Showing papers on "Pancreatitis published in 1992"

A better model of acute pancreatitis for evaluating therapy.

Abstract: Existing models of acute pancreatitis have limitations to studying novel therapy. Whereas some produce mild self-limited pancreatitis, others result in sudden necrotizing injury. The authors developed an improved model providing homogeneous moderately severe injury by superimposing secretory hyperstimulation on minimal intraductal bile acid exposure. Sprague-Dawley rats (n = 231) received low-pressure intraductal glycodeoxycholic acid (GDOC) at very low (5 or 10 mmol/L) concentrations followed by intravenous cerulein. Cerulein or GDOC alone caused only very mild inflammation. However, GDOC combined with cerulein was uniformly associated with more edema (p less than 0.0005), acinar necrosis (p less than 0.01), inflammation (p less than 0.006), and hemorrhage (p less than 0.01). Pancreatic injury was further increased and death was potentiated by increasing volume and duration of intraductal low-dose GDOC infusion. There was significant morphologic progression between 6 and 24 hours. The authors conclude that (1) combining minimal intraductal bile acid exposure with intravenous hyperstimulation produces homogeneous pancreatitis of intermediate severity that can be modulated at will; (2) the injury is progressive over at least 24 hours with finite mortality rate; (3) the model provides superior opportunity to study innovative therapy.

Biliary sludge as a cause of acute pancreatitis.

Abstract: Background. In about 20 to 40 percent of cases of acute pancreatitis, no cause can be found, and these are labeled idiopathic. In this study, we sought to determine the frequency with which patients with acute idiopathic pancreatitis have biliary sludge, a suspension of cholesterol monohydrate crystals or calcium bilirubinate granules that is found predominantly in the gallbladder. Methods. Between 1980 and 1988, we prospectively studied 86 patients who had acute pancreatitis. In patients with no known cause of pancreatitis and no ultrasonographic evidence of gallstones or dilatation of the biliary ducts, we determined how often biliary sludge was present and its subsequent fate by repeated microscopical examinations of bile samples and abdominal ultrasonography. The outcome of patients treated by cholecystectomy or papillotomy was compared with that of untreated patients. Results. The pancreatitis was considered idiopathic in 31 of the 86 patients (36 percent), of whom 23 had microscopical evide...

Role of octreotide in the prevention of postoperative complications following pancreatic resection.

Abstract: Though morbidity and mortality rates following pancreatic resection have improved in recent years, they are still around 35% and 5%, respectively. Typical complications, such as pancreatic fistula, abscess, and subsequent sepsis, are chiefly associated with exocrine pancreatic secretion. In order to clarify whether the perioperative inhibition of exocrine pancreatic secretion prevents complications, we assessed the efficacy of octreotide, a long-acting somatostatin analogue. We conducted a randomized, double-blind, placebo-controlled, multicenter trial in 246 patients undergoing major elective pancreatic surgery. Patients were stratified into a high-risk stratum (limited to patients with pancreatic and periampullary tumors) or low-risk stratum (patients with chronic pancreatitis). Patients received octreotide (3 x 100 micrograms) or placebo subcutaneously for 7 days perioperatively. Eleven complications were defined: death, leakage of anastomosis, pancreatic fistula, abscess, fluid collection, shock, sepsis, bleeding, pulmonary insufficiency, renal insufficiency, and postoperative pancreatitis. Two hundred patients underwent pancreatic head resection, 31 patients underwent left resection, and 15 patients had other procedures. The overall mortality rate within 90 days was 4.5%, with 3.2% in the octreotide group and 5.8% in the placebo group. The complication rate was 32% in the patients receiving octreotide (40 of 125 patients) and 55% in patients receiving placebo (67 of 121 patients) (p less than 0.005). In the patients in the high-risk stratum, complications were observed in 26 of the 68 (38%) patients treated with octreotide and in 46 of 71 (65%) patients given placebo (p less than 0.01). Whereas in patients in the low-risk stratum, the complication rate was 25% (14 of 57 patients) in those treated with octreotide and 42% (21 of 50 patients) in patients given placebo (p = NS). The perioperative application of octreotide reduces the occurrence of typical postoperative complications after pancreatic resection, particularly in patients with tumors.

Stenting in severe chronic pancreatitis: results of medium-term follow-up in seventy-six patients.

