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  • 151.
    Budtz-Lilly, Jacob
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery. Aarhus Univ Hosp, Dept Cardiothorac & Vasc Surg, Aarhus, Denmark..
    Venermo, M.
    Helsinki Univ Hosp, Dept Vasc Surg, Helsinki, Finland..
    Debus, S.
    Univ Heart Ctr Hamburg Eppendorf, Dept Vasc Med, Hamburg, Germany..
    Behrendt, C. -A
    Altreuther, M.
    St Olavs Hosp, Dept Vasc Surg, Trondheim, Norway..
    Belles, B.
    Australian & New Zealand Soc Vasc Surg, Melbourne, Vic, Australia..
    Szeberin, Z.
    Semmelweis Univ, Dept Vasc Surg, Budapest, Hungary..
    Eldrup, N.
    Aarhus Univ Hosp, Dept Cardiothorac & Vasc Surg, Aarhus, Denmark.;Natl Univ Hosp Iceland, Dept Surg, Reykjavik, Iceland..
    Danielsson, G.
    Thomson, I.
    Dunedin Publ Hosp, Dunedin Sch Med, Dept Vasc Surg, Dunedin, New Zealand..
    Wigger, P.
    Kantonsspital Winterthur, Dept Cardiovasc Surg, Winterthur, Switzerland..
    Björck, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Loftus, I.
    St Georges Univ London, Dept Vasc Surg, London, England..
    Mani, Kevin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Editor's Choice - Assessment of International Outcomes of Intact Abdominal Aortic Aneurysm Repair over 9 Years2017In: European Journal of Vascular and Endovascular Surgery, ISSN 1078-5884, E-ISSN 1532-2165, Vol. 54, no 1, p. 13-20Article in journal (Refereed)
    Abstract [en]

    Background: Case mix and outcomes of complex surgical procedures vary over time and between regions. This study analyses peri-operative mortality after intact abdominal aortic aneurysm (AAA) repair in 11 countries over 9 years. Methods: Data on primary AAA repair from vascular surgery registries in 11 countries for the years 2005-2009 and 2010-2013 were analysed. Multivariate adjusted logistic regression analyses were carried out to adjust for variations in case mix. Results: A total of 83,253 patients were included. Over the two periods, the proportion of patients >= 80 years old increased (18.5% vs. 23.1%; p < .0001) as did the proportion of endovascular repair (EVAR) (44.3% vs. 60.6; p < .0001). In the latter period, 25.8% of AAAs were less than 5.5 cm. The mean annual volume of open repairs per centre decreased from 12.9 to 10.6 between the two periods (p < .0001), and it increased for EVAR from 10.0 to 17.1 (p < .0001). Overall, peri-operative mortality fell from 3.0% to 2.4% (p < .0001). Mortality for EVAR decreased from 1.5% to 1.1% (p < .0001), but the outcome worsened for open repair from 3.9% to 4.4% (p = .008). The peri-operative risk was greater for octogenarians (overall, 3.6% vs. 2.1%, p < .0001; open, 9.5% vs. 3.6%, p < .0001; EVAR, 1.8% vs. 0.7%, p < .0001), and women (overall, 3.8% vs. 2.2%, p < .0001; open, 6.0% vs. 4.0%, p < .0001; EVAR, 1.9% vs. 0.9%, p < .0001). Peri-operative mortality after repair of AAAs <5.5 cm was 4.4% with open repair and 1.0% with EVAR, p < .0001. Conclusions: In this large international cohort, total peri-operative mortality continues to fall for the treatment of intact AAAs. The number of EVAR procedures now exceeds open procedures. Mortality after EVAR has decreased, but mortality for open operations has increased. The peri-operative mortality for small AM treatment, particularly open surgical repair, is still considerable and should be weighed against the risk of rupture.

  • 152.
    Budtz-Lilly, Jacob
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery. Aarhus University Hospital, Department of Vascular Surgery.
    Vikholm, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Wanhainen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Astudillo, Rafael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Thelin, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Mani, Kevin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Technical eligibility for endovascular treatment of the aortic arch after open type A aortic dissection repair2019In: Journal of Thoracic and Cardiovascular Surgery, ISSN 0022-5223, E-ISSN 1097-685XArticle in journal (Refereed)
    Abstract [en]

    Objective: To report on the technical eligibility of patients previously treated for Stanford type A aorta dissection (AAD) for endovascular aortic arch repair based on contemporary anatomical criteria for an arch inner-branched stentgraft (AIBS). 

     

    Methods: All patients treated for AAD from 2004-2015 at a single aortic centre were identified. Extent of repair and use of circulatory arrest were reported. Survival and reoperation were assessed using Kaplan Meier and competing risk models. Anatomic assessment was performed using 3-dimensional CT-imaging software. Primary outcome was survival ≥ 1 year and fulfilment of the AIBS anatomical criteria. 

     

    Results: A total of 198 patients were included (158 Debakey I, 32 Debakey II, and 8 Intramural hematoma). Mortality was 30-days: 16.2%, 1-year: 19.2%, 10-years: 45.0%. There were 129 patients with imaging beyond 1 year (mean, 47.8 months), while 89 (69.0%) were AIBS eligible. During follow-up, 19 (14.7%) patients met the threshold criteria for aortic arch treatment, of which 14 (73.7%) would be considered eligible for AIBS. Patients who underwent AAD repair with circulatory arrest and no distal clamp were more often eligible for endovascular repair (88.8%) than those operated with a distal clamp (72.5%), p=0.021. Among patients who did not meet the AIBS anatomical criteria, the primary reasons were mechanical valve (40%) and insufficient proximal seal (30%). 

     

    Conclusion: More than two thirds of post AAD patients repair are technically eligible for endovascular AIBS repair. Development of devices that can accommodate a mechanical aortic valve and a greater awareness of sufficient graft length would significantly increase availability.

  • 153.
    Bue, Peter
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Urinary bladder carcinoma, preclinical and clinical studies on EGFR based targeting1998Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Radical cystectomy with bilateral pelvic lymphadenectomy is the standard treatment for muscle-invasive transitional cell carcinoma of the urinary bladder. Despite presumably localised malignancies and efficacious management about 50% of patients will die within 5 years, the majority due to metastatic disease. These cases cannot be identified during the initial staging assessment and are assumed to have micrometastases preoperatively. Thus, there is a need of improved methods for diagnosis and therapy.

    Tumour therapy via targeting means that specific substances carrying cytotoxic agents are transferred selectively to the tumour, directed against tumour specific membrane antigens. Targeted radionuclide therapy could be an attractive way to trace and treat small volumes of tumour ceils. Damage to the normal tissue is limited while the tumour target could be optimally sterilised.

    The epidermal growth factor receptor (EGFR) is known to be overexpressed in bladder. The aim of this work was to assess the possibilities for EGFR based targeting of urinary bladder carcinoma.

    The EGFR expression was investigated using immunohistochemical technique with a monoclonal antibody in primary tumour and concurrent metastases in 20 patients. A major part of the metastatic samples were homogeneously stained and showed a moderate to strong staining of EGFR in the cell-membranes. The expression in primary bladder tumors and metastases were quite similar.

    Binding, internalisation and degradation of EGF-dextran conjugates was investigated in two different bladder cancer cell lines. The EGF conjugate bound specifically to the EGFR in both and was retained intracellular and membrane-bound for longer time than EGF, which was used as control. The degradation was decreased when dextran was coupled to EGF. The binding characteristic of two different sizes of EGF-dextran conjugates in multicellular spheroids of a bladder cancer cell line was investigated. Both conjugates bound to the spheroids and showed increased binding up to 48 hours.

    The binding characteristic of EGF-dextran in a xenograft tumour model was investigated. The specific binding was 90-95% in a control experiment in vitro. Accumulation of the conjugate was found in the tumour xenograft but also a high uptake in the kidneys. This most probably reflected the route of excretion.

    To determine if intravesically administered EGF-conjungate could be selectively accumulated intumor tissue, eight patients received the conjugate intravesically followed by bladder irrigation andtransurethral resection. The uptake was followed with SPECT and the radioactivity in the biopsyspecimens from normal urothelium and tumor areas were measured in a gamma counter. The EGF-dextran conjungate showed a high uptake in tumour compared to macroscopically normal urothel.

    In conclusion EGFR based targeting of urinary bladder carcinoma seems promising both formetastatic and local disease.

  • 154.
    Burdess, Anne
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Mani, Kevin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Tegler, Gustaf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Wanhainen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Early Experience With a Novel Thoracic Stent Design for the Prevention of Distal Stent Graft-Induced New Entry Tears (d-SINE)2018In: Journal of Vascular Surgery, ISSN 0741-5214, E-ISSN 1097-6809, Vol. 68, no 5, p. E153-E153Article in journal (Other academic)
  • 155.
    Burdess, Anne
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Mani, Kevin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Tegler, Gustaf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Wanhainen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Stent-graft induced new entry tears after type B aortic dissection: how to treat and how to prevent?2018In: Journal of Cardiovascular Surgery, ISSN 0021-9509, E-ISSN 1827-191X, Vol. 59, no 6, p. 789-796Article, review/survey (Refereed)
    Abstract [en]

    Progress of aortic disease after stent-graft treatment of aortic dissection includes the risk of stent graft-induced new entry (SINE). In this paper we review the incidence and mechanisms thought to be responsible for retrograde ascending and distal SINE after thoracic endovascular aortic repair (TEVAR) for type B dissection, and examine potential techniques for treatment and prevention. Although the risk of proximal SINE is low, the fatality of this complication requires vigilance in patients who develop new onset symptoms in the early period after TEVAR treatment. Careful technique, minimal oversizing, and use of disease specific stent grafts may reduce the risk for proximal SINE. Distally, SINE is more frequently seen during follow-up in patients treated for chronic dissection. The most important risk factor is oversizing of the stent-graft compared to the true lumen distal landing zone. Development of new disease specific stent grafts with reduced distal radial force may reduce the risk for distal SINE.

  • 156.
    Burdess, Anne
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Wanhainen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Tegler, Gustaf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Mani, Kevin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Fenestrated and Branched Endovascular Repair of Aortic Arch Pathology2018In: Journal of Vascular Surgery, ISSN 0741-5214, E-ISSN 1097-6809, Vol. 68, no 5, p. E154-E154Article in journal (Other academic)
  • 157. Burgaz, Ann
    et al.
    Åkesson, A.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Wolk, A.
    25-hydroxyvitamin D accumulation during summer in elderly women at latitude 60 degrees N2009In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 266, no 5, p. 476-483Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: During half of the year, cutaneous synthesis of 25-hydroxyvitamin D (25(OH)D) is not detectable at northern latitudes, leaving the population dependent on other sources for optimal vitamin D status. During April to September, 25(OH)D status may be improved by solar exposure. In this study, we measured seasonal differences in serum 25(OH)D concentrations and identified the major predictors of summer 25(OH)D concentrations. DESIGN: We assessed serum 25(OH)D concentrations during both winter and summer amongst 100 women, aged 61-83 years, randomly sampled from the Swedish Mammography Cohort. Participants completed two detailed questionnaires covering diet, use of dietary supplements and sun-related behaviour, the first in January through March and a second time in August through September. RESULTS: The mean seasonal increase in serum 25(OH)D concentrations was 38% from mean 72 +/- 23 nmol L(-1) during winter to 99 +/- 29 nmol L(-1) in summer. High summer 25(OH)D concentrations were associated with higher winter concentrations, preference of staying in sun instead of shade, having a nonsensitive skin type and normal body mass index. Based on multiple linear regression modelling, preferring sun, having nonsensitive skin type and normal weight as compared with preferring shade, having sensitive skin type and being obese, was associated with a 64 nmol L(-1) higher 25(OH)D concentrations during summer. CONCLUSIONS: Women with high winter 25(OH)D serum concentrations, with preference of staying in the sun instead of shade during summer, a skin type allowing for longer sun exposure and a normal weight had the highest summer 25(OH)D concentrations.

  • 158.
    Bushati, M.
    et al.
    Catharina Hosp, Dept Surg, POB 1350, NL-5602 ZA Eindhoven, Netherlands;Univ Padua, Surg Clin 1, Dept Surg Oncol & Gastroenterol, Padua, Italy.
    Rovers, K. P.
    Catharina Hosp, Dept Surg, POB 1350, NL-5602 ZA Eindhoven, Netherlands.
    Sommariva, A.
    Veneto Inst Oncol IOV IRCCS, Unit Surg Oncol Esophagus & Digest Tract, Castelfranco Veneto, TV, Italy.
    Sugarbaker, P. H.
    MedStar Washington Hosp Ctr, Ctr Gastrointestinal Malignancies, 106 Irving St NW,Suite 3900, Washington, DC 20010 USA.
    Morris, D. L.
    St George Hosp, Dept Surg, Gray St Kogarah, Sydney, NSW 2217, Australia.
    Yonemura, Y.
    Kishiwada Tokushukai Hosp, Peritoneal Surface Malignancy Ctr, 4-27-1 Kamori Cho, Kishiwada, Osaka 5968522, Japan.
    Quadros, C. A.
    Sao Rafael Hosp, Surg Oncol Unit, Ave Sao Rafael 2152, BR-41253190 Salvador, BA, Brazil.
    Somashekhar, S. P.
    Manipal Hosp, Manipal Comprehens Canc Ctr, Dept Surg Oncol & Robot Surg, 98 HAL Airport Rd, Bengaluru 560017, Karnataka, India.
    Ceelen, W.
    Ghent Univ Hosp Belgium, Dept Gastrointestinal Surg, Ghent, Belgium.
    Dube, P.
    Univ Montreal, Hosp Maisonneuve Rosemont, Dept Surg, Montreal, PQ, Canada.
    Li, Y.
    Capital Med Univ, Beijing Shijitan Hosp, Dept Peritoneal Canc Surg, Beijing, Peoples R China.
    Verwaal, V. J.
    Aarhus Univ Hosp, Dept Surg, Norrebrogade 44, DK-8000 Aarhus, Denmark.
    Glehen, O.
    Hosp Civils Lyon, Dept Surg Oncol, Lyon, France;Lyon Sud Hosp, Lyon Fac Med, Lyon, France.
    Piso, P.
    Hosp Barmherzige Bruder, Dept Gen & Visceral Surg, Regensburg, Germany.
    Spiliotis, J.
    European Interbalkan Med Ctr, Thessaloniki, Greece.
    Teo, M. C. C.
    Natl Canc Ctr Singapore, Singapore, Singapore.
    Gonzalez-Moreno, S.
    Univ Texas MD Anderson Canc Ctr, Surg Oncol, Madrid, Spain.
    Cashin, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Lehmann, K.
    Univ Hosp Zurich, Dept Visceral & Transplantat Surg, Zurich, Switzerland.
    Deraco, M.
    Fdn IRCCS Ist Nazl Tumori, Peritoneal Surface Malignancies Unit, Milan, Italy.
    Moran, B.
    Hampshire Hosp Fdn Trust, Peritoneal Malignancy Inst Basingstoke, Adelmaston Rd, Basingstoke RG24 9NA, Hants, England.
    de Hingh, I. H. J. T.
    Catharina Hosp, Dept Surg, POB 1350, NL-5602 ZA Eindhoven, Netherlands.
    The current practice of cytoreductive surgery and HIPEC for colorectal peritoneal metastases: Results of a worldwide web-based survey of the Peritoneal Surface Oncology Group International (PSOGI)2018In: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 44, no 12, p. 1942-1948Article in journal (Refereed)
    Abstract [en]

    Background: At present, selected patients with resectable colorectal peritoneal metastases (CRC-PM) are increasingly treated with a combination therapy of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). The aim of this study was to investigate the current worldwide practice.

