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  • 901. Zamora-Ros, Raul
    et al.
    Rinaldi, Sabina
    Biessy, Carine
    Tjonneland, Anne
    Halkjaer, Jytte
    Fournier, Agnes
    Boutron-Ruault, Marie-Christine
    Mesrine, Sylvie
    Tikk, Kaja
    Fortner, Renee T.
    Boeing, Heiner
    Foerster, Jana
    Trichopoulou, Antonia
    Trichopoulos, Dimitrios
    Papatesta, Eleni-Maria
    Masala, Giovanna
    Tagliabue, Giovanna
    Panico, Salvatore
    Tumino, Rosario
    Polidoro, Silvia
    Peeters, Petra H. M.
    Bueno-de-Mesquita, H. B(as)
    Weiderpass, Elisabete
    Lund, Eiliv
    Argueelles, Marcial
    Agudo, Antonio
    Molina-Montes, Esther
    Navarro, Carmen
    Barricarte, Aurelio
    Larranaga, Nerea
    Manjer, Jonas
    Almquist, Martin
    Sandström, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Hennings, Joakim
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Tsilidis, Konstantinos K.
    Schmidt, Julie A.
    Khaw, Kay-Thee
    Wareham, Nicholas J.
    Romieu, Isabelle
    Byrnes, Graham
    Gunter, Marc J.
    Riboli, Elio
    Franceschi, Silvia
    Reproductive and menstrual factors and risk of differentiated thyroid carcinoma: The EPIC study2015Inngår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 136, nr 5, s. 1218-1227Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Differentiated thyroid carcinoma (TC) is threefold more common in women than in men and, therefore, a role of female hormones in the etiology of differentiated TC has been suggested. We assessed these hypotheses in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Among 345,157 women (mean age 51) followed for an average of 11 years, 508 differentiated TC cases were identified. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression models. No significant associations were observed between differentiated TC risk and number of pregnancies, breast feeding, menopausal status, and age at menarche and at menopause. Significant associations were found with history of infertility problems (HR 1.70; 95% CI 1.12-2.60), a recent pregnancy (HR for 5 vs. >5 years before recruitment 3.87; 95% CI 1.43-10.46), menopause type (HR for surgical vs. natural menopause: 2.16; 95% CI 1.41-3.31), oral contraceptive (OC) use at recruitment (HR: 0.48; 95% CI 0.25-0.92) and duration of OC use (HR for 9 vs. 1 year: 0.66; 95% CI: 0.50-0.89). An increased risk was also found with hormone replacement therapy use at recruitment (HR=1.30, 95% CI 1.02-1.67), but this was not significant after adjustment for type of menopause (HR=1.22, 95% CI 0.95-1.57). Overall, our findings do not support a strong role of reproductive and menstrual factors, and female hormone use in the etiology of differentiated TC. The few observed associations may be real or accounted for by increased surveillance in women who had infertility problems, recent pregnancies or underwent surgical menopause.

  • 902. Zamora-Ros, Raul
    et al.
    Rinaldi, Sabina
    Tsilidis, Konstantinos K.
    Weiderpass, Elisabete
    Boutron-Ruault, Marie-Christine
    Rostgaard-Hansen, Agnetha Linn
    Tjonneland, Anne
    Clavel-Chapelon, Francoise
    Mesrine, Sylvie
    Katzke, Verena A.
    Kuehn, Tilman
    Foerster, Jana
    Boeing, Heiner
    Trichopoulou, Antonia
    Lagiou, Pagona
    Klinaki, Eleni
    Masala, Giovanna
    Sieri, Sabina
    Ricceri, Fulvio
    Tumino, Rosario
    Mattiello, Amalia
    Peeters, Petra H. M.
    Bueno-de-Mesquita, H. B(as)
    Engeset, Dagrun
    Skeie, Guri
    Argueelles, Marcial
    Agudo, Antonio
    Sanchez, Maria-Jose
    Chirlaque, Maria-Dolores
    Barricarte, Aurelio
    Chamosa, Saioa
    Almquist, Martin
    Tosovic, Ada
    Hennings, Joakim
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Sandström, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Schmidt, Julie A.
    Khaw, Kay-Thee
    Wareham, Nicholas J.
    Cross, Amanda J.
    Slimani, Nadia
    Byrnes, Graham
    Romieu, Isabelle
    Riboli, Elio
    Franceschi, Silvia
    Energy and macronutrient intake and risk of differentiated thyroid carcinoma in the European Prospective Investigation into Cancer and Nutrition study2016Inngår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 138, nr 1, s. 65-73Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Incidence rates of differentiated thyroid carcinoma (TC) have increased in many countries. Adiposity and dietary risk factors may play a role, but little is known on the influence of energy intake and macronutrient composition. The aim of this study was to investigate the associations between TC and the intake of energy, macronutrients, glycemic index (GI) and glycemic load in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The study included 477,274 middle-age participants (70.2% women) from ten European countries. Dietary data were collected using country-specific validated dietary questionnaires. Total carbohydrates, proteins, fats, saturated, monounsaturated and polyunsaturated fats (PUFA), starch, sugar, and fiber were computed as g/1,000 kcal. Multivariable Cox regression was used to calculate multivariable adjusted hazard ratios (HR) and 95% confidence interval (CI) by intake quartile (Q). After a mean follow-up time of 11 years, differentiated TC was diagnosed in 556 participants (90% women). Overall, we found significant associations only with total energy (HRQ4vs.Q1, 1.29; 95% CI, 1.00-1.68) and PUFA intakes (HRQ4vs.Q1, 0.74; 95% CI, 0.57-0.95). However, the associations with starch and sugar intake and GI were significantly heterogeneous across body mass index (BMI) groups, i.e., positive associations with starch and GI were found in participants with a BMI25 and with sugar intake in those with BMI<25. Moreover, inverse associations with starch and GI were observed in subjects with BMI<25. In conclusion, our results suggest that high total energy and low PUFA intakes may increase the risk of differentiated TC. Positive associations with starch intake and GI in participants with BMI25 suggest that those persons may have a greater insulin response to high starch intake and GI than lean people. What's New? The role of lifestyle factors in the growing numbers of thyroid cancer remains unclear. Here, the authors uncover associations with high total energy intake and low consumption of polyunsaturated fatty acids in a large European cohort (EPIC). They further find positive associations with starch intake and glycemic index only in people with a body mass index equal or larger than 25, possibly implicating an altered insulin response in the etiology of this cancer.

