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  • 251.
    Gimm, Oliver
    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 Surgery in Linköping.
    Duh, Quan-Yang
    Univ Calif San Francisco, CA USA.
    Challenges of training in adrenal surgery2019In: Gland surgery, ISSN 2227-684X, E-ISSN 2227-8575, Vol. 8, p. S3-S9Article, review/survey (Refereed)
    Abstract [en]

    While adrenal tumors are common, adrenalectomy is rather uncommon. This is one reason for the many challenges regarding the training of adrenal surgery. Here we focus on issues that are most pertinent regarding training of the young surgeons performing adrenalectomy. Due to the very limited literature, what is presented is mainly based on personal experience and/or from the literature published for other surgical operations and subspecialties. The discussed challenges include indications for surgery, surgical approaches and extent, and intraoperative complications. With advances in adrenal surgery, we expect some old challenges to be resolved, and some new challenges to arise. These challenges will be faced in order to continue to help our younger trainee acquire the knowledge and skills to best care for our patients with adrenal diseases.

  • 252.
    Ginstman, Charlotte
    et al.
    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.
    Frisk, Jessica
    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 Norrköping.
    Carlsson, Björn
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology.
    Ärlemalm, A.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology.
    Hägg, Staffan
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology. Futurum, Jönköping, Sweden.
    Brynhildsen, Jan
    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.
    Plasma concentrations of etonogestrel in women using oral desogestrel before and after Roux-en-Y gastric bypass surgery: a pharmacokinetic study2019In: British Journal of Obstetrics and Gynecology, ISSN 1470-0328, E-ISSN 1471-0528, Vol. 126, no 4, p. 486-492Article in journal (Refereed)
    Abstract [en]

    Objective

    To investigate whether Roux‐en‐Y gastric bypass (RYGB) affects oral desogestrel (etonogestrel) pharmacokinetics.

    Design

    Single centre, open label, phase‐2 pharmacokinetic study.

    Setting

    University hospital of Linköping, Sweden.

    Population

    Fourteen women with planned RYGB surgery were included; nine women aged 18–45 years using 75 micrograms desogestrel completed the study.

    Methods

    Steady‐state etonogestrel pharmacokinetic (PK) parameters were measured on three occasions for each individual (at 8 ± 6 weeks before surgery, and at 12 ± 2 and 52 ± 2 weeks after surgery). Each patient served as her own control. On each occasion, serum samples were collected during a 24‐hour period and etonogestrel concentrations were determined with ultra‐performance liquid chromatography/tandem mass spectrometry.

    Main outcome measures

    Area under the plasma concentration time curve of etonogestrel (AUC0–24 hours).

    Results

    All women had significant postoperative weight loss. There were no significant differences in AUC0–24 hours, terminal half‐lives (t½), time to peak serum concentrations (Tmax), or apparent oral clearances of etonogestrel (CLoral) before and after gastric bypass surgery on any occasion. Peak serum concentrations (Cmax) increased after 52 ± 2 weeks compared with preoperative values (0.817 ng/ml versus 0.590 ng/ml, P = 0.024).

    Conclusion

    To our knowledge, this is the first study to investigate the effects on desogestrel pharmacokinetics after RYGB. This study did not reveal any clinically significant changes in etonogestrel pharmacokinetics, suggesting that oral desogestrel may be used by women after RYGB surgery. The sample size was limited, however, and therefore the results should be interpreted cautiously.

  • 253.
    Ginstman, Charlotte
    et al.
    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 Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Frisk, Jessica
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping. Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Ottosson, Johan
    University of Örebro, Sweden.
    Brynhildsen, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Contraceptive Use Before and After Gastric Bypass: a Questionnaire Study2015In: Obesity Surgery, ISSN 0960-8923, E-ISSN 1708-0428, Vol. 25, no 11, p. 2066-2070Article in journal (Refereed)
    Abstract [en]

    At present, women are recommended to avoid pregnancy 12-18 months after bariatric surgery. Our aim in this study was to describe patterns of contraceptive use before and after gastric bypass in Sweden, and to describe the contraceptive counseling given preoperatively to women undergoing gastric bypass. In October 2012, a questionnaire was sent to 1000 Swedish women who all had undergone gastric bypass during 2010. The women had been included in the Scandinavian Obesity Surgery Register at time of surgery. The main outcome measures were patterns of use of contraception before and after bariatric surgery. The response rate was 57 %. The most commonly used contraceptive methods were intrauterine devices, 29 % preoperatively and 26 % postoperatively even though there was a postoperative switch from the copper intrauterine device to the levonorgestrel intrauterine system. Thirty percent did not use any contraceptive during the first 12 months after surgery. Sixty percent of the responders were aware of the recommendations to avoid pregnancy after surgery. Many women who undergo bariatric surgery are not using any contraceptive method despite the recommendation that they should avoid pregnancy for at least 12 months. There is a great need to improve contraceptive counseling for this growing group of women.

  • 254.
    Gnosa, Sebastian
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Capodanno, Alessandra
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Dahl Ejby Jensen, Lasse
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology.
    Sun, Xiao-Feng
    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.
    AEG-1 knockdown in colon cancer cell lines inhibits radiation-enhanced migration and invasion in vitro and in a novel in vivo zebrafish model2016In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 7, no 49, p. 81634-81644Article in journal (Refereed)
    Abstract [en]

    Background Radiotherapy is a well-established anti-cancer treatment. Although radiotherapy has been shown to significantly decrease the local relapse in rectal cancer patients, the rate of distant metastasis is still very high. Several studies have shown that radiation enhances migration and invasion both in vitro and in vivo. The aim of this study was to evaluate whether AEG-1 is involved in radiation-enhanced migration and invasion in vitro and in a novel in vivo zebrafish model.

    Materials and Methods We evaluated the involvement of AEG-1 in migration and invasion and radiation-enhanced migration and invasion by Boyden chamber assay in three colon cancer cell lines and respective AEG-1 knockdown cell lines. Furthermore, we injected the cells in zebrafish embryos and evaluated the amount of disseminated cells into the tail.

    Results Migration and invasion was decreased in all the AEG-1 knockdown cell lines. Furthermore, radiation enhanced migration and invasion, while AEG-1 knockdown could abolish this effect. The results from the zebrafish model confirmed the results obtained in vitro. MMP-9 secretion and expression were decreased in AEG-1 knockdown cells.

    Conclusion Our results demonstrate that AEG-1 knockdown inhibits migration and invasion, as well as radiation-enhanced migration and invasion. We speculate that this is done via the downregulation of the intrinsic or radiation-enhanced MMP-9 expression. The zebrafish model can be used to study early events in radiation-enhanced invasion.

  • 255.
    Gnosa, Sebastian
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Ticha, Ivana
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Institute of Pathology, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic.
    Haapaniemi, Staffan
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping.
    Sun, Xiao-Feng
    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.
    MTDH genetic variants in colorectal cancer patients2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6Article in journal (Refereed)
    Abstract [en]

    Colorectal cancer (CRC) is the second most common cancer worldwide and accounts for around 8.5% of all cancer related death. The colorectal carcinogenesis is a complex process of genetic alterations. For better prognosis it is very important to understand the composition of genetic alterations in a tumor. Astrocyte elevated gene-1 (AEG-1) has been shown to be overexpressed in CRC and had prognostic significance. The aim of this study was to determine the frequency and the spectrum of MTDH variants, and their relationship to clinicopathological variables in CRC patients. The study included tumors from 356 unselected CRC patients. Mutation analysis of the MTDH gene, including coding region and adjacent intronic sequences, was performed by direct DNA sequencing. We detected 42 intronic variants, whereby 25 were novel. Furthermore, we found eight exonic variants of which four, one missense (c.977C>G) and three frameshift mutations (c.533delA, c.1731delA, c.1340dupA), were novel. In silico prediction analyses revealed that four variants c.232G>T, c.533delA, c.1340dupA and c.1731delA were deleterious. There were no correlations between the MTDH variants and tumor stage, differentiation or patient survival. The detection of pathogenic mutations and alterations in functional protein domains suggest their involvement in tumorigenesis, although none of the variants had prognostic potential.

  • 256.
    Gonzalez, Javier Martin
    et al.
    Univ Copenhagen, Denmark.
    Baudet, Aurelie
    Lund Univ, Sweden.
    Abelechian, Sahar
    Univ Copenhagen, Denmark.
    Bonderup, Kasper
    Univ Copenhagen, Denmark.
    dAltri, Teresa
    Univ Copenhagen, Denmark.
    Porse, Bo
    Univ Copenhagen, Denmark.
    Brakebusch, Cord
    Univ Copenhagen, Denmark.
    Juliusson, Gunnar
    Lund Univ, Sweden; Skane Univ Hosp, 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. Lund Univ, Sweden.
    A new genetic tool to improve immune-compromised mouse models: Derivation and CRISPR/Cas9-mediated targeting of NRG embryonic stem cell lines2018In: Genesis, ISSN 1526-954X, E-ISSN 1526-968X, Vol. 56, no 9, article id e23238Article in journal (Refereed)
    Abstract [en]

    Development of human hematopoietic stem cells and differentiation of embryonic stem (ES) cells/induced pluripotent stem (iPS) cells to hematopoietic stem cells are poorly understood. NOD (Non-obese diabetic)-derived mouse strains, such as NSG (NOD-Scid-il2Rg) or NRG (NOD-Rag1-il2Rg), are the best available models for studying the function of fetal and adult human hematopoietic cells as well as ES/iPS cell-derived hematopoietic stem cells. Unfortunately, engraftment of human hematopoietic stem cells is very variable in these models. Introduction of additional permissive mutations into these complex genetic backgrounds of the NRG/NSG mice by natural breeding is a very demanding task in terms of time and resources. Specifically, since the genetic elements defining the NSG/NRG phenotypes have not yet been fully characterized, intense backcrossing is required to ensure transmission of the full phenotype. Here we describe the derivation of embryonic stem cell (ESC) lines from NRG pre-implantation embryos generated by in vitro fertilization followed by the CRISPR/CAS9 targeting of the Gata-2 locus. After injection into morula stage embryos, cells from three tested lines gave rise to chimeric adult mice showing high contribution of the ESCs (70%-100%), assessed by coat color. Moreover, these lines have been successfully targeted using Cas9/CRISPR technology, and the mutant cells have been shown to remain germ line competent. Therefore, these new NRG ESC lines combined with genome editing nucleases bring a powerful genetic tool that facilitates the generation of new NOD-based mouse models with the aim to improve the existing xenograft models.

  • 257.
    Gopinath, Madhumala
    et al.
    Department of Allied Health Sciences, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai-603103, India.
    Di Liddo, Rosa
    Department of Pharmacology and Pharmaceutical Sciences, University of Padova, Padova, Italy.
    Marotta, Francesco
    ReGenera RandD International for Aging Intervention, Milano-Beijing, Italy-China, VCC Preventive Medical Promotion Foundation, Beijing, China.
    Murugesan, Ramachandran
    Department of Allied Health Sciences, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai-603103, India.
    Banerjee, Antara
    Department of Allied Health Sciences, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai-603103, India.
    Sriramulu, Sushmitha
    Department of Allied Health Sciences, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai-603103, India.
    Jothimani, Ganesan
    Department of Allied Health Sciences, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai-603103, India.
    Subramaniam, Vimala Devi
    Department of Allied Health Sciences, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai-603103, India.
    Narasimhan, Srinivasan
    Department of Allied Health Sciences, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai-603103, India.
    Priya K, Swarna
    Department of Gynecology and Pediatrics, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai-603103, India.
    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.
    Pathak, Surajit
    Department of Allied Health Sciences, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai-603103, India.
    Role of Hippo Pathway Effector Tafazzin Protein in Maintaining Stemness of Umbilical Cord-Derived Mesenchymal Stem Cells (UC-MSC)2018In: International Journal of Hematology-Oncology and Stem Cell Research, ISSN 2008-3009, E-ISSN 2008-2207, Vol. 12, no 2, p. 153-165Article, review/survey (Refereed)
    Abstract [en]

    Tafazzin (TAZ) protein has been upregulated in various types of human cancers, although the basis for elevation is uncertain, it has been made definite that the effect of mutation in the hippo pathway, particularly when it is switched off, considerably activates tafazzin transcriptionally and thus this results in tissue or tumor overgrowth. Recent perceptions into the activity of tafazzin, have ascribed to it, a role as stem cell factor in mouse mesenchymal and as well as in neural stem cells. Being a downstream molecule in Hippo signalling, phosphorylation or dephosphorylation of tafazzin gene regulates its transcriptional activity and the stemness of mesenchymal stem cells. Commonly, extracellular matrix controls the stem cell fate commitment and perhaps tafazzin controls stemness through altering the extra cellular matrix. Extracellular matrix is generally made up of prime proteoglycans and the fate stabilization of the resulting lineages is surveilled by engineering these glycans. Tafazzin degradation and addition of proteoglycans affect physical attributes of the extracellular matrix that drives cell differentiation into various lineages. Thus, tafazzin along with major glycans present in the extracellular matrix is involved in imparting stemness. However, there are incoherent molecular events, wherein both tafazzin and the extracellular matrix components, together either activate or inhibit differentiation of stem cells. This review discusses about the role of tafazzin oncoprotein as a stemness factor.

