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  • 301.
    Heitz, F.
    et al.
    Evangelische Huyssens Stiftung, Germany; Charite Univ Med Berlin, Germany; Free Univ Berlin, Germany; Humboldt Unive Berlin, Germany; Berlin Inst Hlth, Germany; AGO Study Grp, Germany.
    Harter, P.
    Evangelische Huyssens Stiftung, Germany; AGO Study Grp, Germany.
    Åvall-Lundqvist, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Karolinska Inst, Linkoping, Sweden; NSGO Study Grp, Germany.
    Reuss, A.
    Coordinating Ctr Clin Trials, Germany; AGO Study Grp, Germany.
    Pautier, P.
    Inst Gustave Roussy, France; GINECO Study Grp, Germany.
    Cormio, G.
    Univ Bari, Italy; Natl Canc Inst Giovanni Paolo II, Italy; MITO Study Grp, Germany.
    Colombo, N.
    Univ Milano Bicocca, Italy; Inst Europeo Oncol, Italy; MaNGO Study Grp, Germany.
    Reinthaller, A.
    Med Univ Vienna, Austria; AGO Austria Study Grp, Austria.
    Vergote, I.
    Univ Leuven, Belgium; BGOG Study Grp, Austria.
    Poveda, A.
    Inst Valenciano Oncol, Spain; GEICO Study Grp, Spain.
    Ottevanger, P. B.
    Radboud Univ Nijmegen, Netherlands; DGOG Study Grp, Spain.
    Hanker, L. C.
    Univ Schleswig Holstein, Germany; AGO Study Grp, Germany.
    Leminen, A.
    Womens Hosp Med Ctr, Finland; NSGO Study Grp, Germany.
    Alexandre, J.
    Hop Univ Paris Ctr, France; GINECO Study Grp, Germany.
    Canzler, U.
    Tech Univ Dresden, Germany; AGO Study Grp, Germany.
    Sehouli, J.
    Charite Campus Virchow Klinikum, Germany; AGO Study Grp, Germany.
    Herrstedt, J.
    Odense Univ Hosp, Denmark; Zealand Univ, Denmark; NSGO Study Grp, Germany.
    Fiane, B.
    Stavanger Univ Hosp, Norway; NSGO Study Grp, Germany.
    Merger, M.
    Boehringer Ingelheim Pharma GmbH and Co KG, Germany.
    du Bois, A.
    AGO Study Grp, Germany.
    Early tumor regrowth is a contributor to impaired survival in patients with completely resected advanced ovarian cancer. An exploratory analysis of the Intergroup trial AGO-OVAR 122019In: Gynecologic Oncology, ISSN 0090-8258, E-ISSN 1095-6859, Vol. 152, no 2, p. 235-242Article in journal (Refereed)
    Abstract [en]

    Objective. Surgical assessment of residual tumor provides the strongest prognostic information in advanced ovarian cancer (AOC), with the best outcome observed after complete resection. Postoperative radiological assessment before initiation of chemotherapy can supplement the information obtained by surgical assessment; however, it may also reveal conflicting findings. Methods. Patients with AOC enrolled in the AGO-OVAR 12 trial underwent baseline imaging before the first chemotherapy cycle. The findings from surgical and radiologic assessment for disease extend were compared. Additionally, an integrated approach was assessed. Results. Complete data from all 3 assessment methods were available for 1345 patients. Of 689 patients with complete resection, tumor was observed in 28% and 22% of patients undergoing radiologic and integrated assessment, respectively. Patients with surgical- radiological and surgical-integrated concordant findings showed a 5-year overall survival (5Y-OS) of 72% and 71%, whereas patients with surgical-radiological and surgical-integrated discordant results showed inferior 5Y-OS of 47% and 49%, respectively. Patients with surgically assessed residual disease had a 5-YOS of 37%. The interval between surgery and baseline assessment was independently associated with discordance between assessment methods, which might reflect early tumor regrowth. Conclusions. Baseline tumor assessment before chemotherapy provides information that stratifies patients with complete resection into different prognostic groups. Integrating the data from different assessment methods might lead to improved definitions of prognostic groups. Further investigation to determine if earlier initiation of chemotherapy after debulking surgery could increase survival of patients with early tumor regrowth is warranted. (C) 2018 Published by Elsevier Inc.

  • 302.
    Hemdan, Tammer
    et al.
    Department of Surgical Sciences, Uppsala University, Uppsala.
    Malmström, Per-Uno
    Department of Surgical Sciences, Uppsala University, Uppsala.
    Jahnson, Staffan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland. Department of Surgical Sciences, Uppsala University, Uppsala.
    Segersten, Ulrika
    Department of Surgical Sciences, Uppsala University, Uppsala.
    Emmprin expression predicts response and survival following cisplatin containing chemotherapy for bladder cancer: A validation study2015In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 194, no 6, p. 1575-1581Article in journal (Refereed)
    Abstract [en]

    Purpose Neoadjuvant chemotherapy before cystectomy is recommended. To our knowledge the subset of patients likely to benefit has not been identified. We validate emmprin and survivin as markers of chemotherapy response. Materials and Methods Tumor specimens were obtained before therapy from a total of 250 patients with T1-T4 bladder cancer enrolled in 2 randomized trials comparing neoadjuvant chemotherapy before cystectomy with a surgery only arm. Protein expression was determined by immunohistochemistry. Results Expression was categorized according to predefined cutoffs reported in the literature. Data were analyzed with the Kaplan-Meier method and Cox models. Patients in the chemotherapy cohort with negative emmprin expression had significantly higher down staging overall survival than those with positive expression (71% vs 38%, p <0.001). The values for cancer specific survival were 76% and 56%, respectively (p <0.027). In the cystectomy only cohort emmprin expression was not associated with overall survival (46% vs 35%, p = 0.23) or cancer specific survival (55% vs 51%, p = 0.64). Emmprin negative patients had an absolute risk reduction of 25% in overall survival (95% CI 11-40) and a number needed to treat of 4 (95% CI 2.5-9.3). Survivin expression was not useful as a biomarker in this study. Limitations were the retrospective design and heterogeneity coupled with the time difference between the trials. Conclusions Patients with emmprin negative tumors have a better response to neoadjuvant chemotherapy before cystectomy than those with positive expression. © 2015 American Urological Association Education and Research, Inc.

  • 303.
    Henfridsson, Pia
    et al.
    Univ Gothenburg, Sweden.
    Laurenius, Anna
    Univ Gothenburg, Sweden.
    Wallengren, Ola
    Univ Gothenburg, Sweden.
    Beamish, Andrew J.
    Univ Gothenburg, Sweden.
    Dahlgren, Jovanna
    Univ Gothenburg, Sweden.
    Flodmark, Carl-Erik
    Skane Univ Hosp, Sweden.
    Marcus, Claude
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Olbers, Torsten
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping. Univ Gothenburg, Sweden.
    Gronowitz, Eva
    Univ Gothenburg, Sweden.
    Ellegard, Lars
    Univ Gothenburg, Sweden.
    Micronutrient intake and biochemistry in adolescents adherent or nonadherent to supplements 5 years after Roux-en-Y gastric bypass surgery2019In: Surgery for Obesity and Related Diseases, ISSN 1550-7289, E-ISSN 1878-7533, Vol. 15, no 9, p. 1494-1502Article in journal (Refereed)
    Abstract [en]

    Background: Roux-en-Y gastric bypass (RYGB) is an effective obesity treatment in adults and has become established in adolescents. Lower adherence to supplementation in adolescents confers a risk for long-term nutritional deficiencies. Objectives: To assess adherence to supplementation, micronutrient intake, and biochemistry in adolescents through 5 years after RYGB. Setting: University hospitals, multicenter study, Sweden. Methods: Micronutrient intake and adherence to supplementation were assessed by diet history interviews and biochemistry preoperatively, 1, 2, and 5 years after RYGB in 85 adolescents (67% females), aged 16.5 years (+/- 1.2) with a body mass index of 45.5 kg/m(2) (+/- 6.0). Adherence was defined as taking prescribed supplements amp;gt;= 3 times a week. Micronutrient intake and biochemistry were compared with matched controls at 5 years. Results: Over 75% completed the dietary assessments across 5 years after RYGB. Adherence ranged between 44-61% through 5 years. At 5 years, ferritin and hemoglobin decreased (P amp;lt; .04) and 61% had iron deficiency (P amp;lt;= .001). Among females with iron deficiency, most did not adhere to supplementation (P = .005), and 59% of these had anemia (P amp;lt; .001). Vitamin D insufficiency continued after surgery and 80% of participants who did not adhere to supplementation had insufficiency (P = .002). Adolescents not adhering had lower levels of vitamin D, B-12, and fern tin (females) compared with both adhering adolescents and the control group (all P amp;lt; .04). Conclusions: Half of adolescents after RYGB reported sufficient long-term adherence to supplementation. Adhering to supplements and reporting a higher micronutrient intake were associated with more favorable biochemistry. Results support the recommendations for monitoring micronutrient intake and biochemistry in all patients who have undergone RYGB surgery, and the recommendation of higher preventive supplementation of vitamin D and iron in both sexes. As hypothesized, adolescents not adhering had a higher prevalence of long-term micronutrient deficiencies. (C) 2019 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

  • 304.
    Henfridsson, Pia
    et al.
    Univ Gothenburg, Sweden.
    Laurenius, Anna
    Univ Gothenburg, Sweden.
    Wallengren, Ola
    Univ Gothenburg, Sweden.
    Gronowitz, Eva
    Univ Gothenburg, Sweden.
    Dahlgren, Jovanna
    Univ Gothenburg, Sweden.
    Flodmark, Carl-Erik
    Skane Univ Hosp, Sweden.
    Marcus, Claude
    Karolinska Inst, Sweden.
    Olbers, Torsten
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping. Univ Gothenburg, Sweden.
    Ellegard, Lars
    Univ Gothenburg, Sweden.
    Five-year changes in dietary intake and body composition in adolescents with severe obesity undergoing laparoscopic Roux-en-Y gastric bypass surgery2019In: Surgery for Obesity and Related Diseases, ISSN 1550-7289, E-ISSN 1878-7533, Vol. 15, no 1, p. 51-58Article in journal (Refereed)
    Abstract [en]

    Background: Information is scarce on long-term changes in energy intake (EI), dietary energy density (DED), and body composition in adolescents undergoing laparoscopic Roux-en-Y gastric bypass (RYGB). Objectives: To investigate long-term changes in EI, DED, and body composition in adolescents after LRYGB. Setting: University hospitals, multicenter study, Sweden. Methods: Eighty-five adolescents (67% girls; mean +/- standard deviation, age 16.0 +/- 1.2 yr, body mass index 45.5 +/- 6.1 kg/m(2)) were assessed preoperatively (baseline) and 1, 2, and 5 years after LRYGB with diet history interviews and dual-energy x-ray absorptiometry. Matched obese adolescent controls receiving nonsurgical treatment were assessed only at 5 years. Results: Weight decreased 31%, 33%, and 28% at 1, 2, and 5 years after LRYGB (P amp;lt; .001) while controls gained 13% over 5 years (P amp;lt; .001). Dietary assessments were completed in 98%, 93%, 87%, and 75% at baseline and 1, 2, and 5 years, respectively, and in 65% of controls. Baseline EI (2558 kcal/d), decreased by 34%, 22%, and 10% after 1, 2, and 5 years (P amp;lt; .05). DED decreased at 1 year (P -= .03). Macronutrient distribution was not different from controls at 5 years, but EI and DED were 31% and 14% lower (P amp;lt; .015). Fat, fat-free, and muscle mass decreased through 5 years after LRYGB (P amp;lt; .001). Boys preserved muscle mass more than girls (P amp;lt; .01). Adequate protein intake was associated with preservation of muscle mass (P=.003). Conclusions: In adolescents undergoing LRYGB EI remained 10% lower 5 years after surgery. Decreased EI and DED, rather than macronutrient distribution, are important factors in weight loss after surgery. Higher protein intake may facilitate preservation of muscle mass. (C) 2018 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

  • 305.
    Henriksson, Martin
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Society and Health. Linköping University, Faculty of Medicine and Health Sciences.
    Björnsson, Bergthor
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Eilard, M. Sternby
    Univ Gothenburg, Sweden.
    Lindell, G.
    Lund Univ, Sweden.
    Strömberg, C.
    Karolinska Univ Hosp, Sweden.
    Hemmingsson, O.
    Umea Univ, Sweden.
    Isaksson, B.
    Uppsala Univ, Sweden.
    Rizell, M.
    Univ Gothenburg, Sweden.
    Sandström, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Treatment patterns and survival in patients with hepatocellular carcinoma in the Swedish national registry SweLiv2020In: BJS OPEN, ISSN 2474-9842, Vol. 4, no 1, p. 109-117Article in journal (Refereed)
    Abstract [en]

    Background Consistent data on clinical features, treatment modalities and long-term survival in patients with hepatocellular carcinoma (HCC) using nationwide quality registers are lacking. This study aimed to describe treatment patterns and survival outcomes in patients diagnosed with HCC using a national maintained database. Methods Characteristics and treatment patterns in patients diagnosed with HCC and registered in the national register of liver and bile duct tumours (SweLiv) between 2009 and 2016 were reviewed. Overall survival (OS) was estimated using Kaplan-Meier analysis and the log rank test to compare subgroups for clinical features, treatment modalities and outcomes according to the year of treatment. Results A total of 3376 patients with HCC were registered over 8 years, 246 (7 center dot 3 per cent) of whom underwent transplantation. Some 501 (14 center dot 8 per cent) and 390 patients (11 center dot 6 per cent) had resection and ablation as primary treatment. Transarterial chemoembolization and systemic sorafenib treatment were intended in 476 (14 center dot 1 per cent) and 426 patients (12 center dot 6 per cent) respectively; the remaining 1337 (39 center dot 6 per cent) were registered but referred for best supportive care (BSC). The 5-year survival rate was approximately 75 per cent in the transplantation group. Median OS was 4 center dot 6 (i.q.r. 2 center dot 0 to not reached) years after resection and 3 center dot 1 (2 center dot 3-6 center dot 7) years following ablation. In patients referred for palliative treatment, median survival was 1 center dot 4 (0 center dot 8-2 center dot 9), 0 center dot 5 (0 center dot 3-1 center dot 2) and 0 center dot 3 (0 center dot 1-1 center dot 0) years for the TACE, sorafenib and BSC groups respectively (P amp;lt; 0 center dot 001). Median survival was 0 center dot 9 years for the total HCC cohort in 2009-2012, before publication of the Swedish national treatment programme, increasing to 1 center dot 4 years in 2013-2016 (P amp;lt; 0 center dot 001). Conclusion The survival outcomes reported were in line with previous results from smaller cohorts. The introduction of national guidelines may have contributed to improved survival among patients with HCC in Sweden.