  • 903.
    Zhao, Ying
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi. Umeå Heart Centre.
    Lindqvist, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi. Umeå Heart Centre.
    Holmgren, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi. Umeå Heart Centre.
    Henein, Michael Y
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi. Umeå Heart Centre.
    Accentuated left ventricular lateral wall function compensates for septal dyssynchrony after valve replacement for aortic stenosis2013Inngår i: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 164, nr 3, s. 339-344Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: The interventricular septal motion becomes reversed after aortic valve replacement (AVR) for aortic stenosis (AS) despite maintained stroke volume (SV). We hypothesis that left ventricular (LV) lateral wall compensates for such disturbances, in order to secure normal SV. METHODS: We studied 29 severe AS patients (age 63±11years, 18 males) with normal ejection fraction (EF) before, 6months and 12months after AVR and compared them with 29 age- and gender-matched controls, using speckle tracking echocardiography. RESULTS: In patients, the LVEF and SV remained unchanged throughout. Before AVR, the septal radial motion, septal and lateral strain were reduced (p<0.001). Peak septal and lateral displacements, times from QRS to peak displacement were all not different from controls. Six months after AVR, septal radial motion reversed (p<0.001), lateral strain increased (p<0.05), peak septal displacement reduced (p<0.01) while lateral displacement increased (p<0.05). Time to peak septal displacement delayed (p<0.01) in contrast to lateral displacement which became early (p<0.05), resulting in a significant septal-lateral time delay (p<0.01). The accentuation of LV lateral wall correlated with septal displacement time delay (r=0.60, p<0.001) and septal-lateral time delay (r=0.64, p<0.001). SV correlated with lateral displacement (r=0.39, p<0.05). The systolic strain was correlated with opposite wall displacement (p<0.05 for both). There was no correlation between these measurements before and 12month after AVR. CONCLUSIONS: Accentuated lateral wall displacement compensates for septal dyssynchrony in order to maintain normal LVEF and SV. The continuing recovery of these disturbances 12months after complete mass regression suggests an ongoing reverse remodeling.

  • 904.
    Zhao, Ying
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Lindqvist, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Nilsson, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Holmgren, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Näslund, Ulf
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Henein, Michael Y
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Trans-catheter aortic valve implantation: early recovery of left and preservation of right ventricular function2011Inngår i: Interactive Cardiovascular and Thoracic Surgery, ISSN 1569-9293, E-ISSN 1569-9285, Vol. 12, nr 1, s. 35-39Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    This study aimed to assess the early effect of trans-catheter aortic valve implantation (TAVI) on right (RV) and left ventricular (LV) function in severe aortic stenosis (AS) patients. Twenty AS patients (age 79±6 years) were examined before, one week and six weeks after TAVI using Doppler echocardiography. LV ejection fraction (EF), long-axis [mitral annular plane systolic excursion (MAPSE)] and RV long-axis [tricuspid annular plane systolic excursion (TAPSE)] function, septal radial motion were studied. Results were compared with 30 AS patients before and one week after aortic valve replacement (AVR) as well as 30 normals (reference group). Before TAVI, LVEF was reduced and E/A was higher than the reference and AVR groups (P<0.05 for all). MAPSE, TAPSE and septal motion were equally reduced in TAVI and AVR patients (P<0.05 for all). One week after the TAVI, EF increased in patients with values <50% before the procedure. In contrast, AVR resulted in reversed septal motion (P<0.001) and depressed TAPSE (P<0.001). The extent of reversed septal motion correlated with that of TAPSE in the patients group as a whole after procedures (r=0.78, P<0.001). Six weeks after TAVI, RV function remained unchanged, but LVEF increased and E/A decreased (P<0.05 for both). Thus, TAVI procedure results in significant early improvement of LV systolic and diastolic function particularly in patients with reduced EF and preserves RV systolic function.

  • 905. Zheng, Jiaojiao
    et al.
    Rutegård, Martin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi. Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM).
    Santoni, Giola
    Wallner, Bengt
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Johansson, Ingegerd
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Tandläkarutbildning.
    Sund, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Xie, Shao-Hua
    Lagergren, Jesper
    Prediabetes and diabetes in relation to risk of gastric adenocarcinoma2019Inngår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 120, nr 12, s. 1147-1152Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Whether prediabetes or diabetes increases the risk of gastric adenocarcinoma is not clear.

