Esko Kemppainen

Early prediction of organ failure by combined markers in patients with acute pancreatitis.

Several biological markers and clinical scoring systems have been used to predict the course of acute pancreatitis. Because organ failure is the most severe complication of the disease, prognostic markers and their combinations that would predict organ failure on hospital admission were sought.

The endoscopic management of pancreatic fistulas.

BackgroundInterest in the use of therapeutic endoscopy for the treatment of pancreatic diseases has been on the increase for several years. Our aim was to assess the efficacy of endoscopic retrograde cholangiopancreaticography (ERCP) in the treatment of pancreatic fistulas.MethodsWe evaluated the results of therapeutic ERCP in 50 patients with pancreatic fistula treated at the Helsinki University Central Hospital from 1998 to 2003.ResultsThe success rate of fistula closure after therapeutic ERCP was 82%. Five patients required operative treatment when ERCP was unsuccessful. There was little morbidity and no procedure-related mortality. Four patients died because severe illnesses made them unfit for any further procedures.ConclusionERCP is a safe and effective modality and should be considered as first-line therapy in the management of pancreatic fistula.

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.

Pancreatic Secretory Trypsin Inhibitor (SPINK1) Gene Mutations in Patients With Acute Pancreatitis

Objectives: Mutations in the secretory trypsin inhibitor (SPINK1) gene have been found to be associated with hereditary and chronic pancreatitis. There are no previous reports on SPINK1 mutations in patients with acute pancreatitis (AP). Methods: The study population consists of 371 patients with AP, of which 207 patients had mild and 164 had a severe form of the disease. The etiologies of AP were identified. Four hundred fifty-nine blood donors served as controls. SPINK1 N34S and P55S mutations were detected by minisequencing and confirmed by direct sequencing. Results: The N34S mutation was found in 29 (7.8%) of the patients and in 12 (2.6%) of the controls (P < 0.0001, Fisher exact test). There was no difference in the frequency of the P55SS mutation between the groups. A majority of the patients (n = 229; 61.7%) had alcohol-induced AP. The frequency of the N34S mutation was higher in the subgroups of severe AP (15/164; 9.1%) and alcohol-induced AP (21/229; 9.2%), but the differences were not statistically significant. No differences in age at admission and number of attacks of AP were observed between the groups. Conclusion: SPINK1 N34S mutation enhances the susceptibility of AP.

Recent advances in the surgical management of necrotizing pancreatitis

Purpose of reviewTo summarize advances and new concepts in the surgical management of necrotizing pancreatitis published within the past year with emphasis on the evolving importance of the recognition of abdominal compartment syndrome as a significant contributor to early development of organ failure. Recent findingsUnderdiagnosed and untreated, abdominal compartment syndrome is a potential contributing factor to the development of early organ failure in patients with severe acute pancreatitis and warrants routine measurement of intra-abdominal pressure in patients treated for severe pancreatitis. The current estimate of the prevalence of intra-abdominal hypertension in severe acute pancreatitis is about 40%, with about 10% overall developing abdominal compartment syndrome, associated with increased hospital mortality rates. Early surgical decompression without exploring the pancreas further seems to be the most effective treatment. Primary fascial closure of the abdominal wall following abdominal decompression can be attempted, but in most cases the prolonged inflammatory process in the abdomen and the risk of recurrent abdominal compartment syndrome favors use of gradual closure or delayed reconstruction of the abdominal wall. SummaryRecent studies confirm the overall validity of the established surgical principles for necrotizing pancreatitis: delayed necrosectomy in patients with infected peripancreatic necrosis, mostly nonoperative management of sterile necrosis, and delayed cholecystectomy in severe gallstone-associated pancreatitis. The role of abdominal compartment syndrome as an important contributing factor to early development of multiple organ failure and the potential benefit of surgical decompression are gaining support from recent reports and should be carefully assessed in future studies.

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.

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.

