Sari Räty

The recurrence of acute alcohol-associated pancreatitis can be reduced: a randomized controlled trial.

BACKGROUND & AIMS In the long term, half of patients with their first alcohol-associated acute pancreatitis (AP) develop acute recurrence, alcohol consumption being the main risk factor. None of the recent national or international guidelines for treatment include recommendations aimed to decrease recurrences, possibly because of a lack of studies. This study investigated whether AP recurrences can be reduced. METHODS One hundred and twenty patients admitted to a university hospital for their first alcohol-associated AP were randomized either to repeated intervention (n = 59) or initial intervention only (n = 61). The patients in the 2 groups did not differ. A registered nurse performed an intervention in both groups before discharge, after which it was repeated in the study group at 6-month intervals at the gastrointestinal outpatient clinic. Acute recurrences during the next 2 years were monitored. RESULTS There were 9 recurrent AP episodes in 5 patients in the repeated-intervention group compared with 20 episodes (P = .02) in 13 patients (P = .04) in the control group. The recurrence rates were similar during the first 6 months (4 vs 5 episodes), after which the repeated-intervention group had fewer recurrences than the control group (5 vs 15 episodes; P = .02). CONCLUSIONS The repeated visits at 6-month intervals at the gastrointestinal outpatient clinic, consisting of an intervention against alcohol consumption, appear to be better than the single standardized intervention alone during hospitalization in reducing the development of recurrent AP during a 2-year period.

Growth and Osteogenic Differentiation of Adipose Stem Cells on PLA/Bioactive Glass and PLA/β-TCP Scaffolds

The aim of this study was to compare the effects of novel three-dimensional composite scaffolds consisting of a bioactive phase (bioactive glass or beta-tricalcium phosphate [beta-TCP] 10 and 20 wt%) incorporated within a polylactic acid (PLA) matrix on viability, distribution, proliferation, and osteogenic differentiation of human adipose stem cells (ASCs). The viability and distribution of ASCs on the bioactive composite scaffolds was evaluated using Live/Dead fluorescence staining, environmental scanning electron microscopy, and scanning electron microscopy. There were no differences between the two concentrations of bioactive glass and beta-TCP in PLA scaffolds on proliferation and osteogenic differentiation of ASCs. After 2 weeks of culture, DNA content and alkaline phosphatase (ALP) activity of ASCs cultured on PLA/beta-TCP composite scaffolds were higher relative to other scaffold types. Interestingly, the cell number was significantly lower, but the relative ALP/DNA ratio of ASCs was significantly higher in PLA/bioactive glass scaffolds than in other three scaffold types. These results indicate that the PLA/beta-TCP composite scaffolds significantly enhance ASC proliferation and total ALP activity compared to other scaffold types. This supports the potential future use of PLA/beta-TCP composites as effective scaffolds for tissue engineering and as bone replacement materials.

Post-ERCP pancreatitis: reduction by routine antibiotics.