    Methods: This cohort study included 111,198 participants in the Northern Swedish Health and Disease Study. The participants were followed up from November 1985 to April 2017. The exposure to prediabetes or diabetes was assessed by oral glucose tolerance tests and self-reports. The incidence of the outcome gastric adenocarcinoma was identified from the Swedish Cancer Registry. Multivariable Cox regressions were used to analyse the associations between prediabetes or diabetes and the risk of gastric adenocarcinoma, providing hazard ratios (HR) with 95% confidence intervals (CI), with adjustment for sex, age, calendar year, body mass index, tobacco smoking and education level.

    Results: Compared with normoglycaemic participants, the risk of gastric adenocarcinoma was not increased among participants with prediabetes (HR 1.07, 95% CI 0.79–1.44), diabetes (HR 0.77, 95% CI 0.46–1.29) or any of these exposures (HR 0.96, 95% CI 0.73–1.27). No associations were identified between prediabetes or diabetes and the risk of gastric adenocarcinoma in stratified analyses or in analyses separating cardia and non-cardia gastric adenocarcinoma.

    Conclusions: This study does not support the hypothesis that prediabetes or diabetes increases the risk of gastric adenocarcinoma.

  • 906.
    Åberg, Torkel
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Symposium for the future of cardiac surgery. Working group report. If retreat, how?2004Inngår i: European Journal of Cardio-Thoracic Surgery, ISSN 1010-7940, E-ISSN 1873-734X, Vol. 26, nr Suppl 1, s. S72-S73Artikkel i tidsskrift (Annet (populærvitenskap, debatt, mm))
  • 907.
    Åberg, Torkel
    et al.
    Umeå universitet, Medicinsk fakultet, Kirurgisk och perioperativ vetenskap, Kirurgi.
    Hentschel, J
    Engström, Karl Gunnar
    Umeå universitet, Medicinsk fakultet, Kirurgisk och perioperativ vetenskap, Kirurgi.
    Nio års registrering vid hjärtcentrum visar att medicinska resultat förbättrats2004Inngår i: Läkartidningen, Vol. 102, s. 26-29Artikkel i tidsskrift (Fagfellevurdert)
  • 908.
    Åberg, Torkel
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Hentschel, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Improved total quality by monitoring of a cardiothoracic unit. Medical, administrative and economic data followed for 9 years.2004Inngår i: Interactive Cardiovascular and Thoracic Surgery, ISSN 1569-9293, E-ISSN 1569-9285, Vol. 3, nr 1, s. 33-40Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    To describe monitoring of a cardio-thoracic department from a total quality aspect point of view and to follow the development over 9 years. During the time period 1994-2002 a total of 10,828 cardio-thoracic operations were performed. Capacity, demographic, risk, quality, outcome and economic data were prospectively collected in various registries and analysed. Mean (and median) age increased from 64.2 to 65.3 (66-67). Patients above 70 years increased from 33.6 to 38.7% and above 80 from 2.9 to 5.5%. Operative mortality was unchanged over the time periods at slightly over 2%, with 1-year mortality 6-7%. Mortality for primary, elective coronary artery bypass grafting was 0.26% during the last 3 years. The rate of postoperative complications remained unchanged or decreased with few exceptions: Patients with postoperative confusion increased from 5.0 to 8.1% and patients with a need for face mask ventilation increased from 2.4 to 4.0%. Mean postoperative ventilation time was unchanged at around 22 h, whereas the median decreased from 9.5 to 5.3 h. The workload created by elderly patients was especially noticeable in the intensive care unit (ICU) as both number of postoperative deviations and ICU hours increased as a function of age. Cost per operation decreased by 11%. Total medical rationalisation was higher as salaries increased over time. Mean length of stay decreased by 3 days. Hospital staff hours per operation decreased whereas hospital staff hours per patient hour increased. Physician cost per operation was unchanged. Patient, staff and referring physician satisfaction was high. Several areas for improvement have been found. Monitoring and general feedback of total quality factors has shown itself a powerful tool to detect and follow large and subtle changes in the practice of cardio-thoracic surgery. Most followed factors show improvement in spite of an increase in mean and median age. Several areas may be defined where further development might decrease the trauma to the patient. Aiming at a total quality and patient safety system, monitoring is an essential prerequisite.

  • 909.
    Åden Bygdell, Simon
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    PSA-density; usefulness in lowering the numbers diagnosed with low risk prostate cancer2016Independent thesis Basic level (professional degree), 20 poäng / 30 hpOppgave
  • 910.
    Åhman, Sara
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Rehabiliteringsmedicin.
    Saveman, Britt-Inger
    Umeå universitet, Medicinska fakulteten, Institutionen för omvårdnad. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Styrke, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Björnstig, Ulf
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Stålnacke, Britt-Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Rehabiliteringsmedicin.
    Long-term follow-up of patients with mild traumatic brain injury: a mixed-methods study2013Inngår i: Journal of Rehabilitation Medicine, ISSN 1650-1977, E-ISSN 1651-2081, Vol. 45, nr 8, s. 758-764Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: To characterize the long-term consequences of mild traumatic brain injury regarding post-concussion symptoms, post-traumatic stress, and quality of life; and to investigate differences between men and women.

