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.

Abnormal accumulation of intestinal fluid following ingestion of an unabsorbable carbohydrate in patients with irritable bowel syndrome: an MRI study.

BACKGROUND: Postprandial discomfort following intake of poorly absorbable, but fermentable carbohydrates is a common complaint in patients with irritable bowel syndrome (IBS). We used lactulose as a model substance for this group of symptom triggering carbohydrates, aiming to visualize the intestinal response in IBS patients compared to healthy controls. METHODS: Patients with IBS according to Rome III criteria (n = 52) and healthy controls (n = 16) underwent a lactulose challenge test. By using magnetic resonance imaging, we measured small bowel water content (SBWC), and distension (diameter) of the distal ileum and the colon, both in fasting state and 1 h after ingestion of 10 g lactulose. We recorded symptoms after lactulose ingestion. KEY RESULTS: Lactulose provoked significantly more symptoms in IBS patients than in healthy controls (p < 0.0001). SBWC increased more in the patient group compared to the control group (p = 0.0005). The postprandial diameter of the terminal ileum was larger in patients with IBS and the postprandial diameter of the ascending colon was smaller in patients with diarrhea-predominant phenotype (IBS-D). Symptoms were not correlated with change in SBWC (r = 0.05; p = 0.11), nor to the diameters of the terminal ileum or the colon. CONCLUSIONS & INFERENCES: Compared to healthy controls, IBS patients developed more symptoms and had an abnormal accumulation of fluid in the small bowel in response to ingestion of the unabsorbable carbohydrate lactulose. This may be due to impaired motor activity of the small intestine or impaired function of the ileocecal segment.

Imatinib mesylate alleviates diarrhea in a mouse model of intestinal allergy.

BACKGROUND: When sensitized epicutaneously and challenged orally with ovalbumin, Balb/c mice develop allergen-induced diarrhea. As mast cells play important roles in diarrhea, we studied whether allergic diarrhea could be alleviated with imatinib mesylate. METHODS: Balb/c mice were sensitized and challenged with ovalbumin and treated orally with imatinib. Cytokine mRNA expressions were determined with quantitative RT-PCR and numbers of small intestinal mast cells determined by staining for chloroacetate esterase and mucosal mast cell protease-1. Immunofluorescence staining was used to assess the intestinal CCL1 expression. KEY RESULTS: Ovalbumin-sensitized and challenged Balb/c mice developed diarrhea, which was associated with increased number of mast cells and expression of interleukin (IL)-4 and -13, and chemokines CCL1 and CCL17 in the small intestine. Treatment with imatinib reduced the incidence of diarrhea, inhibited the development of mastocytosis and jejunal mRNA expression of IL-13, CCL1, CCL17 and CCL22. Mast cell-deficient W/W(-V) mice, and surprisingly, also their mast cell-competent control (+/+) littermates failed to develop diarrhea as a response to ovalbumin. This strain-dependent difference was associated with the inability of +/+ and W/W(-V) mice to increase the number of intestinal mast cells and expression of IL-4, IL-13, CCL1 and CCL17 after ovalbumin challenge. CONCLUSIONS & INFERENCES: Development of allergic diarrhea is associated with the ability of mice to develop intestinal mastocytosis. Imatinib inhibited the development of intestinal mastocytosis, reduced the incidence of diarrhea, and reduced the expression of IL-13, CCL1, and CCL17. Targeting intestinal mast cells could be a feasible approach to treat allergic diarrhea.

Functional and clinical aspects of the B-cell-activating factor (BAFF): a narrative review.

B-cell-activating factor (BAFF) influences peripheral B-cell survival, maturation and immunoglobulin class-switch recombination and has a range of potential clinical implications. Biological functions of BAFF and its relevance in various clinical disorders including currently investigated BAFF-targeting therapies are reviewed and discussed based on PubMed search of relevant articles. Serum levels of BAFF are increased in autoimmune diseases including autoimmune hepatitis and primary biliary cirrhosis where BAFF concentrations are related to titres of autoantibodies and disease progression. Increased BAFF levels are found in synovial, bronchoalveolar and gut lavage fluids, suggesting local class switching and immunoglobulin production. Clinical relevance and diagnostic potential of BAFF are also noted in patients with allergic diseases, malignancies and infections including hepatitis C virus. BAFF antagonists are promising new therapeutic agents, currently being tried in B-cell-related autoimmune diseases. Serum level of BAFF may indicate disease mechanisms and the degree of activity. Determination of BAFF in different body compartments like synovium, airways and gut may also have clinical implications. Results of ongoing clinical trials with BAFF antagonists are eagerly awaited.

Intestinal B cell-activating factor: an indicator of non-IgE-mediated hypersensitivity reactions to food?

