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AbstractObjective:Chronic pancreatitis (CP) is the most common cause of pancreatic exocrine insufficiency (PEI). Management of PEI due to CP is achieved through lifelong treatment with pancreatic enzyme replacement therapy (PERT). To the authors’ knowledge, no cost-effectiveness analysis on the benefit of PERT in CP patients with PEI has been performed to date. The objective of this analysis was to examine the cost-effectiveness of Creon (pancreatin minimicrospheres [MMS]), one of the main PERTs available in Poland, in treating patients with CP-related PEI.Methods:The cost-effectiveness of pancreatin MMS in the treatment of patients with CP-related PEI vs no PERT treatment was estimated using a decision analysis based on clinical data from relevant studies. The model horizon was 20 years. Main outcomes included the percentage of patients with controlled PEI, survival, total medical costs, number of quality-adjusted life years (QALYs), and the incremental cost-effectiveness ratio (ICER). All costs were analysed from the Polish payer perspective.Results:The model included clinical data from 176 patients treated in five pancreatin MMS randomized trials. Treatment with pancreatin MMS resulted in a considerably higher proportion of patients with controlled PEI compared to those not treated with any PERT. Over a horizon of 20 years, the total treatment cost and the ICER for pancreatin MMS was €8223 and €6312 per QALY, respectively.Limitations:Important limitations include the lack of long-term and comparative clinical data available. The use of ‘no PERT treatment’ as a comparator against pancreatin MMS treatment may not accurately reflect current practice in Poland.Conclusions:Treatment of CP-related PEI with pancreatin MMS is cost-effective from a Polish payer perspective, with an ICER below the accepted ‘willingness to pay’ threshold of 3-times gross domestic product (GDP) per capita. These results are likely to apply to other European countries.

Introduction:The following is a summary of the official guidelines of the Italian Association for the Study of the Pancreas regarding the medical, endoscopic and surgical management of acute pancreatitis. Statements:Clinical features together with elevation of the plasma concentrations of pancreatic enzymes are the cornerstones of diagnosis (recommendation A). Contrast-enhanced computed tomography (CT) provides good evidence for the presence of pancreatitis (recommendation C) and it should be carried out 48–72 h after the onset of symptoms in patients with predicted severe pancreatitis. Severity assessment is essential for the selection of the proper initial treatment in the management of acute pancreatitis (recommendation A) and should be done using the APACHE II score, serum C-reactive protein and CT assessment (recommendation C). The etiology of acute pancreatitis should be able to be determined in at least 80% of cases (recommendation B). An adequate volume of intravenous fluid should be administered promptly to correct the volume deficit and maintain basal fluid requirements (recommendation A); analgesia is crucial for the correct treatment of the disease (recommendation A). Enteral feeding is indicated in severe necrotizing pancreatitis and it is better than total parenteral nutrition (recommendation A). The use of prophylactic broad-spectrum antibiotics reduces infection rates in CT-proven necrotizing pancreatitis (recommendation A). Infected pancreatic necrosis in patients with clinical signs and symptoms of sepsis is an indication for intervention, including surgery and radiological drainage (recommendation B). Conclusions:The participants agreed to revise the guidelines every 3 years in order to re-evaluate each question on the management of acute pancreatitis patients according to the most recent literature.

Aims:To explore the quality of life in patients treated medically during the acute phase of pancreatitis as well as at 2 and 12 months after discharge from the hospital. Patients:40 patients were studied. The etiology of the pancreatitis was biliary causes in 31 patients and non-biliary causes in 9; mild disease was present in 29 patients and severe disease in 11. 30 patients completed the two surveys at 2 and 12 months after hospital discharge. Methods:The SF-12 and EORTC QLQ-C30 questionnaires were used for the purpose of the study. Results:The two physical and mental component summaries of SF-12, all the domains of EORTC QLQ-C30 (except for physical functioning and cognitive functioning) and some symptom scales of EORTC QLQ-C30 (fatigue, nausea/ vomiting, pain, and constipation) were significantly impaired during the acute phase of pancreatitis. There was a significant improvement in the SF-12 physical component summary, and global health, role functioning, social functioning, nausea/vomiting, pain, dyspnea, and financial difficulties (EORTC QLQ-C30) at 2 months after discharge as compared to the basal evaluation. Similar results were found after 12 months except for the mental component score at 12-month evaluation, which was significantly impaired in acute pancreatitis patients in comparison to the norms. The physical functioning of the EORTC QLQ-C30 at basal evaluation was significantly impaired in patients with severe pancreatitis in comparison to patients with mild pancreatitis. Conclusions:Two different patterns can be recognized in the quality of life of patients with acute pancreatitis: physical impairment is immediately present followed by mental impairment which appears progressively in the follow-up period.

