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Query: UMLS:C0030305 (pancreatitis)
 16,014 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pancreatitis and pancreatic cancer represent two major diseases of the exocrine pancreas. Pancreatitis exhibits both acute and chronic manifestations. The commonest causes of acute pancreatitis are gallstones and alcohol abuse; the latter is also the predominant cause of chronic pancreatitis. Recent evidence indicates that endotoxinemia, which occurs in alcoholics due to increased gut permeability, may trigger overt necroinflammation of the pancreas in alcoholics and one that may also play a critical role in progression to chronic pancreatitis (acinar atrophy and fibrosis) via activation of pancreatic stellate cells (PSCs). Chronic pancreatitis is a major risk factor for the development of pancreatic cancer, which is the fourth leading cause of cancer-related deaths in humans. Increasing attention has been paid in recent years to the role of the stroma in pancreatic cancer progression. It is now well established that PSCs play a key role in the production of cancer stroma and that they interact closely with cancer cells to create a tumor facilitatory environment that stimulates local tumor growth and distant metastasis. This review summarizes recent advances in our understanding of the pathogenesis of alcoholic pancreatitis and pancreatic cancer, with particular reference to the central role played by PSCs in both diseases. An improved knowledge of PSC biology has the potential to provide an insight into pathways that may be therapeutically targeted to inhibit PSC activation, thereby inhibiting the development of fibrosis in chronic pancreatitis and interrupting stellate cell-cancer cell interactions so as to retard cancer progression.
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PMID:New insights into alcoholic pancreatitis and pancreatic cancer. 1979 99

Severe acute pancreatitis is a potentially life-threatening disease. Pancreatic necrosis is associated with an aggravated prognosis, while superimposed infection is almost always lethal without surgery. Bacterial translocation mainly from the gut is the most widely accepted mechanism in the pathogenesis of infected pancreatic necrosis. Infected pancreatic necrosis should be suspected in the presence of the usual markers of systemic inflammation (i.e., fever and leukocytosis), organ failure, or a protracted severe clinical course. The diagnostic method of choice to confirm the diagnosis of pancreatic necrosis is contrast-enhanced computed tomography, where necrotic areas are evidenced as regions without enhancement. The presence of pancreatic necrotic infection should be based on a combination of clinical manifestations, results of laboratory investigation (mainly increased levels of CRP and / or procalcitonin), and can be confirmed by image-guided fine-needle aspiration and gram stain /culture of the aspirates. Surgery remains the treatment of choice for the management of infected pancreatic necrosis and involves open necrosectomy (debridement) and wide drainage of the peripancreatic areas, often in association with continuous irrigation. Planned reoperations may be required to achieve complete removal of the necrotic / infected material. The timing of surgery is of paramount importance; ideally, surgery should be performed after 2 or 3 weeks from the onset of pancreatitis. Recently, various minimally invasive approaches have been described, but they have not been compared in prospective trials with the classical open surgery. Antibiotic therapy is routinely used in patients with infected necrotizing pancreatitis, in conjunction with surgical debridement; its role, however, in the management of patients with sterile necrosis is recently questioned. Nutritional support should be taken into consideration in these patients; enteral nutrition should be preferred over total parenteral nutrition to improve the anatomical and functional integrity of the gut mucosa, thereby preventing bacterial translocation.
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PMID:Current trends in the management of infected necrotizing pancreatitis. 2018 Jul 53

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) in acute pancreatitis still represents a substantial problem, with a mortality rate in the range of 30%-40%. The present review evaluates underlying pathophysiological mechanisms in both ALI and ARDS and potential clinical implications. Several mediators and pathophysiological pathways are involved during the different phases of ALI and ARDS. The initial exudative phase is characterized by diffuse alveolar damage, microvascular injury and influx of inflammatory cells. This phase is followed by a fibro-proliferative phase with lung repair, type II pneumocyte hypoplasia and proliferation of fibroblasts. Proteases derived from polymorphonuclear neutrophils, various pro-inflammatory mediators, and phospholipases are all involved, among others. Contributing factors that promote pancreatitis-associated ALI may be found in the gut and mesenteric lymphatics. There is a lack of complete understanding of the underlying mechanisms, and by improving our knowledge, novel tools for prevention and intervention may be developed, thus contributing to improved outcome.
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PMID:Acute lung injury and ARDS in acute pancreatitis: mechanisms and potential intervention. 2044 Aug 49