    DESIGN: Retrospective mixed-methods study.Subjects/patients and methods: Of 214 patients with mild traumatic brain injury seeking acute care, 163 answered questionnaires concerning post-concussion symptoms (Rivermead Post-Concussion Symptoms Questionnaire; RPQ), post-traumatic stress (Impact of Event Scale; IES), and quality of life (Short Form Health Survey; SF-36) 3 years post-injury. A total of 21 patients underwent a medical examination in connection with the survey. The patients were contacted 11 years later, and 10 were interviewed. Interview data were analysed with content analysis.

    RESULTS: The mean total RPQ score was 12.7 (standard deviation; SD 12.9); 10.5 (SD 11.9) for men and 15.9 (SD 13.8) for women (p = 0.006). The 5 most common symptoms were fatigue (53.4%), poor memory (52.5%), headache (50.9%), frustration (47.9%) and depression (47.2%). The mean total IES score was 9.6 (SD 12.9) 7.1 (SD 10.3) for men and 13.0 (SD 15.2) for women (p = 0.004). In general, the studied population had low scores on the Short Form Health Survey (SF-36). The interviews revealed that some patients still had disabling post-concussion symptoms and consequences in many areas of life 11 years after the injury event.

    CONCLUSION: Long-term consequences were present for approximately 50% of the patients 3 years after mild traumatic brain injury and were also reported 11 years after mild traumatic brain injury. This needs to be taken into account by healthcare professionals and society in general when dealing with people who have undergone mild traumatic brain injury.

  • 911.
    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.

  • 912.
    Öberg, Åke
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi. Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Immunologi/immunkemi.
    Prognostic factors in colorectal cancer: aspects of tumour dissemination2002Doktoravhandling, med artikler (Annet vitenskapelig)
  • 913.
    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.

  • 914.
    Öberg, Åke
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Lindmark, Gudrun
    Department of Surgery, Helsingborgs Lasarett, Lund University, Helsingborg, Sweden.
    Israelsson, Anne CE
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Immunologi/immunkemi.
    Hammarström, Sten G
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Immunologi/immunkemi.
    Hammarström, Marie-Louise KC
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Immunologi/immunkemi.
    Detection of occult tumour cells in lymph nodes of colorectal cancer patients using real-time quantitative RT-PCR for CEA and CK20 mRNAS2004Inngår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 111, nr 1, s. 101-110Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The purpose of our study was to develop specific, sensitive, objective assays for early detection of disseminated tumour cells in patients with colorectal cancer (CRC). Carcinoembryonic antigen (CEA) and cytokeratin 20 (CK20) were chosen as markers because they are selectively expressed in epithelial cells with maintained expression in CRC. Real-time quantitative RT-PCR assays with RNA copy standards were constructed. Regional lymph nodes were collected from patients with CRC (n = 51) and benign intestinal disease (n = 10). Results were compared to routine histopathology and anti-CEA immunohistochemistry. Lymph node levels of CEA and CK20 mRNA correlated strongly (p < 0.0001, r = 0.8). Lymph nodes from non-CRC patients had <0.01 CEA and <0.001 CK20 mRNA copies/18S rRNA unit. Lymph nodes from 3/6 Dukes' A, 17/26 Dukes' B, 10/10 Dukes' C and 7/9 Dukes' D patients had CEA mRNA levels above cut-off. Corresponding figures for CK20 mRNA were 3/6, 10/26, 9/10 and 5/9, respectively. CEA mRNA levels varied from 0.001 to 100 copies/18S rRNA unit in Dukes' A and B, and 50% of the Dukes' B patients had CEA mRNA levels within the range of Dukes' C patients. Three Dukes' B patients have died from CRC or developed distant metastases. All 3 had high CEA and CK20 mRNA levels. Determination of mRNA was superior to immunohistochemistry in showing CEA expression in lymph nodes. The present qRT-PCR assay for CEA mRNA seems to be a superior tool to identify individuals with disseminated tumour cells. Future extended studies will establish the clinically most relevant cut-off level.

  • 915.
    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.

  • 916.
    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.

  • 917.
    Ödling Davidsson, Fredrik
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Johagen, Daniel
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Appelblad, Micael
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Svenmarker, Staffan
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Reversal of Heparin After Cardiac Surgery: Protamine Titration Using a Statistical Model2015Inngår i: Journal of Cardiothoracic and Vascular Anesthesia, ISSN 1053-0770, E-ISSN 1532-8422, Vol. 29, nr 3, s. 710-714Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: To establish a statistical model for determination of protamine dose in conjunction with cardiopulmonary bypass. Design: Prospective.

    Setting: University hospital.

    Participants: Ninety consecutive cardiac surgical patients.

    Interventions: None.

    Measurements and Main Results: A series of clinically oriented variables were introduced into a statistical model for projection of the protamine dose after cardiopulmonary bypass. The following significant predictors were identified using multivariable regression analysis: The patient's body surface area, the administered dose of heparin, heparin clearance, and the preoperative platelet count. The statistical model projected the protamine dose within 3 +/- 23 mg of the point-of-care test used as reference.

    Conclusion: Protamine dosing based on statistical modeling represents an alternative to point-of-care tests.

  • 918.
    Öhlund, Daniel
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Basement membrane collagens in pancreatic cancer: novel stroma-derived tumor markers and regulators of cancer cell growth2010Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Background: Among the common malignancies, pancreatic cancer has the shortest long-term survival. The aggressive, rapid, and infiltrative growth pattern of pancreatic cancer, together with the lack of specific symptoms, often leads to late diagnosis. Metastases are frequently found at the time of diagnosis, which prevents curative surgical treatment. Good tumor markers would enable early detection, thus improving the prognosis. Unfortunately, no such markers are available in the clinic.