    Methods: HIPEC experts from 19 countries were invited through the Peritoneal Surface Oncology Group International (PSOGI) to complete an online survey concerning their personal expertise and current hospital and country wide practice.

    Results: It is estimated that currently more than 3800 patients with CRC-PM (synchronous and metachronous) are annually treated with CRS and HIPEC in 430 centers. Integration of CRS and HIPEC in national guidelines varies, resulting in large treatment disparities between countries. Amongst the experts, there was general agreement on issues related to indication, surgical technique and follow up but less on systemic chemotherapy or proactive strategies.

    Conclusion: This international survey demonstrates that CRS and HIPEC is now performed on a large scale for CRC-PM patients. Variation in treatment may result in heterogeneity in surgical and oncological outcomes, emphasising the necessity to reach consensus on several issues of this comprehensive procedure. Future initiatives directed at achieving an international consensus statement are needed.

  • 159. Butt, Salma
    et al.
    Butt, Talha
    Jirstrom, Karin
    Hartman, Linda
    Amini, Rose-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Zhou, Wenjing
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Wärnberg, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Borgquist, Signe
    The Target for Statins, HMG-CoA Reductase, Is Expressed in Ductal Carcinoma-In Situ and May Predict Patient Response to Radiotherapy2014In: Annals of Surgical Oncology, ISSN 1068-9265, E-ISSN 1534-4681, Vol. 21, no 9, p. 2911-2919Article in journal (Refereed)
    Abstract [en]

    Background. Patients with ductal carcinoma-in-situ (DCIS) are currently not prescribed adjuvant systemic treatment after surgery and radiotherapy. Prediction of DCIS patients who would benefit from radiotherapy is warranted. Statins have been suggested to exert radio-sensitizing effects. The target for cholesterol-lowering statins is HMG-CoA reductase (HMGCR), the rate-limiting enzyme in the mevalonate pathway. The aim of this study was to examine HMGCR expression in DCIS and study its treatment predictive value. Methods. A population-based cohort including 458 women diagnosed with primary DCIS between 1986 and 2004 were followed until November 2011 to study long-term survival. Tumor tissue microarrays were constructed, and immunohistochemical analyses were performed to detect cytoplasmic protein expression of HMGCR. The association between DCIS HMGCR expression and invasive breast cancer recurrence-free survival (RFSinv) and overall survival (OS) was analyzed by Kaplan-Meier curves, log rank test, and Cox proportional hazard analysis. Results. HMGCR was strongly expressed in 24 % of the assessed DCIS samples, moderately expressed in 46 %, and weakly expressed in 23 %; no expression was detected in 7 % of the samples. During the follow-up time (median 13.8 years), 61 patients were diagnosed with an invasive breast cancer recurrence, and 80 patients died. A crude analysis showed no survival benefit from radiotherapy. However, patients with strong HMGCR expression showed an improved RFSinv (log rank, p = 0.03) and OS (log rank, p = 0.04) after radiotherapy. No statistically significant interaction was observed for HMGCR and radiotherapy (RFSinv p = 0.69 and OS p = 0.29). Conclusions. This study demonstrates HMGCR expression in DCIS and suggests HMGCR as a predictive marker of response to postoperative radiotherapy in DCIS, although the test for interaction was nonsignificant. Future DCIS studies addressing the potential of statin treatment targeting HMGCR are warranted.

  • 160.
    Byberg, Liisa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Gedeborg, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Ahlbom, Anders
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Berglund, Lars G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Wolk, Alicja
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Total mortality after changes in leisure time physical activity in 50 year old men: 35 year follow-up of population based cohort2009In: BMJ. British Medical Journal, E-ISSN 1756-1833, Vol. 338, p. b688-Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To examine how change in level of physical activity after middle age influences mortality and to compare it with the effect of smoking cessation. DESIGN: Population based cohort study with follow-up over 35 years. SETTING: Municipality of Uppsala, Sweden. PARTICIPANTS: 2205 men aged 50 in 1970-3 who were re-examined at ages 60, 70, 77, and 82 years. MAIN OUTCOME MEASURE: Total (all cause) mortality. RESULTS: The absolute mortality rate was 27.1, 23.6, and 18.4 per 1000 person years in the groups with low, medium, and high physical activity, respectively. The relative rate reduction attributable to high physical activity was 32% for low and 22% for medium physical activity. Men who increased their physical activity level between the ages of 50 and 60 continued to have a higher mortality rate during the first five years of follow-up (adjusted hazard ratio 2.64, 95% confidence interval 1.32 to 5.27, compared with unchanged high physical activity). After 10 years of follow-up their increased physical activity was associated with reduced mortality to the level of men with unchanged high physical activity (1.10, 0.87 to 1.38). The reduction in mortality associated with increased physical activity (0.51, 0.26 to 0.97, compared with unchanged low physical activity) was similar to that associated with smoking cessation (0.64, 0.53 to 0.78, compared with continued smoking). CONCLUSIONS: Increased physical activity in middle age is eventually followed by a reduction in mortality to the same level as seen among men with constantly high physical activity. This reduction is comparable with that associated with smoking cessation.

  • 161.
    Byberg, Liisa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    Gedeborg, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ahlbom, Anders
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Berglund, Lars G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Wolk, Alicja
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Total mortality after changes in leisure time physical activity in 50 year old men: 35 year follow-up of population based cohort (Reprinted from BMJ, vol 338, b688, 2009)2009In: British Journal of Sports Medicine, ISSN 0306-3674, E-ISSN 1473-0480, Vol. 43, no 7, p. 482-Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To examine how change in level of physical activity after middle age influences mortality and to compare it with the effect of smoking cessation.

    DESIGN: Population based cohort study with follow-up over 35 years.

    SETTING: Municipality of Uppsala, Sweden.

    PARTICIPANTS: 2205 men aged 50 in 1970-3 who were reexamined at ages 60, 70, 77, and 82 years.

    MAIN OUTCOME MEASURE: Total (all cause) mortality.

    RESULTS: The absolute mortality rate was 27.1, 23.6, and 18.4 per 1000 person years in the groups with low, medium, and high physical activity, respectively. The relative rate reduction attributable to high physical activity was 32% for low and 22% for medium physical activity. Men who increased their physical activity level between the ages of 50 and 60 continued to have a higher mortality rate during the first five years of follow-up (adjusted hazard ratio 2.64, 95% confidence interval 1.32 to 5.27, compared with unchanged high physical activity). After 10 years of follow-up their increased physical activity was associated with reduced mortality to the level of men with unchanged high physical activity (1.10, 0.87 to 1.38). The reduction in mortality associated with increased physical activity (0.51, 0.26 to 0.97, compared with unchanged low physical activity) was similar to that associated with smoking cessation (0.64, 0.53 to 0.78, compared with continued smoking).

    CONCLUSIONS: Increased physical activity in middle age is eventually followed by a reduction in mortality to the same level as seen among men with constantly high physical activity. This reduction is comparable with that associated with smoking cessation

  • 162.
    Bäckman, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Persson, Carl-Axel
    An observational study evaluating tacrolimus dose, exposure, and medication adherence after conversion from twice- to once-daily tacrolimus in liver and kidney transplant recipients2014In: Annals of Transplantation, ISSN 1425-9524, E-ISSN 2329-0358, Vol. 19, p. 138-144Article in journal (Refereed)
    Abstract [en]

    Background: Immunosuppression regimens in transplantation medicine are complex. Drugs with extended release action have simplified medication dosing without affecting efficacy. Material/Methods: This prospective, observational, multicenter study, conducted in a routine medical practice setting, evaluated changes in tacrolimus daily dose and trough levels and patient-reported medication adherence at day 90 after 1:1 ( mg: mg) conversion to once-daily tacrolimus in adult liver and kidney transplant recipients. Results: Data from 224 recipients of a liver (n=19) or kidney (n=205) transplant, average age 51 +/- 14.5 years, were evaluated. The mean change in tacrolimus daily dose was +0.04 mg/day. Dose remained stable after conversion in 62.5%,was lower in 15.6%, and higher in 22% of patients. Trough level after conversion was lower in 62.6% and higher in 36.5%; generally, levels were 12.8% lower than pre-conversion levels. No acute rejection, graft loss, or serious safety events were observed. Two deaths occurred due to myocardial infarction. Conversion helped 19% to less frequently forget medications and 55% reported no difference in remembering to take the once-daily dose after conversion. The change in dosing frequency was identified as '' better" for 55%. Conclusions: Tacrolimus daily dose remained stable while trough levels were significantly lower after conversion to once-daily dosing. Safety and efficacy were maintained; reduced dosing frequency had no apparent influence on patient-reported medication adherence.

  • 163.
    Bäckström, Josefin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Family Members of Patients with Burns: Experiences of a Distressful Episode2013Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    A severe burn is a trauma associated with long lasting consequences, not only for the survivor but also for the family. Although it is recognized that family members are central in providing social support for the patients, previous research has not focused extensively on this group. The aims of this thesis were to increase knowledge about psychological symptoms and health-related quality of life (HRQoL) in family members of patients with burns, as well as to explore their experiences of burn care and rehabilitation. The research questions were approached using quantitative and qualitative methods.

    The results showed that most family members demonstrate normal to mild levels of psychological symptoms, while one third demonstrate moderate to severe symptoms during care. The symptoms decreased over time and could be predicted to a certain degree by early symptoms.

    Further, family members’ report of HRQoL is similar to that of the general population. An improvement is seen over time and HRQoL could be predicted in part by earlier life events and psychological symptoms.

    Family members’ experiences were explored in an interview study. Qualitative content analysis revealed that the time in hospital is stressful, although there were experiences of a positive character.  Family members might benefit from being cared for in a more individualized way. The communication between health care providers and the family members could be improved.

    Finally, a qualitative content analysis revealed that family members’ experiences and views concerning support is highly individual. There were experiences of sufficient support as well as lack of professional support. Treatment of family members should be modified according to personal circumstances, and it is important to actively include family members in the care process, both before and after discharge.

    In summary, being a family member of a burn survivor is a distressful experience, not only during care but in many cases also after discharge. The treatment of family members within burn care should be individualized. Some persons are more vulnerable than others and it might be possible to identify those in need of support while care is still ongoing.

    List of papers
    1. Prediction of psychological symptoms in family members of patients with burns 1 year after injury
    Open this publication in new window or tab >>Prediction of psychological symptoms in family members of patients with burns 1 year after injury
    2013 (English)In: Journal of Advanced Nursing, ISSN 0309-2402, E-ISSN 1365-2648, Vol. 69, no 2, p. 384-393Article in journal (Refereed) Published
    Abstract [en]

    Aim

    To report a study of predictors of psychological symptoms in family members of patients with burns.

    Background

    Family members are important as a source of social support for patients undergoing prolonged rehabilitation. Little is known about psychological symptoms of family members of patients with burns, especially in the long term.

    Design

    The design of the study was prospective and longitudinal.

    Methods

    Forty-four family members of adult patients treated in a burn centre between 2000-2007 completed questionnaires during care and at 3, 6, and 12 months after injury. Psychological symptoms were assessed with the Hospital Anxiety and Depression Scale. Predictors for anxiety and depression were explored in regression analyses.

    Results

    The mean scores indicated normal to mild symptoms in general. Moderate and severe symptom levels during care and at 12 months were demonstrated on the anxiety subscale by 15/44 and 5/39, respectively, and on the depression subscale by 5/44 and 0/39 of the family members, respectively. In the final regression models, the primary predictor was psychological symptoms at the previous assessment. Other predictors were previous life events, age, and the coping strategy avoidance.

    Conclusion

    Family members of patients with burns demonstrate normal to mild levels of psychological symptoms that decrease over time. One-third show moderate to severe anxiety symptoms during care and may benefit from counselling. Previous symptoms predict later symptoms, indicating that screening with a validated instrument is useful. The results provide guidance for nurses in assessing and planning adequate interventions for family members.