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  • 258.
    Gothlin Eremo, Anna
    et al.
    University of Örebro, Sweden.
    Tina, Elisabet
    Örebro University Hospital, Sweden.
    Wegman, Pia
    Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Stål, Olle
    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.
    Fransen, Karin
    University of Örebro, Sweden.
    Fornander, Tommy
    Karolinska University Hospital, Sweden; Regional Cancer Centre Stockholm Gotland, Sweden.
    Wingren, Sten
    University of Örebro, Sweden.
    HER4 tumor expression in breast cancer patients randomized to treatment with or without tamoxifen2015In: International Journal of Oncology, ISSN 1019-6439, Vol. 47, no 4, p. 1311-1320Article in journal (Refereed)
    Abstract [en]

    The human epidermal growth factor receptor (HER) 4 is a relative of HER2 and has been associated to endocrine breast cancer and prediction of tamoxifen response. In addition to PI3K/Akt and MAPK pathway activation, ligand binding to HER4 triggers proteolytic cleavage and release of an intracellular receptor domain (4ICD) with signaling properties. The aim of the present study was to analyze HER4 protein expression and intracellular localization in breast cancer tissue from patients randomized to treatment with or without adjuvant tamoxifen. To investigate HER4 expression and localization in response to estradiol (E2) and 4-hydroxytamoxifen (4-OHT) exposure, we also performed in vitro studies. Cytoplasmic, nuclear and membrane expression of HER4 protein was evaluated by immunohistochemical staining in tumor tissue from 912 breast cancer patients. Three different breast epithelia cancer cell lines were exposed to E2 and 4-OHT and mRNA expression was analyzed using qPCR. Further, nuclear and cytoplasmic proteins were separated and analyzed with western blotting. We found an association between nuclear HER4 protein expression and ER-positivity (P=0.004). Furthermore, significant association was found between cytoplasmic HER4 and ER-negativity (Pless than0.0005), PgR-negativity (Pless than0.0005), tumor size greater than20 mm (P=0.001) and HER2-negativity (P=0.008). However, no overall significance of HER4 on recurrence-free survival was found. After E2 exposure, HER4 mRNA and protein expression had decreased in two cell lines in vitro yet no changes in nuclear or cytoplasmic protein fractions were seen. In conclusion, nuclear HER4 seem to be co-located with ER, however, we did not find support for overall HER4 expression in independently predicting response of tamoxifen treatment. The possible influence of separate isoforms was not tested and future studies may further evaluate HER4 significance.

  • 259.
    Green, Henrik
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Division of Gene Technology, Royal Institute of Technology, Solna, Sweden/ Royal Institute Technology, Sweden; National Board Forens Med, Department Forens Genet and Forens Toxicol, Linkoping, Sweden.
    Hasmats, Johanna
    Royal Institute Technology, Sweden.
    Kupershmidt, Ilya
    Royal Institute Technology, Sweden; NextBio, CA USA.
    Edsgard, Daniel
    Royal Institute Technology, Sweden.
    de Petris, Luigi
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Lewensohn, Rolf
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Blackhall, Fiona
    Christie Hospital, England; University of Manchester, England.
    Vikingsson, Svante
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Besse, Benjamin
    University of Paris 11, France.
    Lindgren, Andrea
    Linköping University, Department of Medical and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Respiratory Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Branden, Eva
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Koyi, Hirsh
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Peterson, Curt
    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 Oncology.
    Lundeberg, Joakim
    Royal Institute Technology, Sweden.
    Using Whole-Exome Sequencing to Identify Genetic Markers for Carboplatin and Gemcitabine-Induced Toxicities2016In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 22, no 2, p. 366-373Article in journal (Refereed)
    Abstract [en]

    Purpose: Chemotherapies are associated with significant interindividual variability in therapeutic effect and adverse drug reactions. In lung cancer, the use of gemcitabine and carboplatin induces grade 3 or 4 myelosuppression in about a quarter of the patients, while an equal fraction of patients is basically unaffected in terms of myelosuppressive side effects. We therefore set out to identify genetic markers for gemcitabine/carboplatin-induced myelosuppression. Experimental Design: We exome sequenced 32 patients that suffered extremely high neutropenia and thrombocytopenia (grade 3 or 4 after first chemotherapy cycle) or were virtually unaffected (grade 0 or 1). The genetic differences/polymorphism between the groups were compared using six different bioinformatics strategies: (i) whole-exome nonsynonymous single-nucleotide variants association analysis, (ii) deviation from Hardy-Weinberg equilibrium, (iii) analysis of genes selected by a priori biologic knowledge, (iv) analysis of genes selected from gene expression meta-analysis of toxicity datasets, (v) Ingenuity Pathway Analysis, and (vi) FunCoup network enrichment analysis. Results: A total of 53 genetic variants that differed among these groups were validated in an additional 291 patients and were correlated to the patients myelosuppression. In the validation, we identified rs1453542 in OR4D6 (P = 0.0008; OR, 5.2; 95% CI, 1.8-18) as a marker for gemcitabine/carboplatin-induced neutropenia and rs5925720 in DDX53 (P = 0.0015; OR, 0.36; 95% CI, 0.17-0.71) as a marker for thrombocytopenia. Patients homozygous for the minor allele of rs1453542 had a higher risk of neutropenia, and for rs5925720 the minor allele was associated with a lower risk for thrombocytopenia. Conclusions: We have identified two new genetic markers with the potential to predict myelosuppression induced by gemcitabine/ carboplatin chemotherapy. (C)2015 AACR.

  • 260.
    Gregers, Jannie
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. University of Copenhagen Hospital, Denmark.
    Green, Henrik
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. KTH Royal Institute Technology, Sweden; National Board Forens Med, Department Forens Genet and Forens Toxicol, Linkoping, Sweden.
    Christensen, I. J.
    Rigshosp, Denmark.
    Dalhoff, K.
    Bispebjerg Hospital, Denmark.
    Schroeder, H.
    University Hospital Skejby, Denmark.
    Carlsen, N.
    Odense University Hospital, Denmark.
    Rosthoej, S.
    University Hospital Aalborg, Denmark.
    Lausen, B.
    University of Copenhagen, Denmark.
    Schmiegelow, K.
    University of Copenhagen, Denmark; University of Copenhagen, Denmark.
    Peterson, Curt
    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 Oncology.
    Polymorphisms in the ABCB1 gene and effect on outcome and toxicity in childhood acute lymphoblastic leukemia2015In: The Pharmacogenomics Journal, ISSN 1470-269X, E-ISSN 1473-1150, Vol. 15, no 4, p. 372-379Article in journal (Refereed)
    Abstract [en]

    The membrane transporter P-glycoprotein, encoded by the ABCB1 gene, influences the pharmacokinetics of anti-cancer drugs. We hypothesized that variants of ABCB1 affect outcome and toxicity in childhood acute lymphoblastic leukemia (ALL). We studied 522 Danish children with ALL, 93% of all those eligible. Risk of relapse was increased 2.9-fold for patients with the 1199GA variant versus 1199GG (P = 0.001), and reduced 61% and 40%, respectively, for patients with the 3435CT or 3435TT variants versus 3435CC (overall P = 0.02). The degree of bone marrow toxicity during doxorubicin, vincristine and prednisolone induction therapy was more prominent in patients with 3435TT variant versus 3435CT/3435CC (P = 0.01/P less than 0.0001). We observed more liver toxicity after high-dose methotrexate in patients with 3435CC variant versus 3435CT/TT ( P = 0.03). In conclusion, there is a statistically significant association between ABCB1 polymorphisms, efficacy and toxicity in the treatment of ALL, and ABCB1 1199G greater than A may be a new possible predictive marker for outcome in childhood ALL.

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  • 261.
    Gunnarsson, N.
    et al.
    Umeå University, Sweden.
    Hoglund, M.
    University Hospital, Uppsala, Sweden.
    Stenke, L.
    Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    Sandin, F.
    Regional Cancer Centre, Uppsala, Sweden.
    Bjorkholm, M.
    Karolinska University Hospital, Sweden; Karolinska Institute, 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.
    Lambe, M.
    Regional Cancer Centre, Uppsala, Sweden; Karolinska Institute, Sweden.
    Markevarn, B.
    University Hospital, Umeå, Sweden.
    Olsson-Stromberg, U.
    University Hospital, Uppsala, Sweden; University Hospital, Uppsala, Sweden.
    Wadenvik, H.
    Sahlgrens University Hospital, Sweden.
    Richter, J.
    Skåne University Hospital, Sweden.
    Sjalander, A.
    Umeå University, Sweden.
    No increased prevalence of malignancies among first-degree relatives of 800 patients with chronic myeloid leukemia: a population-based study in Sweden2017In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 31, no 8, p. 1825-1827Article in journal (Other academic)
    Abstract [en]

    n/a

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  • 262.
    Gunnarsson, N.
    et al.
    Umeå University, Sweden.
    Höglund, M.
    University of Uppsala Hospital, Sweden.
    Stenke, L.
    Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    Wallberg-Jonsson, S.
    Umeå University, Sweden.
    Sandin, F.
    Regional Cancer Centre, Sweden.
    Björkholm, M.
    Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    Dreimane, Arta
    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 Haematology.
    Lambe, M.
    Regional Cancer Centre, Sweden; Karolinska Institute, Sweden.
    Markevarn, B.
    University of Umeå Hospital, Sweden.
    Olsson-Stromberg, U.
    University of Uppsala Hospital, Sweden.
    Wadenvik, H.
    Sahlgrens University Hospital, Sweden.
    Richter, J.
    Skåne University Hospital, Sweden.
    Sjalander, A.
    Umeå University, Sweden.
    Increased prevalence of prior malignancies and autoimmune diseases in patients diagnosed with chronic myeloid leukemia2016In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 30, no 7, p. 1562-1567Article in journal (Refereed)
    Abstract [en]

    We recently reported an increased incidence of second malignancies in chronic myeloid leukemia (CML) patients treated with tyrosine kinase inhibitors (TKI). To elucidate whether this increase may be linked, not to TKI but rather to a hereditary or acquired susceptibility to develop cancer, we estimated the prevalence of malignancies, autoimmune disease (AD) and chronic inflammatory disease (CID) in CML patients prior to their CML diagnosis. Nationwide population-based registers were used to identify patients diagnosed with CML in Sweden 2002-2012 and to estimate the prevalence of other malignancies, AD and CID prior to their CML diagnosis. For each patient with CML, five matched controls were selected from the general population. Conditional logistic regression was used to calculate odds ratios (OR). Nine hundred and eighty-four CML patients were assessed, representing more than 45 000 person-years of follow-up. Compared with matched controls, the prevalence of prior malignancies and AD was elevated in CML patients: OR 1.47 (95% confidence interval (CI) 1.20-1.82) and 1.55 (95% CI 1.21-1.98), respectively. No associations were detected between CML and previous CID. An increased prevalence of other malignancies and AD prior to the diagnosis of CML suggest that a hereditary or acquired predisposition to cancer and/or autoimmunity is involved in the pathogenesis of CML.