    The tumor stroma is defined as the non-malignant cells and the extracellular matrix (ECM) of a cancer. Pancreatic cancer is characterized by an abundant tumor stroma, rich in ECM proteins such as collagens, which have been shown to play important roles in tumor progression. Furthermore, pancreatic cancer cells produce large quantities of ECM proteins, especially the basement membrane (BM) protein type IV collagen. All epithelial cells are anchored to a BM, which must be degraded in order for an in situ cancer to become invasive. Matrix metalloproteinases (MMPs) are enzymes involved in BM degradation.

    In this thesis, the tumor stroma of pancreatic cancer is studied, focusing on the BM proteins type IV and type XVIII collagen, with the aim to clarify if the stroma could be a source of novel tumor markers for this form of cancer. Additionally, the role of type IV collagen produced by the cancer cells is studied.

    Methods: Expression patterns of type IV and type XVIII collagen, MMPs involved in collagen degradation, and collagen receptors (integrins) were studied by immunoflourescence in both normal and pancreatic cancer tissue, and in pancreatic cancer cell lines. Circulating plasma levels of type IV and type XVIII collagen and conventional tumor markers (TPS, Ca 19-9, CEA and Ca 125) were measured in controls and pancreatic cancer patients at the time of diagnosis and after treatment.

    The role of cancer cell produced type IV collagen was studied in human pancreatic cancer cell lines by functional blocking of integrin receptors (integrin a1, a2 and b1) and integrin-binding sites on type IV collagen, and by siRNA-induced down-regulation of type IV collagen synthesis. Proliferation was analyzed by a luminescence based cell viability assay, migration by time-lapse microscopy, and apoptosis by M30-neoepitope detection.

    Results: MMPs involved in BM degradation were upregulated in pancreatic cancer tissue. The expression of type XVIII collagen shifted from a general BM expression pattern in normal tissue, to mainly being found in the tumor vasculature in pancreatic cancer. Type IV collagen, on the other hand, remained highly expressed in the vicinity of the cancer cells. The a1, a2, and b1 integrin receptors were highly expressed at the cancer cell surface.

    Both down-regulation of type IV collagen synthesis and blocking the integrin/type IV collagen interaction decreased cell proliferation and migration. The proliferative capacity was rescued by the addition of exogenous type IV collagen.

    Furthermore, the circulating levels of both type IV and type XVIII collagen were increased in pancreatic cancer patients at the time of diagnosis compared to controls. After treatment, the levels were normalized for type XVIII collagen, whereas the levels of type IV collagen remained high after surgery. High postoperative levels of type IV collagen were associated with short overall survival. A similar association to short survival was found for preoperative type XVIII collagen levels. No such associations to survival could be detected for the conventional markers.

     

    Conclusion: The results of this thesis show that type IV and type XVIII collagens can serve as tumor markers for pancreatic cancer with advantages compared to conventionally used markers. Additionally, evidence is provided of an autocrine loop, involving type IV collagen and its integrin receptors, with importance for retaining a proliferative and migratory phenotype in pancreatic cancer cells.

  • 919.
    Öhlund, Daniel
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi. Cold Spring Harbor Laboratory and Lustgarten Foundation Pancreatic Cancer Research Laboratory, Cold Spring Harbor, NY 11724.
    Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer2017Inngår i: Journal of Experimental Medicine, ISSN 0022-1007, E-ISSN 1540-9538, Vol. 214, nr 3, s. 579-596Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Pancreatic stellate cells (PSCs) differentiate into cancer-associated fibroblasts (CAFs) that produce desmoplastic stroma, thereby modulating disease progression and therapeutic response in pancreatic ductal adenocarcinoma (PDA). However, it is unknown whether CAFs uniformly carry out these tasks or if subtypes of CAFs with distinct phenotypes in PDA exist. We identified a CAF subpopulation with elevated expression of a-smooth muscle actin (alpha SMA) located immediately adjacent to neoplastic cells in mouse and human PDA tissue. We recapitulated this finding in co-cultures of murine PSCs and PDA organoids, and demonstrated that organoid-activated CAFs produced desmoplastic stroma. The co-cultures showed cooperative interactions and revealed another distinct subpopulation of CAFs, located more distantly from neoplastic cells, which lacked elevated aSMA expression and instead secreted IL6 and additional inflammatory mediators. These findings were corroborated in mouse and human PDA tissue, providing direct evidence for CAF heterogeneity in PDA tumor biology with implications for disease etiology and therapeutic development.

  • 920.
    Öhlund, Daniel
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Ardnor, Bjarne
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Öman, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Naredi, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Sund, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Expression pattern and circulating levels of endostatin in patients with pancreas cancer2008Inngår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 122, nr 12, s. 2805-2810Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Endostatin is a potent inhibitor of angiogenesis that is cleaved from the basement membrane protein type XVIII collagen. Expression of endostatin has recently been shown by Western blot analysis of tissue lysates in normal pancreas and pancreas cancer tissue. We show here that the expression pattern of type XVIII collagen/endostatin is shifted from a general basement membrane staining and is mainly located in the vasculature during tumor progression. This shift in type XVIII collagen/endostatin expression pattern coincides with an up-regulation of MMPs involved in endostatin processing in the tumor microenvironment, such as MMP-3, MMP-9 and MMP-13. The circulating levels of endostatin was analyzed in patients with pancreas cancer and compared to that of healthy controls, as well as after surgical treatment or in a group of nonoperable patients after intraperitoneal fluorouracil (5-FU) chemotherapy. The results show that patients with pancreas cancer have increased circulating levels of endostatin and that these levels are normalized after surgery or intraperitoneal chemotherapy. These findings indicate that endostatin could be used as a biomarker for pancreas cancer progression.

