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  • 151. Tivenius, Mathilda
    et al.
    Näsvall, Pia
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap. Sunderby Reasearch Unit, Umeå University, Luleå, Sweden.
    Sandblom, Gabriel
    Parastomal hernias causing symptoms or requiring surgical repair after colorectal cancer surgery - a national population-based cohort study2019Inngår i: International Journal of Colorectal Disease, ISSN 0179-1958, E-ISSN 1432-1262, Vol. 34, nr 7, s. 1267-1272Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    PurposeParastomal hernia is a complication with high morbidity that affects the patient's quality of life. The aim of this study was to assess the cumulative incidence of parastomal hernia in patients who have undergone colorectal cancer surgery and to identify potential risk factors that could predispose to the development of this type of hernia in a large population-based cohort over a long follow-up period.MethodsThe Swedish Colorectal Cancer Registry and the National Patient Register were used to collect study cohort data between January 2007 and September 2013. All patients undergoing colorectal cancer surgery including a permanent stoma were included in the study group.ResultsA total of 39,984 patients were registered during the study period. Of these, 7649 received a permanent stoma. Multivariate proportional hazard analysis, based on 6329 patients for whom all covariates could be retrieved, showed that the only independent risk factor for developing a parastomal hernia was BMI30 (HR 1.49; 95% CI 1.02-2.17; p<0.037). A slightly elevated hazard ratio was found for preoperative radiotherapy (HR 1.36; 95% CI 0.96-1.91; p<0.070). The cumulative incidence of patients diagnosed or surgically treated for parastomal hernia over a follow-up period of 5years was 7.7% (95% CI 6.1-9.2%).ConclusionsThe cumulative incidence of parastomal hernia causing symptoms or requiring surgery after 5years was at least 7.7%. Obesity increases the risk of developing parastomal hernia.

  • 152. Turck, Dominique
    et al.
    Michaelsen, Kim F.
    Shamir, Raanan
    Braegger, Christian
    Campoy, Cristina
    Colomb, Virginie
    Decsi, Tamas
    Domellöf, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Fewtrell, Mary
    Kolacek, Sanja
    Mihatsch, Walter
    Moreno, Luis A.
    van Goudoever, Johannes
    World Health Organization 2006 Child Growth Standards and 2007 Growth Reference Charts: A Discussion Paper by the Committee on Nutrition of the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition2013Inngår i: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 57, nr 2, s. 258-264Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Growth charts are essential for evaluating children's health including their nutrition; however, the evaluation of child growth trajectories and consequently the decision to intervene are highly dependent on the growth charts used. The aim of this discussion paper of the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition Committee on Nutrition is to provide information on the background and rationale of the World Health Organization (WHO) 2006 child growth standards and WHO 2007 growth reference charts, describe their development, outline their main innovative aspects, discuss potential limitations, and make recommendations. WHO 2006 child growth standards (0-5 years) are based on prospectively collected data describing the growth of healthy infants who were breast-fed according to WHO recommendations, showing a pattern of linear growth, which is remarkably consistent between different countries and ethnic groups. WHO 2007 growth reference charts (5-19 years) are based mainly on a re-analysis of National Centre for Health Statistics data from 1977, without information on feeding. European Society for Paediatric Gastroenterology, Hepatology, and Nutrition Committee on Nutrition recommends that WHO child growth standards should be used to monitor growth in all children in the age range 0 to 2 years in Europe, whether breast- or formula-fed, and that they should be considered to be used in the age range 2 to 5 years. Implementation of the WHO child growth standards should be preceded by evaluation of the implication of their use on national healthcare policies. Health professionals should be guided on their use and interpretation and an adequate communication strategy should be available locally to ensure that parents receive clear and consistent advice. The decision on whether to implement the WHO growth references (5-19 years) should be made by national bodies because the growth pattern during the 5- to 19-year period differs between populations.

  • 153.
    Van Guelpen, Bethany
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Hultdin, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Johansson, Ingegerd
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Kariologi.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Stenling, Roger
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Riboli, E
    Winkvist, A
    Palmqvist, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Low folate levels may protect against colorectal cancer2006Inngår i: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 55, nr 10, s. 1461-1466Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    BACKGROUND AND AIMS: Dietary folate is believed to protect against colorectal cancer (CRC). However, few studies have addressed the role of circulating levels of folate. The aim of this study was to relate prediagnostic plasma folate and homocysteine concentrations and the methylenetetrahydrofolate reductase (MTHFR) 677C>T and 1298A>C polymorphisms to the risk of developing CRC.

    SUBJECTS: Subjects were 226 cases and 437 matched referents from the population based Northern Sweden Health and Disease Cohort.

    RESULTS: We observed a bell-shaped association between plasma folate concentrations and CRC risk; multivariate odds ratio for middle versus lowest quintile 2.00 (95% confidence interval (CI) 1.13-3.56). In subjects with follow up times greater than the median of 4.2 years however, plasma folate concentrations were strongly positively related to CRC risk; multivariate odds ratio for highest versus lowest quintile 3.87 (95% CI 1.52-9.87; p trend = 0.007). Homocysteine was not associated with CRC risk. Multivariate odds ratios for the MTHFR polymorphisms were, for 677 TT versus CC, 0.41 (95% CI 0.19-0.85; p trend = 0.062), and for 1298 CC versus AA, 1.62 (95% CI 0.94-2.81; p trend = 0.028). Interaction analysis suggested that the result for 1298A>C may have been largely due to linkage disequilibrium with 677C>T. The reduced CRC risk in 677 TT homozygotes was independent of plasma folate status.

    CONCLUSIONS: Our findings suggest a decreased CRC risk in subjects with low folate status. This possibility of a detrimental component to the role of folate in carcinogenesis could have implications in the ongoing debate in Europe concerning mandatory folate fortification of foods.

  • 154. Visuri, I.
    et al.
    Eriksson, C.
    Mardberg, E.
    Grip, O.
    Gustavsson, A.
    Hjortswang, H.
    Karling, Pontus
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Montgomery, S.
    Myrelid, P.
    Olen, O.
    Ludvigsson, J. F.
    Halfvarson, J.
    Anti-TNF agent drug survival in patients with IBD: real-world comparisons of individual anti-TNF agents based on the Swedish National Quality Registry for IBD (SWIBREG)2019Inngår i: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 13, s. S443-S444Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    Background: Studies comparing drug survival in different anti-tumour necrosis factor (TNF) agents in IBD patients are scarce, especially for second-line anti-TNF agents. We aimed to (A) assess drug survival and predictors of response and adverse drug reactions to first-line anti-TNF treatment and (B) examine drug survival for individual anti-TNF agents when used as second-line anti-TNF. Methods: Well-characterised patients with IBD (n = 955)  starting their first anti-TNF treatment between 2006 and 2016 (Table  1), were identified from the Swedish National Quality Registry for IBD (SWIBREG). Drug survival was examined, stratified by reason for discontinuation, that is, lack/loss of clinical effectiveness or adverse drug reactions. Multi-variable Cox regression models were used to identify predictors of drug survival. Drug survival for the second anti-TNF was assessed by type of first anti-TNF agent. Results: Risk factors at baseline for shorter drug survival, in patients with Crohn’s disease, were use of infliximab as first-line anti-TNF (compared with adalimumab, adjusted HR  =  1.95, 95% CI: 1.19‒3.18) (Figure 1A) and colonic disease (L2) (compared with ileal disease (L1) and ileocolonic disease (L3), adjusted HR = 2.16, 95% CI: 1.25‒3.74). Consistently, Crohn’s disease patients who switched from adalimumab to infliximab had shorter drug survival, compared with those who switched from infliximab to adalimumab (Figure  1B). A  normalisation of CRP level at 3 months was associated with decreased risk of short drug survival in both Crohn’s disease (adjusted HR = 0.40, 95% CI: 0.19‒0.81) and ulcerative colitis (adjusted HR = 0.40, 95% CI: 0.19‒0.86). In Crohn’s disease, but not in ulcerative colitis, immunomodulators were associated with a lower risk of short drug survival due to adverse drug reactions (adjusted HR = 0.50, 95% CI: 0.31‒0.82). Conclusions: Drug survival duration was longer for adalimumab compared with infliximab both when used as first anti-TNF agent and when used as second-line treatment. The consistent pattern indicates that these differences are not only explained by channelling bias (differential prescribing behaviour).

