M. Lempinen

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.

Jejunal diverticulosis: a potentially dangerous entity

Although jejunal diverticulosis is a rare entity and usually asymptomatic, it may cause chronic symptoms and acute complications. Because of the rarity of the entity, diagnosis is often delayed, resulting in unnecessary morbidity and mortality. The purpose of this study was to draw attention to jejunal diverticula and their complications. The medical records of 8 consecutive patients with complications due to small‐bowel diverticula treated at our department during the past 4 years were reviewed. All diverticula were located in the jejunum. Seven patients had acute complications, 3 patients had an intra‐abdominal abscess, 2 had free perforation with diffuse peritonitis, 1 had a bowel occlusion and 1 patient had concomitant bleeding and occlusion. One patient presented with chronic symptoms. A preoperative diagnosis of jejunal diverticula, before explorative laparotomy, was not reached in any of the 7 patients with acute symptoms. In the patient with chronic symptoms, multiple jejunal diverticula complicated by a jejuno‐colic fistula and foreign body were found at laparotomy. On patient died of multiorgan failure. Small‐bowel diverticulosis is a rare entity, but it should not be regarded as a clinically insignificant finding. It may be difficult to make a preoperative diagnosis. Patients with incidentally detected proximal jejunal diverticula, at imaging studies or at laparotomy, warrant close observation and awareness that the diverticula may cause serious complications.

Urinary trypsinogen activation peptide as a marker of severe acute pancreatitis.

Trypsinogen activation peptide (TAP) may be an early marker of severe pancreatitis. Previous studies have included all patients with organ failure in the group with severe pancreatitis, although patients with transient organ failure may have a good prognosis. The aim of this study was to determine the value of urinary TAP estimation for prediction of severity of acute pancreatitis, and to validate use of several markers of prediction of severity against a new, stringent definition of severity.

Mutations N34S and P55S of the SPINK1 gene in patients with chronic pancreatitis or pancreatic cancer and in healthy subjects: A report from Finland

Objective Mutations in the Kazal type 1 serine protease inhibitor (SPINK1) gene have recently been associated with chronic pancreatitis (CP), an established risk factor for pancreatic cancer. The aim of this study was to investigate the frequency of the SPINK1 gene mutations (N34S and P55S) in patients with CP, or pancreatic cancer, and in healthy subjects in Finland. Material and methods The N34S and P55S mutations were determined by PCR amplification followed by solid-phase minisequencing in 116 patients with CP and in 188 with pancreatic cancer. In patients with CP, alcohol was the aetiological factor in 87 (75%), pancreas divisum in 4 (3%), gallstones in 5 (5%) and 20 patients (17%) had an idiopathic disease; 459 healthy individuals were enrolled as controls. Results The frequency of the N34S mutation was significantly higher in patients with CP (14/116, 12%) than in controls (12/459, 2.6%) (p<0.0001). There was no difference in the frequency of the P55S mutation between patients with CP (1/116, 0.9%) and controls (6/459, 1.3%). The N34S mutation was present in 9 (10%) out of 87 patients with alcoholic CP, and in 5 (25%) patients with idiopathic CP. No SPINK1 mutations were found in patients with CP caused by anatomical variations or gallstones. Among the 188 patients with a pancreatic malignant tumour, the N34S mutation was present in 7 cases (3.7%). The frequency of the N34S mutation in healthy controls in this study was significantly higher than earlier reported in other countries (p=0.03). Conclusions The SPINK1 N34S mutation was significantly associated with an increased risk of CP. The association of the N34S mutation with alcoholic CP was marginally stronger than in earlier studies, whereas in the Finnish population in general, this mutation was significantly more frequent than reported elsewhere.

Treatment of Pancreatic Fistulas with Somatostatin and Total Parenteral Nutrition

Nineteen pancreatic fistulas were treated with somatostatin (ST) and total parenteral nutrition (TPN). Five of the fistulas developed in an uninflamed pancreas, whereas 14 fistulas developed secondary to a necrotizing or chronic pancreatitis. Fistular output varied between 20 and 800 ml/day (median, 160 ml) during TPN before ST treatment; amylase concentration was 10,500-800,000 UI/l. Twelve of 16 (75%) fistulas were contaminated with bacteria. Thirteen of 19 (68%) fistulas closed after a median treatment of 7 (range, 2-14) days. Seven of eight fistulas with open drainage to the bowel healed, whereas only one of six with obstructed drainage closed. All of the uninfected fistulas and half of the infected fistulas closed. The findings suggest that somatostatin treatment speeds up the closure of pancreatic fistulas with open drainage to the bowel but is not beneficial when the intestinal drainage of the fistular region to the bowel is obstructed.

Trypsinogen-2 and trypsinogen activation peptide (TAP) in urine of patients with acute pancreatitis

BACKGROUND AND AIMS There is an obvious clinical need for a simple test that can identify patients at risk of developing severe acute pancreatitis. In this work we compared urinary trypsinogen-2 with urinary trypsinogen activation peptide (TAP) and serum C-reactive protein (CRP) for early differentiation between mild and severe acute pancreatitis. PATIENTS AND METHODS The study population consisted of 127 consecutive patients with acute pancreatitis of whom 29 had severe disease. Urinary trypsinogen-2 was measured by a quantitative immunofluorometric assay and TAP by a competitive immunoassay. Serum CRP was determined by immunoturbidimetry. RESULTS The sensitivity and specificity to identify severe acute pancreatitis on admission was 72% and 81% for urinary trypsinogen-2, 64% and 82% for urinary TAP, and 29% and 93% for serum CRP, respectively. At 24 h after admission, the values were 82% and 78% for urinary trypsinogen-2, 52% and 92% for urinary TAP, and 84% and 72% for serum CRP, respectively. Receiver-operating characteristics curve analysis showed that the area under the curve was larger for urinary trypsinogen-2 than for urinary TAP and serum CRP on admission and 24 h after admission. On admission the positive likelihood ration for urinary trypsiongen-2 was 3.7, for urinary TAP 3.6, and 4.3 for serum CRP, respectively. The corresponding negative likelihood ratios were 0.34, 0.43, and 0.76, respectively. CONCLUSION Urinary trypsinogen-2 was superior to serum CRP and as god as or even better than urinary TAP and in the early prediction of disease severity in acute pancreatitis. These results suggest that it could be a valuable adjunct in the early assessment of the severity of acute pancreatitis.