    Keywords
    burns, family members, injury, nursing, psychological symptoms, rehabilitation
    National Category
    Psychiatry Nursing Surgery
    Research subject
    Psychiatry; Caring Sciences in Medical Sciences
    Identifiers
    urn:nbn:se:uu:diva-190020 (URN)10.1111/j.1365-2648.2012.06017.x (DOI)000313722600014 ()22509932 (PubMedID)
    Available from: 2013-01-07 Created: 2013-01-07 Last updated: 2017-12-06Bibliographically approved
    2. Health-related quality of life in family members of patients with burns
    Open this publication in new window or tab >>Health-related quality of life in family members of patients with burns
    Show others...
    2014 (English)In: Journal of Burn Care & Research, ISSN 1559-047X, E-ISSN 1559-0488, Vol. 35, no 3, p. 243-250Article in journal (Refereed) Published
    Abstract [en]

    A severe burn not only affects the patients, but may also have a great impact on the lives of family members. It is known that family members of patients with burns experience psychological distress, but health-related quality of life (HRQoL) has not been studied in this group. The aim was to study predictors of HRQoL in family members of patients with burns. Forty-four family members of adult patients treated in a burn center, between 2000 and 2007, completed questionnaires during care, and at 3, 6, and 12 months after injury. HRQoL was assessed with the EuroQol 5D (EQ-5D), which consists of the dimensions: mobility, self-care, usual activities, pain, and anxiety/depression. The questionnaire generates an EQ-5D index and a visual analog scale (VAS) score. Overall, the EQ-5D index was similar to that of the general population. A slight improvement in HRQoL was found in the VAS scores and in the anxiety/depression dimension over time. In regression models, HRQoL was primarily predicted by earlier life events, symptoms of post-traumatic stress disorder, and HRQoL, assessed during the patients’ hospitalization. In summary, HRQoL assessed with VAS scores increased slightly during the first year postburn, and early screening for life events and psychological symptoms, and HRQoL might be useful in identifying family members in need of support.

    Keywords
    burns, family members, injury, health related quality of life, rehabilitation
    National Category
    Psychiatry Surgery Nursing
    Research subject
    Psychiatry; Caring Sciences in Medical Sciences
    Identifiers
    urn:nbn:se:uu:diva-208623 (URN)10.1097/BCR.0b013e318295744e (DOI)000335394600015 ()
    Available from: 2013-10-06 Created: 2013-10-06 Last updated: 2017-12-06Bibliographically approved
    3. Family members of patients with severe burns: Experiences during care and rehabilitation
    Open this publication in new window or tab >>Family members of patients with severe burns: Experiences during care and rehabilitation
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    The aim was to explore experiences of care and rehabilitation in family members of patients with burns. Ten semi-structured interviews analyzed using qualitative content analysis resulted in seven categories related to the care: Feeling distress, Receiving excellent care, Being treated in an insensitive way, Reluctance towards giving care, Being the hub of the family network, Feeling hope, and Being thankful. Six categories were related to rehabilitation: Ambiguous feelings, Difficulties after discharge, Being forced to take responsibility, Handling the situation, Gaining support and Being thankful. Although there are positive experiences during care, family members experience the time in hospital and after discharge as distressful and could benefit from being cared for in a more individualized way. Improved communication between caregivers and the family member may be important. Family members need to be included in the planning of care and support offered at discharge could ease the burden on these individuals.

    Keywords
    burns, experience, family members, nursing, recovery
    National Category
    Nursing Psychiatry Surgery
    Research subject
    Psychiatry; Caring Sciences in Medical Sciences
    Identifiers
    urn:nbn:se:uu:diva-208624 (URN)
    Available from: 2013-10-07 Created: 2013-10-06 Last updated: 2014-01-23
    4. Family members’ experiences of support during care and rehabilitation of patients with severe burns
    Open this publication in new window or tab >>Family members’ experiences of support during care and rehabilitation of patients with severe burns
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Aim: The aim of this study was to explore family members’ experiences of support during burn care and during the rehabilitation phase after hospital discharge.

    Background: Family members are important in the recovery process of patients with severe burns; however, few previous studies have focused on how this group experiences and values support during care and rehabilitation.

    Methods: Ten semi-structured interviews with family members of patients treated at the national burn centres were recorded digitally, transcribed verbatim, and analysed using content analysis. The informants were included nationwide, most were females, and different socioeconomic groups were represented.

    Results: Categories related to experiences during care were: Nonsupport, Professional support, Support from family and friends, A wish for support, and That little something extra. Categories related to experiences during rehabilitation were: Nonsupport, Professional support, Support from family and friends, Support from the injured person and Religion. Support from other family members and friends was generally considered the most important source of support, and there was a wish for more proactive support from care professionals.

    Conclusion: The experience of support is individual, which makes supporting family members a complex task. Individualized treatment of family members and their inclusion in the care process are of central importance, as is identifying specific needs for support both during the time in hospital and during rehabilitation. It is important to be proactive and offer support.

    Keywords
    burns, experience, family members, nursing, recovery, support
    National Category
    Nursing Surgery Psychiatry
    Research subject
    Psychiatry; Caring Sciences in Medical Sciences
    Identifiers
    urn:nbn:se:uu:diva-208625 (URN)
    Available from: 2013-10-07 Created: 2013-10-06 Last updated: 2014-01-23
  • 164.
    Bäckström, Josefin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Ekselius, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Gerdin, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Willebrand, Mimmie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Prediction of psychological symptoms in family members of patients with burns 1 year after injury2013In: Journal of Advanced Nursing, ISSN 0309-2402, E-ISSN 1365-2648, Vol. 69, no 2, p. 384-393Article in journal (Refereed)
    Abstract [en]

    Aim

    To report a study of predictors of psychological symptoms in family members of patients with burns.

    Background

    Family members are important as a source of social support for patients undergoing prolonged rehabilitation. Little is known about psychological symptoms of family members of patients with burns, especially in the long term.

    Design

    The design of the study was prospective and longitudinal.

    Methods

    Forty-four family members of adult patients treated in a burn centre between 2000-2007 completed questionnaires during care and at 3, 6, and 12 months after injury. Psychological symptoms were assessed with the Hospital Anxiety and Depression Scale. Predictors for anxiety and depression were explored in regression analyses.

    Results

    The mean scores indicated normal to mild symptoms in general. Moderate and severe symptom levels during care and at 12 months were demonstrated on the anxiety subscale by 15/44 and 5/39, respectively, and on the depression subscale by 5/44 and 0/39 of the family members, respectively. In the final regression models, the primary predictor was psychological symptoms at the previous assessment. Other predictors were previous life events, age, and the coping strategy avoidance.

    Conclusion

    Family members of patients with burns demonstrate normal to mild levels of psychological symptoms that decrease over time. One-third show moderate to severe anxiety symptoms during care and may benefit from counselling. Previous symptoms predict later symptoms, indicating that screening with a validated instrument is useful. The results provide guidance for nurses in assessing and planning adequate interventions for family members.

  • 165.
    Bäckström, Josefin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Kristina, Haglund
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Sjöberg, Folke
    Linköpings universitet, Institutionen för klinisk och experimentell medicin.
    Willebrand, Mimmie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Family members’ experiences of support during care and rehabilitation of patients with severe burnsManuscript (preprint) (Other academic)
    Abstract [en]

    Aim: The aim of this study was to explore family members’ experiences of support during burn care and during the rehabilitation phase after hospital discharge.

    Background: Family members are important in the recovery process of patients with severe burns; however, few previous studies have focused on how this group experiences and values support during care and rehabilitation.

    Methods: Ten semi-structured interviews with family members of patients treated at the national burn centres were recorded digitally, transcribed verbatim, and analysed using content analysis. The informants were included nationwide, most were females, and different socioeconomic groups were represented.

    Results: Categories related to experiences during care were: Nonsupport, Professional support, Support from family and friends, A wish for support, and That little something extra. Categories related to experiences during rehabilitation were: Nonsupport, Professional support, Support from family and friends, Support from the injured person and Religion. Support from other family members and friends was generally considered the most important source of support, and there was a wish for more proactive support from care professionals.

    Conclusion: The experience of support is individual, which makes supporting family members a complex task. Individualized treatment of family members and their inclusion in the care process are of central importance, as is identifying specific needs for support both during the time in hospital and during rehabilitation. It is important to be proactive and offer support.

  • 166.
    Bäckström, Josefin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Willebrand, Mimmie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Sjöberg, Folke
    Linköpings universitet, Institutionen för klinisk och experimentell medicin.
    Haglund, Kristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Family members of patients with severe burns: Experiences during care and rehabilitationManuscript (preprint) (Other academic)
    Abstract [en]

    The aim was to explore experiences of care and rehabilitation in family members of patients with burns. Ten semi-structured interviews analyzed using qualitative content analysis resulted in seven categories related to the care: Feeling distress, Receiving excellent care, Being treated in an insensitive way, Reluctance towards giving care, Being the hub of the family network, Feeling hope, and Being thankful. Six categories were related to rehabilitation: Ambiguous feelings, Difficulties after discharge, Being forced to take responsibility, Handling the situation, Gaining support and Being thankful. Although there are positive experiences during care, family members experience the time in hospital and after discharge as distressful and could benefit from being cared for in a more individualized way. Improved communication between caregivers and the family member may be important. Family members need to be included in the planning of care and support offered at discharge could ease the burden on these individuals.

  • 167.
    Bäckström, Josefin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Öster, Caisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Gerdin, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Ekselius, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Willebrand, Mimmie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Health-related quality of life in family members of patients with burns2014In: Journal of Burn Care & Research, ISSN 1559-047X, E-ISSN 1559-0488, Vol. 35, no 3, p. 243-250Article in journal (Refereed)
    Abstract [en]

    A severe burn not only affects the patients, but may also have a great impact on the lives of family members. It is known that family members of patients with burns experience psychological distress, but health-related quality of life (HRQoL) has not been studied in this group. The aim was to study predictors of HRQoL in family members of patients with burns. Forty-four family members of adult patients treated in a burn center, between 2000 and 2007, completed questionnaires during care, and at 3, 6, and 12 months after injury. HRQoL was assessed with the EuroQol 5D (EQ-5D), which consists of the dimensions: mobility, self-care, usual activities, pain, and anxiety/depression. The questionnaire generates an EQ-5D index and a visual analog scale (VAS) score. Overall, the EQ-5D index was similar to that of the general population. A slight improvement in HRQoL was found in the VAS scores and in the anxiety/depression dimension over time. In regression models, HRQoL was primarily predicted by earlier life events, symptoms of post-traumatic stress disorder, and HRQoL, assessed during the patients’ hospitalization. In summary, HRQoL assessed with VAS scores increased slightly during the first year postburn, and early screening for life events and psychological symptoms, and HRQoL might be useful in identifying family members in need of support.

  • 168.
    Caballero-Corbalan, José
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology.
    Brandhorst, Heide
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology.
    Asif, Sana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology.
    Korsgren, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology.
    Engelse, Marten
    Leiden Univ, Med Ctr, Dept Nephrol, Leiden, Netherlands.
    de Koning, Eelco
    Leiden Univ, Med Ctr, Dept Nephrol, Leiden, Netherlands.
    Pattou, Francois
    Univ Hosp, INSERM ERIT M 0106 Diabet Cell Therapy, Lille, France.
    Kerr-Conte, Julie
    Univ Hosp, INSERM ERIT M 0106 Diabet Cell Therapy, Lille, France.
    Brandhorst, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology.
    Mammalian Tissue-Free Liberase: A New GMP-Graded Enzyme Blend for Human Islet Isolation2010In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 90, no 3, p. 332-333Article in journal (Refereed)
  • 169.
    Caballero-Corbalán, José
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Islet Transplantation a Technical Challenge: Studies on Human Pancreas Preservation and Enzymatic Digestion2011Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Islet transplantation has found its niche in diabetes treatment. It has contributed to a better quality of life and better glycemic control of patients with diabetes suffering from severe hypoglycemia that are not eligible for vascularized pancreas transplantation. Islet isolation is a technically challenging procedure. The different studies within this doctoral thesis aim to improve and standardize different steps in the isolation procedure. They are in particular looking to improve human pancreas preservation during cold storage, to optimize islet release from the exocrine tissue and to assess whether the isolated islet yield can be predicted from a biopsy.

    We found that pancreas preservation with pre-oxygenated perfluorodecalin (two-layer method) did not improve the ischemic tolerance of the human pancreas as compared to cold storage with the University of Wisconsin (UW) solution. Furthermore, in pancreas with long cold ischemia time (CIT) (>10 hours), Histidine-Tryptophan-Ketoglutarate (HTK) had a limited preservation capacity as compared with the UW solution with respect to isolation outcome. We also found that during enzymatic pancreas digestion, Vitacyte HA was able to provide a similar islet yield and quality as Serva NB1 with less collagenase activity and shorter digestion time. We further describe the first experience with a new GMP manufactured enzyme called Liberase MTF-S for successful human islet isolation. Finally, we found that the isolated islet yield could not be predicted from a biopsy taken from the head of the pancreas concerning solely morphological parameters of the islets tissue.

    The improvement of pancreas preservation will allow for marginal organs with prolonged cold ischemia time to expand the donor pool. Better knowledge of how the pancreatic extracellular matrix is digested by collagenase will lead to a fast and predictable islet release from the exocrine tissue. By standardizing the isolation procedure and improving organ selection we will increase the success rate in human islet isolation, thereby making islet transplantation available for more patients.

    List of papers
    1. No beneficial effect of two-layer storage compared with UW-storage on human islet isolation and transplantation
    Open this publication in new window or tab >>No beneficial effect of two-layer storage compared with UW-storage on human islet isolation and transplantation
    Show others...
    2007 (English)In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 84, no 7, p. 864-869Article in journal (Refereed) Published
    Abstract [en]

    Background. Shipment of pancreata between distant centers is frequently associated with prolonged cold ischemia time (CIT) that leads to poorer outcomes for islet transplantation. Clinical pilot trials have indicated that oxygenation of explanted human pancreata utilizing the two-layer method (TLM) allows the use of marginal donor pancreata for islet transplantation. The present study aimed to clarify whether TLM enhances the ischemic tolerance of human pancreata. Methods. We analyzed retrospectively the outcome of 200 human islet isolations performed after TLM preservation or storage in University of Wisconsin solution (UWS). Results. Donor characteristics and digestion parameters did not vary significantly between TLM-preserved and UWS-stored pancreata. No differences were observed between experimental groups with regard to islet yield, purity, or dynamic glucose stimulation index after either short or prolonged CIT. However, CIT and stimulation index were negatively correlated in each experimental group. The isolation outcome in donors aged ≥60 years was not increased after TLM preservation when compared to UWS storage. No effect was observed regarding islet posttransplant function in recipients with established kidney grafts. Conclusions. The present study suggests that the ischemic tolerance of human pancreata cannot be extended by TLM preservation. In addition, TLM does not seem to improve the isolation outcome for pancreata from elderly donors.

