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Query: UMLS:C0149521 (chronic pancreatitis)
 7,199 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic alcohol intake accounts for 60-90% of the cases of chronic pancreatitis, but other etiologies have been recognized and described in the very recent years. Genetic causes include mutations of the cationic trypsinogen gene PRSS1 (100 families in France), of its inhibitor SPINK1 and of the CFTR gene involved in cystic fibrosis. Auto-immune pancreatitis is often part of an "IgG4-related systemic disease" involving the biliary tract, the salivary glands, the retroperitoneum and/or the kidneys. Diagnostic criteria are now well-defined (HISORt of the Mayo Clinic), with ductal and parenchymal lesions on imaging that may mimick pancreatic adenocarcinoma. Corticoids are efficacious but recurrences are frequent and long-term outcome is still poorly known.
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PMID:[From the chronic pancreatitis to chronic pancreatites]. 1971 57

The paper presents the data available in the literature on mutations in known genes in pancreatitis, such as cationic trypsinogen (PRSS1), pancreatic secretory trypsin inhibitor (PSTI/SPINK1), cystic fibrosis (CFTR), and apolipoprotein E (APOE) genes, as well as the new candidate gene--chymotrypsinogen (CTRC). It also gives the results of the authors studies estimating the spread of the mutations in the PRSS1 (2.5%), PSTI/SPINK1 (3.3%), and CFTR (0.8%) genes, as well as APOE polymorphism in patients with pancreatitis. It is shown that the E4 allele of the APOE gene was more frequently identified in patients with acute pancreatitis than in those with chronic pancreatitis (0.143 +/- 0.05 and 0.026 +/- 0.02, respectively; p < 0.05). An overview is given of 7 major classes of candidate genes implicated in the pathogenesis of cholesterol cholelithiasis (CL): hepatic enzymes regulating blood lipid composition; receptors of lipoproteins, hepatic and intestinal membrane and intracellular transport proteins; factors regulating the transcription of lipids and bile salts, cholecystokinin and its receptors, and mucin. In the authors' epidemiological study, the spread of APOE alleles and genotypes did not differ in women with and without CL; low molecular-weight apolipoprotein(a) isoforms (B, S2) were significantly found in patients with CL than in those without CL; the spread of the CG genotype in the TRPM8 gene was significantly lower in women with cholesterol CL than that in the Novosibirsk population. These polymorphisms have been proved to be associated with bile cholesterol concentrations in women with cholesterol CL. The opposite effect of the APOE4 allele on gallbladder stone formation processes is demonstrated, by using the APOE polymorphism as an example, which shows it necessary to examine each specific population to elicit a possible association between the polymorphism of different genes and gastrointestinal tract diseases.
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PMID:[Genetic aspects of digestive diseases. Part 1]. 2038 81

In the past, chronic pancreatitis has been regarded as a fairly uniform and largely untreatable disorder that most commonly affects patients who both lack gainful employment or adequate insurance coverage and have a tendency to smoke and drink. Large clinical trials suggest that this perception is not only misguided and discriminatory but also not based on facts. We forgot that the perception of chronic liver disease was similar before World War II, and just like liver cirrhosis the fibrosis and cirrhosis of the pancreas--i.e. chronic pancreatitis--is the end result of a range of environmental, inflammatory, infectious and genetic disorders. A growing number of these have only recently been recognized as a distinct entity and several of which are becoming truly treatable. A large proportion of the risk for developing pancreatitis is conveyed by genetic risk factors, and we estimate that less than half of those have been identified so far. The same holds true for protective factors that can prevent pancreatitis, even in the face of excessive alcohol abuse. Various gene mutations and polymorphisms appear to determine an individual's susceptibility for developing pancreatic disease, for the severity of the disease, and for the disease progression. The spectrum of genotype/phenotype associations ranges from straightforward autosomal dominant traits with near-complete penetrance, as for the most common mutations in the cationic trypsinogen gene (PRSS1), to moderate risks factors without mendelian inheritance patterns, as for SPINK1 and CFTR mutations, to very subtle risk associations and disease modifiers that can only be identified in large cohort studies, as for the chymotrypsin C, calcium-sensing receptor and the anionic trypsin (PRSS2) mutations. Only a better understanding of the disease mechanisms that underlie these changes will make an individualized therapy of pancreatic disorders a realistic option.
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PMID:Advances in the etiology of chronic pancreatitis. 2081 6