  • 155. Volk, Joana K.
    et al.
    Nyström, Elisabeth E. L.
    van der Post, Sjoerd
    Abad, Beatriz M.
    Schroeder, Bjoern
    Wallenberg Laboratory and Sahlgrenska Center for Cardiovascular and Metabolic Research, Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
    Johansson, Åsa
    Svensson, Frida
    Jäverfelt, Sofia
    Johansson, Malin E. V.
    Hansson, Gunnar C.
    Birchenough, George M. H.
    The Nlrp6 inflammasome is not required for baseline colonic inner mucus layer formation or function2019Inngår i: Journal of Experimental Medicine, ISSN 0022-1007, E-ISSN 1540-9538, Vol. 216, nr 11, s. 2602-2618Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The inner mucus layer (IML) is a critical barrier that protects the colonic epithelium from luminal threats and inflammatory bowel disease. Innate immune signaling is thought to regulate IML formation via goblet cell Nlrp6 inflammasome activity that controls secretion of the mucus structural component Muc2. We report that isolated colonic goblet cells express components of several inflammasomes; however, analysis of IML properties in multiple inflammasome-deficient mice, including littermate-controlled Nlrp6−/−, detect a functional IML barrier in all strains. Analysis of mice lacking inflammasome substrate cytokines identifies a defective IML in Il18−/− mice, but this phenotype is ultimately traced to a microbiota-driven, Il18-independent effect. Analysis of phenotypic transfer between IML-deficient and IML-intact mice finds that the Bacteroidales family S24-7 (Muribaculaceae) and genus Adlercrutzia consistently positively covary with IML barrier function. Together, our results demonstrate that baseline IML formation and function is independent of inflammasome activity and highlights the role of the microbiota in determining IML barrier function.

  • 156.
    Wallner, Bengt
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Björ, Ove
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Andreasson, Anna
    Hellström, Per M.
    Forsberg, Anna M.
    Talley, Nicholas J.
    Agreus, Lars
    Identifying clinically relevant sliding hiatal hernias: a population-based endoscopy study2018Inngår i: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 53, nr 6, s. 657-660Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives: The clinical relevance of small to moderate sliding hiatal hernias is controversial. The aims of the present study were to (1) investigate which symptoms are associated with sliding hiatal hernias and (2) define the length of a sliding hiatal hernia at which gastrointestinal symptoms occur.

    Methods: A study population representative of the general Swedish population answered a questionnaire regarding gastrointestinal symptoms and was investigated with an upper endoscopy. The length of any sliding hiatal hernia was measured.

    Results: Only reflux-related symptoms were associated with length of the hiatal hernia (acid regurgitation OR 1.46, CI 1.19–1.79, heartburn OR 1.27, CI 1.05–1.54), and the association did not become significant until an axial hiatal hernia length of 2 cm.

    Conclusions: Only reflux symptoms could be attributed to sliding hiatal hernias. Hiatal hernias less than 2 cm should be considered clinically insignificant.

  • 157.
    Wallner, Bengt
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Björ, Ove
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Andreasson, Anna
    Vieth, Michael
    Schmidt, Peter T.
    Hellstrom, Per M.
    Forsberg, Anna
    Talley, Nicholas J.
    Agreus, Lars
    Z-line alterations and gastroesophageal reflux: an endoscopic population-based prospective cohort study2019Inngår i: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 54, nr 9, s. 1065-1069Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background and study aims: Barrett's esophagus is a premalignant condition in the distal esophagus associated with esophageal adenocarcinoma. Since gastroesophageal reflux is known to be of etiological importance in both Barrett's esophagus and esophageal adenocarcinoma, we aimed to study which endoscopic alterations at the Z-line can be attributed to a previous history of reflux symptoms. Patients and methods: From 1988, a population cohort in Sweden has been prospectively studied regarding gastrointestinal symptoms, using a validated questionnaire. In 2012, the population was invited to undergo a gastroscopy and participate in the present study. In order to determine which endoscopic alterations that can be attributed to a previous history of gastroesophageal reflux, three different endoscopic definitions of columnar-lined esophagus (CLE) were used: (1) ZAP I, An irregular Z-line with a suspicion of tongue-like protrusions; (2) ZAP II/III, Distinct, obvious tongues of metaplastic columnar epithelium; (3) CLE >= 1 cm, The Prague C/M-classification with a minimum length of 1 cm. Results: A total of 165 community subjects were included in the study. Of these, 40 had CLE >= 1 cm, 99 had ZAP I, and 26 had ZAP II/III. ZAP II/III was associated with an over threefold risk of previous GER symptoms (OR: 3.60, CI: 1.49-8.70). No association was found between gastroesophageal reflux and ZAP I (OR: 2.06, CI: 0.85-5.00), or CLE >= 1 cm (OR: 1.64, CI: 0.77-3.49). Conclusions: In a general community, the only endoscopic alteration to the Z-line definitely linked to longstanding GER symptoms was the presence of obvious tongues of metaplastic columnar epithelium (ZAP II/III).

  • 158. Webb, Charlotta
    et al.
    Myléus, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Norström, Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Hammarroth, Solveig
    Högberg, Lotta
    Lagerqvist, Carina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Rosén, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Sandström, Olof
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Stenhammar, Lars
    Ivarsson, Anneli
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Carlsson, Annelie
    High adherence to a gluten-free diet in adolescents with screening-detected celiac disease2015Inngår i: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 60, nr 1, s. 54-59Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVES: To evaluate the gluten-free diet (GFD) adherenceafter one year of follow-up in children with screening-detected celiac disease (CD) in a general population. METHODS: A total of 18,325 12 year olds were invited to participate in apopulation-based CD screening (ETICS- Exploring the Iceberg of Celiacs in Sweden), of whom 13,279 participated. In 240 children, CD was detected through elevated anti-tissue transglutaminase antibodies 2 (TG2-IgA) and verified by a small-intestinal biopsy. This sub-study included the 210 children with TG2-IgAevaluated both at the initialbiopsy occasion and at the one-year follow-up. GFD adherence was evaluated by a combination of TG2-IgA measurements and self-reported adherence (n = 193). RESULTS: After one year, 83% (179/210) had normalizedTG2-IgA levels (<5U/mL). Among those who had >50 U/mL at diagnosis,25% (16/63) still had elevated TG2-IgA but for the majority their initial values were more than halved. Most reported a high level ofGFD adherence ('always' 75%(158/193) and 'often' 14%(30/193)), and 75% (145/193) reported always adhereingcombined with normalized TG2-IgA. Although reporting that they were always adherent, 13 (6.7%) had not yet normalized their TG2-IgA levels completely, however, a majority of these initially had the highestTG2-IgA levels. CONCLUSIONS: GFD adherence is high in adolescents with CD detected by screening of the general population of Swedish 12yearolds. Almost all had normalized serology and reported GFD adherenceat the one-year follow-up. However, a few adolescents whoreported GFD adherence still had elevated TG2-IgA levelssuggesting more severe disease and/or non-adherence.

  • 159. Webb, Charlotta
    et al.
    Norström, Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Myléus, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Ivarsson, Anneli
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Halvarsson, Britta
    Högberg, Lotta
    Lagerqvist, Carina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Rosén, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Sandström, Olof
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Stenhammar, Lars
    Carlsson, Annelie
    Celiac disease can be predicted by high levels of anti-tissue transglutaminase antibodies in population-based screening2015Inngår i: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 60, nr 6, s. 787-791Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVES: To evaluate any potential correlation between anti-tissue transglutaminase antibodies of type immunoglobulin A (tTG-IgA) and the degree of gluten induced enteropathy in children participating in a screening study for celiac disease (CD) and to assess to what extent the revised ESPGHAN (European Society for Paediatric Gastroenterology, Hepatology and Nutrition) guidelines cover this group of patients.

    METHODS: This is a sub-study of a cross-sectional CD screening study, ETICS (Exploring the Iceberg of Celiacs in Sweden), a two-phased study performed during 2005-2006 and 2009-2010. The 13,279 participating children had a blood test obtained and those with positive tTG-IgA were recommended a small intestinal biopsy. The tTG-IgA levels at the time of biopsy were compared with the assessment of the biopsy.

