Intraductal Secretin Test Is as Useful as Duodenal Secretin Test in Assessing Exocrine Pancreatic Function

We assessed the clinical usefulness of theintraductal secretin test in order to ascertain whetherit can substitute for the conventional duodenal secretintest. Duodenal juice was obtained with a triple-lumen tube and pure pancreatic juice was obtained byretrograde cannulation of the main pancreatic duct usinga duodenofiberscope. Pancreatic secretion was stimulatedby a bolus intravenous injection of secretin (100 units). The two tests showed comparableinterindividual coefficients of variation, significantlygood correlations, and comparable diagnosticefficiencies. The intraductal secretin test showed noless reproducibility than that of the duodenalsecretin test as reported in the literature. In theintraductal secretin test, secretory volume, peak flowrate, bicarbonate output, and lipase output yielded the best diagnostic efficiency, followed by amylaseoutput and maximal bicarbonate concentration. In theintraductal secretin test, a 10-min collection providedas much information as a 20-min collection. We conclude, therefore, that the 10-minintraductal secretin test is as useful as theconventional duodenal secretin test in assessingexocrine pancreatic function and that the mostdiscriminatory parameters are secretory volume, bicarbonate output, andamylase (or lipase) output.     

Short-Term and Long-Term Pancreatic Exocrine and Endocrine Functions After Pancreatectomy

Exocrine and endocrine functions of the pancreaswere assessed in 44 Japanese patients who underwentpancreatic head resection. Functions were analyzedcomparing levels before surgery, at a short-termfollow-up (<2 months), and at a long-term follow-up(12-31 months). The N-benzoyl-L-tyrosyl-p-aminobenzoicacid (BT-PABA) excretion test, fasting blood sugar (FBS)level, and oral glucose tolerance test (OGTT) were used to determine pancreatic function. Thepatients were divided into three groups according to thesize of the main pancreatic duct: group 1, 15 patientswith a normal sized duct (3 mm); group 2, 20 with a moderately dilated duct (>3 mm,<10 mm); and group 3, 9 with a markedly dilated duct(10 mm). The mean BT-PABA value (6-hr urinary PABArecovery rate) in group 1 showed no change during the postoperative period. In contrast, theBT-PABA values in groups 2 and 3 had dropped by theshort-term follow-up and returned to the preoperativelevel by the long-term examination. FBS and 120-min OGTT levels were not different between the threegroups preoperatively. Although these values showed nochange in all the three groups at the short-termmeasurements, the FBS in group 3 and 120-min levels in all the three groups had increased at thelong-term. These findings suggest that exocrinepancreatic function shows a short-term deterioration inpatients with a dilated pancreatic duct but recovers to the preoperative level over the long term afterpancreatic head resection. Endocrine insufficiency,however, may occur at a long-term point after surgeryirrespective of the preoperative pancreatic ductal dilatation.     

Melatonin Reduces Lipid Peroxidation and Tissue Edema in Cerulein-Induced Acute Pancreatitis in Rats

Since oxygen free radicals and lipidperoxidation have been implicated in the pathogenesis ofan early stage of acute pancreatitis, we examinedwhether melatonin, a recently discovered free-radicalscavenger, could attenuate pancreatic injury inSprague-Dawley rats with cerulein-induced pancreatitis.Acute pancreatitis was induced by four intraperitonealinjections of cerulein (50 g/kg body wt) given at1-hr intervals. Thirty minutes after the lastcerulein injection, the rats were killed and the degreeof pancreatic edema, the level of lipid peroxidation inthe pancreas, and serum amylase activity were increased significantly. Pretreatment with melatonin (10or 50 mg/kg body wt) 30 min before each ceruleininjection resulted in a significant reduction inpancreatic edema and the levels of lipid peroxidation.Serum amylase activity, however, was notsignificantly influenced by either dose of melatonin.Moreover, we found that cerulein administration wasassociated with stomach edema as well as high levels oflipid peroxidation in the stomach and smallintestine, which were also reduced by melatonin.Melatonin's protective effects in cerulein-treated ratspresumably relate to its radical scavenging ability andto other antioxidative processes induced bymelatonin.     