Cholangitis and pancreatitis are severe complications of endoscopic retrograde cholangiopancreatography (ERCP). Antibiotics have been considered important in preventing cholangitis, especially in those with jaundice. Some have suggested that bacteria may play a role in the induction of post-ERCP pancreatitis. It is not clear, however, whether the incidence of post-ERCP pancreatitis could be reduced by antibiotic prophylaxis, as is the case with septic complications. In this prospective study, a total of 321 consecutive patients were randomized to the following two groups: (1) a prophylaxis group (n = 161) that was given 2 g of cephtazidime intravenously 30 minutes before ERCP, and (2) a control group (n = 160) that received no antibiotics. All patients admitted to the hospital for ERCP who had not taken any antibiotics during the preceding week were included. Patients who were allergic to cephalosporins, patients with immune deficiency or any other condition requiring antibiotic prophylaxis, patients with clinical jaundice, and pregnant patients were excluded. In the final analysis six patients were excluded because of a diagnosis of bile duct obstruction but with unsuccessful biliary drainage that required immediate antibiotic treatment. The diagnosis of cholangitis was based on a rising fever, an increase in the C-reactive protein (CRP) level, and increases in leukocyte count and liver function values, which were associated with bacteremia in some. The diagnosis of acute pancreatitis was based on clinical findings, and increases in the serum amylase level (>900 IU/L), CRP level, and leukocyte count with no increase in liver chemical values. The control group had significantly more patients with post-ERCP pancreatitis (15 of 160 in the prophylaxis group vs. 4 of 155 in the control group; P = 0.009) and cholangitis (7 of 160 vs. 0 of 155; P = 0.009) compared to the prophylaxis group. Nine patients in the prophylaxis group (6%) and 15 patients in the control group (9%) had remarkably increased serum amylase levels (>900 III/L) after ERCP, but clinical signs of acute pancreatitis with leukocytosis, CRF’ reaction, and pain developed in four of nine patients in the prophylaxis group compared to 15 of 15 patients with hyperamylasemia in the control group (P = 0.003). In a multivariate analysis, the lack of antibiotic prophylaxis (odds ratio 6.63, P = 0.03) and sphincterotomy (odds ratio 5.60, P = 0.05) were independent risk factors for the development of post-ERCP pancreatitis. We conclude that antibiotic prophylaxis effectively decreases the risk of pancreatitis, in addition to cholangitis after ERCP, and can thus be routinely recommended prior to ERCP These results suggest that bacteria could play a role in the pathogenesis of post-ERCP pancreatitis.

Resection of the Head of the Pancreas in Finland: Effects of Hospital and Surgeon on Short-term and Long-term Results

Background: To study the effect of hospital volume and surgeon volume on postoperative hospital mortality, morbidity and long-term survival after resection of the head of the pancreas in a nationwide study (case record study), taking into a consideration risk factors found important in series based on experience in one hospital. Method: The case record investigation of 374 patients identified from the National Hospital Discharge Database as having undergone resection of the head of the pancreas between 1990 and 1994 in Finland. Results: The records of 350 patients were obtained for analysis. Operations were performed in 33 hospitals by 98 surgeons (average 2.1/year/hospital and 0.7/year/surgeon). Hospital mortality was 36/350 (10%), increasing from 4 and 7 to 13% with decreasing hospital volume from > 10 and 5-10 to < 5 respectively ( P < 0.05) and increasing from 3 and 10 to 14% with decreasing surgeon volume from > 3 and 1-3 to < 1, respectively ( P < 0.05). Most deaths were caused by surgical or technical complications (31/36 = 86%). Besides hospital mortality, postoperative complications, re-operations and hospital stay were also affected by surgeon volume. In the univariate analysis, also the age of the patient had an effect on the hospital mortality, and preoperative biliary stenting on the uncomplicated recovery, but in the multivariate analysis hospital mortality was independently affected by age (OR 0.94, P = 0.004) and surgeon volume (OR 1.3, P = 0.04), re-operations by surgeon volume (OR 1.10, P = 0.05) and hospital volume (OR 1.03, P = 0.05), postoperative complications by using the preoperative stent (OR 0.45, P = 0.02). Long-term survival was dependent on the histology of the specimen and by uncomplicated recovery, but not by hospital volume or surgeon volume. Conclusion: To decrease postoperative morbidity, mortality and hospital stay, pancreatic head surgery needs to be concentrated to only a few hospitals and to a few surgeons.

