Pancreatic secretion after secretin and cholecystokinin stimulation in chronic alcoholics with and without cirrhosis

We have studied the volume, protein concentration, total protein, and chymotrypsin and trypsin outputs in pure pancreatic juice (PPJ) following endoscopic cannulation of the pancreatic duct in 11 male and 2 female patients with advanced alcoholic cirrhosis (AC). Results were compared to those obtained from 21 nonalcoholic volunteers (NAV) and 26 chronic alcoholic (CA) patients without cirrhosis. Intravenous stimulation with secretin followed 10 min later by intravenous cholecystokinin-pancreozymin (CCK-PZ) resulted in highly significant increases in volumes during both phases of pancreatic stimulation in AC compared to NAV and CA. Protein concentration and total output during secretin stimulation was not different among the three groups. During CCK-PZ stimulation, CA exhibited a significant elevation in protein concentration and total output compared to NAV and AC. Although total chymotrypsin output was lower in secretin-stimulated CA than other groups, no other differences between the groups were observed in either of the hormone-stimulation phases. Marked elevations in trypsin output were observed in secretin-stimulated AC and in CCK-PZ-stimulated AC and CA. The high PPJ volume and the relatively low protein concentration observed in AC may effect a washout phenomenon resulting in a decreased tendency for ductal protein precipitation in these patients.     

Alcoholism and alcoholic organ damage and genetic polymorphisms of alcohol metabolizing enzymes in Chinese patients

It is still not clear why some alcoholic patients acquire certain organ-specific complications of alcoholism whereas other alcoholic patients acquire different ones. As we know the liver alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), and cytochrome P4502E1 (P4502E1) are polymorphic at the ADH2, ADH3, and ALDH2 loci and the 5'-flanking region of the P4502E1. The aim of this study was to investigate the differences between Chinese alcoholic patients with cirrhosis and acute pancreatitis by studying the genetic polymorphisms of ADH2, ADH3, ALDH2, and P4502E1. Genotyping of ADH2, ADH3, ALDH2, and P4502E1 was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods on peripheral white blood cell DNA from 75 alcoholic cirrhotic patients, 48 acute alcoholic pancreatitis patients, 19 heavy drinkers without liver disease or pancreatitis, and 235 controls. The results showed that the frequencies of the alleles ADH2*1 and ALDH2*1 in the alcoholic cirrhotic patients were significantly higher than those in the nonalcoholic controls. In acute alcoholic pancreatitis patients, only the frequency of allele ALDH2*1, not ADH2*1 was significantly higher than in the nonalcoholic controls. The allele frequency of ADH2*1 in acute pancreatitis patients was significantly lower (P < .01) than in alcoholic cirrhotic patients. The daily amount of alcohol consumption was significantly lower in patients with acute pancreatitis than in patients with cirrhosis (P < .0005). The genotype distributions of P4502E1, detected by RsaI and PstI, were not different among alcoholic cirrhotic patients, alcoholic pancreatitis patients, heavy drinker, and nonalcoholic controls. In conclusion, ALDH2*1 is the most important alcohol metabolizing gene affecting predisposition to alcoholism whereas the ADH2*2 gene may influence susceptibility to acute alcoholic pancreatitis. The patients with alcohol-induced cirrhosis and with alcohol-induced acute pancreatitis are of two different subpopulations.(Hepatology 1997 Jan;25(1):112-7)     

Exocrine Pancreatic Function in Chronic Liver Diseases

To confirm the respective influence of chronic alcoholism and liver disease on exocrine pancreatic function in cholecystokinin secretin (CS), tests were performed on patients with chronic liver cirrhosis (LC) and non-cirrhotic (nLC) disease of alcoholic (A) and nonalcoholic (nA) etiology. Results were compared in four subgroups (ALC, N = 26; AnLC, N = 45; nALC, N = 18; and nAnLC, N = 43). Volume of duodenal juice and bicarbonate output (BO) were increased and maximal bicarbonate concentration was decreased in ALC, compared with those in normal controls. Comparison of LC and nLC indicated that the volume, BO, and amylase output (AO) were greater in LC than in nLC of alcoholic etiology, but not in those of nonalcoholic etiology. The initial disappearance rate (KICG) of indocyanine green (ICG) excretion correlated with a parameter of CS test in alcoholic liver disease (vs. volume: r = -0.51, p less than 0.01 vs BO: r = -0.40, p less than 0.01), but not in nonalcoholic liver disease. Concurrent chronic pancreatitis with pain and definite exocrine insufficiency was observed in only one ALC patient and in four AnLC patients, but in none of the nonalcoholics. In alcoholic liver disease, exocrine pancreatic secretion tends to increase with severity of liver damage, but concurrence of definite chronic pancreatitis is not correlated with the severity.     