Noninvasive Monitoring of Hemodynamic Changes in Acute Pancreatitis in Rabbits

Hemodynamic parameters of experimental acutenecrotizing pancreatitis (AP) were monitored by means ofechocardiography in rabbits. Left ventricular (LV)systolic and diastolic parameters were determined before and 1, 3, 6, 12, 18, and 24 hr afterinjection of taurocholic acid in the pancreatic duct inAP animals. Temporary LV dilatation was observed 6 hrafter the AP induction [LV end-diastolic (ED) diameter from 1.16 ± 0.04 to 1.22 ± 0.04cm, P < 0.05, ED volume from 2.98 ± 0.34 to3.57 ± 0.75 ml, P < 0.05] without decrease insystolic function. Cardiac output (CO) and stroke volume(StV) was increased in both groups 3 hr after the operation (from 0.53 ±0.15 to 0.71 ± 0.06 L/min, P < 0.05 in AP),but in the AP animals it remained high. However, 24 hrafter AP induction, both the CO and the StV weredecreased significantly. The LV diastolic function was impaired 1 hrafter AP induction, but had recovered after 12 hr. Inconclusion, an early diastolic impairment followed by LVenlargement could be noninvasively observed in experimental AP in rabbits.     

Gastric Transit and Pharmacodynamics of a Two-Millimeter Enteric-Coated Pancreatin Microsphere Preparation in Patients with Chronic Pancreatitis

It has been suggested that enteric-coatedpancreatin microsphere (ECPM) preparations with spheresizes larger than 1.7 mm pass through the stomach at aslower rate than a meal and therefore may be less efficacious in restoring pancreatic enzymeactivity than preparations with smaller sphere sizes.The aim of this study was to investigate the gastrictransit profile of a 2-mm ECPM preparation in relation to that of a solid meal and to simultaneouslymeasure enzyme activities in eight patients withpancreatic exocrine insufficiency due to chronicpancreatitis. Gastric transit was assessed bydouble-isotope scintigraphy. A pancake was labeled with^99mTc. A 2-mm ECPM preparation was labeledwith ¹⁷¹Er. Intraluminal pancreatic enzymeactivities were assessed during a 6-hr period with thecholesteryl-[¹⁴C]octanoate breath test (for carboxyl ester lipaseactivity) and the N -benzoyl-L-tyrosyl-p aminobenzoicacid/p-aminosalicylic acid (NBT-PABA/PAS) test (forchymotrypsin activity). The ECPM preparation passedthrough the stomach more rapidly (median 24 min) thanthe pancake (median 52 min, P < 0.05). During ECPMtherapy, mean cumulative ¹⁴CO₂outputs rose significantly from 30% to 70% (P <0.05), but remained below outcomes in healthy volunteers. Mean cumulative plasmaPABA concentrations rose significantly from 46% to 87%(P < 0.05) and were not significantly different fromoutcomes in healthy volunteers. In chronic pancreatitis, a 2-mm ECPM preparation does not pass throughthe stomach more slowly than a solid meal, but in factfaster. Digestion of ester lipids and proteins showed animprovement to subnormal and normal levels,respectively.     

Octreotide Ameliorates Glucose Intolerance Following Acute Experimental Pancreatitis