Postoperative acute pancreatitis as a major determinant of postoperative delayed gastric emptying after pancreaticoduodenectomy

The aim of this study was to prospectively analyze the possible association of delayed gastric emptying and postoperative pancreatic complications after pancreaticoduodenectomy. Although hospital mortality after pancreaticoduodenectomy is minimal, morbidity is still high; delayed gastric emptying is one of the most frequent complications. Thirty-nine consecutive patients undergoing pancreaticoduodenectomy were included in this study: 14 females and 25 males (median age 65 years; range, 7–82). Delayed gastric emptying was defined as the need for a nasogastric tube or recurrent vomiting that prevented normal feeding on the 10th postoperative day. Blood analysis was performed on postoperative days 4, 6, and 10; Gastrografin examination on day 6; CT scan on days 2 and 5; and drain amylases were measured on day 5. Pancreatitis was defined as pancreatitis changes in CT scan interpreted by an experienced radiologist without knowing other data. Pancreatic fistula was defined according to the recent international recommendations. We had no mortality. Twelve patients (31%) developed delayed gastric emptying. Surgical (9/12 vs. 5/27; P=0.001) but not medical complications occurred more often in the delayed gastric emptying group. Of the single complications, postoperative CT-detected pancreatitis (6/12 vs. 4/27; P=0.03) and postoperative pancreatic fistula (5/12 vs. 1/27; P=0.0007) were significantly associated with delayed gastric emptying compared with the patients without delayed gastric emptying. This pancreatitis was already detected in CT scan on day 2 in most patients (6/10, 60%). In delayed gastric emptying patients, the only parameters in blood analysis that differed significantly from patients without this complication were serum amylase activity (mean±SEM, 715±205 vs. 152±70 IU/L; P=0.02), blood leukocyte count (16±2 vs. 9±0.6 × 109/L; P=0.007) and serum C-reactive protein (CRP) concentration (144±28 vs. 51±14 mg/L, P=0.01). Postoperative pancreatic (subclinical) fistula was also associated with postoperative pancreatitis (6/10 vs. 0/29; P=0.003). Preoperative coronary artery disease (OR=16; 95% CI, 1.0-241; P=0.05) and soft pancreatic texture at operation (OR=9; 95% CI, 1.4-52; P=0.02) were significant risk factors for the development of postoperative pancreatitis. The diagnosis of delayed gastric emptying after pancreaticoduodenectomy often follows postoperative pancreatitis. Delayed gastric emptying is also associated with postoperative pancreatic fistula, for which this pancreatitis seems to be a risk factor. Preoperative coronary artery disease and soft texture of the pancreas are significant risk factors for postoperative CT-detected pancreatitis.

Obstructed pancreaticojejunostomy partly explains exocrine insufficiency after pancreatic head resection.

Objective. The majority of patients with long-term survival after pancreatic head resection suffer from pancreatic exocrine insufficiency. The objective of this study was to investigate whether this is due to glandular malfunction or obstructed pancreaticojejunal anastomosis. Material and methods. Twenty-six patients (10 M, 16 F, mean age 61 years, range 34–81 years) were re-examined a median of 52 months (range 3–76 months) after pancreatic head resection and end-to-end invaginated pancreaticojejunostomy. Pancreatic exocrine function was measured by fecal elastase-1 assay. The size of the pancreatic remnant, glandular secretion and the flow through the anastomosis were analyzed with secretin-stimulated dynamic magnetic resonance pancreatography (D-MRP). Results. All patients had pancreatic exocrine insufficiency, 24 (92%) of them having severe insufficiency. Eighteen patients (69%) reported moderate to severe diarrhea. Lowest fecal elastase-1 concentrations were associated with the initial diagnosis of chronic pancreatitis or ductal adenocarcinoma, suggesting preoperative primary or secondary chronic pancreatitis as important determinants. The size of the remnant gland did not correlate with the fecal elastase-1 concentrations. D-MRP failed in three patients. Severe glandular malfunctions were found in 7 (30%) of the 23 successful D-MRP examinations. The anastomosis was totally obstructed in 5 patients (22%) or partially obstructed in 6 (26%) but remained perfectly open in 5 patients (22%). The five patients with perfect anastomoses had the highest measured median fecal elastase-1 activity. Conclusions. Although late diarrhea and pancreatic exocrine insufficiency may be partly induced already by the disease treated with resection, at least half may be explained by obstructed anastomosis. To obtain better late functional results, improvements may be required in the surgical techniques.

