Tom Schröder

Early antibiotic treatment in acute necrotising pancreatitis

Despite improvements in surgical treatment and intensive care, mortality from severe acute pancreatitis remains high. We have carried out a randomised study of 60 consecutive patients with alcohol-induced necrotising pancreatitis to find out whether early antibiotic treatment can improve outcome. 30 patients were assigned cefuroxime (4.5 g/day intravenously) from admission. In the second group, no antibiotic treatment was given until clinical or microbiologically verified infection or after a secondary rise in C-reactive protein. The inclusion criteria were C-reactive protein concentration above 120 mg/L within 48 h of admission and low enhancement (< 30 Hounsfield units) on contrast-enhanced computed tomography. There were more infectious complications in the non-antibiotic than in the antibiotic group (mean per patient 1.8 vs 1.0, p = 0.01). The most common cause of sepsis was Staphylococcus epidermidis; positive cultures were obtained from pancreatic necrosis or the central venous line in 14 of 18 patients with suspected but blood-culture-negative sepsis. Mortality was higher in the non-antibiotic group (seven vs one in the antibiotic group; p = 0.03). Four of the eight patients who died had cultures from pancreatic necrosis positive for Staph epidermidis. We conclude that cefuroxime given early in necrotising pancreatitis is beneficial and may reduce mortality, probably by decreasing the frequency of sepsis.

C-reactive protein (CRP) and serum phospholipase A2 in the assessment of the severity of acute pancreatitis.

The present study examines the value of C-reactive protein (CRP) determinations in the assessment of the severity of acute pancreatitis and the correlation of CRP with serum phospholipase A2 activity and the clinical status. Fifty three patients with acute pancreatitis were studied; 17 with haemorrhagic pancreatitis and 36 with a mild form of the disease. S-phospholipase A2 activity increased significantly (p less than 0.05) in patients with fatal pancreatitis but not in those with mild disease. Phospholipase A2 concentrations were below 10 nmol FFA/ml min in mild, while they rose to 20-40 nmol FFA/ml min in haemorrhagic pancreatitis. In fatal cases very high (up to 50-60 nmol FFA/ml min) serum phospholipase A2 concentrations were recorded. The increase in CRP was greater in the patients with severe pancreatitis. One day after admission mean CRP was 280 mg/l in patients with haemorrhagic and 45 mg/l in those with the mild pancreatitis (p less than 0.001). High CRP values also correlated with the prognostic signs indicative of severe pancreatitis. CRP and S-phospholipase A2 determinations are valuable in the early assessment of the severity of acute pancreatitis, but the CRP assay is much easier to include in hospital routine.

Early Detection of Acute Fulminant Pancreatitis by Contrast-Enhanced Computed Tomography

Twenty-eight consecutive patients with a first attack of acute alcohol-induced pancreatitis were examined by computed tomography (CT). After a survey scan of the abdomen a rapid contrast bolus (400 mg I/kg) was given intravenously, and the contrast enhancement of the pancreatic parenchyma was measured from a consecutive series of pancreatic scans. Nine patients with a fulminant course of the disease were operated on, and haemorrhagic necrotizing pancreatitis was found in eight. In all of these the contrast enhancement was decreased or absent. Patients recovering by conservative treatment showed normal or increased enhancement. The contrast enhancement seems to constitute a useful criterion for the early differentiation of acute fulminant pancreatitis from less severe forms of the disease.

Inhibition of serum phospholipase-A2 in acute pancreatitis by pharmacological agents in vitro