    RESULTS: There were 267 children included, of whom 230 were diagnosed with CD. Out of all children, 67 children had low tTG-IgA levels (<5 U/mL), whereof 55% had Marsh 3 lesions. All children with tTG-IgA levels exceeding 10 times the upper limit of normal values of 5 U/mL, i.e. 50 U/mL, were diagnosed with CD. Lowering the cut-off to 3 U/mL, all but one child with 30 U/mL got CD diagnosis.

    CONCLUSION: By adapting the revised ESPGHAN criteria, biopsies could have been omitted in a fourth of all cases. Our results indicate, that the criteria might be useful even on screened children. Further studies are needed to confirm whether the 2012 ESPGHAN guidelines should be revised to also apply to the populations being screened.

  • 160.
    Werner, Mårten
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Autoimmune hepatitis in Sweden2009Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Autoimmune hepatitis (AIH) was identified as an entity by the Swedish professor Jan Waldenström in the 1950s. It was then denoted lupoid hepatitis, characterized by liver inflammation and most often affecting young women. During the years the diagnosis has become more defined (as the non A non B hepatitis has been identified as Hepatitis C) and now can be safely separated from other diseases with liver inflammation. Studies of epidemiological data and long term prognosis have been scarce in the literature. Within a collaboration between the university hospitals in Sweden, we collected what we believe is the largest cohort in the world of patients with AIH. Data from the medical records of 473 individuals was, after AIH-score calculations where the diagnosis was confirmed, collected in a data base, in which most of the analysis was done. Data from the Swedish national registers of cancer, death cause, and birth register was searched for these patients as well as controls. The aim of the thesis was to explore epidemiological and clinical outcome of AIH.The onset of AIH may be at any age, but the incidence seems to increase after 50 years of age; 75% are females, the overall incidence (0.85/ 100,000 inhabitants and year) and prevalence (11/100,000 inhabitants) are figures that are within the range of another but smaller Scandinavian study. Approximately 30 % had cirrhosis already at diagnosis and 87% displayed at some time positive auto-antibodies indicating AIH (Smooth muscle ab and or antinuclear ab).  Indications of future risk for liver transplantation or death is an advanced AIH at diagnosis with liver cirrhosis, decompensated liver disease, elevated PK INR as well as age. Acute hepatitis-like onset seems to carry a lower risk for later liver transplantation or death. Current Swedish national therapy traditions with immune suppression seem to be well tolerated. Five and ten years overall life expectancy does not differ from controls. Thirty-five women gave birth to 63 children, for 3 after liver transplantation of the mother. Thirteen of the women had liver cirrhosis. Current pharmacological treatment seems to be safe both for the patient and the foetus. Thirty percent of the patients experienced flair after delivery. It has been supposed that there is an overrisk for hepatocellular cancer (HCC) associated with AIH. Our figures are the first in the world to be presented that confirms a twenty-three fold overrisk (95% Confidence Interval 7.5-54.3) for hepatobiliar cancer. We found as well an overrisk of non-Hodgkin lymphomas of 13.09 (95% CI 4.2-30.6).Conclusion:  Our epidemiological results confirm that AIH is a fairly uncommon disease, and that many already at time of diagnosis have an advanced disease with liver cirrhosis. There is a clear overrisk for HCC and lymphoma. For those women with AIH who become pregnant the prognosis for the child as well as for the mother is good, even for those women who already have compensated cirrhosis. There is a risk for relapse after delivery. The overall survival for AIH patients with current therapy is good.

  • 161.
    Werner, Mårten
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Björnsson, Einar
    Prytz, Hanne
    Lindgren, Stefan
    Almer, Sven
    Broomé, Ulrika
    Wallerstedt, Sven
    Sandberg-Gertzén, Hanna
    Hultcrantz, Rolf
    Sangfeldt, Per
    Nilsson, Jenny
    Danielsson, Åke
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Autoimmune hepatitis among fertile women: strategies during pregnancy and breastfeeding?2007Inngår i: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 42, nr 8, s. 986-991Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: In published studies there is a lack of data about the risks, management and how women with autoimmune hepatitis (AIH) decide on and are advised about pregnancy. The aim of this study was to investigate how women with AIH consider pregnancies, are advised and pharmacologically treated, as well as the outcome.

    MATERIAL AND METHODS: A questionnaire was mailed to 128 women with AIH diagnosed during their fertile period and data from the Swedish National Birth Register was also used for matched controls.

    RESULTS: There was an 83% response rate to the questionnaires. Sixty-three pregnancies were reported by 35 women. 48% did not consult their doctors before getting pregnant. More than half of the women reduced or stopped the immune suppression during pregnancy or breastfeeding. Some women were advised to abstain from pregnancy or even to have an abortion. Caesarean sections were performed more frequently in the AIH group (16% compared with 6.5% in the control group p<0.01).There were no significant differences in the number of stillborn infants or infants with malformations. However, 30% of the patients experienced flare-up after delivery.

    CONCLUSIONS: In general, the outcome of pregnancy in women with AIH seems to be good. Current pharmacological treatment appears to be safe, including azathioprine during pregnancy and lactation. After delivery an active preparedness to increase pharmacotherapy should be considered.

  • 162.
    Werner, Mårten
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Prytz, Hanne
    Ohlsson, Bodil
    Almer, Sven
    Björnsson, Einar
    Bergquist, Annika
    Wallerstedt, Sven
    Sandberg-Gertzén, Hanna
    Hultcrantz, Rolf
    Sangfelt, Per
    Weiland, Ola
    Danielsson, Åke
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Epidemiology and the initial presentation of autoimmune hepatitis in Sweden: a nationwide study2008Inngår i: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 43, nr 10, s. 1232-1240Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: Autoimmune hepatitis (AIH) is a chronic liver disease, which if untreated can lead to cirrhosis and hepatic failure. The aim of the study was to investigate the incidence, prevalence, diagnostic tradition and clinical initial presentation of AIH.

    MATERIAL AND METHODS: Analyses were performed in 473 patients identified as having probable or definite AIH. RESULTS: The incidence of AIH was 0.85/100,000 (95% CI 0.69-1.01) inhabitants, which is somewhat lower than reported previously. The point prevalence amounted to 10.7/100,000 (95% CI 8.8-13.1), and 76% of the cases were females. The age-related incidence curve was bimodal but men were found to have only one incidence peak in the late teens, whereas women had a peak after menopause. AIH was presented as a spectrum of clinical settings from detected "en passant" to acute liver failure. Almost 30% of patients already had liver cirrhosis at diagnosis. Autoantibodies indicative of AIH type 1 were found in 79% of cases. Other concomitant autoimmune diseases were frequently found (49%).

    CONCLUSIONS: The incidence and prevalence figures confirm that AIH is a fairly uncommon disease in the Swedish population. Symptoms at presentation were unspecific, but almost half of the patients were jaundiced, with around 30% having liver cirrhosis. The majority of Swedish AIH patients had AIH type 1.

  • 163.
    West, Christina E.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Jenmalm, Maria C.
    Transfer of Probiotic Bacteria From Mother to Child: A Matter of Strain Specificity?2015Inngår i: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 61, nr 2, s. 157-158Artikkel i tidsskrift (Annet vitenskapelig)
  • 164. Westfelt, Petter
    et al.
    Hedman, Leif
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi. Karolinska Institutet.
    Lindkvist, Mikael Axelsson
    Enochsson, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Fellander-Tsai, Li
    Schmidt, Peter Thelin
    Training nonanesthetist administration of propofol for gastrointestinal endoscopy in scenario-based full-scale hybrid simulation - a pilot study2013Inngår i: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 48, nr 11, s. 1354-1358Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective. The use of nonanesthetist-administered propofol (NAAP) in GI endoscopy has long been controversial. In the setting of NAAP, acute situations can develop during endoscopy and thus training before starting with NAAPs is considered crucial. The aim was to evaluate a pilot study on crew resource management (CRM)-based training of teams of endoscopists and endoscopy nurses in NAAP in a full-scale hybrid simulation consisting of a full-scale human patient simulator and an endoscopy simulator. Our hypothesis was that the training would increase the self-efficacy of the participants. Material and methods. Four scenarios were created, each with typical side effects of propofol administration. All scenarios included the need for prompt decision-making and treatment. Colonoscopy, gastroscopy or endoscopic retrograde cholangiopancreatography (ERCP) cases were assigned to the course participants in coherence with their main clinical expertise in order to facilitate situated and contextualized training. Twenty-one participants (ten doctors and eleven nurses) completed a questionnaire on self-efficacy before and after the course. A questionnaire regarding the quality and yield of the course was also completed. Results. For all participants, the self-efficacy score was 26.0 (24.0-28.0; interquartile range) before training and 30.0 (27.0-30.5) after training (p = 0.0003). The ten doctors had a self-efficacy score before training of 26.5 (25.0-29.5) and 30.0 (29.0-33.0) after (p = 0.0078). The eleven nurses scored 24.0 (22.0-26.0) before and 28.0 (27.0-30.0) after training (p = 0.0098). Conclusions. Systematic target focused scenario-based training with hybrid simulation of NAAP in endoscopy resulted in increased self-efficacy in both nurses and physicians.