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  • 306.
    Hilborn, Erik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Gacic, Jelena
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Fornander, Tommy
    Karolinska Institute, Sweden.
    Nordenskjöld, Bo
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Stål, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Jansson, Agneta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Androgen receptor expression predicts beneficial tamoxifen response in oestrogen receptor-alpha-negative breast cancer2016In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 114, no 3, p. 248-255Article in journal (Refereed)
    Abstract [en]

    Background: Although the androgen receptor (AR) is frequently expressed in breast cancer, its relevance in the disease is not fully understood. In addition, the relevance of AR in determining tamoxifen treatment efficiency requires evaluation. Purpose: To investigate the tamoxifen predictive relevance of the AR protein expression in breast cancer. Methods Patients were randomised to tamoxifen 40 mg daily for 2 or 5 years or to no endocrine treatment. Mean follow-up was 15 years. Hazard ratios were calculated with recurrence-free survival as end point. Results: In patients with oestrogen receptor (ER)-negative tumours, expression of AR predicted decreased recurrence rate with tamoxifen (hazard ratio (HR) = 0.34; 95% confidence interval (CI) = 0.14-0.81; P = 0.015), whereas the opposite was seen in the AR- group (HR = 2.92; 95% CI = 1.16-7.31; P = 0.022). Interaction test was significant P &lt; 0.001. Patients with triple-negative and AR+ tumours benefitted from tamoxifen treatment (HR = 0.12; 95% CI = 0.014-0.95 P = 0.044), whereas patients with AR- tumours had worse outcome when treated with tamoxifen (HR = 3.98; 95% CI = 1.32-12.03; P = 0.014). Interaction test was significant P = 0.003. Patients with ER+ tumours showed benefit from tamoxifen treatment regardless of AR expression. Conclusions: AR can predict tamoxifen treatment benefit in patients with ER- tumours and triple-negative breast cancer.

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  • 307.
    Hilborn, Erik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Stål, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Alexeyenko, Andrey
    Karolinska Institute, Sweden; National Bioinformat Infrastruct Sweden, Sweden.
    Jansson, Agneta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    The regulation of hydroxysteroid 17 beta-dehydrogenase type 1 and 2 gene expression in breast cancer cell lines by estradiol, dihydrotestosterone, microRNAs, and genes related to breast cancer2017In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 8, no 37, p. 62183-62194Article in journal (Refereed)
    Abstract [en]

    Aim. To investigate the influence of estrogen, androgen, microRNAs, and genes implicated in breast cancer on the expression of HSD17B1 and HSD17B2. Materials. Breast cancer cell lines ZR-75-1, MCF7, T47D, SK-BR-3, and the immortalized epithelial cell line MCF10A were used. Cells were treated either with estradiol or dihydrotestosterone for 6, 24, 48 hours, or 7 days or treated with miRNAs or siRNAs predicted to influence HSD17B expression Results and discussion. Estradiol treatment decreased HSD17B1 expression and had a time-dependent effect on HSD17B2 expression. This effect was lost in estrogen receptor-alpha down-regulated or negative cell lines. Dihydrotestosterone treatment increased HSD17B2 expression, with limited effect on HSD17B1 expression. No effect was seen in cells without AR or in combination with the AR inhibitor hydroxyflutamide. The miRNA-17 up-regulated HSD17B1, while miRNA-210 and miRNA-7-5p had up- and down-regulatory effect and miRNA-1304-3p reduced HSD17B1 expression. The miRNA-204-5p, 498, 205-3p and 579-3p reduced HSD17B2 expression. Downregulation of CX3CL1, EPHB6, and TP63 increased HSD17B1 and HSD17B2 expression, while GREB1 downregulation suppressed HSD17B1 and promoted HSD17B2 expression. Conclusion. We show that HSD17B1 and HSD17B2 are controlled by estradiol, dihydrotestosterone, and miRNAs, as well as modulated by several breast cancer-related genes, which could have future clinical applications.

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  • 308.
    Hilborn, Erik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Stål, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Jansson, Agneta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Estrogen and androgen-converting enzymes 17 beta-hydroxysteroid dehydrogenase and their involvement in cancer: with a special focus on 17 beta-hydroxysteroid dehydrogenase type 1, 2, and breast cancer2017In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 8, no 18, p. 30552-30562Article, review/survey (Refereed)
    Abstract [en]

    Sex steroid hormones such as estrogens and androgens are involved in the development and differentiation of the breast tissue. The activity and concentration of sex steroids is determined by the availability from the circulation, and on local conversion. This conversion is primarily mediated by aromatase, steroid sulfatase, and 17 beta-hydroxysteroid dehydrogenases. In postmenopausal women, this is the primary source of estrogens in the breast. Up to 70-80% of all breast cancers express the estrogen receptor-a, responsible for promoting the growth of the tissue. Further, 60-80% express the androgen receptor, which has been shown to have tissue protective effects in estrogen receptor positive breast cancer, and a more ambiguous response in estrogen receptor negative breast cancers. In this review, we summarize the function and clinical relevance in cancer for 17 beta-hydroxysteroid dehydrogenases 1, which facilitates the reduction of estrone to estradiol, dehydroepiandrosterone to androstendiol and dihydrotestosterone to 3 alpha- and 3 beta-diol as well as 17 beta-hydroxysteroid dehydrogenases 2 which mediates the oxidation of estradiol to estrone, testosterone to androstenedione and androstendiol to dehydroepiandrosterone. The expression of 17 beta-hydroxysteroid dehydrogenases 1 and 2 alone and in combination has been shown to predict patient outcome, and inhibition of 17 beta-hydroxysteroid dehydrogenases 1 has been proposed to be a prime candidate for inhibition in patients who develop aromatase inhibitor resistance or in combination with aromatase inhibitors as a first line treatment. Here we review the status of inhibitors against 17 beta-hydroxysteroid dehydrogenases 1. In addition, we review the involvement of 17 beta-hydroxysteroid dehydrogenases 4, 5, 7, and 14 in breast cancer.

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  • 309.
    Hjalmarsson, Claes
    et al.
    Kalmar Hospital, Sweden; Halland Hospital, Sweden.
    Karlberg, Jonas
    Halland Hospital, Sweden.
    Tornqvist, Pelle
    Halland Hospital, Sweden.
    Arbman, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping.
    Frisk, Bjorn
    Skaraborg Hospital, Sweden.
    Modin, Marina
    Skaraborg Hospital, Sweden.
    Orally Administered Trimethoprim-Sulfamethoxazole and Metronidazole as Infection Prophylaxis in Elective Colorectal Surgery2015In: Surgical Infections, ISSN 1096-2964, E-ISSN 1557-8674, Vol. 16, no 5, p. 604-610Article in journal (Refereed)
    Abstract [en]

    Background: This randomized clinical trial evaluated orally administered trimethoprim-sulfamethoxazole and metronidazole (TSM) in elective colorectal surgery as prophylactic for post-operative surgical site infections (SSI). Methods: Patients undergoing elective colorectal resection were evaluated for inclusion. Randomized subjects received either orally administered TSM or intravenously administered cefuroxime and metronidazole (control group, CXM). The primary endpoint was the rate of SSI. Results: A total of 1073 subjects were randomized to either control (540) or TSM (533). 486 patients in the TSM group and 499 in the control group were followed-up with after 4 weeks. Thirty-seven (3.8%) patients were afflicted by SSI at discharge from hospital and 69 (7.0%) at follow-up four weeks after surgery. After four weeks, the rate of incisional SSI was 7.0% in the TSM group and 3.6% in the control group (p=0.022). For organ/space SSI and the other complications monitored in the study, no differences were observed between the groups. Conclusion: Orally administered TSM as prophylaxis before elective colorectal surgery results in a low rate of organ/space SSI but an increased rate of incisional SSI compared with intravenously administered cefuroxime and metronidazole. Thus, when considering orally administered TSM, because of environmental concerns or for economic reasons, the slightly increased infection rate has to be kept in mind.

  • 310.
    Hjerpe, Elisabet
    et al.
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Staf, Christian
    Sahlgrens Univ Hosp, Sweden.
    Dahm-Kahler, Pernilla
    Sahlgrens Univ Hosp, Sweden.
    Stalberg, Karin
    Uppsala Univ, Sweden.
    Bjurberg, Maria
    Skåne Univ Hosp, Sweden; Lund Univ, Sweden.
    Holmberg, Erik
    Sahlgrens Univ Hosp, Sweden; Sahlgrens Acad, Sweden.
    Borgfeldt, Christer
    Skåne Univ Hosp, Sweden; Lund Univ, Sweden.
    Tholander, Bengt
    Uppsala Univ Hosp, Sweden.
    Hellman, Kristina
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Kjölhede, Preben
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Högberg, Thomas
    Lund Univ, Sweden.
    Rosenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Åvall-Lundqvist, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Karolinska Inst, Sweden.
    Lymph node metastases as only qualifier for stage IV serous ovarian cancer confers longer survival than other sites of distant disease - a Swedish Gynecologic Cancer Group (SweGCG) study2018In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 57, no 3, p. 331-337Article in journal (Refereed)
    Abstract [en]

    Background: The International Federation of Gynecology and Obstetrics (FIGO) ovarian cancer staging system includes no sub-stage for lymph nodes (LN) as only distant disease manifestation. We explore the prognostic implication of LN as only stage IV classifier in serous ovarian cancer.Method: This is a nation-wide, population-based study on 551 women with serous stage IV cancers diagnosed between 2009-2014. We compare overall survival (OS) in women with LN as only distant metastatic site to those with pleural metastases only and to patients with other/multiple stage IV manifestations. Cox regression models were used for uni- and multivariable estimations.Results: Of 551stage IV cases, distant metastatic site was registered in 433. Median OS for women with LN (n=51) was 41.4 months, compared to 25.2 and 26.8 months for patients with pleural (n=195) or other/multiple (n=187) distant metastases (p=.0007). The corresponding five-year survival rates were 32, 11 and 22%, respectively. Multivariable analyzes confirmed shorter survival for women with pleural (HR 2.99, p=.001) or other/multiple distant sites (HR 2.67, p=.007), as compared to LN cases. LN only patients lived 9.1 months longer after primary than after interval surgery, but this difference was not significant (p=.245).Conclusion: Women with stage IV serous ovarian cancer having lymph nodes as only distant metastatic site live longer than other stage IV patients.

  • 311.
    Hjorth-Hansen, H.
    et al.
    St Olavs Hospital, Norway; Norwegian University of Science and Technology NTNU, Norway.
    Stentoft, J.
    Aarhus University Hospital, Denmark.
    Richter, J.
    Skåne University Hospital, Sweden.
    Koskenvesa, P.
    University of Helsinki, Finland; Helsinki University Hospital, Sweden.
    Hoeglund, M.
    University of Uppsala Hospital, Sweden.
    Dreimane, Arta
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Haematology.
    Porkka, K.
    University of Helsinki, Finland; Helsinki University Hospital, Sweden.
    Gedde-Dahl, T.
    Oslo University Hospital, Norway.
    Gjertsen, B. T.
    Haukeland Hospital, Norway; University of Bergen, Norway.
    Gruber, F. X.
    University Hospital North Norway, Norway.
    Stenke, L.
    Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    Eriksson, K. M.
    Sunderbysjukhuset, Sweden.
    Markevarn, B.
    Umeå University Hospital, Sweden.
    Lubking, A.
    University of Helsinki, Finland; Helsinki University Hospital, Sweden.
    Vestergaard, H.
    Odense University Hospital, Denmark.
    Udby, L.
    Roskilde Hospital, Denmark.
    Bjerrum, O. W.
    University of Copenhagen Hospital, Denmark.
    Persson, I.
    Uppsala University, Sweden.
    Mustjoki, S.
    University of Helsinki, Finland; Helsinki University Hospital, Sweden; University of Helsinki, Finland.
    Olsson-Stromberg, U.
    University of Uppsala Hospital, Sweden.
    Safety and efficacy of the combination of pegylated interferon-alpha 2b and dasatinib in newly diagnosed chronic-phase chronic myeloid leukemia patients2016In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 30, no 9, p. 1853-1860Article in journal (Refereed)
    Abstract [en]

    Dasatinib (DAS) and interferon-a have antileukemic and immunostimulatory effects and induce deep responses in chronic myeloid leukemia (CML). We assigned 40 newly diagnosed chronic-phase CML patients to receive DAS 100 mg o.d. followed by addition of pegylated interferon-alpha 2b (PegIFN) after 3 months (M3). The starting dose of PegIFN was 15 mu g/week and it increased to 25 mu g/week at M6 until M15. The combination was well tolerated with manageable toxicity. Of the patients, 84% remained on PegIFN at M12 and 91% (DAS) and 73% (PegIFN) of assigned dose was given. Only one patient had a pleural effusion during first year, and three more during the second year. After introduction of PegIFN we observed a steep increase in response rates. Major molecular response was achieved in 10%, 57%, 84% and 89% of patients at M3, M6, M12 and M18, respectively. At M12, MR4 was achieved by 46% and MR4.5 by 27% of patients. No patients progressed to advanced phase. In conclusion, the combination treatment appeared safe with very promising efficacy. A randomized comparison of DAS +/- PegIFN is warranted.

