[Risk factors for pancreatitis and pancreatic cancer].

AIM: To identify and compare the frequency of alcohol consumption, tobacco smoking, levels of main macronutrients, vitamins and mineral elements consumption in patients with acute (AP) and chronic pancreatitis (CP) and pancreatic cancer (PC). MATERIALS AND METHODS: At the observational clinical cross-sectional uncontrolled case-study 65 patients with AP or CP (group 1) and 45 patients with PC (group 2) were examined. A survey of patients was carried out: questionnaire on tobacco smoking, a frequency questionnaire on alcohol consumption, a questionnaire for assessing the frequency of food consumption. RESULTS: The frequency of smoking (33.8, 20.0%; p0.05), alcohol consumption 1 times/week during the last year (21.5, 15.6%; p0.05) did not differ significantly between the two groups. The highest consumption rates of total, vegetable, animal protein, total carbohydrates, refined sugar, animal fat, cholesterol, MUFA, dietary fiber, vitamins (-carotene, vitamin B1, B2, C, PP), mineral elements (iron, potassium, calcium, magnesium, sodium, phosphorus) and the daily energy content of the diet were determined in PC than in the AP and CP group. Among patients of group 1, deficient intake of fat-soluble vitamin A (93.3, 54.8%; p=0.009) and vitamin E (80.0, 48.4%; p=0.041) was more common in the subgroup of patients with excretory pancreatic insufficiency than without it, and the chance of having hypercholesterolemia was associated with a deficient intake of vitamin E [Ex(B)=3.3, 95% CI 1.59.3; p=0.027]. CONCLUSION: There were no differences in the frequency of smoking and alcohol consumption between patients with AP and CP and PC. The highest indices of the main macronutrients, daily energy content of the diet, micronutrients (except for vitamins A, E) were found in PC than in the group of patients with AP and CP. Among patients with AP and CP with excretory pancreatic insufficiency, a lower intake of fat-soluble vitamins was noted and associations of hypercholesterolemia with deficient intake of vitamin E were obtained.

ACG Clinical Guideline: Chronic Pancreatitis.

Chronic pancreatitis (CP) is historically defined as an irreversible inflammatory condition of the pancreas leading to varying degrees of exocrine and endocrine dysfunction. Recently however, the paradigm for the diagnosis has changed in that it breaks with the traditional clinicopathologic-based definition of disease, focusing instead on diagnosing the underlying pathologic process early in the disease course and managing the syndrome more holistically to change the natural course of disease and minimize adverse disease effects. Currently, the most accepted mechanistically derived definition of CP is a pathologic fibroinflammatory syndrome of the pancreas in individuals with genetic, environmental, and/or other risk factors who develop persistent pathologic responses to parenchymal injury or stress. The most common symptom of CP is abdominal pain, with other symptoms such as exocrine pancreatic insufficiency and diabetes developing at highly variable rates. CP is most commonly caused by toxins such as alcohol or tobacco use, genetic polymorphisms, and recurrent attacks of acute pancreatitis, although no history of acute pancreatitis is seen in many patients. Diagnosis is made usually on cross-sectional imaging, with modalities such as endoscopic ultrasonography and pancreatic function tests playing a secondary role. Total pancreatectomy represents the only known cure for CP, although difficulty in patient selection and the complications inherent to this intervention make it usually an unattractive option. This guideline will provide an evidence-based practical approach to the diagnosis and management of CP for the general gastroenterologist.

Emerging Role of Chinese Herbal Medicines in the Treatment of Pancreatic Fibrosis.

Pancreatic fibrosis is the main pathologic characteristic in chronic pancreatitis (CP), a common disease that arises from surgery. Pancreatitis is caused by various etiologies, but the mechanism of fibrosis is not completely understood. Existing clinical approaches mainly focus on mitigating the symptoms and therefore do not cure the phenomena. In recent years, there has been a heightened interest in the use of Chinese herbal medicine (CHMs) in the prevention and cure of CP as expressed by increasing numbers of clinical and experimental research. Despite early cell culture and animal models, CHMs are able to interact with plenty of molecular targets involved in the pathogenesis of pancreatic fibrosis mostly via the TGF- ß /Smads pathway; however, integrated and up-to-date communication in this domain is unavailable. This review focuses on the research progress of CHMs against pancreatic fibrosis due to CP in vitro and in vivo and summarizes the potential mechanisms. We also outlined the toxicology of some CHMs for fibrosis treatment in order to provide a fuller understanding of drug safety. This review may provide reference for further innovative drug research and the future development of treatments for CP with pancreatic fibrosis.

Hepcidin knockout mice spontaneously develop chronic pancreatitis owing to cytoplasmic iron overload in acinar cells.

