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  • 151. Enochsson, Lars
    et al.
    Sandblom, Gabriel
    Österberg, Johanna
    Thulin, Anders
    Hallerbäck, Bengt
    Persson, Gunnar
    Kvalitetsregister för gallstenskirurgi har förbättrat vården2015In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 112, article id DCE6Article in journal (Refereed)
    Abstract [sv]

    The Swedish Registry for cholecystectomy and endoscopic retrograde cholangiopancreatography (ERCP) (GallRiks) is a validated register with high coverage. The registry started on May 1, 2005 and serves as a base for audit on gallstone disease treatment and also provides a database for clinical research. The aim of this study is to present an overview of the clinical consequences and implementations in patient care that GallRiks research may have contributed to during a 10-year period. Results from studies on GallRiks data have reduced the use of antibiotic and thromboembolic prophylaxis as well as showed the importance of intraoperative cholangiography. Furthermore, the studies on GallRiks data have most probably changed the treatment strategies in ERCP. Studies on GallRiks data have changed and improved the management of patients in Sweden who undergo gallstone surgery or ERCP.

  • 152. Enochsson, Lars
    et al.
    Thulin, Anders
    Osterberg, Johanna
    Sandblom, Gabriel
    Persson, Gunnar
    The Swedish Registry of Gallstone Surgery and Endoscopic Retrograde Cholangiopancreatography (GallRiks): A nationwide registry for quality assurance of gallstone surgery.2013In: JAMA Surgery, ISSN 2168-6254, E-ISSN 2168-6262, Vol. 148, no 5, p. 471-8Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To describe the process of initiating and organizing a nationwide validated web-based quality registry of gallstone surgery and endoscopic retrograde cholangiopancreatography (ERCP) and to present some clinical data and the impact the registry has had on the clinical treatment of gallstones.

    DESIGN: Observational, population-based registry study.

    SETTING: Data from the nationwide Swedish Registry of Gallstone Surgery and ERCP (GallRiks).

    PATIENTS: From May 1, 2005, to December 31, 2011, 63 685 cholecystectomies (laparoscopic and open) and 37 860 ERCPs have been prospectively registered in GallRiks.

    INTERVENTIONS: Cholecystectomies, laparoscopic or conventional, as well as ERCP in a population-based setting.

    MAIN OUTCOME MEASURES: Registrations of all cholecystectomies and ERCPs are performed online by the surgeon or endoscopist. Thirty-day follow-up of both gallstone surgery and ERCP is mandatory, as is an additional 6-month follow-up of the cholecystectomies. Scores on the 36-Item Short Form Health Survey are registered preoperatively and 6 months postoperatively in elective cholecystectomies at selected units.

    RESULTS: The 30-day overall complication rate is 6.1% in elective cholecystectomy, 11.2% in urgent cholecystectomy, and 12.0% following ERCP. The use of antibiotic and thromboembolic prophylaxis in elective laparoscopic cholecystectomy in Sweden has decreased by 8.7% and 17.8% (2006-2011), respectively, mainly owing to presentation of GallRiks data both at meetings and published in peer-reviewed publications. The large database has also enabled several research projects, including one demonstrating that the intention to perform intraoperative cholangiography reduced the risk of death after cholecystectomy. The database has reached greater than 90% national coverage and is continuously validated.

    CONCLUSIONS: GallRiks is a validated national quality registry for gallstone surgery and ERCP, serving as a base for audit of gallstone disease treatment. It also provides a database for clinical research.

  • 153. Erba, P
    et al.
    Wettstein, R
    Tolnay, M
    Rieger, UM
    Pierer, G
    Kalbermatten, Daniel F
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery. Department of Plastic, Reconstructive and Aesthetic Surgery, University Hospital of Basel, CH-4031 Basel, Switzerland.
    Neurocutaneous sural flap in paraplegic patients2009In: Journal of Plastic, Reconstructive & Aesthetic Surgery, ISSN 1748-6815, E-ISSN 1532-1959, Vol. 62, no 8, p. 1094-1098Article in journal (Refereed)
    Abstract [en]

    Neurocutaneous flaps have been demonstrated to be a reliable option in different groups of patients but it remains unclear if distally-based sural flaps can be safety used in paraplegic patients because they suffer from significant nervous system alterations. The aim of this proof-of-concept study is to demonstrate that these flaps are reliable in paraplegic patients. We prospectively analysed a group (n = 6) of paraplegic patients who underwent reversed sural flap surgery for ulcers on the lateral malleolus. Measurement of area and photographic documentation techniques have been employed to quantify the defect area. Sural nerve biopsies have been analysed histologically with several different staining techniques to assess the neurovascular network and the myelinisation of the nerve. The patients showed uneventful wound heating, except one case that suffered a partial flap necrosis that heated by secondary intention. Histologic analysis revealed an intact neurovascular network and myelinated nerve fibres. In this small series of paraplegic patients that underwent a distally-based sural flap, the complication rate was low, with only one case of superficial partial necrosis demonstrating the reliability and safety of the flap in this subset of patients. Histologic evaluation of sural. nerve biopsies revealed an almost normal morphology. A possible explanation of this phenomenon is that the dorsal root ganglia remain intact in paraplegic patients and can preserve neural characteristics in the peripheral sensory nerve system.

  • 154. Eriksson, Lisbeth
    et al.
    Lindström, Britta
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy.
    Ekenberg, Lilly
    Patients' experiences of telerehabilitation at home after shoulder joint replacement2011In: Journal of Telemedicine and Telecare, ISSN 1357-633X, E-ISSN 1758-1109, Vol. 17, p. 25-30Article in journal (Refereed)
    Abstract [en]

    We investigated the experience of ten patients who received video-based physiotherapy at home for two months after a shoulder joint replacement. Videoconferencing took place via the patient's home broadband connection at a bandwidth of 256-768 kbit/s. Qualitative interviews were carried out, transcribed and analysed. Through qualitative content analysis six categories were identified: (1) a different reinforced communication; (2) pain-free exercising as an effective routine; (3) from a dependent patient to a strengthened person at home; (4) closeness at a distance; (5) facilitated daily living; and (6) continuous physiotherapy chain. The access to bodily knowledge, continuity, collaboration and being at home were all aspects that contributed to the patients' recovery. The patients described experiences of safety, and strengthening during their daily exercise routine at home. The frequent interplay with the patient during telerehabilitation made it possible for the physiotherapist to make an individual judgement about each patient; this could be one reason for the positive findings. Home video-based physiotherapy may be useful in other kinds of physiotherapy.

  • 155. Fahlström, Andreas
    et al.
    Tobieson, Lovisa
    Redebrandt, Henrietta Nittby
    Zeberg, Hugo
    Bartek, Jiri, Jr.
    Bartley, Andreas
    Erkki, Maria
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. Umeå University Hospital.
    Hessington, Amel
    Troberg, Ebba
    Mirza, Sadia
    Tsitsopoulos, Parmenion P.
    Marklund, Niklas
    Differences in neurosurgical treatment of intracerebral haemorrhage: a nation-wide observational study of 578 consecutive patients2019In: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 161, no 5, p. 955-965Article in journal (Refereed)
    Abstract [en]

    Background: Supratentorial intracerebral haemorrhage (ICH) carries an excessive mortality and morbidity. Although surgical ICH treatment can be life-saving, the indications for surgery in larger cohorts of ICH patients are controversial and not well defined. We hypothesised that surgical indications vary substantially among neurosurgical centres in Sweden.

    Objective: In this nation-wide retrospective observational study, differences in treatment strategies among all neurosurgical departments in Sweden were evaluated.

    Methods: Patient records, neuroimaging and clinical outcome focused on 30-day mortality were collected on each operated ICH patient treated at any of the six neurosurgical centres in Sweden from 1 January 2011 to 31 December 2015.

    Results: In total, 578 consecutive surgically treated ICH patients were evaluated. There was a similar incidence of surgical treatment among different neurosurgical catchment areas. Patient selection for surgery was similar among the centres in terms of patient age, pre-operative level of consciousness and co-morbidities, but differed in ICH volume, proportion of deep-seated vs. lobar ICH and pre-operative signs of herniation (p < .05). Post-operative patient management strategies, including the use of ICP-monitoring, CSF-drainage and mechanical ventilation, varied among centres (p < .05). The 30-day mortality ranged between 10 and 28%.

    Conclusions: Although indications for surgical treatment of ICH in the six Swedish neurosurgical centres were homogenous with regard to age and pre-operative level of consciousness, important differences in ICH volume, proportion of deep-seated haemorrhages and pre-operative signs of herniation were observed, and there was a substantial variability in post-operative management. The present results reflect the need for refined evidence-based guidelines for surgical management of ICH.

  • 156. Falconer, Henrik
    et al.
    Palsdottir, Kolbrun
    Stalberg, Karin
    Dahm-Kahler, Pernilla
    Ottander, Ulrika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences.
    Lundin, Evelyn Serreyn
    Wijk, Lena
    Kimmig, Rainer
    Jensen, Pernille Tine
    Eriksson, Ane Gerda Zahl
    Maenpaa, Johanna
    Persson, Jan
    Salehi, Sahar
    Robot-assisted approach to cervical cancer (RACC): an international multi-center, open-label randomized controlled trial2019In: International Journal of Gynecological Cancer, ISSN 1048-891X, E-ISSN 1525-1438, Vol. 29, no 6, p. 1072-1076Article in journal (Refereed)
    Abstract [en]

    Background Radical hysterectomy with pelvic lymphadenectomy represents the standard treatment for early-stage cervical cancer. Results from a recent randomized controlled trial demonstrate that minimally invasive surgery is inferior to laparotomy with regards to disease-free and overall survival. Primary Objective To investigate the oncologic safety of robot-assisted surgery for early-stage cervical cancer as compared with standard laparotomy. Study Hypothesis Robot-assisted laparoscopic radical hysterectomy is non-inferior to laparotomy in regards to recurrence-free survival with the advantage of fewer post-operative complications and superior patient-reported outcomes. Trial Design Prospective, multi-institutional, international, open-label randomized clinical trial. Consecutive women with early-stage cervical cancer will be assessed for eligibility and subsequently randomized 1:1 to either robot-assisted laparoscopic surgery or laparotomy. Institutional review board approval will be required from all participating institutions. The trial is coordinated from Karolinska University Hospital, Sweden. Major Inclusion/Exclusion Criteria Women over 18 with cervical cancer FIGO (2018) stages IB1, IB2, and IIA1 squamous, adenocarcinoma, or adenosquamous will be included. Women are not eligible if they have evidence of metastatic disease, serious co-morbidity, or a secondary invasive neoplasm in the past 5 years. Primary Endpoint Recurrence-free survival at 5 years between women who underwent robot-assisted laparoscopic surgery versus laparotomy for early-stage cervical cancer. Sample Size The clinical non-inferiority margin in this study is defined as a 5-year recurrence-free survival not worsened by >7.5%. With an expected recurrence-free survival of 85%, the study needs to observe 127 events with a one-sided level of significance (alpha) of 5% and a power (1-beta) of 80%. With 5 years of recruitment and 3 years of follow-up, the necessary number of events will be reached if the study can recruit a total of 768 patients. Estimated Dates for Completing Accrual and Presenting Results Trial launch is estimated to be May 2019 and the trial is estimated to close in May 2027 with presentation of data shortly thereafter.

  • 157. Falk, Peter
    et al.
    Ruiz-Jasbon, Fernando
    Strigård, Karin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Gunnarsson, Ulf
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Ivarsson, Marie-Lois
    An ex vivo model using human peritoneum to explore mesh-tissue integration2017In: Biology open, ISSN 2046-6390, Vol. 6, no 9, p. 1391-1395Article in journal (Refereed)
    Abstract [en]

    Biological compatibility, in terms of implantation of foreign mesh material in hernia surgery, still needs experimental investigation. Present study develops an experimental model using human peritoneum to study the integration between tissue and different mesh material. The ex vivo model using peritoneal tissue was studied with different mesh material, and integration was monitored over time using microscopy.It could be demonstrated that the peritoneal model may be kept viable in culture for several weeks. Cell migration was seen after 7-10 days in culture and could be further monitored over several weeks. The use of a human artificial model environment enabling the investigation of tissue/mesh integration has, to our knowledge, not been described previously.This proof-of-concept model was developed, for the investigation of peritoneal biology and the integration between tissue and different mesh material. It has the potential to be useful in studies on other important biological mechanisms involving the peritoneum.

