molecular pathology of intraductal papillary mucinous neoplasms of the pancreas

Since the first description of intraductal papillary mucinous neoplasms(IPMNs)of the pancreas in the eighties,their identification has dramatically increased in the last decades,hand to hand with the improvements in diagnostic imaging and sampling techniques for the study of pancreatic diseases.However,the heterogeneity of IPMNs and their malignant potential make difficult the management of these lesions.The objective of this review is to identify the molecular characteristics of IPMNs in order to recognize potential markers for the discrimination of more aggressive IPMNs requiring surgical resection from benign IPMNs that could be observed.We briefly summarize recent research findings on the genetics and epigenetics of intraductal papillary mucinous neoplasms,identifying some genes,molecular mechanisms and cellular signaling pathways correlated to the pathogenesis of IPMNs and their progression to malignancy.The knowledge of molecular biology of IPMNs has impressively developed over the last few years.A great amount of genes functioning as oncogenes or tumor suppressor genes have been identified,in pancreatic juice or in blood or in the samples from the pancreatic resections,but further researches are required to use these informations for clinical intent,in order to better define the natural history of these diseases and to improve their management.

Selection criteria in resectable pancreatic cancer: A biological and morphological approach

Pancreatic ductal adenocarcinoma(PDA) remains one of the most aggressive tumors with a low rate of survival. Surgery is the only curative treatment for PDA, although only 20% of patients are resectable at diagnosis. During the last decade there was an improvement in survival in patients affected by PDA, possibly explained by the advances in cancer therapy and by improve patient selection by pancreatic surgeons. It is necessary to select patients not only on the basis of surgical resectability, but also on the basis of the biological nature of the tumor. Specific preoperative criteria can be identified in order to select patients who will benefit from surgical resection. Duration of symptoms and level of carbohydrate antigen 19.9 in resectable disease should be considered to avoid R1 resection and early relapse. Radiological assessment can help surgeons to distinguish resectable disease from borderline resectable disease and locally advanced pancreatic cancer. Better patient selection can increase survival rate and neoadjuvant treatment can help surgeons select patients who will benefit from surgery.

Feasibility of therapeutic endoscopic ultrasound in the bridge-to-surgery scenario:The example of pancreatic adenocarcinoma

Upfront resection is becoming a rarer indication for pancreatic ductal adenocarcinoma,as biologic behavior and natural history of the disease has boosted indications for neoadjuvant treatments.Jaundice,gastric outlet obstruction and acute cholecystitis can frequently complicate this window of opportunity,resulting in potentially deleterious chemotherapy discontinuation,whose resumption relies on effective,prompt and long-lasting management of these complications.Although therapeutic endoscopic ultrasound(t-EUS)can potentially offer some advantages over comparators,its use in potentially resectable patients is primal and has unfairly been restricted for fear of potential technical difficulties during subsequent surgery.This is a narrative review of available evidence regarding EUS-guided choledochoduodenostomy,gastrojejunostomy and gallbladder drainage in the bridge-to-surgery scenario.Proof-ofconcept evidence suggests no influence of t-EUS procedures on outcomes of eventual subsequent surgery.Moreover,the very high efficacy-invasiveness ratio over comparators in managing pancreatic cancer-related symptoms or complications can provide a powerful weapon against chemotherapy discontinuation,potentially resulting in higher subsequent resectability.Available evidence is discussed in this short paper,together with technical notes that might be useful for endoscopists and surgeons operating in this scenario.No published evidence supports restricting t-EUS in potential surgical candidates,especially in the setting of pancreatic cancer patients undergoing neoadjuvant chemotherapy.Bridge-to-surgery tEUS deserves further prospective evaluation.

Management of hepatic metastases of well/moderately differentiated neuroendocrine tumors of the digestive tract

In neuroendocrine tumors(NETs),liver metastases(LM)represent the most crucial prognostic factor,irrespective of the primary tumor site.At diagnosis,about 65-95%of gastroenteropancreatic neuroendocrine tumors(GEP-NETs)show hepatic metastasis.Management strategies of LM are heterogeneous and range from systemic therapy to liver-directed procedures.The type of systemic therapy used is dependent on the grade and proliferation of the tumor and includes somatostatin analogues,interferon,m-Tor and tyrosine kinase inhibitors,and chemotherapy.Angiographic liver-directed techniques,such as transarterial embolization/chemoembolization and selective internal radiation therapy,offer excellent palliation for patients with liver-predominant disease.In highly selected cases,liver transplantation and peptide receptor radionuclide therapy are considered.The relatively low disease incidence and the diversity of presentation have led to a lack of well-conducted randomized controlled trials comparing the efficacy of different treatment options.Experience indicates that surgery is the only treatment that offers potential for cure.For unresectable lesions,the absence of data from rigorous trials limits the validity of many publications that detail management.In this review we will discuss the existing approaches for hepatic metastases from GEP-NETs.