Massimo Falconi

MicroRNA Expression Abnormalities in Pancreatic Endocrine and Acinar Tumors Are Associated With Distinctive Pathologic Features and Clinical Behavior

PURPOSE We investigated the global microRNA expression patterns in normal pancreas, pancreatic endocrine tumors and acinar carcinomas to evaluate their involvement in transformation and malignant progression of these tumor types. MicroRNAs are small noncoding RNAs that regulate gene expression by targeting specific mRNAs for degradation or translation inhibition. Recent evidence indicates that microRNAs can contribute to tumor development and progression and may have diagnostic and prognostic value in several human malignancies. MATERIALS AND METHODS Using a custom microarray, we studied the global microRNA expression in 12 nontumor pancreas and 44 pancreatic primary tumors, including 12 insulinomas, 28 nonfunctioning endocrine tumors, and four acinar carcinomas. RESULTS Our data showed that a common pattern of microRNA expression distinguishes any tumor type from normal pancreas, suggesting that this set of microRNAs might be involved in pancreatic tumorigenesis; the expression of miR-103 and miR-107, associated with lack of expression of miR-155, discriminates tumors from normal; a set of 10 microRNAs distinguishes endocrine from acinar tumors and is possibly associated with either normal endocrine differentiation or endocrine tumorigenesis; miR-204 is primarily expressed in insulinomas and correlates with immunohistochemical expression of insulin; and the overexpression of miR-21 is strongly associated with both a high Ki67 proliferation index and presence of liver metastasis. CONCLUSION These results suggest that alteration in microRNA expression is related to endocrine and acinar neoplastic transformation and progression of malignancy, and might prove useful in distinguishing tumors with different clinical behavior.

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.

Cancer of the Exocrine Pancreas: Surgery and Multimodal Treatment

The optimal management of pancreatic ductal carcinoma remains poorly defined. Radical resection is possible in about 20–30% of patients, with an overall 5-year survival rate of only 20% [1]. In recent years, perioperative morbidity and mortality have significantly decreased, and different clinical trials have suggested an important role for adjuvant therapy [2].

Pancreatic Decompression in Chronic Pancreatitis

Chronic pancreatitis is a disease characterised by a dynamic course giving rise to fibrotic involution of the pancreatic parenchyma with a consequent progressive loss of both exocrine and endocrine function.

Non-Adenocarcinoma Pancreatic Tumors

Diagnosis, localization and surgical as well as medical treatment of most endocrine pancreatic tumors is nowadays clearly established and not a matter of debate. This is especially true for sporadic benign insulinomas, gastrinomas or more rare tumors like VIPomas or glucagonomas. Controversies still exist in hereditary tumors, mainly in symptomatic gastrinomas and insulinomas, occurring within the syndrome of multiple endocrine neoplasia type I (MEN I). Since the recent description of the mutation in chromosome 11 associated with MEN I [1] the question of how we should deal with asymptomatic patients detected by genetic and/or biochemical screening also became controversial.