The long-term effects of octreotide, thesynthetic analog of the hormone somatostatin, on acuteexperimental pancreatitis were studied. Acutepancreatitis was induced in rats by intraparenchymalinjections of 0.5 ml 5% or 10% sodium taurocholate.Octreotide (10 mg/kg/day, subcutaneously), or salineinjections as controls, were started four hours later,and their effects were assessed 30, 60, and 90 daysafter the induction of pancreatitis. Neitherintrapancreatic saline injections nor octreotideadministration without the induction of pancreatitiscaused any biochemical or histological abnormalities.Taurocholate-induced pancreatitis was followed by remarkablehyperglycemia, which was ameliorated by octreotide.Thirty days after induction of pancreatitis, glucoselevels were 269 ± 21 mg/100 ml and 153 ±17 mg/100 ml in the control and octreotide treated animals,respectively (P < 0.02). Octreotide administrationwas associated with increased pH values after 60 and 90days (P < 0.05 for the 90 days group). The levels ofhematocrit, calcium, and amylase were already within thenormal ranges after 30 days and were unaffected byoctreotide. There were no signs of chronic exocrineinsufficiency and all the surviving rats gained weight during the follow-up. However, the relativeweights of the pancreases of the octreotide-treatedanimals were higher than those of the controls 30 daysafter IOP. Histopathological evaluation demonstrated regeneration of the pancreatic tissue, andincreased number and hypertrophy of the islets ofLangherhans. There were no significant differenceswhether the octreotide treatment was given for only 48or 96 hr. Survival was significantly improved byoctreotide; only one octreotide-treated rat (2.5%) with10% taurocholate-induced pancreatitis died, while six(15%) of the control animals succumbed (P < 0.05). These studies provided data on the sequelae ofacute pancreatitis and showed that octreotide may havelong-term beneficial effects in this disease.     

Golimumab Ameliorates Pancreatic Inflammatory Response in the Cerulein-Induced Acute Pancreatitis in Rats

Background:The aim of the study was to evaluate whether a new and successful treatment opportunity can be provided in acute pancreatitis and may prevent symptomatic treatments and show its effect through etiopathogenesis. Therefore, we want to investigate the efficacy of golimumab in an experimental rat model of cerulein-induced acute pancreatitis.Methods:A total of 35 rats, including 7 rats in each group, were distributed into 5 groups (sham, acute pancreatitis, placebo, acute pancreatitis + golimumab 5 mg/kg, and acute pancreatitis + golimumab 10 mg/kg). An experimental cerulein-induced acute pancreatitis model was accomplished by intraperitoneal cerulein injections. After sacrification, rat blood samples were collected for amylase, IL-6, and IL-1beta measurements. Histopathological analysis of the pancreas was performed with Tunel and hematoxylin & eosin staining.Results:Amylase, IL-6, and IL-1beta levels were found to be increased in the acute pancreatitis group. IL-1beta, amylase, IL-6 levels, and pancreatic inflammation were all significantly decreased in golimumab groups (P < .01). Moreover, in both golimumab groups, golimumab treatment significantly reduced apoptosis in pancreatic tissues (P < .05). Golimumab treatment was found to significantly reduce edema formation, inflammation, vacuolization, and fat necrosis of pancreatic tissues (P < .05).Conclusion:Firstly in the literature, we investigated the efficacy of golimumab in the experimental acute pancreatitis model. In the light of our findings, it could be suggested that golimumab may be an effective and safe therapeutic option in the treatment of patients with acute pancreatitis.     

Irreversible Exocrine Pancreatic Insufficiency in Alcoholic Rats Without Chronic Pancreatitis After Alcohol Withdrawal

Background: 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. Methods: 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. Results: 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. Conclusions: 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.     

Pseudocysts in Acute Nonalcoholic Pancreatitis (Incidence and Natural History)

Epidemiological studies on pancreaticpseudocysts are retrospective analyses on alcoholicpatients. The aims of this study were to investigate theincidence, natural history, and predictors of theappearance and disappearance of pancreatic fluidcollections and pseudocysts after nonalcoholic acutepancreatitis. We carried out a prospective cohort studyin a series of 926 patients with acute pancreatitis.Pancreatic fluid collections or pseudocysts were treatedonly after complications. We studied pancreatic fluidcollections from 83 patients (8.9%): 48 of whomdeveloped pseudocysts (5.1%). Both were less frequent after biliary pancreatitis (P < 0.0001). Inthe first 60 days of follow-up, patients with fluidcollections or pseudocysts showed more complicationsthan spontaneous disappearance; two of them died. After the 60th day, spontaneous disappearancewas more frequent, and at one year the cumulativeincidence of complications and spontaneous disappearancewas 36% and 56%, respectively. A total of 33 patients with fluid collection needed interventionaltreatment (surgery or percutaneous or endoscopicdrainage). Pseudocysts that were small (<5 cm) ordeveloped in the tail had a higher incidence ofspontaneous disappearance: 22/24 (91.7%) and 11/12 (91.7%),respectively. In conclusion, fluid collections andpseudocysts after nonalcoholic pancreatitis have a lowincidence of complications and mortality with a high rate of spontaneous disappearance. Wesuggest treating them only aftercomplications.     