  • 921.
    Öhlund, Daniel
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Franklin, Oskar
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Lundberg, Erik
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Lundin, Christina
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Sund, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Type IV collagen enhances pancreatic cancer cell proliferation and migration through an autocrine loopManuskript (preprint) (Annet vitenskapelig)
  • 922.
    Öhlund, Daniel
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Franklin, Oskar
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Lundberg, Erik
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Lundin, Christina
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Sund, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Type IV collagen stimulates pancreatic cancer cell proliferation, migration, and inhibits apoptosis through an autocrine loop2013Inngår i: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 13, artikkel-id 154Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Pancreatic cancer shows a highly aggressive and infiltrative growth pattern and is characterized by an abundant tumor stroma known to interact with the cancer cells, and to influence tumor growth and drug resistance. Cancer cells actively take part in the production of extracellular matrix proteins, which then become deposited into the tumor stroma. Type IV collagen, an important component of the basement membrane, is highly expressed by pancreatic cancer cells both in vivo and in vitro. In this study, the cellular effects of type IV collagen produced by the cancer cells were characterized.

    Methods: The expression of type IV collagen and its integrin receptors were examined in vivo in human pancreatic cancer tissue. The cellular effects of type IV collagen were studied in pancreatic cancer cell lines by reducing type IV collagen expression through RNA interference and by functional receptor blocking of integrins and their binding-sites on the type IV collagen molecule.

    Results: We show that type IV collagen is expressed close to the cancer cells in vivo, forming basement membrane like structures on the cancer cell surface that colocalize with the integrin receptors. Furthermore, the interaction between type IV collagen produced by the cancer cell, and integrins on the surface of the cancer cells, are important for continuous cancer cell growth, maintenance of a migratory phenotype, and for avoiding apoptosis.

    Conclusion: We show that type IV collagen provides essential cell survival signals to the pancreatic cancer cells through an autocrine loop.

  • 923.
    Öhlund, Daniel
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Lundin, Christina
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Ardnor, Bjarne
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Öman, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Naredi, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Sund, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Type IV collagen is a tumour stroma-derived biomarker for pancreas cancer2009Inngår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 101, nr 1, s. 91-97Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Pancreas cancer is a dreaded disease with high mortality, despite progress in surgical and oncological treatments in recent years. The field is hampered by a lack of good prognostic and predictive tumour biomarkers to be used during follow-up of patients.

    METHODS: The circulating level of type IV collagen was measured by ELISA in pancreas cancer patients and controls. The expression pattern of type IV collagen in normal pancreas, pancreas cancer tissue and in pancreas cancer cell lines was studied by immunofluorescence and Western blot techniques.

    RESULTS: Patients with pancreas cancer have significantly increased circulating levels of type IV collagen. In pancreas cancer tissue high levels of type IV collagen expression was found in close proximity to cancer cells in the tumour stroma. Furthermore, pancreas cancer cells were found to produce and secrete type IV collagen in vitro, which in part can explain the high type IV collagen expression observed in pancreas cancer tissue, and the increased circulating levels in pancreas cancer patients. Of clinical importance, our results show that the circulating level of type IV collagen after surgery is strongly related to prognosis in patients treated for pancreas cancer by pancreatico-duodenectomy with curative intent. Persisting high levels of circulating type IV collagen after surgery indicates a quick relapse in disease and poor survival.

    CONCLUSION: Our results most importantly show that stroma related substances can be evaluated as potential cancer biomarkers, and thereby underline the importance of the tumour microenvironment also in this context.

  • 924.
    Öhlund, Daniel
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Lundin, Christina
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Öman, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Naredi, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Sund, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Basement membrane fragments as pancreatic tumour markers: a comparison to conventional markersManuskript (preprint) (Annet vitenskapelig)
  • 925.
    Öman, Mikael
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Fredriksson, Rikard
    Bylund, Per-Olof
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Björnstig, Ulf
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Analysis of the mechanism of injury in non-fatal vehicle-to-pedestrian and vehicle-to-bicyclist frontal crashes in Sweden2016Inngår i: International Journal of Injury Control and Safety Promotion, ISSN 1745-7300, E-ISSN 1745-7319, Vol. 23, nr 4, s. 405-412Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The aim of this paper is to analyse and compare injuries and injury sources in pedestrian and bicyclist non-fatal real-life frontal passengercar crashes, considering in what way pedestrian injury mitigation systems also might be adequate for bicyclists. Data from 203 non-fatal vehicle-to-pedestrian and vehicle-to-bicyclist crashes from 1997 through 2006 in a city in northern Sweden were analysed by use of the hospitals injury data base in addition to interviews with the injured. In vehicle-to-pedestrian crashes (n = 103) head and neck injuries were in general due to hitting the windscreen frame, while in vehicle-to-bicycle crashes (n = 100) head and neck injuries were typically sustained by ground impact. Abdominal, pelvic and thoracic injuries in pedestrians and thoracic injuries in bicyclists were in general caused by impacting the bonnet. In vehicle-to-pedestrian crashes, energy reducing airbags at critical impact points with low yielding ability on the car, as the bonnet and the windscreen frame, might reduce injuries. As vehicle-to-bicyclist crashes occurred mostly in good lighting conditions and visibility and the ground impact causing almost four times as many injuries as an impact to the different regions of the car, crash avoidance systems as well as separating bicyclists from motor traffic, may contribute to mitigate these injuries.