  • 312.
    Hjorth-Hansen, Henrik
    et al.
    St Olavs Hospital, Norway; Norwegian University of Science and Technology NTNU, Norway.
    Stenke, Leif
    Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    Söderlund, Stina
    University of Uppsala Hospital, Sweden.
    Dreimane, Arta
    Linköping University, Department of Medical and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Haematology. Linköping University, Faculty of Medicine and Health Sciences.
    Ehrencrona, Hans
    Skåne University Hospital, Sweden.
    Gedde-Dahl, Tobias
    University of Oslo, Norway.
    Tore Gjertsen, Bjorn
    Haukeland Hospital, Norway; University of Bergen, Norway.
    Hoglund, Martin
    University of Uppsala Hospital, Sweden.
    Koskenvesa, Perttu
    University of Helsinki, Finland; University of Helsinki, Finland.
    Lotfi, Kourosh
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology.
    Majeed, Waleed
    Stavanger University Hospital, Norway.
    Markevarn, Berit
    Umeå University Hospital, Sweden.
    Ohm, Lotta
    Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    Olsson-Stromberg, Ulla
    University of Uppsala Hospital, Sweden.
    Remes, Kari
    Turku University, Finland.
    Suominen, Merja
    Kanta Hame Central Hospital, Finland.
    Simonsson, Bengt
    University of Uppsala Hospital, Sweden.
    Porkka, Kimmo
    University of Helsinki, Finland; University of Helsinki, Finland.
    Mustjoki, Satu
    University of Helsinki, Finland; University of Helsinki, Finland.
    Richter, Johan
    Skåne University Hospital, Sweden.
    Dasatinib induces fast and deep responses in newly diagnosed chronic myeloid leukaemia patients in chronic phase: clinical results from a randomised phase-2 study (NordCML006)2015In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 94, no 3, p. 243-250Article in journal (Refereed)
    Abstract [en]

    We randomised 46 newly diagnosed patients with chronic myeloid leukaemia (median age 56) to receive dasatinib 100mg QD or imatinib 400mg QD and report outcome as an intention-to-treat analysis with 36months follow-up. Early cytogenetic and molecular responses were superior in the dasatinib group, with a tendency that imatinib patients caught up with time. For instance, MR3.0 was reached at 3months in 36% vs. 8% (P=0.02), at 12months in 81% vs. 46% (P=0.02) and at 18months in 73% vs. 65% (n.s.) of the patients in the two groups. In contrast, MR4.5 was consistently superior in the dasatinib group at all time points from 6months onwards, reaching 61% vs. 21% (Pless than0.05) at 36months. Sixty-four vs. 71% of the patients in the dasatinib and imatinib arms, respectively, remained on assigned drug. Dasatinib dose was frequently reduced, but with maintained excellent effect. One imatinib patient progressed to blastic phase, but no CML-related deaths occurred. In conclusion, our data compare favourably with those of the dasatinib registration study, DASISION. The fast and deep molecular responses induced by dasatinib compared with imatinib may be exploited to increase the proportion of patients who can achieve a treatment-free remission after treatment discontinuation.

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  • 313.
    Holm, Åsa
    et al.
    Linköping University, Department of Mathematics, Optimization . Linköping University, Faculty of Science & Engineering.
    Carlsson Tedgren, Åsa
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Larsson, Torbjörn
    Linköping University, Department of Mathematics, Optimization . Linköping University, The Institute of Technology.
    Heuristics for Integrated Optimization of Catheter Positioning and Dwell Time Distribution in Prostate HDR Brachytherapy2016In: Annals of Operations Research, ISSN 0254-5330, E-ISSN 1572-9338, Vol. 236, no 2, p. 319-339Article in journal (Refereed)
    Abstract [en]

    High dose-rate (HDR) brachytherapy is a kind of radiotherapy used to treat, among others, prostate cancer. When applied to prostate cancer a radioactive source is moved through catheters implanted into the prostate. For each patient a treatment plan is constructed that decide for example catheter placement and dwell time distribution, that is where to stop the radioactive source and for how long.

    Mathematical optimization methods has been used to find quality plans with respect to dwell time distribution, however few optimization approaches regarding catheter placement have been studied. In this article we present an integrated optimization model that optimize catheter placement and dwell time distribution simultaneously. Our results show that integrating the two decisions yields greatly improved plans, from 15% to 94% improvement.

    Since the presented model is computationally demanding to solve we also present three heuristics: tabu search, variable neighbourhood search and genetic algorithm. Of these variable neighbourhood search is clearly the best, outperforming a state-of-the-art optimization software (CPLEX) and the two other heuristics.

  • 314.
    Holmbom, Martin
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Giske, Christian G.
    Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden.; Clinical Microbiology, Karolinska University Hospital, Stockholm, Sweden..
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Östholm Balkhed, Åse
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Claesson, Carina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Nilsson, Lennart E
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Hoffmann, Mikael
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    14-Year Survey in a Swedish County Reveals a Pronounced Increase in Bloodstream Infections (BSI). Comorbidity: An Independent Risk Factor for Both BSI and Mortality2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 11Article in journal (Refereed)
    Abstract [en]

    Objectives: we assessed the incidence, risk factors and outcome of BSI over a 14-year period (2000-2013) in a Swedish county.

    Methods: retrospective cohort study on culture confirmed BSI among patients in the county of Östergötland, Sweden, with approximately 440,000 inhabitants. A BSI was defined as either community-onset BSI (CO-BSI) or hospital-acquired BSI (HA-BSI).

    Results: of a total of 11,480 BSIs, 67% were CO-BSI and 33% HA-BSI. The incidence of BSI increased by 64% from 945 to 1,546 per 100,000 hospital admissions per year during the study period. The most prominent increase, 83% was observed within the CO-BSI cohort whilst HA-BSI increased by 32%. Prescriptions of antibiotics in outpatient care decreased with 24% from 422 to 322 prescriptions dispensed/1,000 inhabitants/year, whereas antibiotics prescribed in hospital increased by 67% (from 424 to 709 DDD per 1,000 days of care). The overall 30-day mortality for HA-BSIs was 17.2%, compared to 10.6% for CO-BSIs, with an average yearly increase per 100,000 hospital admissions of 2 and 5% respectively. The proportion of patients with one or more comorbidities, increased from 20.8 to 55.3%. In multivariate analyses, risk factors for mortality within 30 days were: HA-BSI (2.22); two or more comorbidities (1.89); single comorbidity (1.56); CO-BSI (1.21); male (1.05); and high age (1.04).

    Conclusion: this survey revealed an alarming increase in the incidence of BSI over the 14-year study period. Interventions to decrease BSI in general should be considered together with robust antibiotic stewardship programmes to avoid both over- and underuse of antibiotics.

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  • 315.
    Homeyer, Andre
    et al.
    Fraunhofer MEVIS, Germany.
    Nasr, Patrik
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Engel, Christiane
    Fraunhofer MEVIS, Germany.
    Kechagias, Stergios
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Lundberg, Peter
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Ekstedt, Mattias
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Kost, Henning
    Fraunhofer MEVIS, Germany.
    Weiss, Nick
    Fraunhofer MEVIS, Germany.
    Palmer, Tim
    University of Leeds, England.
    Karl Hahn, Horst
    Fraunhofer MEVIS, Germany.
    Treanor, Darren
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. University of Leeds, England; Leeds Teaching Hospital NHS Trust, England.
    Lundström, Claes
    Linköping University, Department of Science and Technology, Media and Information Technology. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Automated quantification of steatosis: agreement with stereological point counting2017In: Diagnostic Pathology, ISSN 1746-1596, E-ISSN 1746-1596, Vol. 12, article id 80Article in journal (Refereed)
    Abstract [en]

    Background: Steatosis is routinely assessed histologically in clinical practice and research. Automated image analysis can reduce the effort of quantifying steatosis. Since reproducibility is essential for practical use, we have evaluated different analysis methods in terms of their agreement with stereological point counting (SPC) performed by a hepatologist. Methods: The evaluation was based on a large and representative data set of 970 histological images from human patients with different liver diseases. Three of the evaluated methods were built on previously published approaches. One method incorporated a new approach to improve the robustness to image variability. Results: The new method showed the strongest agreement with the expert. At 20x resolution, it reproduced steatosis area fractions with a mean absolute error of 0.011 for absent or mild steatosis and 0.036 for moderate or severe steatosis. At 10x resolution, it was more accurate than and twice as fast as all other methods at 20x resolution. When compared with SPC performed by two additional human observers, its error was substantially lower than one and only slightly above the other observer. Conclusions: The results suggest that the new method can be a suitable automated replacement for SPC. Before further improvements can be verified, it is necessary to thoroughly assess the variability of SPC between human observers.

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  • 316.
    Hoshino, Ayuko
    et al.
    Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA.
    Costa-Silva, Bruno
    Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA.
    Shen, Tang-Long
    Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA; National Taiwan University, Taiwan; National Taiwan University, Taiwan.
    Rodrigues, Goncalo
    Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA; University of Porto, Portugal.
    Hashimoto, Ayako
    Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA; University of Tokyo, Japan.
    Tesic Mark, Milica
    Rockefeller University, NY 10065 USA.
    Molina, Henrik
    Rockefeller University, NY 10065 USA.
    Kohsaka, Shinji
    Mem Sloan Kettering Cancer Centre, NY 10065 USA.
    Di Giannatale, Angela
    Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA.
    Ceder, Sophia
    Karolinska Institute, Sweden.
    Singh, Swarnima
    Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA.
    Williams, Caitlin
    Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA.
    Soplop, Nadine
    Rockefeller University, NY 10065 USA.
    Uryu, Kunihiro
    Rockefeller University, NY 10065 USA.
    Pharmer, Lindsay
    Mem Sloan Kettering Cancer Centre, NY 10065 USA.
    King, Tari
    Mem Sloan Kettering Cancer Centre, NY 10065 USA.
    Bojmar, Linda
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA.
    Davies, Alexander E.
    University of Calif Berkeley, CA 94720 USA.
    Ararso, Yonathan
    Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA.
    Zhang, Tuo
    Weill Cornell Med, NY 10021 USA.
    Zhang, Haiying
    Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA.
    Hernandez, Jonathan
    Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA; Mem Sloan Kettering Cancer Centre, NY 10065 USA.
    Weiss, Joshua M.
    Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA.
    Dumont-Cole, Vanessa D.
    Mem Sloan Kettering Cancer Centre, NY 10065 USA.
    Kramer, Kimberly
    Mem Sloan Kettering Cancer Centre, NY 10065 USA.
    Wexler, Leonard H.
    Mem Sloan Kettering Cancer Centre, NY 10065 USA.
    Narendran, Aru
    Alberta Childrens Prov Gen Hospital, Canada.
    Schwartz, Gary K.
    Columbia University, NY 10032 USA.
    Healey, John H.
    Mem Sloan Kettering Cancer Centre, NY 10065 USA.
    Sandström, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Jorgen Labori, Knut
    Oslo University Hospital, Norway.
    Kure, Elin H.
    Oslo University Hospital, Norway.
    Grandgenett, Paul M.
    University of Nebraska Medical Centre, NE 68198 USA.
    Hollingsworth, Michael A.
    University of Nebraska Medical Centre, NE 68198 USA.
    de Sousa, Maria
    Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA; University of Porto, Portugal.
    Kaur, Sukhwinder
    University of Nebraska Medical Centre, NE 68198 USA.
    Jain, Maneesh
    University of Nebraska Medical Centre, NE 68198 USA.
    Mallya, Kavita
    University of Nebraska Medical Centre, NE 68198 USA.
    Batra, Surinder K.
    University of Nebraska Medical Centre, NE 68198 USA.
    Jarnagin, William R.
    Mem Sloan Kettering Cancer Centre, NY 10065 USA.
    Brady, Mary S.
    Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA; Mem Sloan Kettering Cancer Centre, NY 10065 USA.
    Fodstad, Oystein
    Oslo University Hospital, Norway; University of Oslo, Norway.
    Muller, Volkmar
    University of Medical Centre, Germany.
    Pantel, Klaus
    University of Medical Centre Hamburg Eppendorf, Germany.
    Minn, Andy J.
    University of Penn, PA 19104 USA.
    Bissell, Mina J.
    University of Calif Berkeley, CA 94720 USA.
    Garcia, Benjamin A.
    University of Penn, PA 19104 USA.
    Kang, Yibin
    Princeton University, NJ 08544 USA; Rutgers Cancer Institute New Jersey, NJ 08903 USA.
    Rajasekhar, Vinagolu K.
    Mem Sloan Kettering Cancer Centre, NY 10065 USA.
    Ghajar, Cyrus M.
    Fred Hutchinson Cancer Research Centre, WA 98109 USA.
    Matei, Irina
    Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA.
    Peinado, Hector
    Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA; Spanish National Cancer Research Centre CNIO, Spain.
    Bromberg, Jacqueline
    Mem Sloan Kettering Cancer Centre, NY 10065 USA; Weill Cornell Med, NY 10021 USA.
    Lyden, David
    Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA; Mem Sloan Kettering Cancer Centre, NY 10065 USA.
    Tumour exosome integrins determine organotropic metastasis2015In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 527, no 7578, p. 329-+Article in journal (Refereed)
    Abstract [en]

    Ever since Stephen Pagets 1889 hypothesis, metastatic organotropism has remained one of cancers greatest mysteries. Here we demonstrate that exosomes from mouse and human lung-, liver-and brain-tropic tumour cells fuse preferentially with resident cells at their predicted destination, namely lung fibroblasts and epithelial cells, liver Kupffer cells and brain endothelial cells. We show that tumour-derived exosomes uptaken by organ-specific cells prepare the pre-metastatic niche. Treatment with exosomes from lung-tropic models redirected the metastasis of bone-tropic tumour cells. Exosome proteomics revealed distinct integrin expression patterns, in which the exosomal integrins alpha(6)beta(4) and alpha(6)beta(1) were associated with lung metastasis, while exosomal integrin alpha(v)beta(5) was linked to liver metastasis. Targeting the integrins alpha(6)beta(4) and alpha(v)beta(5) decreased exosome uptake, as well as lung and liver metastasis, respectively. We demonstrate that exosome integrin uptake by resident cells activates Src phosphorylation and pro-inflammatory S100 gene expression. Finally, our clinical data indicate that exosomal integrins could be used to predict organ-specific metastasis.

  • 317.
    Hu, Wenjun
    et al.
    Sichuan Univ, Peoples R China.
    Lei, Linping
    Sichuan Univ, Peoples R China.
    Xie, Xuqin
    Sichuan Univ, Peoples R China.
    Huang, Libin
    Sichuan Univ, Peoples R China.
    Cui, Qian
    Univ Elect Sci and Technol China, Peoples R China.
    Dang, Tang
    Huazhong Univ Sci and Technol, Peoples R China.
    Liu, Gang Logan
    Huazhong Univ Sci and Technol, Peoples R China.
    Li, Yuan
    Sichuan Univ, Peoples R China.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Zhou, Zongguang
    Sichuan Univ, Peoples R China.
    Heterogeneous nuclear ribonucleoprotein L facilitates recruitment of 53BP1 and BRCA1 at the DNA break sites induced by oxaliplatin in colorectal cancer2019In: Cell Death and Disease, ISSN 2041-4889, E-ISSN 2041-4889, Vol. 10, article id 550Article in journal (Refereed)
    Abstract [en]

    Although oxaliplatin is an effective chemotherapeutic drug for treatment of colorectal cancer (CRC), tumor cells can develop mechanisms to evade oxaliplatin-induced cell death and show high tolerance and acquired resistance to this drug. Heterogeneous nuclear ribonucleoprotein L (hnRNP L) has been proved to play a critical role in DNA repair during IgH class switch recombination (CSR) in B lymphocytes, while, its role in CRC and chemotherapeutic resistance remain unknown. Our study aims to uncover an unidentified mechanism of regulating DNA double-strand breaks (DSBs) by hnRNP L in CRC cells treated by oxaliplatin. In present study, we observed that knockdown of hnRNP L enhanced the level of DNA breakage and sensitivity of CRC cells to oxaliplatin. The expression of key DNA repair factors (BRCA1, 53BP1, and ATM) was unaffected by hnRNP L knockdown, thereby excluding the likelihood of hnRNP L mediation via mRNA regulation. Moreover, we observed that phosphorylation level of ATM changed oppositely to 53BP1 and BRCA1 in the CRC cells (SW620 and HCT116) which exhibit synergistic effect by oxaliplatin plus hnRNP L impairment. And similar phenomenon was observed in the foci formation of these critical repair factors. We also found that hnRNP L binds directly with these DNA repair factors through its RNA-recognition motifs (RRMs). Analysis of cell death indicated that the RRMs of hnRNP L are required for cell survival under incubation with oxaliplatin. In conclusion, hnRNP L is critical for the recruitment of the DNA repair factors in oxaliplatin-induced DSBs. Targeting hnRNP L is a promising new clinical approach that could enhance the effectiveness of current chemotherapeutic treatment in patients with resistance to oxaliplatin.

