Ellen Andersson

The effect of intestinal ischemia and reperfusion injury on ICAM-1 expression, endothelial barrier function, neutrophil tissue influx, and protease inhibitor levels in rats.

Multiple organ dysfunction syndrome (MODS) is mediated by complex mechanisms in which interactions between activated leukocytes and endothelial cells play a central role. ICAM-1 (intercellular adhesion molecule-1) mediates firm adhesion and transendothelial migration of activated leukocytes from postcapillary venules into the tissue. The present study evaluated the ICAM-1 expression in various organs after 40 min of intestinal ischemia and 1, 3, 6, 12 h of reperfusion (I/R) in the rat, using a dual monoclonal antibody technique (n = 36). Endothelial barrier permeability, using the vascular leakage of radiolabeled human serum albumin was also assessed (n = 12). Neutrophil sequestration in the lungs was quantitated by myeloperoxidase activity and plasma protease inhibitor levels were measured with electroimmunoassay. Significant regional differences were found in ICAM-1 expression between organs, both constitutively and after I/R-injury. The highest constitutive levels were observed in the liver and lungs, followed by the kidneys. The constitutive ICAM-1 expression in the intestines and in the heart was about 1/20 compared with that found in the liver and lungs. The brain and muscle had levels of about 1/150 of that in the liver and lungs. After intestinal I/R, significant increases (17–45%) were found in the lungs, intestines, brain, heart, and muscle. Albumin leakage index (ALI) in all examined organs and myeloperoxidase activity in the lungs increased after I/R-injury. Serum levels of albumin and most protease inhibitors decreased significantly after I/R challenge. Intestinal I/R results in an increase of systemic ICAM-1 expression with marked organ variability. The upregulation of ICAM-1 could represent a crucial step in the adherence- and migration process of activated leukocytes and potentially in the development of tissue injury.

Prevention of abdominal adhesions--present state and what's beyond the horizon?

Intra-abdominal adhesions are normally found after most surgical procedures. Many of the adhesions are asymptomatic, but in about 5% they will lead to readmission due to adhesion-related disorders, such as small bowel obstruction, pelvic pain and infertility. This review discusses possible ways to prevent abdominal adhesions and provides an update as comes to where we stand today in research regarding experimental and clinical use of various antiadhesive agents.

Percutaneous cholecystostomy: A bridge to surgery or definite management of acute cholecystitis in high-risk patients?

Objective. Cholecystectomy is the standard treatment for acute cholecystitis, but in high-risk patients with serious comorbidity and in patients of advanced age there is substantial morbidity and mortality associated with the intervention. In these selected patients, percutaneous cholecystostomy (PCS) is an alternative mode of management. The aim of the present study was to evaluate the outcome of PCS in selected patients with acute cholecystitis. Material and methods. Thirty-five patients, representing 0.6% of all acute cholecystitis patients managed during the period 1994–2003, were subjected to PCS. Patients’ charts were reviewed retrospectively for age, gender, comorbidity, hospital stay, procedure, complications and final outcome, including requirement of additional interventions. Results. PCS was considered successful in 34/35 patients, 26 of whom responded within 3 days. Two patients required additional cholecystectomy 3 days and 20 months, respectively, after the PCS procedure. Two patients underwent endoscopic retrograde cholangiopancreatography (ERCP) and one patient underwent rotation lithotripsy. Four patients suffered recurrent biliary complaints after the acute episode of cholecystitis, while the only serious procedure-related complication was bile leakage from the gallbladder in one patient, which necessitated cholecystectomy. Conclusions. PCS is a comparatively safe and efficient procedure in the treatment of acute cholecystitis in high-risk patients with serious comorbidity and in elderly patients, contraindicating the general anaesthesia required for laparoscopic or open cholecystectomy.

Major haemorrhagic complications of acute pancreatitis.

Haemorrhage is a rare, potentially fatal complication in acute pancreatitis (AP). The aim was to investigate the incidence, management and outcome related to this complication.

Alterations of adhesion molecule expression and inflammatory mediators in acute lung injury induced by septic and non-septic challenges.