  • 263.
    Gunnarsson, Niklas
    et al.
    Umeå University, Sweden.
    Stenke, Leif
    Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    Hoglund, Martin
    University of Uppsala Hospital, Sweden; University of Uppsala Hospital, Sweden.
    Sandin, Fredrik
    Regional Cancer Centre, Sweden.
    Bjorkholm, Magnus
    Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    Dreimane, Arta
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Haematology. Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Lambe, Mats
    Regional Cancer Centre, Sweden; Karolinska Institute, Sweden.
    Markevarn, Berit
    Umeå University Hospital, Sweden.
    Olsson-Stromberg, Ulla
    University of Uppsala Hospital, Sweden; University of Uppsala Hospital, Sweden.
    Richter, Johan
    Skåne University Hospital, Sweden.
    Wadenvik, Hans
    Sahlgrens University Hospital, Sweden.
    Wallvik, Jonas
    Umeå University, Sweden.
    Sjalander, Anders
    Umeå University, Sweden.
    Second malignancies following treatment of chronic myeloid leukaemia in the tyrosine kinase inhibitor era2015In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 169, no 5, p. 683-688Article in journal (Refereed)
    Abstract [en]

    Given that tyrosine kinase inhibitors (TKIs) have dramatically improved the survival of patients with chronic myeloid leukaemia (CML), we were interested in examining the possible risk of long-term adverse events, such as the emergence of other neoplasms. Therefore, we studied the development of second malignancies in 868 patients diagnosed with CML between 2002 and 2011 using the Swedish CML register, cross-linked to the Swedish Cancer register. With a median follow-up of 37 (range 0-99)years, 65 (75%) patients developed 75 second malignancies (non-haematological), 52 of which were of the invasive type. Compared to expected rates in the background population, the risk of second malignancies was higher in the CML cohort, with a standardized incidence ratio (SIR) of 152 (95% CI 113-199). The SIR before and after the second year following diagnosis of CML was 158 and 147, respectively. Among specific cancer types, gastrointestinal and nose and throat cancer were significantly increased. Founded on a population-based material, our results indicate that CML patients treated in the TKI era are at an increased risk of developing a second malignancy, with indications that this risk may more likely be linked to CML itself rather than to the TKI treatment.

  • 264.
    Gustafsson, Agneta
    et al.
    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.
    Karlsson, Henrik
    Kalmar County Hospital, Sweden.
    Nilsson, Kerstin A.
    Geijer, Hakan
    Örebro University Hospital, Sweden.
    Olsson, Anna
    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).
    A visual grading study for different administered activity levels in bone scintigraphy2015In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 35, no 3, p. 231-236Article in journal (Refereed)
    Abstract [en]

    IntroductionThe aim of the study is to assess the administered activity levels versus visual-based image quality using visual grading regression (VGR) including an assessment of the newly stated image criteria for whole-body bone scintigraphy. Materials and methodsA total of 90 patients was included and grouped in three levels of administered activity: 400, 500 and 600 MBq. Six clinical image criteria regarding image quality was formulated by experienced nuclear medicine physicians. Visual grading was performed in all images, where three physicians rated the fulfilment of the image criteria on a four-step ordinal scale. The results were analysed using VGR. A count analysis was also made where the total number of counts in both views was registered. ResultsThe administered activity of 600 MBq gives significantly better image quality than 400 MBq in five of six criteria (Pless than005). Comparing the administered activity of 600 MBq to 500 MBq, four criteria of six show significantly better image quality (Pless than005). The administered activity of 500 MBq gives no significantly better image quality than 400 Mbq (Pless than005). The count analysis shows that none of the three levels of administrated activity fulfil the recommendations by the EANM. ConclusionThere was a significant improvement in perceived image quality using an activity level of 600 MBq compared to lower activity levels in whole-body bone scintigraphy for the gamma camera equipment end set-up used in this study. This type of visual-based grading study seems to be a valuable tool and easy to implement in the clinical environment.

  • 265.
    Gustafsson, Anna
    et al.
    Lund University, Sweden.
    Schilcher, Jörg
    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.
    Grassi, Lorenzo
    Lund 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.
    Isaksson, Hanna
    Lund University, Sweden.
    Strains caused by daily loading might be responsible for delayed healing of an incomplete atypical femoral fracture2016In: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 88, p. 125-130Article in journal (Refereed)
    Abstract [en]

    Atypical femoral fractures are insufficiency fractures in the lateral femoral diaphysis or subtrochanteric region that mainly affect older patients on bisphosphonate therapy. Delayed healing is often seen in patients with incomplete fractures (cracks), and histology of bone biopsies shows mainly necrotic material inside the crack. We hypothesized that the magnitude of the strains produced in the soft tissue inside the crack during normal walk exceeds the limit for new bone formation, and thereby inhibit healink. A patient specific finite element model was developed, based on clinical CT images and high resolution CT images of a biopsy from the crack site. Strain distributions in the femur and inside the crack were calculated for load cases representing normal walk. The models predicted large strains inside the crack, with strain levels above 10% in more than three quarters of the crack volume. According to two different tissue differentiation theories, bone would only form in less than 1-5% cif the crack volume. This can explain the impaired healing generally seen in incomplete atypical fractures. Furthermore, the microgeometry of the crack highly influenced the strain distributions. Hence, a realistic microgeometry needs to be considered when modeling the crack. Histology of the biopsy showed signs of remodeling in the bone tissue adjacent to the fracture line, while the crack itself contained mainly necrotic material and signs of healing only in portions that seemed to have been widened by resorption. In conclusion, the poor healing capacity of incomplete atypical femoral fractures can be explained by biomechanical factors, and daily low impact activities are enough to cause strain magnitudes that prohibit bone formation. (C) 2016 Elsevier Inc. All rights reserved.

  • 266.
    Gustafsson, E.
    et al.
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    Litström, Emma
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    Berterö, Carina
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    Drott, Jenny
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    Reliability testing of oxaliplatin-associated neurotoxicity questionnaire (OANQ), a pilot study2016In: Supportive Care in Cancer, ISSN 0941-4355, E-ISSN 1433-7339, Vol. 24, no 2, p. 747-754Article in journal (Refereed)
    Abstract [en]

    PURPOSE:

    The purpose of this study was to test the reliability of the Swedish version of the Oxaliplatin-Associated Neurotoxicity Questionnaire (OANQ) administrated throughout a self-reported mobile phone-based system, a pilot study.

    METHODS:

    Twenty-three patients from two university hospitals and two regional hospitals who had been treated with oxaliplatin were included through purposive sampling between autumn 2013 to autumn 2014. A test-retest was performed through a mobile phone-based system, with a recall period of 1 h to determine the reliability of the questionnaire.

    RESULTS:

    Internal consistency was strong for the three domains of the scale (α > 0.840). The statistical analyses for the test-retest indicated that the OANQ was stable. Intraclass correlation (ICC) for symptom items and effect on daily activities items showed an overall excellent reproducibility at 69 and 83 %, respectively. The weighted kappa for symptom items and daily activities items showed an overall almost perfect agreement at 59 and 52 %, respectively. A paired samples t test did not reveal any significant differences between the two measures.

    CONCLUSIONS:

    The OANQ was tested and considered a reliable assessment for capturing the oxaliplatin-induced peripheral neurotoxicity (OIPN) in patients receiving oxaliplatin. However, further reliability testing of the OANQ is needed.

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  • 267.
    Gustafsson, Elin
    et al.
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Litström, Emma
    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.
    Berterö, Carina
    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.
    Reliability testing of Oxaliplatin-Associated Neurotoxicity Questionnaire (OANQ)2015Conference paper (Refereed)
  • 268.
    Hager, Jakob
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping.
    Henriksson, Martin
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences.
    Carlsson, Per
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery. Linköping University, Faculty of Medicine and Health Sciences.
    Lundgren, Fredrik
    Department of Surgery, Kalmar County Hospital, Kalmar, Sweden.
    Revisiting the cost-effectiveness of screening 65-year-old men for abdominal aortic aneurysm based on data from an implemented screening programme.2017In: International Journal of Angiology, ISSN 0392-9590, E-ISSN 1827-1839, Vol. 36, no 6, p. 517-525Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Health economic analyses based on randomized trials have shown that screening for abdominal aortic aneurysm (AAA) cost-effectively decreases AAA-related, as well as all- cause mortality. However, follow-up from implemented screening programmes now reveal substantially changed conditions in terms of prevalence, attendance rate, costs and mortality after intervention. Our aim was to evaluate whether screening for AAA among 65-year-old men is cost-effective based on contemporary data on prevalence and attendance rates from an ongoing AAA screening programme.

    METHODS: A decision-analytic model, previously used to analyse the cost-effectiveness of an AAA screening programme prior to implementation in clinical practice, was updated using data collected from an implemented screening programme as well as data from contemporary published data and the Swedish register for vascular surgery (Swedvasc).

    RESULTS: The base-case analysis showed that the cost per life-year gained and quality-adjusted life year (QALY) gained were €4832 and €6325, respectively. Based on conventional threshold values of cost-effectiveness, the probability of screening being cost-effective was high.

    CONCLUSION: Despite the reduction of AAA-prevalence and changes in AAA-management over time, screening 65-year-old men for AAA still appears to yield health outcomes at a cost below conventional thresholds of cost-effectiveness.

  • 269.
    Hagg, Mary
    et al.
    Hudiksvall Hospital, Sweden; Uppsala University, Sweden.
    Tibbling, Lita
    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.
    Effect of IQoro (R) training on impaired postural control and oropharyngeal motor function in patients with dysphagia after stroke2016In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 136, no 7, p. 742-748Article in journal (Refereed)
    Abstract [en]

    Conclusion All patients with dysphagia after stroke have impaired postural control. IQoro (R) screen (IQS) training gives a significant and lasting improvement of postural control running parallel with significant improvement of oropharyngeal motor dysfunction (OPMD). Objectives The present investigation aimed at studying the frequency of impaired postural control in patients with stroke-related dysphagia and if IQS training has any effect on impaired postural control in parallel with effect on OPMD. Method A prospective clinical study was carried out with 26 adult patients with stroke-related dysphagia. The training effect was compared between patients consecutively investigated at two different time periods, the first period with 15 patients included in the study more than half a year after stroke, the second period with 11 patients included within 1 month after stroke. Postural control tests and different oropharyngeal motor tests were performed before and after 3 months of oropharyngeal sensorimotor training with an IQS, and at a late follow-up (median 59 weeks after end of training). Result All patients had impaired postural control at baseline. Significant improvement in postural control and OPMD was observed after the completion of IQS training in both intervention groups. The improvements were still present at the late follow-up.

  • 270.
    Hagg, 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.
    Esophageal dysphagia and reflux symptoms before and after oral IQoro(R) training2015In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 21, no 24, p. 7558-7562Article in journal (Refereed)
    Abstract [en]

    AIM: To examine whether muscle training with an oral IQoro(R) screen (IQS) improves esophageal dysphagia and reflux symptoms. METHODS: A total of 43 adult patients (21 women and 22 men) were consecutively referred to a swallowing center for the treatment and investigation of long-lasting nonstenotic esophageal dysphagia. Hiatal hernia was confirmed by radiologic examination in 21 patients before enrollment in the study (group A; median age 52 years, range: 19-85 years). No hiatal hernia was detected by radiologic examination in the remaining 22 patients (group B; median age 57 years, range: 22-85 years). Before and after training with an oral IQS for 6-8 mo, the patients were evaluated using a symptom questionnaire (esophageal dysphagia and acid chest symptoms; score 0-3), visual analogue scale (ability to swallow food: score 0-100), lip force test (greater than= 15 N), velopharyngeal closure test (greater than= 10 s), orofacial motor tests, and an oral sensory test. Another twelve patients (median age 53 years, range: 22-68 years) with hiatal hernia were evaluated using oral IQS traction maneuvers with pressure recordings of the upper esophageal sphincter and hiatus canal as assessed by high-resolution manometry. RESULTS: Esophageal dysphagia was present in all 43 patients at entry, and 98% of patients showed improvement after IQS training [mean score (range): 2.5 (1-3) vs 0.9 (0-2), P less than 0.001]. Symptoms of reflux were reported before training in 86% of the patients who showed improvement at follow-up [1.7 (0-3) vs 0.5 (0-2), P less than 0.001). The visual analogue scale scores were classified as pathologic in all 43 patients, and 100% showed improvement after IQS training [71 (30-100) vs 22 (0-50), P less than 0.001]. No significant difference in symptom frequency was found between groups A and B before or after IQS training. The lip force test [31 N (12-80 N) vs 54 N (27-116), P less than 0.001] and velopharyngeal closure test values [28 s (5-74 s) vs 34 s (13-80 s), P less than 0.001] were significantly higher after IQS training. The oral IQS traction results showed an increase in mean pressure in the diaphragmatic hiatus region from 0 mmHg at rest (range: 0-0 mmHG) to 65 mmHg (range: 20-100 mmHg). CONCLUSION: Oral IQS training can relieve/improve esophageal dysphagia and reflux symptoms in adults, likely due to improved hiatal competence.

