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Dahm-Kähler, P., Borgfeldt, C., Holmberg, E., Staf, C., Falconer, H., Bjurberg, M., . . . Åvall-Lundqvist, E. (2017). Population-based study of survival for women with serous cancer of the ovary, fallopian tube, peritoneum or undesignated origin - on behalf of the Swedish gynecological cancer group (SweGCG).. Gynecologic Oncology, 144(1), 167-173
Open this publication in new window or tab >>Population-based study of survival for women with serous cancer of the ovary, fallopian tube, peritoneum or undesignated origin - on behalf of the Swedish gynecological cancer group (SweGCG).
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2017 (English)In: Gynecologic Oncology, ISSN 0090-8258, E-ISSN 1095-6859, Vol. 144, no 1, p. 167-173Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: The aim of the study was to determine survival outcome in patients with serous cancer in the ovary, fallopian tube, peritoneum and of undesignated origin.

METHODS: Nation-wide population-based study of women≥18years with histologically verified non-uterine serous cancer, included in the Swedish Quality Registry for primary cancer of the ovary, fallopian tube and peritoneum diagnosed 2009-2013. Relative survival (RS) was estimated using the Ederer II method. Simple and multivariable analyses were estimated by Poisson regression models.

RESULTS: Of 5627 women identified, 1246 (22%) had borderline tumors and 4381 had malignant tumors. In total, 2359 women had serous cancer; 71% originated in the ovary (OC), 9% in the fallopian tube (FTC), 9% in the peritoneum (PPC) and 11% at an undesignated primary site (UPS). Estimated RS at 5-years was 37%; for FTC 54%, 40% for OC, 34% for PPC and 13% for UPS. In multivariable regression analyses restricted to women who had undergone primary or interval debulking surgery for OC, FTC and PPC, site of origin was not independently associated with survival. Significant associations with worse survival were found for advanced stages (RR 2.63, P<0.001), moderate (RR 1.90, P<0.047) and poor differentiation (RR 2.20, P<0.009), neoadjuvant chemotherapy (RR1.33, P<0.022), residual tumor (RR 2.65, P<0.001) and platinum single (2.34, P<0.001) compared to platinum combination chemotherapy.

CONCLUSION: Survival was poorer for serous cancer at UPS than for ovarian, fallopian tube and peritoneal cancer. Serous cancer at UPS needs to be addressed when reporting and comparing survival rates of ovarian cancer.

Place, publisher, year, edition, pages
Academic Press, 2017
Keywords
Ovarian cancer, Serous cancer, Survival, Cancer origin
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-133707 (URN)10.1016/j.ygyno.2016.10.039 (DOI)000392367000030 ()27817932 (PubMedID)2-s2.0-85005865079 (Scopus ID)
Note

Funding agencies: Swedish Cancer Society; Cancer Society in Stockholm

Available from: 2017-01-07 Created: 2017-01-07 Last updated: 2018-05-02Bibliographically approved
Grundström, H., Kjølhede, P., Berterö, C. & Alehagen, S. (2016). “A challenge” – healthcare professionals' experiences when meeting women with symptoms that might indicate endometriosis. Sexual & Reproductive HealthCare, 7, 65-69
Open this publication in new window or tab >>“A challenge” – healthcare professionals' experiences when meeting women with symptoms that might indicate endometriosis
2016 (English)In: Sexual & Reproductive HealthCare, ISSN 1877-5756, E-ISSN 1877-5764, Vol. 7, p. 65-69Article in journal (Refereed) Published
Abstract [en]

Objective

The aim of the study was to identify and describe the experiences of healthcare professionals when meeting women with symptoms that might indicate endometriosis.

Methods

Semi-structured interviews were conducted with 10 gynecologists, six general practitioners and nine midwives working at one university hospital, one central hospital, one private gynecology clinic and five healthcare centers in south-east Sweden. The interviews were recorded and transcribed verbatim and analyzed using qualitative conventional content analysis.

Results

Three clusters were identified: the corroborating encounter, the normal variation of menstruation cycles, and the suspicion of endometriosis. The healthcare professionals tried to make a corroborating encounter by acknowledging the woman, taking time to listen, and giving an explanation for the problems. Healthcare professionals had different ways to determine what was normal as regards menstrual pain, ovulation pain and dyspareunia. They also needed to have the competence to act and react when the symptoms indicated endometriosis.

Conclusions

Meeting women with symptoms that might indicate endometriosis is challenging and demands a certain level of competence from healthcare professionals. Sometimes the symptoms are camouflaged as “normal” menstruation pain, making it hard to satisfy the needs of this patient group.

Keywords
Chronic pelvic pain;Dysmenorrhea;Endometriosis;Healthcare professional;Qualitative study
National Category
Nursing
Identifiers
urn:nbn:se:liu:diva-124016 (URN)10.1016/j.srhc.2015.11.003 (DOI)000370089000012 ()
Available from: 2016-01-18 Created: 2016-01-18 Last updated: 2018-09-10
Morad, V., Abrahamsson, A., Kjölhede, P. & Dabrosin, C. (2016). Adipokines and Vascular Endothelial Growth Factor in Normal Human Breast Tissue in Vivo - Correlations and Attenuation by Dietary Flaxseed. Journal of mammary gland biology and neoplasia, 21(1-2), 69-76
Open this publication in new window or tab >>Adipokines and Vascular Endothelial Growth Factor in Normal Human Breast Tissue in Vivo - Correlations and Attenuation by Dietary Flaxseed
2016 (English)In: Journal of mammary gland biology and neoplasia, ISSN 1083-3021, E-ISSN 1573-7039, Vol. 21, no 1-2, p. 69-76Article in journal (Refereed) Published
Abstract [en]