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  • 318.
    Huang, Ya-Yao
    et al.
    PET Center, Department of Nuclear Medicine, National Taiwan University Hospital, Taipei, Taiwan.
    Taylor, Stephen
    Department of Nuclear Medicine, Royal Brisbane and Women’s Hospital, Herston, Australia.
    Koziorowski, Jacek
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Chang, Yu-Ning
    Molecular Imaging Center, National Taiwan University, Taipei, Taiwan.
    Kao, Wei-Hua
    PET Center, Department of Nuclear Medicine, National Taiwan University Hospital, Taipei, Taiwan.
    Tzen, Kai-Yuan
    PET Center, Department of Nuclear Medicine, National Taiwan University Hospital, Taipei, Taiwan; Molecular Imaging Center, National Taiwan University, Taipei, Taiwan.
    Shiue, Chyng-Yann
    PET Center, Department of Nuclear Medicine, National Taiwan University Hospital, Taipei, Taiwan; Molecular Imaging Center, National Taiwan University, Taipei, Taiwan; PET Center, Department of Nuclear Medicine, Tri-Service General Hospital, Taipei, Taiwan.
    A two‐center study for the quality control of [18F]FDG using FASTlab phosphate cassettes2016In: Annals of Nuclear Medicine, ISSN 0914-7187, E-ISSN 1864-6433, Vol. 30, no 8, p. 563-571Article in journal (Refereed)
    Abstract [en]

    Objective: The GE FASTlab radiosynthesis module is routinely used for the production of [18F]FDG, utilizing the commercially available phosphate cassettes. Because of the observation of a white precipitate in the product vial before the product expiry time, we re-examined the quality of the produced [18F]FDG solution.

    Methods: Phosphate buffered [18F]FDG solution was synthesized on the FASTlab and analyzed at both National Taiwan University Hospital (NTUH) of Taiwan and Royal Brisbane and Women’s Hospital (RBWH) of Australia. In addition to the standard product quality control (QC), the concentration of aluminum (Al3+) as probable cause of the precipitations in the [18F]FDG solution was analyzed by inductively coupled plasma mass spectrometry (ICP-MS at RBWH) and inductively coupled plasma optical emission spectrometry (ICP-OES at NTUH), and using three semi-quantitative methods at NTUH, Advantec® Alumi Check Test Strip, Quantofix® Aluminum Test Strip and MColortest™ Aluminum Test kit.

    Results: The precipitates were observed in the [18F]FDG solution within 24 (NTUH) and 6 (RBWH) hours after the end of synthesis in 38–100 % of the batches, dependent on the batch of the FASTlab cassettes. Addition of metal-free HCl(aq) to aliquots of [18F]FDG containing precipitate, followed by ICP-MS analysis revealed Al3+ concentrations of 70–80 ppm. Al3+ concentrations of 10–12 ppm were detected in [18F]FDG batches that did not show any precipitation. In contrast, less than 5 ppm of the residual Al3+ was detected by semi-quantitative methods in all batches.

    Conclusion: The US (USP), British (BP), European (EP) and Japanese (JP) pharmacopeias demand that [18F]FDG for injection should be clear and particulate free within the given shelf-life/expiration time. To avoid Al-phosphate precipitation within the product expiry time, FASTlab citrate cassettes, rather than phosphate cassettes, should be used for [18F]FDG production. Although testing for Al3+ is not listed in the [18F]FDG monographs of the USP, BP and EP, residual Al3+ levels should be considered in the interests of patient safety.

  • 319.
    Hulegardh, Erik
    et al.
    Sahlgrens University Hospital, Sweden; Sahlgrens University Hospital, Sweden.
    Nilsson, Christer
    Karolinska University Hospital, Sweden.
    Lazarevic, Vladimir
    Swedish Acute Myeloid Leukemia Grp; Skåne University Hospital, Sweden; Skåne University Hospital, Sweden; Lund University, Sweden.
    Garelius, Hege
    Swedish Acute Myeloid Leukemia Grp; Sahlgrens University Hospital, Sweden; Sahlgrens University Hospital, Sweden.
    Antunovic, Petar
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Haematology. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Swedish Acute Myeloid Leukemia Grp.
    Rangert Derolf, Asa
    Swedish Acute Myeloid Leukemia Grp; Karolinska University Hospital, Sweden; Karolinska University Hospital, Sweden.
    Mollgard, Lars
    Swedish Acute Myeloid Leukemia Grp; Sahlgrens University Hospital, Sweden; Sahlgrens University Hospital, Sweden.
    Uggla, Bertil
    Swedish Acute Myeloid Leukemia Grp; Örebro University Hospital, Sweden.
    Wennstrom, Lovisa
    Swedish Acute Myeloid Leukemia Grp; Sahlgrens University Hospital, Sweden; Sahlgrens University Hospital, Sweden.
    Wahlin, Anders
    Swedish Acute Myeloid Leukemia Grp; Umeå University, Sweden; Norrland University Hospital, Sweden.
    Hoglund, Martin
    Swedish Acute Myeloid Leukemia Grp; Academic Hospital, Sweden; Academic Hospital, Sweden.
    Juliusson, Gunnar
    Skåne University Hospital, Sweden; Skåne University Hospital, Sweden; Lund University, Sweden;Swedish Acute Myeloid Leukemia Grp.
    Stockelberg, Dick
    Swedish Acute Myeloid Leukemia Grp; Sahlgrens University Hospital, Sweden; Sahlgrens University Hospital, Sweden.
    Lehmann, Soren
    Swedish Acute Myeloid Leukemia Grp; Karolinska University Hospital, Sweden.
    Characterization and prognostic features of secondary acute myeloid leukemia in a population-based setting: A report from the Swedish Acute Leukemia Registry2015In: American Journal of Hematology, ISSN 0361-8609, E-ISSN 1096-8652, Vol. 90, no 3, p. 208-214Article in journal (Refereed)
    Abstract [en]

    Patients with secondary acute myeloid leukemia (AML) often escape inclusion in clinical trials and thus, population-based studies are crucial for its accurate characterization. In this first large population-based study on secondary AML, we studied AML with an antecedent hematological disease (AHD-AML) or therapy-related AML (t-AML) in the population-based Swedish Acute Leukemia Registry. The study included 3,363 adult patients of which 2,474 (73.6%) had de novo AML, 630 (18.7%) AHD-AML, and 259 (7.7%) t-AML. Secondary AML differed significantly compared to de novo AML with respect to age, gender, and cytogenetic risk. Complete remission (CR) rates were significantly lower but early death rates similar in secondary AML. In a multivariable analysis, AHD-AML (HR 1.51; 95% CI 1.26-1.79) and t-AML (1.72; 1.38-2.15) were independent risk factors for poor survival. The negative impact of AHD-AML and t-AML on survival was highly age dependent with a considerable impact in younger patients, but without independent prognostic value in the elderly. Although patients with secondary leukemia did poorly with intensive treatment, early death rates and survival were significantly worse with palliative treatment. We conclude that secondary AML in a population-based setting has a striking impact on survival in younger AML patients, whereas it lacks prognostic value among the elderly patients.

  • 320.
    Hult, Mari
    et al.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Bonn, Stephanie E.
    Karolinska Inst, Sweden.
    Brandt, Lena
    Karolinska Inst, Sweden.
    Wirén, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping.
    Lagerros, Ylva Trolle
    Karolinska Inst, Sweden; Stockholm Hlth Serv, Sweden.
    Womens Satisfaction with and Reasons to Seek Bariatric Surgerya Prospective Study in Sweden with 1-Year Follow-up2019In: Obesity Surgery, ISSN 0960-8923, E-ISSN 1708-0428, Vol. 29, no 7, p. 2059-2070Article in journal (Refereed)
    Abstract [en]

    Background/Objectives Despite profound weight loss after bariatric surgery, some patients are dissatisfied with the results. Pre-surgery expectations, as well as post-surgery items of satisfaction, need to be clarified. The main objective in this study was to investigate the primary reasons to seek bariatric surgery and assess items of satisfaction 1-year post-surgery. Subjects/Methods This is a prospective cohort study of women (n = 50) undergoing bariatric surgery in Stockholm, Sweden. Presurgery assessment included reasons to seek surgery, expected weight loss, co-morbidities, and quality of life. Post-surgery assessment included items of satisfaction, weight loss, co-morbidities, and quality of life. In total, two women did not undergo surgery, and 40 women had complete data from all pre- and post-surgery assessments. Results Mean change in body mass index (BMI) pre- and post-surgery was -12.9 (3.7) kg/m(2). At 1-year post-surgery, the mean percent of excess weight loss (% EWL) was 86.9 (26.3). Pre-surgery, the most reported reason to seek surgery was "weight loss" (47.9%), while the most reported item of satisfaction post-surgery was "improved self-esteem" (55.6%). Satisfaction with the result 1-year post-surgery was associated with the extent of % EWL. Satisfied patients (n = 32) had a mean % EWL of 94.6 (22.9), while those not satisfied (n = 8) had a mean % EWL of 59.9 (17.6). Conclusions The primary reason to seek bariatric surgery was weight loss. However, despite profound weight loss, improved self-esteem was the item of most satisfaction post-surgery. Our findings may be useful in the clinical setting when informing patients pre- surgery about what to expect as well as when meeting a patient post-surgery to discuss results.

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  • 321.
    Hultcrantz, M.
    et al.
    Karolinska Inst, Sweden; Mem Sloan Kettering Canc Ctr, NY 10021 USA.
    Landtblom, A. Ravn
    Stockholm South Hosp, Sweden; Karolinska Inst, Sweden.
    Andreasson, B.
    NU Hosp Grp, Sweden.
    Samuelsson, J.
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Haematology.
    Dickman, P. W.
    Karolinska Inst, Sweden.
    Kristinsson, S. Y.
    Univ Iceland, Iceland; Landspitali Natl Univ Hosp, Iceland.
    Bjorkholm, M.
    Karolinska Inst, Sweden.
    Andersson, T. M-L
    Karolinska Inst, Sweden.
    Incidence of myeloproliferative neoplasms - trends by subgroup and age in a population-based study in Sweden2020In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 287, no 4, p. 448-454Article in journal (Refereed)
    Abstract [en]

    Background The reported incidence of Philadelphia-negative myeloproliferative neoplasms (MPNs) differs substantially between previous reports, likely due to true regional differences in incidence and/or variations in the quality and coverage of the cancer registers. Objective We therefore assessed MPN incidence in Sweden during recent years using prospectively collected information captured in Swedish health registers. Methods Patients with MPNs were identified through the Swedish Cancer Register and Swedish Blood Cancer Register between 2000 and 2014. Information on the Swedish population was obtained from the Human Mortality Database. Crude and age-standardized incidence rates of MPNs with 95% confidence intervals (CIs) were calculated. Results A total of 6281 MPN cases were reported to the Swedish Cancer Register and Swedish Blood Cancer Register during 2000-2014. The age-standardized, to the Swedish population in 2000, incidence for all MPNs was 4.45 (95% confidence interval [CI] 4.34-4.56)/100 000 person-years. The age-standardized incidence for polycythemia vera was 1.48 (1.42-1.54), for essential thrombocythemia 1.60 (1.53-1.66) and for primary myelofibrosis 0.52 (0.48-0.56)/100 000 person-years, respectively. The incidence rate of MPNs was substantially higher in the older compared to the younger age groups. The incidence increased during the study period, likely to do better reporting and increasing age of the general population. Conclusion The reported MPN incidences in our study, which were in the higher interval of previously published studies, are likely more accurate compared to previous reports due to the population-based setting and high level of coverage in the Swedish Cancer and Blood Cancer Registers.

  • 322.
    Hägg, Mary
    et al.
    Hudiksvall Hospital, Sweden; Uppsala University, Sweden.
    Tibbling, Lita
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Franzen, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping.
    Effect of IQoro(R) training in hiatal hernia patients with misdirected swallowing and esophageal retention symptoms2015In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 135, no 7, p. 635-639Article, review/survey (Refereed)
    Abstract [en]

    Conclusion: Misdirected swallowing can be triggered by esophageal retention and hiatal incompetence. The results show that oral IQoro(R) screen (IQS) training improves misdirected swallowing, hoarseness, cough, esophageal retention, and globus symptoms in patients with hiatal hernia. Objectives: The present study investigated whether muscle training with an IQS influences symptoms of misdirected swallowing and esophageal retention in patients with hiatal hernia. Methods: A total of 28 adult patients with hiatal hernia suffering from misdirected swallowing and esophageal retention symptoms for more than 1 year before entry to the study were evaluated before and after training with an IQS. The patients had to fill out a questionnaire regarding symptoms of misdirected swallowing, hoarseness, cough, esophageal retention, and suprasternal globus, which were scored from 0-3, and a VAS on the ability to swallow food. The effect of IQS traction on diaphragmatic hiatus (DH) pressure was recorded in 12 patients with hiatal hernia using high resolution manometry (HRM). Results: Upon entry into the study, misdirected swallowing, globus sensation, and esophageal retention symptoms were present in all 28 patients, hoarseness in 79%, and cough in 86%. Significant improvement was found for all symptoms after oral IQS training (p less than 0.001). Traction with an IQS resulted in a 65 mmHg increase in the mean HRM pressure of the DH.