  • 271.
    Haggstrom, Christel
    et al.
    Uppsala Univ, Sweden; Umea Univ, Sweden.
    Garmo, Hans
    Kings Coll London, England; Reg Canc Ctr Uppsala Orebro, Sweden.
    de Luna, Xavier
    Umea Univ, Sweden.
    Van Hemelrijck, Mieke
    Kings Coll London, England; Karolinska Inst, Sweden.
    Soderkvist, Karin
    Umea 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.
    Strock, Viveka
    Sahlgrens Univ Hosp, Sweden.
    Hosseini, Abolfazl
    Karolinska Univ Hosp, Sweden.
    Gardmark, Truls
    Danderyd Hosp, Sweden.
    Malmstrom, Per-Uno
    Uppsala Univ, 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.
    Liedberg, Fredrik
    Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    Holmberg, Lars
    Uppsala Univ, Sweden; Kings Coll London, England.
    Survival after radiotherapy versus radical cystectomy for primary muscle-invasive bladder cancer: A Swedish nationwide population-based cohort study2019In: Cancer Medicine, ISSN 2045-7634, E-ISSN 2045-7634, Vol. 8, no 5, p. 2196-2204Article in journal (Refereed)
    Abstract [en]

    Background Studies of survival comparing radical cystectomy (RC) and radiotherapy for muscle-invasive bladder cancer have provided inconsistent results and have methodological limitations. The aim of the study was to investigate risk of death after radiotherapy as compared to RC. Methods We selected patients with muscle-invasive urothelial carcinoma without distant metastases, treated with radiotherapy or RC from 1997 to 2014 in the Bladder Cancer Data Base Sweden (BladderBaSe) and estimated absolute and relative risk of bladder cancer death and all-cause death. In a group of patients, theoretically eligible for a trial comparing radiotherapy and RC, we calculated risk difference in an instrumental variable analysis. We have not investigated chemoradiotherapy as this treatment was not used in the study time period. Results The study included 3 309 patients, of those 17% were treated with radiotherapy and 83% with RC. Patients treated with radiotherapy were older, had more advanced comorbidity, and had a higher risk of death as compared to patients treated with RC (relative risks of 1.5-1.6). In the "trial population," all-cause death risk difference was 6 per 100 patients lower after radiotherapy at 5 years of follow-up, 95% confidence interval -41 to 29. Conclusion(s) Patient selection between the treatments make it difficult to evaluate results from conventionally adjusted and propensity-score matched survival analysis. When taking into account unmeasured confounding by instrumental variable analysis, no differences in survival was found between the treatments for a selected group of patients. Further clinical studies are needed to characterize this group of patients, which can serve as a basis for future comparison studies for treatment recommendations.

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  • 272.
    Hagman, H.
    et al.
    County Hospital Ryhov, Sweden.
    Frodin, J. -E.
    Karolinska University Hospital, Sweden.
    Berglund, A.
    University of Uppsala Hospital, Sweden.
    Sundberg, J.
    Skåne University Hospital, Sweden.
    Vestermark, L. W.
    Odense University Hospital, Denmark.
    Albertsson, Maria
    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 Oncology.
    Fernebro, E.
    Vaxjo Hospital, Sweden.
    Johnsson, A.
    Skåne University Hospital, Sweden.
    A randomized study of KRAS-guided maintenance therapy with bevacizumab, erlotinib or metronomic capecitabine after first-line induction treatment of metastatic colorectal cancer: the Nordic ACT2 trial2016In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 27, no 1, p. 140-147Article in journal (Refereed)
    Abstract [en]

    Maintenance treatment (mt) with bevacizumab (bev) +/- erlotinib (erlo) has modest effect after induction chemotherapy in metastatic colorectal cancer (mCRC). We hypothesized the efficacy of erlo to be dependent on KRAS mutational status and investigated this by exploring mt strategies with bev +/- erlo and low-dose capecitabine (cap). Included patients had mCRC scheduled for first-line therapy, Eastern Cooperative Oncology Group (ECOG) 0-1 and no major comorbidities. Treatment with XELOX/FOLFOX or XELIRI/FOLFIRI + bev was given for 18 weeks. After induction, patients without progression were eligible for randomization to mt; KRAS wild-type (wt) patients were randomized to bev +/- erlo (arms wt-BE, N = 36 versus wt-B, N = 35), KRAS mutated (mut) patients were randomized to bev or metronomic cap (arms mut-B, N = 34 versus mut-C, N = 33). Primary end point was progression-free survival (PFS) rate (PFSr) at 3 months after start of mt. A pooled analysis of KRAS wt patients from the previous ACT study was performed. We included 233 patients. Median age was 64 years, 62% male, 68% ECOG 0, 52% with primary tumor in situ. A total of 138 patients started mt after randomization. PFSr was 64.7% versus 63.6% in wt-B versus wt-BE, P = 1.000; and 75% versus 66.7% in mut-B versus mut-C, P = 0.579, with no significant difference in median PFS and overall survival (OS). In the pooled cohort, median PFS was 3.7 months in wt-B (N = 64) and 5.7 months in wt-BE (N = 62) (hazard ratios 1.03, 95% confidence interval 0.70-1.50, P = 0.867). The frequency of any grade 3/4 toxicities during mt was: 28%/58%/18%/15% (wt-B/wt-BE/mut-B/mut-C). Addition of erlo to bev as mt in KRAS wt mCRC did not significantly improve PFS or OS, but it did increase toxicity. KRAS status does not seem to influence the outcome of treatment with erlotinib. Metronomic cap warrants further investigation in mt strategies, given our explorative results. NCT01229813.

  • 273.
    Haj-Hosseini, Neda
    et al.
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Gimm, Oliver
    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.
    Höög, Anders
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Johansson, Kenth
    Landstinget i Kalmar län och Sahlgrenska universitetssjukhus, Västra Götalandsregion.
    Optiska metoder för identifiering av bisköldkörtel och sköldkörtel2017Conference paper (Refereed)
    Abstract [sv]

    Identifiering av bisköldkörtlar är viktigt vid sköldkörtel- och bisköldkörtelkirurgi och kan vara svårt då de liknar omgivande vävnad såsom fett och lymfkörtlar. Peroperativ detektering av dessa vävnader kan förbättra möjligheten att bota patienter med hyperparathyroidism och minska risken för bisköldkörtelskador vid thyroideakirurgi. Optiska metoder är potentiella tekniker för att möjliggöra detta. Optiska tekniker utvärderades på vävnadsprover från patienter vid bisköldkörtel- och sköldkörteloperation. Teknikerna bestod av nära infraröd fluorescens (NIR) spektroskopi och optisk koherenstomografi (OCT) som ger en bild av vävnadens mikrostruktur liknande till ultraljud med högre upplösning (10 μm).

  • 274.
    Haj-Hosseini, Neda
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Milos, Peter
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Richter, Johan
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Hildesjö, Camilla
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Hallbeck, Martin
    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 Pathology and Clinical Genetics.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    Detection of brain tumor using fluorescence and optical coherence tomography2015Conference paper (Refereed)
    Abstract [en]

    Resection of brain tumor is a challenging task as the tumor does not have clear borders and the malignant types specifically have often a diffuse and infiltrative pattern of growth. We have previously implemented and evaluated a fluorescence spectroscopy based handheld probe for detecting the 5-aminolevulinic acid induced protoporphyrin IX (PpIX) in the gliomas. To add another dimension to the brain tumor detection and volumetric analysis of the tissue that exhibits fluorescence, optical coherence tomography was investigated on tumor specimens.

    Material and Methods:

    A fluorescence microscopy and a spectroscopy system as reported previously were used for detecting the fluorescence signals [1, 2]. A total of 50 patients have been included for intraoperative assessment of the tumor borders using the fluorescence techniques. A spectral domain OCT imaging system (TELESTO II, Thorlabs, Inc., NJ, USA) with central wavelength of 1325 nm was used to study the tissue microstructure post operatively. The system has a resolution of 13 and 5.5 μm in the lateral and axial directions, respectively. Tissue specimens from three patients undergoing brain tumor surgery were studied using the OCT system.

    Results and Conclusion:

    Using fluorescence spectroscopy the tumor could be detected with a sensitivity of 0.84 which was significantly higher than that of the surgical microscope (0.30). Brain tissue appeared rather homogeneous in the OCT images however the highly malignant tissue showed a clear structural difference from the non-malignant or low malignant brain tumor tissue which could be related to the fluorescence signal intensities.

  • 275.
    Haj-Hosseini, Neda
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Medicine and Health Sciences.
    Petersson, Pernilla
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Gimm, Oliver
    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.
    Shabo, Ivan
    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.
    Optical Coherence Tomography for Pathological Analysis of Thyroid2016Conference paper (Refereed)
  • 276.
    Haj-Hosseini, Neda
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Stepp, Herbert
    Ludwig Maximilians Universitet, München.
    Markwardt, Niklas
    Ludwig Maximilians Universitet, München.
    Gimm, Oliver
    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 Linköping.
    Shabo, Ivan
    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 Linköping.
    Optical biopsy during thyroid and parathyroid surgery2015Conference paper (Refereed)
  • 277.
    Hall, Kirsten Sundby
    et al.
    Oslo Univ Hosp, Norway.
    Bruland, Oyvind S.
    Oslo Univ Hosp, Norway; Univ Oslo, Norway.
    Bjerkehagen, Bodil
    Oslo Univ Hosp, Norway.
    Zaikova, Olga
    Oslo Univ Hosp, Norway.
    Engellau, Jacob
    Oslo Univ Hosp, Norway.
    Hagberg, Oskar
    Reg Canc Ctr South, Sweden.
    Hansson, Lina
    Sahlgrens Univ Hosp, Sweden.
    Hagberg, Hans
    Uppsala Univ Hosp, Sweden.
    Ahlstrom, Marie
    Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    Knobel, Heidi
    St Olavs Univ Hosp, Norway.
    Papworth, Karin
    Norrlands Univ Hosp, Sweden.
    Zemmler, Maja
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Goplen, Dorota
    Haukeland Hosp, Norway.
    Bauer, Henrik C. F.
    Karolinska Inst, Sweden.
    Eriksson, Mikael
    Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    Adjuvant chemotherapy and postoperative radiotherapy in high-risk soft tissue sarcoma patients defined by biological risk factors-A Scandinavian Sarcoma Group study (SSG XX)2018In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 99, p. 78-85Article in journal (Refereed)
    Abstract [en]

    Purpose: To investigate the outcome following adjuvant doxorubicin and ifosfamide in a prospective non-randomised study based on a soft tissue sarcoma (STS) patient subgroup defined by specific morphological characteristics previously shown to be at a high-risk of metastatic relapse. The expected 5-year cumulative incidence of metastases in patients with this risk profile has previously been reported to be about 50% without adjuvant chemotherapy. Methods: High-risk STS was defined as high-grade morphology (according to the Federation Nationale des Centres de Lutte Contre le Cancer [FNCLCC] grade II-III) and either vascular invasion or at least two of the following criteria: tumour size amp;gt;= 8.0 cm, infiltrative growth and necrosis. Six cycles of doxorubicin (60 mg/m(2)) and ifosfamide (6 g/m(2)) were given. Postoperative accelerated radiotherapy was applied and scheduled between cycles 3 and 4. Results: For the 150 eligible patients, median follow-up time for metastases-free survival was 3.9 years (range 0.2-8.7). Five-year metastases-free survival (MFS) was 70.4% (95% confidence interval [CI]: 63.1-78.4) with a local recurrence rate of 14.0% (95% CI: 7.8-20.2). For overall survival (OS), the median follow-up time was 4.4 years (range: 0.2-8.7). The five-year OS was 76.1% (95% CI: 68.8-84.2). Tumour size, deep location and reduced dose intensity (amp;lt;80%) had a negative impact on survival. Toxicity was moderate with no treatment-related death. Conclusions: A benefit of adjuvant chemotherapy, compared to similar historical control groups, was demonstrated in STS patients with defined poor prognostic factors. Vascular invasion, tumour size, growth pattern and necrosis may identify patients in need of adjuvant chemotherapy. (C) 2018 Elsevier Ltd. All rights reserved.

  • 278.
    Hallböök, Olof
    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 Surgery in Linköping.
    Sjödahl, Rune
    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.
    Långvarigt Trendelenburgs läge kan orsaka ögonskador: Kortad operationstid i tippat läge och justering av tippningsvinkeln kan minska risken2018In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 115Article in journal (Refereed)
    Abstract [en]

    Risk of optic nerve injury after prolonged Trendelenburgs position Postoperative loss of vision due to acute ischaemic optic nerve injury is a rare complication following pelvic surgery. A steep Trendelenburgs position of the patient, high intraabdominal pressure and a long operative time in Trendelenburgs position are recognised risk factors associated with robot-assisted pelvic surgery. This manuscript presents the underlying pathophysiologic mechanism. Practical tips and tricks for prevention are discussed.