To evaluate the clinicalvalue of a new direct and competitive immunoassay for trypsinogen activation peptide (TAP) determination in acute pancreatitis (AP).

Abstract: Background: The diagnostic value of the determination of the serum pancreatic polypeptide (PP) and gastrin concentrations after a standard meal for early diagnosis of patients with multiple endocrine neoplasia type 1 (MEN 1) is controversial. The aim of this study was to clarify this issue. Thirteen patients with MEN 1, seven healthy family members, and eight healthy controls were studied. Plasma PP and serum gastrin were measured before and after the ingestion of a standardized meal. The meal caused a statistically significant (p<0.05) increase of both PP and gastrin in all three groups studied. Concerning PP, no statistically significant difference was observed between patients and controls. In family members, the values were significantly (p<0.05) lower than in the other two groups. On the whole, no significant differences in gastrin levels were noted between patients and controls; in family members, the values were significantly (p<0.05) lower than in patients. All patients who had abnormally high postprandial values of PP and gastrin also had abnormally high basal values of these two peptides. The determination of serum PP and gastrin levels after a meal stimulation test in patients with MEN 1 adds no information about the presence of pancreatic endocrine tumors over that provided by basal values of the two peptides.

Aim.To compare the efficacy of two different schedules of gabexate mesilate (900 mg/day, or 1, 500 mg/day) in the treatment of severe acute pancreatitis.

We studied serum elastase 1 concentrations in patients with pancreatic disease to assess its diagnostic value and compare its sensitivity and specificity with that of amylase and pancreatic isoamylase. Markedly raised concentrations of elastase 1 were found in all twenty-nine patients with acute pancreatitis (amylase was elevated in all but three and pancreatic isoamylase in all but one). Serial measurements of the three enzymes in acute pancreatitis showed that elastase remained elevated longer than amylase and pancreatic isoamylase. The majority of chronic pancreatitis patients studied during a painful relapse (16 out of 21, 76 per cent) had elastase concentrations above the upper normal limit. Amylase and pancreatic isoamylase were elevated in 11 (52 per cent) and in 13 (62 per cent), respectively. Most patients with chronic pancreatitis studied during clinical remission (39 out of 43) had serum elastase levels either within (n = 24) or below (n = 15) the control range. The latter had severe exocrine pancreatic insufficiency and steatorrhoea. In carcinoma of the pancreas, 20 out of 32 (63 per cent) had abnormal serum elastase concentrations; 16 were higher and 4 lower than the control range. Amylase was abnormal in 10 (31 per cent) (8 high, 2 low), and pancreatic isoamylase was abnormal in 16 (50 per cent) (11 high, 5 low). In 46 control patients with non-pancreatic abdominal pain, serum elastase concentrations were not significantly different from those in healthy controls. Elastase was slightly raised in two, whereas amylase and pancreatic isoamylase were elevated in seven and eight, respectively. We conclude that serum elastase 1 is a highly sensitive and specific indicator of pancreatic disease.