The lung is frequently the first failing organ during the sequential development of multiple organ dysfunction under both septic or non-septic conditions. The present study compared polymorphisms of tumor necrosis factor (TNFα), monocyte chemoattractant protein-1 (MCP-1), and adhesion molecule (AM) expression on circulating, recruited, and migrating leukocytes in the development of lung injury after induction of acute pancreatitis (AP) or abdominal sepsis by cecal ligation and puncture (CLP). Pulmonary alveolar barrier and endothelial barrier permeability dysfunction were measured. The expression of AMs (CD11b, CD11b/c, CD31, CD54 and CD62L) on leukocytes isolated from blood, lung tissue, and bronchoalveolar space were measured by flowcytometry. Plasma exudation to the interstitial tissue and the bronchoalveolar space significantly increased 1 and 3 hours after induction of pancreatitis and to the bronchoalveolar space from 6 hours after sepsis. Bronchoalveolar levels of MCP-1 significantly increased earlier than plasma exudation to the alveoli in both pancreatitis and sepsis. Alterations in expression of adhesion molecules on bronchoalveolar lavage (BAL) leukocytes can represent a marker reflecting leukocyte activation in the lung tissue, since both BAL and lung tissue leukocytes showed similar patterns of changes. Expression of adhesion molecules on circulating leukocytes increased 1 hour after induction of pancreatitis. Activating phenotypes of circulating, lung tissue and bronchoalveolar leukocytes may thus be responsible for the-development and severity of secondary lung injury.

Clinical impact of abdominal adhesions: What is the magnitude of the problem?

Abdominal adhesions occur after almost every intraabdominal surgical procedure. Research during recent years has brought about vast health-care costs. The purpose of this educational review is to bring the reader up to date in the field of clinical intra-abdominal adhesions and includes discussions concerning the problems following abdominal adhesions including small-bowel obstruction, reoperations, female infertility and pain, pelvic and abdominal, as well as financial aspects. The development of adhesions could be considered as a normal reaction of the peritoneal surface following injury. Adhesion formation is a consequence of the inflammatory response and the subsequent healing process [1]. Adhesion formation per se and the greater omentum have a beneficial role in the peritoneal defence by trapping bacteria and thereby diminishing bacteraemia and generalized peritonitis [2,3]. Together with diaphragmatic lymphatic uptake, the peritoneal membrane, peritoneal macrophages and overall peripheral immune functions, the formation of intra-abdominal adhesions will represent an important defence mechanism provided in the peritoneum [4]. Intra-abdominal adhesions are found in as many as 93% of patients who have undergone intraabdominal surgery [5,6]. Close to 10% of the population has intra-abdominal adhesions without any prior laparotomies owing to, for example, inflammatory disease in the abdomen and/or congenital defects [6,7]. Normally, most adhesions are asymptomatic, but will, however, cause problems in a small proportion of patients. These postsurgical, adhesion-related problems include smallbowel obstruction (SBO), female infertility, as well as pelvic pain and abdominal pain. The formation of adhesions also causes secondary problems such as the prolongation and endangering of future intraabdominal operations [8,9].

Exocrine insufficiency in acute pancreatitis.

Little is known about the exocrine pancreatic function during both the acute stage and during the first weeks after an episode of acute pancreatitis. Impairment of the secretion of pancreatic enzymes in the acute phase of pancreatitis has been suggested, but results from previous studies are not conclusive (1–3). Follow-up studies have shown that a considerably large group of patients may suffer from long-lasting exocrine insufficiency after acute pancreatitis, at least during the first 12–18 months after the acute episode (4–9). During the acute phase of pancreatitis, the secretory insufficiency may possess various effects, such as imposing increased stress on the inflamed pancreas with an increased demand of enzymatic release. It may also lead to atrophy of the gut mucosa as it is deprived of the hypothetic trophic action of the pancreatic enzymes. A more long-lasting exocrine insufficiency may lead to symptoms traditionally associated with chronic pancreatitis, such as malabsorption, steatorrhoea, pain and weight loss. In this review we summarize the literature available on the exocrine function in acute pancreatitis during the acute phase, during the convalescent phase and in follow-up studies, and discuss the potential value of pancreatic enzyme supplementation in acute pancreatitis.

