cholecystokinin and Pancreatitis--Chronic

We review important new clinical observations in chronic pancreatitis made in the last year.. Cholecystokinin-stimulated endoscopic pancreatic function testing has low specificity for diagnosis of early chronic pancreatitis, likely because of correctable technical limitations or failure to exclude confounding diseases. Fecal elastase 1 is a poor test for diagnosing pancreatic malabsorption. A 2-week trial of corticosteroids may differentiate autoimmune pancreatitis (AIP) from pancreatic cancer in select patients. A genetic screen may help to predict relapse of AIP. Repeated, 6-month visits to counsel against alcohol use may reduce recurrent attacks of alcoholic pancreatitis. A five-component antioxidant cocktail may reduce the frequency of pain in chronic pancreatitis by 1.5 days per month.. Researchers this last year have further characterized clinical aspects of chronic pancreatitis that may lead to improved detection of early chronic pancreatitis and AIP, risk stratification and application of risk-lowering strategies to prevent relapses in AIP or the development of recurrent (and possibly chronic) alcoholic pancreatitis and new evidence that antioxidants may have a modest effect on reducing the dominant symptom in chronic pancreatitis, abdominal pain.

Topics: Adrenal Cortex Hormones; Alcohol Drinking; Antioxidants; Cholecystokinin; Diagnosis, Differential; Endoscopy; Feces; Genetic Testing; Humans; Pancreatic Elastase; Pancreatic Function Tests; Pancreatitis, Chronic

Direct pancreatic function tests have been the mainstay for the diagnosis of pancreatic exocrine insufficiency. Due to their cumbersome nature and limited availability there is a continuous search for a rapid and inexpensive test of pancreatic function. Endoscopic approaches to evaluate pancreatic function have been assessed. This article critically reviews the current evidence related to this novel approach, outlining some elements for further refinement.

Topics: Adult; Child, Preschool; Cholecystokinin; Endoscopy, Digestive System; Gastrointestinal Agents; Humans; Pancreatic Function Tests; Pancreatitis, Chronic; Secretin

Chronic pancreatitis represents a condition that is challenging for clinicians secondary to the difficulty in making an accurate diagnosis and the less than satisfactory means of managing chronic pain. This review emphasises the various manifestations that patients with chronic pancreatitis may have and describes recent advances in medical and surgical therapy. It is probable that many patients with chronic abdominal pain are suffering from chronic pancreatitis that is not appreciated. As the pathophysiology of this disorder is better understood it is probable that the treatment will be more successful.

Topics: Cholangiopancreatography, Endoscopic Retrograde; Cholecystokinin; Clinical Enzyme Tests; Diagnosis, Differential; Endoscopy, Digestive System; Female; Humans; Islets of Langerhans Transplantation; Malabsorption Syndromes; Male; Nerve Block; Oxidative Stress; Pain; Pain Management; Pancreas; Pancreatitis, Chronic

Topics: Abdominal Injuries; Cholecystokinin; Diagnosis, Differential; Dogs; Drug Therapy; Gastrointestinal Hormones; Humans; Pancreatic Extracts; Pancreatin; Pancreatitis; Pancreatitis, Chronic; Pathology; Physiology; Research; Surgical Procedures, Operative

The Food and Drug Administration in 2006 required that all pancreatic enzyme products demonstrate bioavailability of lipase, amylase, and protease in the proximal small intestine.. In this phase I open-label, randomized, crossover trial, 17 adult chronic pancreatitis (CP) patients with severe exocrine pancreatic insufficiency (EPI) underwent two separate gastroduodenal perfusion procedures (Dreiling tube suctioning and [. Zenpep administration with a test meal was associated with significant increase in duodenal aspiration of lipase (p = 0.046), chymotrypsin (p = 0.008), and amylase (p = 0.001), compared to the test meal alone, indicating release of enzymes to the duodenum. Lipase delivery was higher in the pH subpopulation (the efficacy population with acid hypersecretors excluded) (p = 0.01). Recovery of [. In CP patients with severe EPI, lipase, chymotrypsin and amylase were released rapidly into the duodenum after ingestion of Zenpep plus meal compared to meals alone. Results also reflected the known pH threshold for enzyme release from enteric coated products.