This review discusses gastrointestinal manifestations of parathyroid diseases. Parathyroid hormone is the primary regulator of calcium physiology. Hypoparathyroidism can be idiopathic, hereditary, or secondary to surgery in the neck. Hyperparathyroidism is usually from adenomas or hyperplasia. Hypoparathyroidism is associated with steatorrhea that may improve with medium-chain triglycerides, correction of the hypoparathyroidism, or administration of vitamin D. Hyperparathyroidism results in constipation because of reduction in neuromuscular excitability by high calcium levels. According to old literature, the incidence of peptic ulcer disease (PUD) in patients with hyperparathyroidism is 9% compared with autopsy rates of 4% to 5%. Any association is difficult to prove today, as hyperparathyroidism is usually mild due to early detection of cases through routine automated measurements of calcium. In addition, PUD is less prevalent now than before the advent of proton pump inhibitors. The presence of ulcers or ulcer symptoms may correct in some patients after parathyroidectomy, suggesting an association. The incidence of pancreatitis in patients with primary hyperparathyroidism ranges from 1.5% to 12% and may be because of the hypercalcemia. Complicating the issue is secondary hyperparathyroidism in response to hypocalcemia from pancreatitis. Pancreatitis may improve in some individuals after parathyroidectomy. Pancreatitis may follow parathyroid surgery because of an acute rise in calcium levels with manipulation of the parathyroid glands or to a blunted response of calcitonin-producing cells from fatigue. Parathyroid diseases have a few distinct effects on the gut: steatorrhea in hypoparathyroidism, and constipation, PUD, and pancreatitis in hyperparathyroidism.
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PMID:The parathyroids and the gut. 2048 90

Recent studies have shown that pretreatment with ghrelin exhibits protective effect in the gut. Administration of ghrelin reduces gastric mucosal damage, as well as inhibits the development of experimental pancreatitis. However, this protective effect requires administration of ghrelin before gastric or pancreatic damage and thus has a limited clinical value. The aim of present study was to assess the influence of ghrelin administered after development of acute pancreatitis on the course of this disease. Acute pancreatitis was induced by cerulein. Ghrelin was administered twice a day for 1, 2, 4, 6 or 9 days at the dose of 4, 8 or 16 nmol/kg/dose. The first dose of ghrelin was given 24 hours after last injection of cerulein. The severity of acute pancreatitis was assessed between 0 h and 10 days after cessation of cerulein administration. Administration of caerulein led to the development of acute edematous pancreatitis and maximal severity of this disease was observed 24 hours after induction of pancreatitis. Treatment with ghrelin reduced morphological signs of pancreatic damage such as pancreatic edema, leukocyte infiltration and vacuolization of acinar cells, and led to earlier regeneration of the pancreas. Also biochemical indexes of the severity of acute pancreatitis, serum activity of lipase and amylase were significantly reduced in animals treated with ghrelin. These effects were accompanied by an increase in the pancreatic DNA synthesis and a decrease in serum level of pro-inflammatory interleukin-1b. Administration of ghrelin improved pancreatic blood flow in rats with acute pancreatitis. We conclude that: (1) treatment with ghrelin exhibits therapeutic effect in caerulein-induced experimental acute pancreatitis; (2) this effect is related, at least in part, to the improvement of pancreatic blood flow, reduction in proinflammatory interleukin-1beta and stimulation of pancreatic cell proliferation.
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PMID:Therapeutic effect of ghrelin in the course of cerulein-induced acute pancreatitis in rats. 2081 69

Kaposi sarcoma is an acquired immunodeficiency syndrome-related disease that mainly involves the skin, gastrointestinal gut, and lungs. Whole-body 18F-fluorodeoxyglucose-positron emission tomography and computed tomography (FDG-PET/CT) scanning is useful for simultaneous detection of multiple lesions of Kaposi sarcoma. We present a 67-year-old man with a history of infection with human immunodeficiency virus who presented with numerous cutaneous lesions. FDG-PET/CT images showed lesions in the skin, lung, and lymph nodes. The gastrointestinal lesions were detected using gastric fiberscopy (GF) and colon fiberscopy (CF). After Kaposi sarcoma therapy, the uptake in the lesions of the skin, lung, and lymph nodes decreased, but new lesions were detected in the pancreas and lumbar spine. He had pancreatitis and Candida spondilitis. Whole-body FDG-PET/CT is useful for detecting lesions and determining the extension to which the disease has spread, adding the gastrointestinal lesions by GF and CF. After therapy, FDG-PET/CT can be used to demonstrate which lesions remain active and to determine the overall response to treatment. In this case, we show how useful FDG-PET/CT is and how difficult it is to treat Kaposi sarcoma.
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PMID:Whole-body 18F-fluorodeoxyglucose positron emission tomography/computed tomography images before and after chemotherapy for Kaposi sarcoma and highly active antiretrovirus therapy. 2119 42

Severe acute pancreatitis (SAP) is associated with significant morbidity and mortality. The majority of deaths related to SAP are the result of infectious complications. Although bacterial infections are most commonly encountered, fungal infections are increasingly being recognized. Candida is the most common fungal infection. The occurrence of fungal infection in patients with acute pancreatitis adversely affects the clinical course, leading to a higher incidence of systemic complications, and possibly mortality as well. Important risk factors for fungal infection in patients with acute pancreatitis include broad-spectrum antibiotics, prolonged hospitalization and surgical/endoscopic interventions, use of total parenteral nutrition, and mechanical ventilation. Patients with higher severity of pancreatitis are at a greater risk. The pathogenesis of fungal infection in patients with acute pancreatitis is multifactorial. Translocation of microorganisms across the gut epithelium, lymphocyte dysfunction, and the virulence of the invading microorganisms play important roles. Histological demonstration of fungi remains the gold standard of diagnosis, but a positive biopsy is rarely obtained. The role of biomarkers in the diagnosis is being investigated. As early diagnosis and treatment can lead to improved outcome, a high index of suspicion is required for prompt diagnosis. Limiting the use of broad-spectrum antibiotics, early introduction of enteral nutrition, and timely change of vascular catheters are important preventive strategies. The role of antifungal prophylaxis remains controversial. Surgical necrosectomy with antifungal therapy is the most widely used treatment approach. Clinical trials on antifungal prophylaxis are needed, and indications for surgical intervention need to be clearly defined.
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PMID:Fungal infections in severe acute pancreatitis. 2129 17