BACKGROUND: Medically confirmed hypersensitivity reactions to food are usually IgE-mediated. Non-IgE-mediated reactions are not only seldom recognized but also more difficult to diagnose. AIM: To examine B cell-activating factor (BAFF) in serum and gut lavage fluid of patients with self-reported food hypersensitivity, and to study its relationship to atopic disease. METHODS: Gut lavage fluid was obtained from 60 and serum from another 17 patients with self-reported food hypersensitivity. Twenty healthy volunteers served as controls, gut lavage fluid was obtained in all, serum from 11 of 20. The patients were divided into atopic and non-atopic subgroups. BAFF was measured by ELISA in both serum and gut lavage fluid. RESULTS: B cell-activating factor levels in serum and gut lavage fluid were significantly higher in patients than in controls (P < 0.03 and P < 0.002 respectively). Non-atopic patients had significantly higher levels of BAFF in serum than both atopic patients (P < 0.05) and controls (P < 0.05). There was no significant correlation between serum levels of BAFF and IgE. CONCLUSIONS: The results suggest that BAFF might be a new mediating mechanism in food hypersensitivity reactions. Significantly higher levels in non-atopic compared with atopic patients, and no correlation between BAFF and IgE, suggest that BAFF might be involved particularly in non-IgE-mediated reactions.

Indications of 'atopic bowel' in patients with self-reported food hypersensitivity.

BACKGROUND: An association between atopic disease and gastrointestinal complaints has been suggested. AIM: To explore the association between atopic disease, gastrointestinal symptoms, and possible gastrointestinal manifestations of atopic disease in patients with self-reported food hypersensitivity. METHODS: Symptoms, skin prick tests, serum markers of allergy and intestinal permeability were recorded in 71 adult patients. Eosinophils, tryptase- and IgE-positive cells were counted in duodenal biopsies. RESULTS: Sixty-six (93%) patients had irritable bowel syndrome (IBS) and 43 (61%) had atopic disease, predominantly rhinoconjunctivitis. All 43 were sensitized to inhalant allergens, 29 (41%) to food allergens, but food challenges were negative. Serum total IgE and duodenal IgE-positive cell counts were significantly correlated (P < 0.0001) and both were significantly higher in atopic than in non-atopic patients (P < 0.0001 and P = 0.003 respectively). IgE-positive cells appeared to be 'armed' mast cells. Intestinal permeability was significantly elevated in atopic compared with non-atopic patients (P = 0.02). Gastrointestinal symptoms and numbers of tryptase-positive mast cells and eosinophils did not differ between groups. CONCLUSIONS: Patients with self-reported food hypersensitivity had a high prevalence of IBS and atopic disease. Atopic patients had increased intestinal permeability and density of IgE-bearing cells compared with non-atopic patients, but gastrointestinal symptoms did not differ between groups.

Job stress and coping strategies in patients with subjective food hypersensitivity.

Psychological distress may be causally related to multiple, unexplained somatic symptoms. We have investigated job stress, coping strategies and subjective health complaints in patients with subjective food hypersensitivity. Sixty-four patients were compared with 65 controls. All participants filled in questionnaires focusing on job stress, job demands and control, work environment, coping strategies and subjective health complaints. Compared with controls, patients scored significantly lower on job stress and job demands, and significantly higher on authority over job decisions. Coping strategies and satisfaction with work environment did not differ significantly between the two groups, but the patients reported significantly more subjective health complaints than the controls. Scores on job stress and job demands were generally low in patients with subjective food hypersensitivity. It is unlikely, therefore, that the patients' high scores on subjective health complaints are causally related to the work situation.

A dose-ranging, placebo-controlled, pilot trial of Acotiamide in patients with functional dyspepsia.

Impaired gastric accommodation, hypersensitivity to distension and delayed gastric emptying are major pathophysiological mechanisms in functional dyspepsia (FD). Acotiamide (Z-338) was well-tolerated in healthy volunteers. To determine the effect of three doses of Acotiamide on major pathophysiological mechanisms, symptoms, quality of life (QOL) and safety in functional dyspeptics. A phase IIa, randomized, double-blind, placebo-controlled study (14, 21 and 28 days, respectively, for run-in, study drug administration and follow-up). Gastric accommodation, sensitivity to distension and gastric emptying were assessed by barostat and (13)C breath test, symptoms by daily diary cards and QOL by SF-36. A total of 71 patients were enrolled (62 evaluable). There was no effect on gastric emptying and sensitivity to distension. 300 mg was better than placebo for meal accommodation (P = 0.024). 100 mg was better than placebo at week 2 for upper abdominal bloating (P = 0.001) and overall symptom score (P = 0.022), and at week 3 for bloating (P = 0.008) and heartburn (P = 0.041). 100 mg was also better than placebo for QOL (physical function) (P = 0.003). Acotiamide was safe and well-tolerated in patients with FD. The involved mechanism could at least in part depend on an effect on meal-induced accommodation. 100 mg Acotiamide exhibited the potential to improve FD symptoms and QOL. Further studies are indicated.