Treatment with anti-factor VIIa in acute pancreatitis in rats : Blocking both coagulation and inflammation?

Objective. Acute pancreatitis starts as an autodigestive process restricted to the pancreas and progresses to a systemic inflammation via cytokine release into the blood stream. Several inhibitors of the coagulation cascade, including active-site-inactivated factor VIIa, have shown anti-inflammatory properties in other inflammatory models than acute pancreatitis. Free radical scavengers have proven useful in reducing the oxidative damage during hyperinflammatory conditions. The aim of this study was to investigate whether pretreatment with FVIIai would have any effect on the multiple organ dysfunction syndrome (MODS) in severe acute pancreatitis. Material and methods. Experimental acute pancreatitis was induced by intraductal infusion of taurodeoxycholate in the pancreatic duct. The animals were pretreated with N-acetyl-cysteine and active-site-inactivated factor VIIa. Neutrophil infiltration in the lungs, ileum and colon was quantified by myeloperoxidase activity. Inflammatory markers, IL-6 and MIP-2, were measured using ELISA. Results. Tissue infiltration of neutrophils in the lungs, ileum and colon significantly increased during acute pancreatitis as compared to sham operation. These levels were reduced by pretreatment with N-acetylcysteine and active-site-inactivated factor VIIa. Levels of interleukin-6 and macrophage inflammatory protein-2 increased significantly during acute pancreatitis. Pretreatment with NAC and FVIIai reduced these levels. Conclusions. Both N-acetylcysteine and active-site-inactivated factor VIIa showed powerful anti-inflammatory properties in experimental acute pancreatitis. As they exert their effects through different physiological mechanisms, they represent potential candidates for future multimodal treatment of acute pancreatitis.

Acute phase response in acute pancreatitis: a comparison with abdominal sepsis.

Background: Increased knowledge on the underlying pathophysiological mechanisms in acute pancreatitis (AP) and abdominal sepsis (AS) is essential, not least for the development of novel ways of treatment. The present study aims at determining dynamic changes in the systemic inflammatory response in AP and AS. Methods: AP was induced by the intraductal injection of sodium taurodeoxycholate in the rat, while AS was induced by caecal ligation and puncture. The animals were killed 1, 3, 6 and 9 h after challenge. Plasma exudation of radiolabelled albumin, myeloperoxidase (MPO), TNF‐α, MCP‐1, superoxide and hydrogen peroxide was measured. Results: Leakage index of human serum albumin showed a significant increase early (1 h) after induction of AP and later (9 h) in AS compared to controls (P < 0.05). Hydrogen peroxide generation by circulating monocytes/macrophages was high early (1 h) in AP and after 3 and 6 h in AS. Superoxide generation increased by time after both challenges. MPO activity increased significantly, starting at 3 h in both AP and AS (P < 0.05). TNF‐α increased significantly at 6 and 9 h in both models. Conclusion: Our results indicate differences in the release of systemic inflammatory mediators and cellular response in AP and AS. However, potential similarities in end‐effect, such as the development of remote organ injury (lungs), may exist as implied by the MPO results. Further investigations of the mechanisms are crucial.

Acute pancreatitis - from cellular signalling to complicated clinical course.

Acute pancreatitis (AP) is a common disease that has a mild to moderate course in most cases. During the last decade, a change in diagnostic facilities as well as improved intensive care have influenced both morbidity and mortality in AP. Still, however, a number of controversies and unresolved questions remain regarding AP. These include prognostic factors and how these may be used to improve outcome, diagnostic possibilities, their indications and optimal timing, and the systemic inflammatory reaction (systemic inflammatory response syndrome--SIRS) and its effect on the concomitant course of the disease and potential development of organ failure. The role of the gut has been suggested to be important in severe AP, but has recently been somewhat questioned. Despite extensive research, pharmacological and medical intervention of proven clinical value is scarce. Various aspects on surgical interventions, including endoscopic sphincterotomy, cholecystectomy and necrosectomy, as regards indications and timing, will be reviewed. Last, but not least, are the management of late complications and long-term outcome for patients with especially severe AP.