  • 158. Fang, Jun
    et al.
    Jia, Jinping
    Makowski, Matthew
    Xu, Mai
    Wang, Zhaoming
    Zhang, Tongwu
    Hoskins, Jason W
    Choi, Jiyeon
    Han, Younghun
    Zhang, Mingfeng
    Thomas, Janelle
    Kovacs, Michael
    Collins, Irene
    Dzyadyk, Marta
    Thompson, Abbey
    O'Neill, Maura
    Das, Sudipto
    Lan, Qi
    Koster, Roelof
    Stolzenberg-Solomon, Rachael S
    Kraft, Peter
    Wolpin, Brian M
    Jansen, Pascal W T C
    Olson, Sara
    McGlynn, Katherine A
    Kanetsky, Peter A
    Chatterjee, Nilanjan
    Barrett, Jennifer H
    Dunning, Alison M
    Taylor, John C
    Newton-Bishop, Julia A
    Bishop, D Timothy
    Andresson, Thorkell
    Petersen, Gloria M
    Amos, Christopher I
    Iles, Mark M
    Nathanson, Katherine L
    Landi, Maria Teresa
    Vermeulen, Michiel
    Brown, Kevin M
    Amundadottir, Laufey T
    Functional characterization of a multi-cancer risk locus on chr5p15.33 reveals regulation of TERT by ZNF148.2017In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 8, article id 15034Article in journal (Refereed)
    Abstract [en]

    Genome wide association studies (GWAS) have mapped multiple independent cancer susceptibility loci to chr5p15.33. Here, we show that fine-mapping of pancreatic and testicular cancer GWAS within one of these loci (Region 2 in CLPTM1L) focuses the signal to nine highly correlated SNPs. Of these, rs36115365-C associated with increased pancreatic and testicular but decreased lung cancer and melanoma risk, and exhibited preferred protein-binding and enhanced regulatory activity. Transcriptional gene silencing of this regulatory element repressed TERT expression in an allele-specific manner. Proteomic analysis identifies allele-preferred binding of Zinc finger protein 148 (ZNF148) to rs36115365-C, further supported by binding of purified recombinant ZNF148. Knockdown of ZNF148 results in reduced TERT expression, telomerase activity and telomere length. Our results indicate that the association with chr5p15.33-Region 2 may be explained by rs36115365, a variant influencing TERT expression via ZNF148 in a manner consistent with elevated TERT in carriers of the C allele.

  • 159.
    Farahmand, Dan
    et al.
    Hydrocephalus Research Unit, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Qvarlander, Sara
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Wikkelsö, Carsten
    Hydrocephalus Research Unit, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Tisell, Magnus
    Hydrocephalus Research Unit, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Intracranial pressure in hydrocephalus: impact of shunt adjustments and body positions2015In: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 86, no 2, p. 222-228Article in journal (Refereed)
    Abstract [en]

    Background The association between intracranial pressure (ICP) and different shunt valve opening pressures in relation to body positions is fundamental for understanding the physiological function of the shunt.

    Objective To analyse the ICP and ICP wave amplitude (AMP) at different shunt settings and body positions in patients with hydrocephalus.

    Methods In this prospective study 15 patients with communicating hydrocephalus were implanted with a ligated adjustable ventriculoperitoneal shunt. They also received a portable intraparenchymatous ICP-monitoring device. Postoperative ICP and AMP were recorded with the patients in three different body positions (supine, sitting and walking) and with the shunt ligated and open at high, medium and low valve settings. In each patient 12 10 min segments were coded, blinded and analysed for mean ICP and mean AMP using an automated computer algorithm.

    Results Mean ICP and mean AMP were lower at all three valve settings compared with the ligated shunt state (p<0.001). Overall, when compared with the supine position, mean ICP was 11.5 +/- 1.1 (mean +/- SD) mm Hg lower when sitting and 10.5 +/- 1.1 mm Hg lower when walking (p<0.001). Mean ICP was overall 1.1 mm Hg higher (p=0.042) when walking compared with sitting. The maximal adjustability difference (highest vs lowest valve setting) was 4.4 mm Hg.

    Conclusions Changing from a supine to an upright position reduced ICP while AMP only increased at trend level. Lowering of the shunt valve opening pressure decreased ICP and AMP but the difference in mean ICP in vivo between the highest and lowest opening pressures was less than half that previously observed in vitro.

  • 160. Fedirko, V.
    et al.
    Lukanova, A.
    Bamia, C.
    Trichopolou, A.
    Trepo, E.
    Noethlings, U.
    Schlesinger, S.
    Aleksandrova, K.
    Boffetta, P.
    Tjonneland, A.
    Johnsen, N. F.
    Overvad, K.
    Fagherazzi, G.
    Racine, A.
    Boutron-Ruault, M. C.
    Grote, V.
    Kaaks, R.
    Boeing, H.
    Naska, A.
    Adarakis, G.
    Valanou, E.
    Palli, D.
    Sieri, S.
    Tumino, R.
    Vineis, P.
    Panico, S.
    Bueno-de-Mesquita, H. B(as).
    Siersema, P. D.
    Peeters, P. H.
    Weiderpass, E.
    Skeie, G.
    Engeset, D.
    Quiros, J. R.
    Zamora-Ros, R.
    Sanchez, M. J.
    Amiano, P.
    Huerta, J. M.
    Barricarte, A.
    Johansen, D.
    Lindkvist, B.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Werner, Mårten
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Crowe, F.
    Khaw, K. T.
    Ferrari, P.
    Romieu, I.
    Chuang, S. C.
    Riboli, E.
    Jenab, M.
    Glycemic index, glycemic load, dietary carbohydrate, and dietary fiber intake and risk of liver and biliary tract cancers in Western Europeans2013In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 24, no 2, p. 543-553Article in journal (Refereed)
    Abstract [en]

    The type and quantity of dietary carbohydrate as quantified by glycemic index (GI) and glycemic load (GL), and dietary fiber may influence the risk of liver and biliary tract cancers, but convincing evidence is lacking. The association between dietary GI/GL and carbohydrate intake with hepatocellular carcinoma (HCC; N = 191), intrahepatic bile duct (IBD; N = 66), and biliary tract (N = 236) cancer risk was investigated in 477 206 participants of the European Prospective Investigation into Cancer and Nutrition cohort. Dietary intake was assessed by country-specific, validated dietary questionnaires. Hazard ratios and 95% confidence intervals were estimated from proportional hazard models. HBV/HCV status was measured in a nested case-control subset. Higher dietary GI, GL, or increased intake of total carbohydrate was not associated with liver or biliary tract cancer risk. For HCC, divergent risk estimates were observed for total sugar = 1.43 (1.17-1.74) per 50 g/day, total starch = 0.70 (0.55-0.90) per 50 g/day, and total dietary fiber = 0.70 (0.52-0.93) per 10 g/day. The findings for dietary fiber were confirmed among HBV/HCV-free participants [0.48 (0.23-1.01)]. Similar associations were observed for IBD [dietary fiber = 0.59 (0.37-0.99) per 10 g/day], but not biliary tract cancer. Findings suggest that higher consumption of dietary fiber and lower consumption of total sugars are associated with lower HCC risk. In addition, high dietary fiber intake could be associated with lower IBD cancer risk.

  • 161. Fedirko, V
    et al.
    Trichopolou, A
    Bamia, C
    Duarte-Salles, T
    Trepo, E
    Aleksandrova, K
    Nöthlings, U
    Lukanova, A
    Lagiou, P
    Boffetta, P
    Trichopoulos, D
    Katzke, VA
    Overvad, K
    Tjønneland, A
    Hansen, L
    Boutron-Ruault, MC
    Fagherazzi, G
    Bastide, N
    Panico, S
    Grioni, S
    Vineis, P
    Palli, D
    Tumino, R
    Bueno-de-Mesquita, HB
    Peeters, PH
    Skeie, G
    Engeset, D
    Parr, CL
    Jakszyn, P
    Sánchez, MJ
    Barricarte, A
    Amiano, P
    Chirlaque, M
    Quirós, JR
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Werner, Mårten
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Sonestedt, E
    Ericson, U
    Key, TJ
    Khaw, KT
    Ferrari, P
    Romieu, I
    Riboli, E
    Jenab, M
    Consumption of fish and meats and risk of hepatocellular carcinoma: the European Prospective Investigation into Cancer and Nutrition (EPIC)2013In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 24, no 8, p. 2166-2173Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: While higher intake of fish and lower consumption of red/processed meats have been suggested to play a protective role in the etiology of several cancers, prospective evidence for hepatocellular carcinoma (HCC) is limited, particularly in Western European populations.

    METHODS: The associations of fish and meats with HCC risk were analyzed in the EPIC cohort. Between 1992 and 2010, 191 incident HCC were identified among 477 206 participants. Baseline diet was assessed using validated dietary questionnaires. A single 24-h diet recall from a cohort subsample was used for calibration. Multivariable proportional hazard regression was utilized to estimate hazard ratios (HR) and 95% confidence intervals (CI). In a nested case-control subset (HCC = 122), HBV/HCV status and liver function biomarkers were measured.

    RESULTS: HCC risk was inversely associated with intake of total fish (per 20 g/day increase, HR = 0.83, 95% CI 0.74-0.95 and HR = 0.80, 95% CI 0.69-0.97 before and after calibration, respectively). This inverse association was also suggested after adjusting for HBV/HCV status and liver function score (per 20-g/day increase, RR = 0.86, 95% CI 0.66-1.11 and RR = 0.74, 95% CI 0.50-1.09, respectively) in a nested case-control subset. Intakes of total meats or subgroups of red/processed meats, and poultry were not associated with HCC risk.

    CONCLUSIONS: In this large European cohort, total fish intake is associated with lower HCC risk.

  • 162. Fedirko, Veronika
    et al.
    Duarte-Salles, Talita
    Bamia, Christina
    Trichopoulou, Antonia
    Aleksandrova, Krasimira
    Trichopoulos, Dimitrios
    Trepo, Elisabeth
    Tjønneland, Anne
    Olsen, Anja
    Overvad, Kim
    Boutron-Ruault, Marie-Christine
    Clavel-Chapelon, Françoise
    Kvaskoff, Marina
    Kühn, Tilman
    Lukanova, Annie
    Boeing, Heiner
    Buijsse, Brian
    Klinaki, Eleni
    Tsimakidi, Chrysanthi
    Naccarati, Alessio
    Tagliabue, Giovanna
    Panico, Salvatore
    Tumino, Rosario
    Palli, Domenico
    Bueno-de-Mesquita, H Bas
    Siersema, Peter D
    Peters, Petra H
    Lund, Eiliv
    Brustad, Magritt
    Standahl Olsen, Karina
    Weiderpass Vainio, Elisabete
    Zamora, Raul
    Sánchez, María-José
    Ardanaz, Eva
    Amiano, Pilar
    Navarro, Carmen
    Quirós, J Ramón
    Werner, Mårten
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Lindkvist, Björn
    Malm, Johan
    Travis, Ruth C
    Khaw, Kay-Tee
    Stepien, Magdalena
    Scalbert, Augustin
    Romieu, Isabelle
    Lagiou, Pagona
    Riboli, Elio
    Jenab, Mazda
    Pre-diagnostic circulating vitamin D levels and risk of hepatocellular carcinoma in European populations: a nested case-control study2014In: Hepatology, ISSN 0270-9139, E-ISSN 1527-3350, Vol. 60, no 4, p. 1222-1230Article in journal (Refereed)
    Abstract [en]

    The association between vitamin D status and hepatocellular carcinoma has not been well investigated, despite experimental evidence supporting an important role of vitamin D in liver pathophysiology. Our objective was to investigate the association between pre-diagnostic circulating 25-hydroxyvitamin D [25(OH)D] serum levels and risk of hepatocellular carcinoma in a prospective, nested case-control study among 520,000 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Each case (n = 138) diagnosed between 1992 and 2010 was matched to one control by age, sex, study center, date and time of blood collection, and fasting status. Serum baseline levels of 25(OH)D were measured by liquid chromatography/tandem mass spectrometry. Multivariable incident rate ratios (IRR) of hepatocellular carcinoma associated with continuous (per 10 nmol/L) or categorical levels (tertiles or a priori-defined categories) of pre-diagnostic 25(OH)D. Higher 25(OH)D levels were associated with a 49% reduction in the risk of hepatocellular carcinoma (highest vs. lowest tertile: multivariable IRR = 0.51, 95% confidence interval, 0.26 to 0.99; Ptrend = 0.04; per 10 nmol/L increase: IRR = 0.80, 95% confidence interval, 0.68-0.94). The finding did not vary substantially by time from enrolment to diagnosis, and did not change after adjustment for biomarkers of pre-existing liver damage, nor chronic infection with hepatitis B or C viruses. The findings were not modified by body size or smoking status. Conclusion: In this prospective study on Western European populations, serum levels of 25(OH)D were inversely associated with risk of hepatocellular carcinoma. Given the rising incidence of this cancer in low-risk developed countries and the strong public health interest surrounding the potentially cancer-protective roles of vitamin D, additional studies in different populations are required. (Hepatology 2014;).

