H. van Goor

IAP/APA evidence-based guidelines for the management of acute pancreatitis.

BACKGROUNDnThere have been substantial improvements in the management of acute pancreatitis since the publication of the International Association of Pancreatology (IAP) treatment guidelines in 2002. A collaboration of the IAP and the American Pancreatic Association (APA) was undertaken to revise these guidelines using an evidence-based approach.nnnMETHODSnTwelve multidisciplinary review groups performed systematic literature reviews to answer 38 predefined clinical questions. Recommendations were graded using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The review groups presented their recommendations during the 2012 joint IAP/APA meeting. At this one-day, interactive conference, relevant remarks were voiced and overall agreement on each recommendation was quantified using plenary voting.nnnRESULTSnThe 38 recommendations covered 12 topics related to the clinical management of acute pancreatitis: A) diagnosis of acute pancreatitis and etiology, B) prognostication/predicting severity, C) imaging, D) fluid therapy, E) intensive care management, F) preventing infectious complications, G) nutritional support, H) biliary tract management, I) indications for intervention in necrotizing pancreatitis, J) timing of intervention in necrotizing pancreatitis, K) intervention strategies in necrotizing pancreatitis, and L) timing of cholecystectomy. Using the GRADE system, 21 of the 38 (55%) recommendations, were rated as strong and plenary voting revealed strong agreement for 34 (89%) recommendations.nnnCONCLUSIONSnThe 2012 IAP/APA guidelines provide recommendations concerning key aspects of medical and surgical management of acute pancreatitis based on the currently available evidence. These recommendations should serve as a reference standard for current management and guide future clinical research on acute pancreatitis.

Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis

Severe acute respiratory syndrome (SARS) is an acute infectious disease that spreads mainly via the respiratory route. A distinct coronavirus (SARS‐CoV) has been identified as the aetiological agent of SARS. Recently, a metallopeptidase named angiotensin‐converting enzyme 2 (ACE2) has been identified as the functional receptor for SARS‐CoV. Although ACE2 mRNA is known to be present in virtually all organs, its protein expression is largely unknown. Since identifying the possible route of infection has major implications for understanding the pathogenesis and future treatment strategies for SARS, the present study investigated the localization of ACE2 protein in various human organs (oral and nasal mucosa, nasopharynx, lung, stomach, small intestine, colon, skin, lymph nodes, thymus, bone marrow, spleen, liver, kidney, and brain). The most remarkable finding was the surface expression of ACE2 protein on lung alveolar epithelial cells and enterocytes of the small intestine. Furthermore, ACE2 was present in arterial and venous endothelial cells and arterial smooth muscle cells in all organs studied. In conclusion, ACE2 is abundantly present in humans in the epithelia of the lung and small intestine, which might provide possible routes of entry for the SARS‐CoV. This epithelial expression, together with the presence of ACE2 in vascular endothelium, also provides a first step in understanding the pathogenesis of the main SARS disease manifestations. Copyright

Expression of nitric oxide synthases and formation of nitrotyrosine and reactive oxygen species in inflammatory bowel disease

Nitric oxide (NO) and reactive oxygen species (ROS) are important mediators in the pathogenesis of inflammatory bowel disease (IBD). NO in IBD can be either harmful or protective. NO can react with superoxide anions (O2.−), yielding the toxic oxidizing agent peroxynitrite (ONOO−). Peroxynitrite induces nitration of tyrosine residues (nitrotyrosine), leading to changes of protein structure and function. The aim of this study was to identify the cellular source of inducible nitric oxide synthase (iNOS) and to localize superoxide anion‐producing cells in mucosal biopsies from patients with active IBD. Additional studies were performed to look at nitrotyrosine formation as a measure of peroxynitrite‐mediated tissue damage. For this, antibodies against iNOS, endothelial NOS (eNOS), and nitrotyrosine were used. ROS‐producing cells were detected cytochemically. Inflamed mucosa of patients with active IBD showed intense iNOS staining in the epithelial cells. iNOS could not be detected in non‐inflamed mucosa of IBD patients and control subjects. eNOS was present in blood vessels, without any difference in the staining intensity between IBD patients and control subjects. ROS‐producing cells were increased in the lamina propria of IBD patients; a fraction of these cells were CD15‐positive. Nitrotyrosine formation was found on ROS‐positive cells. These results show that iNOS is induced in epithelial cells from patients with active ulcerative colitis or Crohns disease. Nitration of proteins was detected only on the ROS‐producing cells at some distance from the iNOS‐producing epithelial cells. These findings indicate that tissue damage during active inflammation in IBD patients is probably more related to ROS‐producing cells than to NO. One may speculate that NO has a protective role when during active inflammation other mucosal defence systems are impaired. Copyright

Renal ACE2 expression in human kidney disease

Angiotensin‐converting enzyme 2 (ACE2) is a recently discovered homologue of angiotensin‐converting enzyme (ACE) that is thought to counterbalance ACE. ACE2 cleaves angiotensin I and angiotensin II into the inactive angiotensin 1–9, and the vasodilator and anti‐proliferative angiotensin 1–7, respectively. ACE2 is known to be present in human kidney, but no data on renal disease are available to date. Renal biopsies from 58 patients with diverse primary and secondary renal diseases were studied (hypertensive nephropathy n = 5, IgA glomerulopathy n = 8, minimal change nephropathy n = 7, diabetic nephropathy n = 8, focal glomerulosclerosis n = 5, vasculitis n = 7, and membranous glomerulopathy n = 18) in addition to 17 renal transplants and 18 samples from normal renal tissue. Immunohistochemical staining for ACE2 was scored semi‐quantitatively. In control kidneys, ACE2 was present in tubular and glomerular epithelium and in vascular smooth muscle cells and the endothelium of interlobular arteries. In all primary and secondary renal diseases, and renal transplants, neo‐expression of ACE2 was found in glomerular and peritubular capillary endothelium. There were no differences between the various renal disorders, or between acute and chronic rejection and control transplants. ACE inhibitor treatment did not alter ACE2 expression. In primary and secondary renal disease, and in transplanted kidneys, neo‐expression of ACE2 occurs in glomerular and peritubular capillary endothelium. Further studies should elucidate the possible protective mechanisms involved in the de novo expression of ACE2 in renal disease. Copyright