Topics: Adult; Aged; Amylases; Biological Availability; Cholecystokinin; Chymotrypsin; Cross-Over Studies; Drug Delivery Systems; Duodenum; Exocrine Pancreatic Insufficiency; Female; Humans; Intestine, Small; Lipase; Male; Middle Aged; Pancreatic Extracts; Pancreatitis, Chronic; Trypsin; Young Adult

We have previously demonstrated that the pancreas can recover from chronic pancreatitis (CP) lesions in the cerulein-induced mouse model. To explore how pancreatic recovery is achieved at the molecular level, we used RNA-sequencing (seq) and profiled transcriptomes during CP transition to recovery. CP was induced by intraperitoneally injecting cerulein in C57BL/6 mice. Time-matched controls (CON) were given normal saline. Pancreata were harvested from mice 4 days after the final injections (designated as CP and CON) or 4 weeks after the final injections (designated as CP recovery (CPR) and control recovery (CONR)). Pancreatic RNAs were extracted for RNA-seq and quantitative (q) PCR validation. Using RNA-seq, we identified a total of 3,600 differentially expressed genes (DEGs) in CP versus CON and 166 DEGs in CPR versus CONR. There are 132 DEGs overlapped between CP and CPR and 34 DEGs unique to CPR. A number of selected pancreatic fibrosis-relevant DEGs were validated by qPCR. The top 20 gene sets enriched from DEGs shared between CP and CPR are relevant to extracellular matrix and cancer biology, whereas the top 10 gene sets enriched from DEGs specific to CPR are pertinent to DNA methylation and specific signaling pathways. In conclusion, we identified a distinct set of DEGs in association with extracellular matrix and cancer cell activities to contrast CP and CPR. Once during ongoing CP recovery, DEGs relevant to DNA methylation and specific signaling pathways were induced to express. The DEGs shared between CP and CPR and the DEGs specific to CPR may serve as the unique transcriptomic signatures and biomarkers for determining CP recovery and monitoring potential therapeutic responses at the molecular level to reflect pancreatic histological resolution.

Topics: Animals; Ceruletide; Cholecystokinin; Disease Models, Animal; Extracellular Matrix; Female; Gene Expression Profiling; Gene Expression Regulation; Male; Mice; Mice, Inbred C57BL; Pancreas; Pancreatitis, Chronic; RNA-Seq; Signal Transduction; Transcriptome

Current endoscopic pancreatic function test (ePFT) methods use either secretin or cholecystokinin (CCK) to measure pancreatic function.. To evaluate a novel ePFT protocol that includes both secretin and CCK stimulation and to assess which fluid parameters best discriminate patients with chronic pancreatitis (CP).. Prospective, cross-sectional diagnostic study.. Single, tertiary-care institution.. Healthy volunteers and patients evaluated for CP were included.. All patients underwent a combined secretin-CCK ePFT. Patients evaluated for CP also underwent EUS during the same endoscopic session.. Duodenal fluid bicarbonate, lipase, and amylase concentrations were measured after CCK and secretin stimulation. Results were compared based on the presence of CP detected by EUS (≥5 features).. Twenty healthy volunteers and 69 patients evaluated for CP completed the secretin and CCK ePFT. Patients with an EUS score of 5 or higher had significantly decreased peak bicarbonate concentrations (72 mmol) compared with patients with an EUS score lower than 5 (90 mmol) and healthy subjects (108 mmol) (P < .001). Peak concentrations of amylase and lipase and total fluid volume were not significantly different between patients with CP and controls. Receiver-operating characteristic analysis revealed that peak bicarbonate concentration had superior discrimination for CP (area under the curve [AUC] 0.738) compared with peak amylase (AUC 0.677) and peak lipase (AUC 0.627). The addition of enzyme concentration measurement did not improve discrimination compared with peak bicarbonate alone.. Secretin and cholecystokinin endoscopic pancreatic function test (SC ePFT) results were not compared with those of single hormone ePFTs.. The addition of CCK infusion and enzyme concentration measurement to a standard secretin ePFT does not enhance the diagnosis of CP.

Topics: Acinar Cells; Adult; Amylases; Area Under Curve; Bicarbonates; Chi-Square Distribution; Cholecystokinin; Cross-Sectional Studies; Duodenoscopy; Duodenum; Endosonography; Female; Humans; Lipase; Male; Middle Aged; Pancreatic Function Tests; Pancreatitis, Chronic; Prospective Studies; ROC Curve; Secretin; Statistics, Nonparametric

To ascertain correlations between pancreatic secretion disturbances and stage and complications of chronic pancreatitis (CP).. The examination covered 81 CP patients (32 females, 49 males, mean age 55.9 +/- 1.8 years). Alcohol pancreatitis (AP) was diagnosed in 52 of them, biliary pancreatitis--in 29, complicated pancreatitis--in 25 patients. The control group consisted of 22 patients without symptoms of gastrointestinal disease.. By the results of clinical, device, laboratory and morphological tests we recognize 3 variants of CP course. Variant A: duration under 5 years, distinct pain syndrome, pancreatic fecal elastase (E-1) level insignificantly decreased, elevated blood levels of acetylcholine (Ac), serotonin (5-NT), cholecystokinin (CCK), secretin is subnormal. Pancreatic tissue is inflamed and swollen. Variant B: duration 5-10 years, E-1 under 100 mcg/g, moderate pain syndrome, prevalence of 5-NT as a stimulator of pancreatic secretory activity. CCK is high and secretin is low. Further progress of fibrous changes by ultrasound investigation, abdominal CT leads to calcinosis in pancreatic tissue. Variant C: duration 10 years and longer, weak pain syndrome, further rise of 5-NT concentration, decompensation of regulatory mechanisms of secretory pancreatic activity, CCK is high, secretin is subnormal.. Changes in correlations between neuromediators and hormones in CP reflect adaptation aimed at retension of secretory pancreatic activity in significant fibrous changes of pancreatic tissue.

