Acute pancreatitis at the beginning of the 21st century: The state of the art

Acute pancreatitis is an acute inflammatory disease of the pancreas which can lead to a systemic inflammatory response syndrome with significant morbidity and mortality in 20% of patients. Gallstones and alcohol consumption are the most frequent causes of pancreatitis in adults. The treatment of mild acute pancreatitis is conservative and supportive; however severe episodes characterized by necrosis of the pancreatic tissue may require surgical intervention. Advanced understanding of the pathology, and increased interest in assessment of disease severity are the cornerstones of future management strategies of this complex and heterogeneous disease in the 21st century.

Differences between main-duct and branch-duct intraductal papillary mucinous neoplasms of the pancreas

In the last decade,intraductal papillary mucinous neoplasms(IPMNs) have become commonly diagnosed.From a morphological standpoint,they are classified in main-duct IPMNs(MD-IPMNs) and branch-duct IPMNs(BD-IPMNs),depending on the type of involvement of the pancreatic ductal system by the neoplasm.Despite the fact that our understanding of their natural history is still incomplete,recent data indicate that MD-IPMNs and BD-IPMNs show significant differences in terms of biological behaviour with MD-IPMNs at higher risk of malignant degeneration.In the present paper,clinical and epidemiological characteristics,rates of malignancy and the natural history of MD-IPMNs and BD-IPMNs are analyzed.The profile of IPMNs involving both the main pancreatic duct and its side branches(combined-IPMNs) are also discussed.Finally,general recommendations for management based on these differences are given.

Management of ampullary neoplasms: A tailored approach between endoscopy and surgery

Ampullary neoplasms,although rare,present distinctive clinical and pathological features from other neoplastic lesions of the periampullary region.No specific guidelines about their management are available,and they are often assimilated either to biliary tract or to pancreatic carcinomas.Due to their location,they tend to become symptomatic at an earlier stage compared to pancreatic malignancies.This behaviour results in a higher resectability rate at diagnosis.From a pathological point of view they arise in a zone of transition between two different epithelia,and,according to their origin,may be divided into pancreatobiliary or intestinal type.This classification has a substantial impact on prognosis.In most cases,pancreaticoduodenectomy represents the treatment of choice when there is an overt or highly suspicious malignant behaviour.The rate of potentially curative resection is as high as 90% and in high-volume centres an acceptable rate of complications is reported.In selected situations less invasive approaches,such as ampullectomy,have been advocated,although there are some concerns mainly because of a higher recurrence rate associated with limited resections for invasive carcinomas.Importantly,these methods have the drawback of not including an appropriate lymphadenectomy,while nodal involvement has been shown to be frequently present also in apparently lowrisk carcinomas.Endoscopic ampullectomy is now the procedure of choice in case of low up to high-grade dysplasia providing a proper assessment of the T status by endoscopic ultrasound.In the present paper the evidence currently available is reviewed,with the aim of offering an updated framework for diagnosis and management of this specific type of disease.

Extent of surgical resections for intraductal papillary mucinous neoplasms

Intraductal papillary mucinous neoplasms(IPMNs) can involve the main pancreatic duct(MD-IPMNs) or its secondary branches(BD-IPMNs) in a segmental of multifocal/diffuse fashion.Growing evidence indicates that BDIPMNs are less likely to harbour cancer and in selected cases these lesions can be managed non operatively.For surgery,clarification is required on:(1) when to resect an IPMN;(2) which type of resection should be performed;and(3) how much pancreas should be resected.In recent years parenchyma-sparing resections as well as laparoscopic procedures have being performed more frequently by pancreatic surgeons in order to decrease the rate of postoperative pancreatic insufficiency and to minimize the surgical impact of these operations.However,oncological radicality is of paramount importance,and extended resections up to total pancreatectomy may be necessary in the setting of IPMNs.In this article the type and extension of surgical resections in patients with MD-IPMNs and BD-IPMNs are analyzed,evaluating perioperative and long-term outcomes.The role of standard and parenchyma-sparing resections is discussed as well as different strategies in the case of multifocal neoplasms.