IMMUNOHISTOCHEMICAL DEMONSTRATION OF DNA-INCORPORATED 5-BROMODEOXYURIDINE IN FROZEN AND PLASTIC EMBEDDED SECTIONS

SummaryThe application of an immunohistochemical method in the detection of replicating cells, that have incorporated 5-bromodeoxyuridine (BrdUrd), was studied on frozen and plastic embedded sections of different rat tissues. Hydrolysis conditions employed in the Feulgen procedure are essential in making the incorporated BrdUrd accessible to the monoclonal anti-BrdUrd antibodies. To demonstrate the incorporated BrdUrd in plastic embedded sections a subsequent etching with xylene and digestion with protease is necessary. Data obtained with this method are completely comparable with those found by the tritiated thymidine method. In comparison with the thymidine method, the BrdUrd method is much less time consuming and does not require precautions in working with radioactivity. The BrdUrd-method enables a more precise localization as is especially shown in the plastic embedded sections.

Adhesiolysis-Related Morbidity in Abdominal Surgery.

Objective:To determine the incidence of bowel injury in operations requiring adhesiolysis and to assess the impact of adhesiolysis on the incidence of surgical complications, postoperative morbidity, and costs. Background:Morbidity of adhesiolysis during abdominal surgery seems an important health care problem, but the direct impact of adhesiolysis on inadvertent organ damage, morbidity, and costs is unknown. Methods:In a prospective cohort study, detailed data on adhesiolysis were gathered by direct observation during elective abdominal surgery. Comparison was made between surgical procedures with and without adhesiolysis on the incidence of inadvertent bowel defects. Secondary outcomes were the effect of adhesiolysis and bowel injury on surgical complications, other morbidity, and costs. Results:A total of 755 (out of 844) surgeries in 715 patients were included. Adhesiolysis was required in 475 (62.9%) of operations. Median adhesiolysis time was 20 minutes (range: 1–177). Fifty patients (10.5%) undergoing adhesiolysis inadvertently incurred bowel defect, compared with 0 (0%) without adhesiolysis (P < 0.001). In univariate and multivariate analyses, adhesiolysis was associated with an increase of sepsis incidence [odds ratio (OR): 5.12; 95% confidence interval (CI): 1.06–24.71], intra-abdominal complications (OR: 3.46; 95% CI: 1.49–8.05) and wound infection (OR: 2.45; 95% CI: 1.01–5.94), longer hospital stay (2.06 ± 1.06 days), and higher hospital costs [

Association between macrophage activation and function of micro-encapsulated rat islets

18,579 (15,204–21,954) vs

Pancreas-preserving total duodenectomy versus standard pancreatoduodenectomy for patients with familial adenomatous polyposis and polyps in the duodenum†

14,063 (12,471–15,655)]. Mortality after adhesiolysis complicated by a bowel defect was 4 out of 50 (8%), compared with 7 out of 425 (1.6%) after uncomplicated adhesiolysis (OR: 5.19; 95% CI: 1.47–18.41). Conclusions:Adhesiolysis and inadvertent bowel injury have a large negative effect on the convalescence after abdominal surgery. The awareness of adhesion-related morbidity during reoperation and the prevention of postsurgical adhesion deserve priority in research and clinical practice.

Increased Expression of Inducible Nitric Oxide Synthase in Circulating Monocytes from Patients with Active Inflammatory Bowel Disease

Aims/hypothesisSurvival of microencapsulated islet grafts is limited, even when inflammatory reactions against the capsules are restricted to a small portion of less than 10%.MethodsThis study investigates both in vivo in rat recipients and in vitro whether cellular overgrowth on this minority of the capsules contributes to limitations in the functional survival of the 90% of the encapsulated islets which remain free of any cellular overgrowth.ResultsIn successful rat recipients of an allogenic microencapsulated islet graft we found that the vast majority of cells in the capsular overgrowth were activated ED-1 and ED-2 positive macrophages which were found in numbers of approximately 1500 per capsule. Co-culture of encapsulated islets with 1500 (nr8383) rat-macrophages per capsule showed that the activation of macrophages was caused by islet-derived bioactive factors since TNF-α and IL-1β secretion by macrophages was induced by islet-containing capsules and not by empty capsules. This activation of macrophages was associated with a decrease in function of the encapsulated islets as evidenced by a quantitatively reduced (35%) insulin response in static incubation and a slower response in perifusion.Conclusion/interpretationPresent research aims to design strategies for the temporary inhibition of macrophage activation since macrophages are predominantly present in the first two months after implantation. These strategies will serve as a pertinent basis for future clinical application of microencapsulated islets.

THE APPLICATION OF LIPID-SOLUBLE STAINS IN PLASTIC-EMBEDDED SECTIONS

Pancreas‐preserving total duodenectomy (PPTD) was introduced as a replacement for pancreatoduodenectomy (PD) for familial adenomatous polyposis (FAP). This study analysed the results of PPTD in the Netherlands and reviewed the relevant literature.