Sphincter of oddi manometry

Summary Conclusion. In chronic alcohol abusers with no pancreatic disease, secretin was found to induce a paradoxical spasmodic response in the sphincter of Oddi (SO) instead of the relaxation observed in controls. Cerulein, on the contrary, had a normal relaxing effect on the SO. Background. We previously reported SO dyskinesia in cases of chronic pancreatitis. Here we investigated whether chronic alcohol consumption may have contributed to the genesis of this dyskinesia. Methods. SO and main pancreatic duct pressures were recorded endoscopically with a dual electronic pressure sensor in 27 chronic alcohol abusers and compared with the values obtained in 15 normal controls. These pressures were recorded both in the basal state and after applying hormonal stimulation by injecting either secretin (1 CU/kg) or cerulein (75 ng/kg). Results. Cerulein relaxed the SO in both the controls and the chronic alcohol abusers, whereas it transiently enhanced the main pancreatic duct (MPD) pressure. Secretin induced a wave of MPD hyperpressure (+15.4±3.0 mm Hg) in both groups of subjects, but in the alcoholic group, instead of relaxing SO, it significantly enhanced the amplitude of phasic contractions (+32.6±8.4 mm Hg). The SO basal pressure was also paradoxically enhanced by secretin in the alcoholic patients (28.8±8.2 vs 10.1±2.4 mm Hg).     

Comparative study of pancreatic polypeptide (PP) secretion, endocrine and exocrine function, and structural damage in chronic alcohol induced pancreatitis (CAIP)

The serum pancreatic polypeptide response to intravenous Boots secretin (1.5 U/kg), glucose tolerance, and insulin responses have been studied in 25 patients with chronic alcohol induced pancreatitis of varying severity, and these results compared with a secretin-pancreozymin test, and the structural damage noted on pancreatography. For the pancreatic polypeptide response 16 healthy subjects acted as controls. There was a marked reduction in pancreatic polypeptide response in patients with advanced structural changes of chronic alcohol induced pancreatitis compared with patients with minimal/moderate changes (p less than 0.01) and with healthy controls (p less than 0.05) although there was no difference between the latter two groups. Similarly, while the ratio of peak to mean basal pancreatic polypeptide concentration was also significantly reduced in patients with advanced changes compared with healthy controls (p less than 0.05) there was a marked degree of overlap in patients with lesser degrees of structural damage and control subjects. For all patients with chronic alcohol induced pancreatitis, however, there was a significant correlation between the pancreatic polypeptide response and each parameter of the standard secretin-pancreozymin test and with glucose tolerance and the integrated insulin response. We conclude therefore that while the secretin stimulated pancreatic polypeptide response correlates significantly with accepted tests of pancreatic structure and function, there is a significant degree of overlap in the response obtained in patients who have minimal/moderate damage and healthy controls making the test insufficiently sensitive for routine diagnostic use.     

Morphological and Functional Evaluation of the Pancreatic Duct with Secretin-Stimulated Magnetic Resonance Cholangiopancreatography in Alcoholic Pancreatitis Patients