Incidence,Risk Factors and Clinical Course of Pancreatic Fluid Collections in Acute Pancreatitis

Background

Acute pancreatitis is an acute inflammatory process of the pancreas with variable involvement of other regional tissues or remote organ systems. Acute fluid collections and pseudocyst formation are the most frequent complications of acute pancreatitis.

Aims

The aims of this study were to evaluate the incidence, risk factors, and clinical course of pancreatic fluid collections and pseudocyst formation following acute pancreatitis.

Methods

A prospective multicenter study was conducted in five participating centers with 302 patients diagnosed with acute pancreatitis from January 2011 to July 2012.

Results

The incidence of pancreatic fluid collections and pseudocyst was 42.7 and 6.3 %, respectively. Patients with fluid collections were significantly younger, compared to those without fluid collections (51.5 ± 15.9 vs. 60.4 ± 16.5 years, P = 0.000). The proportion of alcoholic etiology (54.3 %) in patients with fluid collections was significantly higher compared to other etiologies (P = 0.000). C-reactive protein (CRP) (48 h) was significantly higher in patients with fluid collections, compared to patients without fluid collections (39.2 ± 77.4 vs. 15.1 ± 36.2 mg/dL, P = 0.016). LDH (48 h) was significantly higher in patients with pseudocyst formation, compared to patients with complete resolution (1,317.6 ± 706.4 vs. 478.7 ± 190.5 IU/L, P = 0.000). Pancreatic fluid collections showed spontaneous resolution in 69.8 % (90/129) and 84.2 % of the pseudocysts disappeared or decreased in size during follow up.

Conclusions

Age, CRP (48 h), and alcohol etiology are risk factors for pancreatic fluid collections. LDH (48 h) appears to be a risk factor for pseudocyst formation. Most pseudocysts showed a decrease in size or spontaneous resolution with conservative management.     

Induction of Proliferation in Isolated Guinea Pig Gastric Epithelium During Restitution After Superficial Injury

Immediate repair of the gastrointestinalepithelium after superficial injury is calledrestitution. It is based on the migration of thesurviving mucoid neck cells over the area of injury. Theinvolvement of growth factors in the process has beenrecently documented. They are known to enhance theprocess (ie, EGF, FGF, TGF-) and to activate thebasolateral Na⁺-H⁺-antiport (EGF).They may exert their effect by activating intracellular tyrosinekinases or by inducing chemotaxis. Yet, their precisemechanism of action in the process is unknown. The aimof the present study was to investigate the effect of modulation of the signal transductionpathway on the occurrence of proliferative mucoid neckand foveolar cells in guinea pig gastric epithelium.Therefore guinea pig gastric epithelium was mounted in Ussing chambers in vitro and perfused 4 hrafter superficial injury with 1.25 M NaCl. The potentialdifference over the epithelium and tissue resistancewere recorded simultaneously. The tissue was exposed either to cycloheximide, genistein, or to4-phorbol myristate 13-acetate (PMA) during the 4-hrrecovery, and the expression of proliferative cells wasassessed by staining the tissue for proliferative cells (Ki-67). The mean proliferative index oftissues subjected to NaCl injury was significantlyhigher than that of uninjured control tissues after 4 hrof restitution. Inhibition of the signaling pathway with genistein decreased the proliferative indexsignificantly, while its stimulation with phorbolmyristate increased it. Both electrophysiologic andmorphologic restitution were sensitive to genistein, but not to PMA or cycloheximide. Superficialepithelial injury results in a significantly increasedoccurrence of proliferative cells in isolated guinea piggastric epithelium. This endogenous activation of the tissue is sensitive to inhibition bytyrosine kinases and to stimulation by protein kinases.Electrophysiologic and morphologic recovery are alsoaffected by the modulation of the signaling pathway. This suggests that it is involved in theimmediate repair process.     