Difference in microbes contaminating pancreatic necrosis in biliary and alcoholic pancreatitis

SummaryConclusionThere are differences in the microbiology of infected pancreatic necrosis in alcoholic and biliary pancreatitis. One possible explanation may be different routes of contamination.BackgroundInfection is a severe complication in acute pancreatitis. Bacteria are found in 40–70% of all patients suffering from necrotizing pancreatitis. We investigated whether there were any differences in microbes isolated from pancreatic necrosis in biliary and alcoholic pancreatitis.MethodsMicrobiological tests were conducted on necrosis taken at the operation for pancreatitis with the etiology of (group A) alcoholic pancreatitis (n=47) and (group B) biliary pancreatitis (n=23). Patients with simultaneous cholecystitis were excluded. The time from the first symptoms to the operation or the extent of necrosis did not differ between the groups.ResultsMicrobes were isolated more often in the cultures from group B than group A (17/23=74% vs 15/47=32%,p=0.001). The most common were Gram-positive bacteria in group A and Gram-negative bacteria in group B. From the first week, from the onset of symptoms to the operation, Gram-negative bacteria were isolated significantly more often in the cultures from group B patients than from group A patients (8/10=80% vs 1/5=20%,p=0.04). In multivariate analysis, we found that biliary pancreatitis was an independent risk factor (adds ratio 5.5, 95% confidence interval [CI] 0.59–52.10) of contamination of necrosis with Gram-negative bacteria.

Abstinence after First Acute Alcohol-Associated Pancreatitis Protects Against Recurrent Pancreatitis and Minimizes the Risk of Pancreatic Dysfunction

AIMS To determine the recurrence of pancreatitis and subsequent pancreatic function in patients who stop drinking after the first episode of alcohol-associated pancreatitis. METHODS Of a total of 118 patients suffering from their first alcohol-associated pancreatitis, 18 (all men, age median 47 (27-71) years) met the inclusion criterion for abstinence during follow-up. The criterion for abstinence was alcohol consumption <24 g per 2 months (self-estimated), which is in line with questionnaires eliciting alcohol consumption and dependency (Alcohol Use Disorders Identification Test < 8 and Short Alcohol Dependence Data < 9). Recurrent attacks of acute pancreatitis were studied. Smoking, body mass index and laboratory tests detecting heavy consumption of alcohol were recorded. Blood and faecal tests were studied to assess endocrine and exocrine pancreatic function. RESULTS During a mean follow-up time of 5.15 (1.83-9.13) years and a total of 92.7 patient-years, there were no recurrent attacks of acute pancreatitis among the 18 abstainers. Two patients had diabetes prior to and one was diagnosed immediately after the first episode of acute pancreatitis. One patient had impaired glucose metabolism at 2 years. Two patients had low insulin secretion in glucagon-C-peptide test, one at 4 years and the other at 5 years. Only one patient (6%) maintained low elastase-1 activity during the abstinence follow-up. Of the 100 non-abstainers, 34% had at least one recurrence during the follow-up. CONCLUSION Regardless of the mediator mechanisms of acute alcoholic pancreatitis, abstinence after the first episode protects against recurrent attacks. Pancreatic dysfunction is also rare among abstinent patients.

Delayed gastric emptying and intestinal hormones following pancreatoduodenectomy.