    Keywords
    Clinical islet transplantation, Cold storage, Marginal donors, Two-layer method
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-16849 (URN)10.1097/01.tp.0000284584.60600.ab (DOI)000250232600010 ()17984839 (PubMedID)
    Available from: 2008-06-05 Created: 2008-06-05 Last updated: 2017-12-08Bibliographically approved
    2. Using HTK for Prolonged Pancreas Preservation Prior to Human Islet Isolation
    Open this publication in new window or tab >>Using HTK for Prolonged Pancreas Preservation Prior to Human Islet Isolation
    Show others...
    2012 (English)In: Journal of Surgical Research, ISSN 0022-4804, E-ISSN 1095-8673, Vol. 175, no 1, p. 163-168Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND: Histidine-tryptophan-ketoglutarate (HTK) has been established as an alternative to University-of-Wisconsin solution (UWS) for abdominal organ preservation, but data about HTK efficiency to preserve pancreata during prolonged cold ischemia time (CIT) are conflicting. In human islet transplantation, HTK provided similar isolation outcomes after short CIT. The present study aimed to investigate whether islets can be successfully isolated from HTK-preserved pancreata after prolonged CIT compared with UWS.

    MATERIALS AND METHODS: Sixty-four human pancreata retrieved from donors meeting criteria for kidney donation were perfused utilizing either HTK or UWS and preserved for more or less than 10 h prior to islet isolation. Along with parameters related to isolation and islet quality assessment, the dry-to-wet weight ratio was evaluated.

    RESULTS: Donor- and procurement-related factors did not vary between HTK- and UWS-perfused pancreata. The dry-to-wet weight ratio was lower in HTK-preserved pancreata indicated tissue edema (21.0% ± 3.5% versus 24.8% ± 2.0%, P = 0.007). Isolation-related variables differed between experimental groups after prolonged CIT with respect to purified packed tissue volume (9.1 ± 5.0 versus 17.2 ± 8.1 μL/g, P = 0.004) and islet yield (1910 ± 980 versus 3150 ± 1420 IE/g, P = 0.012). Islet purity and survival after culture were similar after HTK or UWS perfusion. The preservation solution did not affect in vitro function and transplantability of isolated islets.

    CONCLUSIONS: Compared with UWS, HTK has similar efficiency to preserve human pancreata for subsequent islet isolation during <10 h CIT but seems to be limited for prolonged cold storage.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-156890 (URN)10.1016/j.jss.2011.03.012 (DOI)000303472500031 ()21550052 (PubMedID)
    Available from: 2011-08-10 Created: 2011-08-10 Last updated: 2017-12-08Bibliographically approved
    3. Vitacyte Collagenase HA: A Novel Enzyme Blend for Efficient Human Islet Isolation
    Open this publication in new window or tab >>Vitacyte Collagenase HA: A Novel Enzyme Blend for Efficient Human Islet Isolation
    Show others...
    2009 (English)In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 88, no 12, p. 1400-1402Article in journal, Letter (Refereed) Published
    National Category
    Surgery Medical and Health Sciences
    Research subject
    Medical Science
    Identifiers
    urn:nbn:se:uu:diva-111858 (URN)10.1097/TP.0b013e3181bd1441 (DOI)000273200000013 ()20029339 (PubMedID)
    Note

    Letter. Authors were listed in the wrong order in the original publication (erratum in Transplantation, 2010, vol. 89, issue 7, p. 907)

    Available from: 2009-12-28 Created: 2009-12-28 Last updated: 2017-12-12Bibliographically approved
    4. Mammalian Tissue-Free Liberase: A New GMP-Graded Enzyme Blend for Human Islet Isolation
    Open this publication in new window or tab >>Mammalian Tissue-Free Liberase: A New GMP-Graded Enzyme Blend for Human Islet Isolation
    Show others...
    2010 (English)In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 90, no 3, p. 332-333Article in journal, Letter (Refereed) Published
    National Category
    Surgery
    Identifiers
    urn:nbn:se:uu:diva-135881 (URN)10.1097/TP.0b013e3181e117e3 (DOI)000280581200020 ()
    Available from: 2010-12-13 Created: 2010-12-09 Last updated: 2019-01-24Bibliographically approved
    5. Predicting the outcome of human islet isolation
    Open this publication in new window or tab >>Predicting the outcome of human islet isolation
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Background. Islet transplantation is currently being explored as a possible treatment to diabetes mellitus. Islet isolation from the human pancreas is a technically demanding process and the success rate even in the most experienced GMP facilities is only about 50%. The aim of this study was to investigate whether isolation outcome can be predicted from a pancreas biopsy taken during organ procurement.

    Methods. The outcome of 29 human islet isolations was retrospectively studied. Biopsies from the pancreatic head were immunostained for insulin to study islet morphology and size distribution utilizing a digital analysis system. Isolations were categorized as successful if they yielded more than 2000 IE/g. 

    Results. Pellet volume after collagenase digestion and islet purity was higher in the successful group. None of the morphology variables, i.e. islet number (IN/mm2), islet equivalent number (IE/IN) and percentage of insulin positive area in the biopsy, differed significantly between the study groups.

    Conclusions. No single morphological feature observed in a biopsy taken from the head of pancreas can predict the outcome of islet isolation from the human pancreas, even if using the same enzyme blend in standardized human islet isolation procedure.

    Identifiers
    urn:nbn:se:uu:diva-156891 (URN)
    Available from: 2011-08-10 Created: 2011-08-10 Last updated: 2011-11-03
  • 170.
    Caballero-Corbalán, José
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology.
    Friberg, Andrew S.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology.
    Brandhorst, Heide
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology.
    Nilsson, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology.
    Andersson, Helene H.
    Felldin, Maria
    Foss, Aksel
    Salmela, Kaija
    Tibell, Annika
    Tufveson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Korsgren, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology.
    Brandhorst, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology.
    Vitacyte Collagenase HA: A Novel Enzyme Blend for Efficient Human Islet Isolation2009In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 88, no 12, p. 1400-1402Article in journal (Refereed)
  • 171.
    Calì-Cassi, Lorenzo
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Rozen, Shai M.
    Mani, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Thorir, Audolfsson
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Gangadasu, Reddy
    Rodríguez-Lorenzo, Andrés
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    The Anatomical Basis of the Lumbar Artery PerforatorFlap: A Cadaveric and Computer Tomography AngiogramStudy2016In: Clinics in Surgery Journal, ISSN 2474-1647, Vol. 1, article id 1270Article in journal (Refereed)
    Abstract [en]

    Background: Lumbar skin flaps based on cutaneous perforators arising from the lumbar artery have been described for coverage of lumbosacral defects and as free flaps for autologous breast reconstruction. Thus, the purpose of this study is to clarify anatomical aspects of the lumbar artery perforator flaps pertaining improvement in utility and design of this flap. Methods: Five fresh human bodies were dissected and twenty three-dimensional computed tomographic (CT) angiographic previously used for the evaluation of the deep inferior epigastric perforator flap in patients that underwent breast reconstruction were evaluated. All cutaneous lumbar artery perforators were analyzed for total number, location, and external diameter. Results: The number of perforators observed per side was 1.6±0.84 in the CT angiography and 3±1.05 in the cadaver study. Data from CT angiographies showed a mean diameter of the pedicle of 2.76±0.74 mm. This perforators were located at the mean distance from the midline (spinal process) of 76.56±6.97 mm, the mean length pedicle were 19.88±7.57 mm. Data from the cadaveric dissection study the mean diameter of the pedicle were 1.96±0.57 mm, the mean distance from the midline were 69.6±22.5 mm. Conclusion: The lumbar artery perforator flap is based on a perforator that has a predictable location and presents a good caliber. Versatility of design of a pedicled flap as a propeller, bilobed or transposition flap based on this reliable perforator can be useful to reconstruct complex defects in the lumbar area. Preoperative planning with CT angiography is recommended to assess the location and caliber of the perforator allowing a better design of the flap

  • 172.
    Carlander, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden..
    Wagner, Philippe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Uppsala Univ, Vastmanland Cty Hosp, Dept Surg, S-72189 Vasteras, Sweden..
    Gimm, Oliver
    Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden.;Linkoping Univ Hosp, Dept Surg, S-58185 Linkoping, Sweden..
    Nordenstrom, Erik
    Univ Lund Hosp, Dept Surg, Malmo, Sweden..
    Jansson, Svante
    Sahlgrens Univ Hosp, Dept Surg, Gothenburg, Sweden..
    Bergkvist, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Uppsala Univ, Vastmanland Cty Hosp, Dept Surg, S-72189 Vasteras, Sweden..
    Johansson, Kenth
    Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden.;Sahlgrens Univ Hosp, Dept Surg, Gothenburg, Sweden.;Vastervik Hosp, Dept Surg, Vastervik, Sweden..
    Risk of Complications with Energy-Based Surgical Devices in Thyroid Surgery: A National Multicenter Register Study2016In: World Journal of Surgery, ISSN 0364-2313, E-ISSN 1432-2323, Vol. 40, no 1, p. 117-123Article in journal (Refereed)
    Abstract [en]

    Energy-based surgical devices (EBD) combining cutting and coagulation are increasingly used in thyroid surgery. However, there is a lack of information about potential benefits and risk of complications outside controlled trials. The aims of this national multicenter register study were to describe the use of EDB, their potential effect on complication rates, and on operation time. The Scandinavian Quality Register for Thyroid and Parathyroid surgery includes 35 surgical units in Sweden and covered 88 % of the thyroid procedures performed during 2008-2009. The use of the EBD was specifically registered for 12 months, and 1297 patients were included. Surgically related complications and operation time were evaluated. The clamp-and-tie group (C-A-T) constituted the control group for comparison with procedures where EBD was used. The thyroid procedures performed included C-A-T (16.6 %), bipolar electrosurgery (ES: 56.5 %), electronic vessel sealing (EVS: 12.2 %), and ultrasonic dissection (UD: 14.5 %). Mean operative time was longer with EVS (p < 0.001) and shorter with UD (p < 0.05) than in the other groups. The bipolar ES group and the EVS group had higher incidence of calcium treatment at discharge and after 6 weeks than the UD group. No significant difference in nerve injury was found between the groups. There was a significant more frequent use of topical hemostatic agents in the EBD group compared to C-A-T. In this national multicenter study, the use of UD shortened and EVS increased operating time. There was a higher risk of calcium treatment at discharge and after 6 weeks after use of EVS and bipolar ES than after UD use. There was a significant more frequent use of topical hemostatic agents in the EBD groups compared to C-A-T.

  • 173.
    Carling, Tobias
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Udelsman, Robert
    Parathyroid tumors2003In: Curr Treat Options Oncol, Vol. 4, no 4, p. 319-328Article in journal (Refereed)
  • 174.
    Carlsson, Per-Ola
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Transplantation and regenerative medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Espes, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Transplantation and regenerative medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Sedigh, Amir
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Rotem, Avi
    Zimermann, Baruch
    Grinberg, Helena
    Goldman, Tali
    Barkai, Uriel
    Avni, Yuval
    Westermark, Gunilla T.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Carlbom, Lina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Antaros Medical AB, Mölndal, Sweden.
    Eriksson, Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry.
    Olerud, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Korsgren, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Transplantation of macroencapsulated human islets within the bioartificial pancreas βAir to patients with type 1 diabetes mellitus2018In: American Journal of Transplantation, ISSN 1600-6135, E-ISSN 1600-6143, Vol. 18, no 7, p. 1735-1744Article in journal (Refereed)
    Abstract [en]

    Macroencapsulation devices provide the dual possibility to immunoprotect transplanted cells while also being retrievable; the latter bearing importance for safety in future trials with stem-cell derived cells. However, macroencapsulation entails a problem with oxygen supply to the encapsulated cells. The βAir device solves this with an incorporated refillable oxygen tank. This phase 1 study evaluated the safety and efficacy of implanting the βAir device containing allogeneic human pancreatic islets to patients with type 1 diabetes. Four patients were transplanted with 1-2 βAir devices, each containing 155000-180000 IEQ (i.e. 1800-4600 IEQ per kg body weight), and monitored for 3-6 months, followed by the recovery of devices. Implantation of the βAir device was safe and successfully prevented immunization and rejection of the transplanted tissue. However, although beta cells survived in the device, only minute levels of circulating C-peptide were observed with no impact on metabolic control. Fibrotic tissue with immune cells was formed in capsule surroundings. Recovered devices displayed a blunted glucose-stimulated insulin response, and amyloid formation in the endocrine tissue. We conclude that the βAir device is safe and can support survival of allogeneic islets for several months, although the function of the transplanted cells was limited.

  • 175.
    Carstam, Louise
    et al.
    Sahlgrens Univ Hosp, Dept Neurosurg, Gothenburg, Sweden; Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Gothenburg, Sweden.
    Smits, Anja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology. Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Gothenburg, Sweden.
    Milos, Peter
    Linköping Univ Hosp, Dept Neurosurg, Linköping, Sweden.
    Corell, Alba
    Sahlgrens Univ Hosp, Dept Neurosurg, Gothenburg, Sweden.
    Henriksson, Roger
    Reg Canc Ctr Stockholm Gotland, Stockholm, Sweden; Univ Umeå, Dept Radiat Sci & Oncol, Umeå, Sweden.
    Bartek, Jiri Jr
    Karolinska Univ Hosp, Dept Neurosurg, Stockholm, Sweden; Karolinska Inst, Dept Neurosci, Stockholm, Sweden; Karolinska Inst, Dept Med, Stockholm, Sweden; Copenhagen Univ Hosp, Rigshosp, Dept Neurosurg, Copenhagen, Denmark.
    Jakola, Asgeir Store
    Sahlgrens Univ Hosp, Dept Neurosurg, Gothenburg, Sweden; Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Gothenburg, Sweden; St Olavs Univ Hosp HF, Dept Neurosurg, Trondheim, Norway.
    Neurosurgical patterns of care for diffuse low-grade gliomas in Sweden between 2005 and 20152018In: Neurooncology Practice, ISSN 2054-2577, Vol. 6, no 2, p. 124-133Article in journal (Refereed)
    Abstract [en]

    Background: In the last decade, increasing evidence has evolved for early and maximal safe resection of diffuse low-grade gliomas (LGGs) regarding survival. However, changes in clinical practice are known to occur slowly and we do not know if the scientific evidence has yet resulted in changes in neurosurgical patterns of care.