Differential Induction of HSP60 and HSP72 by Different Stress Situations in Rats (Correlation with Cerulein-Induced Pancreatitis)

We previously reported that water-immersionstress specifically induced the synthesis of a 60-kDaheat-shock protein (HSP60, chaperonin homolog) inpancreatic cells and preinduction of HSP60 completely prevented development of cerulein-inducedpancreatitis in the rat in an HSP60 quantitativelydependent manner. In order to study the cytoprotectivefunction of a 72-kDa heat-shock protein (HSP72,stress-inducible hsp70), the effect of specific preinduction ofHSP72 by hyperthermia on cerulein-induced pancreatitiswas investigated and compared with the effect ofpreinduction of HSP60 in this study. Expression of HSP60 and HSP72 in the pancreas wasinvestigated by immunoblot before and after waterimmersion or hyperthermia. Following pretreatment withwater-immersion stress or hyperthermia, the rats wereinjected with cerulein (40 g/kg, intraperitoneally).The pancreas wet weight and serum amylase concentrationwere measured before and after cerulein injection.Hyperthermia (42.5°C, 20 min) specifically induced HSP72 in the pancreas. The synthesis of HSP60was specifically induced by water-immersion stress inthe pancreas. Cerulein-induced pancreatitis was clearlyprevented by specific preinduction of HSP60 by water-immersion stress. However, preinductionof HSP72 by hyperthermia had no preventive effect oncerulein-induced pancreatitis. Our findings suggest thatHSP60 and HSP72 have distinct functions in the pancreas, and their induction mechanisms arealso different in vivo. These results could be importantfor understanding the mechanism of adaptivecytoprotection in the pancreas mediated byheat-shock proteins.     

Hepatic Denervation Ameliorates Sodium and Water Retention in Experimental Cirrhosis in Rats

Increased activity in the hepatic sympatheticnervous system may exacerbate salt and water retentionin patients with liver cirrhosis. The aim of this studywas to evaluate sodium and water homeostasis in rats with cirrhosis induced bydiethylnitrosamine and to investigate the influence ofhepatic denervation in this model. Animals wererandomized into three groups: diethylnitrosamine-treatedrats with (N = 13) and without (N = 8) hepaticdenervation and control rats (N = 8). Rats were fed anormal salt diet (0.23% sodium ad libitum). The 24-hrmeasurements for sodium balance, water balance, andcreatinine clearance were performed every two weeks for 12weeks after surgery. Diethylnitrosamine-inducedcirrhosis was confirmed histologically. The cumulativechange in sodium balance in the innervateddiethylnitrosamine-treated rat increased progressively and wassignificantly higher than the control during the lastfour weeks of the study. Meanwhile, rats with hepaticdenervation showed significantly smaller changes incumulative sodium balance at week 12 than those in theinnervated group. The cumulative changes in waterbalance in the innervated group were significantlygreater at weeks 10 and 12 than those of the denervatedand control group, which remained unchangedthroughout the study. Creatinine clearance in theinnervated group decreased at weeks 10 and 12 byapproximately 70% from baseline (P < 0.05); incontrast, it did not change significantly in the denervatedgroup and control group throughout the study. Theseresults demonstrated that hepatic denervationameliorates sodium and water retention as well asglomerular function in cirrhosis model in rats.     

Comparison of Ultrasound-Secretin Test and Sphincter of Oddi Manometry in Patients with Recurrent Acute Pancreatitis