  • 165.
    Widbom, L.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Schneede, Jørn
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Farmakologi.
    Karling, Pontus
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Hultdin, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Higher plasma cotinine is associated with an increased risk for later developing IBD, especially among users of combusted tobacco2019Inngår i: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 13, s. S508-S508Artikkel i tidsskrift (Annet vitenskapelig)
  • 166. Wilczek, Henryk E
    et al.
    Stangou, Arie J
    Suhr, Ole B
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Larsson, Marie E.
    Ericzon, Bo-Goran
    Liver transplantation for familial amyloidosis: the 20-year report from the familial amyloidotic polyneuropathy world transplant registry (fapwtr)2011Inngår i: Hepatology Supplement: The 62nd Annual Meeting of the American Association for the Study of Liver Diseases: The Liver Meeting 2011, Philadelphia, Pa: W.B. Saunders , 2011, Vol. 54, s. 413A-414AKonferansepaper (Fagfellevurdert)
  • 167.
    Wixner, Jonas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Gastrointestinal disturbances in hereditary transthyretin amyloidosis2014Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Background

    Transthyretin amyloid (ATTR) amyloidosis is a systemic disorder caused by amyloid deposits formed by misfolded transthyretin (TTR) monomers. Two main forms exist – wild-type and hereditary ATTR amyloidosis, the latter associated with TTR gene mutations. Wild-type ATTR amyloidosis has a late onset and primarily cardiac manifestations, whereas hereditary ATTR amyloidosis is a rare autosomal dominant condition with a considerable phenotypic diversity. Both disorders are present all over the world, but endemic areas of the hereditary form are found in Sweden, Portugal, Brazil and Japan. Gastrointestinal (GI) complications are common in hereditary ATTR amyloidosis and play an important role in the patients’ morbidity and mortality. Malfunction of the autonomic and enteric nervous systems has been proposed to contribute to the GI disturbances, but the underlying mechanisms have not been fully elucidated. The aims of this thesis were to assess the prevalence of GI disturbances for different subtypes of ATTR amyloidosis, to further explore the mechanisms behind these disturbances, and to evaluate the outcome of the patients’ GI function after liver transplantation, which currently is the standard treatment for hereditary ATTR amyloidosis.

    Methods

    The Transthyretin Amyloidosis Outcomes Survey (THAOS) is the first global, multicenter, longitudinal, observational survey that collects data on patients with ATTR amyloidosis. THAOS enrollment data were used to assess the prevalence of GI symptoms and to evaluate their impact on nutritional status (mBMI) and health-related quality of life (EQ-5D Index Score). Data from routine investigations of heart-rate variability and cardio-vascular response to tilt tests were utilized to evaluate the impact of autonomic neuropathy on the scintigraphically measured gastric emptying half-times in Swedish patients with hereditary ATTR amyloidosis. Gastric wall autopsy specimens from Japanese patients with hereditary ATTR amyloidosis and Japanese non-amyloidosis controls were analyzed with immunohistochemistry and computerized image analysis to assess the densities of interstitial cells of Cajal (ICC) and nervous tissue. Data from gastric emptying scintigraphies and validated questionnaires were used to evaluate the outcome of Swedish patients’ GI function after liver transplantation for hereditary ATTR amyloidosis.

    Results

    Sixty-three percent of the patients with TTR mutations and 15 % of those with wild-type ATTR amyloidosis reported GI symptoms at enrollment into THAOS. Subsequent analyses focused on patients with TTR mutations and, among them, unintentional weight loss was the most frequent symptom (32 %) followed by early satiety (26 %). Early-onset patients (<50 years of age) reported GI symptoms more frequently than late-onset cases (70 % vs. 50 %, p <0.01), and GI symptoms were more common in patients with the V30M mutation than in those with non-V30M mutations (69 % vs. 56 %, p <0.01). Both upper and lower GI symptoms were significant negative predictors of nutritional status and health-related quality of life (p <0.01 for both). Weak but significant correlations were found between gastric emptying half-times and the function of both the sympathetic (rs = -0.4, p <0.01) and parasympathetic (rs = -0.3, p <0.01) nervous systems. The densities of c-Kit-immunoreactive ICC were significantly lower in the circular (median density 0.0 vs. 2.6, p <0.01) and longitudinal (median density 0.0 vs. 1.8, p <0.01) muscle layers of the gastric wall in patients compared to controls. Yet, no significant differences in protein gene product 9.5-immunoreactive nervous cells were found between patients and controls either in the circular (median density 3.0 vs. 6.8, p = 0.17) or longitudinal (median density 1.4 vs. 2.5, p = 0.10) muscle layers. Lastly, the patients’ GI symptoms scores had increased slightly from before liver transplantation to the follow-ups performed in median two and nine years after transplantation (median score 7 vs. 10 vs. 13, p <0.01). However, their gastric emptying half-times (median half-time 137 vs. 132 vs. 125 min, p = 0.52) and nutritional statuses (median mBMI 975 vs. 991 vs. 973, p = 0.75) were maintained at follow-ups in median two and five years after transplantation.

    Conclusion

    GI disturbances are common in hereditary ATTR amyloidosis and have a negative impact on the patients’ nutritional status and health-related quality of life. Fortunately, a liver transplantation appears to halt the progressive GI involvement of the disease, although the patients’ GI symptoms tend to increase after transplantation. An autonomic neuropathy and a depletion of gastrointestinal ICC seem to contribute to the GI disturbances, but additional factors must be involved.

  • 168.
    Wixner, Jonas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Karling, Pontus
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Rydh, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Hornsten, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Klinisk fysiologi.
    Wiklund, Urban
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Anan, Intissar
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Suhr, Ole B.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Gastric emptying in hereditary transthyretin amyloidosis: the impact of autonomic neuropathy2012Inngår i: Neurogastroenterology and Motility, ISSN 1350-1925, E-ISSN 1365-2982, Vol. 24, nr 12, s. 1111-e568Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Gastrointestinal (GI) complications are common in hereditary transthyretin amyloidosis and an autonomic dysfunction has been considered to explain these symptoms. The aim of this study was to investigate the impact of autonomic neuropathy on gastric emptying in hereditary transthyretin amyloidosis and to relate these findings to nutritional status, GI symptoms, gender, and age at disease onset.

    Methods: Gastric emptying was evaluated with gastric emptying scintigraphy. Spectral analysis of the heart rate variability and cardiovascular responses after tilt test were used to assess the autonomic function. The nutritional status was evaluated with the modified body mass index (s-albumine x BMI).

    Key Results: Gastric retention was found in about one-third of the patients. A weak correlation was found between the scintigraphic gastric emptying rate and both the sympathetic (rs = -0.397, P < 0.001) and parasympathetic function (rs = -0.282, P = 0.002). The gastric emptying rate was slower in those with lower or both upper and lower GI symptoms compared with those without symptoms (median T50 123 vs 113 min, P = 0.042 and 192 vs 113 min, P = 0.003, respectively). Multiple logistic regression analysis showed that age of onset (OR 0.10, CI 0.020.52) and sympathetic dysfunction (OR 0.23, CI 0.100.51), but not gender (OR 0.76, CI 0.311.84) and parasympathetic dysfunction (OR 1.81, CI 0.724.56), contributed to gastric retention.

    Conclusions and Inferences: Gastric retention is common in hereditary transthyretin amyloidosis early after onset. Autonomic neuropathy only weakly correlates with gastric retention and therefore additional factors must be involved.