  • 163. Ferrari, Pietro
    et al.
    Rinaldi, Sabina
    Jenab, Mazda
    Lukanova, Annekatrin
    Olsen, Anja
    Tjonneland, Anne
    Overvad, Kim
    Clavel-Chapelon, Francoise
    Fagherazzi, Guy
    Touillaud, Marina
    Kaaks, Rudolf
    von Ruesten, Anne
    Boeing, Heiner
    Trichopoulou, Antonia
    Lagiou, Pagona
    Benetou, Vassiliki
    Grioni, Sara
    Panico, Salvatore
    Masala, Giovanna
    Tumino, Rosario
    Polidoro, Silvia
    Bakker, Marije F.
    van Gils, Carla H.
    Ros, Martine M.
    Bueno-de-Mesquita, H. Bas
    Krum-Hansen, Sanda
    Engeset, Dagrun
    Skeie, Guri
    Pilar, Amiano
    Sanchez, Maria-Jose
    Buckland, Genevieve
    Ardanaz, Eva
    Chirlaque, Dolores
    Rodriguez, Laudina
    Travis, Ruth
    Key, Tim
    Khaw, Kay-Tee
    Wareham, Nicholas J.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Slimani, Nadia
    Norat, Teresa
    Aune, Dagfinn
    Riboli, Elio
    Romieu, Isabelle
    Dietary fiber intake and risk of hormonal receptor-defined breast cancer in the European Prospective Investigation into Cancer and Nutrition study2013In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 97, no 2, p. 344-353Article in journal (Refereed)
    Abstract [en]

    Background: Limited scientific evidence has characterized the association between dietary fiber intake and risk of breast cancer (BC) by menopausal status and hormone receptor expression in tumors. ' Objective: We investigated the relation between total dietary fiber and its main food sources (vegetables, fruit, cereals, and legumes) and BC risk by using data from the European Prospective Investigation into Cancer and Nutrition (EPIC). Design: A total of 11,576 invasive BC cases in 334,849 EPIC women mostly aged 35-70 y at baseline were identified over a median follow-up of 11.5 y. Dietary fiber was estimated from country-specific dietary questionnaires. Multivariable Cox proportional hazards regression models were used to quantify the association between dietary variables and BC risk with energy adjustment by using the residual method. Subgroup analyses were performed by menopausal status and estrogen receptor (ER) and progesterone receptor (PR) expression in tumors. Results: BC risk was inversely associated with intakes of total dietary fiber [hazard ratio comparing fifth quintile to first quintile (HRQ5-Q1): 0.95; 95% CI: 0.89, 1.01; P-trend = 0.03] and fiber from vegetables (0.90; 0.84, 0.96; P-trend < 0.01) but not with fiber from fruit, cereals, or legumes. Overall, associations were homogeneous by menopausal status and ER and PR expression in tumors. For vegetable fiber, stronger associations were observed for estrogen receptor-negative and progesterone receptor-negative (HRQ5-Q1: 0.74; 95% CI: 0.59, 0.93; P-trend = 0.01) than for estrogen receptor-positive and progesterone receptor-positive tumors (0.92: 0.81, 1.03; P-trend = 0.05), with P-heterogeneity = 0.09. Conclusion: Diets rich in dietary fiber and, particularly, fiber from vegetables may be associated with a small reduction in risk of BC, independently of menopausal status. 

  • 164.
    Ferry, Tomas
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Bergström, Ulrica
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Hedström, Erik M
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Lorentzon, Ronny
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Zeisig, Eva
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Epidemiology of acute knee injuries seen at the Emergency Department at Umeå University Hospital, Sweden, during 15 years2014In: Knee Surgery, Sports Traumatology, Arthroscopy, ISSN 0942-2056, E-ISSN 1433-7347, Vol. 22, no 5, p. 1149-1155Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To describe the incidence and injury distribution of knee injuries in the general population of a European setting. METHODS: Retrospective study of all knee injuries registered at the Emergency Department at Umeå University Hospital, Sweden, during 1995-2009 in relation to age, sex, diagnosis, location and activity at the time of injury, mechanism of injury, and treatment and/or follow-up plan. RESULTS: During 1995-2009, 12,663 knee injuries were registered, 8 % of all injuries. The incidence of knee injuries resulting in a visit to the Emergency Department was six cases per 1,000 person years. One-third of all injuries occurred during sports. And 30 % were 15-24 years. More men than women were injured during sporting activities and women were mostly injured during transportation. CONCLUSION: Knee injuries in a general population are common and the injury distribution varies with age and sex. Sports activities and young age were prominent features of the injured population. LEVEL OF EVIDENCE: IV.

  • 165. Fisher, James L.
    et al.
    Pettersson, David
    Palmisano, Sadie
    Schwartzbaum, Judith A.
    Edwards, Colin G.
    Mathiesen, Tiit
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Prochazka, Michaela
    Bergenheim, Tommy
    Florentzson, Rut
    Harder, Henrik
    Nyberg, Gunnar
    Siesjo, Peter
    Feychting, Maria
    Loud Noise Exposure and Acoustic Neuroma2014In: American Journal of Epidemiology, ISSN 0002-9262, E-ISSN 1476-6256, Vol. 180, no 1, p. 58-67Article in journal (Refereed)
    Abstract [en]

    The results from studies of loud noise exposure and acoustic neuroma are conflicting. A population-based case-control study of 451 acoustic neuroma patients and 710 age-, sex-, and region-matched controls was conducted in Sweden between 2002 and 2007. Occupational exposure was based on historical measurements of occupational noise (321 job titles summarized by a job exposure matrix) and compared with self-reported occupational noise exposure. We also evaluated self-reported noise exposure during leisure activity. Conditional logistic regression was used to estimate odds ratios. There was no statistically significant association between acoustic neuroma and persistent occupational noise exposure, either with or without hearing protection. Exposure to loud noise from leisure activity without hearing protection was more common among acoustic neuroma cases (odds ratio = 1.47, 95% confidence interval: 1.06, 2.03). Statistically significant odds ratios were found for specific leisure activities including attending concerts/clubs/sporting events (odds ratio = 1.82, 95% confidence interval: 1.09, 3.04) and participating in workouts accompanied by loud music (odds ratio = 2.84, 95% confidence interval: 1.37, 5.89). Our findings do not support an association between occupational exposure to loud noise and acoustic neuroma. Although we report statistically significant associations between leisure-time exposures to loud noise without hearing protection and acoustic neuroma, especially among women, we cannot rule out recall bias as an alternative explanation.

  • 166.
    Floodeen, Hannah
    et al.
    Department of Surgery, Örebro University Hospital, Örebro, Sweden.
    Hallböök, Olof
    Department of Surgery, Linköping University Hospital, Linköping, Sweden.
    Rutegård, Jörgen
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Sjödahl, Rune
    Department of Surgery, Linköping University Hospital, Linköping, Sweden.
    Matthiessen, Peter
    Department of Surgery, Örebro University Hospital, Örebro, Sweden.
    Early and late symptomatic anastomotic leakage following low anterior resection of the rectum for cancer: are they different entities?2013In: Colorectal Disease, ISSN 1462-8910, E-ISSN 1463-1318, Vol. 15, no 3, p. 334-340Article in journal (Refereed)
    Abstract [en]

    Aim The aim of the study was to compare patients with symptomatic anastomotic leakage following low anterior resection of the rectum (LAR) for cancer diagnosed during the initial hospital stay with those in whom leakage was diagnosed after hospital discharge. Method Forty-five patients undergoing LAR (n=234) entered into a randomized multicentre trial (NCT 00636948), who developed symptomatic anastomotic leakage, were identified. A comparison was made between patients diagnosed during the initial hospital stay on median postoperative day 8 (early leakage, EL; n=27) and patients diagnosed after hospital discharge at median postoperative day 22 (late leakage, LL; n=18). Patient characteristics, operative details, postoperative course and anatomical localization of the leakage were analysed. Results Leakage from the circular stapler line of an end-to-end anastomosis was more common in EL, while leakage from the stapler line of the efferent limb of the J-pouch or side-to-end anastomosis tended to be more frequent in LL (P=0.057). Intra-operative blood loss (P=0.006) and operation time (P=0.071) were increased in EL compared with LL. On postoperative day 5, EL performed worse than LL with regard to temperature (P=0.021), oral intake (P=0.006) and recovery of bowel activity (P=0.054). Anastomotic leakage was diagnosed most often by a rectal contrast study in EL and by CT scan in LL. The median initial hospital stay was 28days for EL and 10days for LL (P<0.001). Conclusion The present study has demonstrated that symptomatic anastomotic leakage can present before and after hospital discharge and raises the question of whether early and late leakage after LAR may be different entities.

  • 167.
    Folkesson, J
    et al.
    Department of Surgical Sciences, Uppsala University Hospital, Uppsala, Sweden.
    Nilsson, J
    Påhlman, L
    Glimelius, B
    Gunnarsson, Ulf
    Department of Surgical Sciences, Uppsala University Hospital, Uppsala, Sweden.
    The circular stapling device as a risk factor for anastomotic leakage.2004In: Colorectal Disease, ISSN 1462-8910, E-ISSN 1463-1318, Vol. 6, no 4, p. 275-9Article in journal (Refereed)
    Abstract [en]

    AIM: To investigate the relation between the type of circular stapler and anastomotic leak in rectal cancer surgery.

    BACKGROUND: During the past decades results from rectal cancer surgery have improved considerably regarding risk of local recurrence and survival. Two main paradigm changes are considered to be the cause for this: the introduction of total mesorectal excision (TME) and the increasing use of radiotherapy. However, rectal cancer surgery is associated with an unacceptably high frequency of complications of which anastomotic leak is one of the most severe ones. The hypothesis was raised that the choice of stapler influenced the leakage rates.

    METHODS: A questionnaire was sent to all departments of surgery (n = 66) performing rectal cancer surgery in Sweden to determine the choice of circular stapler when performing anterior resection for rectal cancer. These data were linked to the Swedish Rectal Cancer Registry for the period 1995-99.

    RESULTS: A total of 3316 patients had an anterior resection. The choice of circular stapling device was determined in 70% of the cases. When stapler A was used, the leakage rate was 11% whereas it was 7% when stapler B was used (P = 0.0039). In the cases where it was impossible to determine which stapler had been used the leakage rate was 8%.

    CONCLUSION: Quality control is an important part of medicine and the present study suggests that it also must include surgical instruments. A prospective randomised study is needed to confirm the results.

  • 168.
    Folkesson, Joakim
    et al.
    Department of Surgical Sciences and Oncology, Radiology, and Clinical Immunology, Uppsala University Hospital, Uppsala, Sweden.
    Birgisson, Helgi
    Department of Surgical Sciences and Oncology, Radiology, and Clinical Immunology, Uppsala University Hospital, Uppsala, Sweden.
    Pahlman, Lars
    Department of Surgical Sciences and Oncology, Radiology, and Clinical Immunology, Uppsala University Hospital, Uppsala, Sweden.
    Cedermark, Bjorn
    Glimelius, Bengt
    Gunnarsson, Ulf
    Departments of Surgical Sciences and Oncology, Radiology, and Clinical Immunology, Uppsala University Hospital, Uppsala, Sweden.
    Swedish Rectal Cancer Trial: long lasting benefits from radiotherapy on survival and local recurrence rate2005In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 23, no 24, p. 5644-5650Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To evaluate the long-term effects on survival and recurrence rates of preoperative radiotherapy in the treatment of curatively operated rectal cancer patients.

    PATIENTS AND METHODS: Of 1,168 randomly assigned patients in the Swedish Rectal Cancer Trial between 1987 and 1990, 908 had curative surgery; 454 of these patients had surgery alone, and 454 were administered preoperative radiotherapy (25 Gy in 5 days) followed by surgery within 1 week. Follow-up was performed by matching against three Swedish nationwide registries (the Swedish Cancer Register, the Hospital Discharge Register, and the Cause of Death Register).