Abstract: Between January 1985 and September 1989, 75 patients presenting with severe chronic pancreatitis with distal stricture and upstream dilatation underwent stenting of the main pancreatic duct (MPD) through the major papilla (n = 54) or minor papilla (n = 21) in order to drain the predominant duct through a 10F plastic prosthesis. All patients had undergone biliary and pancreatic sphincterotomy with a few cases of complications, and the majority (84%) also ESWL in the period from October 1987 onwards without complications. Relief of pain (94%) occurred parallel to a decrease in the MPD diameter. In a mean follow-up period of 37 months improvement of the nutrition status and relief of pain was seen. Clogging of these large plastic stents was treated by replacement or by another endoscopic or surgical procedure. Complications were treated endoscopically. Further measures necessary due to failure of stenting consisted of laterolateral pancreatico-jejunostomy in 15% of patients and placement of self-expanding 18F metal mesh stents in 29%. There was no mortality due to surgery. It is concluded that stenting of distal strictures in the MPD can lead to rapid resolution of pancreatic pain due to ductal hypertension and is the best means for determining the cause of pain, providing an alternative to surgery. Significant improvement of a stricture by prolonged stenting is however unusual, and such patients treated endoscopically require close follow-up with stent replacement approximately once a year.

Endotoxaemia and serum tumour necrosis factor as prognostic markers in severe acute pancreatitis.

Abstract: Endotoxaemia and circulating tumour necrosis factor are important prognostic factors in severe sepsis and are implicated in the pathogenesis of septic shock. Because clinical and pathological features in acute pancreatitis are similar to septic shock this study sought to determine whether endotoxin and tumour necrosis factor were prognostic factors in 38 patients with prognostically severe acute pancreatitis. Endotoxaemia, present in 19/37 (51%) patients on day 1, was more common in nonsurvivors than survivors (10/11, 91% v 9/26, 35%, p = 0.003). Day 1 serum endotoxin concentrations were higher in patients with a severe outcome (median (interquartile range) 314 (173-563) pg/ml v 0 (0-185) pg/ml, p<0.01) and in non-survivors (266 (173-586) pg/ml v 0 (0-165) pg/ml, p<0.01). Serum tumour necrosis factor was detectable in 47 of 109 samples (43%) from 38 patients (median 35 pg/ml, range 5-943 pg/ml). Day 1 serum tumour necrosis factor correlated with a worse prognostic score and a severe outcome in all patients (n = 38, r = 0.36, p = 0.027; r = 0.33, p<0.05) and with mortality in patients with gall stones (n = 23, r = 0.50, p = 0.02). Our data suggest that endotoxin and tumour necrosis factor could be prognostic factors in severe acute pancreatitis.

Interleukin-8 and neutrophil activation in acute pancreatitis.

Abstract: It has been suggested that leucocytes play an important role in the pathogenesis of complicated pancreatitis. Indeed, increased plasma concentrations of neutrophil elastase as a marker of neutrophil activation could be detected in patients with a severe course of the disease. Recently, interleukin-8 (IL-8) has been described as a novel neutrophil activating peptide. To determine the role of IL-8 in acute pancreatitis we measured its serum concentrations by a specific enzyme-linked immunosorbent assay in 10 patients with acute pancreatitis daily during the first week of hospitalization. IL-8 levels were compared with plasma concentrations of neutrophil elastase and the clinical course of the disease. Three of the patients had uncomplicated pancreatitis, while seven showed various extrapancreatic complications. Patients with complicated pancreatitis had statistically significant (P less than 0.05) higher mean values of IL-8 (121 +/- 41 pg/ml-1 vs. 13 +/- 6 pg ml-1, mean +/- SEM) and neutrophil elastase (547 +/- 35 ng ml-1 vs. 250 +/- 20 ng ml-1) than patients with uncomplicated disease. There was a positive correlation (r = 0.52, P less than 0.0001) between IL-8 and neutrophil elastase in the lower concentration range of IL-8 (less than 100 pg ml-1). At IL-8 levels greater than 100 pg ml-1 neutrophil elastase was always greatly elevated; however, under these conditions the relationship between IL-8 and elastase was no longer linear. No measurable IL-8 concentrations were found when plasma elastase was less than 200 ng ml-1. During follow-up, initially elevated IL-8 concentrations decreased in correlation with clinical improvement.(ABSTRACT TRUNCATED AT 250 WORDS)

Early surgical débridement of symptomatic pancreatic necrosis is beneficial irrespective of infection