We review important new clinical observations in pancreas divisum (PD) made since 2007. PD is common and has the same prevalence in the general population and idiopathic pancreatitis (IP). Up to 53% of patients with PD and IP have underlying idiopathic chronic pancreatitis (CP), and in rigorous prospective clinical follow-up and/or natural history studies, many with idiopathic recurrent acute pancreatitis (IRAP) have idiopathic CP. According to retrospective studies, PD does not modify the natural course of nonalcoholic or alcoholic CP. CFTR and/or SPINK1 gene mutations associate with IP (idiopathic CP and IRAP) independently of the presence of PD. More than one third of patients with pancreatitis or presumed pancreaticobiliary pain respond to placebo. Authors of uncontrolled studies report a significant symptomatic response to surgery and endotherapy in patients with IP and PD, but the response remains unproven and is largely limited to those with IRAP and not idiopathic CP or chronic pain.
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PMID:Pancreas divisum. 2122 60

CFTR mutations enhance susceptibility for idiopathic chronic pancreatitis (ICP) and congenital bilateral absence of the vas deferens (CBAVD); however, it is unknown why CFTR heterozygotes are at increased disease risk. We recently showed that common CFTR variants are associated with aberrantly spliced transcripts. Here, we genotyped for common CFTR variants and tested for associations in two ICP (ICP-A: 126 patients, 319 controls; ICP-B: 666 patients, 1,181 controls) and a CBAVD population (305 patients, 319 controls). Haplotype H10 (TG11-T7-470V) conferred protection (ICP-A: OR 0.19, P<0.0001; ICP-B: OR 0.78, P = 0.06; CBAVD OR 0.08, P<0.001), whereas haplotype H3 (TG10-T7-470M) increased disease risk (ICP-A: OR 8.34, P = 0.003; ICP-B: OR 1.88, P = 0.007; CBAVD: OR 5.67, P = 0.01). The risk of heterozygous CFTR mutations carriers for ICP (OR 2.44, P<0.001) and CBAVD (OR 14.73, P<0.001) was fully abrogated by the H10/H10 genotype. Similarly, ICP risk of heterozygous p.Asn34Ser SPINK1 mutation carriers (OR 10.34, P<0.001) was compensated by H10/H10. Thus, common CFTR haplotypes modulate ICP and CBAVD susceptibility alone and in heterozygous CFTR and p.Asn34Ser mutation carriers. Determination of these haplotypes helps to stratify carriers into high- and low-risk subjects, providing helpful information for genetic counseling.
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PMID:Common CFTR haplotypes and susceptibility to chronic pancreatitis and congenital bilateral absence of the vas deferens. 2152 Mar 37

It is now generally believed that pancreatitis results from pancreatic autodigestion. An inappropriate conversion of pancreatic zymogens to active enzymes within the pancreatic parenchyma is thought to initiate the inflammatory process. A key role has been attributed to the activation of trypsinogen to trypsin, converting all proteolytic proenzymes to their active form. Several gain-of-function mutations in the cationic trypsinogen gene (PRSS1) have been identified in patients with chronic pancreatitis (CP). These mutations lead to enhanced intrapancreatic trypsinogen activation. In contrast, a variant in the anionic trypsinogen (PRSS2) gene, p.G191R, has been described that mitigates intrapancreatic trypsin activity and thereby plays a protective role. Beside trypsinogen mutations, loss-of-function variants in SPINK1, encoding a pancreatic trypsin inhibitor, are strongly associated with idiopathic CP. Approximately 15-40% of patients with so-called idiopathic CP carry p.N34S on one allele or on both alleles. Chymotrypsin C (CTRC) degrades all human trypsin isoforms with high specificity. Two CTRC alterations, p.R254W and p.K247_R254del, are significantly associated with idiopathic as well as alcohol-related CP. Functional analysis of the variants revealed impaired activity and/or reduced secretion. Thus, loss-of-function mutations in CTRC predispose to pancreatitis by diminishing its protective trypsin-degrading activity. Albeit the association between CFTR, the gene mutated in cystic fibrosis, and idiopathic CP is now well established, the pathogenic mechanisms are poorly understood. Nearly 25-30% of patients carry at least one CFTR mutation, but few patients only were compound-heterozygous. Several patients, however, are trans-heterozygous for a CFTR alteration and a PRSS1, SPINK1, or CTRC variant, respectively.
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PMID:Genetics of pancreatitis: a guide for clinicians. 2152 53