    Methods: The Swedish Brain Tumor Registry was used to identify all patients with a first-time histopathological diagnosis of LGG between 2005 and 2015. For analysis of surgical treatment patterns, we subdivided assessed time periods into 2005-2008, 2009-2012, and 2013-2015. Population-based data on patient and disease characteristics, surgical management, and outcomes were extracted.

    Results: A total of 548 patients with diffuse World Health Organization grade II gliomas were identified: 142 diagnosed during 2005-2008, 244 during 2009-2012, and 162 during 2013-2015. Resection as opposed to biopsy was performed in 64.3% during 2005-2008, 74.2% during 2009-2012, and 74.1% during 2013-2015 (P = .08). There was no difference among the 3 periods regarding overall survival (P = .11). However, post hoc analysis of data from the 4 (out of 6) centers that covered all 3 time periods demonstrated a resection rate of 64.3% during 2005-2008, 77.4% during 2009-2012, and 75.4% during 2013-2015 (P = .02) and longer survival of patients diagnosed 2009 and onward (P = .04).

    Conclusion: In this nationwide, population-based study we observed a shift over time in favor of LGG resection. Further, a positive correlation between the more active surgical strategy and longer survival is shown, although no causality can be claimed because of possible confounding factors.

  • 176.
    Cashin, Peter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Nygren, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Mahteme, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Considerations on the Selection Process for Cytoreductive Surgery and Hyperthermic IntraPeritoneal Chemotherapy for Colorectal Carcinomatosis Reply2015In: Annals of Surgery, ISSN 0003-4932, E-ISSN 1528-1140, Vol. 262, no 2, p. e48-e49Article in journal (Refereed)
  • 177.
    Cashin, Peter H
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Cytoreductive Surgery and Intraperitoneal Chemotherapy in Patients with Peritoneal Metastases from Colorectal Cancer: Aspects of loco-regional treatment outcome, patient selection, and chemo-sensitivity 2012Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Previously, peritoneal metastases(PM) from colorectal cancer(CRC) have been considered a terminal and generalised form of cancer. A new treatment strategy combining cytoreductive surgery(CRS) and intraperitoneal chemotherapy(IPC) has recently shown promising results. The aim of this thesis was to investigate different aspects of this treatment in order to optimise the treatment and to clarify its potential as a new treatment option. Treatment outcome, patient selection, method of IPC (hyperthermic intraperitoneal chemotherapy-HIPEC vs. sequential postoperative intraperitoneal chemotherapy-SPIC) and choice of drugs for IPC were the aspects covered in this thesis.

    The treatment outcome of CRS and IPC according to the median overall survival ranged from 24 to 34 months with 5-year overall survival ranging from 20 to 40% depending on the IPC treatment administered. Furthermore, the 5-year disease-free survival was impressive at 32% for patients receiving HIPEC. This establishes the curative potential of this treatment. Due to current inadequacies of radiological imaging, a score (Corep score) was developed for patient selection purposes. This score had a sensitivity of 80% and specificity of 100% in identifying patients with short cancer-specific survival after the treatment (<12 months). Further studies are needed to elucidate the clinical usefulness of the Corep score. HIPEC was associated with better survival than the SPIC method at similar morbidity and mortality rates, suggesting that HIPEC be the method of preference. Concerning the choice of drugs, the last study investigated the chemo-sensitivity of different PM tumour-types with a special focus on CRC. While CRC samples were generally more resistant, the ratio of the in vivo concentration compared to the ex vivo concentration giving a 50% tumour cell death showed that oxaliplatin had the best profile across all PM tumour types as well as for CRC. This needs further confirmation in a clinical trial.

    List of papers
    1. Cytoreductive Surgery and Intraperitoneal Chemotherapy for Colorectal Peritoneal Carcinomatosis: Prognosis and Treatment of Recurrences in a Cohort Study
    Open this publication in new window or tab >>Cytoreductive Surgery and Intraperitoneal Chemotherapy for Colorectal Peritoneal Carcinomatosis: Prognosis and Treatment of Recurrences in a Cohort Study
    2012 (English)In: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 38, no 6, p. 509-515Article in journal (Refereed) Published
    Abstract [en]

    Background

    Cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC) treatment of colorectal peritoneal carcinomatosis (PC) is gaining acceptance, but controversy remains. The primary aims were to analyze the outcome and prognostic variables of colorectal PC patients treated with CRS and IPC, and to report on the outcome of additional surgical treatments of subsequent recurrences.

    Methods

    Patients referred for treatment of colorectal PC between 1996 and 2010 were included in a cohort. The following data was collected: clinicopathological parameters, survival, recurrences, perioperative chemotherapy and type of IPC (hyperthermic intraperitoneal chemotherapy, HIPEC; or sequential postoperative intraperitoneal chemotherapy, SPIC). Multivariable analyses were conducted on potential prognostic factors for overall survival (OS).

    Results

    In the 151-patient cohort, the median OS was 34months (range: 2-77) for CRS and HIPEC with five-year survival predicted at 40% (five-year disease-free survival 32%). For CRS and SPIC, the OS was 25months (range: 2-188) with five-year survival at 18%.  Open-and-close patients survived 6months (range: 0-14) with no five-year survival (HIPEC vs. SPIC p=0.047, SPIC vs. open-and-close p<0.001). Adjuvant systemic chemotherapy was a noteworthy independent prognostic factor in the multivariable analysis. OS for patients undergoing additional surgical treatment of recurrences was 25months vs. 10months with best supportive care or palliative chemotherapy (p=0.01).

    Conclusion

    Substantial long-term survival is possible in patients with colorectal PC. HIPEC was associated with better OS than SPIC and adjuvant systemic chemotherapy may improve the outcome in patients. Good OS is achievable in selected patients undergoing additional surgical treatment of isolated liver or peritoneal recurrences after prior complete CRS.

    Keywords
    HIPEC, Intraperitoneal chemotherapy, Colorectal cancer, Peritoneal carcinomatosis, Cytoreductive surgery, Recurrences
    National Category
    Surgery
    Research subject
    Surgery
    Identifiers
    urn:nbn:se:uu:diva-169544 (URN)10.1016/j.ejso.2012.03.001 (DOI)000304510600008 ()
    Available from: 2012-03-05 Created: 2012-03-02 Last updated: 2017-12-07Bibliographically approved
    2. Patient Selection for Cytoreductive Surgery in Colorectal Peritoneal Carcinomatosis using Serum Tumour Markers – an Observational Cohort Study
    Open this publication in new window or tab >>Patient Selection for Cytoreductive Surgery in Colorectal Peritoneal Carcinomatosis using Serum Tumour Markers – an Observational Cohort Study
    2012 (English)In: Annals of Surgery, ISSN 0003-4932, E-ISSN 1528-1140, Vol. 256, no 6, p. 1078-1083Article in journal (Refereed) Published
    Abstract [en]

    Objective: There were 2 objectives: first, to investigate how many patients were excluded from surgery on the basis of the radiological extent of the peritoneal carcinomatosis (PC) or the clinical examination; and second, to develop a score based primarily on serum tumor markers (STMs) that could predict short cancer-specific survival (<12 months). Background: Patient selection and prediction of prognosis is crucial for successful treatment of colorectal PC. Methods: All patients with colorectal PC referred for cytoreductive surgery and intraperitoneal chemotherapy (2005-2008) at Uppsala University hospital were included. Patients were divided into 2 groups-nonsurgery and surgery. Clinicopathological and laboratory parameters were collected in the surgery group. A Corep (COloREctal-Pc) score was developed using hazard ratios from histology, hematological status, serial serum tumor markers (STMs), and STM changes over time. Sensitivity, specificity, positive predicted value (PPV), and negative predicted value (NPV) were calculated in a second validating dataset (n = 24) with a survival cutoff of less than 12 months. Results: A total of 107 patients were included in the study, 42 in the nonsurgery group and 65 in the surgery group. In the nonsurgery group, 2 patients were excluded solely on the basis of the radiological extent of PC and 7 patients on clinical examination. The Corep score ranged from 0 to 18. A score of 6 or more showed a validated sensitivity of 80%, specificity 100%, PPV 1.0, and NPV 0.93. Conclusions: Radiological extent of PC was not a main deciding factor for treatment decisions and had less impact than the clinical examination. The Corep score identified patients with short cancer-specific survival that may not be suitable for treatment.

    Keywords
    colorectal cancer, corep score, cytoreductive surgery, hyperthermic intraperitoneal chemotherapy, HIPEC, patient selection, serum tumour markers, peritoneal carcinomatosis, peritoneal metastases
    National Category
    Surgery
    Research subject
    Surgery
    Identifiers
    urn:nbn:se:uu:diva-169548 (URN)10.1097/SLA.0b013e318254f281 (DOI)000312261000038 ()
    Available from: 2012-03-05 Created: 2012-03-02 Last updated: 2017-12-07Bibliographically approved
    3. Intraoperative hyperthermic versus postoperative normothermic intraperitoneal chemotherapy for colonic peritoneal carcinomatosis: a case-control study
    Open this publication in new window or tab >>Intraoperative hyperthermic versus postoperative normothermic intraperitoneal chemotherapy for colonic peritoneal carcinomatosis: a case-control study
    2012 (English)In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 23, no 3, p. 647-652Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND:

    Cytoreductive surgery and intraperitoneal chemotherapy has improved prognosis in patients with peritoneal carcinomatosis. The main modes of intraperitoneal chemotherapy treatment are peroperative hyperthermic intraperitoneal chemotherapy (HIPEC) and normothermic sequential postoperative intraperitoneal chemotherapy (SPIC). The aim of this study was to compare HIPEC and SPIC with respect to overall survival, disease-free survival, morbidity, and mortality in patients with peritoneal carcinomatosis from colon cancer.

    PATIENTS AND METHODS:

    A matched case-control study was conducted in patients with surgical macroscopic complete removal of carcinomatosis; matching was according to the peritoneal cancer index score. Thirty-two patients were included, 16 in each group (HIPEC and SPIC). Overall survival, disease-free survival, morbidity, mortality, and clinicopathological parameters were compared.

    RESULTS:

    Median overall survival was 36.5 months in the HIPEC group and 23.9 months in the SPIC group (P = 0.01). Median disease-free survival for these groups was 22.8 (HIPEC) and 13.0 months (SPIC; P = 0.02). Morbidity was not statistically different, 19% in SPIC and 37% in HIPEC. Postoperative mortality was observed in one patient in each group.

    CONCLUSION:

    HIPEC was associated with improved overall survival and disease-free survival compared with SPIC at similar morbidity and mortality, suggesting that HIPEC is the treatment of choice in colonic peritoneal carcinomatosis.

    Place, publisher, year, edition, pages
    Oxford University Press, 2012
    National Category
    Surgery
    Research subject
    Surgery
    Identifiers
    urn:nbn:se:uu:diva-165543 (URN)10.1093/annonc/mdr301 (DOI)000300733300016 ()21685413 (PubMedID)
    Available from: 2012-01-09 Created: 2012-01-09 Last updated: 2017-12-08Bibliographically approved
    4. Activity ex vivo of cytotoxic drugs in patient samples of peritoneal carcinomatosis with special focus on colorectal cancer
    Open this publication in new window or tab >>Activity ex vivo of cytotoxic drugs in patient samples of peritoneal carcinomatosis with special focus on colorectal cancer
    Show others...
    2013 (English)In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 13, p. 435-Article in journal (Refereed) Published
    Abstract [en]

    Background: The optimal choice of cytotoxic drugs for intraperitoneal chemotherapy (IPC) in conjunction with cytoreductive surgery (CRS) for treatment of peritoneal carcinomatosis(PC) is poorly defined. We investigated drug sensitivity ex vivo in patient samples of various PC tumor types and correlated clinical outcome to drug sensitivity within the subset of PC fromcolorectal cancer (CRC). 

    Methods: PC tissue samples (n = 174) from mesothelioma, pseudomyxoma peritonei (PMP), ovarian cancer, CRC or appendix cancer were analyzed ex vivo for sensitivity to oxaliplatin, cisplatin, mitomycin C, melphalan, irinotecan, docetaxel, doxorubicin and 5-FU. Clinicopathological variables and outcome data were collected for the CRC subset. 

    Results: Mesothelioma and ovarian cancer were generally more drug sensitive than CRC, appendix cancer and PMP. Oxaliplatin showed the most favorable ratio between achievable IPC concentration and ex vivo drug sensitivity. Drug sensitivity in CRC varied considerably between individual samples. Ex vivo drug sensitivity did not obviously correlate to time-to-progression (TTP) in individual patients. 

    Conclusions: Drug-sensitivity varies considerably between PC diagnoses and individual patients arguing for individualized therapy in IPC rather than standard diagnosis-specific therapy. However, in the current paradigm of treatment according to diagnosis, oxaliplatin is seemingly the preferred drug for IPC from a drug sensitivity and concentration perspective. Inthe CRC subset, analysis of correlation between ex vivo drug sensitivity and TTP was inconclusive due to the heterogeneous nature of the data.

