Trends in indications, complications and outcomes for venous resection during pancreatoduodenectomy.

BACKGROUND: Pancreatoduodenectomy with superior mesenteric-portal vein resection has become a common procedure in pancreatic surgery. The aim of this study was to compare standard pancreatoduodenectomy with pancreatoduodenectomy plus venous resection at a high-volume centre, and to examine trends in management and outcome over a decade for the latter procedure. METHODS: This retrospective observational study included all patients undergoing pancreatoduodenectomy with or without venous resection at Oslo University Hospital between January 2006 and December 2015. Trends were evaluated by assessing preoperative clinical and radiological characteristics, as well as perioperative outcomes in three time intervals (early, intermediate and late). RESULTS: A total of 784 patients had a pancreatoduodenectomy, of whom 127 (16·2 per cent) underwent venous resection. Venous resection resulted in a longer operating time (median 422 versus 312 min; P = 0·001) and greater estimated blood loss (EBL) (median 700 versus 500 ml; P = 0·004) than standard pancreatoduodenectomy. The rate of severe complications was significantly higher for pancreatoduodenectomy with venous resection (37·0 versus 26·3 per cent; P = 0·014). The overall burden of complications, evaluated using the Comprehensive Complication Index (CCI), did not differ (median score 8·7 versus 8·7; P = 0·175). Trends in venous resection over time showed a significant reduction in EBL (median 1050 versus 375 ml; P = 0·001) and duration of hospital stay (median 14 versus 9 days; P = 0·011) between the early and late periods. However, despite an improvement in the intermediate period, severe complication rates returned to baseline in the late period (18 of 43 versus 9 of 42 versus 20 of 42 patients in early, intermediate and late periods respectively; P = 0·032), as did CCI scores (median 20·9 versus 0 versus 20·9; P = 0·041). CONCLUSION: Despite an initial improvement in severe complications for venous resection during pancreatoduodenectomy, this was not maintained over time. Every fourth patient with venous resection needed relaparotomy, most frequently for bleeding.

White matter lesion severity is associated with reduced cognitive performances in patients with normal CSF Abeta42 levels.

OBJECTIVE: To identify possible associations between white matter lesions (WML) and cognition in patients with memory complaints, stratified in groups with normal and low cerebrospinal fluid (CSF) Abeta42 values. MATERIAL AND METHODS: 215 consecutive patients with subjective memory complaints were retrospectively included. Patients were stratified into two groups with normal (n = 127) or low (n = 88) CSF Abeta42 levels (cut-off is 450 ng/l). Cognitive scores from the Mini-Mental State Examination (MMSE) and the Neurobehavioral Cognitive Status Examination (Cognistat) were used as continuous dependent variables in linear regression. WML load was used as a continuous independent variable and was scored with a visual rating scale. The regression model was corrected for possible confounding factors. RESULTS: WML were significantly associated with MMSE and all Cognistat subscores except language (repetition and naming) and attention in patients with normal CSF Abeta42 levels. No significant associations were observed in patients with low CSF Abeta42. CONCLUSIONS: WML were associated with affection of multiple cognitive domains, including delayed recall and executive functions, in patients with normal CSF Abeta42 levels. The lack of such associations for patients with low CSF Abeta42 (i.e. with evidence for amyloid deposition), suggests that amyloid pathology may obscure cognitive effects of WML.

Magnetic resonance enteroclysis in the diagnosis of small-intestinal Crohn's disease: diagnostic accuracy and inter- and intra-observer agreement.

PURPOSE: To evaluate the diagnostic accuracy and inter- and intra-observer agreement of magnetic resonance enteroclysis (MRE) in patients with or without Crohn's disease of the small intestine. MATERIAL AND METHODS: 60 consecutive patients with or without Crohn's disease examined with MRE were included. Two observers independently reviewed the MRE examinations, searching for 12 pathological signs. The reference standard was ileoscopy or surgery of the terminal ileum performed in 41 patients. RESULTS: Crohn's disease of the small intestine was found in 24 (40%) patients. MRE findings of increased intestinal wall thickness, intestinal wall enhancement, intestinal wall ulcer, and inflammatory activity of the terminal ileum showed high sensitivity, specificity, and positive and negative predictive values. Intestinal stenosis had sensitivities ranging from 43% to 100%, depending on the cut-off value. Inter- and intra-observer agreement was good or excellent for most pathological signs. However, observer agreement of intestinal wall edema was only fair and moderate. CONCLUSION: MRE evaluated Crohn's disease with a high diagnostic accuracy in the terminal ileum. Most MRE variables were evaluated with good or excellent observer agreement, indicating that the method was highly reproducible. Our study supports the notion that MRE is an appropriate method for diagnosing Crohn's disease.

Complement activation directly induced by Helicobacter pylori.