    RESULTS: Median follow-up time was 13 years (range, 3 to 15 years). The overall survival rate in the irradiated group was 38% v 30% in the nonirradiated group (P = .008). The cancer-specific survival rate in the irradiated group was 72% v 62% in the nonirradiated group (P = .03), and the local recurrence rate was 9% v 26% (P < .001), respectively. The reduction of local recurrence rates was observed at all tumor heights, although it was not statistically significant for tumors greater than 10 cm from the anal verge.

    CONCLUSION: Preoperative radiotherapy with 25 Gy in 1 week before curative surgery for rectal cancer is beneficial for overall and cancer-specific survival and local recurrence rates after long-term follow-up.

  • 169.
    Folkesson, Joakim
    et al.
    Department of Surgery, Uppsala University Hospital, 751 85, Uppsala, Sweden .
    Brown, Steven S R
    Sheffield Teaching Hospitals, Sheffield, UK .
    Gunnarsson, Ulf
    Centre of Surgical Gastroenterology, Karolinska University Hospital, Huddinge and Karolinska Institute, Stockholm, Sweden.
    Påhlman, Lars
    Department of Surgery, Uppsala University Hospital, 751 85, Uppsala, Sweden .
    Randomised multicentre trial of circular stapling devices2012In: International Journal of Colorectal Disease, ISSN 0179-1958, E-ISSN 1432-1262, Vol. 27, no 2, p. 227-232Article in journal (Refereed)
    Abstract [en]

    PURPOSE: In a register study, the risk of anastomotic leakage correlated to the choice of circular stapling device with a 4% difference between the two brands used. Based on those data, a randomised multicentre study was started to explore the risk of an anastomotic leakage based upon the surgical device.

    METHODS: Patients above 18 years with a rectal cancer, able to give informed consent, and scheduled for an anterior resection were eligible for the study. Perioperative randomisation was to Ethicon™ PROXIMATE™ ILS™ or Autosuture™ Premium Plus CEEA™. Anastomotic leakage was defined as a clinically manifest leak.

    RESULTS: Five hundred twenty-nine patients were randomised (58% male). A leak occurred in 8.3%. The anastomoses created by PROXIMATE™ ILS™ leaked in 25/265 (9.4%) anastomoses, and the Premium Plus CEEA™ leaked in 19/260 (7.3%), p = .419.

    CONCLUSION: No difference in the leak rate could be revealed. Several centres replaced one of the staplers by a new product, and the study was ended before the stipulated number of patients was reached. In the future, surgical devices may have to prove superiority in randomised trials or be monitored in quality registers before they can be introduced into day to day surgical practice. The study was registered at ClinicalTrials.gov: NCT00399009.

  • 170.
    Folkesson, Joakim
    et al.
    Department of Surgical Sciences, Uppsala University Hospital, Uppsala, Sweden.
    Johansson, Robert
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Påhlman, Lars
    Department of Surgical Sciences, Uppsala University Hospital, Uppsala, Sweden.
    Gunnarsson, Ulf
    Department of Surgical Sciences, Uppsala University Hospital, Uppsala, Sweden.
    Population-based study of local surgery for rectal cancer2007In: The British journal of surgery, ISSN 1365-2168, Vol. 94, no 11, p. 1421-1426Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The aim was to determine long-term survival and recurrence rates after local excision of rectal cancer from a prospectively registered population-based database. METHODS: Swedish Rectal Cancer Registry data from 1995 to 2001, including 10 181 patients of whom 643 (6.3 per cent) had a local excision, were analysed. Complete 5-year follow-up data from 1995 to 1998 were available. Cumulative relative and cancer-specific survival rates, and rates of local recurrence and distant metastases, were calculated by actuarial methods. RESULTS: The 5-year cancer-specific survival rate for 256 patients with stage I disease who had local excision was 95.3 (95 per cent confidence interval 91.5 to 99.1) per cent. The 5-year local recurrence rate was 7.2 per cent. After adjustment for age, sex, tumour stage and preoperative radiotherapy, the relative risk of death from cancer was the same as that after major resection. CONCLUSION: Population-based results after local excision of rectal cancer are the same as those reported in controlled series for early-stage tumours after abdominal resection. A low relative survival and a high median age indicate the use of local excision in patients with a high level of co-morbidity. To achieve acceptable long-term results, optimal preoperative and postoperative staging is needed.

  • 171.
    Fong, Gloria
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Backman, Ludvig
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Andersson, Gustav
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Scott, Alexander
    Vancouver Coastal Health and Research Institute.
    Danielson, Patrik
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Human tenocytes are stimulated to proliferate by acetylcholine through an EGFR signalling pathway2013In: Cell and Tissue Research, ISSN 0302-766X, E-ISSN 1432-0878, Vol. 351, no 3, p. 465-475Article in journal (Refereed)
    Abstract [en]

    Studies of human patellar and Achilles tendons have shown that primary tendon fibroblasts (tenocytes) not only have the capacity to produce acetylcholine (ACh) but also express muscarinic ACh receptors (mAChRs) through which ACh can exert its effects. In patients with tendinopathy (chronic tendon pain) with tendinosis, the tendon tissue is characterised by hypercellularity and angiogenesis, both of which might be influenced by ACh. In this study, we have tested the hypothesis that ACh increases the proliferation rate of tenocytes through mAChR stimulation and have examined whether this mechanism operates via the extracellular activation of the epidermal growth factor receptor (EGFR), as shown in other fibroblastic cells. By use of primary human tendon cell cultures, we identified cells expressing vimentin, tenomodulin and scleraxis and found that these cells also contained enzymes related to ACh synthesis and release (choline acetyltransferase and vesicular acetylcholine transporter). The cells furthermore expressed mAChRs of several subtypes. Exogenously administered ACh stimulated proliferation and increased the viability of tenocytes in vitro. When the cells were exposed to atropine (an mAChR antagonist) or the EGFR inhibitor AG1478, the proliferative effect of ACh decreased. Western blot revealed increased phosphorylation, after ACh stimulation, for both EGFR and the extracellular-signal-regulated kinases 1 and 2. Given that tenocytes have been shown to produce ACh and express mAChRs, this study provides evidence of a possible autocrine loop that might contribute to the hypercellularity seen in tendinosis tendon tissue.

  • 172.
    Forsberg, Rebecca
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Train crashes: consequences for passengers2012Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: Globally, and in Sweden, passenger railway transport is steadily increasing. Sweden has been relatively free from severe train crashes in the last decades, but the railway infrastructure is alarmingly worn and overburdened, which may be one reason for an increasing number of reported mishaps. Worldwide, major train crashes/disasters are a frequent cause of mass casualty incidents. Several shortcomings, especially within the crash and post-crash phases cause severe consequences for the passengers.

    Aim: To investigate the consequences of train crashes on passengers, focusing on factors of importance in the crash and post-crash phases. The specific aims are: (I) to identify the historical development and magnitude of passenger train disasters globally on various continents and countries, (II, III) to identify injury panorama and injury objects in two train crashes, (IV) to explore survivor´s experiences from a train crash, and (V) to explore their experiences of journalists and media coverage.

    Methods: Study I is a register study based on 529 railway disasters worldwide, whereas studies II-V are case studies from the two latest severe train crashes in Sweden (Nosaby and Kimstad). These studies are based on 73 and 21 passengers respectively. Studies I-III is essentially quantitative where descriptive statistics (I, III), multivariate analysis (III), and content analysis (II, III) are used. Studies II and III are also supplemented by semi-structured interviews. Studies IV and V are qualitative and the interviews (n=14, n=30) have been analyzed with qualitative content analysis. Study IV is also supplemented with quantitative data.

    Results: The number of railway disasters, fatalities, and non-fatally injured passengers has increased throughout the last hundred years - particularly during the last four decades (1970–2009) when 88% of all disasters occurred (I). Passengers in the first overturned carriage suffered most severe and lethal injuries (III). Internal structures such as tables, chairs, internal walls, as well as luggage, other passengers (II, III), glass (II), and wood pellets (III) induced many of the injuries. Those who traveled facing forward with a table in front of them, in carriages that did not overturn, were more likely to sustain injuries to their abdomen/pelvis than those without a table (III). Passengers who traveled rear facing had higher rates of whiplash injuries. Surviving a train crash was experienced as "living in a mode of existential threat". The long term consequences however were diverse for different persons (IV). All experienced that they had cheated death, but some became "shackled by history", whereas others overcame the "haunting of unforgettable memories." The centrality of others and the importance of reconstructing the turn of events were important when "dealing with the unthinkable". The media coverage were experienced as positive in the recovery process and the journalists were also perceived as helpful (V). By some the journalist’s nevertheless were also perceived as harmful or negligible, and the subsequent media coverage as either uncomfortable or insignificant.

    Conclusion: Despite extensive crash avoidance systems severe railway crashes still occur. Improved interior safety, as has been implemented in the automobile and aviation industries, would have an important reduction in injuries and facilitate evacuation. Being surrounded by family, friends, fellow passengers and participating in crash investigations, and experiencing descriptive media coverage were some crucial factors when dealing with the traumatic event and should be promoted.

  • 173.
    Forsberg, Rebecca
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Holgersson, Annelie
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Bodén, Ida
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Björnstig, Ulf
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    A study of a mass casualty train crash, focusing on the cause of injuries2014In: Journal of Transportation Safety & Security, ISSN 1943-9962, Vol. 6, no 2, p. 152-166Article in journal (Refereed)
    Abstract [en]

    This case study includes 73 fatally and nonfatally injured passengers from a level-crossing train crash in Nosaby, Sweden, in 2004. The aim was to identify the injury panorama and the injury objects and to determine the injury-inducing variables. Data were analyzed with descriptive statistics, quantitative content analysis, and multivariate data analysis. The first carriage overturned, and its occupants were the ones who suffered the most severe and lethal injuries. Injury type and injury location for these passengers also differed significantly from the passengers on the other two carriages. Tables significantly influenced injury type and injury location in all carriages, whereas the injured persons’ seating position had significant effect only in the second and third carriage. Those who had travelled facing forward with a table in front of them in Carriages 2 and 3 were more likely to have sustained injuries to their abdomen or pelvis. Other injury-inducing objects were seats, interior structures, wood pellets from the truck, and other passengers. Neck sprains were significantly more prevalent among those who had travelled facing backward. Improved train crashworthiness also needs to include interior safety, which would have a potential to reduce crash injuries.

  • 174.
    Forsberg, Rebecca
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Iglesias Vazquez, Jose Antonio
    A Case Study of the High-speed Train Crash Outside Santiago de Compostela, Galicia, Spain2016In: Prehospital and Disaster Medicine, ISSN 1049-023X, E-ISSN 1945-1938, Vol. 31, no 2, p. 163-168Article in journal (Refereed)
    Abstract [en]

    Introduction: The worldwide use of rail transport has increased, and the train speeds are escalating. Concurrently, the number of train disasters has been amplified globally. Consequently, railway safety has become an important issue for the future. High-velocity crashes increase the risk for injuries and mortality; nevertheless, there are relatively few studies on high-speed train crashes and the influencing factors on travelers' injuries occurring in the crash phase. The aim of this study was to investigate the fatal and non-fatal injuries and the main interacting factors that contributed to the injury process in the crash phase of the 2013 high-velocity train crash that occurred at Angrois, outside Santiago de Compostela, Spain. Methods: Hospital records (n = 157) of all the injured who were admitted to the six hospitals in the region were reviewed and compiled by descriptive statistics. The instant fatalities (n = 63) were collected on site. Influencing crash factors were observed on the crash site, by carriage inspections, and by reviewing official reports concerning the approximated train speed. Results: The main interacting factors that contributed in the injury process in the crash phase were, among other things, the train speed, the design of the concrete structure of the curve, the robustness of the carriage exterior, and the interior environment of the carriages. Of the 222 people on board (218 passengers and four crew), 99% (n = 220) were fatally or non-fatally injured in the crash. Thirty-three percent (n = 72) suffered fatal injuries, of which 88% (n = 63) died at the crash site and 13% (n = 9) at the hospital. Twenty-one percent (n = 32) of those admitted to hospital suffered multi-trauma (ie, extensive, severe, and/or critical injuries). The head, face, and neck sustained 42% (n = 123) of the injuries followed by the trunk (chest, abdomen, and pelvis; n = 92; 32%). Fractures were the most frequent (n = 200; 69%) injury. Conclusion: A mass-casualty incident with an extensive amount of fatal, severe, and critical injuries is most probable with a high-velocity train; this presents prehospital challenges. This finding draws attention to the importance of more robust carriage exteriors and injury minimizing designs of both railway carriages and the surrounding environment to reduce injuries and fatalities in future high-speed crashes.