Objectives The aim of this investigation was to evaluate the pancreatographic findings and dynamics of pancreatic duct diameter, as determined by secretin-enhanced magnetic resonance cholangiopancreatography (S-MRCP), in patients with acute alcoholic pancreatitis or chronic alcoholic pancreatitis and in a control group. Methods S-MRCP was performed in patients with acute alcoholic pancreatitis who did not manifest the functional and radiological (ultrasonography and computed tomography) criteria of chronic pancreatitis (n = 21), in patients with chronic alcoholic pancreatitis (n = 28) and in a control group (n = 16). The diameter of the main pancreatic duct (MPD) was monitored before secretin administration and at 3 and 10 min after secretin administration. Morphological features were also assessed before and after the administration of secretin. Results All ductal diameters were significantly larger in chronic alcoholic pancreatitis (P < 0.0001). There were no differences in MPD caliber between patients with acute alcoholic pancreatitis and the control group. The percentage of variation between basal MPD diameter and at 3 min post-secretin administration was lower in patients with chronic (35.5%) pancreatitis than in those with acute alcoholic pancreatitis (52.3%) and the control group (52.5%). There were no significant differences between patients with acute alcoholic pancreatitis and the control group in terms of the frequency of visualization of side branches, ductal narrowing, intraluminal filling defects, and ductal irregularity. One patient with acute alcoholic pancreatitis presented ductal criteria of chronic pancreatitis following the administration of secretin. Conclusions The dynamics of MPD visualized on S-MRCP in patients with acute alcoholic pancreatitis is similar to that observed in the control group and different from that observed in patients with chronic alcoholic pancreatitis. There were no significant differences between patients with acute alcoholic pancreatitis and the control group in terms of morphological pancreatographic features.     

135例慢性胰腺炎临床病例分析

探讨慢性胰腺炎的不同病因和临床表现特点。回顾性分析本院135例慢性胰腺炎的住院患者的主要病因包括胆道系统疾病(31．85％)和酒精中毒(35．56％),其他病因包括特发性、自身免疫性疾病、外伤或遗传等。酒精性CP临床症状发生的比例较胆源性高,特别是腹痛、腹泻、糖尿病的发生率明显高于胆源性CP。酒精性与非酒精性CP组、对照组相比,TG、HDL-C、G／HDL-C差别显著。胆道系统疾病和酒精中毒为CP主要病因,近年来酒精性因素呈上升趋势。临床表现上,酒精性较胆源性CP的发生率高。TG／HDL-C比值可能有助于鉴别酒精性和非酒精性胰腺炎。     

Effects of intravenous alcohol on pancreatic and biliary secretion in man

Two groups of men, nonalcoholics (mean daily alcohol consumption<40 g) and alcoholics (mean daily alcohol consumption>100 g) were compared with respect to the effects of intravenous ethanol on hormonally (secretin+CCK) submaximally stimulated pancreatic and bile secretion and chymotrypsin secretion during the basal state and after a Lundh test meal. Intravenous ethanol injection (600 mg/kg) significantly decreased pancreatic secretion of lipase (–74%), chymotrypsin (–78%), volume (–53%), and bicarbonate (–58%), in nonalcoholic but not in alcoholic men: The secretory pattern of the exocrine pancreatic response to an intravenous infusion of ethanol was therefore changed by the regular consumption of ethanol. The chymotrypsin concentration during the basal state was higher in alcoholic than in nonalcoholic men. This difference progressively disappeared after a test meal showing that chronic alcohol consumption modifies more basal than meal-stimulated pancreatic secretion.     

Calcium content of duodenal juice

Summary Duodenal intubation and stimulation with secretin (1 U./kg. body weight and 3 U./kg. body weight) were performed in 20 normal subjects and 18 patients with chronic pancreatitis, 4 with alcoholic cirrhosis, 4 with carcinoma of the pancreas, and 2 with hyperparathyroidism. Calcium, bicarbonate, and amylase content of the duodenal fluid was estimated.Basal fasting calcium concentration in normal subjects was 3.0 mg./100 ml.; after the injection of secretin, 1 U./kg. body weight, the concentration was 2.3 mg./100 ml. Larger doses of secretin produced a fall in calcium concentration to a low of 1.8 mg./100 ml. with 3 U./kg. body weight, but the rate of secretion of calcium was independent of secretin dose.Subjects with chronic pancreatitis and alcoholic cirrhosis had increased basal and postsecretin concentration of calcium in duodenal fluid, but the output of calcium was more variable. Two patients with hyperparathyroidism had evidence of normal pancreatic function in response to standard secretin tests, but showed increased calcium concentration in basal fasting juice.The implications of these findings are discussed in terms of pancreatic calcification and the association between pancreatitis and hyperparathyroidism.The technical assistance of Miss S. Arunsakul is gratefully acknowledged. Thanks are also due to Boots Co. and Vitrum Co. for generous grants of secretin.     