BACKGROUND AND AIMS: Helicobacter pylori is a frequent gram-negative colonizer of the human stomach. Its interaction with complement may be involved in the pathogenesis of chronic gastritis, and was mechanistically studied in vitro. METHODS: Four H. pylori strains, 2 cytotoxin-associated genes (cag)A+ and 2 cagA-, were isolated from infected patients. Bacteria or purified H. pylori lipopolysaccharides (LPSs) were incubated with nonimmune serum at 37 degrees C; the activation products C3b/iC3b/C3c (C3bc) and terminal complement complex (TCC) were then quantified by immunoassays. The serum sensitivity of 1 strain (L01, cagA+) was tested by counting the numbers of colony-forming units. RESULTS: All strains and LPSs generated large amounts of C3bc and TCC. Blocking of the classic complement pathway by the calcium chelator ethylene glycol tetraacetic acid (EGTA) markedly reduced the complement products, suggesting that H. pylori and its LPSs directly engage the classic activation pathway. H. pylori was shown to be serum sensitive, but 30% or more nonimmune serum was necessary to induce marked killing. After 5 minutes, swelled bacteria coated with C3bc and TCC were shown. CONCLUSIONS: H. pylori is complement sensitive and activates the classic pathway even in the absence of specific antibodies. Released cell wall constituents such as LPSs can activate complement and may explain why this bacterium induces gastric pathology without invading the mucosa.

[Does reduced microbial exposure contribute to increased prevalence of allergy?]. / Bidrar vår reduserte mikrobielle belastning til økt forekomst av allergi?

Diseases associated with atopic allergy such as asthma, hay fever and eczema have increased dramatically in westernised societies over the last decades. Reduced microbial exposure during the first years of life, which we find in societies with a high standard of living, may be disadvantageous in terms of mucosal sensitisation to allergy. Recent studies have suggested an inverse relationship between allergic disorders and infections with intracellular pathogens including tuberculosis, measles, and hepatitis A. Because many intracellular pathogens generate predominantly a T helper 1 (Th1)-cell cytokine profile, and because Th1 and Th2 cell-mediated immune mechanisms are subjected to cross-regulation, it is possible that exposure to certain microorganisms may repress or abolish development of atopic allergy.

Increased mucosal production of monomeric IgA1 but no IgA1 protease activity in Helicobacter pylori gastritis.

Immunoglobulin A and IgM are subjected to epithelial transport only when they are produced as polymers with incorporated J chain. Immunocytes containing various Ig isotypes and associated J chain in gastric mucosa, as well as IgA-degrading protease activity in Helicobacter pylori cultures, were examined. Gastric body specimens from 15 H. pylori-positive and 14 H. pylori-negative patients were studied by paired immunofluorescence for IgA, IgA1, IgA2, IgG, or IgM and concurrent cellular J chain. H. pylori isolates were incubated with IgA1 or secretory IgA and examined by immunoelectrophoresis for cleavage products. A substantial increase of Ig-producing cells occurred in chronic gastritis, particularly in the IgA1 isotype, but H. pylori was shown to possess neither IgA1-specific nor nonspecific IgA-degrading protease activity. Regardless of infection status, reduced J chain expression was observed for all immunocyte isotypes (except for IgM) in inflamed compared with normal gastric body mucosa, the median positivity for IgA1 cells being reduced to 58.7% versus 87.9% (P = 0.0002), and for IgA2 cells to 48.9% versus 87.8% (P = 0.0002). This down-regulation of the J chain suggested that a large fraction of IgA monomers is produced in gastritis.

[Physiopathology of Helicobacter pylori infection]. / Patofysiologi ved Helicobacter pylori-infeksjon.

The gastric juice of Helicobacter pylori-infected individuals contains substantially higher levels of phospholipase A2 (PLA2) than that of individuals who are not infected. We present a new theory for how this H. pylori-induced PLA2 activity in gastric juice may play a major role in the development of peptic ulcer disease. When activated at neutral pH (pH 6.5-7.0), PLA2 may damage the surfactant-like, phospholipid-rich layer which constitutes an important part of the mucus barrier. Pepsin and other proteases, activated at low pH (pH 1.0-3.5), may then denature and cleave PLA2-exposed proteins. Peptic ulcers therefore tend to develop in regions exposed to changing luminal pH, such as the duodenal bulb when acid production is high or normal, or in the stomach when acid secretion is low.

Expression of cell membrane complement regulatory glycoproteins along the normal and diseased human gastrointestinal tract.

BACKGROUND/AIMS: Uncontrolled complement activation may be of immunopathological importance in inflammatory diseases of the gastrointestinal tract. Expression of membrane bound factors that regulate complement activation was therefore studied in situ. METHODS: Frozen tissue specimens were obtained from patients with Helicobacter pylori gastritis, coeliac disease, Crohn's disease, or ulcerative colitis, and from histologically normal controls. Sections were examined by immunofluorescence with monoclonal antibodies to protectin (CD59), decay accelerating factor (DAF), and membrane cofactor protein (MCP). RESULTS: Protectin and MCP were widely expressed in normal and diseased mucosae. MCP was generally observed basolaterally on all epithelial cells, whereas apical protectin expression was more intense on the epithelium of normal colonic mucosa than in the normal duodenum (p = 0.001). Epithelial DAF and to some extent protectin were upregulated in gastritis, coeliac disease, and inflammatory bowel disease. Areas of the stomach with intestinal metaplasia expressed DAF, unlike the adjacent gastric epithelium. Parietal cells of the gastric body expressed neither protectin nor DAF. CONCLUSION: Epithelial complement inhibitory molecules were expressed differently at various normal gastrointestinal sites and also in association with mucosal disease, suggesting variable protective potential. Such molecules could play a role in the development of gastric atrophy by protecting areas of intestinal metaplasia. Conversely, parietal cells appeared to be potentially vulnerable targets for complement attack.