  • 175.
    Franklin, Karl A.
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Haglund, Bengt
    Axelsson, Susanna
    Holmlund, Thorbjörn
    Rehnqvist, Nina
    Rosen, Måns
    Frequency of serious complications after surgery for snoring and sleep apnea2011In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 131, no 3, p. 298-302Article in journal (Refereed)
    Abstract [en]

    Conclusion: No case of death related to surgery in the form of uvulopalatopharyngoplasty, uvulopalatoplasty or nasal surgery for snoring or sleep apnea has been recorded in Sweden among 4876 patients treated between 1997 and 2005. Severe complications of surgery in the peri-and postoperative period, especially in the form of bleedings and infections, were most common after uvulopalatopharyngoplasty, occurring in 3.7%. Objective: To investigate the frequency of serious complications, including death, of surgery for treatment of snoring and sleep apnea. Methods: All Swedish adults who were treated surgically because of snoring or sleep apnea from January 1997 to December 2005 were identified in the National Patient Register. Mortality and serious complications within 30 days from surgery were obtained from the National Cause of Death Register and the National Patient Register. Results: A total of 4876 patients were treated surgically. Uvulopalatopharyngoplasty was performed in 3572 patients, uvulopalatoplasty in 929 patients, and nasal surgery in 375 patients. None of the surgically treated patients died in the peri-and postoperative period. Severe complications, mainly bleedings and infections, were recorded in 37.1 per 1000 patients treated with uvulopalatopharyngoplasty, in 5.6 per 1000 patients after uvulopalatoplasty, and in 8.8 per 1000 patients after nasal surgery.

  • 176.
    Franklin, Karl A
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Rehnqvist, Nina
    Freyschuss, Bo
    Axelsson, Susanna
    Obesity surgery in sleep apnea? The effect should be studied in RCTs.2008In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 105, no 37, p. 2499-2500Article in journal (Other (popular science, discussion, etc.))
  • 177.
    Franklin, Oskar
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Stromal components and micro-RNAs as biomarkers in pancreatic cancer2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background Pancreatic ductal adenocarcinoma (PDAC) patients have the poorest 5-year survival rates of all cancer forms. It is difficult to diagnose at early disease stages, tumour relapse after surgery is common, and current chemotherapies are ineffective. Carbohydrate antigen 19-9 (Ca 19-9), the only clinically implemented PDAC biomarker, is insufficient for diagnostic and screening purposes.

    PDAC tumours are characterised by a voluminous stroma that is rich in extracellular matrix (ECM) molecules such as collagens, hyaluronan (HA) and matricellular proteins. These stromal components have been suggested to promote PDAC cell migration, proliferation, evasion of apoptosis and chemotherapy resistance. Those events are mediated via interactions with adhesion receptors, such as integrins and CD44 receptors expressed on cancer cell surfaces.

    Micro-RNAs (miRNA) post-transcriptionally regulate gene expression in health and disease. At the time of PDAC diagnosis, miRNA levels are altered both in plasma and tumour tissue. Before PDAC diagnosis, tissue miRNA levels are altered in precursor lesions, raising the possibility that plasma miRNAs might aid in early detection.

    In this thesis, it is hypothesised that stromal components and miRNAs can serve as tissue or blood based biomarkers in PDAC. The aims are: (1) to characterise the expression of stromal components and their receptors in normal and cancerous tissue; (2) to find potential stroma-associated tissue and blood-based biomarkers for diagnosis and prognosis estimates; (3) to determine the cellular effects of type IV collagen (Col IV) in PDAC; (4) to determine if plasma miRNAs that are altered in manifest PDAC can be used to diagnose PDAC earlier.

    Methods The expression patterns of Col IV, Col IV-binding integrin subunits (α1, α2, β1), Endostatin, Osteopontin (OPN) and Tenascin C (TNC) were analysed in frozen PDAC and normal pancreatic tissue. A tissue microarray (TMA) was constructed using formalin-fixed, paraffin-embedded primary tumours and lymph node metastases. The TMA was used to study the expression levels and associations with survival of the standard CD44 receptor (CD44s), its variant isoform 6 (CD44v6), HA, OPN and Col IV. Circulating levels of HA, Col IV, Endostatin, OPN and TNC were measured in PDAC patients and healthy individuals, and compared with conventional tumour markers (Ca 19-9, CEA, Ca 125 and TPS). The functional roles of Col IV were studied in PDAC cell lines by: (1) growth on different matrices (2) blocking Col IV binding integrin subunits, (3) blocking the Col IV domains 7s, CB3 and NC1, and (4) by down regulation of PDAC cell synthesis of Col IV using siRNA transfection. Plasma miRNAs alterations were screened for in samples from patients with manifest disease, using real-time quantitative PCR (RT-qPCR). To find early miRNA alterations, levels of those miRNAs that were altered at diagnosis were measured in prediagnostic plasma samples.

    Results High tissue expression of both the standard CD44 receptor (CD44s) and its variant isoform CD44v6 as well as low expression of stromal OPN were associated with poor survival. In addition, high CD44s and low OPN predicted poor survival independent of established prognostic factors.

    Circulating Col IV, Endostatin, OPN, TNC and HA were increased in preoperative samples from PDAC patients. Preoperatively, higher levels of serum-HA and plasma-Endostatin were associated with shorter survival. Postoperatively, higher levels of Col IV, Endostatin and OPN were associated with shorter survival. On the contrary, only one of the conventional tumour markers was associated with survival (Ca 125).

    Col IV stimulated PDAC cell proliferation and migration and inhibited apoptosis in vitro, dependent on the collagenous domain (CB3) of Col IV and the Col IV binding integrin subunit β1. Reduced endogenous Col IV synthesis inhibited these effects, suggesting that PDAC cells synthesise Col IV to stimulate tumour-promoting events via a newly discovered autocrine loop.

    15 miRNAs were altered in early stage PDAC patients and the combination of these markers outperformed Ca 19-9 in discriminating patients from healthy individuals. However, none of the miRNAs were altered in prediagnostic samples, suggesting that plasma miRNA alterations appear late in the disease course.

    Conclusions Up regulated stromal components in PDAC tumours are detectable in blood samples and are potential diagnostic and prognostic biomarkers in PDAC. High circulating levels of Col IV, Endostatin, OPN and HA predict poor survival, as well as high expression of CD44s and CD44v6 and low expression of OPN in tumour tissue. PDAC cells synthesise Col IV, which forms BM-like structures close to cancer cells and promote tumour progression in vitro via an autocrine loop. Several plasma-miRNAs are altered in PDAC, but are not useful for early discovery. 

  • 178.
    Fransson, Filip
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Kyrk, Tobias
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Skagerlind, Malin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Rinsing the extra corporeal circuit with a heparin and albumin solution reduces the need for systemic anticoagulant in hemodialysis2013In: International Journal of Artificial Organs, ISSN 0391-3988, E-ISSN 1724-6040, Vol. 36, no 10, p. 725-729Article in journal (Refereed)
    Abstract [en]

    Background: Systemic anticoagulation during hemodialysis (HD) increases the risk for bleeding complications pre- or post-operatively. Based on the concept of blood-membrane interaction, we developed a heparin-albumin solution to rinse the dialysis circuit before start. The aim of this study was to investigate if this method was a valuable tool for our patients at risk for bleeding complications.

    Material and methods: This retrospective, comparative, quality assessment study included 248 HD in 68 patients; Group 1: 178 treatments were performed at patients for risk of bleeding using heparin-albumin-priming and Group 2: 70 acute HD were performed on patients without increased risk of bleeding using a bolus of heparin at start and a continuous infusion of heparin. In Group 1 additional heparin was given upon suspicion of progressive clotting. One L saline contained albumin (1 g/I) and heparin (5000 U/I) used for priming. Excess priming solution was removed by filling the circuit with blood at start of treatment.

    Results: In Group 1, a mean total dose of 2000 U of heparin was given during the HD (18% performed HD without any heparin) and Group 2 used a mean total dose of 5500 U (p<0.001). There was no increased incidence of clotting in Group 1 versus Group 2 compared to standard HD. No bleeding complications were reported during any of the HA-priming treatments.

    Conclusions: Heparin-albumin priming resulted in a reduced total dose of heparin. There was no increased clotting and no incidence of bleeding was reported in either group.

  • 179.
    Fredriksson, Katarina
    et al.
    Department of Anesthesiology and Intensive Care, Karolinska University Hospital, Huddinge, Sweden.
    Hammarqvist, Folke
    Gastrocentrum, Department of Surgery, Karolinska University Hospital, Huddinge, Sweden.
    Strigård, Karin
    Gastrocentrum, Department of Surgery, Karolinska University Hospital, Huddinge, Sweden.
    Hultenby, Kjell
    Clinical Research Center at Karolinska University Hospital, Huddinge, Sweden.
    Ljungqvist, Olle
    Center for Gastrointestinal Disease at Ersta Hospital, CLINTEC, Karolinska Institutet, Stockholm, Sweden.
    Wernerman, Jan
    Department of Anesthesiology and Intensive Care, Karolinska University Hospital, Huddinge, Sweden.
    Rooyackers, Olav
    Department of Anesthesiology and Intensive Care, Karolinska University Hospital, Huddinge, Sweden.
    Derangements in mitochondrial metabolism in intercostal and leg muscle of critically ill patients with sepsis-induced multiple organ failure.2006In: American Journal of Physiology. Endocrinology and Metabolism, ISSN 0193-1849, E-ISSN 1522-1555, Vol. 291, no 5, p. 1044-1050Article in journal (Refereed)
    Abstract [en]

    Critically ill patients treated for multiple organ failure often develop muscle dysfunction. Here we test the hypothesis that mitochondrial and energy metabolism are deranged in leg and intercostal muscle of critically ill patients with sepsis-induced multiple organ failure. Ten critically ill patients suffering from sepsis-induced multiple organ failure and requiring mechanical ventilation were included in the study. A group (n = 10) of metabolically healthy age- and sex-matched patients undergoing elective surgery were used as controls. Muscle biopsies were obtained from the vastus lateralis (leg) and intercostal muscle. The activities of citrate synthase and mitochondrial respiratory chain complexes I and IV and concentrations of ATP, creatine phosphate, and lactate were analyzed. Morphological evaluation of mitochondria was performed by electron microscopy. Activities of citrate synthase and complex I were 53 and 60% lower, respectively, in intercostal muscle of the patients but not in leg muscle compared with controls. The activity of complex IV was 30% lower in leg muscle but not in intercostal muscle. Concentrations of ATP and creatine phosphate were, respectively, 40 and 34% lower, and lactate concentrations were 43% higher in leg muscle but not in intercostal muscle. We conclude that both leg and intercostal muscle show a twofold decrease in mitochondrial content in intensive care unit patients with multiple organ failure, which is associated with lower concentrations of energy-rich phosphates and an increased anaerobic energy production in leg muscle but not in intercostal muscle.

  • 180.
    Frestadius, Johnny
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery.
    Long term follow-up after interposition arthroplasty of the carpometacarpale 1-joint ad modum Hulin2015Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 181. Fridén, Jan
    et al.
    Pontén, Eva
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Department of Orthopaedics, Uppsala University, Uppsala, Sweden.
    Lieber, Richard L
    Effect of muscle tension during tendon transfer on sarcomerogenesis in a rabbit model2000In: Journal of Hand Surgery-American Volume, ISSN 0363-5023, E-ISSN 1531-6564, Vol. 25, no 1, p. 138-143Article in journal (Refereed)
    Abstract [en]

    Sarcomere number change was investigated in an animal model of tendon transfer. In 9 adult New Zealand white rabbits, the flexor digitorum longus muscle was cut distally and transferred and woven into the tibialis anterior tendon. Ankles were then immobilized for 3 weeks in 75 degrees flexion. Transferred flexor digitorum longus muscles were harvested and complete architectural analysis was performed. Sarcomere lengths were measured using laser diffraction. Serial sarcomere number in transferred flexor digitorum longus fibers was a strong function of the sarcomere length at the time of transfer. A highly significant negative correlation between these 2 parameters was approximated by a linear relationship. Based on this finding, we conclude that serial sarcomere number is significantly affected by the degree of stretch during the transfer itself. This could easily compromise the purpose of surgical tendon transfer by reducing the procedure to little more than a tenodesis.