Abstract: In order to assess the recent trend of nonoperative management of pancreatic necrosis, we reviewed 82 variables in 73 consecutive patients with symptomatic necrotizing pancreatitis. The mortality rate for the series was 25% (18 of 73). The only preintervention variables that correlated with mortality were APACHE II score greater than 15 (p = 0.01), preintervention blood transfusion (p less than 0.001), respiratory failure (p less than 0.001), and shock (p less than 0.01). Patients who developed recurrent sepsis following the initial intervention had a significantly higher mortality rate (17 of 34) than those who did not (1 of 39) (p less than 0.001). The rate of recurrent sepsis varied widely among individual surgeons and correlated with APACHE II score. The presence of infected versus noninfected necrosis did not correlate significantly with outcome. When percutaneous radiologically guided drainage was the initial therapeutic modality (n = 6), recurrent sepsis requiring surgical drainage inevitably occurred. Patients treated with percutaneous drainage (often in combination with surgical drainage) had a longer hospital stay (82 versus 42 days, p less than 0.001), spent more days in the intensive care unit (31 versus 6 days, p less than 0.001), and required more days of total parenteral nutrition (57 versus 27 days, p less than 0.001) than those treated solely by surgical means. We conclude that aggressive initial surgical debridement should be the first step in managing symptomatic pancreatic necrosis and that the presence of infection should not be the sole determinant of intervention.

Splenic and portal venous obstruction in chronic pancreatitis : a prospective longitudinal study of a medical-surgical series of 266 patients

Abstract: The aim of this study was a prospective search for splenoportal venous obstruction (SPVO) in a medical-surgical series of 266 patients with chronic pancreatitis who were followed up a mean time of 8.2 years. SPVO was systematically searched for using ultrasonography and then confirmed by angiography or computed tomography. SPVO was found in 35 patients (13.2%) but was symptomatic in only two. Initial obstruction involved the splenic vein in 22 patients, the portal vein in 10, and the superior mesenteric vein in three. Since venous obstruction extended from the splenic to the portal vein in five patients, the prevalence of portal obstruction was 5.6% (15/266). Acute pancreatitis and pseudocysts were the probable cause of SPVO in 91.4% of our cases. Half the cases of splenic venous obstruction were related to pseudocysts of the caudal pancreas. Esophageal varices were found in two patients and gastric varices in four at the time of diagnosis and during follow-up. At the end of follow-up, 12 patients had undergone splenopancreatectomy (N=11) or splenectomy (N=1). Only one patient was operated on for massive esophageal variceal bleeding, and another patient died due to intractable colic variceal bleeding. In four of six patients operated on with portal vein obstruction, surgery was difficult due to venous collaterals. Ten patients were not operated on and 13 patients operated on were not treated for SPVO. The mean follow-up after diagnosis of SPVO for these final 23 patients was 28.9 months. None of these patients bled. We concluded that in chronic pancreatitis: (1) the prevalence of SPVO is 13.2%; (2) SPVO should be systematically searched for in patients with acute pancreatitis or pseudocysts, especially if therapeutic decisions would be modified by a diagnosis of SPVO; (3) the risk of digestive variceal bleeding is lower than previously reported; and (4) portal vein obstruction seems to be riskier than splenic vein obstruction, especially if surgery is needed.

The morphological basis for the evolution of acute pancreatitis into chronic pancreatitis.

Abstract: The pathogenesis of chronic pancreatitis is still unsettled. The most commonly cited theory postulates that the deposition of protein plugs which later calcify leads to duct obstruction with subsequent fibrotic replacement of the acinar tissue upstream of the occlusion [13]. Alternatively, we have proposed a working hypothesis that relates the pathogenesis of chronic pancreatitis with that of acute pancreatitis [8, 9]. The sequence of events that we believe may connect acute with chronic pancreatitis starts with interstitial fat necrosis and hemorrhage that induces perilobular fibrosis. Perilobular fibrosis, in turn, may also distort the interlobular ducts, creating stenoses and dilatations. The ducts, once altered, hamper the normal flow of pancreatic secretions, thereby enabling the precipitation of proteins (protein plugs) and eventually their calcification (calculi). If duct obstruction becomes more extensive, the acinar cells upstream of such a stenosis disappear, leaving dense intralobular fibrosis.

Role of interleukin-6 in acute pancreatitis. Comparison with C-reactive protein and phospholipase A.