Effect of gastric hypersecretion on the canine duodenum.

The neutralization of acid introduced into the duodenum has been found to be less intensive in patients with duodenal ulcer than in controls. The present work studied the possibility that chronic gastric hypersecretion injures the duodenal mucosa and thereby influences the neutralization system. Gastric hypersecretion was provoked for 3 weeks in 3 dogs by a daily injection of a gastrin preparation with prolonged effect. After a subcutaneous injection of this preparation given together with a test meal the acidity of both gastric and duodenal contents was found to increase significantly. After the 3 weeks of gastric hypersecretion the pancreatic bicarbonate response to exogenous secretin was unchanged, while the bicarbonate response to duodenal acidification was decreased from 2.03 mEq/30 min to 1.27 mEq/30 min (p less than 0.05), compatible with an impaired secretin release. Also the concentration of lactase, maltase, sucrase, and alkaline phosphatase in mucosal biopsies from the second part of the duodenum was significantly reduced (p less than 0.001). These results indicate that gastric hypersecretion causes mucosal damage in the duodenum and thereby reduces the release of secretin.     

Hypersecretion of biliary fatty acids in patients with exocrine pancreatic disease

Summary The fatty acid composition of bile secreted into the duodenum in the first 10 min after an intravenous (i.v.) injection of Boots secretin (2 CHRu kg^-1) has been analysed by gas liquid chromatography in 11 healthy volunteers, 8 patients without pancreatic disease, 27 patients with exocrine pancreatic disease who had not altered their diet substantially (acute pancreatitis 8; chronic pancreatitis 16; cancer 3) and 11 patients with exocrine pancreatic disease on low fat intakes (40 g/day) for at least 6 months. The mean values for total fatty acid outputs (after back transformation of the logged data) were significantly higher in each subgroup of patients with pancreatic disease on their usual diets (acute 134, chronic 189, cancer 235 mg) than in the two subgroups of controls (30 and 55 mg), due to significant increases in the outputs of every fatty acid, C16:0 through to C22:5. This finding, which was usually not apparent in patients with pancreatic disease on low-fat diets, may reflect the combined influence of dietary fat intakes and hepatic enzyme induction. Comparison of the fatty acid outputs in endoscopically collected bile and duodenal juice after separate injections of secretin three hours apart indicate that: (a) analysis of duodenal juice within 10 min of stimulation by Boots secretin provides valuable information on the composition of hepatic bile; (b) the increased phospholipid output in the untreated patients is due to hypersecretion and does not merely represent a ‘washout’ phenomenon.     

Secretin Stimulated Pancreatic Polypeptide: A Test for Chronic Pancreatitis

Abstract: The level of serum pancreatic polypeptide (PP) in response to intravenous Boots secretin has been measured by radioimmunoassay in 50 patients with documented chronic pancreatitis and 33 controls with no evidence of pancreatitis. Both groups showed significant increases in serum PP but patients with chronic pancreatitis had a significantly smaller response than controls. An abnormal PP response to Boots secretin has been defined as a peaklbasal ratio of less than five. Using this criterion, 90% of patients with chronic pancreatitis had a ratio of less than 5. whereas 91% of controls had a ratio of 5 or greater. There was a 92% correlation between a normal or abnormal pancreatic bicarbonate concentration and a normal or abnormal peakl basal PP ratio in response to Boots secretin. These results suggest that the serum PP response to Boots secretin may provide a simple, inexpensive and noninvasive method of accurately diagnosing chronic pancreatitis .     

Hypersecretion of biliary fatty acids in patients with exocrine pancreatic disease