Background/Aims: Delayed gastric emptying (DGE) is frequently reported in patients following pancreatoduodenectomy (PD). The present study tested the hypothesis that gastrointestinal hormones known to effect gastric emptying contribute to DGE in patients after PD. Methods: Patients with (delayed, n = 9) or without clinical signs of DGE (non-delayed, n = 22) after PD were investigated. Plasma concentrations of motilin, glucagon-like peptide-1 (GLP-1), neurotensin, and peptide YY (PYY) and the gastric emptying rate (GER), assessed by the paracetamol absorption method were measured after a liquid meal on postoperative day 11. Results: Days with a nasogastric tube (p < 0.01), days until solid food was tolerated (p < 0.05), and hospital stay (p < 0.001) were increased in delayed compared to non-delayed patients. The total and incremental integrated peptide responses of motilin and GLP-1 were similar, but the responses of neurotensin and PYY were reduced, in delayed compared to non-delayed patients, whether considered on clinical grounds or by measured GER (p < 0.05–0.005). Conclusion: Neurotensin and PYY slow the rate of gastric emptying in humans. Therefore, our findings suggest that reduced hormone responses were the consequence of DGE arising from delayed delivery of nutrients to the distal intestine where the endocrine cells secrete neurotensin and PYY reside.

Alcoholic, But Not Biliary, Pancreatitis Varies Seasonally in Occurrence

Background: Alcohol is the most common cause of acute pancreatitis in Finland (70%). The amount of alcohol consumed has been shown to be associated with the prevalence of pancreatitis in the country, and also to be an important determinant of the severity of the first episode of acute alcoholic pancreatitis. We have a clinical suspicion that the use of alcohol and the incidence of pancreatitis are increased during holiday periods in summer, although no seasonal variations have been reported in a German population. Methods: Between 1972 and 1992 a total of 1556 episodes with acute alcoholic pancreatitis were treated at Tampere University Hospital; 552 were first episodes and 1004 were recurrent. For comparison, we investigated 297 episodes of acute biliary pancreatitis treated in that same time period. We investigated the monthly prevalence of acute alcoholic (first and recurrent) pancreatitis and compared this with the monthly absolute alcohol consumption. Results: Taking all alcoholic pancreatitis episodes into account, significant differences can be seen between prevalence and month of onset of the disease ( P r < r 0.0001), whereas among biliary pancreatitis episodes there were no differences ( P r = r 0.3). Prevalence of acute alcoholic pancreatitis was significantly higher than the expected prevalence in July and August, and the amount of alcohol consumption (100% alcohol, litres) was highest during these same months. Also during March, October and December the prevalence was higher than expected. Conclusion: Months with holiday seasons, Christmas, Easter, summer and autumn, are associated with the highest alcohol consumption and the highest prevalence of acute alcoholic pancreatitis.BACKGROUND Alcohol is the most common cause of acute pancreatitis in Finland (70%). The amount of alcohol consumed has been shown to be associated with the prevalence of pancreatitis in the country, and also to be an important determinant of the severity of the first episode of acute alcoholic pancreatitis. We have a clinical suspicion that the use of alcohol and the incidence of pancreatitis are increased during holiday periods in summer, although no seasonal variations have been reported in a German population. METHODS Between 1972 and 1992 a total of 1556 episodes with acute alcoholic pancreatitis were treated at Tampere University Hospital; 552 were first episodes and 1004 were recurrent. For comparison, we investigated 297 episodes of acute biliary pancreatitis treated in that same time period. We investigated the monthly prevalence of acute alcoholic (first and recurrent) pancreatitis and compared this with the monthly absolute alcohol consumption. RESULTS Taking all alcoholic pancreatitis episodes into account, significant differences can be seen between prevalence and month of onset of the disease (P < 0.0001), whereas among biliary pancreatitis episodes there were no differences (P = 0.3). Prevalence of acute alcoholic pancreatitis was significantly higher than the expected prevalence in July and August, and the amount of alcohol consumption (100% alcohol, litres) was highest during these same months. Also during March, October and December the prevalence was higher than expected. CONCLUSION Months with holiday seasons, Christmas, Easter, summer and autumn, are associated with the highest alcohol consumption and the highest prevalence of acute alcoholic pancreatitis.