Alcohol abuse is the leading etiologic factor of pancreatitis, although many heavy drinkers do not develop pancreatic damage. Alcohol promotes pancreatitis through a combination of remote (e.g., increased gut permeability to bacterial products such as lipopolysaccharide) and more proximal effects (e.g., altered pancreatic cholinergic inputs), including oxidative damage at the level of the pancreatic acinar cell. Recent evidence indicates that alcohol exposure to rodents disturbs proteostasis in the exocrine pancreas, an effect counterbalanced by homeostatic processes that include both the unfolded protein response (UPR) and autophagy. A corollary to this notion is that pancreatitis results when adaptive responses are insufficiently robust to alleviate the cellular stress caused by alcohol.
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PMID:Drinking and driving pancreatitis: links between endoplasmic reticulum stress and autophagy. 2146 Jun 13

This review provides some aspects on the physiology of stimulation and inhibition of pancreatic digestive enzyme secretion and the pathophysiology of pancreatic acinar cell function leading to pancreatitis. Cholecystokinin (CCK) stimulates both directly via CCK-A receptors on acinar cells and indirectly via CCK-B receptors on nerves, followed by acetylcholine release, pancreatic enzyme secretion. It is still not known whether CCK-A receptors exist in human acinar cells, in contrast to acinar cells of rodents where CCK-A receptors have been well described. CCK has numerous actions both in the periphery and in the central nervous systems. CCK inhibits gastric motility and regulates satiety. Another major function of CCK is stimulation of gallbladder contraction. This function enables that bile acids act simultaneously with pancreatic lipolytic enzymes. Secretin is a major stimulator of bicarbonate secretion. Trypsinogen is activated by the gut mucosal enzyme enterokinase. The other pancreatic proenzymes are activated by trypsin. Termination of enzyme secretion may be regulated by negative feedback mechanisms via destruction of CCK-releasing peptides by trypsin. Furthermore, the ileum may act as a brake by release of inhibitory hormones such as PYY and somatostatin. In the pathophysiology of acute pancreatitis, fusion of zymogen granules with lysosomes leading to intracellular activation of trypsinogen is regarded as an initiation step. This activation of trypsinogen may be caused by the lysosomal enzyme cathepsin B. However, autoactivation of trypsinogen itself may be a possibility in pathogenesis. Autoactivation is enhanced in certain mutations of trypsinogen. Furthermore, an imbalance of protease inhibitors and active proteases may be involved. The role of pancreatic lipolytic enzymes, the role of bicarbonate secretion, and toxic Ca(2+) signals by excessive liberation from the endoplasmic reticulum have to be discussed in the pathogenesis of acute pancreatitis.
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PMID:New advances in cell physiology and pathophysiology of the exocrine pancreas. 2152 56

Prophylactic probiotic therapy has shown beneficial effects in an experimental rat model for acute pancreatitis on the health status of the animals. Mechanisms by which probiotic therapy interferes with severity of acute pancreatitis and associated sepsis, however, are poorly understood. The aims of this study were to identify the probiotic-induced changes in the gut microbiota and to correlate these changes to disease outcome. Duodenum and ileum samples were obtained from healthy and diseased rats subjected to pancreatitis for 7 days and prophylactically treated with either a multispecies probiotic mixture or a placebo. Intestinal microbiota was characterized by terminal-restriction fragment length polymorphism (T-RFLP) analyses of PCR-amplified 16S rRNA gene fragments. These analyses showed that during acute pancreatitis the host-specific ileal microbiota was replaced by an "acute pancreatitis-associated microbiota." This replacement was not reversed by administration of the probiotic mixture. An increase, however, was observed in the relative abundance of a novel bacterial phylotype most closely related to Clostridium lituseburense and referred to as commensal rat ileum bacterium (CRIB). Specific primers targeting the CRIB 16S rRNA gene sequence were developed to detect this phylotype by quantitative PCR. An ileal abundance of CRIB 16S rRNA genes of more than 7.5% of the total bacterial 16S rRNA gene pool was correlated with reduced duodenal bacterial overgrowth, reduced bacterial translocation to remote organs, improved pancreas pathology, and reduced proinflammatory cytokine levels in plasma. Our current findings and future studies involving this uncharacterized bacterial phylotype will contribute to unraveling one of the potential mechanisms of probiotic therapy.
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PMID:Correlation between protection against sepsis by probiotic therapy and stimulation of a novel bacterial phylotype. 2192 17


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