  • 182.
    Fränneby, Ulf
    et al.
    Department of Surgery, Sodersjukhuset, Stockholm, Sweden.
    Gunnarsson, Ulf
    Department of Surgery, Akademiska Sjukhuser, Uppsala, Sweden.
    Andersson, M
    Department of Surgery, Mora District Hospital, Mora, Sweden.
    Heuman, R
    Department of Surgery, Mora District Hospital, Mora, Sweden.
    Nordin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Nyrén, Olof
    Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
    Sandblom, Gabriel
    Department of Surgery, University Hospital of Lund, Lund, Sweden.
    Validation of an Inguinal Pain Questionnaire for assessment of chronic pain after groin hernia repair.2008In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 95, no 4, p. 488-493Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Long-term pain is an important outcome after inguinal hernia repair. The aim of this study was to test the validity and reliability of a specific Inguinal Pain Questionnaire (IPQ). METHODS: The study recruited patients aged between 15 and 85 years who had undergone primary inguinal or femoral hernia repair. To test the validity of the questionnaire, 100 patients received the IPQ and the Brief Pain Inventory (BPI) 1 and 4 weeks after surgery (group 1). To test reliability and internal consistency, 100 patients received the IPQ on two occasions 1 month apart, 3 years after surgery (group 2). Non-surgery-related pain was analysed in group 3 (2853 patients). RESULTS: A significant decrease in IPQ-rated pain intensity was observed in the first 4 weeks after surgery (P < 0.001). Significant correlations with corresponding BPI pain intensity items corroborated the criterion validity (P < 0.050). Logical incoherence did not exceed 5.5 per cent for any item. Values for kappa in the test-retest in group 2 were higher than 0.5 for all but three items. Cronbach's alpha was 0.83 for questions on pain intensity and 0.74 for interference with daily activities. CONCLUSION: This study found good validity and reliability for the IPQ, making it a useful instrument for assessing pain following groin hernia repair.

  • 183.
    Fränneby, Ulf
    et al.
    Dept of Surgery, Sodersjukhuset, Stockholm, Sweden.
    Gunnarsson, Ulf
    The Department of Surgical Sciences, Akademiska sjukhuset, Colorectal Unit, Uppsala University, SE 751 85, Uppsala, Sweden.
    Wollert, S
    Sandblom, G
    Discordance between the patient's and surgeon's perception of complications following hernia surgery.2005In: Hernia, ISSN 1265-4906, E-ISSN 1248-9204, Vol. 9, no 2, p. 145-9Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The study was undertaken in order to assess the degree of concordance between the patient's and surgeon's perceptions of adverse events after groin hernia surgery.

    METHODS: 206 patients who underwent elective surgery for groin hernia at Samariterhemmet, Uppsala, Sweden in 2003 were invited to a follow-up visit after 3-6 weeks. At this visit the patient was instructed to answer a questionnaire including 12 questions concerning postoperative complications. A postoperative history was taken and a clinical examination performed by a surgeon who was not present at the operation and did not know the outcome of the questionnaire. All complications noted by the physician were recorded for corresponding questions in the questionnaire.

    RESULTS: 174 (84.5%) patients attended the follow up, 161 men and 13 women. A total of 190 complications were revealed by the questionnaire, 32 of which had caused the patient to seek help from the health-care system. There were 131 complications registered as a result of the follow-up clinical examinations and history. Kappa levels ranged from 0.11 for urinary complications to 0.56 for constipation.

    CONCLUSION: In general, the concordance was poor. These results emphasise the importance of providing detailed information about the usual postoperative course prior to the operation. Whereas the surgeon, from a professional point of view, has a better idea about what should be expected in the postoperative period and how any complications should be categorised, only the patient has a complete picture of the symptoms and adverse events. This makes it impossible to reach complete agreement between the patient's and surgeon's perceptions of complications, even under the most ideal circumstances.

  • 184.
    Fränneby, Ulf
    et al.
    Department of Surgery, Södersjukhuset, Stockholm.
    Sandblom, Gabriel
    Department of Surgery, Akademiska Sjukhuset, Uppsala.
    Nordin, Pär
    Department of Surgery, östersunds Sjukhus, östersund.
    Nyrén, Olof
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm.
    Gunnarsson, Ulf
    Department of Surgery, Akademiska Sjukhuset, Uppsala, Sweden.
    Risk factors for long-term pain after hernia surgery2006In: Annals of Surgery, ISSN 0003-4932, E-ISSN 1528-1140, Vol. 244, no 2, p. 212-219Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To estimate the prevalence of residual pain 2 to 3 years after hernia surgery, to identify factors associated with its occurrence, and to assess the consequences for the patient.

    SUMMARY BACKGROUND DATA: Iatrogenic chronic pain is a neglected problem that may totally annul the benefits from hernia repair.

    METHODS: From the population-based Swedish Hernia Register 3000 patients aged 15 to 85 years were sampled from the 9280 patients registered as having undergone a primary groin hernia operation in the year 2000. Of these, the 2853 patients still alive in 2003 were requested to fill in a postal questionnaire.

    RESULTS: After 2 reminders, 2456 patients (86%), 2299 men and 157 women responded. In response to a question about "worst perceived pain last week," 758 patients (31%) reported pain to some extent. In 144 cases (6%), the pain interfered with daily activities. Age below median, a high level of pain before the operation, and occurrence of any postoperative complication were found to significantly and independently predict long-term pain in multivariate logistic analysis when "worst pain last week" was used as outcome variable. The same variables, along with a repair technique using anterior approach, were found to predict long-term pain with "pain right now" as outcome variable.

    CONCLUSION: Pain that is at least partly disabling appears to occur more often than recurrences. The prevalence of long-term pain can be reduced by preventing postoperative complications. The impact of repair technique on the risk of long-term pain shown in our study should be further assessed in randomized controlled trials.

  • 185.
    Fränneby, Ulf
    et al.
    Department of Surgery, Södersjukhuset, Stockholm, Sweden.
    Sandblom, Gabriel
    Lund University Hospital, Lund, Sweden.
    Nyrén, Olof
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Nordin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Gunnarsson, Ulf
    Akademiska Sjukhuset, Uppsala, Sweden.
    Self-reported adverse events after groin hernia repair, a study based on a national register.2008In: Value in Health, ISSN 1098-3015, E-ISSN 1524-4733, Vol. 11, no 5, p. 927-932Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: In most clinics, follow-up after inguinal hernia surgery is not a routine procedure and complications may pass unnoticed, thus impairing quality assessment. The aim of this study was to investigate the frequency, spectrum, and risk factors of short-term adverse events after groin hernia repair. METHODS: All patients aged 15 years or older with a primary unilateral inguinal or femoral hernia repair recorded in the Swedish Hernia Register (SHR) between November 1 and December 31, 2002 were sent a questionnaire asking about complications within the first 30 postoperative days. RESULTS: Of the 1643 recorded patients, 1448 (88.1%) responded: 1341 (92.6%) were men and 107 (7.4%) women, mean age 59 years. There were 195 (11.9%) nonresponders. Postoperative complications reported in the questionnaire were hematoma in 203 (14.0%) patients, severe pain in 168 (11.6%), testicular pain in 120 (8.3%), and infection in 105 (7.3%). Adverse events were reported in the questionnaire by 391 (23.8%) patients, whereas only 85 (5.2%) were affected according to the SHR. Risk factors for postoperative complications were age below the median (59 years) among the studied hernia patients (OR 1.36; 95% CI 1.06-1.74) and laparoscopic repair (OR 2.66; 95% CI 1.17-6.05). CONCLUSION: Questionnaires provide valuable additional information concerning postoperative complications. We recommend that they become an integrated part of routine postoperative assessment.

  • 186.
    Fröjse, Rolf
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences.
    Exploring Intestinal Ischemia: An experimental study2005Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background and aims: Unrecognized intestinal mucosal ischemia in severely ill patients may trigger development of multiple organ failure. Such ischemia can be evaluated by intraluminal tonometry reflecting mucosal PCO2 and intramucosal pH (pHi). The aims were to develop an apparatus for continuous saline tonometry (CST), to analyse circulatory control mechanisms during intestinal hypoperfusion and to evaluate the effect of dopexamine on intestinal circulation.

    Methods: A modified standard tonometry catheter was integrated in a closed system with circulating saline. By measuring saline PCO2 in a measurement unit pHi could be calculated. This novel system was tested in vitro and in vivo. In a porcine study, CST was evaluated against standard saline tonometry, tissue oxygenation (PO2 TISSUE), jejunal mucosal perfusion (laser doppler flowmetry; LDF) and mesenteric net lactate flux during graded reductions of superior mesenteric arterial pressure (PSMA). Local control mechanisms for maintenance of intestinal oxygenation were analysed. Effects of dopexamine on the intestinal vascular bed were explored. Mucosal lactate production was assessed by microdialysis.

    Results: CST measured accurate PCO2 values and changes in pHi during restricted intestinal circulation and at reperfusion. Local control mechanisms were insufficient at a PSMA of 30 mmHg, pHi was reduced to 7.10 and intestinal net lactate production was demonstrated. Absence of anaerobic intestinal metabolism was verified at PSMA ≥ 50 mmHg, pHi ≥ 7.22 and a PCO2 gap ≤ 15.8 mmHg. Dopexamine induced negative regional metabolic effects at the lowest PSMA, as expressed by decreased PO2 TISSUE and pHi, increased PCO2 gap and intestinal net lactate production.

    Conclusions: CST reflected changes in pHi, induced by intestinal hypoperfusion and at reperfusion. Levels of PSMA, pHi and PCO2 gap as indicators of aerobic conditions were defined. Dopexamine induced a decrease of PO2 TISSUE and pHi as well as an increase in lactate flux at the lowest PSMA level.

  • 187.
    Fytagoridis, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Blomstedt, Patric
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Complications and side effects of deep brain stimulation in the posterior subthalamic area.2010In: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 88, no 2, p. 88-93Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The posterior subthalamic area (PSA), including the zona incerta and prelemniscal radiation (Raprl), has recently been presented in number of publications as a promising target for deep brain stimulation (DBS) in the treatment of various movement disorders. In order to evaluate the safety of the procedure, we analyzed our initial 40 patients for complications and side effects. METHODS: 40 patients treated with PSA DBS for Parkinson's disease, essential tremor and other forms of tremor were included. RESULTS: The most severe complication was 1 transient mild hemiparesis and 1 infection. Minor complications and side effects were relatively frequent, including mild transient dysphasia in 22.5% of the patients. CONCLUSIONS: Few serious complications were encountered, and we consider the PSA to be a safe target for DBS.

  • 188.
    Fytagoridis, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. Neurosurgery, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm. Asia-Pacific Centre for Neuromodulation, Queensland Brain Institute, University of Queensland.
    Heard, Tomas
    Samuelsson, Jennifer
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. Department of Neurosurgery, Sahlgrenska University Hospital, Göteborg.
    Zsigmond, Peter
    Jiltsova, Elena
    Skyrman, Simon
    Skoglund, Thomas
    Coyne, Terry
    Silburn, Peter
    Blomstedt, Patric
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Surgical Replacement of Implantable Pulse Generator in Deep Brain Stimulation: Adverse Events and Risk Factors in a Multicenter Cohort2016In: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 94, no 4, p. 235-239Article in journal (Refereed)
    Abstract [en]

    Background: Deep brain stimulation (DBS) is a growing treatment modality, and most DBS systems require replacement of the implantable pulse generator (IPG) every few years. The literature regarding the potential impact of adverse events of IPG replacement on the longevity of DBS treatments is rather scarce. Objective: To investigate the incidence of adverse events, including postoperative infections, associated with IPG replacements in a multicenter cohort. Methods: The medical records of 808 patients from one Australian and five Swedish DBS centers with a total of 1,293 IPG replacements were audited. A logistic regression model was used to ascertain the influence of possible predictors on the incidence of adverse events. Results: The overall incidence of major infections was 2.3% per procedure, 3.7% per patient and 1.7% per replaced IPG. For 28 of 30 patients this resulted in partial or complete DBS system removal. There was an increased risk of infection for males (OR 3.6, p = 0.026), and the risk of infection increased with the number of prior IPG replacements (OR 1.6, p < 0.005). Conclusions: The risk of postoperative infection with DBS IPG replacement increases with the number of previous procedures. There is a need to reduce the frequency of IPG replacements. 