    National Category
    Cancer and Oncology
    Identifiers
    urn:nbn:se:uu:diva-172441 (URN)10.1186/1471-2407-13-435 (DOI)000325079100001 ()
    Available from: 2012-04-10 Created: 2012-04-10 Last updated: 2017-12-07Bibliographically approved
  • 178.
    Cashin, Peter H.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Dranichnikov, Faoz
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Mahteme, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Cytoreductive Surgery and Hyperthermic Intra-Peritoneal Chemotherapy Treatment of Colorectal Peritoneal Metastases: Cohort Analysis of High Volume Disease and Cure Rate2014In: Journal of Surgical Oncology, ISSN 0022-4790, E-ISSN 1096-9098, Vol. 110, no 2, p. 203-206Article in journal (Refereed)
    Abstract [en]

    Background: Cytoreductive surgery (CRS) and hyperthermic intra-peritoneal chemotherapy (HIPEC) treatment of colorectal peritoneal metastases (PM) is an established treatment alternative. The study aim was, first, to investigate the outcome of high-volume disease defined by the peritoneal cancer index (PCI) 20; second, to report the long-term disease-free survival of patients with >5 years observation. Methods: Consecutive patients with colorectal PM from a prospective HIPEC database between 2004 and 2010 were included, 67 patients. Clinicopathological and outcome parameters were compared between low PCI (n = 40) and high PCI (n = 27). A subgroup analysis on patients with >5 years observation was performed (n = 32). Disease-free survival after 5 years defined cure. Results: Median overall survival (OS) was 28 months, low PCI-group 33 months versus high PCI-group 17 months (P = 0.03). Median OS of patients with complete CRS (n = 56) was 30 months, low PCI-group 37 months versus high PCI-group 27 months (P = 0.2), with 5-year survival of 31% and 21%, respectively. No difference in morbidity/mortality. The cure rate was 22% in the subgroup (7/32) and 28% in those with complete CRS (7/25). Two patients in the cured group had PCI 29 and 34. Discussion: Treatment of high-volume disease may result in long-term survival and even cure. The key is to reach a complete CRS. The overall cure rate is 22%. 

  • 179.
    Cashin, Peter H
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Nygren, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Mahteme, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Cytoreductive Surgery and Intraperitoneal Chemotherapy for Colorectal Peritoneal Carcinomatosis: Prognosis and Treatment of Recurrences in a Cohort Study2012In: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 38, no 6, p. 509-515Article in journal (Refereed)
    Abstract [en]

    Background

    Cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC) treatment of colorectal peritoneal carcinomatosis (PC) is gaining acceptance, but controversy remains. The primary aims were to analyze the outcome and prognostic variables of colorectal PC patients treated with CRS and IPC, and to report on the outcome of additional surgical treatments of subsequent recurrences.

    Methods

    Patients referred for treatment of colorectal PC between 1996 and 2010 were included in a cohort. The following data was collected: clinicopathological parameters, survival, recurrences, perioperative chemotherapy and type of IPC (hyperthermic intraperitoneal chemotherapy, HIPEC; or sequential postoperative intraperitoneal chemotherapy, SPIC). Multivariable analyses were conducted on potential prognostic factors for overall survival (OS).

    Results

    In the 151-patient cohort, the median OS was 34months (range: 2-77) for CRS and HIPEC with five-year survival predicted at 40% (five-year disease-free survival 32%). For CRS and SPIC, the OS was 25months (range: 2-188) with five-year survival at 18%.  Open-and-close patients survived 6months (range: 0-14) with no five-year survival (HIPEC vs. SPIC p=0.047, SPIC vs. open-and-close p<0.001). Adjuvant systemic chemotherapy was a noteworthy independent prognostic factor in the multivariable analysis. OS for patients undergoing additional surgical treatment of recurrences was 25months vs. 10months with best supportive care or palliative chemotherapy (p=0.01).

    Conclusion

    Substantial long-term survival is possible in patients with colorectal PC. HIPEC was associated with better OS than SPIC and adjuvant systemic chemotherapy may improve the outcome in patients. Good OS is achievable in selected patients undergoing additional surgical treatment of isolated liver or peritoneal recurrences after prior complete CRS.

  • 180.
    Cashin, Peter H
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Nygren, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Mahteme, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Intraoperative hyperthermic versus postoperative normothermic intraperitoneal chemotherapy for colonic peritoneal carcinomatosis: a case-control study2012In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 23, no 3, p. 647-652Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Cytoreductive surgery and intraperitoneal chemotherapy has improved prognosis in patients with peritoneal carcinomatosis. The main modes of intraperitoneal chemotherapy treatment are peroperative hyperthermic intraperitoneal chemotherapy (HIPEC) and normothermic sequential postoperative intraperitoneal chemotherapy (SPIC). The aim of this study was to compare HIPEC and SPIC with respect to overall survival, disease-free survival, morbidity, and mortality in patients with peritoneal carcinomatosis from colon cancer.

    PATIENTS AND METHODS:

    A matched case-control study was conducted in patients with surgical macroscopic complete removal of carcinomatosis; matching was according to the peritoneal cancer index score. Thirty-two patients were included, 16 in each group (HIPEC and SPIC). Overall survival, disease-free survival, morbidity, mortality, and clinicopathological parameters were compared.

    RESULTS:

    Median overall survival was 36.5 months in the HIPEC group and 23.9 months in the SPIC group (P = 0.01). Median disease-free survival for these groups was 22.8 (HIPEC) and 13.0 months (SPIC; P = 0.02). Morbidity was not statistically different, 19% in SPIC and 37% in HIPEC. Postoperative mortality was observed in one patient in each group.

    CONCLUSION:

    HIPEC was associated with improved overall survival and disease-free survival compared with SPIC at similar morbidity and mortality, suggesting that HIPEC is the treatment of choice in colonic peritoneal carcinomatosis.

  • 181.
    Cashin, Peter H
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Nygren, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Mahteme, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Patient Selection for Cytoreductive Surgery in Colorectal Peritoneal Carcinomatosis using Serum Tumour Markers – an Observational Cohort Study2012In: Annals of Surgery, ISSN 0003-4932, E-ISSN 1528-1140, Vol. 256, no 6, p. 1078-1083Article in journal (Refereed)
    Abstract [en]

    Objective: There were 2 objectives: first, to investigate how many patients were excluded from surgery on the basis of the radiological extent of the peritoneal carcinomatosis (PC) or the clinical examination; and second, to develop a score based primarily on serum tumor markers (STMs) that could predict short cancer-specific survival (<12 months). Background: Patient selection and prediction of prognosis is crucial for successful treatment of colorectal PC. Methods: All patients with colorectal PC referred for cytoreductive surgery and intraperitoneal chemotherapy (2005-2008) at Uppsala University hospital were included. Patients were divided into 2 groups-nonsurgery and surgery. Clinicopathological and laboratory parameters were collected in the surgery group. A Corep (COloREctal-Pc) score was developed using hazard ratios from histology, hematological status, serial serum tumor markers (STMs), and STM changes over time. Sensitivity, specificity, positive predicted value (PPV), and negative predicted value (NPV) were calculated in a second validating dataset (n = 24) with a survival cutoff of less than 12 months. Results: A total of 107 patients were included in the study, 42 in the nonsurgery group and 65 in the surgery group. In the nonsurgery group, 2 patients were excluded solely on the basis of the radiological extent of PC and 7 patients on clinical examination. The Corep score ranged from 0 to 18. A score of 6 or more showed a validated sensitivity of 80%, specificity 100%, PPV 1.0, and NPV 0.93. Conclusions: Radiological extent of PC was not a main deciding factor for treatment decisions and had less impact than the clinical examination. The Corep score identified patients with short cancer-specific survival that may not be suitable for treatment.

  • 182.
    Cashin, Peter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Mahteme, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery. Uppsala Canc Clin, Uppsala, Sweden.
    Syk, I.
    Lund Univ, Sect Surg, Dept Clin Sci, Malmo, Sweden.
    Frodin, J. E.
    Karolinska Inst, Dept Oncol & Pathol, S-17176 Stockholm, Sweden.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Karolinska Inst, Dept Oncol & Pathol, S-17176 Stockholm, Sweden.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Quality of life and cost effectiveness in a randomized trial of patients with colorectal cancer and peritoneal metastases2018In: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 44, no 7, p. 983-990Article in journal (Refereed)
    Abstract [en]

    Background: The aim was to compare health-related quality-of-life (HRQOL) and cost-effectiveness between cytoreductive surgery with intraperitoneal chemotherapy (CRS + IPC) and systemic chemotherapy for patients with colorectal peritoneal metastases. Methods: Patients included in the Swedish Peritoneal Trial comparing CRS + IPC and systemic chemotherapy completed the EORTC QLQ-C30 and SF-36 questionnaires at baseline, 2, 4, 6, 12, 18, and 24 months. HRQOL at 24 months was the primary endpoint. EORTC sum score, SF-36 physical and mental component scores at 24 months were calculated and compared for each arm and then referenced against general population values. Two quality-adjusted life-year (QALY) indices were applied (EORTC-8D and SF-6D) and an incremental cost-effectiveness ratio (ICER) per QALY gained was calculated. A projected life-time ICER per QALY gained was calculated using predicted survival according to Swedish population statistics. Results: No statistical differences in HRQOL between the arms were noted at 24 months. Descriptively, survivors in the surgery arm had higher summary scores than the general population at 24 months, whereas survivors in the chemotherapy arm had lower scores. The projected life-time QALY benefit was 3.8 QALYs in favor of the surgery arm (p=0.06) with an ICER per QALY gained at 310,000 SEK (EORTC-8D) or 362,000 SEK (SF-6D) corresponding to 26,700-31,200 GBP. Conclusion: The HRQOL in patients with colorectal peritoneal metastases undergoing CRS + IPC appear similar to those receiving systemic chemotherapy. Two-year survivors in the CRS + IPC arm have comparable HRQOL to a general population reference. The treatment is cost-effective according to NICE guidelines.

  • 183.
    Cervin, Anne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Popliteal Artery Aneurysms: - epidemiology, treatment and results2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Popliteal aneurysms (PA) are limb threatening, since the aneurysm thrombose and emboli from the aneurysm sac occlude the distal vessels, resulting in chronic or acute limb ischaemia. Open surgical repair (OSR) has been challenged by endovascular repair (ER), a minimal invasive technique. Little is known of long-term result, and comparisons of the methods have been difficult, since patients chosen for ER are mainly asymptomatic and have better outflow.

    The overall aim of this thesis was to study epidemiology and risk factors to optimize patient selection and techniques for surgical treatment of PA.

    Papers I and II: Data on all patients treated 2008-2012 (592 PAs in 499 patients) were analysed in the Swedish Vascular registry, Swedvasc. Patency was inferior after ER, in particular for patients with acute ischaemia. Nested in this cohort, a case-control study was performed, and the legs treated by ER (77) were matched, by indication, with twice the number treated with OSR (154). Medical records and radiologic images were collected and examined in a core-lab. In this matched cohort, the only independent risk factors for occlusion were ER and poor outflow. In a sub-group analysis of ER, risk factors for occlusion were acute ischaemia, poor out-flow, smaller stent graft diameter and elongation.

    Paper III: Prevalence of PA was studied in men, screened for abdominal aortic aneurysm (AAA) and of sub aneurysmal aorta, 25-29 mm. Prevalence of PA was high, 14.2%, and correlated with dilatation of the iliac arteries.

    Paper IV: Operations for ruptured PA (rPA) were identified in Swedvasc 1987-2012, medical records were reviewed. Compared with patients treated for other indications, they were 8 years older, had twice as large aneurysms (mean 64 mm) and many were treated with anticoagulants. The initial clinical picture was misleading.

    In conclusion, when treating PA the preferred surgical technique is OSR with a vein graft. Anatomical features of the popliteal artery and outflow vessels affect outcome. These findings are important for future surgical decision making.

    List of papers
    1. Treatment of Popliteal Aneurysm by Open and Endovascular Surgery: A Contemporary Study of 592 Procedures in Sweden
    Open this publication in new window or tab >>Treatment of Popliteal Aneurysm by Open and Endovascular Surgery: A Contemporary Study of 592 Procedures in Sweden
    Show others...
    2015 (English)In: European Journal of Vascular and Endovascular Surgery, ISSN 1078-5884, E-ISSN 1532-2165, Vol. 50, no 3, p. 342-350Article in journal (Refereed) Published
    Abstract [en]

    WHAT THIS STUDY ADDS

    Previous comparisons between open and endovascular repair of popliteal aneurysms have focused on asymptomatic patients, and have short follow up. This study is strengthened by the fact that it is contemporary, population based, without any selection bias, reporting on all kinds of presentations, and has approximately 90% 1 year follow up data. It shows that endovascular repair has significantly inferior results compared with open repair, in particular in the group of patients who present with acute ischaemia. We believe these results will make many vascular surgeons think twice before they treat patients endovascularly in the future. Background: Popliteal aneurysm (PA) is traditionally treated by open repair (OR). Endovascular repair (ER) has become more common. The aim was to describe time trends and compare results (OR/ER). Methods: The Swedish vascular registry, Swedvasc, has a specific PA module. Data were collected (2008-2012) and supplemented with a specific protocol (response rate 99.1%). Data were compared with previously published data (1994-2002) from the same database. Results: The number of operations for PA was 15.7/million person-years (8.3 during 1994-2001). Of 592 interventions for PA (499 patients), 174 (29.4%) were treated for acute ischaemia, 13 (2.2%) for rupture, 105 (17.7%) for other symptoms, and 300 (50.7%) were asymptomatic (31.5% were treated for acute ischaemia, 1994-2002, p = .58). There were no differences in background characteristics between OR and ER in the acute ischaennia group. The symptomatic and asymptomatic groups treated with ER were older (p = .006, p < .001). ER increased 3.6 fold (4.7% 1994-2002, 16.7% 2008-2012, p = .0001). Of those treated for acute ischaemia, a stent graft was used in 27 (16.4%). Secondary patency after ER was 70.4% at 30 days and 47.6% at 1 year, versus 93.1% and 86.8% after OR (p = .001, < .001). The amputation rate at 30 days was 14.8% after ER, 3.7% after OR (p = .022), and 17.4% and 6.8% at 1 year (p = .098). A stent graft was used in 18.3% for asymptomatic PA. Secondary patency after ER was 94.5% at 30 days and 83.7% at 1 year, compared with 98.8% and 93.5% after OR (p = .043 and 0.026). OR was performed with vein graft in 87.6% (395/451), with better primary and secondary patency at 1 year than prosthetic grafts (p = .002 and < .001), and with a posterior approach in 20.8% (121/581). Conclusions: The number of operations for PA doubled while the indications remained similar. ER patency was inferior to OR, especially after treatment for acute ischaemia, and the amputation risk tended to be higher, despite similar pre-operative characteristics.

