Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0149521 (chronic pancreatitis)
 7,199 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Approximately 20% of medical and surgical patients in hospital have an alcohol use disorder (AUD). Diagnosis of chronic alcohol abuse is performed by specific medical history, examination and validated tests. Biomarkers are a means of diagnosing chronic alcoholism in sedated, intubated and emergency patients. Chronic alcohol consumption damages the central nervous and cardiovascular system, the liver and the immune system. In medical ICUs more than 50% of liver injuries and chronic pancreatitis are due to chronic alcohol abuse. The alcohol withdrawal syndrome is emerging in 25% of AUD patients in intensive care after reduction of sedative drugs. Long term alcohol abuse also leads to cardiac arrhythmias, dilatative cardiomyopathy and hypotonic circulatory dysregulation. Bleeding complications are two-fold increased during and after surgery. Immune suppression results in an increased incidence of infectious complications like pneumonia, wound infection and urinary tract infection. In particular, septic encephalopathy is often misinterpreted as alcohol withdrawal syndrome. Due to the fact that AUD patients show a two to five-fold higher rate of postoperative complications they require increased attention to avoid latency of treatment and the development of multiple organ failure. Prophylaxis in terms of drug therapy or abstinence intervals and brief intervention strategies can help to prevent or ease some of these complications and can decrease the rate of long-term injuries.
 ...
PMID:[Alcohol use disorder: risks in anesthesia and intensive care medicine]. 1652 Oct 4

This paper reviews the current literature on chronic pancreatitis (CP). Despite marked progress in diagnostic tools, predominately imaging methods, no consensus has been reached on the nomenclature of CP, ie diagnosis, classification, staging, pathomechanisms of pain and its optimal treatment. A major problem is that no single reliable diagnostic test exists for early-stage CP except histopathology (rarely available). This stage is characterised typically by recurrent acute pancreatitis +/- necrosis (eg pseudocysts). Acute pancreatitis is a well-defined condition caused in 80% of cases by gallstones or alcohol abuse. Alcoholic pancreatitis, in contrast to biliary pancreatitis, progresses to CP in the majority of patients. However, a definite CP-diagnosis is often delayed because progressive dysfunction and/or calcification, the clinical markers of CP, develop on average 5 years from disease onset. The progression rate is variable and depends on several factors eg aetiology, smoking, continued alcohol abuse. Repeated function testing eg by the faecal elastase test, is the best alternative for histology to monitor progression (or non-progression) of suspected (probable) to definite CP. The pathomechanism of pain in CP is multifactorial and data from different series are hardly comparable mainly because insufficient data of the various variables ie diagnosis, classification, staging of CP, pain pattern and presumptive pain cause, are provided. Pain in CP is rarely intractable except in the presence of cancer, opiate addiction or extra-pancreatic pain causes. Local complications like pseudocysts or obstructive cholestasis are the most common causes of severe persistent pain which can be relieved promptly by an appropriate drainage procedure. Notably, partial to complete pain relief is a common feature in 50-80% of patients with late-stage CP irrespective of surgery and about 50% of CP-patients never need surgery (or endoscopic intervention). The spontaneous "burn-out" thesis of CP is in accordance with this observation although precise data of this phenomenon are scarce. Recent observations indicate that the progression to late-stage CP is markedly delayed in non-alcoholic compared to alcoholic CP. Therefore, spontaneous pain relief is also delayed but it occurs in close association with severe exocrine insufficiency suggesting that aetiology has a major impact on the duration of early-stage CP and that the "burn-out" thesis appears valid both in uncomplicated alcoholic and nonalcoholic late-stage CP. For treatment of steatorrhea and diabetes the reader is referred to recent reviews. Mortality and survival are closely related to aetiology with an increased death rate of about 50% within 20 years from onset in alcoholic CP compared to a markedly better prognosis in hereditary and idiopathic "juvenile" CP. The risk of pancreatic cancer is increased particularly in nonalcoholic CP based on the longer survival, whereas the risk of extra-pancreatic (smoking-related) cancer is about 12-fold higher in alcoholic CP.
 ...
PMID:Diagnosis and management of chronic pancreatitis: current knowledge. 1663 63