Iron is both an essential and a potentially toxic element, and its systemic homeostasis is controlled by the iron hormone hepcidin. Hepcidin binds to the cellular iron exporter ferroportin, causes its degradation, and thereby diminishes iron uptake from the intestine and the release of iron from macrophages. Given that hepcidin-resistant ferroportin mutant mice show exocrine pancreas dysfunction, we analysed pancreata of aging hepcidin knockout (KO) mice. Hepcidin and Hfe KO mice were compared with wild-type (WT) mice kept on standard or iron-rich diets. Twelve-month-old hepcidin KO mice were subjected to daily minihepcidin PR73 treatment for 1 week. Six-month-old hepcidin KO mice showed cytoplasmic acinar iron overload and mild pancreatitis, together with elevated expression of the iron uptake mediators DMT1 and Zip14. Acinar atrophy, massive macrophage infiltration, fatty changes and pancreas fibrosis were noted in 1-year-old hepcidin KO mice. As an underlying mechanism, 6-month-old hepcidin KO mice showed increased pancreatic oxidative stress, with elevated DNA damage, apoptosis and activated nuclear factor-κB (NF-κB) signalling. Neither iron overload nor pancreatic damage was observed in WT mice fed iron-rich diet or in Hfe KO mice. Minihepcidin application to hepcidin KO mice led to an improvement in general health status and to iron redistribution from acinar cells to macrophages. It also resulted in decreased NF-κB activation and reduced DNA damage. In conclusion, loss of hepcidin signalling in mice leads to iron overload-induced chronic pancreatitis that is not seen in situations with less severe iron accumulation. The observed tissue injury can be reversed by hepcidin supplementation. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Intake patterns of food nutrients and other substances associated with chronic pancreatitis.

BACKGROUND/OBJECTIVES: While alcohol is considered the most common aetiological factor for chronic pancreatitis, the intake of various nutrient and other substances is thought to act as cofactors in the pathogenesis of the disease due to modulation of oxidative stress. This study examined incident cases of acute pancreatitis to determine the dietary and other intakes that characterize those harbouring underlying chronic pancreatitis. METHODS: Cases of acute pancreatitis presenting to a single institution were prospectively recruited (n = 153). The presence of chronic pancreatitis was defined by a composite of clinical, biochemical and radiological criteria. Information was obtained on the intake of dietary macro- and micronutrients, coffee, tobacco and alcohol in the period just prior to the acute exacerbation. Univariate and multivariate analyses of association were undertaken. Principal components analysis (PCA) was employed to elicit patterns of intake. RESULTS: After adjustment for key demographic variables, no individual nutrient or other substance showed a significant association with chronic pancreatitis. However, following PCA there emerged a significant positive association with a so-called "stimulant" intake pattern and a negative association with a so-called "nutritive" pattern. CONCLUSIONS: Preceding an acute exacerbation, patients with underlying chronic pancreatitis are more likely to substitute food-based intake for combinations of other substances, such as tobacco and coffee. This finding may have application in the clinical setting as part of a chronic disease management protocol.

Chronic pancreatitis.

PURPOSE OF REVIEW: We review important new clinical observations in chronic pancreatitis made in the past year. RECENT FINDINGS: Cigarette smoking is a dose-dependent risk factor for acute pancreatitis, recurrent acute pancreatitis, and chronic pancreatitis. A minority of chronic alcohol consumers develop recurrent acute pancreatitis but very heavy drinking associates with chronic pancreatitis. More patients with alcohol-induced chronic pancreatitis have cirrhosis than patients with cirrhosis have chronic pancreatitis (39 vs. 18%). Most patients with asymptomatic hyperenzymemia have no pancreatic lesions. Pancreatic calcifications are most frequently due to chronic pancreatitis, followed by cystic neoplasms and other disorders. The new Rosemont consensus classification of endoscopic ultrasonography criteria for chronic pancreatitis is unvalidated. Zinc deficiency correlates only with severe chronic pancreatitis and the fecal elastase test is an inaccurate marker of pancreatic steatorrhea. Patients commonly receive insufficient lipase to abolish pancreatic steatorrhea. Ultrastructural neuropathies are common to chronic pancreatitis and pancreatic cancer and correlate with pain severity. SUMMARY: Results of this year's investigations further elucidated risk factors for pancreatic disease, the natural history of alcoholic pancreatitis, the differential diagnosis of pancreatic calcifications, the diagnosis of chronic pancreatitis with the Rosemont criteria, the limited diagnostic utility of fecal elastate test and zinc measurements, the proper dosing of pancreatic enzyme supplements, and treatment of pancreatic pain.