  • 279.
    Hammerman, Malin
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Blomgran, Parmis
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Dansac, Arie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Eliasson, Pernilla T.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Aspenberg, 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 Orthopaedics in Linköping.
    Different gene response to mechanical loading during early and late phases of rat Achilles tendon healing2017In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 123, no 4, p. 800-815Article in journal (Refereed)
    Abstract [en]

    Mechanical loading stimulates tendon healing both when applied in the inflammatory phase and in the early remodeling phase of the process, although not necessarily via the same mechanisms. We investigated the gene response to mechanical loading in these two phases of tendon healing. The right Achilles tendon in rats was transected, and the hindlimbs were unloaded by tail suspension. The rats were exposed to 5 min of treadmill running 3 or 14 days after tendon transection. Thereafter, they were resuspended for 15 min or 3 h until euthanasia. The controls were suspended continuously. Gene analysis was first performed by microarray analysis followed by quantitative RTPCR on selected genes, focusing on inflammation. Fifteen minutes after loading, the most important genes seemed to be the transcription factors EGR1 and C-FOS, regardless of healing phase. These transcription factors might promote tendon cell proliferation and differentiation, stimulate collagen production, and regulate inflammation. Three hours after loading on day 3, inflammation was strongly affected. Seven inflammation-related genes were upregulated according to PCR: CCL20, CCL7, IL-6, NFIL3, PTX3, SOCS1, and TLR2. These genes can be connected to macrophages, T cells, and recruitment of leukocytes. According to Ingenuity Pathway Analysis, the recruitment of leukocytes was increased by loading on day 3, which also was confirmed by histology. This inflammation-related gene response was not seen on day 14. Our results suggest that the immediate gene response after mechanical loading is similar in the early and late phases of healing but the late gene response is different. NEW amp; NOTEWORTHY This study investigates the direct effect of mechanical loading on gene expression during different healing phases in tendon healing. One isolated episode of mechanical loading was studied in otherwise unloaded healing tendons. This enabled us to study a time sequence, i.e., which genes were the first ones to be regulated after the loading episode.

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  • 280.
    Hammerman, Malin
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Blomgran, Parmis
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Ramstedt, Sandra
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Aspenberg, Per
    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 Health Sciences.
    COX-2 inhibition impairs mechanical stimulation of early tendon healing in rats by reducing the response to microdamage2015In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 119, no 5, p. 534-540Article in journal (Refereed)
    Abstract [en]

    Early tendon healing can be stimulated by mechanical loading and inhibited by cyclooxygenase (COX) inhibitors (nonsteroidal anti-inflammatory drugs). Therefore, we investigated if impairment of tendon healing by a COX-2 inhibitor (parecoxib) is related to loading. Because loading might infer microdamage, which also stimulates healing, we also investigated if this effect is inhibited by parecoxib. The Achilles tendon was transected in 114 rats. Three degrees of loading were used: full loading, partial unloading, and unloading (no unloading, Botox injections in the plantar flexor muscles, or Botox in combination with tail suspension). For each loading condition, the rats received either parecoxib or saline. In a second experiment, rats were unloaded with Botox, and the tendon was subjected to microdamage by needling combined with either saline or parecoxib. Mechanical testing day 7 showed that there was a significant interaction between loading and parecoxib for peak force at failure (P less than 0.01). However, logarithmic values showed no significant interaction, meaning that we could not exclude that the inhibitory effect of parecoxib was proportionate to the degree of loading. Microbleeding was common in the healing tissue, suggesting that loading caused microdamage. Needling increased peak force at failure (P less than 0.01), and this effect of microdamage was almost abolished by parecoxib (P less than 0.01). Taken together, this suggests that COX-2 inhibition impairs the positive effects of mechanical loading during tendon healing, mainly by reducing the response to microdamage.

  • 281.
    Hammerman, Malin
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Dietrich, Franciele
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Blomgran, Parmis
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Eliasson, Pernilla T.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Aspenberg, 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 Orthopaedics in Linköping.
    Different mechanisms activated by mild versus strong loading in rat Achilles tendon healing2018In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 7, article id e0201211Article in journal (Refereed)
    Abstract [en]

    Background Mechanical loading stimulates Achilles tendon healing. However, various degrees of loading appear to have different effects on the mechanical properties of the healing tendon, and strong loading might create microdamage in the tissue. This suggests that different mechanisms might be activated depending on the magnitude of loading. The aim of this study was to investigate these mechanisms further. Methods Female rats had their right Achilles tendon cut transversely and divided into three groups: 1) unloading (calf muscle paralysis by Botox injections, combined with joint fixation by a steel-orthosis), 2) mild loading (Botox only), 3) strong loading (free cage activity). Gene expression was analyzed by PCR, 5 days post-injury, and mechanical testing 8 days post-injury. The occurrence of microdamage was analyzed 3, 5, or 14 days post-injury, by measuring leakage of injected fluorescence-labelled albumin in the healing tendon tissue. Results Peak force, peak stress, and elastic modulus of the healing tendons gradually improved with increased loading as well as the expression of extracellular matrix genes. In contrast, only strong loading increased transverse area and affected inflammation genes. Strong loading led to higher fluorescence (as a sign of microdamage) compared to mild loading at 3 and 5 days post-injury, but not at 14 days. Discussion Our results show that strong loading improves both the quality and quantity of the healing tendon, while mild loading only improves the quality. Strong loading also induces microdamage and alters the inflammatory response. This suggests that mild loading exert its effect via mechanotransduction mechanisms, while strong loading exert its effect both via mechanotransduction and the creation of microdamage. Conclusion In conclusion, mild loading is enough to increase the quality of the healing tendon without inducing microdamage and alter the inflammation in the tissue. This supports the general conception that early mobilization of a ruptured tendon in patients is advantageous.

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  • 282.
    Han, Shuangshuang
    et al.
    Hebei Med Univ, Peoples R China.
    Jiang, Xia
    Hebei Med 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.
    Zhang, Hong
    Orebro Univ, Sweden.
    Li, Chao
    Hebei Med Univ, Peoples R China.
    Zhao, Zengren
    Hebei Med Univ, Peoples R China.
    Yu, Weifang
    Hebei Med Univ, Peoples R China.
    Application value of CyTOF 2 mass cytometer technology at single-cell level in human gastric cancer cells2019In: Experimental Cell Research, ISSN 0014-4827, E-ISSN 1090-2422, Vol. 384, no 1, article id UNSP 111568Article in journal (Refereed)
    Abstract [en]

    Chemotherapy and radiotherapy are main adjuvant therapies for the treatment of gastric cancer, the treatment effects are individual difference, but the specific mechanism is unknown. CyTOF 2 mass cytometer (CyTOF) enables the detecting up to 135 parameters on single cell, the emergence of which is an opportunity for proteomics research. We first tried to apply CyTOF technique to gastric cancer cells. We verified applicability of CyTOF in gastric cancer cells, and analyzed the responses of seventeen proteins to chemoradiotherapy in human gastric cancer AGS cells. To analyze the high dimensional CyTOF data, we used two statistical and visualization tools including viSNE and Citrus. Two specific clusters were found which had differences in protein expression profiles. CyTOF technology is proved feasibility and value at single cell level of gastric cancer.

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  • 283.
    Hansson, Edvin
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Westinghouse Electric Sweden AB, Västerås, Sweden.
    Pettersson, Håkan
    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.
    Fortin, C
    Carl Zeiss SAS, Marley-le-Roi, France.
    Eriksson, Martin
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Swedish Radiation Safety Authority, Stockholm, Sweden.
    Uranium aerosols at a nuclear fuel fabrication plant: Characterization using scanning electron microscopy and energy dispersive X-ray spectroscopy2017In: Spectrochimica Acta Part B - Atomic Spectroscopy, ISSN 0584-8547, E-ISSN 1873-3565, p. 130-137Article in journal (Refereed)
    Abstract [en]

    Detailed aerosol knowledge is essential in numerous applications, including risk assessment in nuclear industry. Cascade impactor sampling of uranium aerosols in the breathing zone of nuclear operators was carried out at a nuclear fuel fabrication plant. Collected aerosols were evaluated using scanning electron microscopy and energy dispersive X-ray spectroscopy. Imaging revealed remarkable variations in aerosol morphology at the different workshops, and a presence of very large particles (up to ≅ 100 × 50 μm2) in the operator breathing zone. Characteristic X-ray analysis showed varying uranium weight percentages of aerosols and, frequently, traces of nitrogen, fluorine and iron. The analysis method, in combination with cascade impactor sampling, can be a powerful tool for characterization of aerosols. The uranium aerosol source term for risk assessment in nuclear fuel fabrication appears to be highly complex.

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  • 284.
    Harle, Karolina
    et al.
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Lindgren, Margareta
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    Hallböök, Olof
    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.
    Experience of living with an enterocutaneous fistula2015In: Journal of Clinical Nursing, ISSN 0962-1067, E-ISSN 1365-2702, Vol. 24, no 15-16, p. 2175-2183Article in journal (Refereed)
    Abstract [en]

    Aims and objectives. The purpose of this study was to describe patients experiences of living with an enterocutaneous fistula. Background. An enterocutaneous fistula is a complex and serious illness that usually occurs as a complication from surgery or spontaneously as a result of an underlying disease. The illness is demanding both physically and mentally and causes substantial medical and nursing problems for the afflicted individual. Design. A descriptive design with a qualitative approach. Methods. In-depth interviews were performed with nine participants who had experiences of living with an enterocutaneous fistula. The analysis was conducted using descriptive phenomenology according to Giorgi. Results. The essence of this study was that living with an enterocutaneous fistula is about handling an illness that causes several limitations in daily life and the following five themes emerged from the data: restrictions in daily life, approaches to illness, emotions, dependence and need of support. A constant fear of leakage from the fistula appliance, being dependent on intravenous fluids and being dependent on health care professionals caused isolation and social restriction. Conclusions. The participants had many strategies for handling their illness. By being well trained, engaged and having a positive and understanding approach, health care professionals can encourage hope, motivation and self-care. This can lead to decreased dependence and help the patient to better handle their illness. Relevance to clinical practice. The competence of health care professionals is essential in the care of patients with an enterocutaneous fistula.

  • 285.
    Hartana, C. A.
    et al.
    Karolinska Inst, Sweden.
    Bergman, E. Ahlen
    Karolinska Inst, Sweden.
    Broome, A.
    Karolinska Inst, Sweden.
    Berglund, S.
    Karolinska Inst, Sweden.
    Johansson, M.
    Sundsvall Hosp, Sweden.
    Alamdari, F.
    Vastmanland Hosp, Sweden.
    Jakubczyk, T.
    Lanssjukhuset Ryhov, Sweden.
    Huge, Ylva
    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.
    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.
    Palmqvist, K.
    Ostersund Cty Hosp, Sweden.
    Holmstroem, B.
    Akad Univ Hosp, Sweden.
    Glise, H.
    Karolinska Inst, Sweden.
    Riklund, K.
    Umea Univ, Sweden.
    Sherif, A.
    Umea Univ, Sweden.
    Winqvist, O.
    Karolinska Inst, Sweden.
    Tissue-resident memory T cells are epigenetically cytotoxic with signs of exhaustion in human urinary bladder cancer2018In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 194, no 1, p. 39-53Article in journal (Refereed)
    Abstract [en]

    Tissue-resident memory T (T-RM) cells are CD8(+) T lymphocytes that reside in the tissues, including tumours. This T cell subset possesses a magnitude of cytotoxicity, but its epigenetic regulation has not been studied. Here, we investigate the impact of perforin DNA methylation in T-RM cells and correlate it with their functional potential. Fifty-three urothelial urinary bladder cancer (UBC) patients were recruited prospectively. The DNA methylation status of the perforin gene (PRF1) locus in T-RM cells was investigated by pyrosequencing. Flow cytometry with ViSNE analysis and in-vitro stimulation were used to evaluate T-RM cell phenotypes. We discovered that tumour T-RM cells have low DNA methylation in the PRF1 locus (32amp;lt;boldamp;gt;amp;lt;/boldamp;gt;9% methylation), which corresponds to increased numbers of perforin-expressing T-RM cells. Surprisingly, programmed cell death 1 (PD-1) expression is high in tumour T-RM cells, suggesting exhaustion. Following interleukin-15 and T cell receptor stimulation, perforin and T-bet expressions are enhanced, indicating that T-RM cells from tumours are not terminally exhausted. Moreover, a high number of T-RM cells infiltrating the tumours corresponds to lower tumour stage in patients. In conclusion, T-RM cells from UBC tumours are epigenetically cytotoxic with signs of exhaustion. This finding identifies T-RM cells as potential new targets for cancer immunotherapy.