  • 926.
    Öman, Mikael
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Lundqvist, Stefan
    Gustavsson, Bengt
    Hafström, Lars-Olof
    Naredi, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Phase I/II trial of intraperitoneal 5-Fluorouracil with and without intravenous Vasopressin in non-resectable pancreatic cancer2005Inngår i: Cancer Chemotherapy and Pharmacology, ISSN 0344-5704, E-ISSN 1432-0843, Vol. 56, nr 6, s. 603-609Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Systemic palliative treatment with chemotherapy against advanced pancreas cancer has low effectiveness despite considerable toxicity. Aim: To investigate the safety, toxicity and tumour response of intraperitoneal 5-Fluorouracil (5-FU) with intravenous Leucovorin and to monitor 5-FU pharmacokinetics in plasma during intraperitoneal instillation with and without vasopressin in patients with non-resectable pancreas cancer. Patients/methods: Between 1994 and 2003, 68 patients with non-resectable pancreas cancer TNM stage III and IV, were enrolled to receive intraperitoneal 5-FU instillation 750–1500 mg/m2 and intravenous Leucovorin 100 mg/m2 for two days every third week. Tumour response, performance status and toxicity were recorded. Seventeen patients were also treated with intravenous vasopressin 0.1 IU/minute for 180 minutes, during intraperitoneal 5-FU instillation. Area under the curve (AUC) and peak concentration (Cmax) of 5-FU in plasma were analysed. Results: The treatment was well tolerated with minor toxicity. One complete response (54.1+ months) and 2 partial responses were observed. Time to progression was 4.4 months (0.8–54.1+), and median survival was 8.0 months (0.8–54.1+). There was a significant reduction of 5-FU Cmax in plasma the second day of treatment if vasopressin was used (3.4 ± 2.5 and 6.1 ± 5.4 μmol/l, respectively, p<0.05). 5-FU AUC in plasma was not significantly affected by vasopressin either day of treatment. Conclusion: Intraperitoneal 5-FU is a safe treatment with low toxicity to patients with non-resectable pancreas cancer. Tumour response was 4.4% and median survival time 8.0 months. Addition of vasopressin did not significantly decrease plasma 5-FU AUC but reduced Cmax on day 2 of treatment.

  • 927.
    Öman, Mikael
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Tölli, Jukka
    Blind, Per-Jonas
    Naredi, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Hafström, Lars-Olof
    133Xe clearance estimates the effect of vasopressin on peritoneal blood flow in rats2004Inngår i: Hepato-Gastroenterology, ISSN 0172-6390, Vol. 51, nr 58, s. 1037-1041Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND/AIMS: When assessing the peritoneal microcirculation with invasive methods, interference with the mechanisms of vaso-regulation may occur. The 133Xe clearance technique renders the possibility, by minimal invasiveness, to estimate the influence of a vasoactive agent on the peritoneal microcirculation. METHODOLOGY: Ten to 15MBq of 133Xe were injected in the abdominal cavity in thirty-eight Wistar-FU (W-FU) rats and 35 Lister-Hooded (LH) rats. A NaI (Tl)-scintillation detector registered activity before and during vasopressin infusion. Gamma camera imaging confirmed the washout from the abdominal cavity. The laser Doppler flowmetry technique was used as a comparison. RESULTS: Vasopressin at 0.07 IU/kg/min IV significantly reduced 133Xe-clearance by 37% (p = 0.029) and 52% (p=0.036) and laser Doppler flowmetry by 69% (p=0.0019) and 44% (p=0.0039) in W-FU and LH rats, respectively. A linear correlation between dose of vasopressin and relative decrease in 133Xe clearance was demonstrated in the W-FU rat model (r2=0.98, p=0.023). The 133Xe clearance from the abdominal cavity in rat using a single-compartment model or the slow compartment in a double-compartment model gave reproducible information. CONCLUSIONS: The usefulness of this mini-invasive technique for sequential measurements before and during intervention will render the 133Xe clearance suitable for assessment of blood flow changes in the abdominal cavity.