Phospholipase-A2 has been suggested as having a role in the pathophysiology of acute pancreatitis. The inhibition of phospholipase-A2 was studied in vitro using 17 pharmacological agents in the search for a specific therapy for acute pancreatitis. The inhibitory effect was tested using an isotopic assay system with 2-palmitoyl-(1-14C)-labelled dipalmitoyl phosphatidylcholine as a substrate and 10 microliters of serum from patients with acute necrotizing pancreatitis as an enzyme source. Among all agents tested, anti-inflammatory drugs inhibited enzyme activity most significantly: indomethacin (9.0 x 10(-3) mol l-1) decreased the phospholipase-A2 activity to one- tenth. The weak inhibitory effect could also be demonstrated using a lower concentration of 2 x 10(-5) mol l-1, which can be achieved after intravenous administration of 50 mg of this drug. The other drugs inhibited the enzyme activity at concentrations higher than those achieved after intravenous injections in clinical use. Diclofenac (3.1 x 10(-2) mol l-1) reduced the phospholipase-A2 activity by 93%, ketoprofen (2.0 x 10(-2) mol l-1) or chlorpromazine (1.4 x 10(-2) mol l-1) by 90%, tobramycin (1.7 x 10(-2) mol l-1) by 84%, doxycycline (9.0 x 10(-3) mol l-1) by 61%, dexamethasone (1.7 x 10(-3) mol l-1) by 62%, methylprednisolone (3.8 x 10(-2) mol l-1) by 50%, and pindolol (1.0 x 10(-4) mol l-1) by 59%. A weak inhibition of phospholipase-A2 activity was demonstrated by betamethasone, bupivacaine, digoxin, hydrocortisone, lidocaine, metoprolol, propranolol, and vancomycin. Indomethacin proved the most potent of the tested agents in inhibiting phospholipase-A2 activity in serum from patients with acute pancreatitis and should be further studied in vivo.

Serum complex of trypsin 2 and alpha 1 antitrypsin as diagnostic and prognostic marker of acute pancreatitis: clinical study in consecutive patients.

Abstract Objective: To estimate the usefulness of serum concentrations of the complex of trypsin 2 and (alpha)1 antitrypsin in diagnosing and assessing the severity of acute pancreatitis in comparison with serum C reactive protein, amylase, and trypsinogen 2 concentrations (reference markers). Design: Markers were measured in consecutive patients admitted with acute abdominal pain that was either due to pancreatitis or to other disease unrelated to the pancreas (controls). Setting: Department of surgery of a teaching hospital in Helsinki. Subjects: 110 patients with acute pancreatitis and 66 with acute abdominal diseases of extrapancreatic origin. On the basis of the clinical course, acute pancreatitis was classified as mild (82 patients) or severe (28 patients). Main outcome measures: Clinical diagnosis of acute pancreatitis and severity of the disease. Results: At admission all patients with acute pancreatitis had clearly raised concentrations of trypsin 2-(alpha)1 antitrypsin complex (32 μg/l), whereas only three of the controls had such values. Of the markers studied, trypsin 2-(alpha)1 antitrypsin complex had the largest area under the receiver operating curve, both in differentiating acute pancreatitis from extrapancreatic disease and in differentiating mild from severe disease. Conclusions: Of the markers studied, trypsin 2-(alpha)1 antitrypsin complex was the most accurate in differentiating between acute pancreatitis and extrapancreatic disease and in predicting a severe course for acute pancreatitis. Key messages This complex can be accurately measured in a sensitive immunoassay In this study the diagnostic and prognostic accuracy of serum concentrations of trypsin 2-(alpha)1 antitrypsin complex was determined in acute pancreatitis The complex was more accurate than trypsinogen 2, C reactive protein, and amylase in differentiating between acute pancreatitis and extrapancreatic disease and in predicting a severe course for the disease If the immunoassay could be automated determination of concentrations of trypsin 2-(alpha)1 antitrypsin complex could greatly improve the diagnosis of this common and potentially lethal disease

Diagnostic evaluation and aggressive surgical approach in bleeding pseudoaneurysms associated with pancreatic pseudocysts

Hemorrhage is an uncommon but serious complication of pancreatic pseudocysts. When gastrointestinal bleeding or intra-abdominal hemorrhage is associated with a pancreatic pseudocyst and the usual sources of bleeding are not detected by endoscopy, the rupture of a pseudoaneurysm inside the pseudocyst should be suspected. We present 13 cases, 11 associated with chronic and 2 with late complications after acute necrotizing pancreatitis. On the basis of sonographic findings, bleeding site was suspected in 8 of 11 patients (73%). Computed tomography (CT) was performed on 10, and bleeding was suspected in 8 (80%). The pseudoaneurysm itself was detected by CT in one and by ultrasonography in none. Visceral angiography was performed on five patients, and the pseudoaneurysm was evident in all. External drainage with arterial ligation was done as a primary operation in five patients; four of them later underwent pancreatic resection because of rebleeding. In eight cases pancreatic resection was the initial operation; none of these patients continued to bleed or needed reoperation because of the same pseudoaneurysm. There were no intraoperative deaths, but one patient died postoperatively. Aggressive diagnostic evaluation and surgical approach are associated with a reduction in mortality and morbidity in this serious complication of pancreatic pseudocysts.