  • 286. Order onlineBuy this publication >>
    Hasselgren, Kristina
    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 Linköping.
    Colorectal Liver Metastases – Different Aspects on Treatment with Associated Liver Partition and Portal Vein Ligation for Staged Hepatectomy and on Portal Vein Occlusion2020Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Introduction: For patients with colorectal liver metastases (CRLM), the only treatment with a possibility for long-term survival and cure is radical resection. The majority of patients are at the time of diagnosis not assessed as resectable because they have advanced disease in the liver or unresectable extrahepatic disease or are too frail to withstand liver surgery. Patients who at the time of diagnosis are not assessed as resectable may be treated with conversion chemotherapy to downsize the tumor burden and render the patient eligible for resection. One concern with chemotherapy administered preoperatively has been the potential negative effect on the future liver remnant (FLR), especially for patients with a low volume of the FLR who are undergoing techniques to increase the volume. Established techniques to increase the volume are portal vein occlusion (PVO) and two-staged hepatectomy (TSH). A more recent method is Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS). Due to the relative novelty of ALPPS, the long-term oncological results are not known. For patients with CRLM, resection of liver metastases is more favorable from a health economic perspective than palliative treatment and results in a higher quality of life than palliative chemotherapy. For patients undergoing ALPPS as well as TSH, the data are scarce.

    Aim: The aim of the first study was to determine whether preoperative chemotherapy has a negative impact on the volume increase for patients undergoing ALPPS. The aim of the second study was to analyze the temporal course of the volume increase in the FLR for patients undergoing PVO. The aim of the third study was to study the long-term outcome for patients randomized to ALPPS or TSH. The aim of the fourth study was to perform a health economic analysis of patients randomized to ALPPS or TSH.

    Methods: The first study was based on data from the ALPPS registry, which is an international registry initiated 2012. All patients included in the registry between 2012 and 2016 were included. The patients were divided into the following four groups: no preoperative chemotherapy, 1 regimen of neoadjuvant chemotherapy, more than 1 regimen, and more than 1 regimen with the addition of monoclonal antibodies. The volume increase between interventions 1 and 2 was analyzed. In the second study, a retrospective analysis was performed of patients randomized to TSH. Forty-eight patients were included. The volume increase of the FLR was analyzed as the kinetic growth rate (KGR). The KGR was calculated from PVO until radical hepatectomy or exclusion, as well as between the first and second radiological evaluations. In the third and fourth studies, patients randomized to ALPPS and TSH were included. In the third study, survival, as well as factors affecting the outcome, were analyzed. In the fourth study, a calculation of resource use was performed, as was an analysis of health-related quality of life (HRQoL) for the groups.

    Results: In the first study, it was found that chemotherapy had no negative impact on the volume increase for patients undergoing ALPPS. In the second study, it was found that the volume increase of the FLR was largest the first week after ALPPS. In the third study, it was found that patients randomized to ALPPS had a longer survival than those randomized to TSH. Of the factors affecting the outcome, resection of liver metastases had a significant impact. In the fourth study, no significant difference could be found in resource use or HRQoL for patients randomized to ALPPS over TSH.

    Conclusion: Patients with advanced CRLM undergoing ALPPS should receive preoperative chemotherapy, if indicated. For those undergoing PVO, early evaluation is crucial to evaluate the volume increase, and for those with insufficient increase, additional techniques to increase the volume should be considered. Resection of liver metastases is an important factor to improve the outcome. Further studies are warranted to conclude whether ALPPS or TSH is most effective from a health economic perspective.

    List of papers
    1. Neoadjuvant chemotherapy does not affect future liver remnant growth and outcomes of associating liver partition and portal vein ligation for staged hepatectomy
    Open this publication in new window or tab >>Neoadjuvant chemotherapy does not affect future liver remnant growth and outcomes of associating liver partition and portal vein ligation for staged hepatectomy
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    2017 (English)In: Surgery, ISSN 0039-6060, E-ISSN 1532-7361, Vol. 161, no 5, p. 1255-1265Article in journal (Refereed) Published
    Abstract [en]

    Background. The only potentially curative treatment for patients with colorectal liver metastases is hepatectomy. Associating liver partition and portal vein ligation for staged hepatectomy has emerged as a method of treatment for patients with inadequate future liver remnant. One concern about associating liver partition and portal vein ligation for staged hepatectomy is that preoperative chemotherapy may negatively affect the volume increase of the future liver remnant and outcomes. Methods. This study from the International Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy Registry (NCT01924741) includes 442 patients with colorectal liver metastases registered from 2012-2016. Future liver remnant hypertrophy (absolute increase, percent increase, and kinetic growth rate) and clinical outcome were analyzed retrospectively in relation to type and amount of chemotherapy. The analyzed groups included patients with no chemotherapy, 1 regimen of chemotherapy, amp;gt; 1 regimen, and a group that received monoclonal antibodies in addition to chemotherapy. Results. Ninety percent of the patients received neoadjuvant oncologic therapy including 42% with 1 regimen of chemotherapy, 44% with monoclonal antibodies, and 4% with amp;gt; 1 regimen. Future liver remnant increased between 74-92% with the largest increase in the group with 1 regimen of chemotherapy. The increase in milliliters was between 241 mL (amp;gt; 1 regimen) and 306 mL (1 regimen). Kinetic growth rate was between 14-18% per week and was greatest for the group with 1 regimen of chemotherapy. No statistical significance was found between the groups with any of the measurements of future liver remnant hypertrophy. Conclusion. Neoadjuvant chemotherapy, including monoclonal antibodies, does not negatively affect future liver remnant growth. Patients with colorectal liver metastases who might be potential candidates for associating liver partition and portal vein ligation for staged hepatectomy should be considered for neoadjuvant chemotherapy. (Surgery 2017;161:1255-65.)

    Place, publisher, year, edition, pages
    MOSBY-ELSEVIER, 2017
    National Category
    Surgery
    Identifiers
    urn:nbn:se:liu:diva-137854 (URN)10.1016/j.surg.2016.11.033 (DOI)000400318000011 ()28081953 (PubMedID)
    Available from: 2017-06-02 Created: 2017-06-02 Last updated: 2020-04-28
    2. Future Liver Remnant (FLR) Increase in Patients with Colorectal Liver Metastases Is Highest the First Week After Portal Vein Occlusion: FLR Increase in Patients with CRLM Is Highest the First Week After PVO.
    Open this publication in new window or tab >>Future Liver Remnant (FLR) Increase in Patients with Colorectal Liver Metastases Is Highest the First Week After Portal Vein Occlusion: FLR Increase in Patients with CRLM Is Highest the First Week After PVO.
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    2019 (English)In: Journal of Gastrointestinal Surgery, ISSN 1091-255X, E-ISSN 1873-4626, Vol. 23, no 3, p. 556-562Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND: Portal vein occlusion (PVO) is an established method to increase the volume of the future liver remnant (FLR). The main reasons for not proceeding to radical hepatectomy are lack of volume increase and tumor progression due to a wait-time interval of up to 8 weeks. The hypothesis was that the increase in FLR volume is not linear and is largest during the first weeks.

    METHODS: Patients with colorectal liver metastases (CRLM) and standardized future liver remnant (sFLR) < 30% treated with PVO were prospectively included. All patients had at least one CT evaluation before radical hepatectomy.

    RESULTS: Forty-eight patients were included. During the first week after PVO, the kinetic growth rate (KGR) was 5.4 (± 4), compared to 1.5 (± 2) between the first and second CT (p < 0.05). For patients reaching adequate FLR and therefore treated with radical hepatectomy, the KGR was 7 (± 4) the first week, compared to 4.3 (± 2) for patients who failed to reach a sufficient volume (p = 0.4). During the interval between the first and second CT, the KGR was 2.2 (± 2), respectively (± 0.1) (p = 0.017).

    DISCUSSION: The increase in liver volume after PVO is largest during the first week. As KGR decreases over time, it is important to shorten the interval between PVO and the first volume evaluation; this may aid in decision-making and reduce unnecessary waiting time.

    Place, publisher, year, edition, pages
    Springer, 2019
    Keywords
    Colorectal liver metastases, Future liver remnant, Liver surgery, Portal vein embolization, Portal vein ligation
    National Category
    Surgery
    Identifiers
    urn:nbn:se:liu:diva-163892 (URN)10.1007/s11605-018-4031-3 (DOI)000461287300014 ()30465187 (PubMedID)
    Note

    Funding Agencies|LIO-534891, FORSS-560521, FORSS-660121, and FORSS-753-621

    Available from: 2020-02-25 Created: 2020-02-25 Last updated: 2020-04-28
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  • 287.
    Hasselgren, Kristina
    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 Surgery in Linköping.
    Halldestam, Ingvar
    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.
    Fraser, M. P.
    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.
    Benjaminsson Nyberg, Pernilla
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Gasslander, Thomas
    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.
    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.
    Does the Introduction of Laparoscopic Distal Pancreatectomy Jeopardize Patient Safety and Well-Being?2016In: Scandinavian Journal of Surgery, ISSN 1457-4969, E-ISSN 1799-7267, Vol. 105, no 4, p. 223-227Article in journal (Refereed)
    Abstract [en]

    Background/Purpose: Despite retrospective data indicating short-term superiority for laparoscopic distal pancreatectomy compared to open distal pancreatectomy, the implementation of the procedure has been slow. The aim of this study was to investigate whether patients operated with laparoscopic distal pancreatectomy during the early phase of introduction are at higher risk for complications than patients operated with open distal pancreatectomy.

    Methods: A retrospective single-center analysis of patients operated with laparoscopic distal pancreatectomy (n=37) from the introduction of the procedure and comparison regarding demographic data, preoperative data, operative factors, and postoperative outcomes to patients operated with open distal pancreatectomy was done.

    Results: Operation duration shortened (195 vs 143min, p=0.04) and severe complications reduced (37% vs 6%, p=0.02) significantly in the laparoscopic distal pancreatectomy group between the first half of the study and the second half. Blood loss was significantly (pamp;lt;0.001) lower in the laparoscopic distal pancreatectomy group (75mL) than in the open distal pancreatectomy group (550mL), while complication rate and hospital stay as well as the percentage of radical resections were the same.

    Conclusion: Laparoscopic distal pancreatectomy can be introduced without jeopardizing patient safety and well-being during the early learning curve. The procedures should be compared in a prospective randomized manner.

  • 288.
    Hasselgren, Kristina
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Isaksson, Bengt
    Uppsala Univ, Sweden.
    Ardnor, Bjarne
    Umea Univ, Sweden.
    Lindell, Gert
    Lund Univ, Sweden.
    Rizell, Magnus
    Univ Gothenburg, Sweden.
    Stromberg, Cecilia
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Loftås, Per
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Björnsson, Bergthor
    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 Linköping.
    Sandström, Per
    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 Linköping.
    Liver resection is beneficial for patients with colorectal liver metastases and extrahepatic disease2020In: Annals of Translational Medicine, ISSN 2305-5839, E-ISSN 2305-5847, Vol. 8, no 4, article id 109Article in journal (Refereed)
    Abstract [en]

    Background: Liver metastases are the most common cause of death for patients with colorectal cancer and affect up to half of the patients. Liver resection is an established method that can potentially be curative. For patients with extrahepatic disease (EHD), the role of liver surgery is less established. Methods: This is a retrospective study based on data from the national quality registry SweLiv. Data were obtained between 2009 and 2015. SweLiv is a validated registry and has been in use since 2009, with coverage above 95%. Patients with liver metastases and EHD were analyzed and cross-checked against the national death cause registry for survival analysis. Results: During the study period, 2,174 patients underwent surgery for colorectal liver metastases (CRLM), and 277 patients with EHD were treated with resection or ablation. The estimated median survival time for the entire cohort from liver resection/ablation was 40 months (95% CI, 32-47). The survival time for patients treated with liver resection was 45 months compared to 26 months for patients treated with ablation (95% CI 38-53, 18-33, P=0.001). A subgroup analysis of resected patients revealed that the group with pulmonary metastases had a significantly longer estimated median survival (50 months; 95 % CI, 39-60) than the group with lymph node metastases (32 months; 95% CI, 7-58) or peritoneal carcinomatosis (28 months; 95% CI, 14-41) (P=0.022 and 0.012, respectively). Other negative prognostic factors were major liver resection and nonradical liver resection. Conclusions: For patients with liver metastases and limited EHD, liver resection results in prolonged survival compared to what can be expected from chemotherapy alone.