  • 323.
    Häggström, Christel
    et al.
    Uppsala University, Sweden; Umeå University, Sweden.
    Liedberg, Fredrik
    Skåne University Hospital, Sweden; Lund University, Sweden.
    Hagberg, Oskar
    Regional Cancer Centre South, Sweden.
    Aljabery, Firas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Strock, Viveka
    Sahlgrens University Hospital, Sweden.
    Hosseini, Abolfazl
    Karolinska University Hospital, Sweden.
    Gardmark, Truls
    Karolinska Institute, Sweden.
    Sherif, Amir
    Umeå University, Sweden.
    Malmstrom, Per-Uno
    Uppsala University, Sweden.
    Garmo, Hans
    Kings Coll London, England; Regional Cancer Centre Uppsala Örebro, Sweden.
    Jahnson, Staffan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Holmberg, Lars
    Uppsala University, Sweden; Kings Coll London, England.
    Cohort profile: The Swedish National Register of Urinary Bladder Cancer (SNRUBC) and the Bladder Cancer Data Base Sweden (BladderBaSe)2017In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 7, no 9, article id e016606Article in journal (Refereed)
    Abstract [en]

    Purpose To monitor the quality of bladder cancer care, the Swedish National Register of Urinary Bladder Cancer (SNRUBC) was initiated in 1997. During 2015, in order to study trends in incidence, effects of treatment and survival of men and women with bladder cancer, we linked the SNRUBC to other national healthcare and demographic registers and constructed the Bladder Cancer Data Base Sweden (BladderBaSe). Participants The SNRUBC is a nationwide register with detailed information on 97% of bladder cancer cases in Sweden as compared with the Swedish Cancer Register. Participants in the SNRUBC have registered data on tumour characteristics at diagnosis, and for 98% of these treatment data have been captured. From 2009, the SNRUBC holds data on 88% of eligible participants for follow-up 5 years after diagnosis of non-muscle invasive bladder cancer, and from 2011, data on surgery details and complications for 85% of participants treated with radical cystectomy. The BladderBaSe includes all data in the SNRUBC from 1997 to 2014, and additional covariates and follow-up data from linked national register sources on comorbidity, socioeconomic factors, detailed information on readmissions and treatment side effects, and causes of death. Findings to date Studies based on data in the SNRUBC have shown inequalities in survival and treatment indication by gender, regions and hospital volume. The BladderBaSe includes 38 658 participants registered in SNRUBC with bladder cancer diagnosed from 1 January 1997 to 31 December 2014. The BladderBaSe initiators are currently in collaboration with researchers from the SNRUBC investigating different aspects of bladder cancer survival. Future plans The SNRUBC and the BladderBaSe project are open for collaborations with national and international research teams. Collaborators can submit proposals for studies and study files can be uploaded to servers for remote access and analysis. For more information, please contact the corresponding author.

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  • 324.
    Håkansson, Irene
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Sandstedt, Anna
    Linköping University, Department of Social and Welfare Studies. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Haematology.
    Lundin, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Askmark, Håkan
    University of Uppsala Hospital, Sweden.
    Pirskanen, Ritva
    Karolinska Institute, Sweden.
    Carlson, Kristina
    University Hospital, Sweden.
    Piehl, Fredrik
    Karolinska Institute, Sweden.
    Hägglund, Hans
    University Hospital, Sweden.
    Successful autologous haematopoietic stem cell transplantation for refractory myasthenia gravis - a case report2017In: Neuromuscular Disorders, ISSN 0960-8966, E-ISSN 1873-2364, Vol. 27, no 1, p. 90-93Article in journal (Refereed)
    Abstract [en]

    Myasthenia gravis (MG) is an autoimmune disease, with immune reactivity against the post-synaptic endplate of the neuromuscular junction. Apart from symptomatic treatment with choline esterase blockers, many patients also require immunomodulatory treatment. Despite existing treatment options, some patients are treatment refractory. We describe a patient with severe MG refractory to corticosteroids, four oral immunosuppressants, cyclophosphamide, rituximab and bortezomib who was treated with autologous haematopoietic stem cell transplantation. Two years after this, the patient has significantly improved in objective tests and in quality of life and leads an active life. Diplopia is her only remaining symptom and she is completely free of medication for MG. We believe that autologous haematopoietic stem cell transplantation can be an effective therapeutic option for carefully selected cases of severe, treatment refractory MG. (c) 2016 Elsevier B.V. All rights reserved.

  • 325.
    Håkansson, Irene
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Tisell, Anders
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Cassel, Petra
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Blennow, K.
    University of Gothenburg, Sweden; Sahlgrens University Hospital, Sweden.
    Zetterberg, H.
    University of Gothenburg, Sweden; Sahlgrens University Hospital, Sweden; UCL Institute Neurol, England.
    Lundberg, Peter
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Dahle, Charlotte
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Vrethem, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Neurofilament light chain in cerebrospinal fluid and prediction of disease activity in clinically isolated syndrome and relapsing-remitting multiple sclerosis2017In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 24, no 5, p. 703-712Article in journal (Refereed)
    Abstract [en]

    Background and purpose: Improved biomarkers are needed to facilitate clinical decision-making and as surrogate endpoints in clinical trials in multiple sclerosis (MS). We assessed whether neurodegenerative and neuroinflammatory markers in cerebrospinal fluid (CSF) at initial sampling could predict disease activity during 2 years of follow-up in patients with clinically isolated syndrome (CIS) and relapsing-remitting MS. Methods: Using multiplex bead array and enzyme-linked immunosorbent assay, CXCL1, CXCL8, CXCL10, CXCL13, CCL20, CCL22, neurofilament light chain (NFL), neurofilament heavy chain, glial fibrillary acidic protein, chitinase-3-like-1, matrix metalloproteinase-9 and osteopontin were analysed in CSF from 41 patients with CIS or relapsing-remitting MS and 22 healthy controls. Disease activity (relapses, magnetic resonance imaging activity or disability worsening) in patients was recorded during 2 years of follow-up in this prospective longitudinal cohort study. Results: In a logistic regression analysis model, NFL in CSF at baseline emerged as the best predictive marker, correctly classifying 93% of patients who showed evidence of disease activity during 2 years of follow-up and 67% of patients who did not, with an overall proportion of 85% (33 of 39 patients) correctly classified. Combining NFL with either neurofilament heavy chain or osteopontin resulted in 87% overall correctly classified patients, whereas combining NFL with a chemokine did not improve results. Conclusions: This study demonstrates the potential prognostic value of NFL in baseline CSF in CIS and relapsing-remitting MS and supports its use as a predictive biomarker of disease activity.

  • 326.
    Högberg, Thomas
    et al.
    Avdelningen för cancerepidemiologi, Skånes universitetssjukhus, Lund.
    Bergfeldt, Kjell
    Regionalt cancercentrum Stockholm–Gotland, Stockholm.
    Borgfeldt, Christer
    Kvinnokliniken, Skånes universitetssjukhus, Lund.
    Holmberg, Erik
    Regionalt cancercentrum Väst, Göteborg.
    Åvall Lundqvist, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Hopp om förbättring av överlevnad i ovarialcancer2015In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 112, no 50, p. 2281-3Article in journal (Refereed)
    Abstract [en]

    Ovarian cancer is the most common cause of death from a gynecologic cancer. Every year around 700 women contracts ovarian cancer in Sweden. The overall survival is among the highest in Europe, but still long term relative survival is only 46%. It is a long-held myth that ovarian cancer is a disease without symptoms. Almost 90% of women have symptoms, even in the early stages. Symptoms that should arise suspicion of ovarian cancer and initiate diagnostic work-up are continuous abdominal extension, early feeling of satiety, pelvic or abdominal pain, urinary urge and postmenopausal bleeding. Women's awareness of symptoms and willingness to seek medical advice and the organization of the health care system are important factors determining cancer survival. Ovarian cancer is a heterogeneous group of diseases with different tumor traits and prognosis. Personalized medicine and preventive measures recognizing recent knowledge about tumor biology will positively affect survival.

  • 327.
    Högström, G.
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Lund Univ, Sweden.
    Ohlsson, H.
    Lund Univ, Sweden.
    Crump, C.
    Lund Univ, Sweden; Icahn Sch Med Mt Sinai, NY 10029 USA.
    Sundquist, J.
    Lund Univ, Sweden.
    Sundquist, K.
    Lund Univ, Sweden.
    Aerobic fitness in late adolescence and the risk of cancer and cancer-associated mortality in adulthood: A prospective nationwide study of 1.2 million Swedish men2019In: Cancer Epidemiology, ISSN 1877-7821, E-ISSN 1877-783X, Vol. 59, p. 58-63Article in journal (Refereed)
    Abstract [en]

    Background: The incidence of cancer has steadily risen. It is important to identify modifiable predictors in early life that may decrease cancer risks and mortality. The present study aims to investigate the relationship between aerobic fitness in adolescence and the subsequent risk of cancer and cancer-associated mortality. Methods: The study included 1 185 439 Swedish men born between 1950 and 1980 that participated in the military conscription (mean age = 18 years). The results from the aerobic fitness test (W-max) was linked to the risk of cancer and cancer-associated mortality during a 40-years follow-up using Cox proportional hazards models. A co-sibling design was employed to take familial factors into account. Results: During a mean follow-up of 27 years 15 093 cases of cancer and 4900 cancer-associated mortalities were registered. Higher W-max (per additional 1 SD) was associated with a decreased risk of cancer at 40 years of follow-up (HR 0.93; 95% CI 0.91-0.96 for cancer and HR 0.82 95% CI 0.76-0.87 for cancer-associated mortality) but not at 5 years of follow-up (HR 1.03; 95% CI 0.99-1.07; and HR 1.04; 95% CI 0.97-1.12). In the co-sibling model the protective effects of high W-max were increased at 40 years of follow-up for cancer (HR 0.91; 95% CI 0.85-0.98) and cancer-associated mortality (HR 0.78; 95% CI 0.68-0.89). Conclusions: These findings identify in late adolescence a potentially modifiable predictor of cancer, with higher aerobic fitness associated with a decreased risk of cancer incidence and mortality later in life.

  • 328.
    Ibrahim, Farzana
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping. Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology.
    Sandström, Per A.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Björnsson, Bergthor
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Lindhoff Larsson, Anna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Drott, Jenny
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping. Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology.
    'I want to know why and need to be involved in my own care…': a qualitative interview study with liver, bile duct or pancreatic cancer patients about their experiences with involvement in care.2019In: Supportive Care in Cancer, ISSN 0941-4355, E-ISSN 1433-7339, Vol. 27, no 7, p. 2561-2567Article in journal (Refereed)
    Abstract [en]

    Purpose

    Patients’ involvement in their own care is important for those with upper abdominal tumours. Care is often conducted according to standardized fast-track care programs (FTCP), and a shorter hospital stay is one of the goals. However, there is no research providing an in-depth perspective on patients’ experiences of involvement in care. In this qualitative study, we explored experiences of involvement among patients who had surgery for upper abdominal tumours and were cared for according to an FTCP.

    Methods

    Qualitative in-depth face-to-face interviews about patient involvement in care were conducted with 20 patients who had surgery for the liver, bile duct, or pancreatic cancer using an open-interview guide.

    Results

    The most important findings are that customized information and active dialogue about care decisions stimulate patient involvement. We identified three themes from the analysed data: involvement depended on the quality of information, communication and involvement during the care period, and safety at discharge.

    Conclusions

    Individualized care and continuous information about treatment and care goals in the FTCP during the care process create trust between patients and healthcare professionals and increase patient experiences of involvement.

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  • 329.
    Ilander, M.
    et al.
    University of Helsinki, Finland; Helsinki University Hospital, Finland.
    Olsson-Stromberg, U.
    Uppsala University Hospital, Sweden; Uppsala University, Sweden.
    Schlums, H.
    Karolinska Institute, Sweden.
    Guilhot, J.
    CHU Poitiers, France.
    Bruck, O.
    University of Helsinki, Finland; Helsinki University Hospital, Finland.
    Lahteenmaki, H.
    University of Helsinki, Finland; Helsinki University Hospital, Finland.
    Kasanen, T.
    University of Helsinki, Finland; Helsinki University Hospital, Finland.
    Koskenvesa, P.
    University of Helsinki, Finland; Helsinki University Hospital, Finland.
    Soderlund, S.
    Uppsala University Hospital, Sweden.
    Hoglund, M.
    Uppsala University Hospital, Sweden.
    Markevarn, B.
    Umeå University Hospital, Sweden.
    Sjalander, A.
    Umeå University, Sweden.
    Lotfi, Kourosh
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Haematology.
    Dreimane, Arta
    Linköping University, Department of Clinical and Experimental Medicine. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Haematology. Linköping University, Faculty of Medicine and Health Sciences.
    Lubking, A.
    Skåne University Hospital, Sweden.
    Holm, E.
    Skåne University Hospital, Sweden.
    Bjoreman, M.
    University Hospital, Sweden.
    Lehmann, S.
    Uppsala University Hospital, Sweden; Uppsala University, Sweden; Karolinska University Hospital, Sweden.
    Stenke, L.
    Karolinska University Hospital, Sweden.
    Ohm, L.
    Karolinska University Hospital, Sweden.
    Gedde-Dahl, T.
    Oslo University Hospital, Norway.
    Majeed, W.
    Stavanger University Hospital, Norway.
    Ehrencrona, H.
    Skåne University Hospital, Sweden.
    Koskela, S.
    Finnish Red Cross Blood Serv, Finland.
    Saussele, S.
    Heidelberg University, Germany.
    Mahon, F-X
    University of Bordeaux Segalen, France.
    Porkka, K.
    University of Helsinki, Finland; Helsinki University Hospital, Finland.
    Hjorth-Hansen, H.
    St Olavs University Hospital, Norway.
    Bryceson, Y. T.
    Karolinska Institute, Sweden.
    Richter, J.
    Skåne University Hospital, Sweden.
    Mustjoki, S.
    University of Helsinki, Finland; Helsinki University Hospital, Finland; University of Helsinki, Finland.
    Increased proportion of mature NK cells is associated with successful imatinib discontinuation in chronic myeloid leukemia2017In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 31, no 5, p. 1108-1116Article in journal (Refereed)
    Abstract [en]

    Recent studies suggest that a proportion of chronic myeloid leukemia (CML) patients in deep molecular remission can discontinue the tyrosine kinase inhibitor (TKI) treatment without disease relapse. In this multi-center, prospective clinical trial (EURO-SKI, NCT01596114) we analyzed the function and phenotype of T and NK cells and their relation to successful TKI cessation. Lymphocyte subclasses were measured from 100 imatinib-treated patients at baseline and 1 month after the discontinuation, and functional characterization of NK and T cells was done from 45 patients. The proportion of NK cells was associated with the molecular relapse-free survival as patients with higher than median NK-cell percentage at the time of drug discontinuation had better probability to stay in remission. Similar association was not found with T or B cells or their subsets. In non-relapsing patients the NK-cell phenotype was mature, whereas patients with more naive CD56(bright) NK cells had decreased relapse-free survival. In addition, the TNF-alpha/IFN-gamma cytokine secretion by NK cells correlated with the successful drug discontinuation. Our results highlight the role of NK cells in sustaining remission and strengthen the status of CML as an immunogenic tumor warranting novel clinical trials with immunomodulating agents.