A new method for the diagnosis of acute hemorrhagic-necrotizing pancreatitis using contrast-enhanced CT

Twenty-eight consecutive patients with a first attack of alcohol-induced pancreatitis were studied using contrast-enhanced CT. The findings on CT were then related to the course of the disease. The patients with acute hemorrhagic-necrotizing pancreatitis showed significantly lower enhancement values of the pancreatic parenchyma than those with milder forms of the disease.The next 20 patients with severe pancreatitis were scanned using a slightly modified procedure. The enhancement values were calculated and plotted on the graphs for the 2 former groups.Two categories of pancreatic enhancement were found: “low enhancement” and “high enhancement.” In all 10 patients with “low-enhancement” values surgery revealed hemorrhagic-necrotizing pancreatitis. In the 10 patients with “highenhancement” values conservative treatment was continued, and the clinical course was nonfulminant in all of them.

Endotoxaemia and acute pancreatitis: correlation between the severity of the disease and the anti-enterobacterial common antigen antibody titre.

Enterobacterial common antigen is a highly immunogenic component of the Gram negative bacterial cell wall that is common to all enteric bacteria. In the present study, the humoral antibody response against enteric bacteria was investigated by measuring antibodies to enterobacterial common antigen in paired serum samples in 38 patients with acute pancreatitis and in 31 healthy subjects. In mild pancreatitis (11 patients), no changes in anti-enterobacterial common antigen titres were observed as compared with healthy controls. Nine of the 10 patients had a significant increase (greater than or equal to 8 times) in anti-enterobacterial common antigen titres during the disease. Similarly, in patients with fulminant (haemorrhagic) pancreatitis who survived, a significant increase in anti-enterobacterial common antigen titres occurred during the course of the disease (in nine of the 11 patients). Paradoxically, only one of the six patients with fulminant pancreatitis with fatal outcome showed a significant increase in his anti-enterobacterial common antigen titre. The results suggest that Gram negative bacterial components escape into the systemic circulation in acute pancreatitis. This may have pathophysiologic significance in this disease.

Contrast-enhanced computed tomography and microangiography of the pancreas in acute human hemorrhagic/necrotizing pancreatitis

Five patients with severe acute pancreatitis had a low contrast enhancement (CE) of the pancreas in computed tomography (CT) and underwent subtotal pancreatectomy. Microangiography and histologic studies were performed on the resected pancreases, and the findings were related to those of CE. All patients had histologically documented hemorrhagic/necrotizing pancreatitis. The more disturbed the vascular anatomy in microangiography, the more hemorrhages and necroses were found in histology. The microangiographic and histologic findings corresponded closely to the low contrast-enhanced CT of the diseased pancreas in each patient. Thus, in the early phase of severe acute pancreatitis, one can detect by noninvasive means which areas of the gland are necrotic and which edematous by a dynamic study of contrastenhanced CT of the pancreas.

Serum Trypsinogen-2 in the Prediction of Outcome in Acute Necrotizing Pancreatitis

BACKGROUND The accuracy of serum trypsinogen-2 in predicting the severity of acute necrotizing pancreatitis (ANP) was prospectively evaluated in 52 consecutive patients. METHODS A new sensitive immunofluorometric assay was used for serum trypsinogen-2, RESULTS Mean values during the first 24 h were 42.1 micrograms/l in control patients, 1435 micrograms/l in uncomplicated cases, and 4090 micrograms/l in complicated or fatal cases. There was a significant difference in serum trypsinogen-2 values between patients with uncomplicated and complicated disease (p = 0.002) already on admission. When a cutoff level of 1000 micrograms/l was used, patients with uncomplicated ANP were differentiated from patients with complicated ANP with a sensitivity of 91% and with a specificity of 71%. CONCLUSIONS The immunofluorometric assay of serum trypsinogen-2 is a sensitive and specific method for prediction of the severity of the disease in necrotizing pancreatitis.