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  • 289.
    Hasselgren, Kristina
    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 Surgery in Linköping.
    Malago, Massimo
    UCL, England.
    Vyas, Soumil
    UCL, England.
    Robles Campos, Ricardo
    Vizgen De La Arrixaca University Hospital, Spain.
    Brusadin, Roberto
    Vizgen De La Arrixaca University Hospital, Spain.
    Linecker, Michael
    University of Zurich Hospital, Switzerland.
    Petrowsky, Henrik
    University of Zurich Hospital, Switzerland.
    Clavien, Pierre Alain
    University of Zurich Hospital, Switzerland.
    Machado, Marcel Autran
    University of Sao Paulo, Brazil.
    Hernandez-Alejandro, Roberto
    University of Rochester, NY USA.
    Wanis, Kerollos
    Western University, Canada.
    Walter, Lars
    Region Östergötland, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    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.
    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.
    Neoadjuvant chemotherapy does not affect future liver remnant growth and outcomes of associating liver partition and portal vein ligation for staged hepatectomy2017In: Surgery, ISSN 0039-6060, E-ISSN 1532-7361, Vol. 161, no 5, p. 1255-1265Article in journal (Refereed)
    Abstract [en]

    Background. The only potentially curative treatment for patients with colorectal liver metastases is hepatectomy. Associating liver partition and portal vein ligation for staged hepatectomy has emerged as a method of treatment for patients with inadequate future liver remnant. One concern about associating liver partition and portal vein ligation for staged hepatectomy is that preoperative chemotherapy may negatively affect the volume increase of the future liver remnant and outcomes. Methods. This study from the International Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy Registry (NCT01924741) includes 442 patients with colorectal liver metastases registered from 2012-2016. Future liver remnant hypertrophy (absolute increase, percent increase, and kinetic growth rate) and clinical outcome were analyzed retrospectively in relation to type and amount of chemotherapy. The analyzed groups included patients with no chemotherapy, 1 regimen of chemotherapy, amp;gt; 1 regimen, and a group that received monoclonal antibodies in addition to chemotherapy. Results. Ninety percent of the patients received neoadjuvant oncologic therapy including 42% with 1 regimen of chemotherapy, 44% with monoclonal antibodies, and 4% with amp;gt; 1 regimen. Future liver remnant increased between 74-92% with the largest increase in the group with 1 regimen of chemotherapy. The increase in milliliters was between 241 mL (amp;gt; 1 regimen) and 306 mL (1 regimen). Kinetic growth rate was between 14-18% per week and was greatest for the group with 1 regimen of chemotherapy. No statistical significance was found between the groups with any of the measurements of future liver remnant hypertrophy. Conclusion. Neoadjuvant chemotherapy, including monoclonal antibodies, does not negatively affect future liver remnant growth. Patients with colorectal liver metastases who might be potential candidates for associating liver partition and portal vein ligation for staged hepatectomy should be considered for neoadjuvant chemotherapy. (Surgery 2017;161:1255-65.)

  • 290.
    Hasselgren, Kristina
    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 Surgery in Linköping.
    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.
    Røsok, Bård Ingvald
    Oslo University Hospital, Norway.
    Sparrelid, Ernesto
    Karolinska University Hospital, Sweden.
    Lindell, Gert
    Skane University Hospital, Sweden.
    Larsen, Peter Nørgaard
    University of Copenhagen, Denmark.
    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.
    Schultz, Nicolai A
    University of Copenhagen, Denmark.
    Björnbeth, Bjorn Atle
    Oslo University Hospital, Norway.
    Isaksson, Bengt
    Akademiska University Hospital, Sweden.
    Rizell, Magnus
    University of Gothenburg, Sweden.
    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.
    Future Liver Remnant (FLR) Increase in Patients with Colorectal Liver Metastases Is Highest the First Week After Portal Vein Occlusion: FLR Increase in Patients with CRLM Is Highest the First Week After PVO.2019In: Journal of Gastrointestinal Surgery, ISSN 1091-255X, E-ISSN 1873-4626, Vol. 23, no 3, p. 556-562Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Portal vein occlusion (PVO) is an established method to increase the volume of the future liver remnant (FLR). The main reasons for not proceeding to radical hepatectomy are lack of volume increase and tumor progression due to a wait-time interval of up to 8 weeks. The hypothesis was that the increase in FLR volume is not linear and is largest during the first weeks.

    METHODS: Patients with colorectal liver metastases (CRLM) and standardized future liver remnant (sFLR) < 30% treated with PVO were prospectively included. All patients had at least one CT evaluation before radical hepatectomy.

    RESULTS: Forty-eight patients were included. During the first week after PVO, the kinetic growth rate (KGR) was 5.4 (± 4), compared to 1.5 (± 2) between the first and second CT (p < 0.05). For patients reaching adequate FLR and therefore treated with radical hepatectomy, the KGR was 7 (± 4) the first week, compared to 4.3 (± 2) for patients who failed to reach a sufficient volume (p = 0.4). During the interval between the first and second CT, the KGR was 2.2 (± 2), respectively (± 0.1) (p = 0.017).

    DISCUSSION: The increase in liver volume after PVO is largest during the first week. As KGR decreases over time, it is important to shorten the interval between PVO and the first volume evaluation; this may aid in decision-making and reduce unnecessary waiting time.

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  • 291.
    Hasselgren, Kristina
    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 Surgery in Linköping.
    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.
    Björnsson, Bergthor
    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.
    Role of associating liver partition and portal vein ligation for staged hepatectomy in colorectal liver metastases: A review2015In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 21, no 15, p. 4491-4498Article, review/survey (Refereed)
    Abstract [en]

    Colorectal cancer is the third most common cancer in the Western world. Approximately half of patients will develop liver metastases, which is the most common cause of death. The only potentially curative treatment is surgical resection. However, many patients retain a to small future liver remnant (FLR) to allow for resection directly. There are therefore strategies to decrease the tumor with neoadjuvant chemotherapy and to increase the FLR. An accepted strategy to increase the FLR is portal vein occlusion (PVO). A concern with this strategy is that a large proportion of patients will never be operated because of progression during the interval between PVO and resection. ALPPS (associating liver partition and portal vein ligation for staged hepatectomy) is a new procedure with a high resection rate. A concern with this approach is the rather high frequency of complications and high mortality, compared to PVO. In this review, it is shown that with ALPPS the resection rate was 97.1% for CRLM and the mortality rate for all diagnoses was 9.6%. The mortality rate was likely lower for patients with CRLM, but some data were lacking in the reports. Due to the novelty of ALPPS, the indications and technique are not yet established but there are arguments for ALPPS in the context of CRLM and a small FLR.

  • 292.
    Hasselgren, Kristina
    et al.
    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.
    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.
    Gasslander, Thomas
    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.
    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.
    Multivisceral Resection in Patients with Advanced Abdominal Tumors2016In: Scandinavian Journal of Surgery, ISSN 1457-4969, E-ISSN 1799-7267, Vol. 105, no 3, p. 147-152Article in journal (Refereed)
    Abstract [en]

    Background/Aim: Multivisceral resection for advanced tumors can result in prolonged survival but may also increase the risk of postoperative morbidity and mortality. The primary aim of this study was to investigate whether extensive resections increase the severity of postoperative complications. Materials and Methods: A retrospective study was conducted between 2009 and 2014 at the Linkoping University Hospital surgical department. All patients with a confirmed or presumed malignant disease who underwent a non-standardized surgical procedure requiring a multivisceral resection were included. The primary endpoint was 90-day complications according to the Clavien-Dindo score. Results: Forty-eight patients were included, with an age range of 17-77years. A median of three organs was resected. The most common diagnoses were neuroendocrine tumor (n=8), gastric cancer (n=7), and gastrointestinal stromal tumor (n=6). One patient died during surgery. Complications grade 3b according to Clavien-Dindo score occurred in 10 patients. R0 resection was achieved in 32 patients. No correlation was observed between the number of anastomoses, perioperative blood loss, operative time, and complications. Only postoperative blood transfusion was correlated with severe complications (p=0.046); however, a tendency toward more complications with an increasing number of resected organs was observed (p=0.06). Conclusion: Multivisceral resection can result in R0, potentially curing patients with advanced tumors. Here, no correlation between extensive resections and complications was observed. Only postoperative blood transfusion was correlated with severe complications.

  • 293.
    Haufe, William
    et al.
    Department of Radiology, University of California, San Diego, San Diego, CA, United states.
    Hooker, Jonathan
    Department of Radiology, University of California, San Diego, San Diego, CA, United States.
    Schlein, Alexandra
    Department of Radiology, University of California, San Diego, San Diego, CA, United States.
    Szeverenyi, Nikolaus
    Department of Radiology, University of California, San Diego, San Diego, CA, United States.
    Borga, Magnus
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV). Advanced MR Analytics AB, Linköping, Sweden.
    Dahlqvist Leinhard, Olof
    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. Advanced MR Analytics AB, Linköping, Sweden.
    Romu, Thobias
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV). Advanced MR Analytics AB, Linköping, Sweden.
    Tunón, Patrik
    Advanced MR Analytics AB, Linköping, Sweden.
    Horgan, Santiago
    Surgery, University of California, San Diego, San Diego, CA, United States.
    Jacobsen, Garth
    Surgery, University of California, San Diego, San Diego, CA, United States.
    Schwimmer, Jeffrey B
    University of California, San Diego, San Diego, CA, United States.
    Reeder, Scott B
    University of Wisconsin, Madison, Madison, WI, United States.
    Sirlin, Claude B.
    Department of Radiology, University of California, San Diego, San Diego, CA, United States.
    Feasibility of an automated tissue segmentation technique in a longitudinal weight loss study2016Conference paper (Other academic)
    Abstract [en]

    To address the problems inherent in manual methods, a novel, semi-automated tissue segmentation image analysis technique has been developed. The purpose of this study was to demonstrate the feasibility and describe preliminary observations of applying this technique to quantify and monitor longitudinal changes in abdominal adipose tissue and thigh muscle volume in obese adults during weight loss. Abdominal adipose tissue and thigh muscle volume decreased during weight loss. As a proportion of body weight, adipose tissue volumes decreased during weight loss. By comparison, as a proportion of body weight, thigh muscle volume increased.

  • 294.
    Haverkamp, Frederike J C
    et al.
    Department of Surgery, Radboudumc, Geert Grooteplein Zuid, 9101, 618 Nijmegen, the Netherlands.
    van Gennip, Lisanne
    Department of Surgery, Radboudumc, Geert Grooteplein Zuid, 9101, 618 Nijmegen, the Netherlands.
    Muhrbeck, Måns
    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.
    Veen, Harald
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Department of Surgery, Radboudumc, Geert Grooteplein Zuid, 9101, 618 Nijmegen, the Netherlands.
    Wladis, Andreas
    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 Disaster Medicine and Traumatology.
    Tan, Edward C T H
    Department of Surgery, Radboudumc, Geert Grooteplein Zuid, 9101, 618 Nijmegen, the Netherlands.
    Global surgery for paediatric casualties in armed conflict2019In: World Journal of Emergency Surgery, ISSN 1749-7922, E-ISSN 1749-7922, Vol. 14, article id 55Article in journal (Refereed)
    Abstract [en]

    Background: Understanding injury patterns specific for paediatric casualties of armed conflict is essential to facilitate preparations by organizations that provide medical care in conflict areas. The aim of this retrospective cohort study is to identify injury patterns and treatment requirements that are specific for paediatric patients in conflict zones.

    Methods: Characteristics of children (age < 15 years) treated in medical facilities supported by the International Committee of the Red Cross (ICRC) between 1988 and 2014 in Kabul, Kao-i-Dang, Lokichogio, Kandahar, Peshawar, Quetta and Goma were analysed; patient characteristics were compared between treatment facilities and with those of adult patients (age ≥ 15 years).

    Results: Of the patients listed in the database, 15% (5843/38,088) were aged < 15 years. The median age was 10 years (IQR 6-12); 75% (4406/5843) were male. Eighty-six percent (5012/5,843) of the admitted children underwent surgery, with a median of 2 surgeries per patient (IQR 1-3). When compared with adult patients, children were more frequently seen with fragment injuries, burns and mine injuries; they had injuries to multiple body regions more often and had higher in-hospital mortality rates.

    Conclusions: Children more often sustained injuries to multiple body regions and had higher in-hospital mortality than adults. These findings could have implications for how the ICRC and other organizations prepare personnel and structure logistics to meet the treatment needs of paediatric victims of armed conflicts.