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  • 330.
    Ingelsson, Björn
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Söderberg, Daniel
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Strid, Tobias
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Söderberg, Anita
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Bergh, Ann-Charlotte
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Loitto, Vesa-Matti
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Lotfi, Kourosh
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Haematology.
    Segelmark, Mårten
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Nephrology.
    Spyrou, Giannis
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Rosén, Anders
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Lymphocytes eject interferogenic mitochondrial DNA webs in response to CpG and non-CpG oligodeoxynucleotides of class C2018In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 115, no 3, p. E478-E487Article in journal (Refereed)
    Abstract [en]

    Circulating mitochondrial DNA (mtDNA) is receiving increasing attention as a danger-associated molecular pattern in conditions such as autoimmunity, cancer, and trauma. We report here that human lymphocytes [B cells, T cells, natural killer (NK) cells], monocytes, and neutrophils derived from healthy blood donors, as well as B cells from chronic lymphocytic leukemia patients, rapidly eject mtDNA as web filament structures upon recognition of CpG and non-CpG oligodeoxynucleotides of class C. The release was quenched by ZnCl2, independent of cell death (apoptosis, necrosis, necroptosis, autophagy), and continued in the presence of TLR9 signaling inhibitors. B-cell mtDNA webs were distinct from neutrophil extracellular traps concerning structure, reactive oxygen species (ROS) dependence, and were devoid of antibacterial proteins. mtDNA webs acted as rapid (within minutes) messengers, priming antiviral type I IFN production. In summary, our findings point at a previously unrecognized role for lymphocytes in antimicrobial defense, utilizing mtDNA webs as signals in synergy with cytokines and natural antibodies, and cast light on the interplay between mitochondria and the immune system.

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  • 331.
    Ingvar, C.
    et al.
    Lund Univ, Sweden.
    Ahlgren, J.
    Uppsala Univ Hosp, Sweden; Orebro Univ, Sweden.
    Emdins, S.
    Umea Univ, Sweden.
    Lofgren, L.
    St Gorans Univ Hosp, Sweden.
    Nordander, M.
    Lund Univ, Sweden.
    Nimeus, E.
    Lund Univ, Sweden.
    Arnesson, Lars-Gunnar
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Long-term outcome of pT1a-b, cN0 breast cancer without axillary dissection or staging: a prospective observational study of 1543 women2020In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168Article in journal (Refereed)
    Abstract [en]

    Background The implementation of screening programmes in Sweden during the mid-1990s increased the number of small node-negative breast cancers. In this era before staging by sentinel node biopsy, routine axillary dissection for staging of early breast cancer was questioned owing to the increased morbidity and lack of perceived benefit. The long-term risk of axillary recurrence when axillary staging is omitted remains unclear. Methods This prospective observational multicentre cohort study included Swedish women diagnosed with breast cancer between 1997 and 2002. The patients had clinically node-negative, pT1a-b, grade I-II tumours. No axillary staging or dissection was performed. The primary outcome was ipsilateral axillary recurrence and survival. Results A total of 1543 patients were included. Breast-conserving surgery (BCS) was performed in 94 center dot 0 per cent and the rest underwent mastectomy. After surgery, 58 center dot 1 per cent of the women received adjuvant radiotherapy, 11 center dot 9 per cent adjuvant endocrine therapy and 31 center dot 5 per cent did not receive any adjuvant treatment. After a median follow-up of 15 center dot 5 years, 6 center dot 4 per cent developed contralateral breast cancer and 16 center dot 5 per cent experienced a recurrence. The first recurrence was local in 116, regional in 47 and distant in 59 patients. The breast cancer-specific survival rate was 93 center dot 7 per cent after 15 years. There were no differences in overall or breast cancer-specific survival between patients who received adjuvant radiotherapy and those who did not. Only 3 center dot 0 per cent of patients had an axillary recurrence, which was isolated in only 1 center dot 0 per cent. Conclusion Axillary surgery can safely be omitted in patients with low-grade, T1a-b, cN0 breast cancers. This large prospective cohort with 15-year follow-up had a very low incidence of axillary recurrences and high breast cancer-specific survival rate.

  • 332.
    Iredahl, Fredrik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Högstedt, Alexandra
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Henricson, Joakim
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology. Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Tesselaar, Erik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Farnebo, Simon
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Skin glucose metabolism and microvascular blood flow during local insulin delivery and after an oral glucose load2016In: Microcirculation, ISSN 1073-9688, E-ISSN 1549-8719, Vol. 23, no 7, p. 597-605Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Insulin causes capillary recruitment in muscle and adipose tissue, but the metabolic and microvascular effects of insulin in the skin have not been studied in detail. The aim of this study was to measure glucose metabolism and microvascular blood flow in the skin during local insulin delivery and after an oral glucose load.

    METHODS: Microdialysis catheters were inserted intracutanously in human subjects. In eight subjects two microdialysis catheters were inserted, one perfused with insulin and one with control solution. First the local effects of insulin was studied, followed by a systemic provocation by an oral glucose load. Additionally, as control experiment, six subjects did not recieve local delivery of insulin or the oral glucose load. During microdialysis the local blood flow was measured by urea clearance and by laser speckle contrast imaging (LSCI).

    RESULTS: Within 15 minutes of local insulin delivery, microvascular blood flow in the skin increased (urea clearance: P=.047, LSCI: P=.002) paralleled by increases in pyruvate (P=.01) and lactate (P=.04), indicating an increase in glucose uptake. An oral glucose load increased urea clearance from the catheters, indicating an increase in skin perfusion, although no perfusion changes were detected with LSCI. The concentration of glucose, pyruvate and lactate increased in the skin after the oral glucose load.

    CONCLUSION: Insulin has metabolic and vasodilatory effects in the skin both when given locally and after systemic delivery through an oral glucose load.

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  • 333.
    Jaako, P.
    et al.
    Lund University, Sweden.
    Ugale, A.
    Lund University, Sweden.
    Wahlestedt, M.
    Lund University, Sweden.
    Velasco-Hernandez, T.
    Lund University, Sweden.
    Cammenga, Jörg
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Haematology.
    Lindström, M. S.
    Karolinska Institute, Sweden.
    Bryder, D.
    Lund University, Sweden.
    Induction of the 5S RNP-Mdm2-p53 ribosomal stress pathway delays the initiation but fails to eradicate established murine acute myeloid leukemia2017In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 31, no 1, p. 213-221Article in journal (Refereed)
    Abstract [en]

    Mutations resulting in constitutive activation of signaling pathways that regulate ribosome biogenesis are among the most common genetic events in acute myeloid leukemia (AML). However, whether ribosome biogenesis presents as a therapeutic target to treat AML remains unexplored. Perturbations in ribosome biogenesis trigger the 5S ribonucleoprotein particle (RNP)-Mdm2-p53 ribosomal stress pathway, and induction of this pathway has been shown to have therapeutic efficacy in Myc-driven lymphoma. In the current study we address the physiological and therapeutic role of the 5S RNP-Mdm2-p53 pathway in AML. By utilizing mice that have defective ribosome biogenesis due to downregulation of ribosomal protein S19 (Rps19), we demonstrate that induction of the 5S RNP-Mdm2-p53 pathway significantly delays the initiation of AML. However, even a severe Rps19 deficiency that normally results in acute bone marrow failure has no consistent efficacy on already established disease. Finally, by using mice that harbor a mutation in the Mdm2 gene disrupting its binding to 5S RNP, we show that loss of the 5S RNP-Mdm2-p53 pathway is dispensable for development of AML. Our study suggests that induction of the 5S RNP-Mdm2-p53 ribosomal stress pathway holds limited potential as a single-agent therapy in the treatment of AML.

  • 334.
    Jahnson, Staffan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Gardmark, Truls
    Karolinska Inst, Sweden.
    Hosseini, Abolfazl
    Karolinska Univ Hosp, Sweden.
    Jedstrom, Tomas
    Orebro Univ Hosp, Sweden.
    Liedberg, Fredrik
    Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    Malmstrom, Per-Uno
    Uppsala Univ, Sweden.
    Rosell, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Health and Developmental Care, Regional Cancer Center South East Sweden.
    Sherif, Amir
    Umea Univ Hosp, Sweden.
    Strock, Viveka
    Sahlgrens Univ Hosp, Sweden.
    Haggstrom, Christel
    Uppsala Univ, Sweden; Umea Univ, Sweden.
    Holmberg, Lars
    Uppsala Univ, Sweden; Kings Coll London, England.
    Aljabery, Firas
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Management and outcome of TaG3 tumours of the urinary bladder in the nationwide, population-based bladder cancer database Sweden (BladderBaSe)In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813Article in journal (Refereed)
    Abstract [en]

    Purpose: To investigate the management of TaG3 tumours of the urinary bladder using nationwide population-based data in relation to the prevailing guidelines, patients characteristics, and outcome. Materials and methods: The Bladder Cancer Data Base Sweden (BladderBaSe), including data from the Swedish National Register for Urinary Bladder Cancer (SNRUBC), was used to study all patients with TaG3 bladder cancer diagnosed from 2008 to 2014. Patients were divided into the following management groups: (1) transurethral resection (TUR) only, (2) TUR and intravesical instillation therapy (IVIT), (3) TUR and second-look resection (SLR), and (4) TUR with both SLR and IVIT. Patient and tumour characteristics and outcome were studied. Results: There were 831 patients (83% males) with a median age of 74 years. SLR was performed more often on younger patients, on men, and less often in the Western and Uppsala/orebro Healthcare regions. IVIT was performed more often with younger patients, with men, in the Western Healthcare region, and less often in the Uppsala/orebro Healthcare region. Death from bladder cancer occurred in 6% of cases within a median of 29 months (0-84 months) and was lower in the TUR/IVIT and TUR/SLR/IVIT groups compared to the other two groups. Conclusion: In the present study, there was, according to the prevailing treatment guidelines, an under-treatment with SLR for older patients, women, and in some healthcare regions and, similarly, there was an under-treatment with IVIT for older patients. Cancer-specific survival and relative survival were lower in the TUR only group compared to the TUR/IVIT and TUR/SLR/IVIT groups.

  • 335.
    Jahnson, Staffan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Hosseini Aliabad, Abolfazl
    Karolinska University Hospital, Sweden.
    Holmang, Sten
    Sahlgrens University Hospital, Sweden.
    Jancke, Georg
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Liedberg, Fredrik
    Skåne University Hospital, Sweden.
    Ljungberg, Borje
    Northern University Hospital, Sweden.
    Malmstrom, Per-Uno
    University of Uppsala Hospital, Sweden.
    Rosell, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Health and Developmental Care, Regional Cancer Center South East Sweden. Linköping University, Faculty of Medicine and Health Sciences.
    Swedish National Registry of Urinary Bladder Cancer: No difference in relative survival over time despite more aggressive treatment2016In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 50, no 1, p. 14-20Article in journal (Refereed)
    Abstract [en]

    Objective. The aim of this study was to use the Swedish National Registry of Urinary Bladder Cancer (SNRUBC) to investigate changes in patient and tumour characteristics, management and survival in bladder cancer cases over a period of 15 years. Materials and methods. All patients with newly detected bladder cancer reported to the SNRUBC during 1997-2011 were included in the study. The cohort was divided into three groups, each representing 5 years of the 15 year study period. Results. The study included 31,266 patients (74% men, 26% women) with a mean age of 72 years. Mean age was 71.7 years in the first subperiod (1997-2001) and 72.5 years in the last subperiod (2007-2011). Clinical T categorization changed from the first to the last subperiod: Ta from 45% to 48%, T1 from 21.6% to 22.4%, and T2-T4 from 27% to 25%. Also from the first to the last subperiod, intravesical treatment after transurethral resection for T1G2 and T1G3 tumours increased from 15% to 40% and from 30% to 50%, respectively, and cystectomy for T2-T4 tumours increased from 30% to 40%. No differences between the analysed subperiods were found regarding relative survival in patients with T1 or T2-T4 tumours, or in the whole cohort. Conclusions. This investigation based on a national bladder cancer registry showed that the age of the patients at diagnosis increased, and the proportion of muscle-invasive tumours decreased. The treatment of all tumour stages became more aggressive but relative survival showed no statistically significant change over time.

  • 336.
    Jahnson, Staffan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Rosell, Johan
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Business support and Development, Regional Cancer Center.
    Abdul-Sattar Aljabery, Firas
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Modulation of the inflammatory response after sclerotherapy for hydrocoele/spermatocoele2019In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 123, no 5A, p. E63-E68Article in journal (Refereed)
    Abstract [en]

    Objective

    To investigate the modulation of the inflammatory response after sclerotherapy for hydrocoele/spermatocoele.

    Patients and Methods

    All patients with hydrocoele or spermatocoele presenting at the Department of Urology, University Hospital, Linköping, Sweden, from 2006 to 2012, were included in this prospective observational study of sclerotherapy for hydrocoele/spermatocoele using polidocanol as a sclerosing agent and adjuvant antibiotic and anti‐inflammatory medication (AAAM) for modulation of the inflammatory response. Patients were clinically evaluated within 24–48 h after a complication or adverse event possibly related to sclerotherapy. Evaluation of cure was scheduled after 3 months and re‐treatment, if necessary was carried out in the same manner as the first treatment. Groups of patients were compared using the chi‐squared test and logistic regression analysis.

    Results

    From a total of 191 patients, AAAM was given to 126, of whom 5% had subclinical epididymitis/swelling (SES) compared to 26% of the patients without AAAM (P < 0.001). No other complication was observed. The rate of cure for the whole group of patients was 93% after one or two treatments and significantly higher in the group with AAAM than in the group without AAAM (96% vs 88%, P = 0.03).

    Conclusions

    Modulation of the inflammatory response after sclerotherapy resulted in a lower incidence of SES and an increased cure rate.