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.

Vagal activation by sham feeding improves gastric motility in functional dyspepsia.

Antral hypomotility and impaired gastric accommodation in patients with functional dyspepsia have been ascribed to vagal dysfunction. We investigated whether vagal stimulation by sham feeding would improve meal-induced gastric motor function in these patients. Fourteen healthy volunteers and 14 functional dyspepsia patients underwent a drink test twice, once with and once without simultaneous sham feeding. After ingesting 500 mL clear meat soup (20 kcal, 37 degrees C) in 4 min, sham feeding was performed for 10 min by chewing a sugar-containing chewing gum while spitting out saliva. Using two- and three-dimensional ultrasound, antral motility index (contraction amplitude x frequency) and intragastric volumes were estimated. Without sham feeding, functional dyspepsia patients had lower motility index than healthy volunteers (area under curve 8.0 +/- 1.2 vs 4.4 +/- 1.0 min(-1), P = 0.04). In functional dyspepsia patients, but not in healthy volunteers, motility index increased and intragastric volume tended to increase by sham feeding (P = 0.04 and P = 0.06 respectively). The change in motility index was negatively correlated to the change in pain score (r = -0.59, P = 0.007). In functional dyspepsia patients, vagal stimulation by sham feeding improves antral motility in response to a soup meal. The result supports the view that impaired vagal stimulation is implicated in the pathogenesis of gastric motility disturbances in functional dyspepsia.

Distension-induced gastric accommodation in functional dyspepsia: effect of autonomic manipulation.

Functional dyspepsia (FD) is associated with impaired gastric accommodation and autonomic dysregulation. The aim of this study was to investigate the effects of autonomic manipulation on distension-induced gastric accommodation in subjects with and without FD, using a newly developed gastric barostat paradigm. Twelve healthy subjects (HS) and 18 subjects with FD had four barostat examinations each: no intervention, intravenous atropine (1 mg), vagal stimulation (mental relaxation with deep breathing) and acute stress stimulation (serial subtraction task). Intrabag pressure increased from 1 to 15 mmHg in 5 min (ramp phase), and was maintained at 15 mmHg for 5 min (tonic phase). Volume responses were analysed using predefined parameters. There were no significant group differences in accommodation variables between HS and subjects with FD. The FD group could be subdivided into two distinct subgroups: subgroup 1 (n = 7, 38%) with low maximum volume and accommodation rate, and subgroup 2 with normal accommodation (n = 11). In subgroup 1, but not in subgroup 2 atropine increased maximum volume and accommodation rate substantially. Neither mental stress nor mental relaxation changed any of the accommodation variables. In a subgroup of subjects with FD, impairment of distension-induced gastric accommodation can be improved by cholinergic blockade, but not by acute physiological autonomic manipulation.

Noninvasive treatment of bronchomalacia, successful ventilation of a severely ill infant.

UNLABELLED: Noninvasive treatment of bronchomalacia. Successful ventilation of a severely ill infant. AIM: To describe an effective treatment of a boy with bronchomalacia by noninvasive mechanical ventilation support. METHODS: We describe a case of a severely ill patient with bronchomalacia from the time he was born and until the age of five. Bi-level positive airway pressure given through a specially adapted full face mask was used to treat his respiratory condition. RESULT: Our patient responded well to the noninvasive treatment of bronchomalacia. CONCLUSION: We found that noninvasive mechanical ventilation support is a low risk and highly effective treatment of infants and children with respiratory distress caused by bronchomalacia.

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.

Variations in case fatality and fatality risk factors of meningococcal disease in Western Norway, 1985-2002.

In a retrospective epidemiological study, 293 meningococcal disease patients hospitalized during 1985-2002, were examined for fatality and risk factors related to death. The overall case fatality rate (CFR) was 8.2%, but increased from 4% during 1985-1993 to 17% during 1994-2002. The latter 9-year period was characterized by more serogroup C infections and more patients with thrombocytopenia on admission to hospital. All patients categorized as meningitis on admission survived. Of the 24 patients who died, 21 had meningococcal skin rash on admission, 23 had an onset to admission time of < or =24 h, and 16 had severe septicaemia with hypotension and/or ecchymoses without meningitis on admission. By multivariate analyses, a short onset to admission time, >50 petechiae, thrombocytopenia and severe septicaemia on admission were associated with fatality. More lives could be saved through earlier admission to hospital. This can be achieved through more information to the public about the early signs of meningococcal septicaemia, with the recommendation to look for skin rash in patients with acute fever during the first day and night.