Conservative therapy is applied to various extent in all subjects with chronic pancreatitis. It includes removal of the provoking agent (most frequently alcohol abuse and biliary disease), dietary regimen, treatment of pain, maldigestion, and diabetes. Removal of the provoking agent prevents progression of the disease and relieves intensity of the main symptoms, particularly of pain. Diet in remission should include approximately 1g of protein/kg body mass. Fat intake should be encouraged within limits of individual tolerance. With low caloric intake carbohydrates should be enriched up to 65 - 70% of total energy intake. Abdominal pain may be due to a complication or to the underlying disease itself. For this reason one approach cannot be effective in all subjects. Conservative methods represent the first line of pain therapy. They include alcohol withdrawal, analgesics, narcotics and negative trypsin-induced feedback control of pancreatic secretion. Pancreatin medication is the cornerstone of maldigestion therapy. This is indicated with weight loss and/or symptoms associated with steatorrhea or with 15 - 20 g stool fat/day without additional symptoms. The effect may be evaluated by increase of body mass, decrease of loose stools and by markers of the nutritional status. Adequate replacement therapy with pancreatic enzymes influences also elaboration and secretion of some gastrointestinal hormones. The appearance of secondary diabetes makes abstinence from alcohol again mandatory. Food intake should be divided into 5 - 6 daily doses and adequate enzyme replacement should be applied. Peroral antidiabetics may be considered at the early stage, but many of these patients ultimately require insulin therapy. Its dosage should be adjusted to glucose urinary losses rather than to adhere to tight normoglycemia because of the increased risk of hypoglycemia. The therapeutic options in chronic pancreatitis may stabilize the disease and prevent its progression. The patients may be at the best asymptomatic, but not cured.
 ...
PMID:[Conservative therapy of chronic pancreatitis]. 1673 30

We report an interesting case of a patient with neither family nor personal history for pancreatic diseases that was admitted to our department in 1982, at the age of 25 years. At that time, medical history, absence of alcohol abuse, and radiological imaging suggested a diagnosis of idiopathic chronic pancreatitis. The patient underwent a left-pancreatectomy, with histological confirmation of chronic pancreatitis. He was asymptomatic until 1988, when episodes of pain arose, requiring a pancreatico-jejunostomy. No further problems ensued until 2004 when radiological investigation following pain-related symptoms revealed enormous dilation of the pancreatic duct. A pylorus-preserving pancreaticoduodenectomy resulting in total pancreatectomy was performed. Histological examination revealed an intraductal papillary mucinous non-invasive carcinoma. Review of the previously resected specimen revealed former misdiagnosis. This tumour usually affects an elderly population and nowadays is recognised as a possible cause of chronic obstructive pancreatitis. This report represents a slippery case of misdiagnosis and demonstrates that follow-up is always mandatory following a diagnosis of idiopathic chronic pancreatitis.
 ...
PMID:A case of intraductal papillary mucinous tumour following recurrent attacks of pancreatitis lasting 26 years. 1684 40

Chronic pancreatitis (CP) is characterized by progressive pancreatic damage that eventually results in significant impairment of exocrine as well as endocrine functions of the gland. In Western societies, the commonest association of chronic pancreatitis is alcohol abuse. Our understanding of the pathogenesis of CP has improved in recent years, though important advances that have been made with respect to delineating the mechanisms responsible for the development of pancreatic fibrosis (a constant feature of CP) following repeated acute attacks of pancreatic necroinflammation (the necrosis-fibrosis concept). The pancreatic stellate cells (PSCs) are now established as key cells in fibrogenesis, particularly when activated either directly by toxic factors associated with pancreatitis (such as ethanol, its metabolites or oxidant stress) or by cytokines released during pancreatic necroinflammation. In recent years, research effort has also focused on the genetic abnormalities that may predispose to CP. Genes regulating trypsinogen activation/inactivation and cystic fibrosis transmembrane conductance regulator (CFTR) function have received particular attention. Mutations in these genes are now increasingly recognized for their potential 'disease modifier' role in distinct forms of CP including alcoholic, tropical, and idiopathic pancreatitis. Treatment of uncomplicated CP is usually conservative with the major aim being to effectively alleviate pain, maldigestion and diabetes, and consequently, to improve the patient's quality of life. Surgical and endoscopic interventions are reserved for complications such as pseudocysts, abscess, and malignancy.
 ...
PMID:Chronic pancreatitis: challenges and advances in pathogenesis, genetics, diagnosis, and therapy. 1763 Nov 65

The pancreas develops from ventral and dorsal buds, which undergo fusion. Failure to fuse results in pancreas divisum, which is defined by separate pancreatic ductal systems draining into the duodenum. Risk of developing pancreatitis is increased in pancreas divisum. MR cholangiopancreatography (MRCP) is the technique of choice for detecting it non-invasively. Annular pancreas is the result of incomplete rotation of the pancreatic bud around the duodenum with the persistence of parenchyma or a fibrous band encircling (stenosing) the duodenum. Acute pancreatitis is usually caused by bile duct stones or alcohol abuse. Contrast-enhanced multi-detector row CT is the method of choice to assess the extent of this disease. In acute pancreatitis, the role of MRCP is mainly limited to finding bile duct stones in patients with suspected biliary pancreatitis. Chronic pancreatitis results in relentless and irreversible loss of exocrine (and sometimes endocrine) function of the pancreas. MDCT even shows subtle calcifications. MRCP is the method of choice for non-invasive assessment of the duct. Inflammatory pseudotumor in chronic pancreatitis and groove pancreatitis are difficult to differentiate from pancreatic cancer. In these cases, multiple imaging methods such as MDCT, MRI and endosonography including biopsy may be used to make a diagnosis.
 ...
PMID:[Pancreas. Congenital changes, acute and chronic pancreatitis]. 1746 82