  • 169.
    Wixner, Jonas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Mundayat, Rajiv
    Pfizer Inc, New York, NY, USA.
    Karayal, Onur N
    Pfizer Inc, New York, NY, USA.
    Anan, Intissar
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Karling, Pontus
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Suhr, Ole B
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    THAOS: Gastrointestinal manifestations of transthyretin amyloidosis - common complications of a rare disease2014Inngår i: Orphanet Journal of Rare Diseases, ISSN 1750-1172, E-ISSN 1750-1172, Vol. 9, nr 1, s. 61-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Transthyretin amyloidosis is a systemic disorder caused by amyloid deposits formed by misfolded transthyretin monomers. Two main forms exist: hereditary and wild-type transthyretin amyloidosis, the former associated with transthyretin gene mutations. There are several disease manifestations; however, gastrointestinal complications are common in the hereditary form. The aim of this study was to explore the prevalence and distribution of gastrointestinal manifestations in transthyretin amyloidosis and to evaluate their impact on the patients' nutritional status and health-related quality of life (HRQoL).

    METHODS: The Transthyretin Amyloidosis Outcomes Survey (THAOS) is the first global, multicenter, longitudinal, observational survey that collects data on patients with transthyretin amyloidosis and the registry is sponsored by Pfizer Inc. This study presents baseline data from patients enrolled in THAOS as of June 2013. The modified body mass index (mBMI), in which BMI is multiplied with serum albumin, was used to assess the nutritional status and the EQ-5D Index was used to assess HRQoL.

    RESULTS: Data from 1579 patients with hereditary transthyretin amyloidosis and 160 patients with wild-type transthyretin amyloidosis were analyzed. Sixty-three percent of those with the hereditary form and 15% of those with the wild-type form reported gastrointestinal symptoms at enrollment. Unintentional weight loss and early satiety were the most frequent symptoms, reported by 32% and 26% of those with transthyretin gene mutations, respectively. Early-onset patients (<50 years) reported gastrointestinal complaints more frequently than those with a late onset (p < 0.001) and gastrointestinal symptoms were more common in patients with the V30M mutation than in those with other mutations (p < 0.001). For patients with predominantly cardiac complications, the prevalence of gastrointestinal manifestations was not evidently higher than that expected in the general population. Both upper and lower gastrointestinal symptoms were significant negative predictors of mBMI and the EQ-5D Index Score (p < 0.001 for all).

    CONCLUSIONS: Gastrointestinal symptoms were common in patients with hereditary transthyretin amyloidosis and had a significant negative impact on their nutritional status and HRQoL. However, patients with wild-type transthyretin amyloidosis or transthyretin mutations associated with predominantly cardiac complications did not show an increased prevalence of gastrointestinal disturbances.

  • 170.
    Wixner, Jonas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Suhr, Ole B.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Anan, Intissar
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Management of gastrointestinal complications in hereditary transthyretin amyloidosis: a single-center experience over 40 years2018Inngår i: Expert Review of Gastroenterology & Hepatology, ISSN 1747-4124, E-ISSN 1747-4132, Vol. 12, nr 1, s. 73-81Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Introduction: Hereditary transthyretin amyloidosis (ATTRm amyloidosis) is a rare disease caused by the deposition and accumulation of insoluble non-native transthyretin fibrils in the body. The disease inevitably results in widespread organ disruption, and poor life expectancy. The GI tract is one organ system vulnerable to disruption and, although the clinical presentation of the disease varies, GI involvement affects most patients with ATTRm amyloidosis.

    Areas covered: This article presents our experience with diagnosing and treating the GI symptoms of ATTRm amyloidosis patients at our center over the last 40 years, in the Swedish clustering area of the disease. Our aim is to help other physicians to better manage GI complications in patients with this rare but widespread condition.

    Expert commentary: GI symptoms are debilitating complications for ATTRm amyloidosis patients to experience, yet with the appropriate questioning and diagnosis methods, symptomatic treatments of these symptoms can be implemented to provide relief. Further, patients with fewer GI complications and a good nutritional status are also better candidates for liver transplantation which, in selected cases, is the best disease-modifying treatment of ATTRm amyloidosis to date.

  • 171.
    Wixner, Jonas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Sundström, Torbjorn
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Karling, Pontus
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Anan, Intissar
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Suhr, Ole B.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Outcome of gastric emptying and gastrointestinal symptoms after liver transplantation for hereditary transthyretin amyloidosis2015Inngår i: BMC Gastroenterology, ISSN 1471-230X, E-ISSN 1471-230X, Vol. 15, artikkel-id 51Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Hereditary transthyretin amyloid (ATTR) amyloidosis is a rare but fatal autosomal dominant condition that is present all over the world. A liver transplantation has been shown to halt the progress of the disease in selected patients and is currently considered to be the standard treatment. Gastrointestinal manifestations are common in hereditary ATTR amyloidosis and are important for the patients' morbidity and mortality. The aim of this study was to evaluate the long-term outcome of gastric emptying, gastrointestinal symptoms and nutritional status after liver transplantation for the disease.

    Methods: Swedish patients with hereditary ATTR amyloidosis transplanted between 1990 and 2012 were included. A standardized method for measuring gastric emptying with a Tc-99m-labelled meal followed by scintigraphy was utilized. Validated questionnaires were used to assess gastrointestinal symptoms and the modified body mass index (mBMI), in which BMI is multiplied by s-albumin, was used to evaluate nutritional status. Non-parametrical statistical tests were used.

    Results: Gastric emptying rates and nutritional statuses were evaluated approximately eight months before and two and five years after liver transplantation, whereas gastrointestinal symptoms were assessed in median nine months before and two and nine years after transplantation. No significant change was found in gastric emptying (median half-time 137 vs. 132 vs. 125 min, p = 0.52) or nutritional status (median mBMI 975 vs. 991 vs. 973, p = 0.75) after transplantation. Gastrointestinal symptom scores, however, had increased significantly over time (median score 7 vs. 10 vs. 13, p < 0.01).

    Conclusions: Gastric emptying and nutritional status were maintained after liver transplantation for hereditary ATTR amyloidosis, although gastrointestinal symptom scores had increased over time.

  • 172.
    Wixner, Jonas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Törnblom, H.
    Karling, Pontus
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Anan, Intissar
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Lindberg, G.
    Abnormal small bowel motility in patients with hereditary transthyretin amyloidosis2018Inngår i: Neurogastroenterology and Motility, ISSN 1350-1925, E-ISSN 1365-2982, Vol. 30, nr 9, artikkel-id e13354Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Gastrointestinal complications are common in hereditary transthyretin amyloid (ATTRm) amyloidosis. The underlying mechanisms have not been fully elucidated, and the patients' small bowel function remains largely unexplored. The aim of the present study was to compare the small bowel motility in ATTRm amyloidosis patients with that in non-amyloidosis patient controls.

    Methods: ATTRm amyloidosis patients undergoing evaluation for liver transplantation were consecutively investigated with 24-hour duodenojejunal manometry (n=19). The somatostatin analogue octreotide was used to induce fasting motility. Patients with age at onset of 50years were defined as late-onset cases. For each patient, three age- and sex-matched patient controls (n=57) were selected from the total pool of investigated patients.

    Key Results: Manometry was judged as abnormal in 58% of the patients and in 26% of the patient controls (P=.01). Patients displayed significantly more daytime phase III migrating motor complexes than patient controls (median 4 vs 2, P<.01), and had a higher frequency of low-amplitude complexes (16% vs 4%; however, this difference did not reach statistical significance, P=.10). Furthermore, late-onset patients showed a delay in octreotide response (5.4 vs 3.8minutes, P<.01), but this was not observed for early-onset patients or within the control group.

    Conclusions and Inferences: Patients with ATTRm amyloidosis displayed abnormalities in their small bowel motility more frequently than non-amyloidosis patient controls, and the manometric pattern was probably best consistent with a combined neuromyopathic disorder. The delayed octreotide response in late-onset patients warrants further investigation.