  • 337.
    Jakobsen Falk, Ingrid
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Lund, Johan
    Karolinska Institute, Sweden.
    Green, Henrik
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. National Board Forens Med, Department Forens Genet and Forens Toxicol, Linkoping, Sweden.
    Gruber, Astrid
    Karolinska Institute, Sweden.
    Alici, Evren
    Karolinska Institute, Sweden.
    Lauri, Birgitta
    Sunderby Hospital, Sweden.
    Blimark, Cecilie
    Sahlgrens University Hospital, Sweden.
    Mellqvist, Ulf-Henrik
    South Elvsborg Hospital, Sweden.
    Swedin, Agneta
    Skåne University Hospital, Sweden.
    Forsberg, Karin
    Norrland University Hospital, Sweden.
    Carlsson, Conny
    Hallands Hospital, Sweden.
    Hardling, Mats
    Uddevalla Central Hospital, Sweden.
    Ahlberg, Lucia
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Haematology.
    Lotfi, Kourosh
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Haematology.
    Nahi, Hareth
    Karolinska Institute, Sweden.
    Pharmacogenetic study of the impact of ABCB1 single-nucleotide polymorphisms on lenalidomide treatment outcomes in patients with multiple myeloma: results from a phase IV observational study and subsequent phase II clinical trial2018In: Cancer Chemotherapy and Pharmacology, ISSN 0344-5704, E-ISSN 1432-0843, Vol. 81, no 1, p. 183-193Article in journal (Refereed)
    Abstract [en]

    Purpose Despite therapeutic advances, patients with multiple myeloma (MM) continue to experience disease relapse and treatment resistance. The gene ABCB1 encodes the drug transporter P-glycoprotein, which confers resistance through drug extrusion across the cell membrane. Lenalidomide (Len) is excreted mainly via the kidneys, and, given the expression of P-gp in the renal tubuli, single-nucleotide polymorphisms (SNPs) in the ABCB1 gene may influence Len plasma concentrations and, subsequently, the outcome of treatment. We, therefore, investigated the influence of ABCB1 genetic variants on Len treatment outcomes and adverse events (AEs). Methods Ninety patients with relapsed or refractory MM, who received the second-line Len plus dexamethasone in the Rev II trial, were genotyped for the ABCB1 SNPs 1199G amp;gt; A (Ser400Asn, rs2229109), 1236C amp;gt; T (silent, rs1128503), 2677G amp;gt; T/A (Ala893Ser, rs2032582), and 3435C amp;gt; T (silent, rs1045642) using pyrosequencing, and correlations to response parameters, outcomes, and AEs were investigated. Results No significant associations were found between genotype and either best response rates or hematological AEs, and 1236C amp;gt; T, 2677G amp;gt; T or 3435C amp;gt; T genotypes had no impact on survival. There was a trend towards increased time to progression (TTP) in patients carrying the 1199A variant, and a significant difference in TTP between genotypes in patients with standard-risk cytogenetics. Conclusions Our findings show a limited influence of ABCB1 genotype on lenalidomide treatment efficacy and safety. The results suggest that 1199G amp;gt; A may be a marker of TTP following Len treatment in standard-risk patients; however, larger studies are needed to validate and clarify the relationship.

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  • 338.
    Jakobsen Falk, Ingrid
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    Willander, Kerstin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Haematology.
    Chaireti, Roza
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Acute Internal Medicine. Karolinska University Hospital, Sweden.
    Lund, Johan
    Huddinge University Hospital, Sweden.
    Nahi, Hareth
    Huddinge University Hospital, Sweden.
    Hermanson, Monica
    Uppsala University, Sweden.
    Green, Henrik
    National Board Forens Med, Department Forens Genet and Forens Toxicol, Linkoping, Sweden.
    Lotfi, Kourosh
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Haematology.
    Söderkvist, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    TP53 mutations and MDM2(SNP309) identify subgroups of AML patients with impaired outcome2015In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 94, no 4, p. 355-362Article in journal (Refereed)
    Abstract [en]

    BackgroundTP53 is commonly mutated in several cancers and confers treatment resistance and poor prognosis. Altered expression of mouse double minute 2 (MDM2), a negative regulator of p53, may also attenuate normal p53 signaling, thereby enhancing tumor transformation and resistance to apoptosis. The single nucleotide polymorphism (SNP) 309 has been reported to increase MDM2 expression and impair normal p53 response. Experimental designWe investigated the frequency and impact of TP53 mutations (TP53mut) and MDM2(SNP309) on treatment outcome and overall survival (OS) in 189 Swedish acute myeloid leukemia patients. The genetic analyses were performed using SSCA and direct sequencing (for mutations in exon 5-8 of TP53) and Pyrosequencing (for the MDM2(SNP309)). ResultsWe found a high frequency (22%) of TP53mut in patients with cytogenetic aberrations, with association to high-risk cytogenetics (Pless than0.001). TP53mut patients had lower response rates (22% compared with 76% CR in TP53 wild-type (wt) patients, Pless than0.001) and reduced OS (2 and 16months, respectively, Pless than0.001). In TP53wt patients with high or intermediate risk cytogenetic aberrations, the MDM2(SNP309) conferred an impaired outcome, with patients carrying the alternative G-allele having shorter OS compared with T/T patients (median 9 vs. 50months, P=0.020). ConclusionsOur results show that TP53mut analysis and MDM2(SNP309) genotyping may be useful tools for prognostication, risk stratification, and selection of patients most likely to benefit from new drugs targeting the p53 signaling pathway.

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  • 339.
    Jakobsson, Gustav L.
    et al.
    Karolinska Institute, Sweden.
    Sternegard, Emil
    Karolinska Institute, Sweden.
    Olen, Ola
    Sachs Childrens Hospital, Sweden; Karolinska Institute, Sweden.
    Myrelid, Pär
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Ljung, Rickard
    Karolinska Institute, Sweden.
    Strid, Hans
    Södra Älvsborgs Sjukhus, Sweden; University of Gothenburg, Sweden.
    Halfvarson, Jonas
    University of Örebro, Sweden.
    Ludvigsson, Jonas F.
    Karolinska Institute, Sweden; Oregon University Hospital, Sweden; University of Nottingham, England; Columbia University, NY USA.
    Validating inflammatory bowel disease (IBD) in the Swedish National Patient Register and the Swedish Quality Register for IBD (SWIBREG)2017In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 52, no 2, p. 216-221Article in journal (Refereed)
    Abstract [en]

    Background: Both the Swedish National Patient Register (NPR) and the Swedish Quality Register for inflammatory bowel disease (IBD, SWIBREG) are important sources of research data and information. However, the validity of a diagnosis of IBD in these registers is unknown. Methods: Medical charts of 129 randomly selected patients from the NPR and 165 patients registered both in SWIBREG and the NPR were reviewed. Patients were classified according to standardized criteria for ulcerative colitis (UC), Crohns disease (CD), or IBD unclassified (IBD-U). Positive predictive values (PPVs) for UC, CD, IBD-U (only SWIBREG), or having any form of IBD were then calculated. Results: For cases with amp;gt;= 2 diagnoses of IBD in the NPR (hospitalizations or non-primary care outpatient visits), the PPV was 93% (95% CI: 87-97) for any IBD, 79% (66-88) for UC and 72% (60-82) for CD. In UC patients with amp;gt;= 2 UC diagnoses but never a CD diagnosis, the PPV increased to 90% (77-97). The PPV for CD in patients with amp;gt;= 2 CD diagnoses but never a UC diagnosis was 81% (67-91)). Combining data from SWIBREG (amp;gt;= 1 record) and the NPR (amp;gt;= 1 record), the PPV was 99% for any IBD (97-100), 96% (89-99) for UC, and 90% (82-96) for CD. Conclusion: The validity of the UC, CD, and IBD diagnoses is high in the NPR but even higher when cases were identified both in SWIBREG and the NPR. These results underline the need for a well-functioning Swedish Quality Register for IBD as a complement to the NPR.

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  • 340.
    Jakola, Asgeir Store
    et al.
    Department of Neurosurgery, Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Neurosurgery, St. Olavs Hospital, Trondheim, Norway; Institute of Neuroscience and Physiology, Department of Clinical Neuroscience, University of Gothenburg, Sahlgrenska Academy, Gothenburg, Sweden.
    Werlenius, Katja
    Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden; Institute of Clinical Sciences, University of Gothenburg, Sahlgrenska Academy, Gothenburg, Sweden.
    Mudaisi, Munila
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Hylin, Sofia
    Department of Neurology, Karolinska University Hospital, Stockholm, Sweden.
    Kinhult, Sara
    Department of Oncology, Skåne University Hospital, Lund, Sweden.
    Bartek, Jiri
    Department of Neurosurgery, Karolinska University Hospital, Stockholm, Sweden; Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
    Salvesen, Øyvind
    Department of Public Health and Nursing, Norwegian University of Science and Technology, Trondheim, Norway.
    Carlsen, Sven Magnus
    Department of Cancer Research and Molecular medicine, Norwegian University of Science and Technology, Trondheim, Norway; Department of Endocrinology, St. Olavs Hospital, Trondheim, Norway.
    Strandéus, Michael
    Department of Oncology, County Hospital Ryhov, Jönköping, Sweden.
    Lindskog, Magnus
    Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden; Section of Oncology, Akademiska University Hospital, Uppsala, Sweden.
    Löfgren, David
    Department of Oncology, Örebro University Hospital, Örebro, Sweden.
    Rydenhag, Bertil
    Department of Neurosurgery, Sahlgrenska University Hospital, Gothenburg, Sweden; Institute of Neuroscience and Physiology, Department of Clinical Neuroscience, University of Gothenburg, Sahlgrenska Academy, Gothenburg, Sweden.
    Carstam, Louise
    Department of Neurosurgery, Sahlgrenska University Hospital, Gothenburg, Sweden; Institute of Neuroscience and Physiology, Department of Clinical Neuroscience, University of Gothenburg, Sahlgrenska Academy, Gothenburg, Sweden.
    Gulati, Sasha
    Department of Neurosurgery, St. Olavs Hospital, Trondheim, Norway; Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway.
    Solheim, Ole
    Department of Neurosurgery, St. Olavs Hospital, Trondheim, Norway; Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway.
    Bartek, Jiri
    Department of Medical Biochemistry and Biophysics, Division of Genome Biology, Science for Life Laboratory,, Karolinska Institute, Stockholm, Sweden; Research Center, Danish Cancer Society, Copenhagen, Denmark.
    Solheim, Tora
    European Palliative Care Research Centre (PRC), Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway; Cancer Clinic, St. Olavs Hospital, Trondheim, Norway.
    Disulfiram repurposing combined with nutritional copper supplement as add-on to chemotherapy in recurrent glioblastoma (DIRECT): Study protocol for a randomized controlled trial2018In: F1000 Research, E-ISSN 2046-1402, Vol. 7, article id 1797Article in journal (Refereed)
    Abstract [en]

    Background: Disulfiram (DSF) is a well-tolerated, inexpensive, generic drug that has been in use to treat alcoholism since the 1950s. There is now independent preclinical data that supports DSF as an anticancer agent, and experimental data suggest that copper may increase its anti-neoplastic properties. There is also some clinical evidence that DSF is a promising anticancer agent in extracranial cancers. In glioblastoma, DSF induced O 6-methylguanine methyltransferase (MGMT) inhibition may increase response to alkylating chemotherapy. A recent phase I study demonstrated the safety of DSF in glioblastoma patients when DSF was administered at doses below 500 mg/day together with chemotherapy. We plan to assess the effects of DSF combined with nutritional copper supplement (DSF-Cu) as an adjuvant to alkylating chemotherapy in glioblastoma treatment. Methods: In an academic, industry independent, multicenter, open label randomized controlled phase II/III trial with parallel group design (1:1) we will assess the efficacy and safety of DSF-Cu in glioblastoma treatment. The study will include 142 patients at the time of first recurrence of glioblastoma where salvage therapy with alkylating chemotherapy is planned. Patients will be randomized to treatment with or without DSF-Cu. Primary end-point is survival at 6 months. Secondary end-points are overall survival, progression free survival, quality of life, contrast enhancing tumor volume and safety. Discussion: There is a need to improve the treatment of recurrent glioblastoma. Results from this randomized controlled trial with DSF-Cu in glioblastoma will serve as preliminary evidence of the future role of DSF-Cu in glioblastoma treatment and a basis for design and power estimations of future studies. In this publication we provide rationale for our choices and discuss methodological issues. Trial registration: The study underwent registration in EudraCT 2016-000167-16 (Date: 30.03.2016,) and Clinicaltrials.gov NCT02678975 (Date: 31.01.2016) before initiating the study.

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  • 341.
    Jancke, Georg
    et al.
    Skåne Univ Hosp, Sweden; Lund Univ, Sweden.
    Aljabery, Firas
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland. Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Gudjonsson, Sigurdur
    Landspitali Univ Hosp, Iceland.
    Hosseini, Abolfazl
    Karolinska Univ Hosp, Sweden.
    Sorenby, Anne
    Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    Wiklund, Peter
    Karolinska Univ Hosp, Sweden.
    Liedberg, Fredrik
    Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    Port-site Metastases After Robot-assisted Radical Cystectomy: Is There a Publication Bias?2018In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 73, no 4, p. 641-642Article in journal (Other academic)
    Abstract [en]

    n/a

  • 342.
    Jancke, Georg
    et al.
    Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    Aljabery, Firas
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Gudjonsson, Sigurdur
    Landspitali Univ Hosp, Iceland.
    Sorenby, Anne
    Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    Liedberg, Fredrik
    Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    Reply to Francesco Montorsi and Giorgio Gandaglias Letter to the Editor re: Georg Jancke, Firas Aljabery, Sigurdur Gudjonsson, et al. Port-site Metastases After Robot-assisted Radical Cystectomy: Is There a Publication Bias?2019In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 75, no 2, p. E32-E33Article in journal (Other academic)
    Abstract [en]

    n/a

  • 343.
    Jancke, Georg
    et al.
    Skåne University Hospital, Sweden; Lund University, Sweden.
    Liedberg, Fredrik
    Skåne University Hospital, Sweden; Lund University, Sweden.
    Aljabery, Firas
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Sherif, Amir
    Norrland University Hospital, Sweden.
    Strock, Viveka
    Sahlgrens University Hospital, Sweden.
    Malmstrom, Per-Uno
    Uppsala Akad Hospital, Sweden.
    Hosseini-Aliabad, Abolfazl
    Karolinska University Hospital, Sweden.
    Jahnson, Staffan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Intravesical instillations and cancer-specific survival in patients with primary carcinoma in situ of the urinary bladder2017In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 51, no 2, p. 124-129Article in journal (Refereed)
    Abstract [en]

    Objective: The aim of this study was to evaluate the use of intravesical treatment and cancer-specific survival of patients with primary carcinoma in situ (CIS). Materials and methods: Data acquisition was based on the Swedish National Registry of Urinary Bladder Cancer by selecting all patients with primary CIS. The analysis covered gender, age, hospital type and hospital volume. Intravesical treatment and death due to bladder cancer were evaluated by multivariate logistic regression and multivariate Cox analysis, respectively. Results: The study included 1041 patients (median age at diagnosis 72 years) with a median follow-up of 65 months. Intravesical instillation therapy was given to 745 patients (72%), and 138 (13%) died from bladder cancer during the observation period. Male gender [odds ratio (OR) = 1.56, 95% confidence interval (CI) 1.13-2.17] and treatment at county (OR = 1.65, 95% CI 1.17-2.33), university (OR =2.12, 95% CI 1.48-3.03) or high-volume (OR= 1.92, 95% CI 1.34-2.75) hospitals were significantly associated with higher odds of intravesical instillations. The age category amp;gt;80 years had a significantly lower chance of receiving intravesical therapy (OR = 0.44, 95% CI 0.26-0.74) and a significantly higher risk of dying from bladder cancer (hazard ratio = 3.03, 95% CI 1.71-5.35). Conclusion: Significantly more frequent use of intravesical treatment of primary CIS was found for males and for patients treated at county, university and high-volume hospitals. Age amp;gt;80 years was significantly related to less intravesical treatment and poorer cancer-specific survival.