Effects of ferrous sulphate and non-ionic iron-polymaltose complex on markers of oxidative tissue damage in patients with inflammatory bowel disease.

BACKGROUND: Iron deficiency is a common complication of inflammatory bowel disease. Oral iron therapy may reinforce intestinal tissue injury by catalyzing production of reactive oxygen species. AIM: To compare the effects of ferrous sulphate and non-ionic iron-polymaltose complex on markers of oxidative tissue damage and clinical disease activity in patients with inflammatory bowel disease. METHODS: Forty-one patients with inflammatory bowel disease and iron deficiency were randomized to treatment with ferrous sulphate 100 mg twice a day or iron-polymaltose complex 200 mg once a day for 14 days. RESULTS: Following ferrous sulphate, plasma malondialdehyde increased (P = 0.02), while urine 8-isoprostaglandin F(2alpha) and plasma antioxidants did not change significantly. Iron-polymaltose complex did not change plasma malondialdehyde, urine 8-isoprostaglandin F(2alpha) or plasma antioxidants. Comparing the two treatments, changes in plasma malondialdehyde tended to differ (P = 0.08), while urine 8-isoprostaglandin F(2alpha) and plasma antioxidants did not differ. Neither ferrous sulphate nor iron-polymaltose complex altered clinical disease activity indices. CONCLUSIONS: Ferrous sulphate increased plasma malondialdehyde, a marker of lipid peroxidation. Comparing treatment with ferrous sulphate and iron-polymaltose complex, changes in plasma malondialdehyde tended to differ. Clinical disease activity was unchanged after both treatments.

Reduced joint pain after short-term duodenal administration of seal oil in patients with inflammatory bowel disease: comparison with soy oil.

BACKGROUND: Rheumatic joint pain is a common extra-intestinal complication of inflammatory bowel disease (IBD). Because the high ratio of n-6 to n-3 fatty acids (FAs) of the Western diet might promote rheumatic disorders, we sought to compare the effects of short-term duodenal administration of n-3-rich seal oil and n-6-rich soy oil on IBD-related joint pain. METHODS: Nineteen patients with IBD-related joint pain were included in the study; 9 had Crohn disease and 10 had ulcerative colitis. Ten millilitres seal oil (n = 10) or soy oil (n = 9) was self-administered through a nasoduodenal feeding tube 3 times daily for 10 days. RESULTS: Compared with soy oil treatment, seal oil significantly reduced the duration of morning stiffness (P = 0.024), number of tender joints (P = 0.035), intensity of pain (P = 0.025) and the doctor's scoring of rheumatic disease activity (P = 0.025) at the end of the 10-day treatment period. Analysis of the effects as area under the curve (area between the curve and baseline, zero) for the entire period from start of treatment until 6 months' post-treatment suggested a long-lasting beneficial effect of seal oil administration on joint pain, whereas soy oil tended (not significantly) to aggravate the condition. Consistently, the serum ratios of n-6 to n-3 FAs (P < 0.01) and arachidonic acid to eicosapentaenoic acid (P < 0.01) were reduced after treatment with seal oil. CONCLUSION: The results suggest distinctive, differential prolonged effects on IBD-related joint pain of short-term duodenal administration of n-3-rich seal oil (significant improvement) and n-6-rich soy oil (tendency to exacerbation).

Drink tests in functional dyspepsia: which drink is best?

BACKGROUND: Drinking capacity is often reduced in functional dyspepsia. Drink tests may therefore have diagnostic potential. A simple drink test in combination with ultrasonography was applied in this study, the aim being to find the best drink for this test. METHODS: On separate days, 10 patients with functional dyspepsia (FD) and 10 healthy controls (C) drank three different test meals (Nutridrink 150 kcal/100 mL, meat soup 4 kcal/100 mL and water) at a rate of 100 mL/min until maximal drinking capacity. Intragastric volume at maximal drinking capacity was determined using 3-dimensional ultrasonography. RESULTS: Drinking capacity (P < 0.05) and intragastric volume (P < 0.01) were significantly lower in patients than in the controls with the meat soup meal, but not with Nutridrink or water. Gastric emptying distinguished significantly (P < 0.05) between patients and controls only with Nutridrink. Gastric emptying of Nutridrink was significantly correlated to the rate by which nausea was induced (P = 0.02), while gastric emptying of meat soup was significantly negatively correlated to the rate by which fullness was induced (P < 0.05). Receiver operating characteristic (ROC) analysis indicated that optimal discrimination between patients and controls was obtained by the combined test results of symptoms per intragastric volume using meat soup as the test meal. CONCLUSION: For the non-invasive diagnosis of functional dyspepsia by a rapid drink test in combination with ultrasonography, a meat soup meal is preferable compared to Nutridrink or water.