Current view of neoadjuvant chemotherapy in primarily resectable pancreatic adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is now the 11th most common cancer and in 2018 there were 458,918 new cases worldwide. In the Czech Republic, a total of 2,173 patients were diagnosed in 2015, ranking the second in incidence worldwide. In contrast to other malignancies, recent research has not brought any major breakthrough in the treatment of PDAC and hence the prognosis remains very serious. Radical resection is the only curative approach, but after the initiation of the standard pathological evaluation of the resected tissue, according to the Leeds protocol, 80% of the resections are R1 (resections with microscopically positive margins). The results of studies in patients with borderline resectable or locally advanced PDAC prefer neoadjuvant chemotherapy or chemoradiotherapy. This approach leads to a higher number of radical R0 resections and better survival. For neoadjuvant treatment in patients with primarily resectable PDAC, most results come from retrospective analysis or phase II trials. However, recently, data from three randomized clinical trials with neoadjuvant therapy for resectable PDAC were presented. These results support the use of chemotherapy or chemoradiotherapy prior to surgery. In the trials published to date, there are differences in chemotherapeutic regimens, cytostatic doses, and the definition of resectability. Thus, up-front resection with adjuvant chemotherapy is still the standard of care and a well-designed randomized trial using neoadjuvant therapy is now necessary.

Diagnostics and therapy of chronic pancreatitis according to UEG guidelines.

Chronic pancreatitis is one of the diseases whose incidence is slightly increasing long-term. Apparently this is related to our current dietary habits and to the way of life in industrialized societies in general. In recent years, chronic pancreatitis has experienced greater diagnostic accuracy and reliability, although we are still unable to diagnose the early stages of the disease. In diagnostics, sophisticated imaging methods are in the forefront, and less frequent is the use of tests that assess the exocrine function of the gland. Non-invasive therapeutic approaches include dietary measures, including an absolute ban on alcohol. Drug therapy consists of the application of drugs containing pancreatic digestive enzymes and the treatment of pancreatic pain. The administration of capsules containing microparticles containing pancreatic enzymes, protected against inactivation of enzymes in an acidic gastric environment, is effective. In the treatment of pancreatic pain, we use a range of analgesic drugs, but abstinence from alcohol itself leads to a decrease in the frequency of pancreatic pain. Surgical therapy is very effective. Among other treatment methods include also endoscopic therapy. From the point of view of diagnosis and therapy, chronic pancreatitis is one of the conditions requiring a multidisciplinary approach. In this review article, we discuss the possibilities of diagnosis and treatment of chronic pancreatitis according to the current recommendations of UEG (United European Gastroenterology).

Is autoimmune pancreatitis a risk factor for pancreatic adenocarcinoma?

Immunoglobulin G4-related diseases (IgG4-RD) are a group of diseases characterized by high serum levels of immunoglobulin G4 (IgG4), increased lymphocyte and plasma cell with IgG4 positivity in the parenchyma of some organs, and storiform fibrosis. The most frequently affected organ is the pancreas. This is an autoimmune form of pancreatitis, which can be divided into two types: Type 1, which is significantly more common than Type 2, is high in IgG4 in the pancreatic parenchyma and shows a fundamental difference in the noted presence of extrapancreatic disorders. In general, chronic inflammation is a risk factor in the development of carcinomas. Chronic pancreatitis is an accepted risk factor for the development of pancreatic cancer. The question is whether this also applies to autoimmune pancreatitis (AIP), which has some mediators of inflammation in common with sporadic pancreatitis, and what role the presence of IgG4 plays. The vast majority of the work on this topic consists of case reports, yet, even based on our own experience, we would like to say that there is a relationship between the autoimmune form of pancreatitis and pancreatic cancer, which usually occurs in the first two years after diagnosis of AIP. Also significant is the fact that the group of people with AIP, who is a clinical manifestation of IgG4-RD, was found to have an even higher incidence of extrapancreatic cancer than in the pancreas itself. Differentiating AIP from pancreatic cancer can sometimes be problematic since these diseases can both present as focal pancreatic lesions. IgG4 has been considered useful for AIP diagnosis, however, IgG4 levels can be slightly elevated, as in the case with pancreatic adenocarcinoma. IgG4 levels of over twice the upper limit are rare among patients with pancreatic adenocarcinoma. However, cases of simultaneous presentation of pancreatic cancer and AIP have been documented and should not be neglected. AIP is a condition where regular followup is mandatory, including from the perspective of possible cancerogenesis.