We assessed the ability of serum human pancreatic secretory trypsin inhibitor (hPSTI) to establish the severity of acute pancreatitis and compared it in this respect to that of serum C-reactive protein (CRP). Of 26 patients studied with acute pancreatitis, 16 had mild pancreatitis, and 10, severe disease. Initial studies were performed at onset of the disease in 20 patients, on the second day of illness in two, and on the third day of illness in the remaining four. In all, serum hPSTI and CRP concentrations were determined on admission and daily for the following 5 days using commercial kits; Ranson's score was evaluated within the first 48 h of admission. Sixty-three healthy subjects and 31 patients with nonpancreatic acute abdomen were also studied. Values of 70 ng/ml for serum hPSTI and 10 mg/dl for serum CRP were taken as limits to distinguish severe from mild-to-moderate acute pancreatitis. When assessed within the first 24 h of pain, serum hPSTI correctly classified 71 of the patients with severe acute pancreatitis, whereas serum CRP did so for 29. In subsequent days, the two markers showed a similar sensitivity in predicting severe acute pancreatitis. Serum hPSTI and CRP were alike in excluding a diagnosis of severe acute pancreatitis. Ranson's score correctly identified 50 of patients with severe illness and 63 of patients with mild pancreatitis. This study indicates that, when assessed within 24 h of pain onset, serum hPSTI is a better predictor of the severity of acute pancreatitis than serum CRP or Ranson's criteria.

It was recently demonstrated in experimental models that, after pancreatic outflow obstruction, serum amylase levels first increase and then progressively decline regardless of whether the obstruction was maintained or relieved. Furthermore, early decompression of the ductal biliary system may prevent the progression of the disease. This finding prompted us to look for a similar pattern in patients with obstructive acute pancreatitis due to biliary stones. Forty-two patients with biliary acute pancreatitis were prospectively studied. Twenty-one patients underwent urgent endoscopic sphincterotomy (ES), and 21 received conservative medical treatment (CMT). The two groups were comparable for sex, age, onset of pain, and seventy. Serum amylase and lipase were determined in all patients on admission and 24 h later. The percentage variation of serum amylase and lipase was calculated considering, for each patient, the concentrations of the two enzymes assayed on admission and 24 h later. On admission, all patients had elevated serum concentrations of amylase (mean ± SEM: ES, 2,560 ± 473 UL; CMT, 1,783 ± 481 U/L) and lipase (ES, 3,037 ± 574 U/L; CMT, 3,179 ± 724 U/L). The serum amylase variation (mean ± SEM) was −65.6 ± 5.5 in the ES and −47.2.1 ± 8.1 in the CMT patients. The serum lipase variation was −59.1 ± 7.7 and −33.1 ± 18 in the same groups, respectively. These differences were not statistically significant. Acute pancreatitis worsened in one patient in the ES group and in seven in the CMT group; this difference was statistically significant (p <0.02). The mean length of hospitalization was 8.9 days in the ES group and 19.7 days in the CMT group (p <0.001). Serum pancreatic enzymes determination is not useful to evaluate the results of the early decompression of biliary duct in human acute pancreatitis. Indeed, early endoscopic sphincterotomy may result in a substantial improvement in the outcome of biliary acute pancreatitis.

Thirty-nine consecutive patients with β-thalassemia major and iron overload were studied by ultrasonography and serum pancreatic enzyme determination to assess the frequency and characteristics of pancreatic damage in this condition. The results were compared with those of a matched group of healthy controls. Most of the thalassemic patients had a markedly increased echogenicity of the pancreas and decreased size of the gland (p <0.001 for both features as compared with controls). Both echogenicity and decreased size of the gland were significantly correlated (p <0.001) with patient age and duration of transfusional therapy. Serum concentrations of trypsin and lipase were significantly lower (p <0.02) in patients than in controls. The lowest enzyme values were found in older patients with longer duration of transfusional therapy, who also had the most marked sonographic changes. The results suggest that the exocrine pancreas is structurally and functionally damaged in the majority of thalassemic patients with iron overload.