Manometry is considered the gold standard forevaluating sphincter of Oddi dysfunction. It hasrecently been demonstrated that the ultrasound (US)secretin test proposed a few years ago as a noninvasive test for the study of sphincter of Oddidysfunction yields a substantial percentage ofpathological findings in patients with acute recurrentpancreatitis. The aim of this study was to compare theresults of the US secretin test with sphincter of Oddimanometry findings in a consecutive series of patientswith recurrent acute pancreatitis. Forty-seven patientsadmitted to our gastrointestinal unit suffering from recurrent acute pancreatitis underwentultrasonographic measurement of the main pancreatic ductat baseline and for 60 min after maximal stimulationwith secretin at 1 IU/kg. According to the US secretin test findings in 35 healthy control subjects,the test results were considered to indicate pathologywhen the duct was still dilated after 20 min. Withinthree to seven days the same patients underwent perendoscopic manometry. Thirty-six patients(17 men, 19 women; mean age 41 ± 15 years) had asuccessful US secretin test and sphincter of Oddimanometry. Eleven patients (30.6%) presented normalmanometric findings. Two of these had an abnormal USsecretin test. Twenty-five patients had abnormalmanometry findings, revealing stenosis in 19 (52.7%) (17with abnormal US secretin test) and dyskinesia in six (five with an abnormal US secretin test).Compared to manometry findings, the US secretin testsensitivity and specificity for sphincter of Oddidysfunction were 88% and 82%, respectively. Inconclusion, most patients with recurrent acute pancreatitishave sphincter of Oddi dysfunction documented by both atthe US secretin test and sphincter of Oddi manometry;results of the US secretin test are reliable compared to sphincter of Oddi manometry, andtherefore the US secretin test may offer a validalternative to the more expensive and invasivemanometric procedure for assessing sphincter of Oddidysfunction in patients with recurrent acutepancreatitis.     

Peptide Leukotriene Receptor Antagonist Diminishes Pancreatic Edema Formation in Rats with Cerulein-Induced Acute Pancreatitis

Background: This study was designed to evaluate the protective effect of a peptide leukotriene receptor antagonist, pranlukast hydrate, against pancreatic injuries during acute pancreatitis. Methods: Acute pancreatitis was induced in rats by intravenous infusion of a supramaximal dose of cerulein (5 μg/kg·h for 4 h). In this model marked hyperamylasemia, a significant increase in pancreatic water content, and a significant increase in pancreatic microvascular leakage of Evans blue dye were observed. Pancreatic subcellular redistribution of the lysosomal enzyme cathepsin B from the lysosomal fraction to the zymogen fraction was also observed. Results: Pretreatment with pranlukast hydrate at a dose of 10 mg/kg (twice, 8 and 4 h before cerulein infusion) significantly inhibited these pancreatic injuries, including hyperamylasemia, increased pancreatic microvascular permeability, and redistribution of cathepsin B in pancreatic acinar cells. Conclusions: These results suggest that peptide leukotrienes may be involved in the pathogenesis of acute pancreatitis in the early stage of the disease and that peptide leukotriene receptor antagonist might be of therapeutic value for treatment of acute pancreatitis.     

Alcohol and Smoking as Risk Factors in Chronic Pancreatitis and Pancreatic Cancer

The aim of this study was to compare alcohol andsmoking as risk factors in the development of chronicpancreatitis and pancreatic cancer. We considered onlymale subjects: (1) 630 patients with chronic pancreatitis who developed 12 pancreatic and 47extrapancreatic cancers; (2) 69 patients withhistologically well documented pancreatic cancer and noclinical history of chronic pancreatitis; and (3) 700 random controls taken from the Verona pollinglist and submitted to a complete medical check-up.Chronic pancreatitis subjects drink more than controlsubjects and more than subjects with pancreatic cancer without chronic pancreatitis (P < 0.001).The percentage of smokers in the group with chronicpancreatitis is significantly higher than that in thecontrol group [odds ratio (OR) 17.3; 95% CI 12.6-23.8; P < 0.001] and in the group with pancreaticcarcinomas but with no history of chronic pancreatitis(OR 5.3; 95% CI 3.0-9.4; P < 0.001). In conclusion,our study shows that: (1) the risk of chronic pancreatitis correlates both with alcoholintake and with cigarette smoking with a trendindicating that the risk increases with increasedalcohol intake and cigarette consumption; (2) alcoholand smoking are statistically independent risk factors forchronic pancreatitis; and (3) the risk of pancreaticcancer correlates positively with cigarette smoking butnot with drinking.     

