P = 0.019, respectively). When considering either all malignancies and PDAC only, the three groups did not differ in survival. Considering all benign diseases, the estimated mean survival was 58 and 78 mo for ≥ and < 75 years of age (YE + A groups), respectively (P = 0.012). CONCLUSION Age is not a contraindication for PD. A careful selection of LE patients allows to obtain good surgical and oncological results.

Screening/surveillance programs for pancreatic cancer in familial high-risk individuals: A systematic review and proportion meta-analysis of screening results

BACKGROUND/OBJECTIVES Screening/surveillance programs for pancreatic cancer (PC) in familial high-risk individuals (FPC-HRI) have been widely reported, but their merits remain unclear. The data reported so far are heterogeneous-especially in terms of screening yield. We performed a systematic review and meta-analysis of currently available data coming from screening/surveillance programs to evaluate the proportion of screening goal achievement (SGA), overall surgery and unnecessary surgery. METHODS We searched MEDLINE, Embase, PubMed and the Cochrane Library database from January 2000 to December 2016to identify studies reporting results of screening/surveillance programs including cohorts of FPC-HRI. The main outcome measures were weighted proportion of SGA, overall surgery, and unnecessary surgery among the FPC-HRI cohort, using a random effects model. SGA was defined as any diagnosis of resectable PC, PanIN3, or high-grade dysplasia intraductal papillary mucinous neoplasm (HGD-IPMN). Unnecessary surgery was defined as any other final pathology. RESULTS In a meta-analysis of 16 studies reporting on 1551 FPC-HRI cases, 30 subjects (1.82%), received a diagnosis of PC, PanIN3 or HGD-IPMNs. The pooled proportion of SGA was 1.4%(95% CI 0.8-2, p < 0.001, I2 = 0%). The pooled proportion of overall surgery was 6%(95% CI 4.1-7.9, p < 0.001, I2 = 60.91%). The pooled proportion of unnecessary surgery was 68.1%(95% CI 59.5-76.7, p < 0.001, I2 = 4.05%); 105 subjects (6.3%) received surgery, and the overall number of diagnoses from non-malignant specimens was 156 (1.5 lesion/subject). CONCLUSIONS The weighted proportion of SGA of screening/surveillance programs published thus far is excellent. However, the probability of receiving surgery during the screening/surveillance program is non-negligible, and unnecessary surgery is a potential negative outcome.

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.