Octreotide (SMS 201–995) is a long-acting somatostatin analogue that inhibits exocrine pancreatic secretion and that has been proposed for treatment of various pancreatic disorders. To gain more information about the mechanism by which octreotide inhibits pancreatic enzyme secretion, we studied the effect of this compound on plasma amino acid uptake by the pancreas in six healthy volunteers aged 22–29 years. Pancreatic amino acid uptake was assessed by measuring plasma amino acid concentration before and during pancreatic enzyme synthesis stimulation with cerulein (50 ng/kg/h). The infusion of cerulein caused a significant decrease (p <0.001) in plasma amino acid concentration. The subcutaneous injection of octreotide at dosages of 12.5, 25, and 50 μg prevented this decrease in a dose-dependent manner. The decrease in amino acid concentration reached a maximum of 19.4 ± 2.4 during cerulein infusion and a maximum of 10.7 ± 2.5, 6.8 ± 1.2, and 2.9 ± 1.2 (means ± SD) when cerulein was preceded by injection of octreotide at 12.5, 25, and 50 mg, respectively. These results indicate that octreotide is able to inhibit the plasma amino acid uptake by pancreatic acinar cells and, consequently, synthesis of pancreatic enzymes. Clinically, this effect could be useful in treatment of pathologic conditions of the pancreas in which it is desirable to suppress acinar cell activity and avoid accumulation of enzymes in acinar cells.

We have measured serum immunoreactive pancreatic elastase 1 concentrations in 90 patients with pancreatic cancer in order to determine its usefulness in the diagnosis of this tumor. Abnormal elastase 1 concentrations were found in only 58 (64.4) of the 90 patients. Fifty (55.5) had abnormally high values, and eight (8.9) had abnormally low values. No significant differences in elastase 1 levels were observed between patients with resectable cancer (n = 15) and those with unresectable cancer (n = 75). Moreover, no significant differences were found between elastase 1 concentrations of patients with pancreatic cancer and those of 71 patients with chronic pancreatitis. We conclude that serum elastase 1 measurement does not represent a significant advance in the diagnosis, whether early or late, of pancreatic cancer.

We have studied the pancreatic secretory response to a normal meal in 5 subjects with an external drainage of the main pancreatic duct carried out after biliary tract surgery. Pancreatic juice was collected at 60-min intervals from 10 amto 7 pm, starting 2 h before and ending 7 h after lunch, and was analyzed for volume, bicarbonate content, and protein content. Large doses of pancreatic extract were given between and during meals. Both bicarbonate and protein output increased rapidly after the beginning of the meal and the increase persisted, with minor fluctuations, for the entire 7-h study period between lunch and dinner. The peak postprandial bicarbonate and protein outputs were higher (on average by 20% and 26%, respectively) than bicarbonate and protein outputs induced by exogenous infusion of submaximal doses of secretin and cerulein. The profile and magnitude of the bicarbonate secretory pattern elicited by food were not substantially different from those of protein secretion. In an additional patient who had undergone a duodenocephalopancreatectomy plus two-thirds distal gastrectomy before the study, the pancreatic response to meals showed an initial phase characterized by an increase in pancreatic secretion during the first postprandial hour followed by a tendency to decrease in the subsequent 2 h, and a later phase (from the fourth postprandial hour to the end of the study) characterized by a more marked and more persistent increase in pancreatic secretion than occurred in the initial 3 h. These data indicate that (a) the pancreatic secretory response to ordinary meals is much more prolonged than is generally believed. The late phase of the response is not dependent on gastric emptying of food into the duodenum, but is probably related to the arrival of chyme in the distal ileum. (b) The pancreatic secretory response to a normal meal is quantitatively slightly higher than that produced by exogenous pancreatic stimulation with submaximal doses of secretin and cerulein. (c) The pattern of postprandial bicarbonate secretion is similar to that for protein.

We have studied the effect of isometheptene, an indirectly acting sympathomimetic with analgesic and antispastic properties, on secretin-cholecystokinin-stimulated pancreatic and biliary outputs. Isometheptene, infused intravenously at a dose of 100 mg in 30 min, significantly inhibited bicarbonate, enzyme, and bilirubin output in eight healthy subjects (compared to control values, the maximum percent inhibition was 34% for bicarbonate, 57% for lipase, 61% for chymotrypsin, and 86% for bilirubin). In four cholecystectomized subjects, the drug inhibited only pancreatic outputs. The inhibitory effect on pancreatic secretion, coupled with the analgesic action, suggest a potential benefit of this drug in acute pancreatic pathology.