    Keywords
    Popliteal artery aneurysm, Open repair, Endovascular, Stent graft, Registry, Amputation
    National Category
    Surgery
    Identifiers
    urn:nbn:se:uu:diva-265621 (URN)10.1016/j.ejvs.2015.03.026 (DOI)000361576800016 ()25911500 (PubMedID)
    Funder
    Swedish Research Council, K2013-64X-20406-07-3
    Available from: 2015-11-04 Created: 2015-11-02 Last updated: 2019-04-10Bibliographically approved
    2. Favourable results after open compared to endovascular repair of popliteal aneurysm: a nested case-control study
    Open this publication in new window or tab >>Favourable results after open compared to endovascular repair of popliteal aneurysm: a nested case-control study
    Show others...
    (English)Manuscript (preprint) (Other academic)
    Keywords
    Popliteal artery aneurysm; Endovascular; Open surgery; Stent graft; Occlusion
    National Category
    Surgery
    Research subject
    Surgery
    Identifiers
    urn:nbn:se:uu:diva-381515 (URN)
    Available from: 2019-04-10 Created: 2019-04-10 Last updated: 2019-04-10
    3. Popliteal aneurysms are common among men with screening detected abdominal aortic aneurysms, and the prevalence is correlated with the diameters of the common iliac arteries
    Open this publication in new window or tab >>Popliteal aneurysms are common among men with screening detected abdominal aortic aneurysms, and the prevalence is correlated with the diameters of the common iliac arteries
    (English)Manuscript (preprint) (Other academic)
    Keywords
    Abdominal aortic aneurysm; Popliteal artery aneurysm; Iliac artery; Screening, Prevalence.
    National Category
    Surgery
    Research subject
    Surgery
    Identifiers
    urn:nbn:se:uu:diva-381518 (URN)
    Available from: 2019-04-10 Created: 2019-04-10 Last updated: 2019-04-10
    4. Ruptured popliteal artery aneurysm
    Open this publication in new window or tab >>Ruptured popliteal artery aneurysm
    2018 (English)In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 105, no 13, p. 1753-1758Article in journal (Refereed) Published
    Abstract [en]

    Background: Popliteal artery aneurysms (PAAs) are generally complicated by thrombosis and distal embolization, whereas rupture is rare. The aim of this study was to describe the clinical characteristics and outcome in a cohort of patients who had surgery for ruptured PAA (rPAA).

    Methods: Operations for rPAA identified from the Swedish Vascular Registry, Swedvasc, 1987-2012. Medical records and imaging were reviewed. Comparison was made with patients treated for PAA without rupture.

    Results: Forty-five patients with rPAA were identified. The proportion with rupture among those operated on for PAA was 2.5 per cent. Patients with rPAA were 8 years older (77.7 versus 69.7years; P < 0.001), had more lung and heart disease (P = 0.003 and P = 0.019 respectively), and a larger mean popliteal aneurysm diameter (63.7 versus 30. 9mm; P < 0.001) than patients with PAA treated for other indications. At time of surgery, 22 of 45 patients were already receiving anticoagulants, seven for concomitant deep venous thrombosis (DVT) in the affected leg. There was extensive swelling of the whole leg in 20 patients. In 27 patients, the initial diagnosis was DVT or a Baker's cyst. All patients underwent surgery, all but three by the open method. There were four amputations, all performed within 1week of surgery. One year after surgery, 26 of the 45 patients were alive. Among these, the reconstructions were patent in 20 of 22 patients.

    Conclusion: The diagnosis of rPAA is difficult, and often delayed. The condition affects old patients, who often are on anticoagulation treatment and have large aneurysms. The immediate surgical results are acceptable, but the condition is associated with a high risk of death within the first year after surgery.

    Place, publisher, year, edition, pages
    WILEY, 2018
    National Category
    Surgery Cardiac and Cardiovascular Systems
    Identifiers
    urn:nbn:se:uu:diva-373014 (URN)10.1002/bjs.10953 (DOI)000450816200010 ()30043540 (PubMedID)
    Available from: 2019-01-10 Created: 2019-01-10 Last updated: 2019-04-10Bibliographically approved
  • 184.
    Cervin, Anne
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Acosta, Stefan
    Department of Clinical Sciences Malmö, Lund University.
    Hultgren, Rebecka
    Department of Vascular Surgery, Karolinska University Hospital, Stockholm.
    Björck, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Falkenberg, Mårten
    Department of Radiology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg.
    Favourable results after open compared to endovascular repair of popliteal aneurysm: a nested case-control studyManuscript (preprint) (Other academic)
  • 185.
    Cervin, Anne
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery. Department of Hybrid and Interventional Surgery, Sahlgrenska University Hospital.
    Björck, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Popliteal aneurysms are common among men with screening detected abdominal aortic aneurysms, and the prevalence is correlated with the diameters of the common iliac arteriesManuscript (preprint) (Other academic)
  • 186.
    Cervin, Anne
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery. Sahlgrens Univ Hosp, Unit Vasc Surg, Dept Hybrid & Intervent Surg, SE-41345 Gothenburg, Sweden.
    Ravn, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery. Univ Southern Denmark, Kolding Hosp, Dept Vasc Surg, Kolding, Denmark.
    Björck, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Ruptured popliteal artery aneurysm2018In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 105, no 13, p. 1753-1758Article in journal (Refereed)
    Abstract [en]

    Background: Popliteal artery aneurysms (PAAs) are generally complicated by thrombosis and distal embolization, whereas rupture is rare. The aim of this study was to describe the clinical characteristics and outcome in a cohort of patients who had surgery for ruptured PAA (rPAA).

    Methods: Operations for rPAA identified from the Swedish Vascular Registry, Swedvasc, 1987-2012. Medical records and imaging were reviewed. Comparison was made with patients treated for PAA without rupture.

    Results: Forty-five patients with rPAA were identified. The proportion with rupture among those operated on for PAA was 2.5 per cent. Patients with rPAA were 8 years older (77.7 versus 69.7years; P < 0.001), had more lung and heart disease (P = 0.003 and P = 0.019 respectively), and a larger mean popliteal aneurysm diameter (63.7 versus 30. 9mm; P < 0.001) than patients with PAA treated for other indications. At time of surgery, 22 of 45 patients were already receiving anticoagulants, seven for concomitant deep venous thrombosis (DVT) in the affected leg. There was extensive swelling of the whole leg in 20 patients. In 27 patients, the initial diagnosis was DVT or a Baker's cyst. All patients underwent surgery, all but three by the open method. There were four amputations, all performed within 1week of surgery. One year after surgery, 26 of the 45 patients were alive. Among these, the reconstructions were patent in 20 of 22 patients.

    Conclusion: The diagnosis of rPAA is difficult, and often delayed. The condition affects old patients, who often are on anticoagulation treatment and have large aneurysms. The immediate surgical results are acceptable, but the condition is associated with a high risk of death within the first year after surgery.

  • 187.
    Cervin, Anne
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery. NU Hosp Org, Trollhattan Uddevalla, Sweden..
    Tjärnstrom, J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery. NU Hosp Org, Trollhattan Uddevalla, Sweden..
    Ravn, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery. Lillebaelt Hosp, Dept Vasc Surg, Lillebaelt, Denmark..
    Acosta, S.
    Malmo Univ Hosp, Vasc Ctr, Malmo, Sweden..
    Hultgren, R.
    Karolinska Inst, Dept Vasc Surg, Stockholm, Sweden..
    Welander, M.
    Linkoping Univ, Dept Vasc Surg, Linkoping, Sweden..
    Björck, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Treatment of Popliteal Aneurysm by Open and Endovascular Surgery: A Contemporary Study of 592 Procedures in Sweden2015In: European Journal of Vascular and Endovascular Surgery, ISSN 1078-5884, E-ISSN 1532-2165, Vol. 50, no 3, p. 342-350Article in journal (Refereed)
    Abstract [en]

    WHAT THIS STUDY ADDS

    Previous comparisons between open and endovascular repair of popliteal aneurysms have focused on asymptomatic patients, and have short follow up. This study is strengthened by the fact that it is contemporary, population based, without any selection bias, reporting on all kinds of presentations, and has approximately 90% 1 year follow up data. It shows that endovascular repair has significantly inferior results compared with open repair, in particular in the group of patients who present with acute ischaemia. We believe these results will make many vascular surgeons think twice before they treat patients endovascularly in the future. Background: Popliteal aneurysm (PA) is traditionally treated by open repair (OR). Endovascular repair (ER) has become more common. The aim was to describe time trends and compare results (OR/ER). Methods: The Swedish vascular registry, Swedvasc, has a specific PA module. Data were collected (2008-2012) and supplemented with a specific protocol (response rate 99.1%). Data were compared with previously published data (1994-2002) from the same database. Results: The number of operations for PA was 15.7/million person-years (8.3 during 1994-2001). Of 592 interventions for PA (499 patients), 174 (29.4%) were treated for acute ischaemia, 13 (2.2%) for rupture, 105 (17.7%) for other symptoms, and 300 (50.7%) were asymptomatic (31.5% were treated for acute ischaemia, 1994-2002, p = .58). There were no differences in background characteristics between OR and ER in the acute ischaennia group. The symptomatic and asymptomatic groups treated with ER were older (p = .006, p < .001). ER increased 3.6 fold (4.7% 1994-2002, 16.7% 2008-2012, p = .0001). Of those treated for acute ischaemia, a stent graft was used in 27 (16.4%). Secondary patency after ER was 70.4% at 30 days and 47.6% at 1 year, versus 93.1% and 86.8% after OR (p = .001, < .001). The amputation rate at 30 days was 14.8% after ER, 3.7% after OR (p = .022), and 17.4% and 6.8% at 1 year (p = .098). A stent graft was used in 18.3% for asymptomatic PA. Secondary patency after ER was 94.5% at 30 days and 83.7% at 1 year, compared with 98.8% and 93.5% after OR (p = .043 and 0.026). OR was performed with vein graft in 87.6% (395/451), with better primary and secondary patency at 1 year than prosthetic grafts (p = .002 and < .001), and with a posterior approach in 20.8% (121/581). Conclusions: The number of operations for PA doubled while the indications remained similar. ER patency was inferior to OR, especially after treatment for acute ischaemia, and the amputation risk tended to be higher, despite similar pre-operative characteristics.

  • 188.
    Cesarini, Kristina G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    The European board qualification in neurosurgery (EBQNS)2007In: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 149, no 10, p. 1084-1085Article in journal (Refereed)
  • 189.
    Chabok, Abbas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Andreasson, Kalle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Nikberg, Maziar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Low risk of complications in patients with first-time acute uncomplicated diverticulitis2017In: International Journal of Colorectal Disease, ISSN 0179-1958, E-ISSN 1432-1262, Vol. 32, no 12, p. 1699-1702Article in journal (Refereed)
    Abstract [en]

    First-time acute uncomplicated diverticulitis (AUD) has been considered to have an increased risk of complication, but the level of evidence is low. The aim of the present study was to evaluate the risk of complications in patients with first-time AUD and in patients with a history of diverticulitis. This paper is a population-based retrospective study at Vastmanland's Hospital, VasterA<yen>s, Sweden, where all patients were identified with a diagnosis of colonic diverticular disease ICD-10 K57.0-9 from January 2010 to December 2014. The records of all patients were surveyed and patients with a computed tomography (CT)-verified AUD were included. Complications defined as CT-verified abscess, perforation, colonic obstruction, fistula, or sepsis within 1 month from the diagnosis of AUD were registered. Of 809 patients with AUD, 642 (79%) had first-time AUD and 167 (21%) had a previous history of AUD with no differences in demographic or clinical characteristics. In total, 16 (2%) patients developed a complication within 1 month irrespective of whether they had a previous history of diverticulitis (P = 0.345). In the binary logistic regression analysis, first-time diverticulitis was not associated with increased risk of complications (OR 1.58; CI 0.52-4.81). The rate of antibiotic therapy was about 7-10% during the time period and outpatient management increased from 7% in 2010 to 61% in 2014. The risk for development of complications is low in AUD with no difference between patients with first-time or recurrent diverticulitis. This result strengthens existing evidence on the benign disease course of AUD.

  • 190.
    Chabok, Abbas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Hjern, F.
    Haapaniemi, S.
    Smedh, Kennet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Randomized clinical trial of antibiotics in acute uncomplicated diverticulitis2012In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 99, no 4, p. 532-539Article in journal (Refereed)
    Abstract [en]

    Background: The standard of care for acute uncomplicated diverticulitis today is antibiotic treatment, although there are no controlled studies supporting this management. The aim was to investigate the need for antibiotic treatment in acute uncomplicated diverticulitis, with the endpoint of recovery without complications after 12 months of follow-up.

    Methods: This multicentre randomized trial involving ten surgical departments in Sweden and one in Iceland recruited 623 patients with computed tomography-verified acute uncomplicated left-sided diverticulitis. Patients were randomized to treatment with (314 patients) or without (309 patients) antibiotics.

    Results: Age, sex, body mass index, co-morbidities, body temperature, white blood cell count and C-reactive protein level on admission were similar in the two groups. Complications such as perforation or abscess formation were found in six patients (1.9 per cent) who received no antibiotics and in three (1.0 per cent) who were treated with antibiotics (P = 0.302). The median hospital stay was 3 days in both groups. Recurrent diverticulitis necessitating readmission to hospital at the 1-year follow-up was similar in the two groups (16 per cent, P = 0.881).

    Conclusion: Antibiotic treatment for acute uncomplicated diverticulitis neither accelerates recovery nor prevents complications or recurrence. It should be reserved for the treatment of complicated diverticulitis.