Topics: Acetylcholine; Biomarkers; Cholecystokinin; Disease Progression; Female; Follow-Up Studies; Humans; Male; Middle Aged; Pancreatitis, Chronic; Prognosis; Secretin; Serotonin

Long-term alcohol consumption alone did not cause chronic pancreatitis (CP) but impaired exocrine pancreatic function. This study is to explore the reversibility of exocrine pancreatic insufficiency in the abstinent rats and its mechanism.. Forty-eight healthy male Wistar rats were divided randomly into 4 groups: 6-month control, 6-month ethanol, 9-month control, and 9-month ethanol + withdrawal. Morphological changes of pancreatic acinar cells were observed. Pancreatic amylase and lipase were measured using an automatic biochemical analyzer. Free fatty acid (FFA) in rat intestinal chyme was measured. Cholecystokinin (CCK) levels were determined by radioimmunoassay. The expression of CCK-A receptors was quantitatively analyzed by Western blot.. Alcohol-induced ultramicrostructure changes of pancreatic acinar cells, including lipid droplets, myelinoid inclusion bodies, dilated rough endoplasmic reticulums, and diminished zymogen granules, were not attenuated after alcohol abstinence. The outputs of amylase and lipase, FFA content in intestinal chyme, and the intestinal and the pancreatic CCK levels in rats were reduced after chronic alcohol intake and were still lower than the control after cessation of alcohol use. Chronic ethanol intake or abstinence did not induce any change in the expression of CCK-A receptors.. Exocrine pancreatic insufficiency was irreversible in alcoholic rats without CP after alcohol withdrawal. It may be attributed to reduced pancreatic CCK, long-standing fatty infiltration, ultramicrostructure injuries in pancreatic acinar cells, and aging.

Topics: Alcoholism; Amylases; Animals; Blotting, Western; Central Nervous System Depressants; Cholecystokinin; Energy Intake; Ethanol; Exocrine Pancreatic Insufficiency; Fatty Acids, Nonesterified; Immunohistochemistry; Intestinal Mucosa; Lipase; Male; Pancreas; Pancreatitis; Pancreatitis, Chronic; Rats; Rats, Wistar; Receptor, Cholecystokinin A; Substance Withdrawal Syndrome; Triglycerides; Weight Gain

Topics: Acute Disease; Cholecystokinin; Humans; Jaundice, Obstructive; Pancreatitis; Pancreatitis, Chronic; Radioimmunoassay

Endoscopic ultrasound (EUS) detects mild and severe structural abnormalities of the pancreas that correlate with fibrosis. Direct pancreatic function tests (PFTs) detect mild exocrine insufficiency associated with early fibrosis. The primary aim of this study was to compare EUS structural criteria with duct-cell and acinar-cell function.. Fifty patients evaluated for chronic pancreatitis underwent combined EUS and secretin endoscopic PFTs (ePFT) on day 1 and CCK ePFT on day 2. EUS images were videotaped and interpreted by consensus of 3 blinded expert reviewers.. There were inverse correlations of EUS consensus score with both duct-cell bicarbonate secretion (R = -0.71, P < .001) and acinar-cell lipase secretion (R = -0.52, P < .001). With secretin ePFT as reference standard, EUS (>or=4 criteria) showed a sensitivity of 71% (95% confidence interval [CI], 53%-89%) and specificity of 92% (95% CI, 75%-99%). With CCK ePFT as reference standard, EUS had a sensitivity of 63% (95% CI, 43%-82%) and specificity of 85% (95% CI, 71%-98%). Main duct dilation, irregularity, calcifications, and visible side-branches were most predictive of exocrine insufficiency (positive predictive value >80% for both acinar- and duct-cell insufficiency).. Acinar- and duct-cell function decreases as EUS structural abnormalities increase. EUS has fair sensitivity and very good specificity compared with secretin and CCK functional reference standards.