We investigated peripheral lymphocyte subsets in 34 consecutive acute pancreatitis patients (21 males, 13 females; mean age, 57 years; range, 16–85 years) studied within 48 h of pain onset and for 5 consecutive days to understand better the immunological response during the course of the disease. The diagnosis was based on characteristic abdominal pain associated with a twofold increase in serum lipase and confirmed by imaging techniques in all patients. Acute pancreatitis was of biliary origin in 25 patients, due to alcohol abuse in 5, due to pancreas divisum in 1, and of unknown origin in 3. Fifteen patients had severe illness and 19 had mild disease. In all patients, total lymphocyte and lymphocyte subset counts were carried out on admission, as well as on the third and fifth day of hospitalization, using a flow cytometric analysis. Twenty-three patients (13 with severe illness and 10 with mild disease) also had a repeat count 1 month after recovery. Twenty-five healthy subjects and 27 patients with nonpancreatic acute abdomen comparable for sex and age were studied as controls. On the first day of the study, the leukocyte number was significantly higher in patients with acute pancreatitis and in those with nonpancreatic acute abdomen with respect to healthy subjects, whereas the number of total and CD4 , CD8, CD3DR−, and CD3−DRlymphocytes was significantly lower in acute pancreatitis patients than in healthy subjects or in patients with nonpancreatic acute abdomen. These subset counts persisted on the third and fifth days of the study. Patients with nonpancreatic acute abdomen and healthy subjects had similar values of total and lymphocyte subsets. The patients with acute pancreatitis studied 1 month after complete recovery had numbers of leukocytes, total lymphocytes, and CD4, CD8, CD3DR−, and CD3−DRlymphocytes similar to those in healthy subjects. Regarding CD3DRlymphocytes, the count in acute pancreatitis patients studied within the first 5 days of hospital admission was similar to that in healthy subjects, but 1 month after complete recovery it was significantly higher in the pancreatitis patients. CD4and CD3DR−lymphocyte counts were significantly lower in patients with severe acute pancreatitis than in patients with mild disease from the third day of illness onward. The CD4-T cell difference was still present 1 month later. The number of total lymphocytes was significantly lower in patients with severe illness relative to those with mild pancreatitis on the fifth day of hospitalization. Results demonstrate that in early phases of acute pancreatitis there was a significant decrease in the number of total lymphocytes and lymphocyte subset counts relative to controls. These counts returned to normal with resolution of the illness.

We collected pure pancreatic juice during an entire day and examined pancreatic secretory changes induced by ordinary meals in a male patient having an external drainage of the main pancreatic duct. The ingestion of breakfast, lunch, and dinner each caused a marked increase in pancreatic secretion above basal levels. The increase in both bicarbonate and protein output was very prolonged. The highest secretory outputs induced by meals were slightly higher than those produced by exogenous administration of submaximal doses of secretin and cerulein. The profile and magnitude of bicarbonate and protein secretion were similar.

The variations of serum levels of amylase, pancreatic isoamylase, lipase, trypsinogen, and elastase 1 were evaluated in 21 patients with acute pancreatitis. The patients were studied for a mean period of 7 consecutive days (range 5- 12 days) after admission to the hospital. On the day of onset of acute pancreatitis, all enzyme levels were abnormally high; pancreatic isoamylase showed the greatest increase compared with its upper normal limit, whereas the increase increment for elastase 1 was the lowest. Subsequently, all enzyme levels except elastase 1 decreased in a parallel fashion. On the eighth day of the study only elastase 1 levels were above normal values in all patients exam-ined, while abnormally high values of lipase were found in 85 of the patients, trypsinogen in 58 of the patients, pancreatic isoamylase in 43, and total amylase in 23. These results indicate that, for the early diagnosis of acute pancreatitis, the determination of any of these enzymes is equally efficient, but that elastase 1 is the most sensitive marker of acute pancreatic damage in later stages of the disease.