Abstract: Plasma values of immunoreactive interleukin-6, C-reactive protein and phospholipase A have been determined in serial samples from 24 patients with acute pancreatitis ('mild' pancreatitis nine, 'severe' pancreatitis 15). Median plasma concentrations of interleukin-6, C-reactive protein, and phospholipase A activity were significantly higher in patients with 'severe' illness (p < 0.001) than those with 'mild' illness. A particularly marked increase in interleukin-6 was found in two patients with necrotising pancreatitis and fatal outcome. Significant correlations between plasma concentrations of interleukin-6 and phospholipase A (p = 0.0218) and C-reactive protein and phospholipase A activity (p < 0.0001) were found in patients with 'severe' disease. These findings in a limited number of patients with acute pancreatitis are promising in that raised interleukin-6 correlated with clinical severity and with two other established markers, C-reactive protein, and phospholipase A activity.

Changes in peptidergic innervation in chronic pancreatitis.

Abstract: SummaryWe sought to identify characteristics of peptidergic innervation that altered in patients with chronic pancreatitis. Pancreatic tissue removed from patients with chronic pancreatitis was analyzed by immunohistochemistry using antisera against neuropeptide Y, tyrosine hydroxylase, vasoactive i

Relation of diagnostic serum amylase levels to aetiology and severity of acute pancreatitis.

Abstract: The sensitivity of diagnostic serum amylase (greater than 1000 iu/l) was assessed in 417 patients with acute pancreatitis as a result of gall stones (258), alcohol (104), or miscellaneous causes (55), of whom 111 (27%) had a clinically severe attack (including 34 deaths). On hospital admission, an amylase value diagnostic of pancreatitis was found in 96.1% of all mild cases and in 87.4% of severe cases (p less than 0.001); at 48 hours these values were 33.3% and 48.2% respectively (p = 0.026). Diagnostic amylase levels for alcoholic patients were found in 86% of mild cases on admission and in 76% of severe cases (p less than 0.001, compared with other groups). The diagnostic levels were also significantly lower at 24 hours for both the alcoholic and miscellaneous groups compared with the gall stone group (p less than 0.001). Eight of 27 (30%) patients with a serum amylase activity less than 1000 iu/l had pancreatic necrosis compared with 12 of the remaining 390 (3.1%) patients (p less than 0.001); the mortality was also significantly different (44% v 5.6% respectively, p less than 0.001). These data support the view that more sensitive tests for acute pancreatitis are needed for routine use especially in those whose disease has an alcoholic aetiology.

Extracorporeal lithotripsy of pancreatic stones in patients with chronic pancreatitis and pain: a prospective follow up study.

Abstract: Extracorporeal shock wave lithotripsy of pancreatic duct stones (largest stone 12 (SD) 6 mm) was performed in 24 patients with abdominal pain and a dilated duct system (main pancreatic duct 10 (3) mm). The procedure was well tolerated in all but two patients, who had a mild pancreatitic attack immediately after lithotripsy. Disintegration of the stones was achieved in 21 patients. This allowed complete clearance of the duct system by an endoscopic approach in 10 (42%) patients and partial clearance in 7 (29%) patients. Within a mean follow up period of 24 (14) months half of the patients showed complete or considerable relief of pain and alleviation of symptoms was achieved in seven patients. Relief of pain occurred more often after complete ductal clearance. There were no fatalities within the follow up period. These findings underline the value of a combined non-surgical approach, using endoscopy and adjuvant shock wave lithotripsy to patients with large pancreatic calculi and pain attacks.

Human pancreatitis-associated protein. Messenger RNA cloning and expression in pancreatic diseases.

Abstract: A human pancreatic cDNA library was screened with the cDNA encoding rat "pancreatitis-associated protein" (PAP). The selected clone encoded a secretory protein structurally related to rat PAP. The protein had the same size as rat PAP and showed 71% amino acid identity, the six half-cystines being in identical positions. Domains of the proteins showing homologies with calcium-dependent lectins were also conserved. In addition, expression in pancreas of the genes encoding the human protein and rat PAP showed similar characteristics: both were expressed at very low levels in control tissue and overexpressed during the acute phase of pancreatitis, contrary to most secretory products. The human protein was therefore named human pancreatitis-associated protein (PAP-H). Antibodies raised to a synthetic peptide of PAP-H detected a single band with an M(r) compatible with PAP-H in Western blot analysis of proteins extracted from a pancreas presenting with acute pancreatitis. In that tissue, the protein could be immunolocalized to the apical regions of acinar cells. An immunoassay was also constructed to quantify the protein in serum. Elevated PAP-H levels were observed in patients with acute pancreatitis and in some patients with chronic pancreatitis. Values were close to background in healthy subjects and in patients with other abdominal diseases. These results confirm that PAP-H synthesis increases during inflammation and suggest a possible use of the protein as biological marker of acute pancreatitis.