  • 189.
    Fytagoridis, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. Department of Clinical Neuroscience, Neurosurgery, Karolinska Institutet, Stockholm.
    Åström, Mattias
    Samuelsson, Jennifer
    Blomstedt, Patric
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Deep Brain Stimulation of the Caudal Zona Incerta: Tremor Control in Relation to the Location of Stimulation Fields2016In: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 94, no 6, p. 363-370Article in journal (Refereed)
    Abstract [en]

    Background: The caudal zona incerta (cZi) and posterior subthalamic area (PSA) are an emerging deep brain stimulation (DBS) target for essential tremor (ET). Objectives: To evaluate the efficacy of tremor control in relation to the anatomical locations of stimulation fields in 50 patients with ET and DBS of the cZi. Methods: A total of 240 contacts were evaluated separately with monopolar stimulation, and amplitudes were optimized for improvement of tremor and hand function. Stimulation fields, i.e., volumes of neural activation, were simulated for each optimized setting and assembled into probabilistic stimulation maps (PSMs). Results: There were differences in the anatomical distribution of PSMs associated with good versus poor tremor control. The location of PSMs which achieved good and excellent tremor control corresponded well with the PSM for the clinically used settings, and they were located within the superior part of the PSA. Conclusions: PSMs may serve as a useful tool for defining the most efficacious anatomical location of stimulation. The best tremor control in this series of cZi DBS was achieved with stimulation of the superior part of the PSA, which corresponds to the final part of the cerebellothalamic projections before they reach the ventral lateral thalamus.

  • 190.
    Fäldt Beding, Anna
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Characterization of the tumor stroma in breast cancer and matching lymph node: A pilot study with Col1 and Col42015Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 191. Gasull, Magda
    et al.
    Pumarega, José
    Kiviranta, Hannu
    Rantakokko, Panu
    Raaschou-Nielsen, Ole
    Bergdahl, Ingvar A.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Sandanger, Torkjel Manning
    Goñi, Fernando
    Cirera, Lluís
    Donat-Vargas, Carolina
    Alguacil, Juan
    Iglesias, Mar
    Tjønneland, Anne
    Overvad, Kim
    Mancini, Francesca Romana
    Boutron-Ruault, Marie-Christine
    Severi, Gianluca
    Johnson, Theron
    Kühn, Tilman
    Trichopoulou, Antonia
    Karakatsani, Anna
    Peppa, Eleni
    Palli, Domenico
    Pala, Valeria
    Tumino, Rosario
    Naccarati, Alessio
    Panico, Salvatore
    Verschuren, Monique
    Vermeulen, Roel
    Rylander, Charlotta
    Haugdahl Nøst, Therese
    Rodríguez-Barranco, Miguel
    Molinuevo, Amaia
    Chirlaque, María-Dolores
    Ardanaz, Eva
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Key, Tim
    Ye, Weimin
    Umeå University, Faculty of Medicine, Department of Biobank Research. Department of Medical Epidemiology and Biostatistics Karolinska Institutet, Stockholm, Sweden.
    Jenab, Mazda
    Michaud, Dominique
    Matullo, Giuseppe
    Canzian, Federico
    Kaaks, Rudolf
    Nieters, Alexandra
    Nöthlings, Ute
    Jeurnink, Suzanne
    Chajes, Veronique
    Matejcic, Marco
    Gunter, Marc
    Aune, Dagfinn
    Riboli, Elio
    Agudo, Antoni
    Gonzalez, Carlos Alberto
    Weiderpass, Elisabete
    Bueno-de-Mesquita, Bas
    Duell, Eric J.
    Vineis, Paolo
    Porta, Miquel
    Methodological issues in a prospective study on plasma concentrations of persistent organic pollutants and pancreatic cancer risk within the EPIC cohort2019In: Environmental Research, ISSN 0013-9351, E-ISSN 1096-0953, Vol. 169, p. 417-433Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The use of biomarkers of environmental exposure to explore new risk factors for pancreatic cancer presents clinical, logistic, and methodological challenges that are also relevant in research on other complex diseases.

    OBJECTIVES: First, to summarize the main design features of a prospective case-control study -nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort- on plasma concentrations of persistent organic pollutants (POPs) and pancreatic cancer risk. And second, to assess the main methodological challenges posed by associations among characteristics and habits of study participants, fasting status, time from blood draw to cancer diagnosis, disease progression bias, basis of cancer diagnosis, and plasma concentrations of lipids and POPs. Results from etiologic analyses on POPs and pancreatic cancer risk, and other analyses, will be reported in future articles.

    METHODS: Study subjects were 1533 participants (513 cases and 1020 controls matched by study centre, sex, age at blood collection, date and time of blood collection, and fasting status) enrolled between 1992 and 2000. Plasma concentrations of 22 POPs were measured by gas chromatography - triple quadrupole mass spectrometry (GC-MS/MS). To estimate the magnitude of the associations we calculated multivariate-adjusted odds ratios by unconditional logistic regression, and adjusted geometric means by General Linear Regression Models.

    RESULTS: There were differences among countries in subjects' characteristics (as age, gender, smoking, lipid and POP concentrations), and in study characteristics (as time from blood collection to index date, year of last follow-up, length of follow-up, basis of cancer diagnosis, and fasting status). Adjusting for centre and time of blood collection, no factors were significantly associated with fasting status. Plasma concentrations of lipids were related to age, body mass index, fasting, country, and smoking. We detected and quantified 16 of the 22 POPs in more than 90% of individuals. All 22 POPs were detected in some participants, and the smallest number of POPs detected in one person was 15 (median, 19) with few differences by country. The highest concentrations were found for p,p'-DDE, PCBs 153 and 180 (median concentration: 3371, 1023, and 810 pg/mL, respectively). We assessed the possible occurrence of disease progression bias (DPB) in eight situations defined by lipid and POP measurements, on one hand, and by four factors: interval from blood draw to index date, tumour subsite, tumour stage, and grade of differentiation, on the other. In seven of the eight situations results supported the absence of DPB.

    CONCLUSIONS: The coexistence of differences across study centres in some design features and participant characteristics is of relevance to other multicentre studies. Relationships among subjects' characteristics and among such characteristics and design features may play important roles in the forthcoming analyses on the association between plasma concentrations of POPs and pancreatic cancer risk.

  • 192. Ge, Wenzhen
    et al.
    Clendenen, Tess V.
    Afanasyeva, Yelena
    Koenig, Karen L.
    Agnoli, Claudia
    Brinton, Louise A.
    Dorgan, Joanne F.
    Eliassen, A. Heather
    Falk, Roni T.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Biobank Research. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Hankinson, Susan E.
    Hoffman-Bolton, Judith
    Key, Timothy J.
    Krogh, Vittorio
    Nichols, Hazel B.
    Sandler, Dale P.
    Schoemaker, Minouk J.
    Sluss, Patrick M.
    Sund, Malin
    Department of Surgery, Umeå University Hospital, Umeå, Sweden.
    Swerdlow, Anthony J.
    Visvanathan, Kala
    Liu, Mengling
    Zeleniuch-Jacquotte, Anne
    Circulating anti-Müllerian hormone and breast cancer risk: a study in ten prospective cohorts2018In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 142, no 11, p. 2215-2226Article in journal (Refereed)
    Abstract [en]

    A strong positive association has been observed between circulating anti‐Müllerian hormone (AMH), a biomarker of ovarian reserve, and breast cancer risk in three prospective studies. Confirming this association is important because of the paucity of biomarkers of breast cancer risk in premenopausal women. We conducted a consortium study including ten prospective cohorts that had collected blood from premenopausal women. A nested case–control design was implemented within each cohort. A total of 2,835 invasive (80%) and in situ (20%) breast cancer cases were individually matched to controls (n = 3,122) on age at blood donation. AMH was measured using a high sensitivity enzyme‐linked immunoabsorbent assay. Conditional logistic regression was applied to the aggregated dataset. There was a statistically significant trend of increasing breast cancer risk with increasing AMH concentration (ptrend across quartiles <0.0001) after adjusting for breast cancer risk factors. The odds ratio (OR) for breast cancer in the top vs. bottom quartile of AMH was 1.60 (95% CI = 1.31–1.94). Though the test for interaction was not statistically significant (pinteraction = 0.15), the trend was statistically significant only for tumors positive for both estrogen receptor (ER) and progesterone receptor (PR): ER+/PR+: ORQ4–Q1 = 1.96, 95% CI = 1.46–2.64, ptrend <0.0001; ER+/PR−: ORQ4–Q1 = 0.82, 95% CI = 0.40–1.68, ptrend = 0.51; ER−/PR+: ORQ4–Q1 = 3.23, 95% CI = 0.48–21.9, ptrend = 0.26; ER−/PR−: ORQ4–Q1 = 1.15, 95% CI = 0.63–2.09, ptrend = 0.60. The association was observed for both pre‐ (ORQ4–Q1= 1.35, 95% CI = 1.05–1.73) and post‐menopausal (ORQ4–Q1 = 1.61, 95% CI = 1.03–2.53) breast cancer (pinteraction = 0.34). In this large consortium study, we confirmed that AMH is associated with breast cancer risk, with a 60% increase in risk for women in the top vs. bottom quartile of AMH.

    What's new? To make informed decisions about screening and prevention, women need tools to accurately assess their breast cancer risk. Young women have few predictive biomarkers to look to; estrogen and progesterone are only weakly predictive before menopause. Anti-Müllerian hormone (AMH), which strongly correlates with age at menopause, may also correlate with breast cancer risk, according to some previous data. Here, the authors test this correlation by conducting nested case-control studies within ten different cohorts. They found that breast cancer risk increased along with increasing AMH concentration, confirming this hormone as a possible biomarker for breast cancer.

  • 193.
    Gkekas, Ioannis
    et al.
    Department of Surgery, Sunderby Medical Center, Luleå, Sweden.
    Palmgren, Jonathan
    Department of Surgery, Sunderby Medical Center, Luleå, Sweden.
    Näsvall, Pia
    Department of Surgery, Sunderby Medical Center, Luleå, Sweden.
    Dahlberg, Michael
    Department of Surgery, Sunderby Medical Center, Luleå, Sweden.
    Intra-abdominal organ strangulation during intraoperative endoscopic retrograde cholangiopancreatography with rendezvous cannulation: case report2015In: Endoscopy, ISSN 0013-726X, E-ISSN 1438-8812, Vol. 47, p. E231-E231Article in journal (Refereed)
  • 194. Grong, Eivind
    et al.
    Kulseng, Bård
    Arbo, Ingerid Brænne
    Nord, Christoffer
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
    Eriksson, Maria
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
    Ahlgren, Ulf
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
    Mårvik, Ronald
    Sleeve gastrectomy, but not duodenojejunostomy, preserves total beta-cell mass in Goto-Kakizaki rats evaluated by three-dimensional optical projection tomography2016In: Surgical Endoscopy, ISSN 0930-2794, E-ISSN 1432-2218, Vol. 30, no 2, p. 532-542Article in journal (Refereed)
    Abstract [en]

    Background In type 2 diabetes mellitus, there is a progressive loss of beta-cell mass. Bariatric surgery has in recent investigations showed promising results in terms of diabetes remission, but little is established regarding the effect of surgery on the survival or regeneration of pancreatic beta-cells. In this study, we aim to explore how bariatric surgery with its subsequent hormonal alterations affects the islets of Langerhans.

    Methods Twenty-four Goto-Kakizaki rats were operated with duodenojejunostomy (DJ), sleeve gastrectomy (SG) or sham operation. From the 38th week after surgery, body weight, fasting blood glucose, glycosylated hemoglobin, mixed meal tolerance with repeated measures of insulin, glucagon-like peptide 1, gastrin and total ghrelin were evaluated. Forty-six weeks after surgery, the animals were euthanized and the total beta-cell mass in all animals was examined by three-dimensional volume quantification by optical projection tomography based on the signal from insulin-specific antibody staining.

    Results Body weight did not differ between groups (Pg = 0.37). SG showed lower fasting blood glucose compared to DJ and sham (Pg = 0.037); HbA1c levels in SG were lower compared to DJ only (p\0.05). GLP-1 levels were elevated for DJ compared to SG and sham (Pg = 0.001), whereas gastrin levels were higher in SG compared to the two other groups (Pg = 0.002). Beta-cell mass was significantly greater in animals operated with SG compared to both DJ and sham (p = 0.036).