  • 928.
    Öman, Mikael
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Tölli, Jukka
    Naredi, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Hafström, Lars-Olof
    Effect of carcinomatosis and intraperitoneal 5-fluorouracil on peritoneal blood flow modulated by vasopressin in the rat as measured with the 133Xe-clearance technique2004Inngår i: Cancer Chemotherapy and Pharmacology, ISSN 0344-5704, E-ISSN 1432-0843, Vol. 54, nr 3, s. 213-218Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose: Intraperitoneal administration of 5-fluorouracil for the treatment of gastrointestinal malignancies results in a greater total drug exposure in the peritoneal fluid than in plasma. Drugs are eliminated from the peritoneal cavity mainly by capillaries leading to the portal venous system and to a lesser extent by lymphatics. The drug itself and the presence of peritoneal carcinomatosis may affect elimination of the drug. The 133Xe-clearance technique allows the influence of a vasoactive agent on the peritoneal blood flow to be estimated with minimal invasiveness. The aim of the present study was to explore whether intraperitoneal 5-FU or peritoneal carcinomatosis affects the peritoneal blood flow and its reactivity to intravenous vasopressin, as measured indirectly with the 133Xe-clearance technique. Methods: The animals used in this study were 63 Wistar-Fu (W-Fu) rats and 67 Lister-Hooded (LH) rats. On day 0, either 5-FU at 25 mg/kg body weight in 25 ml/kg isotonic saline was instilled intraperitoneally, or 1·105 syngeneic tumour cells were inoculated intraperitoneally. On days 1, 2 and 3 in the 5-FU-treated rats, and on days 12–16 in rats inoculated with tumour cells, peritoneal blood flow was analysed with the 133Xeclearance technique, before and during intravenous infusion of vasopressin at 0.07 IU/min/kg body weight. Results: The basal 133Xe-clearance before administration of vasopressin was similar in all groups except in the LH rats treated with 5-FU in which it was significantly lower. Infusion of vasopressin induced a significant decrease in 133Xe-clearance of the same magnitude in controls and in tumour-bearing rats. In the rats given intraperitoneal 5-FU, vasopressin did not reduce the 133Xe-clearance the first day after administration of 5-FU. Conclusions: Intravenous vasopressin at 0.07 IU/ min/kg decreased peritoneal blood flow as measured indirectly with the 133Xe-clearance method. Intraperitoneal 5-FU abrogated the reduction in peritoneal blood flow with intravenous vasopressin the first day after treatment. In contrast, the presence of peritoneal carcinomatosis did not influence peritoneal blood flow, nor the effect of vasopressin

  • 929.
    Österlund, Barbro
    et al.
    Umeå universitet, Medicinsk fakultet, Kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Andersson, Bengt
    Umeå universitet, Medicinsk fakultet, Kirurgisk och perioperativ vetenskap, Kirurgi.
    Häggmark, Sören
    Umeå universitet, Medicinsk fakultet, Kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Jern, Christina
    Johansson, Göran
    Umeå universitet, Medicinsk fakultet, Kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Seeman-Lodding, Helen
    Biber, Björn
    Umeå universitet, Medicinsk fakultet, Kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Myocardial ischemia induces coronary t-PA release in the pig2002Inngår i: Acta Anaesthesiol Scand, Vol. 46, nr 3, s. 271-8Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Tissue-type plasminogen activator (t-PA) is the key factor in initiating endogenous fibrinolysis in the vascular compartment. Regulated release of t-PA from endothelial stores is rapidly induced by several humoral factors as well as coagulation activation products. The aim of the present study was to test the hypothesis that regional myocardial ischemia induces regulated release of t-PA in the coronary vasculature in vivo. METHODS: Healthy anesthetized (pentobarbital) pigs (n=8) were studied before and after a 10-min left anterior descending region coronary artery occlusion (LAD). Coronary fluxes of lactate, total t-PA antigen (ELISA, detecting both complex bound and free fraction) and active t-PA (functional assay detecting biological free fraction) were determined at 1, 3, 5 and 10 min of reflow. RESULTS: Coronary occlusion induced myocardial lactate production in all animals. Net coronary release of total t-PA, which was 21 ng/min during control, increased rapidly during reflow with a peak after only 1 min (136 ng/min), and returned to baseline within 3 min. Net release of active t-PA mirrored the overall net release response, but fell short of statistical significance. CONCLUSION: Data indicate a local myocardial profibrinolytic response following regional ischemia, which may serve as a prompt defence against coronary thromboembolic events.

  • 930.
    Österlund, Barbro
    et al.
    Umeå universitet, Medicinsk fakultet, Kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Holmgren, Anders
    Umeå universitet, Medicinsk fakultet, Kirurgisk och perioperativ vetenskap, Kirurgi.
    Häggmark, Sören
    Umeå universitet, Medicinsk fakultet, Kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Jern, Christina
    Johansson, Göran
    Umeå universitet, Medicinsk fakultet, Kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Seeman-Lodding, Helen
    Biber, Björn
    Umeå universitet, Medicinsk fakultet, Kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Surgical stress induces acute coronary release of tissue-type plasminogen activator in the pig2000Inngår i: Acta Anaesthesiol Scand, Vol. 44, nr 10, s. 1226-31Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Tissue-type plasminogen activator (t-PA) is an endothelium derived key enzyme in the initiation of endogenous fibrinolysis. Acute regulated release of active t-PA occurs within minutes in response to threatening thrombotic vessel occlusion. The aim of this study was to investigate the impact of surgical stimulation on the kinetics of t-PA release in the coronary vascular bed in the pig. METHODS: In anaesthetised pigs (n=16), arterio-venous concentration gradients of t-PA, and plasma flows (retrograde thermodilution) were obtained across the coronary vascular bed before (control) and at 1, 3, 5 and 10 min after sternotomy. RESULTS: At control, no significant coronary net flux (release or uptake) of t-PA was observed, while sternotomy induced a rapid net release of total t-PA (132.6 ng x min(-1)), with an associated increase in active t-PA (93.6 ng x min(-1)). This response, evident already after 1 min, showed a peak at 5 min and returned towards baseline levels within 10 min. No concurrent alterations in aortic levels of active t-PA were found and haemodynamic variables were unaltered. CONCLUSION: The rapidly increasing and transient net coronary release of t-PA after sternotomy suggests that the endothelium actively promotes local endogenous fibrinolysis during surgery. Such events could reflect a dynamic responsiveness to protect the coronary circulation during stress.

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