  • 173. Wolthers, Benjamin Ole
    et al.
    Mogensen, Pernille R.
    Frandsen, Thomas L.
    Abrahamsson, Jonas
    Behrendtz, Mikael
    Heyman, Mats
    Lohi, Olli
    Norén-Nyström, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Ruud, Ellen
    Schmiegelow, Kjeld
    Insulin-dependent diabetes: a chronic complication to acute pancreatitis in childhood acute lymphoblastic leukemia2019Inngår i: Pediatric Blood & Cancer, ISSN 1545-5009, E-ISSN 1545-5017, Vol. 66, nr 1, artikkel-id e27437Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Pancreatitis is a frequent toxicity to acute lymphoblastic leukemia (ALL) treatment, significantly associated with asparaginase use, and may be followed by severe complications such as acute hyperglycaemia, need for mechanical ventilation, pseudocysts, and death. Here, we provide novel data on seven patients diagnosed with diabetes after pancreatitis and still requiring insulin treatment after a median follow-up of 4.2 years (range: 1.7-9.2). We describe the clinical course of pancreatitis and illustrate the association between pancreatic pseudocysts, older age, and development of insulin-dependent diabetes. Together, this study documents the persisting burden of pancreatitis in childhood ALL and underlines the need for plasma glucose level monitoring.

  • 174. Wouters, Mira M.
    et al.
    Lambrechts, Diether
    Knapp, Michael
    Cleynen, Isabelle
    Whorwell, Peter
    Agreus, Lars
    Dlugosz, Aldona
    Schmidt, Peter Thelin
    Halfvarson, Jonas
    Simren, Magnus
    Ohlsson, Bodil
    Karling, Pontus
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Van Wanrooy, Sander
    Mondelaers, Stephanie
    Vermeire, Severine
    Lindberg, Greger
    Spiller, Robin
    Dukes, George
    D'Amato, Mauro
    Boeckxstaens, Guy
    Genetic variants in CDC42 and NXPH1 as susceptibility factors for constipation and diarrhoea predominant irritable bowel syndrome2014Inngår i: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 63, nr 7, s. 1103-1111Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective The complex genetic aetiology underlying irritable bowel syndrome (IBS) needs to be assessed in large-scale genetic studies. Two independent IBS cohorts were genotyped to assess whether genetic variability in immune, neuronal and barrier integrity genes is associated with IBS. Design 384 single nucleotide polymorphisms (SNPs) covering 270 genes were genotyped in an exploratory cohort (935 IBS patients, 639 controls). 33 SNPs with P-uncorrected<0.05 were validated in an independent set of 497 patients and 887 controls. Genotype distributions of single SNPs were assessed using an additive genetic model in IBS and clinical subtypes, IBS-C and IBS-D, both in individual and combined cohorts. Trait anxiety (N=614 patients, 533 controls), lifetime depression (N=654 patients, 533 controls) and mRNA expression in rectal biopsies (N=22 patients, 29 controls) were correlated with SNP genotypes. Results Two SNPs associated independently in the exploratory and validation cohort: rs17837965-CDC42 with IBS-C (ORexploratory=1.59 (1.05 to 1.76); ORvalidation=1.76 (1.03 to 3.01)) and rs2349775-NXPH1 with IBS-D (ORexploratory=1.28 (1.06 to 1.56); ORvalidation=1.42 (1.08 to 1.88)). When combining both cohorts, the association of rs2349775 withstood post hoc correction for multiple testing in the IBS-D subgroup. Additionally, three SNPs in immune-related genes (rs1464510-LPP, rs1881457-IL13, rs2104286-IL2RA), one SNP in a neuronal gene (rs2349775-NXPH1) and two SNPs in epithelial genes (rs245051-SLC26A2, rs17837965-CDC42) were weakly associated with total-IBS (P-uncorrected<0.05). At the functional level, rs1881457 increased IL13 mRNA levels, whereas anxiety and depression scores did not correlate with rs2349775-NXPH1. Conclusions Rs2349775 (NXPH1) and rs17837965 (CDC42) were associated with IBS-D and IBS-C, respectively, in two independent cohorts. Further studies are warranted to validate our findings and to determine the mechanisms underlying IBS pathophysiology.

  • 175. Wu, Chen
    et al.
    Kraft, Peter
    Stolzenberg-Solomon, Rachael
    Steplowski, Emily
    Brotzman, Michelle
    Xu, Mousheng
    Mudgal, Poorva
    Amundadottir, Laufey
    Arslan, Alan A
    Bueno-de-Mesquita, H Bas
    Gross, Myron
    Helzlsouer, Kathy
    Jacobs, Eric J
    Kooperberg, Charles
    Petersen, Gloria M
    Zheng, Wei
    Albanes, Demetrius
    Boutron-Ruault, Marie-Christine
    Buring, Julie E
    Canzian, Federico
    Cao, Guangwen
    Duell, Eric J
    Elena, Joanne W
    Gaziano, J Michael
    Giovannucci, Edward L
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Hutchinson, Amy
    Hunter, David J
    Jenab, Mazda
    Jiang, Guoliang
    Khaw, Kay-Tee
    Lacroix, Andrea
    Li, Zhaoshen
    Mendelsohn, Julie B
    Panico, Salvatore
    Patel, Alpa V
    Qian, Zhi Rong
    Riboli, Elio
    Sesso, Howard
    Shen, Hongbing
    Shu, Xiao-Ou
    Tjonneland, Anne
    Tobias, Geoffrey S
    Trichopoulos, Dimitrios
    Virtamo, Jarmo
    Visvanathan, Kala
    Wactawski-Wende, Jean
    Wang, Chengfeng
    Yu, Kai
    Zeleniuch-Jacquotte, Anne
    Chanock, Stephen
    Hoover, Robert
    Hartge, Patricia
    Fuchs, Charles S
    Lin, Dongxin
    Wolpin, Brian M
    Genome-wide association study of survival in patients with pancreatic adenocarcinoma2014Inngår i: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 63, nr 1, s. 152-160Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND AND OBJECTIVE: Survival of patients with pancreatic adenocarcinoma is limited and few prognostic factors are known. We conducted a two-stage genome-wide association study (GWAS) to identify germline variants associated with survival in patients with pancreatic adenocarcinoma. METHODS: We analysed overall survival in relation to single nucleotide polymorphisms (SNPs) among 1005 patients from two large GWAS datasets, PanScan I and ChinaPC. Cox proportional hazards regression was used in an additive genetic model with adjustment for age, sex, clinical stage and the top four principal components of population stratification. The first stage included 642 cases of European ancestry (PanScan), from which the top SNPs (p≤10(-5)) were advanced to a joint analysis with 363 additional patients from China (ChinaPC). RESULTS: In the first stage of cases of European descent, the top-ranked loci were at chromosomes 11p15.4, 18p11.21 and 1p36.13, tagged by rs12362504 (p=1.63×10(-7)), rs981621 (p=1.65×10(-7)) and rs16861827 (p=3.75×10(-7)), respectively. 131 SNPs with p≤10(-5) were advanced to a joint analysis with cases from the ChinaPC study. In the joint analysis, the top-ranked SNP was rs10500715 (minor allele frequency, 0.37; p=1.72×10(-7)) on chromosome 11p15.4, which is intronic to the SET binding factor 2 (SBF2) gene. The HR (95% CI) for death was 0.74 (0.66 to 0.84) in PanScan I, 0.79 (0.65 to 0.97) in ChinaPC and 0.76 (0.68 to 0.84) in the joint analysis. CONCLUSIONS: Germline genetic variation in the SBF2 locus was associated with overall survival in patients with pancreatic adenocarcinoma of European and Asian ancestry. This association should be investigated in additional large patient cohorts.

  • 176. Yeung, M M
    et al.
    Melgar, S
    Baranov, Vladimir
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Oberg, A
    Danielsson, A
    Hammarström, Sten
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Immunologi/immunkemi.
    Hammarström, Marie-Louise
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Immunologi/immunkemi.
    Characterisation of mucosal lymphoid aggregates in ulcerative colitis: immune cell phenotype and TcR-gammadelta expression.2000Inngår i: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 47, nr 2, s. 215-27Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND AND AIMS: A histopathological feature considered indicative of ulcerative colitis (UC) is the so-called basal lymphoid aggregates. Their relevance in the pathogenesis of UC is, however, unknown. We have performed a comprehensive analysis of the immune cells in these aggregates most likely corresponding to the lymphoid follicular hyperplasia also described in other colitides.

    METHODS: Resection specimens of UC and normal colon were analysed by immunomorphometry, immunoflow cytometry, and immunoelectron microscopy, using a large panel of monoclonal antibodies.