In 134 consecutive patients with acute abdominal pain, we evaluated the clinical role of a new rapid test for serum lipase based on latex agglutination. The results were compared with those obtained with a widely used lipase immunoassay as well as with serum amylase and pancreatic isoamylase measurements. Fifty-five healthy subjects were studied as controls. In 174 cases (121 patients and 53 controls) the results of the two lipase assays were in agreement. A positive lipase latex test was found in 10 of 12 patients with acute pancreatitis, in eight of 24 patients with other pancreatic diseases, and in 14 of 98 with nonpancreatic diseases. The sensitivity and specifity of this test were similar to those of the other pancreatic enzyme assays performed. The results indicate that the lipase latex agglutination test is useful for emergency screening for acute pancreatitis in patients with acute abdominal pain.

A longitudinal study of patients with persistent hyperamylasemia was carried out to evaluate the clinical significance of this condition. Twenty-five outpatients were studied by means of serum amylase, isoamylase (wheat germ-inhibition method), and lipase determination; macroamylase detection; and abdominal ultrasonography over a one-year period. Cellulose acetate electrophoresis was carried out to validate the wheat germ-inhibition tests; the results of the two assays were closely correlated, except in three patients with macroamylasemia. At the time of the study, none of the patients had evident signs or symptoms of pancreatic disease. At initial evaluation, wheat germ test demonstrated an elevation of only salivary isoamylase in 16 patients, of both pancreatic and salivary isoenzyme in two, and only pancreatic isoamylase in six patients (three with macroamylasemia). Normal salivary and pancreatic isoenzymes were found in one patient. Serum lipase was elevated in only one patient who had a mixed hyperamylasemia with predominantly pancreatic isoamylase. At the 12-month follow-up, hyperamylasemia had disappeared in six cases and salivary isoamylase elevation in three; pancreatic isoamylase remained abnormally high in all eight patients in whom it was elevated at initial evaluation, and lipase was abnormally high in three patients with elevated pancreatic isoamylase. Of the five patients with true pancreatic hyperamylasemia, one had a juxtapapillary duodenal diverticulum, one showed a slight ultrasound alteration of the pancreas, and one had a past history of acute pancreatitis. In our study, most cases of chronic hyperamylasemia were of nonpancreatic origin. In the patients with elevated pancreatic isoamylase, there was no clinical evidence of pancreatic damage, although a subclinical pancreatic involvement could not be excluded in some.

In twelve patients affected by small bowel bacterial overgrowth, diagnosed by means of the lactulose hydrogen breath test, the therapeutic efficacy of a non-absorbable derivative of rifamycin, rifaximin, was evaluated. This study showed that this drug has a satisfactory therapeutic efficacy in contaminated small bowel syndrome and, at the doses tested, is free of side-effects.

Serum concentrations of trypsin and elastase 1 were determined in 109 HIV Ab-positive patients (52 asymptomatic HIV-infected patients, 25 with lymphadenopathy syndrome, and 32 with acquired immunodeficiency syndrome) to assess the prevalence of possible pancreatic damage in these patients. Serum trypsin was abnormally elevated in 46 of the 109 patients (42.2%): 19 of the 52 asymptomatic HIV-infected patients (36.6%), 9 of the 25 with lymphadenopathy syndrome (36%), and 18 of the 32 with acquired immunodeficiency syndrome (56.3%). Serum elastase 1 was elevated in 14 of the 109 HIV Ab-positive patients (12.8%): 3 of the 52 asymptomatic HIV-infected patients (5.8%), 3 of the 25 with lymphadenopathy syndrome (12%), and 8 of the 32 with acquired immunodeficiency syndrome (25%). None of the patients with abnormally high serum pancreatic enzyme concentrations had clinically evident pancreatic disease. There was no statistically significant difference in serum levels of trypsin and elastase 1 between drug addicts and nonaddicts, between alcoholics and nonalcoholics, or between those with cytomegalovirus infection and those without. A significant inverse relationship was found between serum enzyme concentrations and the number of CD4+ lymphocytes. The results of this study show that high levels of serum trypsin and elastase are present in an elevated percentage of patients with acquired immunodeficiency syndrome, suggesting that the pancreas is frequently damaged in this disease. The finding of abnormally high serum enzyme concentrations not only in patients with AIDS, but also in asymptomatic carriers and in patients with lymphadenopathy syndrome suggests an association between HIV infection and the development of pancreatic lesions.