    Conclusion Sleeve gastrectomy is superior to duodenojejunostomy and sham operation when comparing the preservation of beta-cell mass 46 weeks after surgery in Goto-Kakizaki rats. This could be related to both the increased gastrin levels and the long-term improvement in glycemic parameters observed after this procedure.

  • 195. Grote, V. A.
    et al.
    Rohrmann, S.
    Nieters, A.
    Dossus, L.
    Tjonneland, A.
    Halkjaer, J.
    Overvad, K.
    Fagherazzi, G.
    Boutron-Ruault, M. C.
    Morois, S.
    Teucher, B.
    Becker, S.
    Sluik, D.
    Boeing, H.
    Trichopoulou, A.
    Lagiou, P.
    Trichopoulos, D.
    Palli, D.
    Pala, V.
    Tumino, R.
    Vineis, P.
    Panico, S.
    Rodriguez, L.
    Duell, E. J.
    Molina-Montes, E.
    Dorronsoro, M.
    Huerta, J. M.
    Ardanaz, E.
    Jeurnink, S. M.
    Beulens, J. W. J.
    Peeters, P. H. M.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Ye, W.
    Lindkvist, B.
    Johansen, D.
    Khaw, K. T.
    Wareham, N.
    Allen, N.
    Crowe, F.
    Jenab, M.
    Romieu, I.
    Michaud, D. S.
    Riboli, E.
    Romaguera, D.
    Bueno-de-Mesquita, H. B.
    Kaaks, R.
    Diabetes mellitus, glycated haemoglobin and C-peptide levels in relation to pancreatic cancer risk: a study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort2011In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 54, no 12, p. 3037-3046Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis: There has been long-standing debate about whether diabetes is a causal risk factor for pancreatic cancer or a consequence of tumour development. Prospective epidemiological studies have shown variable relationships between pancreatic cancer risk and blood markers of glucose and insulin metabolism, overall and as a function of lag times between marker measurements (blood donation) and date of tumour diagnosis.

    Methods: Pre-diagnostic levels of HbA(1c) and C-peptide were measured for 466 participants with pancreatic cancer and 466 individually matched controls within the European Prospective Investigation into Cancer and Nutrition. Conditional logistic regression models were used to estimate ORs for pancreatic cancer.

    Results: Pancreatic cancer risk gradually increased with increasing pre-diagnostic HbA(1c) levels up to an OR of 2.42 (95% CI 1.33, 4.39 highest [>= 6.5%, 48 mmol/mol] vs lowest [<= 5.4%, 36 mmol/mol] category), even for individuals with HbA(1c) levels within the non-diabetic range. C-peptide levels showed no significant relationship with pancreatic cancer risk, irrespective of fasting status. Analyses showed no clear trends towards increasing hyperglycaemia (as marked by HbA(1c) levels) or reduced pancreatic beta cell responsiveness (as marked by C-peptide levels) with decreasing time intervals from blood donation to cancer diagnosis.

    Conclusions/interpretation: Our data on HbA(1c) show that individuals who develop exocrine pancreatic cancer tend to have moderate increases in HbA(1c) levels, relatively independently of obesity and insulin resistance-the classic and major risk factors for type 2 diabetes. While there is no strong difference by lag time, more data are needed on this in order to reach a firm conclusion.

  • 196. Grote, VA
    et al.
    Kaaks, R
    Nieters, A
    Tjonneland, A
    Halkjaer, J
    Overvad, K
    Nielsen, MR Skjelbo
    Boutron-Ruault, MC
    Clavel-Chapelon, F
    Racine, A
    Teucher, B
    Becker, S
    Pischon, T
    Boeing, H
    Trichopoulou, A
    Cassapa, C
    Stratigakou, V
    Palli, D
    Krogh, V
    Tumino, R
    Vineis, P
    Panico, S
    Rodriguez, L
    Duell, EJ
    Sanchez, M-J
    Dorronsoro, M
    Navarro, C
    Gurrea, AB
    Siersema, PD
    Peeters, PHM
    Ye, W
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Lindkvist, B
    Johansen, D
    Khaw, K-T
    Wareham, N
    Allen, NE
    Travis, RC
    Fedirko, V
    Jenab, M
    Michaud, DS
    Chuang, S-C
    Romaguera, D
    Bueno-de-Mesquita, HB
    Rohrmann, S
    Inflammation marker and risk of pancreatic cancer: a nested case-control study within the EPIC cohort2012In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 106, no 11, p. 1866-1874Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Established risk factors for pancreatic cancer include smoking, long-standing diabetes, high body fatness, and chronic pancreatitis, all of which can be characterised by aspects of inflammatory processes. However, prospective studies investigating the relation between inflammatory markers and pancreatic cancer risk are scarce.

    METHODS: We conducted a nested case-control study within the European Prospective Investigation into Cancer and Nutrition, measuring prediagnostic blood levels of C-reactive protein (CRP), interleukin-6 (IL-6), and soluble receptors of tumour necrosis factor-a (sTNF-R1, R2) in 455 pancreatic cancer cases and 455 matched controls. Odds ratios (ORs) were estimated using conditional logistic regression models.

    RESULTS: None of the inflammatory markers were significantly associated with risk of pancreatic cancer overall, although a borderline significant association was observed for higher circulating sTNF-R2 (crude OR = 1.52 (95% confidence interval (CI) 0.97-2.39), highest vs lowest quartile). In women, however, higher sTNF-R1 levels were significantly associated with risk of pancreatic cancer (crude OR = 1.97 (95% CI 1.02-3.79)). For sTNF-R2, risk associations seemed to be stronger for diabetic individuals and those with a higher BMI.

    CONCLUSION: Prospectively, CRP and IL-6 do not seem to have a role in our study with respect to risk of pancreatic cancer, whereas sTNF-R1 seemed to be a risk factor in women and sTNF-R2 might be a mediator in the risk relationship between overweight and diabetes with pancreatic cancer. Further large prospective studies are needed to clarify the role of proinflammatory proteins and cytokines in the pathogenesis of exocrine pancreatic cancer. British Journal of Cancer (2012) 106, 1866-1874. doi:10.1038/bjc.2012.172 www.bjcancer.com Published online 26 April 2012 (C) 2012 Cancer Research UK

  • 197. Grote, Verena A.
    et al.
    Nieters, Alexandra
    Kaaks, Rudolf
    Tjonneland, Anne
    Roswall, Nina
    Overvad, Kim
    Nielsen, Michael R. Skjelbo
    Clavel-Chapelon, Francoise
    Boutron-Ruault, Marie Christine
    Racine, Antoine
    Teucher, Birgit
    Lukanova, Annekatrin
    Boeing, Heiner
    Drogan, Dagmar
    Trichopoulou, Antonia
    Trichopoulos, Dimitrios
    Lagiou, Pagona
    Palli, Domenico
    Sieri, Sabina
    Tumino, Rosario
    Vineis, Paolo
    Mattiello, Amalia
    Argueelles Suarez, Marcial Vicente
    Duell, Eric J.
    Sanchez, Maria-Jose
    Dorronsoro, Miren
    Huerta Castano, Jose Maria
    Barricarte, Aurelio
    Jeurnink, Suzanne M.
    Peeters, Petra H. M.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Ye, Weimin
    Regner, Sara
    Lindkvist, Bjorn
    Khaw, Kay-Tee
    Wareham, Nick
    Allen, Naomi E.
    Crowe, Francesca L.
    Fedirko, Veronika
    Jenab, Mazda
    Romaguera, Dora
    Siddiq, Afshan
    Bueno-de-Mesquita, H. Bas
    Rohrmann, Sabine
    The associations of advanced Glycation end products and its soluble receptor with Pancreatic Cancer risk: A Case-Control Study within the Prospective EPIC Cohort2012In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 21, no 4, p. 619-628Article in journal (Refereed)
    Abstract [en]

    Background: Advanced glycation end products (AGE) and their receptors (RAGE) have been implicated in cancer development through their proinflammatory capabilities. However, prospective data on their association with cancer of specific sites, including pancreatic cancer, are limited. Methods: Prediagnostic blood levels of the AGE product Ne-(carboxymethyl) lysine (CML) and the endogenous secreted receptor for AGE (esRAGE) were measured using ELISA in 454 patients with exocrine pancreatic cancer and individually matched controls within the European Prospective Investigation into Cancer and Nutrition (EPIC). Pancreatic cancer risk was estimated by calculating ORs with corresponding 95% confidence intervals (CI). Results: Elevated CML levels tended to be associated with a reduction in pancreatic cancer risk [OR = 0.57 (95% CI, 0.32-1.01) comparing highest with lowest quintile), whereas no association was observed for esRAGE (OR = 0.98; 95% CI, 0.62-1.54). Adjustments for body mass index and smoking attenuated the inverse associations of CML with pancreatic cancer risk (OR = 0.78; 95% CI, 0.41-1.49). There was an inverse association between esRAGE and risk of pancreatic cancer for cases that were diagnosed within the first 2 years of follow-up [OR = 0.46 (95% CI, 0.22-0.96) for a doubling in concentration], whereas there was no association among those with a longer follow-up (OR = 1.11; 95% CI, 0.88-1.39; P-interaction = 0.002). Conclusions and Impact: Our results do not provide evidence for an association of higher CML or lower esRAGE levels with risk of pancreatic cancer. The role of AGE/RAGE in pancreatic cancer would benefit from further investigations. Cancer Epidemiol Biomarkers Prev; 21(4); 619-28. (C) 2012 AACR.

  • 198.
    Gunnarsson, Ulf
    Department of Surgical Sciences, University Hospital, Uppsala, Sweden.
    Quality assurance in surgical oncology: Colorectal cancer as an example2003In: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 29, no 1, p. 89-94Article in journal (Refereed)
    Abstract [en]

    Quality assurance in surgical oncology is a field of growing importance. National, regional and local systems have been built up in many countries. Often the quality assurance projects are linked to different registers. The advantage of such a link is the possibility of obtaining population-based data from unselected health care institutions. Few discussions of results from such projects have been published. Quality assurance of colorectal cancer surgery implies the development and use of systems for improvement all the way from detection of the cancer to the outcome as survival and patient satisfaction. To achieve this we must know what methods are being used and the outcome of our treatments. Designing processes for improvement necessitates careful planning, including decisions about end-points. Some crucial issues are discussed step-by-step in the present paper. In addition to auditing and providing collegial feedback, quality assurance is a tool for closing the gap between clinical practice and evidence based medicine and for creating new evidences as well as monitoring the introduction of new techniques and their effects.

  • 199.
    Gunnarsson, Ulf
    et al.
    Department of Surgery, Mora Hospital, Sweden.
    Degerman, M
    Davidsson, A
    Heuman, R
    Is elective hernia repair worthwhile in old patients?1999In: European Journal of Surgery, ISSN 1102-4151, E-ISSN 1741-9271, Vol. 165, no 4, p. 326-32Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To find out if elective herniorraphy in patients aged 75 and over is worthwhile.

    DESIGN: Retrospective study.

    SETTING: District hospital, Sweden.

    SUBJECTS: 146 consecutive patients aged 75 years or more, who had their hernias repaired during the period 1992-95.

    MAIN OUTCOME MEASURES: Patient satisfaction measured by a five-point analogue scale. Clinical and personal details, morbidity, mortality, and surgical variables were obtained from case records.

    RESULTS: Community social service was not required by 114 (78%) of the patients and 15 (22%) had no preoperative complaints. Our patients rated their satisfaction with their choice to have an operation, as well as its effect on their preoperative symptoms as 4.9. Emergency operations (p = 0.02), femoral hernias (p = 0.01) and direct inguinal hernias (direct:indirect ratio 0.81) were more common in this age group. Femoral and direct inguinal hernias tended to recur more often than usual. Emergency operation, dementia, and diabetes were associated with a reduced short-term survival.

    CONCLUSION: Elective hernia repair in an elderly population is highly appreciated by the patients, and worthwhile. If coexisting disease and domestic arrangements are controlled, the patients' need for hospital care can be minimised. Mesh is recommended in femoral and direct inguinal hernias, which were associated with an increased reoperation frequency. A more vigilant protocol of indications for hernia surgery in the aged may minimise the need for both emergency and unnecessary operations.

  • 200.
    Gunnarsson, Ulf
    et al.
    Department of Surgery, Mora Hospital, Mora, Sweden .
    Heuman, R
    Patient experience ratings in surgery for recurrent hernia1999In: Hernia, ISSN 1265-4906, E-ISSN 1248-9204, Vol. 3, no 2, p. 69-73Article in journal (Refereed)
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