Management of neuroendocrine carcinomas of the pancreas (WHO G3): A tailored approach between proliferation and morphology

Neuroendocrine carcinomas(NEC) of the pancreas are defined by a mitotic count > 20 mitoses/10 high power fields and/or Ki67 index > 20%, and included all the tumors previously classified as poorly differentiated endocrine carcinomas. These latter are aggressive malignancies with a high propensity for distant metastases and poor prognosis, and they can be further divided into small- and large-cell subtypes. However in the NEC category are included also neuroendocrine tumors with a well differentiated morphology but ki67 index > 20%. This category is associated with better prognosis and does not significantly respond to cisplatin-based chemotherapy, which represents the gold standard therapeutic approach for poorly differentiated NEC. In this review, the differences between well differentiated and poorly differentiated NEC are discussed considering both pathology, imaging features, treatment and prognostic implications. Diagnostic and therapeutic flowcharts are proposed. The need for a revision of current classification system is stressed being well differentiated NEC a more indolent disease compared to poorly differentiated tumors.

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.

Enhanced recovery pathways in pancreatic surgery: State of the art

Pancreatic surgery is being offered to an increasing number of patients every year. Although postoperative outcomes have significantly improved in the last decades, even in high-volume centers patients still experience significant postoperative morbidity and full recovery after surgery takes longer than we think. In recent years, enhanced recovery pathways incorporating a large number of evidence-based perioperative interventions have proved to be beneficial i n t e r m s o f i m p rove d p o s t o p e ra t i ve o u t c o m e s, and accelerated patient recovery in the context of gastrointestinal, genitourinary and orthopedic surgery. The role of these pathways for pancreatic surgery is still unclear as high-quality randomized controlled trials are lacking. To date, non-randomized studies have shown that care pathways for pancreaticoduodenectomy and distal pancreatectomy are safe with no difference in postoperative morbidity, leading to early discharge and no increase in hospital readmissions. Hospital costs are reduced due to better organization of care and resource utilization. However, further research is needed to clarify the effect of enhanced recovery pathways on patient recovery and post-discharge outcomes following pancreatic resection. Future studies should be prospective and follow recent recommendations for the design and reporting of enhanced recovery pathways.

Ampullary somatostatinomas and jejunal gastrointestinal stromal tumor in a patient with Von Recklinghausen's disease

Von Recklinghausen＇s disease is an autosomal dominant hereditary disease associated with a wide number of neoplasms. We report a case of a 47-year-old Caucasian male affected by Von Recklinghausen＇s disease who developed a malignant somatostatinoma of the papilla major and minor associated with jejunal gastrointestinal stromal tumour with uncertain behaviour. At laparotomy, multiple hepatic metastases were evident. Whipple pancreaticoduodenectomy, jejunal resection, extensive lymphadenectomy and multiple hepatic wedge resections were performed. The patient was alive without recurrence after 24 mo. This is the fourth case reported in the world literature of a patient with Von Recklinghausen＇s disease associated with periampuUary somatostatinomas and jejunal stromal tumor. In patients with Von Recklinghausen＇s disease who complain of gastrointestinal symptoms, a high suspicion index for periampullary endocrine tumours and/or gastrointestinal stromal tumour is required. An aggressive surgical approach seems to give long term survival also in metastatic patients.

Gastric metastasis by lung small cell carcinoma

Metastatic tumors of the gastrointestinal tract are rare. We describe a case of gastric metastasis due to primary lung cancer, revealed by an upper gastrointestinal endoscopy （UGIE）. Haematogenous metastases to the stomach are a rare event. To our knowledge, only 55 cases have been described in the international literature. In these patients, the prognosis is very poor. We report herein a case of gastric metastasis by lung small cell carcinoma, with a review of the literature about this rare entity.

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.