  • 344.
    Jancke, Georg
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Rosell, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Health and Developmental Care, Regional Cancer Center South East Sweden. Linköping University, Faculty of Medicine and Health Sciences.
    Jahnson, Staffan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Tumour location adjacent to the ureteric orifice in primary Ta/T1 bladder cancer is predictive of recurrence2016In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 50, no 1, p. 33-38Article in journal (Refereed)
    Abstract [en]

    Objective: The aim of this study was to evaluate tumour growth located around the ureteric orifice (LUO) at primary diagnosis of Ta/T1 urinary bladder cancer in relation to effects on recurrence and progression. Materials and methods: Clinical and pathological characteristics of patients diagnosed with primary Ta/T1 urinary bladder cancer from 1992 to 2007 were recorded prospectively. Location of the primary tumour and growth around the ureteric orifice (within 1 cm) were recorded and correlated with recurrence and progression during further follow-up. Hazard ratios (HRs) were estimated using Cox regression with 95% confidence intervals (CIs) in both univariate and multivariate analysis. Results: The study included 768 evaluable patients with a median follow-up of 60 months. Recurrence was observed in 478 patients (62%) and progression in 71 (9%). Growth of a primary tumour adjacent to the ureteric orifice was associated with recurrence (HR = 1.28, 95% CI = 1.07-1.54) but not progression (HR = 1.04, 95% CI = 0.65-1.67). The most common location of the first recurrence was the posterior bladder wall (29%). Other locations in the bladder did not predict recurrence or progression. Additional factors affecting recurrence were tumour size greater than 15mm, T1 tumour category, multiplicity, malignant or missing/not representative bladder wash cytology and surgery performed by residents. Conclusions: A primary tumour located around the ureteric orifice was predictive of recurrence, which could be taken into account in future follow-up schedules.

  • 345.
    Janson, Annika
    et al.
    Karolinska universitetssjukhuset, Sweden.
    Järvholm, Kajsa
    Skånes universitetssjukvård, Sweden.
    Gronowitz, Eva
    Drottning Silvias barn- och ungdomssjukhus, Sweden.
    Önnerfält, Jenny
    Skånes universitetssjukvård, Sweden.
    Ekbom, Kerstin
    Karolinska universitetssjukhuset, Sweden.
    Engström, My
    Sahlgrenska universitetssjukhuset, Sweden.
    Elimam, Amira
    Karolinska universitetssjukhuset, Sweden.
    Thorell, Anders
    Karolinska institutet, Sweden.
    Sjögren, Lovisa
    Drottning Silvias barn- och ungdomssjukhus, Sweden.
    Dahlgren, Jovanna
    Drottning Silvias barn- och ungdomssjukhus, Sweden.
    Olbers, Torsten
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping.
    Fetmakirurgi bör kunna erbjudas före 18 vid allvarlig fetma2019In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 116Article in journal (Other academic)
  • 346.
    Jarvholm, Kajsa
    et al.
    SKane Univ Hosp, Sweden; Univ Gothenburg, Sweden.
    Bruze, Gustaf
    Karolinska Inst, Sweden.
    Peltonen, Markku
    Natl Inst Hlth and Welf, Finland.
    Marcus, Claude
    Karolinska Inst, Sweden.
    Flodmark, Carl-Erik
    Lund Univ, Sweden.
    Henfridsson, Pia
    Univ Gothenburg, Sweden.
    Beamish, Andrew J.
    Univ Gothenburg, Sweden; Royal Coll Surgeons England, England.
    Gronowitz, Eva
    Univ Gothenburg, Sweden.
    Dahlgren, Jovanna
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Karlsson, Jan
    Orebro Univ, Sweden.
    Olbers, Torsten
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping. Univ Gothenburg, Sweden.
    5-year mental health and eating pattern outcomes following bariatric surgery in adolescents: a prospective cohort study2020In: LANCET CHILD and ADOLESCENT HEALTH, ISSN 2352-4642, Vol. 4, no 3, p. 210-219Article in journal (Refereed)
    Abstract [en]

    Background Mental health problems are prevalent among adolescents with severe obesity, but long-term mental health outcomes after adolescent bariatric surgery are not well known. We aimed to assess mental health outcomes over 5 years of follow-up after Roux-en-Y gastric bypass surgery in adolescents who participated in the Adolescent Morbid Obesity Surgery (AMOS) study. Methods This was a non-randomised matched-control study in adolescents aged 13-18 years who had a BMI of 40 kg/m(2) or higher, or 35 kg/m(2) or higher in addition to obesity-related comorbidity; who had previously undergone failed comprehensive conservative treatment; and were of pubertal Tanner stage III or higher, with height growth velocity beyond peak. A contemporary control group, matched for BMI, age, and sex, who underwent conventional obesity treatment, was obtained from the Swedish Childhood Obesity Treatment Register. Data on dispensed psychiatric drugs and specialist treatment for mental disorders were retrieved from national registers with complete coverage. In the surgical group only, questionnaires were used to assess self-esteem (Rosenberg Self-Esteem [RSE] score), mood (Mood Adjective Checklist [MACL]), and eating patterns (Binge Eating Scale [BES] and Three-Factor Eating Questionnaire-R21 [TFEQ]). This study is registered with ClinicalTrials.gov (NCT00289705). Findings Between April 10, 2006, and May 20, 2009, 81 adolescents (53 [65%] female) underwent Roux-en-Y gastric bypass surgery, and 80 control participants received conventional treatment. The proportion of participants prescribed psychiatric drugs did not differ between groups in the years before study inclusion (pre-baseline; absolute risk difference 5% [95% CI -7 to 16], p=0.4263) or after intervention (10% [-6 to 24], p=0.2175). Treatment for mental and behavioural disorders did not differ between groups before baseline (2% [-10 to 14], p=0.7135); however, adolescents in the surgical group had more specialised psychiatric treatment in the 5 years after obesity treatment than did the control group (15% [1 to 28], p=0.0410). There were few patients who discontinued psychiatric treatment post-surgery (three [4%] receiving psychiatric drug treatment and six [7%] receiving specialised care for a mental disorder before surgery). In the surgical group, self-esteem (RSE score) was improved after 5 years (mixed model mean 21.6 [95% CI 19.9 to 23.4]) relative to baseline (18.9 [17.4 to 20.4], p=0.0059), but overall mood (MACL score) was not (2.8 [2.7 to 2.9] at 5 years vs 2.7 [2.6 to 2.8] at baseline, p=0.0737). Binge eating was improved at 5 years (9.3 [7.4 to 11.2]) relative to baseline (15.0 [13.5 to 16.5], pamp;lt;0.0001). Relative changes in BMI were not associated with the presence or absence of binge eating at baseline. Interpretation Mental health problems persist in adolescents 5 years after bariatric surgery despite substantial weight loss. Although bariatric surgery can improve many aspects of health, alleviation of mental health problems should not be expected, and a multidisciplinary bariatric team should offer long-term mental health support after surgery. Copyright (C) 2020 Elsevier Ltd. All rights reserved.

  • 347.
    Jarvinen, T. L. N.
    et al.
    University of Helsinki, Finland; University of Helsinki, Finland.
    Michaelsson, K.
    Uppsala University, Sweden.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Sievanen, H.
    UKK Institute Health Promot Research, Finland.
    Osteoporosis: the emperor has no clothes2015In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 277, no 6, p. 662-673Article in journal (Refereed)
    Abstract [en]

    Current prevention strategies for low-trauma fractures amongst older persons depend on the notions that fractures are mainly caused by osteoporosis (pathophysiology), that patients at high risk can be identified (screening) and that the risk is amenable to bone-targeted pharmacotherapy (treatment). However, all these three notions can be disputed. PathophysiologyMost fracture patients have fallen, but actually do not have osteoporosis. A high likelihood of falling, in turn, is attributable to an ageing-related decline in physical functioning and general frailty. ScreeningCurrently available fracture risk prediction strategies including bone densitometry and multifactorial prediction tools are unable to identify a large proportion of patients who will sustain a fracture, whereas many of those with a high fracture risk score will not sustain a fracture. TreatmentThe evidence for the viability of bone-targeted pharmacotherapy in preventing hip fracture and other clinical fragility fractures is mainly limited to women aged 65-80years with osteoporosis, whereas the proof of hip fracture-preventing efficacy in women over 80years of age and in men at all ages is meagre or absent. Further, the antihip fracture efficacy shown in clinical trials is absent in real-life studies. Many drugs for the treatment of osteoporosis have also been associated with increased risks of serious adverse events. There are also considerable uncertainties related to the efficacy of drug therapy in preventing clinical vertebral fractures, whereas the efficacy for preventing other fractures (relative risk reductions of 20-25%) remains moderate, particularly in terms of the low absolute risk reduction in fractures with this treatment.

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  • 348.
    Johansson, Joel
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Björnsson, Bergthor
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Ignatova, Simone
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Sandström, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Ekstedt, Mattias
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Littoral cell angioma in a patient with Crohn's disease.2015In: Case Reports in Gastrointestinal Medicine, ISSN 2090-6528, E-ISSN 2090-6536, Vol. 2015, p. 1-4, article id 474969Article in journal (Refereed)
    Abstract [en]

    Littoral cell angioma is a rare vascular tumor of the spleen. The pathogenesis is unknown but the lesion is associated with several malignancies and immunological disorders. The diagnosis requires histopathological examination. The malignant potential of this lesion is unknown, which is why splenectomy is recommend for all cases. Symptomatic cases generally suffer from hypersplenism and pyrexia. A previously healthy 20-year-old female was diagnosed with colonic Crohn's disease; as part of the work-up a magnetic resonance enterography was performed which showed multiple signal changes of the spleen. The patient reported chronic abdominal pain in the left upper quadrant, malaise, and fever. The unknown splenic lesions prompted a laparoscopic splenectomy; pathology revealed a littoral cell angioma. The abdominal pain and malaise remitted but the fever persisted one year despite adequate treatment of the patient's Crohn's disease. Littoral cell angioma is associated with immune-dysregulation including Crohn's disease with several reported cases. Signs and symptoms of hypersplenism and splenic lesions on imaging should raise suspicion of littoral cell angioma in patients with Crohn's disease. Magnetic resonance enterography to assess disease severity in Crohn's disease may provide an opportunity to study the prevalence and natural history of this rare splenic tumor.

  • 349.
    Johansson, Torsten
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    PTH 1-34 (teriparatide) may not improve healing in proximal humerus fractures A randomized, controlled study of 40 patients2016In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 87, no 1, p. 79-82Article in journal (Refereed)
    Abstract [en]

    Background and purpose - There is solid evidence from animal experiments that parathyroid hormone (PTH) improves fracture healing. So far, only 3 papers on PTH and fracture repair in humans have been published. They suggest that PTH may enhance fracture healing, but the results do not appear to justify specific clinical recommendations. This study was carried out to determine whether teriparatide enhances fracture healing of proximal humerus fractures. Patients and methods - 40 post-menopausal women with a proximal humerus fracture were randomized to either daily injections with 20 mu g teriparatide (PTH 1-34 (Forteo)) for 4 weeks or control treatment. At randomization, the patients were asked to assess how their pain at rest and during activity (visual analog scale (VAS)) and also function (DASH score) had been prior to the fracture. At 7 weeks and again at 3 months, their current state was assessed and the tests were repeated, including radiographs. 2 radiologists performed a blind qualitative scoring of the callus at 7 weeks. Callus formation was arbitrarily classified as normal or better. Results - 39 patients completed the follow-up. The radiographic assessment showed a correct correlation, better in the teriparatide group and normal in the control group, in 21 of the 39 cases. There were no statistically significant differences in pain, in use of strong analgesics, or in function between the groups at the follow-up examinations. Interpretation - There were no radiographic signs of enhanced healing or improved clinical results in the group treated with teriparatide

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  • 350.
    Johansson, Torsten
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping. Department Orthopaed, Sweden.
    Lindblad, Maria
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Norrköping.
    Bladh, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Josefsson, Ann
    Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping. Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Sydsjö, Gunilla
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Incidence of Perthes disease in children born between 1973 and 1993: A Swedish nationwide cohort study of 2.1 million individuals2017In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 88, no 1, p. 96-100Article in journal (Refereed)
    Abstract [en]

    Background and purpose - The incidence of Perthes disease as reported in the literature varies widely between and within countries. The etiology of the disease is still unknown. Both environmental and genetic factors have been suggested to play a part in either causing the disease or increasing the susceptibility of an individual. We determined the incidence of Perthes disease in Sweden and investigated possible relationships to parental socioeconomic status, ethnicity, marital status, mothers age when giving birth, parity, number of siblings, and smoking habits. Patients and methods - Six Swedish population-based registers were used, together covering all children born in Sweden from 1973 through 1993. Results - The incidence of Perthes disease in Sweden was 9.3 per 100,000 subjects. The ratio between boys and girls was 3.1:1. The educational level of the father and the mother of a child with Perthes disease was lower than in the controls. The incidence was lower when the fathers were in the highest income bracket (above the 90(th) percentile). A higher proportion of parents of Nordic lineage had children with Perthes disease than parental pairs with one or both who were not of such lineage. Interpretation - This study confirms that there is an association between the incidence of Perthes disease and the socioeconomic status of the parents.

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