  • 191.
    Chabok, Abbas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Smedh, Kenneth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Nilsson, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Stenson, Marianne
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    CT-colonography in the follow-up of acute diverticulitis: patient acceptance and diagnostic accuracy2013In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 48, no 8, p. 979-986Article in journal (Refereed)
    Abstract [en]

    Objective. The aim of this study was to assess CT-colonography (CTC) in the follow-up of diverticulitis regarding patient acceptance and diagnostic accuracy for diverticular disease, adenomas and cancer, with colonoscopy as a reference standard. Methods. A prospective comparative study where half of the patients underwent colonoscopy first, followed immediately by CTC. The other half had the examinations in the reverse order. Patient experiences and findings were registered after every examination, blinded to the examiner. Results. Of a total of 110 consecutive patients, 108 were included in the study, with a median age of 56 years (range 27-84). The success rate was 91% for colonoscopy and 86% for CTC. Examination time was 25 mm for both methods. The mean time for CTC evaluation was 20 mm. Eighty-three per cent of the patients received sedation during colonoscopy. Despite this, patients experienced colonoscopy as more painful (p < 0.001) and uncomfortable (p < 0.001). Diverticulosis and polyps were detected in 94% and 20% with colonoscopy and in 94% and 29% with CTC, respectively. Sensitivity and specificity for CTC in the detection of diverticulosis was 99% and 67%, with a good agreement (kappa = 0.71). Regarding detection of polyps, the sensitivity and specificity were 47% and 75%, with a poor agreement (kappa = 0.17). No cancer was found. Conclusion. CTC was less painful and unpleasant and can be used for colonic investigation in the follow-up of diverticulitis. CTC detected diverticulosis with good accuracy while the detection accuracy of small polyps was poor. CTC is a viable alternative, especially in case of incomplete colonoscopy or in a situation with limited colonoscopy resources.

  • 192. Chambers, I.
    et al.
    Gregson, B.
    Citerio, G.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Howells, Timothy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Kiening, K.
    Mattern, J.
    Nilsson, Pelle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Piper, Ian
    Ragauskas, A.
    Sahuquillo, J.
    Yau, Y. H.
    BrainIT collaborative network: analyses from a high time-resolution dataset of head injured patients2009In: Intracranial Pressure and Brain Monitoring XIII: Mechanisms and Treatment / [ed] Manley, Geoffrey; Hemphill, Claude; Stiver, Shirley, Vienna: Springer , 2009, Vol. 102, p. 223-227Chapter in book (Other academic)
  • 193.
    Chen, L.
    et al.
    Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, Stockholm, Sweden..
    Glimelius, Ingrid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, Stockholm, Sweden..
    Neovius, M.
    Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, Stockholm, Sweden..
    Eloranta, S.
    Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, Stockholm, Sweden..
    Ekberg, S.
    Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, Stockholm, Sweden.;Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Martling, A.
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..
    Smedby, K. E.
    Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, Stockholm, Sweden..
    Risk of disability pension in patients following rectal cancer treatment and surgery2015In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 102, no 11, p. 1426-1432Article in journal (Refereed)
    Abstract [en]

    BackgroundAspects of survivorship, such as long-term ability to work, are increasingly relevant owing to the improved survival of patients with rectal cancer. The aim of this study was to assess risk and determinants of disability pension (DP) in this patient group. MethodsUsing Swedish national clinical and population-based registers, patients with stage I-III rectal cancer aged 18-61years in 1995-2009 were identified at diagnosis and matched with population comparators. Prospectively registered records of DP during follow-up were retrieved up to 2013. Non-proportional and proportional hazards models were used to estimate the incidence rate ratio (IRR) for DP annually and overall. Potential variations in risk by demographic and clinical factors were calculated, with relapse as a time-varying exposure. ResultsA total of 2815 patients were identified and compared with 13465 population comparators. During a median follow-up of 60 (range 0-10) years, 233 per cent of the relapse-free patients and 103 per cent of the population comparators received DP (IRR 240, 95 per cent c.i. 217 to 265). An increased annual risk of DP was evident almost every year until the tenth year of follow-up. Abdominoperineal resection was associated with an increased DP risk compared with anterior resection (IRR 144, 119 to 175). Surgical complications (IRR 133, 110 to 162) and reoperation (IRR 142, 109 to 184), but not radiotherapy or chemotherapy, were associated with risk of DP. ConclusionRelapse-free patients with rectal cancer of working age are at risk of disability pension. Higher than expected

  • 194.
    Chen, Liying
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Experimental studies on thrombosis and thrombolysis: With special reference to importance of lys-plasminogen, active site thrombin inhibitors and stable fish oil1999Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Dissolution and prevention of thrombus in the atherosclerotic coronary artery have become an important part of treatment therapy of acute myocardial infarction. However, the currently most effective thrombolytic agent, recombinant tissue-type plasminogen activator (rt-PA), only elicits 80% recanalization of thrombotically occluded coronary arteries and early occlusion occurs in about 40% of successfullyrecanalized vessels.

    To achieve prompt and persistent thrombolysis, studies were constructed with glu- or lys-plasminogen, the substrate of rt-PA. Dogs with left anterior descending coronary artery (LAD) thrombus were treated with saline, glu-plasminogen or lys-plasminogen followed by infusion of rt-PA. Lys-plasminogen, but not glu-plasminogen, significantly accelerated the thrombolytic process induced by rt-PA and reduced the early reocclusion rate to 0%.Since increased thrombin activity has been associated with a delay in coronary thrombolysis or with early reocclusion, the effects of addition of the direct thrombin inhibitor inogatran were also examined. Inogatran at an optimal dose given with rt-PA totally prevented early reocclusion in the thrombotic coronary artery by inhibiting the generation and activity of thrombin. Aspirin given with suboptimal doses of inogatran did not potentiate the thrombolytic effect of rt-PA, or prevent coronary artery early reocclusion.

    To test whether an oral thrombin inhibitor will delay or prevent the formation of occlusive thrombus, anesthetized dogs were given saline or a single dose of a novel direct low molecular weight thrombin inhibitor melagatran by nasogastric tube before thrombus was induced. The study demonstrated that melagatran significantly delayed the formation of thrombus in the coronary artery through inhibition of thrombin, suggesting that long-term oral treatment with melagatran may be an attractive way to prevent arterial thrombosis.

    These observations imply that local depletion of plasminogen at the site of a thrombus is related to the limited thrombolytic efficacy and short-lasting effects of rt-PA. Generation of large amounts of thrombin is a critical factor in coronary artery thrombosis and early reocclusion after thrombolysis. We also examined the influence of dietary stable fish oil on FeCl3-induced aortic thrombosis in a rat model. The results indicated that dietary stable fish oil decreases the tendency to arterial thrombosis probably by reducing platelet aggregation and oxidative stress-associated arterial injury.

  • 195.
    Chew, Michelle S.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Mangelus, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Enlund, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Spetz, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lyckner, Sara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Surgery was successful - but how did it go for the patient?: Experiences from and hopes for the Swedish Perioperative Register2015In: European Journal of Anaesthesiology, ISSN 0265-0215, E-ISSN 1365-2346, Vol. 32, no 7, p. 453-454Article in journal (Other academic)
  • 196. Chou, J.
    et al.
    Harvey, B. K.
    Ebendal, Ted
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Hoffer, B.
    Wang, .
    Nigrostriatal alterations in bone morphogenetic protein receptor II dominant negative mice2008In: Reconstructive Neurosurgery / [ed] Wen-Ta Chiu, Yung-Hsiao Chiang, Ming-Chien Kao et a.-, Wien: Springer , 2008, Vol. 101, p. 93-98Chapter in book (Other academic)
    Abstract [en]

    BACKGROUND: We previously demonstrated that exogenous application of bone morphogenetic protein 7 (BMP7) reduced 6-hydroxydopamine-mediated neurodegeneration in a rodent model of Parkinson's disease. The purpose of this study is to examine the endogenous neurotrophic properties of BMP Receptor II in dopaminergic neurons of the nigrostriatal pathway. METHODS: Adult male BMPRII dominant negative (BMPRIIDN) mice and their wild type controls (WT) were placed in the activity chambers for 3 days to monitor locomotor activity. Animals were sacrificed for tyrosine hydroxylase (TH) immunostaining. A subgroup of BMPRIIDN and WT mice were injected with high doses of methamphetamine (MA) and were sacrificed for terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) histochemistry at 4 days after injection. RESULTS: BMPRIIDN mice had lower locomotor activity than the WT. There is a significant decrease in TH neuronal number in substantia nigra compacta, TH fiber density in the substantia nigra reticulata, and TH immunoreactivity in striatum in the BMPRIIDN mice, suggesting that deficiency in endogenous BMP signaling reduces dopaminergic innervation and motor function in the nigrostriatal pathway. Administration of MA increased TUNEL labeling in the substantia nigra in the BMPRIIDN mice. CONCLUSIONS: Endogenous BMPs have trophic effects on nigrostriatal dopaminergic neurons. Deficiency in BMP signaling increases vulnerability to insults induced by high doses of MA.

  • 197.
    Chrcanovic, Bruno Ramos
    et al.
    Malmo Univ, Fac Odontol, Dept Prosthodont, Carl Gustafs Vag 34, SE-20506 Malmo, Sweden.
    Nilsson, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery. Zealand Univ Hosp, Dept Oral & Maxillofacial Surg, Koge, Denmark.
    Thor, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Survival and complications of implants to support craniofacial prosthesis: A systematic review2016In: Journal of Cranio-Maxillofacial Surgery, ISSN 1010-5182, E-ISSN 1878-4119, Vol. 44, no 10, p. 1536-1552Article, review/survey (Refereed)
    Abstract [en]

    OBJECTIVE: To assess the survival rate of craniofacial implants (CIs) to support facial prosthesis/epithesis and the prevalence of surgical/biological complications based on previously published studies.

    METHODS: An electronic search was undertaken in March/2016. Only studies with a minimum of 5 patients were included. Untransformed proportions of implant failures for different regions were calculated. A meta-analysis evaluated the influence of radiotherapy on the failure rates. A meta-regression was performed considering the follow-up period as covariate.

    RESULTS: Seventy publications included 2355 patients and 8184 CIs (545 failures). The probability of a failure was 5.5% for all CIs (95%CI 4.5-6.5, P < 0.001), 1.2% for CIs in the auricular region (95%CI 0.8-1.5, P < 0.001), 12.2% for the nasal region (95%CI 9.0-15.5, P = 0.017), and 12.1% for the orbital region (95%CI 9.3-15.0, P < 0.001). Radiotherapy statistically affected the CIs rates (OR 5.80, 95%CI 3.77-8.92, P < 0.00001). There was no statistically significant influence of the follow-up time on the proportion of implant failures (P = 0.814). Soft tissue adverse reactions were the most common complications.

    CONCLUSIONS: Implants placed in the auricular region have a lower probability of failure than those in the nasal and orbital regions. Soft tissue adverse reactions were the most common complications. Radiotherapy significantly affected the CIs failure rates.

  • 198.
    Christersson, Albert
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Sandén, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Clinical outcome after plaster cast fixation for 10 days versus 1 month in reduced distal radius fractures: A prospective randomized study2018In: Scandinavian Journal of Surgery, ISSN 1457-4969, E-ISSN 1799-7267, Vol. 107, no 1, p. 82-90Article in journal (Refereed)
    Abstract [en]

    Introduction: this study aimed to evaluate clinical results after plaster cast fixation for 10 days versus 1 month of moderately displaced and reduced distal radius fractures.Material and Methods: in a prospective randomized study, 109 patients with moderately displaced and conservatively treated distal radius fractures (age ≥50 years) were randomized 10 days after reduction to either removal of the plaster cast and immediate mobilization (active group) or to continued plaster cast fixation for another 3 weeks (control group). Grip strength, pincer strength, range of motion, and pain were assessed at 1, 4, and 12 months after reduction. Clinical outcome was evaluated using three functional assessment scores at 12 months.Results: treatment failed in 3/54 (6%) patients in the active group. one of these patients had the plaster cast reinstituted because of feelings of instability. the fractures in the other two patients displaced severely after mobilization and were therefore treated surgically. for the remaining 51 patients in the active group, the range of wrist motion was slightly better at 1 month compared with the controls, but there were no differences in grip or pincer strength or pain at the 1-month follow-up. there were no differences between the active and control group in any outcome at 4 or 12 months, including functional assessment scores at 12 months.Conclusion: treatment with mobilization 10 days after reduction of moderately displaced distal radius fractures resulted in a few treatment failures compared with none among controls. the only functional benefit for the remaining patients was a small and transient increase in range of motion at the 1-month follow-up. plaster cast removal 10 days after reduction in moderately displaced distal radius fractures is therefore not recommended.

  • 199.
    Christiansson, Lennart
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Spinal cord ischemia: An experimental study of the spinal cord blood supply and peroperative ischemia detection by a new method of intrathecal monitoring2000Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Spinal cord ischemia associated with thoracoabdominal aortic surgery may lead to devastating neurological complications. Improvement in bypass techniques and various adjunctive measures has reduced its incidence, but still 5-10 % of the patients develop postoperative paraplegia. There is no universally accepted method for the detection of spinal cord ischemia. Intraoperative monitoring methods are important for the prediction of ischemia and guidance in aorticreplacement strategy. This thesis presents a new technique for continuous peroperative monitoring of intrathecal oxygenation.

    A multiparameter sensor was used to measure cerebrospinal fluid (CSF) PO2, PCO2 and pH during thoracic aortic cross-clamping in pigs. The findings were experimentally validated by comparisons with epidural laser-Doppler flowmetry and with morphological outcome, as assessed by electron microscopy of immersion fixated spinal cord specimens. The CSF monitoring was used to study functional aspects of segmental and collateral spinal cord blood supply. An experimental model was developed for the study of selective spinal cord ischemia. For this purpose a passive aortic shunt was used.

    The new monitoring method correlated in the experimental situation with measurements of microcirculation and changes in spinal cord ultrastructure associated with aortic cross-clamping. It proved to be sensitive for detecting ischemia and responded rapidly to alterations in spinal cord circulation. The confounding hemodynamic effects of cross-clamping and systemic reperfusion injuries to the spinal cord could be avoided in the selective ischemia model. The shunt model was also used to study the beneficial effects of hyperoxemia during spinal cord hypoperfusion. In conclusion, this thesis presents a new monitoring method for spinal cord oxygenation during experimental aortic occlusion. The thin flexible sensor can be used percutaneously in humans and comparative studies are needed to correlate the findings with neurophysiological evaluations and clinical outcome.

  • 200.
    Christofferson, Rolf
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Läckgren, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Stenberg, Arne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Grottes barnkirurgi och barnurologi2015 (ed. 1)Book (Other academic)
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