The fatty acid composition of bile secreted into the duodenum in the first 10 min after an intravenous (i.v.) injection of Boots secretin (2 CHRu kg-1) has been analysed by gas liquid chromatography in 11 healthy volunteers, 8 patients without pancreatic disease, 27 patients with exocrine pancreatic disease who had not altered their diet substantially (acute pancreatitis 8; chronic pancreatitis 16; cancer 3) and 11 patients with exocrine pancreatic disease on low fat intakes (40 g/day) for at least 6 months. The mean values for total fatty acid outputs (after back transformation of the logged data) were significantly higher in each subgroup of patients with pancreatic disease on their usual diets (acute 134, chronic 189, cancer 235 mg) than in the two subgroups of controls (30 and 55 mg), due to significant increases in the outputs of every fatty acid, C16:0 through to C22:5. This finding, which was usually not apparent in patients with pancreatic disease on low-fat diets, may reflect the combined influence of dietary fat intakes and hepatic enzyme induction. Comparison of the fatty acid outputs in endoscopically collected bile and duodenal juice after separate injections of secretin three hours apart indicate that: (a) analysis of duodenal juice within 10 min of stimulation by Boots secretin provides valuable information on the composition of hepatic bile; (b) the increased phospholipid output in the untreated patients is due to hypersecretion and does not merely represent a 'washout' phenomenon.     

Citrate and calcium secretion in the pure human pancreatic juice of alcoholic and nonalcoholic men and of chronic pancreatitis patients

Citrate, calcium and protein have been estimated in pure pancreatic juice after a secretin and a CCK injection in 4 patients presenting with alcoholic calcified pancreatitis (ACP), 10 controls without evidence of pancreatic disease, drinking more than 130 g alcohol/day, and 10 controls without evidence of pancreatic disease, drinking less than 20 g alcohol/day. Citrate is normally secreted in the pancreatic juice and this secretion increases in parallel with protein after CCK injection. Citrate secretion is significantly decreased in the two alcoholic groups. Calcium secretion is increased in the ACP, and reasons are presented to suggest that this may be due to lesions of the ducts. These modifications could play a role in the formation of pancreatic stones which are mostly built up of calcium carbonate.     

Pure pancreatic juice studies in normal subjects and patients with chronic pancreatitis

Pure pancreatic juice was obtained from within the pancreatic duct in 54 patients after endoscopic cannulation of the papilla of Vater. In all 20 normal subjects there was a brisk response to intravenous injections of GIH secretin in small dosage (1 and 4 CU). Peak bicarbonate concentrations occurred after a 4 CU stimulus, whereas volumes, and bicarbonate and protein outputs were greatest after 70 CU. Total protein and amylase concentrations were highest in the first specimens collected from each patient, and fell rapidly after stimulation. Plateau levels for all indices were achieved 10-20 minutes after starting infusions of secretin and pancreozymin. When normal patients and those with chronic pancreatitis were compared, there was considerable overlap in all indices (volume, bicarbonate and total protein concentrations) after bolus injections of secretin. Most patients with chronic pancreatitis achieved a peak bicarbonate concentration in excess of 100 mmol/l. The median concentrations were not significantly different from normal after any dose of secretin when pooled 10 minute samples were analysed. However there were significant differences in peak bicarbonate concentrations (after 1 and 4 CU, but not after 70 CU), when one minute samples were compared. There were also statistically significant differences in the median 10 minute responses for volume after 1 and 70 CU, for bicarbonate output after 1, 4, and 70 CU, and for protein output after 70 CU. The results of juice studies in patients believed to have early chronic pancreatitis did not differ significantly from those in normal subjects or those with chronic pancreatitis. Endoscopic duct cannulation cannot guarantee complete recovery of pancreatic secretions, and measurements of volume and output may be inaccurate. When standard biochemical indices are used, the diagnostic role of pure juice studies is limited; further research may reveal more specific disease markers.     

Latent portasystemic encephalopathy

Forty patients with chronic liver disease and portal hypertension but without clinical signs of portasystemic encephalopathy (15 patients with nonalcoholic cirrhosis, 15 patients with alcoholic cirrhosis, and 10 patients with minimal EEG changes) and a control group of 12 patients with chronic alcoholic pancreatitis were studied using an extensive psychometric program, which, in the same form, is used for expert reports on driving capacity. Of the cirrhotic patients, 60% were considered unfit to drive; in 25% driving capacity was questionable, 15% (only nonalcoholic cirrhotics) were considered fit to drive. In contrast 75% of the patients with alcoholic pancreatitis were considered fit to drive. Major defects were found only in three heavy alcoholics. Patients with alcoholic cirrhosis scored lower than patients with nonalcoholic cirrhosis. This was due, to differences in liver function rather than to the effect of alcohol consumption. Patients with minimal EEG changes were practically all considered unfit to drive.     