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  • 295.
    Haverkamp, Frederike J. C.
    et al.
    Radboudumc, Netherlands.
    Veen, Harald
    WHO, Switzerland.
    Hoencamp, Rigo
    Alrijne Med Ctr Leiderdorp, Netherlands; Leiden Univ, Netherlands; Minist Def, Netherlands.
    Muhrbeck, Måns
    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.
    von Schreeb, Johan
    Karolinska Inst, Sweden.
    Wladis, Andreas
    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 Disaster Medicine and Traumatology. Int Comm Red Cross, Switzerland.
    Tan, Edward C. T. H.
    Radboudumc, Netherlands.
    Prepared for Mission? A Survey of Medical Personnel Training Needs Within the International Committee of the Red Cross2018In: World Journal of Surgery, ISSN 0364-2313, E-ISSN 1432-2323, Vol. 42, no 11, p. 3493-3500Article in journal (Refereed)
    Abstract [en]

    Background Humanitarian organizations such as the International Committee of the Red Cross (ICRC) provide worldwide protection and medical assistance for victims of disaster and conflict. It is important to gain insight into the training needs of the medical professionals who are deployed to these resource scarce areas to optimally prepare them. This is the first study of its kind to assess the self-perceived preparedness, deployment experiences, and learning needs concerning medical readiness for deployment of ICRC medical personnel. Methods All enlisted ICRC medical employees were invited to participate in a digital questionnaire conducted during March 2017. The survey contained questions about respondents personal background, pre-deployment training, deployment experiences, self-perceived preparedness, and the personal impact of deployment. Results The response rate (consisting of nurses, surgeons, and anesthesiologists) was 54% (153/284). Respondents rated their self-perceived preparedness for adult trauma with a median score of 4.0 on a scale of 1 (very unprepared) to 5 (more than sufficient); and for pediatric trauma with a median score of 3.0. Higher rates of self-perceived preparedness were found in respondents who had previously been deployed with other organizations, or who had attended at least one master class, e.g., the ICRC War Surgery Seminar (p amp;lt; 0.05). Additional training was requested most frequently for pediatrics (65/150), fracture surgery (46/150), and burns treatment (45/150). Conclusion ICRC medical personnel felt sufficiently prepared for deployment. Key points for future ICRC pre-deployment training are to focus on pediatrics, fracture surgery, and burns treatment, and to ensure greater participation in master classes.

  • 296.
    Hayden, Patrick J.
    et al.
    St James Hosp, Ireland.
    Iacobelli, Simona
    Tor Vergata Univ Rome, Italy.
    Antonio Perez-Simon, Jose
    Hosp Univ Virgen Rocio, Spain; Univ Seville, Spain.
    van Biezen, Anja
    Leiden EBMT Data Off, Netherlands.
    Minnema, Monique
    Univ Med Ctr Utrecht, Netherlands.
    Niittyvuopio, Riitta
    HUCH Comprehens Canc Ctr, Finland.
    Schoenland, Stefan
    Heidelberg Univ, Germany.
    Meijer, Ellen
    Vrije Univ Amsterdam Med Ctr, Netherlands.
    Blaise, Didier
    Marseille Inst Paoli Calmettes, France.
    Milpied, Noel
    CHU Bordeaux, France.
    Marquez-Malaver, Francisco J.
    Hosp Univ Virgen Rocio, Spain; Univ Seville, Spain.
    Veelken, Joan Hendrik
    Leiden Univ, Netherlands.
    Maertens, Johan
    Univ Hosp Gasthuisberg, Belgium.
    Michallet, Mauricette
    Ctr Hosp Lyon Sud, France.
    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.
    NGuyen, Stephanie
    Hop La Pitie Salpetriere, France.
    Niederwieser, Dietger
    Univ Hosp Leipzig, Germany.
    Hunault-Berger, Mathilde
    CHRU Angers, France.
    Bourhis, Jean Henri
    Gustave Roussy Inst Cancerol, France.
    Passweg, Jakob
    Univ Hosp Basel, Switzerland.
    Bermudez, Arancha
    FEA Serv Hematol, Spain.
    Chalandon, Yves
    Hop Univ Geneve, Switzerland; Univ Geneva, Switzerland.
    Yakoub-Agha, Ibrahim
    Hop Claude Huriez, France.
    Garderet, Laurent
    Hosp St Antoine, France.
    Kroeger, Nicolaus
    Univ Hosp Eppendorf, Germany.
    Conditioning-based outcomes after allogeneic transplantation for myeloma following a prior autologous transplant (1991-2012) on behalf of EBMT CMWPIn: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609Article in journal (Refereed)
    Abstract [en]

    Objectives The aim of this study was to compare the effect of the intensity of conditioning approaches used in allogeneic transplantation in myeloma-reduced intensity conditioning (RIC), non-myeloablative (NMA), myeloablative conditioning (MAC) or Auto-AlloHCT-on outcomes in patients who had had a prior autologous transplant. Methods A retrospective analysis of the EBMT database (1991-2012) was performed. Results A total of 344 patients aged between 40 and 60 years at the time of alloHCT were identified: 169 RIC, 69 NMA, 65 MAC and 41 Auto-Allo transplants. At a median follow-up of 54 months, the probabilities of overall survival (OS) at 5 years were 39% (95% CI 31%-47%), 45% (95% CI 32%-57%), 19% (95% CI 6%-32%) and 34% (95% CI 17%-51%), respectively. Status at allogeneic HCT other than CR or PR conferred a 70% higher risk of death and a 40% higher risk of relapse. OS was markedly lower in the MAC group (P = .004). MAC alloHCT was associated with a higher risk of death than RIC alloHCT until 2002 (HR = 4.1, P amp;lt; .001) but not after 2002 (HR = 1.2, P = .276). Conclusion From 1991 to 2002, MAC was associated with poorer OS. Between 2003 and 2012, there were no significant differences in outcomes based on these different approaches.

  • 297.
    Hedberg, Suzanne
    et al.
    Univ Gothenburg, Sweden; Sahlgrens 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.
    Petone, Markku
    Natl Inst Hlth and Welf, Finland.
    Osterberg, Johanna
    Mora Hosp, Sweden; 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.
    Ottosson, Johan
    Orebro Univ, Sweden.
    Thorell, Anders
    Karolinska Inst, Sweden; Ersta Hosp, Sweden.
    BEST: Bypass equipoise sleeve trial; rationale and design of a randomized, registry-based, multicenter trial comparing Roux-en-Y gastric bypass with sleeve gastrectomy2019In: Contemporary Clinical Trials, ISSN 1551-7144, E-ISSN 1559-2030, Vol. 84, article id 105809Article in journal (Refereed)
    Abstract [en]

    Background

    Laparoscopic gastric bypass (LGBP) is a well-documented surgical intervention for severe obesity. Recently, laparoscopic sleeve gastrectomy (LSG) has gained increased popularity. Short-term follow-up in limited-sized randomized trials comparing LGBP and LSG show no major differences in weight-loss, adverse events, or effect on comorbidities; however, there is a lack of sufficiently powered, pragmatic, randomized controlled trials comparing the mid- and long-term results of the two methods.

    Method

    BEST is a randomized, registry-based, multicenter trial comparing LGBP and LSG. The trial has two primary outcomes; rates of substantial complications (SC) and total body weight loss. We hypothesize that patients treated with LSG will experience 35% fewer substantial complications during the 5-year follow-up compared to patients treated with LGBP, and that the efficacy of LSG will remain within a non-inferiority margin of 5% in terms of weight loss. Our sample size calculation, using data from the Scandinavian Obesity Surgery Registry (SOReg), shows a power of 80% for SC and > 95% for weight loss at p < .025 with a total of 2100 included patients.

    The design of the trial will also enable comparisons within several relevant patient subgroups.

    Conclusions

    As a large-sized, pragmatic, randomized trial, BEST will provide robust data comparing LGBP with LSG by generating long-term results on weight loss and SC's, as well as secondary outcomes and comparisons within patient subgroups. The use of a well-established registry for registration of all data facilitates a large multicenter trial, and combines the strengths of registry studies with those of a randomized trial.

    Clinical Trials registry: NCT 02767505.

  • 298.
    Hedin, Christina
    et al.
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Sjödahl, Rune
    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.
    Aldman, Åke
    Västerviks sjukhus, Västervik, Sweden.
    Davidson, Thomas
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences.
    Kammerlind, Ann-Sofie
    Region Jönköpings län, Jönköping, Sweden.
    Nodbrant, Per
    Onkologiska kliniken, Länssjukhuset Ryhov, Jönköping, Sweden.
    Agrup, Måns
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Theodorsson, Elvar
    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 Diagnostics, Department of Clinical Chemistry.
    Intraoperativ strålbehandling vid primar operation for bröstcancer: TARGIT-A-studien ej konklusiv2018In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 115, article id EWFFArticle, review/survey (Refereed)
    Abstract [sv]

    The TARGIT-A (TARGeted Intraoperative radioTherapy) multicentre study of early breast cancer compared intraoperative radiotherapy with external radiotherapy. While the intraoperative radiotherapy was standardised, the external postoperative comparison treatment followed established routines in the participating treatment centres resulting in substantial variations in dosages and treatment durations. The uncertainties in the interpretation of the study results created by the design of the TARGIT-A study constitute substantial obstacles to the possible introduction of intraoperative radiotherapy for early breast cancer.

  • 299.
    Heedman, P. A.
    et al.
    Region Östergötland, Center for Health and Developmental Care, Regional Cancer Center South East Sweden. Palliat Educ and Research Centre, Sweden.
    Canslatt, E.
    Lanssjukhuset Kalmar, Sweden.
    Henriks, G.
    Jonköping County Council, Sweden.
    Starkhammar, Hans
    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.
    Fomichov, Victoria
    Region Östergötland, Center for Health and Developmental Care, Regional Cancer Center South East Sweden.
    Sjödahl, Rune
    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 Linköping. Region Östergötland, Center for Health and Developmental Care, Regional Cancer Center South East Sweden.
    Variation at presentation among colon cancer patients with metastases: a population-based study2015In: Colorectal Disease, ISSN 1462-8910, E-ISSN 1463-1318, Vol. 17, no 5, p. 403-408Article in journal (Refereed)
    Abstract [en]

    AimThe study aimed to describe and follow a 2year cohort of colon cancer patients with Stage IV disease from presentation to long-term outcome. MethodThe records of 177 colon cancer patients diagnosed in southeast Sweden during 2009-2010 with disseminated disease at presentation were reviewed retrospectively. ResultsThe patients were heterogeneous with respect to age, performance status and survival. Despite metastatic disease, local symptoms from the primary tumour dominated the initial clinical picture. Forty-one per cent had anaemia. The time from suspicion of colon cancer to established diagnosis of disseminated disease varied from 0 to 231days (emergency cases included, median 12days). The majority (77%) were diagnosed in hospital. In 53% the primary tumour and the metastases were not diagnosed on the same occasion which may increase the risk for misinformation or delays in the care process. The possibility of simultaneous diagnosis was doubled when the patient was investigated as an inpatient. Patients were seen by one to 12 physicians (median three) in the investigation phase, and one to 47 (median 11) from diagnosis until the last record in the hospital notes. The 1-year survival was 46%. ConclusionPatients with metastatic colon cancer at presentation are heterogeneous and warrant an adapted multidisciplinary approach to achieve the goal of individualized treatment for each patient in accordance with the Swedish national cancer strategy.

  • 300.
    Heedman, Per-Anders
    et al.
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment.
    Lagerfelt, Marie
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment.
    Magnusson, Martin
    Region Östergötland, Operations management Region Östergötland, Övrig enhet.
    Sjödahl, Rune
    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.
    Standardiserade vårdförlopp kan ge svårt cancersjuka bättre stöd [High prevalence of advanced cancer disease in patients with serious non-specific symtoms. Experience of a diagnostic pathway in a defined population area in Sweden]2019In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 116Article in journal (Refereed)
    Abstract [en]

    The Swedish fast-track diagnostic pathway was applied during 2017 for 146 patients with serious non-specific symptoms including weight loss, fatigue and anemia. Within five days all patients had a physical examination and a decision was made of radiologic investigations. The waiting time was short for e.g. CT-scan of the abdomen and thorax. A diagnosis of a malignant condition was made in 38 patients (26%) with a median age of 75 (48-91) years. There were 24 men and 14 women. Most common diagnoses were lung cancer and colorectal cancer. Hematologic malignancy was diagnosed in 8 patients. Stage IV disease occurred in 17 of the patients with carcinoma (57%). About 60 benign main diagnoses were made in 108 patients without malignant disease. Two of them have developed cancer during 2018 (breast cancer, pancreatic cancer).

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