The role of metabolic syndrome in the induction of chronic pancreatitis after a first attack of acute pancreatitis - multicenter trial.

BACKGROUND: Metabolic syndrome is a serious societal problem worldwide. In the Czech Republic more than 30% of the adult population are sufferers. The role of recurrent acute pancreatitis in the induction of chronic pancreatitis, following the socalled „mechanistic definition“ of chronic pancreatitis, has been unequivocally confirmed. However, there are a number of factors that may contribute to the development of chronic pancreatitis. The first aim of the study was to determine whether the metabolic syndrome may affect the development of chronic pancreatitis. The second question we asked ourselves was whether even one acute attack of pancreatitis could be an inductive factor in chronic pancreatitis. METHODS: Based on data obtained retrospectively from a total of 264 people diagnosed with chronic pancreatitis in 4 centers, a total of 59 people (22.3%) diagnosed within 36 months of a first attack of acute pancreatitis was obtained. Etiologies of either genetically induced pancreatitis or autoimmune pancreatitis were excluded. Diagnostics to identify the presence of metabolic syndrome were run on the 59 persons so obtained using the criteria from the socalled „harmonized“ definition of 2009 (obesity, arterial hypertension, hypertriglyceridemia, type 2 diabetes mellitus and a decreased level of HDL cholesterol). RESULTS: Comparing the findings of the individual components of metabolic syndrome in persons with chronic pancreatitis after a 1st attack of acute pancreatitis with the metabolic syndrome and in persons with chronic pancreatitis after the 1st attack of acute pancreatitis but without metabolic syndrome, a statistically significant difference in obesity was found (82.5% vs. 28.5%), hypertriglyceridemia (82.3% vs 17.8%) and arterial hypertension (70.5% vs 21.4%). The interval during which chronic pancreatitis occurred after acute pancreatitis averaged 12 months (10-14 months) in subjects with metabolic syndrome, whereas in the group without metabolic syndrome the interval was longer, 20 months (16-29 months). CONCLUSION: Our results show that even one attack of acute pancreatitis (regardless of etiology) can be an inductive factor in chronic pancreatitis. The presence of metabolic syndrome can accelerate the development of chronic pancreatitis after one has had acute pancreatitis.

Causes of Exocrine Pancreatic Insufficiency Other Than Chronic Pancreatitis.

Exocrine pancreatic insufficiency (EPI), an important cause of maldigestion and malnutrition, results from primary pancreatic disease or is secondary to impaired exocrine pancreatic function. Although chronic pancreatitis is the most common cause of EPI, several additional causes exist. These include pancreatic tumors, pancreatic resection procedures, and cystic fibrosis. Other diseases and conditions, such as diabetes mellitus, celiac disease, inflammatory bowel disease, and advanced patient age, have also been shown to be associated with EPI, but the exact etiology of EPI has not been clearly elucidated in these cases. The causes of EPI can be divided into loss of pancreatic parenchyma, inhibition or inactivation of pancreatic secretion, and postcibal pancreatic asynchrony. Pancreatic enzyme replacement therapy (PERT) is indicated for the conditions described above presenting with clinically clear steatorrhea, weight loss, or symptoms related to maldigestion and malabsorption. This review summarizes the current literature concerning those etiologies of EPI less common than chronic pancreatitis, the pathophysiology of the mechanisms of EPI associated with each diagnosis, and treatment recommendations.