The incidence of chronic pancreatitis grows slowly but steadily. At present, alcohol is the most frequent risk factor, although the new forms of so called non-alcoholic chronic pancreatitis, such as genetically induced pancreatitis and its autoimmune variety, are carefully watched. Alcohol consumption continues to be most closely associated with the disease, though it is no more than a risk factor and other aspects, e.g., genetic predisposition, are prerequisite to the disease development. Imaging methods play a fundamental role in diagnosing the disease; non-invasive magnetic resonance and CT, invasive but safe endosonography, and diagnostically rarely used ECRP that, because of its invasive nature, is currently predominantly used for therapeutic purposes. Genetic markers are also exploited, including CFTR mutation, SPINK 1 and PRRS 1 gene, immunoglobulin G4 in the autoimmune form of the disease as well as, alternatively, pancreatic biopsy. Disease symptoms, i.e., pancreatic malabsorption (enzymes with high lipase content) and pancreatic pain are treated conservatively, with paracetamol as the first line therapy for pain followed, if necessary, by so called synaptic analgesics. Alternatively, endoscopic techniques (drainage) or surgery (drainage and resection) are applied. Hereditary and non-hereditary chronic pancreatitis is among the risk factors for pancreatic cancer and thus patients with these diseases should be closely followed up.
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PMID:[Chronic pancreatitis in 2011]. 2216 91

Chronic pancreatitis (CP) is widely prevalent in Asian countries much more so in India and Japan. The phenotype of CP is somewhat similar to that reported from western countries. The prevalent types of CP are mainly idiopathic and alcohol related. Current evidence suggests that the term "tropical pancreatitis" used for idiopathic CP from India is a misnomer. Gallstones' association with CP reported from China remains controversial. There has been ample evidence that mutations in the SPNIK1 and CFTR genes are strongly associated with idiopathic CP in patients from different ethnic backgrounds. Oxidative stress is important in the pathophysiology and antioxidants have been shown to result in significant pain relief with CP. Home-made balanced diet is effective for treating malnutrition in patients with CP. Endoscopic therapy combined with ESWL may provide significant relief in patients with pancreatic ductal calculi/stricture. Surgery is quite effective in CP and may be better than endotherapy.
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PMID:Chronic pancreatitis in India and Asia. 2232 61

Overall, genetically determined diseases of the pancreas are rare. Recently, it was demonstrated that in chronic pancreatitis many patients carry genetic changes in associated genes. Aside from chronic pancreatitis, cystic fibrosis is also characterized by exocrine insufficiency in many patients. Genetic alterations in CFTR can be found in patients suffering from chronic pancreatitis and in patients with cystic fibrosis. According to this fact, the analysis of CFTR alterations in both disease forms has improved the understanding of underlying pathogenetic mechanisms. Shwachman-Diamond and Johanson Blizzard syndrome are rare pancreatic disorders, characterized by exocrine pancreatic insufficiency in addition to other phenotypic features. As such, due to the early onset of both disease forms, diagnosis of cystic fibrosis has to be ruled out in patients with exocrine insufficiency, which can be achieved by performing sweat chloride tests. Even pancreatic cancer can accumulate in some families and a genetic basis was recently demonstrated for some patients. In all mentioned disease entities, a genetic analysis of associated genes has become essential for establishing the diagnosis. Although genetic knowledge and the finding of genetic alterations in different genes has not changed therapy of the mentioned diseases so far, the future will tell in which way genetic knowledge can be integrated to change modalities of therapy.
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PMID:[Genetically determined pancreatic diseases]. 2241 Sep 43

HCO3- -rich fluid in the pancreatic juice (2-3 L/day) is secreted by epithelial cells lining the pancreatic duct tree, while digestive enzymes are secreted by acinar cells with a small amount of Cl- -rich fluid. Ductal HCO3- secretion is not only regulated by gastrointestinal hormones and cholinergic nerves but is also influenced by luminal factors: intraductal pressure, Ca2+ concentration, pathological activation of protease and bile reflux. The maximum HCO3- concentration of the juice under secretin stimulation reaches 140-150 mM. Thus pancreatic duct cells secrete HCO3- against a approximately 7-fold concentration gradient. HCO3- secretion critically depends on the activity of CFTR, a cAMP-dependent anion channel localized in the apical membrane of various epithelia. In the proximal part of pancreatic ducts close to acinar cells HCO3 secretion across the apical membrane is largely mediated by SLC26A6 CI- -HCO3- exchanger. In distal ducts where the luminal HCO3- concentration is already high, most of the HCO3- secretion is mediated by HCO3- conductance of CFTR. CFTR is the causative gene for cystic fibrosis. Loss of function due to severe mutations in both alleles causes typical cystic fibrosis characterized by dehydrated, thick, and viscous luminal fluid/mucus in the respiratory and gastrointestinal tract, pancreatic duct, and vas deferens. A compound heterozygote of mutations/polymorphisms (causing a mild dysfunction of CFTR) involves a risk of developing CFTR-related diseases such as chronic pancreatitis. In cystic fibrosis and certain cases of chronic pancreatitis, the pancreatic duct epithelium secretes a small amount of fluid with neutral-acidic pH, which causes an obstruction of the duct lumen by a protein plug or viscous mucus.
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PMID:Physiology and pathophysiology of bicarbonate secretion by pancreatic duct epithelium. 2251 7


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