Topics: Adult; Aged; Bicarbonates; Cholecystokinin; Endoscopy, Digestive System; Endosonography; Female; Humans; Lipase; Male; Middle Aged; Pancreas; Pancreatic Function Tests; Pancreatitis, Chronic; Radiography; Secretin; Sensitivity and Specificity

To measure content of neuromediators (acetylcholine-Ach, serotonin-5-NT) and gastrointestinal hormones (cholecystokinine-CCK and secretin) in the blood serum of patients with chronic pancreatitis (CP); to study protective properties of the mucus in the duodenum in CP.. CCK and secretin concentrations were estimated by enzyme immunoassay, Ach and 5-NT were measured biochemically basally and after standard meal in 65 CP patients and in the control group. Proteolytic activity of the mucus was assessed by Anson's method. An inhibitory property of the mucus was studied by residual proteolytic activity of pepsine after its incubation with mucus.. In AP patients the response of biologically active substrates to standard meal changed: 5-NT concentration rose from 0.40 +/- 0.07 to 0.55 +/- 0.05 mcg/ml (p < 0.05) while Ach dropped from 1.7 +/- 0.3 to 1.6 +/- 0.3 mmol/l (p > 0.05). BP patients responded to the standard meal with 5-HT concentration rise from 0.28 +/- 0.04 to 0.43 +/- 0.05 mcg/ml (p < 0.05), Ach changed insignificantly (from 1.5 +/- 0.12 to 1.45 +/- 0.21 mmol/l, p > 0.05, reselectively). CCK after standard meal significantly rose both in AP and BP. AP and BP patients had strong direct correlation between concentrations of 5-HT and CCK (r = 0.875439) and weak negative correlation with Ach level (r = -0.2209). In AP and BP patients secretin level weakly negatively correlated both with 5-NT and Ach levels (r = -0.4839 and r = -0.33207, respectively). Reduction of secretin secretion diminished secretion of bicarbonates and mucus with simultaneous change in the quality of mucous gel.. In CP of various etiology there are changes in the level and proportions of neuromediators and hormones causing alterations in the regulation system. These disorders correlate with disturbances in pancreatic excretory function and destructive tissue changes. Bicarbonates secretion decreases and changes quality of the secreted mucus.

Topics: Case-Control Studies; Cholecystokinin; Duodenal Diseases; Female; Humans; Intestinal Mucosa; Male; Middle Aged; Neurotransmitter Agents; Pancreas; Pancreatitis, Chronic; Secretin

Topics: Amylases; Cholecystokinin; Clinical Enzyme Tests; Gastrointestinal Hormones; Humans; Lipase; Pancreatitis; Pancreatitis, Chronic; Secretin

Topics: Carnitine; Cholecystokinin; Digestion; Dogs; Enzymes; Gastrointestinal Hormones; Guinea Pigs; Malabsorption Syndromes; Metabolism; Pancreatic Juice; Pancreatitis; Pancreatitis, Chronic; Pathology; Pharmacology; Research; Secretin; Vitamin B Complex

Topics: Bile Ducts; Cholecystography; Cholecystokinin; Humans; Pancreatitis; Pancreatitis, Chronic

Topics: Cholecystokinin; Diagnosis; Gastrointestinal Hormones; Pancreatitis; Pancreatitis, Chronic

A series of 53 cases of chronic pancreatic disease is described and attention drawn to the frequency with which symptoms are persistent rather than intermittent. A plea is made for the use of the term ;progressive' rather than ;relapsing' in describing many of these cases. Alcohol was an unimportant factor in the aetiology. The possibility of achieving an accurate and early diagnosis using the serum secretin/pancreozymin test is emphasized. The frequent relief of symptoms and the prevention of progress of the disease by surgery, especially sphincterotomy, is recorded.

Topics: Aged; Amylases; Celiac Disease; Cholecystokinin; Clinical Enzyme Tests; Clinical Laboratory Techniques; Gastrointestinal Hormones; Humans; Pancreas; Pancreatic Diseases; Pancreatitis; Pancreatitis, Chronic; Prognosis; Secretin; Statistics as Topic; Surgical Procedures, Operative

A simple evocative test has been used to study pancreatic function. Serial estimations of amylase and lipase in blood serum are made at intervals up to six hours and again at 24 hours after injecting intravenously standard doses of secretin and pancreozymin. The results of 213 tests on a normal group, in pancreatic disease, in biliary and hepatic diseases have been analysed and compared with the results of duodenal intubation and an oral glucose tolerance test. A combined evocative test and oral glucose tolerance test provide evidence of pancreatic dysfunction in the majority of cases of cancer of the pancreas and chronic pancreatitis. The conditions of the test are described and the pathological lesions in which false positive evocative tests may be found are indicated. The simple evocative test provides the earliest biochemical evidence of pancreatic disease in some patients with cancer of the pancreas and chronic pancreatitis.

Topics: Amylases; Cholecystokinin; Clinical Enzyme Tests; Gastrointestinal Hormones; Glucose Tolerance Test; Humans; Lipase; Male; Pancreas; Pancreatic Diseases; Pancreatitis, Chronic; Secretin