    RESULTS: (1) In all cases of UC, colonic lamina propria contained numerous basal aggregates composed of lymphocytes, follicular dendritic cells, and CD80/B7.1 positive dendritic cells. (2) CD4(+)CD28(-) alphabeta T cells and B cells were the dominant cell types in the aggregates. (3) The aggregates contained a large fraction of cells that are normally associated with the epithelium: that is, gammadelta T cells (11 (7)%) and alpha(E)beta(7)(+) cells (26 (13)%). The gammadelta T cells used Vdelta1 and were CD4(-)CD8(-). Immunoelectron microscopy analysis demonstrated TcR-gammadelta internalisation and surface downregulation, indicating that the gammadelta T cells were activated and engaged in the disease process. (4) One third of cells in the aggregates expressed the antiapoptotic protein bcl-2.

    CONCLUSIONS: Basal lymphoid aggregates in UC colon are a consequence of anomalous lymphoid follicular hyperplasia, characterised by abnormal follicular architecture and unusual cell immunophenotypes. The aggregates increase in size with severity of disease, and contain large numbers of apoptosis resistant cells and activated mucosal gammadelta T cells. The latter probably colonise the aggregates as an immunoregulatory response to stressed lymphocytes or as a substitute for defective T helper cells in B cell activation. gammadelta T cells in the aggregates may be characteristic of UC.

  • 177.
    Yeung, Moorix Mo-Wai
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Immunologi/immunkemi.
    Specific and nonspecific immune mechanisms in human gut: a comparative study of normal and ulcerative colitis intestine1996Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The intestine, with its large mucosal surface area, digests and absorbs food nutrients and maintains a beneficial microbial flora in the colon. Local protective immune responses against intestinal pathogens ensure the survival of the individual. These immune reactions are both specific and non-specific in nature. The intestinal epithelium is single-layered and constantly renewed with differentiating epithelial cells moving from the crypt to the luminal surface. Intraepithelial lymphocytes (IEL) are interspersed between the epithelial cells. Ulcerative colitis (UC) is a life-threatening chronic inflammation affecting colon.

    In this study three molecules belonging to the carcinoembryonic antigen (CEA) family, namely CEA proper, nonspecific cross-reacting antigen 50/90 (NCA 50/90) and biliary glycoprotein (BGP), were found to be specifically localized to the apical surface of colonic epithelial cells. Full expression of these molecules occurs when the cells reach the upper 1/3 of the crypts and are maintained on the mature cells at the luminal surface. Ultrastructurally, CEA, NCA50/90 and BGP are localized to microvesicles and microfilaments of the fuzzy coat/glycocalyx as well as to the microvilli of the epithelial cells. Their unique localization and documented bacterial binding capacities suggest that they have a role in innate immunity.

    Functional analysis of IEL in normal jejunum, ileum and colon revealed that IEL are in vivo activated T-lymphocytes expressing mRNA for the cytokines IL-1β, IL-2, IL-8, IFNγ and TNFα and that jejunal IEL have T-cell receptor (TCR)/CD3 dependent cytolytic capacity. As many as 10% of IEL actively produce IFNγ. CD4+TCRαβ+IEL, CD8+TCRαβ+IEL and CD4-CD8-TCRαβ+IEL all had a TH1/cytotoxic cytokine profile. IEL could be further stimulated in vitro to express IL-10, TNFβ and TGFβ1, to proliferate and to secrete IFNγ. Thus, active protection and/or regulation of the epithelium via cell-mediated immune reactions are prominent in the gut.

    UC colon was characterized by a marked lymphocyte infiltration in the lamina propria, 10-50 times the normal level. Most lymphocytes were present in follicle-like cell aggregates containing both T- and B-cells. An unexpected finding was that γδT-cells constituted about 15% of the cells in the aggregates. Such cells are only found intraepithelially in normal gut. γδT-cells of both the intestinal- (TCR-Vδ1/Vγ8) and blood type (TCR-Vδ2/Vγ9) were seen. T-cells in UC colon were activated but nonproliferating and had a down-regulated TCR/CD3 complex. RT-PCR and quantitative immunohistochemistry for cytokine mRNA (n=11) and protein respectively, revealed that the T-cells in UC colon did not produce IL-2, in marked contrast to T-cells in normal colon and to ileal T-cells from UC patients. This was a selective defect since TNFα, IFNγ, IL-1β, IL-8 and TGFβ1 were similarly expressed in normal colon. No TH2 cytokines were seen. Lamina propria leukocytes in UC colon expressed IL-6, a cytokine not found in normal colon. The epithelial cells of UC colon were activated expressing MHC class II antigens, heat shock proteins and the co-stimulatory molecule B7.1/CD80.

    Our study demonstrates that UC is an immunological disease. The immunopathological picture seen in UC colon probably reflects an inappropriate down-regulation of local immune responses perhaps due to a selective loss of the key cytokine IL-2 in a situation of extreme antigenic stress.

  • 178. Yeung, M-W
    et al.
    Melgar, S
    Baranov, Vladimir
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Immunologi/immunkemi.
    Öberg, Å
    Danielsson, Å
    Hammarström, Sten
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Immunologi/immunkemi.
    Hammarström, Marie-Louise
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Immunologi/immunkemi.
    Characterization of mucosal lymphoid aggregates in ulcerative colitis colon: Immune cell phenotypes and TcR-gammadelta expression.2000Inngår i: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 47, s. 215-227Artikkel i tidsskrift (Fagfellevurdert)
  • 179. Zucchelli, Marco
    et al.
    Camilleri, Michael
    Nixon Andreasson, Anna
    Bresso, Francesca
    Dlugosz, Aldona
    Halfvarson, Jonas
    Törkvist, Leif
    Schmidt, Peter T
    Karling, Pontus
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Ohlsson, Bodil
    Duerr, Richard H
    Simren, Magnus
    Lindberg, Greger
    Agreus, Lars
    Carlson, Paula
    Zinsmeister, Alan R
    D'Amato, Mauro
    Association of TNFSF15 polymorphism with irritable bowel syndrome2011Inngår i: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 60, nr 12, s. 1671-1677Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Irritable bowel syndrome (IBS) is the most common gastrointestinal disorder, affecting more than 10% of the general population worldwide. Although a genetic component is suspected, unambiguous susceptibility genes have so far not been identified. This study tested the hypothesis that genes contributing to epithelial barrier integrity, control of mucosal immune responses and interactions with bacteria in the gut are associated with IBS.

    Methods: Single nucleotide polymorphisms (SNPs) corresponding to top signals of association with Crohn's disease at 30 known susceptibility loci were tested for their effect on IBS risk in 1992 individuals from two independent case–control cohorts from Sweden and the USA. Association tests included a conservative Bonferroni correction for multiple comparisons, and were also performed on specific subgroups of patients characterised by constipation (IBS-C), diarrhoea (IBS-D) or alternating constipation and diarrhoea (IBS-A).

    Results: The Crohn's disease risk allele rs4263839 G in the TNFSF15 gene was significantly associated with an increased risk of both IBS (p=2.2×10−5; OR 1.37) and more pronouncedly, IBS-C (p=8.7×10−7; OR 1.79) in the entire sample. Similar associations and risk effects of the same magnitude were observed in the two cohorts analysed separately. A correlation between rs4263839 genotype and TNFSF15 mRNA expression was detected both in peripheral blood and in rectal mucosal biopsies from healthy individuals (combined p=0.0033).

    Conclusions: TNFSF15 is a susceptibility gene for IBS and IBS constipation. As TL1A, the protein encoded by TNFSF15, contributes to the modulation of inflammatory responses, the results support a role of immune activation in IBS.