Mucosal immunity--a major adaptive defence mechanism.

The epithelial glycoprotein called secretory component (SC) is quantitatively the most important receptor of the immune system because it is responsible for external transport of locally produced polymeric IgA (pIgA) to generate remarkably large amounts of secretory IgA. Antibodies of this type constitute the major mediators of specific humoral immunity. Transmembrane SC belongs to the Ig supergene family and functions as a common pIg receptor, also translocating pentameric IgM externally to form secretory IgM. The B cells responsible for mucosal pIg production are initially stimulated in organized mucosa-associated lymphoepithelial structures, particularly the Peyer's patches in the distal small intestine; from these inductive site they migrate as memory cells to exocrine tissues all over the body. Mucous membranes are thus furnished with secretory antibodies in an integrated way, ensuring a variety of specificities at every secretory effector site. There is currently great interest in exploiting this integrated or "common" mucosal immune system for oral vaccination against pathogenic infectious agents and also to induce tolerance in T cell-mediated autoimmune diseases. However, much remains to be learned about mechanisms for antigen uptake and processing necessary to elicit stimulatory or suppressive mucosal immune responses. Moreover, evidence is emerging for the existence of considerable regionalization with regard to functional links between inductive sites and effecter sites of mucosal immunity.

Epithelium related deposition of activated complement in Helicobacter pylori associated gastritis.

BACKGROUND AND AIMS: It is unknown whether Helicobacter pylori infection activates complement in vivo. Mucosal deposition of various activation products of the complement system may contribute to the pathogenesis of chronic gastritis and was therefore studied by immunohistochemistry. PATIENTS AND METHODS: Ethanol fixed antrum or body gastric tissue sections from 24 patients infected with H pylori (determined by bacterial immunohistochemistry) and 22 uninfected patients were examined by immunofluorescence with monoclonal antibodies to activation neoepitopes in C3b and in the terminal complex (TCC). As a control group, biopsy samples from the gastric stump of 23 Billroth II operated patients were studied. RESULTS: Patchy, bright staining for TCC occurred below the surface epithelium and around the glands in H pylori positive and negative gastritis as well as in stump gastritis but seldom in normal mucosa. Activated C3 was present at the apical face of the surface epithelium, significantly more often in the antrum and body from patients with than without H pylori infection (p = 0.05 and p = 0.03 respectively), and particularly in samples with granulocyte infiltration (p = 0.04). Many bacteria were coated with activated C3 towards the pit openings but seldom within the foveolae. CONCLUSIONS: Local complement activation was shown to take place in simple chronic gastritis, associated as well as unassociated with H pylori infection, and also in stump gastritis. The fact that activated C3 was seldom seen on H pylori within the foveolae, suggested that the bacterium evades complement attack in this location.

Helicobacter pylori gastritis and epithelial cell proliferation in patients with reflux oesophagitis after treatment with lansoprazole.

BACKGROUND: Helicobacter pylori gastritis may spread proximally in the stomach during profound acid inhibition. AIMS: To examine histological gastric body changes and epithelial cell proliferation before and after treatment with lansoprazole. PATIENTS AND METHODS: Patients diagnosed as having reflux oesophagitis grade 1 or 2 were enrolled and treated for 12 weeks with lansoprazole (30 mg every morning). After 12 weeks, 103 of the 118 patients appeared endoscopically healed and were asymptomatic; they then received maintenance treatment with 15 or 30 mg lansoprazole daily. Biopsy specimens obtained from similar sites before and after treatment, were available from 90 patients after a median of 64 weeks (range 15-73 weeks). Epithelial cell proliferation was determined by the number of Ki-67 antigen positive cells per gland. RESULTS: Of these 90 patients, 44 (49%) were found to be infected with H pylori. Their median inflammation score had increased from grade 1 before to grade 2 after treatment (p < 0.0001). Initially, the number of Ki-67 antigen positive cells per gland was significantly higher in the H pylori infected than in the uninfected group and increased further after treatment (p < 0.0001). In uninfected patients, no significant change in inflammation or proliferation occurred during treatment. CONCLUSIONS: A marked increase in body gastritis was observed in H pylori infected individuals during long term treatment with the proton pump inhibitor lansoprazole. Epithelial cell proliferation and atrophy also increased in infected but not in uninfected patients.