Clinical Value of Severity Markers in Acute Pancreatitis

Acute pancreatitis is a common digestive disease of which the severity may vary from mild, edematous to severe, necrotizing disease. An improved outcome in the severe form of the disease is based on early identification of disease severity and subsequent focused management of these high-risk patients. However, the ability of clinicians to predict, upon presentation, which patient will have mild or severe acute pancreatitis is not accurate. Prospective systems using clinical criteria have been used to determine severity in patients with acute pancreatitis, such as the Ransons prognostic signs, Glasgow score, and the acute physiology and chronic health evaluation II score (APACHE II). Their application in clinical practise has been limited by the time delay of at least 48 h to judge all parameters in the former two and by being cumbersome and time-consuming in the latter. Contrast-enhanced computed tomography is presently the most accurate non-invasive single method to evaluate the severity of acute pancreatitis. It cannot, however, be performed to all patients with acute pancreatitis. Therefore, considerable interest has grown in the development of reliable biochemical markers that reflect the severity of acute pancreatitis. In this article we critically appraise current and new severity markers of acute pancreatitis in their ability to distinguish between mild and severe disease and their clinical utility.

Microangiography of the Pancreas in Experimental Oedemic and Haemorrhagic Pancreatitis

UNLABELLED Microangiography of the pancreas was performed in five normal piglets and in 10 piglets with oedemic and haemorrhagic pancreatitis in order to evaluate the role of microcirculatory changes in experimental pancreatitis. Acute haemorrhagic pancreatitis was induced by intraductal infusion of trypsin-taurocholate and oedematous pancreatitis correspondingly by infusion of autologous diluted bile. Both types of pancreatitis were confirmed by histological examination. Microangiography of the control animals revealed well-filled arteries, arterioles and capillaries, which formed a dense capillary network. In the areas of histologically documented haemorrhagic pancreatitis, unfilled capillary nets were observed as empty areas in the microangiography. Other areas of focal extravasation of the contrast material could be seen. Arteries and arterioles were well filled. In oedematous pancreatitis, the microangiography was unchanged compared with the control. CONCLUSION Acute experimental haemorrhagic pancreatitis is associated with severe disturbances in the capillary circulation of the pancreas, whereas in oedematous pancreatitis the microangiography of the pancreas is normal.

Pancreatic Blood Flow and Contrast Enhancement in Computed Tomography during Experimental Pancreatitis

The pancreatic blood flow and contrast enhancement in computed tomography (CT) were studied in 10 piglets weighing 17-25 kg with experimental pancreatitis. Each animal served as its own control. CT and blood flow measurements were made both before induction of pancreatitis and 5-6 h after the onset of the disease. Cardiac output was measured by thermodilution, and was kept constant throughout the study by infusion of dextran and saline. Although the pancreatic blood flow remained constant in this experiment, CT showed a significant decrease in contrast enhancement.

Early sequential changes in serum markers of acute pancreatitis induced by endoscopic retrograde cholangiopancreatography.

Background/Aims: Trypsinogen activation is thought to play a crucial role in the pathogenesis of acute pancreatitis (AP). Our aim was to characterize the very early sequential changes of trypsinogen-1, trypsinogen-2, the trypsin-2-α1-antitrypsin complex (T2-AAT), and pancreatic secretory trypsin inhibitor (PSTI) in serum from patients with pancreatitis induced by endoscopic retrograde cholangiopancreatography (ERCP), a model for studying the early phase of the disease in humans. Patients and Methods: The study population consisted of 659 consecutive patients with 897 ERCP procedures. Blood samples were obtained before and at different time points after the procedure. The serum concentrations of trypsinogen-1 and trypsinogen-2, PSTI and T2-AAT were determined by time-resolved immunofluorometric assays. Results: ERCP-induced pancreatitis developed after 50 of the 897 ERCP procedures (5.6%). Sixty-one randomly selected ERCP patients without post-ERCP pancreatitis served as controls. Trypsinogen-1 and trypsinogen-2 showed an equally steep increase during the two first hours after ERCP in patients developing AP, but trypsinogen-1 decreased more rapidly than trypsinogen-2, which remained elevated during the 5-day study period. Serum PSTI also increased rapidly whereas T2-AAT increased more slowly peaking at 24 h. In patients developing post-ERCP pancreatitis the median concentration of trypsinogen-1 was markedly higher than in the controls already before the ERCP procedure. In the control group the concentrations of trypsinogen-1, trypsinogen-2, PSTI and T2-AAT did not change significantly. Conclusions: The rapid increase of trypsinogen-1 and trypsinogen-2 and PSTI in the early phase of AP suggests that release of pancreatic enzymes is the initial event while the delayed increase of T2-AAT may reflect that the capacity of the intrapancreatic PSTI-based inhibitory mechanism has been exhausted.