  • 180.
    Åkesson, Oscar
    et al.
    Dept of Clinical Scienses, Lund University.
    Abrahamsson, Pernilla
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Johansson, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Blind, Per-Jonas
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Surface microdialysis on small bowel serosa in monitoring of ischemia2016Inngår i: Journal of Surgical Research, ISSN 0022-4804, E-ISSN 1095-8673, Vol. 204, nr 1, s. 39-46Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Ischemic injury of an organ causes metabolic change from aerobic to anaerobic metabolism. It has been shown in experimental studies on the heart and liver that such conversion may be detected by conventional microdialysis probes placed intraparenchymatously, as well as on organ surfaces, by assaying lactate, pyruvate, glucose, and glycerol in dialysate. We developed a microdialysis probe (S-mu D) intended for use solely on organ surfaces. The aim of this study was to assess whether the newly developed S-mu D probe could be used for detection and monitoring of small bowel ischemia. Methods: In anesthetized normoventilated pigs, a control S-mu D probe was applied on the jejunal serosa 50 cm downstream from the duodenojejunal junction (DJJ). Starting 100 cm from DJJ, a 100-cm long ischemic segment was created by division of all mesenteric vessels. S-mu Ds were applied at 2.5, 5, 20, and 50 cm from the starting point of ischemia by serosal sutures. A standard mu D probe was placed in the abdominal cavity as a further control. Dialysate was harvested before inducing ischemia and subsequently every 20 min for 4 h. Central venous blood was drawn every hour to monitor systemic lactate, C-reactive protein, and white blood cell count. Results: Microdialysis lactate levels were significantly higher than baseline from 20 min on into protocol time in the ischemic segment and in the control S-mu D probe. The peritoneal cavity probe showed no significant elevation. Lactate levels from the ischemic segment reached a plateau at 60 min. Courses of pyruvate, glucose, and glycerol levels were in accordance with transition from an aerobic to anaerobic metabolism in the bowel wall. No statistically significant changes in hemoglobin, white blood cell count, or lactate values in central venous blood were recorded. Conclusions: Assaying the aforementioned compounds in dialysate, harvested by the newly developed S-mu D probe, allowed detection and monitoring of small bowel ischemia from 20 min on following its onset.

  • 181.
    Åkesson, Oscar
    et al.
    Institutionen för Klinisk Vetenskap, Lunds Universitet.
    Falkenback, Dan
    Institutionen för Klinisk Vetenskap, Lunds Universitet.
    Johansson, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Abrahamsson, Pernilla
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Surface Microdialysis Detects Ischemia After Esophageal Resection: An Experimental Animal Study2019Inngår i: Journal of Surgical Research, ISSN 0022-4804, E-ISSN 1095-8673, Vol. 245, s. 537-543Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: After an esophageal resection, continuity is commonly restored by a gastric tube reconstruction and an intrathoracic anastomosis to the remaining proximal esophagus. Ischemia of the anastomotic region is considered to play a pivotal role in anastomotic leakage. Microdialysis (μD) is an excellent method to measure local biochemical substances and parameters in a specific organ or compartment aiming at early detection of ischemia. This animal study evaluates ischemia of the gastric tube reconstruction using a novel method-μD on organ surfaces. This promising method may have the potential to detect an anastomotic leakage before clinical symptoms develop.

    METHODS: Anesthetized normoventilated pigs were used. Surface microdialysis (S-μD) catheters and an intraparenchymal oxygen tension catheter were placed on the stomach. A gastric tube was made and the gastroepiploic artery was divided halfway along the greater curvature to produce severe ischemia at the top of the gastric tube. μD data from four locations (gastric tube, ileum and peritoneal cavity) were recorded every 20 min during the experiment. Tissue samples from all catheter sites underwent histopathological analysis. Intraparenchymal oxygen partial pressure, systemic blood tests, and hemodynamic parameters were recorded.

    RESULTS: S-μD data showed values indicating severe ischemia at the top of the gastric tube and intermediate ischemia at the level of transection of the gastroepiploic artery. Ischemia was verified by histopathological analysis of tissue samples and intraparenchymal oxygen tension data.

    CONCLUSIONS: S-μD can detect and grade severity of local ischemia in real time, in an animal model.

  • 182.
    Öberg, Åke
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Höyhtyä, Matti
    Tavelin, Björn
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Stenling, Roger
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Lindmark, Gudrun
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Limited value of preoperative serum analyses of matrix metalloproteinases (MMP-2, MMP-9) and tissue inhibitors of matrix metalloproteinases (TIMP-1, TIMP-2) in colorectal cancer2000Inngår i: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 20, nr 2B, s. 1085-1091Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    PURPOSE: We studied whether preoperative serum levels of free MMP-2, the MMP-2/TIMP-2 complex, and total amounts of MMP-9, TIMP-1 and TIMP-2 correlated to the tumor stage and prognosis in colorectal cancer.

    METHODS: Samples from 158 patients operated on for colorectal cancer (100 colon, 58 rectum) and samples from 80 healthy blood donors were analyzed using an ELISA technique. One hundred and thirty-three patients were resected for cure, (31, 61, and 41 in Dukes' stages A, B, and C, respectively). At follow-up in January 1998, 44 patients had died from their cancer after a median time 14 months (range 2-55). Fifteen patients died without tumor relapse. Ninety-nine patients were alive after, a median time of 46 months (range 17-68).

    RESULTS: Wide, overlapping ranges were observed for all factors both in the patients and in the control group. The patients as compared to the control group had significantly higher levels of free MMP-2 and total amounts of MMP-9, TIMP-1 and TIMP-2, whereas the level of the MMP-2/TIMP-2 complex was significantly lower. TIMP-1 was significantly higher in Dukes' D compared to Dukes' A-C cases; the other factors did not correlate to tumor stage. Elevated TIMP-2 levels (median cut-off limit), only, correlated to worse prognosis when analysed in all patients (p < 0.05). None of the factors (median cut-off limit) correlated to survival in Dukes' A-C patients; analyses based on the upper quartile cut-off limit demonstrated that elevated MMP-2 levels correlated to shorter survival time (p < 0.05).

    CONCLUSION: Serum analyses of free MMP-2 the MMP-2/TIMP-2 complex and total amounts of MMP-9, TIMP-1 and TIMP-2 are of limited value for tumor staging and prognosis in colorectal cancer.

  • 183.
    Öberg, Åke
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Samii, S
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Stenling, Roger
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Lindmark, Gudrun
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Different occurrence of CD8+, CD45R0+, and CD68+ immune cells in regional lymph node metastases from colorectal cancer as potential prognostic predictors2002Inngår i: International Journal of Colorectal Disease, ISSN 0179-1958, E-ISSN 1432-1262, Vol. 17, nr 1, s. 25-29Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND AND AIMS: To study whether there are differences in the immunohistochemical staining of CD8, CD45R0, and CD68 of immune cells in regional lymph node metastases from colorectal cancer that are of potential interest in prognostic prediction.

    MATERIALS AND METHODS: Analysis of archival specimens from 93 patients operated on for colorectal cancer (based on monoclonal antibodies, the ABC technique, and semiquantitative classification).

    RESULTS: There was a significant difference in survival time between patients with respect to the number of positive immune cells. The cancer-specific 5-year survival rate was 77% for patients with high numbers of CD8+ cells, compared to 33% for those with lower numbers. The corresponding figures for patients with CD45R0+ cells were 66% vs. 33%, and for patients with CD68+ cells 60% vs. 38%. Significant differences remained among the 74 patients without adjuvant radio/chemotherapy regarding CD8 and CD45R0 but not CD68.

    CONCLUSION: The presence of CD8+, CD45R0+, and CD68+ immune cells in regional lymph node metastases may serve as predictors of patients survival in colorectal cancer Dukes' stage C.

  • 184.
    Öberg, Åke
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Stenling, Roger
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Tavelin, Björn
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Lindmark, Gudrun
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Are lymph node micrometastases of any clinical significance in Dukes' stages A and B colorectal cancer?1998Inngår i: Diseases of the Colon & Rectum, ISSN 0012-3706, E-ISSN 1530-0358, Vol. 41, nr 10, s. 1244-1249Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    PURPOSE: The aim was to investigate the significance of lymph node micrometastases in Dukes Stages A and B colorectal cancer.

    METHODS: Archival specimens were examined from 147 patients (96 colon, 51 rectum; 44 Stage A, 103 Stage B) who had surgery between 1987 and 1994. One lymph node section from each node (colon, 1-11; median, 4; rectum, 1-15; median, 3) was examined with use of an anticytokeratin antibody.

    RESULTS: Forty-seven (32 percent) patients had micrometastases. At follow-up in June 1996, 23 patients had died of cancer or with known tumor relapse, after a median time of 28 (range, 5-67) months; 8 of 47 (17 percent) patients had micrometastases, 15 of 100 (15 percent) did not. No statistically significant differences were observed according to micrometastases when the results were analyzed with respect to Dukes stage or survival time. The median survival time of living patients with micrometastases was 48 (range, 18-97) months, and for patients without micrometastases, 48 (range, 19-111) months. Six of 96 living patients had a tumor relapse; three of these displayed micrometastases.

    CONCLUSION: Lymph node micrometastases are not a useful prognostic marker in Dukes Stages A and B and do not imply different strategies for additional therapy or follow-up.

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