Treatment of Pain with Pancreatic Extracts in Chronic Pancreatitis: Results of a Prospective Placebo-Controlled Multicenter Trial

Abstract: According to the theory of negative feedback regulation of pancreatic enzyme secretion by proteases, treatment with pancreatic extracts has been proposed to lower pain in chronic pancreatitis by decreasing pancreatic duct pressure. We conducted a prospective placebo-controlled double blind multicenter study to investigate the effect of porcine pancreatic extracts on pain in chronic pancreatitis. 47 patients with pain (41 males, 6 females) due to chronic pancreatitis documented by sonography, endoscopic retrograde cholangiopancreatography, and CT were included. Exclusion criteria were steatorrhea above 30 g/day, gastric or pancreatic resections in the history, and serum bilirubin above 1.5 mg/dl. Patients received pancreatic extracts (acid-protected microtablets; Panzytrat -20,000; 5 x 2 capsules/day; proteases/capsule 1,000 Pharmacopoea europaea units) for 14 days followed by treatment with placebo for another 14 days or vice versa. Pain (graded from 0 to 3) and concomitant use of analgesics (N-butylscopolaminiumbromide and tramadol) were recorded by diary. Physical examination and blood chemistry were done at day -1, 15 and 29. Quantitative stool fat was determined at days -2/-1, 13/14 and 27/28. 43 patients completed the studies. Pain improved in most patients irrespective of whether they started with placebo or verum. There was no significant difference between both treatment arms. We conclude that pancreatic extracts are not very efficient in lowering pain.

Hormone-Induced Pancreatitis

Abstract: Intravenous infusion of the synthetic cholecystokinin analogue cerulein at a dose of 0.25 micrograms/kg/h causes maximal stimulation of pancreatic exocrine secretion. The infusion of supramaximal doses of cerulein (5 and 10 micrograms/kg/h) induces a significant increase in pancreatic enzymes in blood, and interstitial edema and inflammatory cell infiltration. This model of hormone-induced pancreatitis works in rats, mice, dogs and hamsters. Besides intravenous infusion, repeated intraperitoneal injections can also be used for induction of pancreatitis. In the early phase of cerulein-induced pancreatitis, large autophagic vacuoles result from fusion of zymogen granules within the acinar cell. This is accompanied by an increase in lysosomal enzyme activity and activation of trypsinogen which finally leads to cellular necrosis. All animals survive the induction of pancreatitis. The pancreas completely regenerates within 6 days after induction of pancreatitis. This model of experimental pancreatitis favors the analysis of intracellular events in the early phase of pancreatitis.

Minimal change chronic pancreatitis.

Abstract: In patients with severe abdominal pain, of pancreatic origin, there are a few with minimal or equivocal findings on pancreatic investigation and in whom the aetiology of their pancreatic disease is elusive. The findings and outcome in 16 of these patients (four men and 12 women) who underwent resection are reported. Pancreatic imaging showed minimal or equivocal findings in all 16; pancreas divisum was present in five. All were managed conservatively at first but resection was required for progression of symptoms. A drainage procedure was performed initially in five patients but relief of pain was at best transitory before further surgery was required. Partial resection was needed in 12, of whom eight required subsequent completion pancreatectomy and four had a one stage total resection. Nine patients are currently pain free after resection or are very much improved, while six are no better and one patient has died from an unrelated cause. Histology of resected specimens showed chronic inflammatory changes accompanied by subtle non-inflammatory changes in all but one. These changes include duct proliferation, duct complex formation, adenomatous nodules, and acinar cell atrophy, the significance of which is unclear. These findings suggest a syndrome of minimal macroscopic and radiological change chronic pancreatitis with pain as its chief clinical feature and a distinct histology, the aetiology of which is unclear. It seems that there is a distinct syndrome of minimal change pancreatitis, among the group of patients which presents with the clinical features of chronic pancreatitis.

Aspects of medical history and exocrine carcinoma of the pancreas: a population-based case-control study in The Netherlands.