Chronic pancreatitis in mice by treatment with choline-deficient ethionine-supplemented diet.

Although chronic pancreatitis is a risk factor for pancreatic ductal adenocarcinoma (PDA), the relationship between chronic pancreatitis and PDA remains obscure. A critical obstacle to understanding the role of chronic pancreatitis is the lack of animal models. To develop one such model, mice were fed long-term with a choline deficient ethionine-supplemented (CDE) diet. Histological evaluation revealed that chronic pancreatitis, characterized by acinar atrophy, fibrosis and well-developed tubular complexes (TCs), was observed after 24 weeks of CDE diet treatment. Furthermore, expression of epidermal growth factor receptor (EGFR) and its ligands; serine protease inhibitor Kazal type 3 (Spink3) and transforming growth factor alpha (TGF alpha) and activation of K-Ras (GTP-Ras formation), which are frequently observed in human PDA, were indeed observed in parallel with TCs formation. Neoplastic lesions were not found after 54 weeks of treatment, suggesting that a continuation of CDE diet or another insult is required for the development of PDA.

[Nutritional repercussions and management of chronic pancreatitis]. / Repercusiones nutricionales y manejo de la pancreatitis crónica.

The pancreas is a retroperitoneal organ that releases water, bicarbonate and digestive enzymes by the main pancreatic duct (MPD) into the duodenum. Chronic pancreatitis (CP) is typically caused, in adults, by chronic alcohol abuse and, less frequently hypertriglyceridemia, primary hyperparathyroidism or cystic fibrosis. Exocrine dysfunction results in malabsorption of fat and subsequent steatorrhea. Damage to pancreatic endocrine function is a late finding in CP and results in hyperglycaemia or overt diabetes mellitus. Care of patients with CP principally involves management of pain. A significant change in the pain pattern or the sudden onset of persistent symptoms suggests the need to rule out other potential etiologies, including peptic ulcer disease, biliary obstruction, pseudocysts, pancreatic carcinoma, and pancreatic duct stricture or stones, then is important to establish a secure diagnosis. Management of pain should then proceed in a judicious stepwise approach avoiding opioids dependence. Patients should be advised to stop alcohol intake. Fat malabsorption and other complications may also arise. Management of steatorrhea should begin with small meals and restriction in fat intake. Pancreatic enzyme supplements can relieve symptoms and reduce malabsorption in patients who do not respond to dietary restriction. Enzymes at high doses should be used with meals. Treatment with acid suppression to reduce inactivation of the enzymes from gastric acid are recommended. Supplementation with medium chain triglycerides and fat soluble vitamin replacement may be required. Management of other complications (such as pseudocysts, bile duct or duodenal obstruction, pancreatic ascites, splenic vein thrombosis and pseudoaneurysms) often requires aggressive approach with the patient kept on total parenteral nutrition to minimize pancreatic stimulation.

[Nutrition, probiotics, antibiotics, antioxidative therapy, endoscopy in chronic pancreatitis]. / Ernährung, Probiotika, Antibiotika, antioxidative Therapie, Endoskopie bei chronischer Pankreatitis.

Treatment of chronic pancreatitis is dependent on the stage of the disease and consists of several arms: treatment of pain when ever possible according to its pathogenesis; treatment of complications primarily by interventional endoscopy, in cases of failure by surgery; therapy of exocrine insufficiency with porcine pancreatic extracts; treatment of endocrine insufficiency with insulin. Pseudocysts can be drained according to their location by either the transgastric, transduodenal, transpapillary or transcutaneous route. Distal prepapillary stenoses of the main pancreatic duct can be handled by placement of a plastic stent; similarily to treatment of biliary strictures. Stones leading to obstruction of the main pancreatic duct can be disintegrated by extracorporeal shock wave lithotripsy (ESWL) and the fragments removed by endoscopy after papillotomy. Transgastral endoscopic drainage of retroperitoneal necroses is still experimental. Prospective randomized multicenter trials comparing surgery with interventional endoscopy are still lacking. Failure of endoscopic therapy or suspicion of tumor is clearly an indication for surgery. There is no need for a specific diet in patients with chronic pancreatitis without having diabetes. In severe attacks, clinically similar to acute pancreatitis, enteral nutrition via a jejunal tube is replacing parenteral nutrition. However, prospective comparative trials are still mandatory. Prophylactic application of antibiotics in patients with pancreatic necrosis is again under debate. Whether probiotics are capable to decrease the risk of secondary pancreatic infection of necrosis has not been thoroughly studied. The hypothesis that capture of oxygen free radicals by drugs such as selenium may prevent frequency and severity of acute relapses has also not been proven.