A Pancreatic Extract-Enriched Diet Corrects Ileal Mucosa Atrophy in Endotoxemic Aged Rats

An altered adaptive response of the pancreas andsmall intestine to nutritional stress has an adverseimpact upon nutritional status in elderly humans orsenescent rats. We evaluated the effects of a pancreatic extract nutritional supplement on intestinalmucosa adaptation in LPS-treated aged rats. Endotoxemicrats were starved for 48 hr and then refed ad libitumfor four days with a standard diet. Afterwards they received, over one week, the standard dietenriched with either pancreatic extract (PE) (2.4 g/day)or casein (isonitrogenous to PE supplement). Healthyaged rats fed ad libitum with a standard diet were studied in parallel. Whereas no changesoccurred in the jejunal segment, an adaptive villushyperplasia was observed in the proximal ileum of ratsreceiving PE without an increase in the brush border hydrolase activities. Our results indicate thatoral PE supplementation exerts a trophic effect on theileal mucosa of aged rats in response to nutritionalstress.     

Sequential Changes in Pancreatic Markers in Acute Pancreatitis

Background: Trypsinogen activation within acinar cells plays a crucial role in the pathogenesis of acute pancreatitis (AP). Our aim was to characterize temporal changes of trypsinogen-1, trypsinogen-2, complexes of trypsin-1- &#33 1 -antitrypsin (T1-AAT) and trypsin-2- &#33 1 -antitrypsin (T2-AAT), trypsinogen activation peptide (TAP) and pancreatic secretory trypsin inhibitor (PSTI) in patients with AP. Methods: The study comprised 64 consecutive patients with AP (19 with severe disease) and 32 controls. The concentrations of trypsinogen-1 and -2, PSTI, T1-AAT and T2-AAT were determined by time-resolved immunofluorometric assays (IFMA), and TAP was measured using a competitive enzyme immunoassay from serum and urine. Results: The concentrations of trypsinogen-1 and -2 in serum reflected similar patterns, but excretion of trypsinogen-1 into urine was markedly lower than that of trypsinogen-2, the concentration of which correlated strongly with disease severity. The concentrations of T1-AAT were no higher in severe AP than in mild AP, while T2-AAT concentrations were significantly higher in severe than in mild disease. PSTI increased over the course of several days, showing strong correlation with disease severity. The concentrations of plasma and urinary TAP decreased rapidly to undetectable levels. During the early phase of AP, TAP correlated with the disease severity in plasma and urine but there was no difference between controls and patients with mild AP. Conclusion: More pronounced changes in trypsinogen-2 and its complex with AAT than in those of trypsinogen-1 were demonstrated, suggesting that trypsinogen-2 might play a more important role in the pathogenesis of AP than earlier believed. Urinary PSTI showed features warranting further investigations as a marker of disease severity.     

Therapeutic Small-Volume Resuscitation Preserves Pancreatic Microcirculation in Acute Experimental Pancreatitis of Graded Severity in Rats

Background: Microcirculatory disorders play a major part in the pathogenesis of acute pancreatitis. Improvement of microcirculation is hypothesized to open a therapeutic window. The aim of this study was to evaluate the effects of small-volume resuscitation in acute pancreatitis. Methods: In rats, acute pancreatitis of graded severity was induced and pancreatic microcirculation was observed in vivo with an epiluminescent microscope. Primary outcome measures were microcirculation, leukocyte adherence, concentration oftrypsinogen-activating peptide, amylase activity and histopathologic tissue damage. Results: In necrotizing pancreatitis patients receiving prophylactic intervention with 7.5% hypertonic saline the functional capillary density was 76%. Postcapillary venular leukocyte adherence was 45% of vein cross-section. The median histopathologic damage scored 8 points. In controls, a complete microcirculatory breakdown was observed, and in the group with therapeutic intervention no significant difference was detected. In intermediate pancreatitis, the number of perfused capillaries remained 55.0 versus 23.3% in controls. Leukocyte adherence was 40.0 versus 51.7%. The histopathologic damage scored 6.0 versus 9.0 points. Trypsinogen-activating peptide concentration was reduced to 164 versus 402 nM in controls. In cerulein pancreatitis, the number of perfused capillaries was equally preserved in both groups. Conclusion: Small-volume resuscitation preserves capillary microcirculation and prevents pancreatic injury in intermediate necrotizing pancreatitis.