Abstract: During 1984-88 a population-based case-control study was carried out in The Netherlands, in collaboration with the International Agency for Research on Cancer, to examine the possible relationship between aspects of medical history and exocrine pancreatic carcinoma in 176 cases and 487 controls. About 58% of patients were interviewed directly. We observed an inverse relationship between medical treatment for allergy-related conditions and the development of pancreatic cancer (30 cases vs. 130 controls, OR 0.57, 95% CI 0.36 to 0.90). A history of gallbladder problems, gallstones, cholecystectomy, stomach or duodenal ulcer, pancreatitis, appendicitis, diabetes or tonsillectomy was not related to risk. In direct responses, compared with once daily, a positive relationship was seen for stool frequency, 10 years ago, of less than once daily (18 cases vs. 40 controls, OR 2.10, 95% CI 1.09 to 4.04). In men, diabetes treated with insulin and diagnosed more than 1 year previously was significantly and positively related to risk (5 cases vs. 1 control, OR 11.66, 95% 1.28 to 105.95). In brief, the results of the present study suggest that a history of allergy-related conditions may protect, whereas a past stool frequency of less than once daily may enhance the risk of cancer of the pancreas. Other elements of the medical history were not consistently related to risk.

Pancreatic exocrine and endocrine function after operations for chronic pancreatitis.

Abstract: Exocrine and endocrine function of the pancreas was assessed in the early postoperative period ( p > 0.10). Endocrine function was initially spared after proximal pancreatectomy, but six additional patients (16%, p < 0.05) required treatment for diabetes at a mean of 19 months (range, 3 to 34). Deterioration in pancreatic function is thus not an invariable immediate consequence of pancreatic drainage procedures or partial pancreatectomy for chronic pancreatitis. Progression of disease must account, in part, for failure of both exocrine and endocrine function on long-term follow-up. Drainage operations appear to delay this progressive decline in pancreatic function.

Cytologic examination of pure pancreatic juice in the diagnosis of pancreatic carcinoma. The endoscopic retrograde intraductal catheter aspiration cytologic technique

Abstract: Background. Although cytologic examination of pure pancreatic juice obtained with a duodenofiberscope has been useful for the diagnosis of pancreatic carcinoma, the rate of false-negative results is reported to be high. To eliminate these false-negative results, the authors developed a new technique, endoscopic retrograde intraductal catheter aspiration cytology, especially for an accurate cytologic diagnosis of carcinoma of the body or tail of the pancreas. Methods. The accuracy of conventional cytologic examination of pure pancreatic juice was assessed in 25 patients with pancreatic carcinoma, 29 patients with pancreatitis, and 52 control subjects. Pure pancreatic juice was collected from the pancreatic duct by endoscopic cannulation using a videoimaging duodenoscope after intravenous administration of secretin. The new endoscopic retrograde intraductal catheter aspiration technique was used in four patients with carcinoma of the body or tail of the pancreas and five patients with localized pancreatitis in whom a correct diagnosis was not made by previous cytologic examination of pure pancreatic juice. Results. Positive cytologic findings were obtained in 76% of the patients with pancreatic carcinoma. Positive cytologic results were more frequent in patients with carcinoma of the head of the pancreas than in those with carcinoma of the body or tail. By the new technique, positive cytologic results were obtained in all of the patients with pancreatic carcinoma. This technique caused no severe complications. Conclusions. This procedure of endoscopic retrograde intraductal catheter aspiration cytology seems useful for diagnosis of pancreatic carcinoma.

Glutathione monoethyl ester ameliorates caerulein-induced pancreatitis in the mouse.

Abstract: Studies in animal models suggest that oxygen radicals may be important in the pathogenesis of acute pancreatitis. Because glutathione is an essential component of the defense against radical-mediated cellular injury, we investigated whether pancreatic glutathione content is influenced by inducing acute pancreatitis and whether augmenting the intracellular supply of glutathione would alter the course of pancreatitis. Caerulein, a decapeptide cholecystokinin analogue, induces acute necrotizing pancreatitis in mice when given in high doses (50 micrograms/kg per h) over a period of 6 h. The pancreatic glutathione content (total, GSH + GSSG) in mice treated with high-dose caerulein fell to 17% of normal within 4 h of beginning caerulein and recovered toward normal after discontinuing caerulein treatment. Mice treated with glutathione monoethyl ester (20 mmol/kg 1 h before caerulein, 10 mmol/kg 3 and 7 h after starting caerulein) were found to have blunted depletion of pancreatic glutathione, diminished histologic evidence of pancreatitis (necrosis, inflammation, and vacuolization), and lower serum amylase values compared with mice treated with caerulein alone. These findings suggest that the profound depletion of pancreatic glutathione caused by hyperstimulation of the pancreas with caerulein is critically important in the pathogenesis of acute caerulein-induced pancreatitis.