Prognosis and prognostic factors in chronic pancreatitis

To evaluate the prognosis and prognostic factors of chronic pancreatitis, 84 patients with alcoholic chronic pancreatitis and 51 with nonalcoholic chronic pancreatitis have been followed for 1-21 years (average of 7.1 years). The follow-up period was defined as the period from diagnosis to death in those who died and to the present in those still alive. The following conclusions were obtained. (1) Patients with alcoholic chronic pancreatitis showed a significantly higher mortality rate (26.2%) and cancer death rate (8.3%) than the age- and sex-matched population. In patients with nonalcoholic chronic pancreatitis, however, the difference did not reach the level of statistical significance, although both rates tended to be higher. (2) Patients with alcoholic chronic pancreatitis showed a significantly poorer prognosis than those with nonalcoholic chronic pancreatitis. (3) Frequent causes of death in chronic pancreatitis were cancer (11 cases) and diabetes-associated conditions (renal failure in three cases, intractable pneumonia in one, hypoglycemic shock in two, and myocardial infarction in two). Death directly from pancreatitis was observed in four. (4) Unfavorable prognostic factors in alcoholic chronic pancreatitis included heavy drinking, continuance of drinking after diagnosis, smoking, insulin-dependent diabetes, and an advanced age. In nonalcoholic chronic pancreatitis, however, patients' age was the only significant prognostic factor; smoking did not reach the level of statistical significance, although it tended to lead to a poorer prognosis.     

Impaired secretin release in chronic alcoholic dogs

Plasma immunoreactive secretin has been compared before and after stimulation by intraduodenal infusion of HCl in 3 dogs who had received 2 g-kg-1-day-1 alcohol for 3 years and 4 non-alcoholic control dogs. After HCl infusion, blood secretin was lower in chronic alcoholic animals than in controls. This decreased post-stimulation concentration of secretin in chronic alcoholic dogs was in contrast to the increased release of gastrin after a meal which has been previously described.     

Nutritional data and etiology of chronic pancreatitis in Mexico

Alcoholism and malnutrition have been implicated commonly in the etiology of chronic pancreatitis (CP). The geographical distribution and clinical and nutritional features differ between the alcoholic and tropical forms of CP. This work presents the etiology and nutritional characteristics of CP in Mexico, a country in which both alcoholism and childhood malnutrition are common. Two well-defined groups of patients have been identified: an alcoholic group composed mainly of males with a mean age at clinical onset of 41 years and a high dietary intake of fat, protein, carbohydrates, and calories; and a nonalcoholic group with a female preponderance, a mean age at onset of 23 years, and a higher intake of protein than controls. We conclude that alcoholic chronic pancreatitis in Mexico is similar to that reported in other temperate countries. Although the nonalcoholic group resembles that observed in tropical countries in many ways, our patients are not malnourished, further questioning the role of childhood malnutrition in the pathogenesis of this type of chronic pancreatitis.     

Trypsin activity

A normal serum amylase level is found in up to 32% of patients with acute alcoholic pancreatitis. This underlines the need for more sensitive diagnostic tests in this frequent cause of pancreatitis. Animal and human studies have shown that chronic alcohol consumption leads to important modifications in trypsinogen metabolism. The present work has prospectively analyzed admission serum trypsin activity with a new biochemical test and usual markers such as amylase, lipase, and immunoreactive trypsin in 32 attacks of acute pancreatitis. Seventeen were due to alcohol and 15 to other causes, including 11 with gallstone pancreatitis. High trypsin activity (median: 235 units/liter; range: 165–853) was found in all patients with acute alcoholic pancreatitis even when the amylase level was normal on admission (3/17: 18%). Trypsin activity did not differ between nonalcoholic pancreatitis (N=15): 84 units/liter (42–98), alcoholic controls (N=15): 77 units/liter (40–122), and healthy controls (N=62): 81 units/liter (15–143). The difference was not related to the severity of disease or circulating α₂-macroglobulin, α₁-protease inhibitor, or immunoreactive trypsinogen levels. Lipase/amylase ratio was less discriminant than trypsin activity between alcoholic and nonalcoholic diseases. We conclude that serum trypsin activity seems specific to acute alcoholic pancreatitis and should be included in new prospective studies assessing biochemical testing of alcohol-related pancreatic diseases.