Vasodilatory shock in severe acute pancreatitis without sepsis: Is there any place for hydrocortisone treatment?

Background:  Hydrocortisone (HC) has been reported to rapidly improve hemodynamics and reduce the time to vasopressor cessation in septic shock, but none has focused on this effect in acute pancreatitis. We therefore performed a study to assess the effects of hydrocortisone on catecholamine‐dependent shock among patients with severe acute pancreatitis.

Triage in a Bomb Disaster with 166 Casualties

AbstractBackground:We describe the surgical response of the Helsinki University Hospitals to a bomb disaster with 166 casualties. According to the Helsinki Area Disaster Plan, severely injured patients were transported to several hospitals with emergency facilities to avoid overtriage.Methods:The patient data were gathered from hospitals, health centers and other doctor visit/ appointments records. Injury Severity Scores (ISS), critical mortality rate and death/wounded ratio were calculated.Results:Of the 166 injured patients, 5 died immediately at the bombing site. Sixty-six patients were transported to the six affiliated hospitals. The mean ISS score for survivors was 12. Seventeen percent of the acute survivors were critically injured (ISS>15). The critical mortality rate was 8%. There were no later deaths; the dead/wounded ratio was 4.4. Operative treatment was performed for 38% of the patients treated in surgical emergency departments.Conclusion:The bombing attack in Myyrmanni shopping center led to 166 casualties, of whom 66 patients were received at six affiliated hospitals in Helsinki and Uusimaa Area. The critical mortality rate was low. A local disaster plan was implemented. The surgical response was rapid and well coordinated. In a mass casualty disaster not all disaster victims need to go to a trauma center.

Smoking and Diverticular Disease of the Colon

It needs to be repeated: smoking is an enormous health hazard. Each year 5–6 million people die from smoking. The causal relationship between cancer deaths (including gastroenterological malignancies) and smoking is very well known, but tobacco causes, in fact, four times as many deaths from non-cancer causes than it does from cancer, cardiovascular diseases being the most frequent. The gastrointestinal tract is also sensitive to the noxious influence of smoking and there is strong evidence that tobacco causes or contributes to many abdominal diseases. To mention a few: smoking raises the risk of peptic ulcer disease, impairs ulcer healing and favours ulcer recurrence. Cigarette smoking also reduces the pressure of the lower esophageal sphincter and worsens gastro-esophageal reflux disease. Smoking appears to be a risk factor for Crohn’s disease and it affects adversely the course of the disease. The relationship between acute pancreatitis and smoking has recently been clarified and, as is well-known from before, there is a strong correlation between acute exacerbations of chronic pancreatitis and development of complications in chronic pancreatitis. An interesting, but equally sad, association has recently been described between tobacco use and the risk of perforation of the inflamed appendix. A general finding is that smoking reduces the overall capacity of tissues to heal after surgical trauma. In this issue of the Scandinavian Journal of Surgery, Turunen and colleagues report having identified a new association between smoking and a gastroenterological disease: smoking affects the complications of diverticular disease of the colon. Smokers tend to develop complications at a younger age than non-smokers and young smokers have a higher risk of recurrent diverticulitis after bowel resection than non-smokers. The picture gets even grimmer by the observation that smokers have more strictures and histological perforations in the operative specimens of the sigmoid colon than non-smokers. As the authors correctly point out, the natural history of diverticular disease is not fully known. Current knowledge is based mainly on retrospective studies and the results may not be all that conclusive. We lack large, prospective, population-based follow-up studies based on documented, solid diagnostic criteria. The available studies are based on clinical criteria of diverticular disease and there is the obvious risk of including misdiagnosed patients is these studies. The inclusion criteria of studies on diverticular disease should include well-defined findings on CT-imaging. The study by Turunen et al is preliminary in the sense that it is retrospective and the main selection criterion was complicated disease. What the study, however, does highlight is that, from now on, smoking should be included as a risk factor in prospective studies on complications of diverticular disease of the colon.