Does the somatostatin analogue octreotide protect against ERCP induced pancreatitis

Abstract: This study evaluates the effect of the long acting somatostatin analogue octreotide on biochemical and clinical parameters of endoscopic retrograde cholangiopancreatography (ERCP) induced pancreatitis. Altogether 245 patients were randomised to receive either octreotide or isotonic saline. Octreotide (100 micrograms) was administered intravenously five minutes before ERCP and subcutaneously 45 minutes after ERCP. There were no significant differences in the median serum amylase and lipase activities at baseline, eight, and 24 hours after ERCP. Five patients (2%) developed clinical pancreatitis--three in the octreotide and two in the placebo groups. Excluding patients who developed pancreatitis, 43 (18%) developed abdominal pain after ERCP--21 in the octreotide and 23 in the placebo groups. There were no significant differences in the median serum amylase and lipase values between the treatment groups. None of the 52 patients who had therapeutic interventions developed pancreatitis. This study suggests that octreotide may not protect against ERCP induced pancreatitis.

Effects of antioxidants and free radical scavengers in three different models of acute pancreatitis.

Abstract: Summary The present studies were done to evaluate the therapeutic potential of several antioxidants and free radical scavengers in three different models of acute pancreatitis. (a) Edematous pancreatitis with acinar cells necrosis was induced by seven hourly intraperitoneal injections of 50 > of caerulein per kg in mice. (b) Hemorrhagic pancreatitis was induced by feeding a choline-deficient, ethionine-supplemented (CDE) diet in mice. (c) Hemorrhagic pancreatitis was induced by retrograde infusion of 0.6 ml of 5% sodium taurocholate into the pancreatic duct in rats. The following antioxidants and free radical scavengers were given at various doses intravenously, subcutaneously, or in-traperitoneally before the onset of pancreatitis: Ebselen [2-phenyl-1,2-benziso-selenazol-3(2H)-one], superoxide dismutase, catalase, deferoxamine (Des-feral), dimethyl sulfoxide, or allopurinol. The severity of pancreatitis was assessed at various times after its onset by determination of serum amylase and pancreatic weight (edema), by grading of histological alterations, and by determination of survival (survival determined in models of hemorrhagic pancreatitis). In general, free radical scavengers and antioxidants ameliorated edema and inflammation to a greater degree than necrosis and the increase in serum amylase. Superoxide dismutase (as did Ebselen in previous studies) exerted beneficial effects on survival in diet-induced pancreatitis in the absence of marked effects on pancreatic necrosis, suggesting that these beneficial effects are due to amelioration of extrapancreatic complications that often contribute to mortality in acute pancreatitis. None of the antioxidants had major beneficial effects in taurocholate-induced hemorrhagic pancreatitis. Thus, formation of free radicals may be important for progression and outcome in diet-induced and, to a lesser degree, in caerulein-induced pancreatitis but not at all in taurocholate-induced pancreatitis. Different models of pancreatitis may, therefore, involve different degrees and mechanisms of free radical formation. Despite the amelioration of edema and the beneficial effects on mortality seen for some antioxidants in some of the models, antioxidants and free radical scavengers appear to have only a limited potential for treatment of acute pancreatitis.

Pancreatitis in children.

Abstract: The pathophysiology of pancreatic autodigestion is poorly understood. Pancreatitis affects all age groups, and the diagnosis is sometimes missed when serum amylase and lipase activities are not measured in the child with abdominal pain. Acute pancreatitis in children has become a more commonly seen condition and the causes have varied. Laboratory and radiological studies play an important role in determining the diagnosis and prognosis. Family history is important in the diagnosis of idiopathic hereditary pancreatitis. Most acute episodes resolve with supportive care, but the mortality in acute pancreatitis is currently about 15% (Hadorn et al., 1980). Endoscopic retrograde cholangiopancreatography or an endoscopic retrograde pancreatogram may be necessary to investigate relapses of pancreatitis. Chronic pancreatitis can be a life-threatening condition requiring lifetime medical management.