Chronic pancreatitis is a fibroinflammatory disease of the pancreas. Etiologically, most cases are related to alcohol abuse and smoking. Recently, gene mutations have been identified as the cause of hereditary pancreatitis. Other chronic pancreatitis types that were defined in recent years are autoimmune pancreatitis (lymphoplasmacytic sclerosing pancreatitis) and paraduodenal pancreatitis ('groove pancreatitis', 'cystic dystrophy of heterotopic pancreas'). This review describes and discusses the main histological findings, the pathogenesis and the clinical features of the various types of chronic pancreatitis. In addition, pseudotumors and other tumor-like lesions are briefly mentioned.
 ...
PMID:Chronic pancreatitis, pseudotumors and other tumor-like lesions. 1748 47

This paper provides a summary of the effects of alcohol abuse on the pathobiologic responses that occur during acute and chronic pancreatitis considering both the human disease and animal/tissue models. The effects are multiple and include ones on cell death leading to necrosis; on inflammation resulting in a sensitized response to pancreatic stress; and fibrosis through effects of ethanol on pancreatic stellate cells and the plasminogen system. Although the effects of alcohol are multiple and complex, it is likely that a combination of a few key effects on these pathobiologic responses drive the increased sensitivity of the pancreas to acute pancreatitis with pancreatic stress and the promotion of chronic pancreatitis with pancreatic injury occurring during acute pancreatitis.
 ...
PMID:Pathobiology of alcoholic pancreatitis. 1759 22

Alcohol abuse is the major cause of chronic inflammation of the pancreas (i.e., chronic pancreatitis). Although it has long been thought that alcoholic pancreatitis is a chronic disease from the outset, evidence is accumulating to indicate that chronic damage in the pancreas may result from repeated attacks of acute tissue inflammation and death (i.e., necroinflammation). Initially, research into the pathogenesis of alcoholic pancreatitis was related to ductular and sphincteric abnormalities. In recent years, the focus has shifted to the type of pancreas cell that produces digestive juices (i.e., acinar cell). Alcohol now is known to exert a number of toxic effects on acinar cells. Notably, acinar cells have been shown to metabolize alcohol (i.e., ethanol) via both oxidative (i.e., involving oxygen) and nonoxidative pathways. The isolation and study of pancreatic stellate cells (PSCs)-the key effectors in the development of connective tissue fibers (i.e., fibrogenesis) in the pancreas-has greatly enhanced our understanding of the pathogenesis of chronic pancreatitis. Pancreatic stellate cells become activated in response to ethanol and acetaldehyde, a toxic byproduct of alcohol metabolism. In addition, PSCs have the capacity to metabolize alcohol via alcohol dehydrogenase (the major oxidizing enzyme for ethanol). The fact that only a small percentage of heavy alcoholics develop chronic pancreatitis has led to the search for precipitating factors of the disease. Several studies have investigated whether variations in ethanol-metabolizing enzymes may be a trigger factor for chronic pancreatitis, but no definite relationship has been established so far.
 ...
PMID:Role of alcohol metabolism in chronic pancreatitis. 1771 1

Although alcohol abuse is the major cause of chronic pancreatitis, the pathogenesis of alcoholic chronic pancreatitis (ACP) remains obscure. A critical obstacle to understanding the mechanism of ACP is lack of animal models. Our objective was to develop one such model. Rats were pair-fed for 8 wk ethanol or control Lieber-DeCarli liquid diet. For the last 2 wk, they received cyclosporin A (CsA; 20 mg/kg once daily) or vehicle. After 1 wk on CsA, one episode of acute pancreatitis was induced by four 20 microg/kg injections of cerulein (Cer); controls received saline. Pancreas was analyzed 1 wk after the acute pancreatitis. CsA or Cer treatments alone did not result in pancreatic injury in either control (C)- or ethanol (E)-fed rats. We found, however, that alcohol dramatically aggravated pathological effect of the combined CsA+Cer treatment on pancreas, resulting in massive loss of acinar cells, persistent inflammatory infiltration, and fibrosis. Macrophages were prominent in the inflammatory infiltrate. Compared with control-fed C+CsA+Cer rats, their ethanol-fed E+CsA+Cer counterparts showed marked increases in pancreatic NF-kappaB activation and cytokine/chemokine mRNA expression, collagen and fibronectin, the expression and activities of matrix metalloproteinase-2 and -9, and activation of pancreatic stellate cells. Thus we have developed a model of alcohol-mediated postacute pancreatitis that reproduces three key responses of human ACP: loss of parenchyma, sustained inflammation, and fibrosis. The results indicate that alcohol impairs recovery from acute pancreatitis, suggesting a mechanism by which alcohol sensitizes pancreas to chronic injury.
 ...
PMID:A rat model reproducing key pathological responses of alcoholic chronic pancreatitis. 1788 79


<< Previous 1 2 3 4 5 6 7 8 9 10