Exposure to sex steroids increases the risk of breast cancer but the exact mechanisms are yet to be elucidated. Events in the microenvironment are important for carcinogenesis. Diet containing phytoestrogens can affect the breast microenvironment and alter the risk of breast cancer. It has previously been shown that estrogen regulates extracellular levels of leptin, adiponectin, and VEGF in normal breast tissue in vivo. Whether these proteins correlate in breast tissue in vivo or if diet addition of flaxseed, a major source of phytoestrogens in Western diets, alters adipokine levels in breast tissue are unknown. We used microdialysis to sample proteins of normal human breast tissue and abdominal subcutaneous fat in situ in 34 pre-and postmenopausal women. In vitro, co-culture of breast cancer cells and primary human adipocytes was used. In vivo, in normal breast tissue, a significant positive correlation between VEGF and leptin was detected. No correlations were found in fat tissue. Co-culture of adipocytes and breast cancer cells per se increased the secretion of VEGF and leptin and enhanced the effects of estradiol compared to culture of either cell type alone. In vitro, inhibition of VEGF diminished the release of leptin while inhibition of leptin had no influence on VEGF secretion. The levels of leptin decreased and adiponectin increased after a dietary addition of 25 g of flaxseed/day for one menstrual cycle. We conclude that VEGF and leptin correlate significantly in normal human breast tissue in vivo and that dietary addition of flaxseed affect adipokine levels in the breast.

Place, publisher, year, edition, pages
SPRINGER/PLENUM PUBLISHERS, 2016
Keywords
Flaxseed; Diet; Microdialysis; Estrogen; Leptin; Adiponectin
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:liu:diva-130433 (URN)10.1007/s10911-016-9352-9 (DOI)000379327000009 ()27059487 (PubMedID)
Available from: 2016-08-07 Created: 2016-08-05 Last updated: 2017-11-28
Rajan, M. R., Nyman, E., Kjölhede, P., Cedersund, G. & Strålfors, P. (2016). Systems-wide Experimental and Modeling Analysis of Insulin Signaling through Forkhead Box Protein O1 (FOXO1) in Human Adipocytes, Normally and in Type 2 Diabetes. Journal of Biological Chemistry, 291(30), 15806-15819
Open this publication in new window or tab >>Systems-wide Experimental and Modeling Analysis of Insulin Signaling through Forkhead Box Protein O1 (FOXO1) in Human Adipocytes, Normally and in Type 2 Diabetes
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2016 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 291, no 30, p. 15806-15819Article in journal (Refereed) Published
Abstract [en]

Insulin resistance is a major aspect of type 2 diabetes (T2D), which results from impaired insulin signaling in target cells. Signaling to regulate forkhead box protein O1 (FOXO1) may be the most important mechanism for insulin to control transcription. Despite this, little is known about how insulin regulates FOXO1 and how FOXO1 may contribute to insulin resistance in adipocytes, which are the most critical cell type in the development of insulin resistance. We report a detailed mechanistic analysis of insulin control of FOXO1 in human adipocytes obtained from non-diabetic subjects and from patients with T2D. We show that FOXO1 is mainly phosphorylated through mTORC2-mediated phosphorylation of protein kinase B at Ser(473) and that this mechanism is unperturbed in T2D. We also demonstrate a cross-talk from the MAPK branch of insulin signaling to stimulate phosphorylation of FOXO1. The cellular abundance and consequently activity of FOXO1 are halved in T2D. Interestingly, inhibition of mTORC1 with rapamycin reduces the abundance of FOXO1 to the levels in T2D. This suggests that the reduction of the concentration of FOXO1 is a consequence of attenuation of mTORC1, which defines much of the diabetic state in human adipocytes. We integrate insulin control of FOXO1 in a network-wide mathematical model of insulin signaling dynamics based on compatible data from human adipocytes. The diabetic state is network-wide explained by attenuation of an mTORC1-to-insulin receptor substrate-1 (IRS1) feedback and reduced abundances of insulin receptor, GLUT4, AS160, ribosomal protein S6, and FOXO1. The model demonstrates that attenuation of the mTORC1-to-IRS1 feedback is a major mechanism of insulin resistance in the diabetic state.

Place, publisher, year, edition, pages
Rockville, Maryland: American Society for Biochemistry and Molecular Biology, 2016
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:liu:diva-130998 (URN)10.1074/jbc.M116.715763 (DOI)000380584200033 ()27226562 (PubMedID)
Note

Funding agencies|Swedish Diabetes Fund, University of Linköping; Swedish Research Council; AstraZeneca

Available from: 2016-09-02 Created: 2016-09-02 Last updated: 2017-04-24Bibliographically approved
Morad, V., Abrahamsson, A., Kjölhede, P. & Dabrosin, C. (2015). Correlation between vascular endothelial growth factor and leptin in normal human breast tissue in vivo.
Open this publication in new window or tab >>Correlation between vascular endothelial growth factor and leptin in normal human breast tissue in vivo
2015 (English)Manuscript (preprint) (Other academic)
Abstract [en]

Introduction: Events in the microenvironment are important for carcinogenesis of the breast. Adipocytes, which produce adipokines with paracrine effects, are the most abundant cell type in breast tissue. Exposure to sex steroids affects the risk of breast cancer. It has previously been shown that estrogen regulates the extracellular levels of leptin, adiponectin, IL-1β, and VEGF in normal human breast tissue in vivo.

Objective: We aimed to determine if there were any relationships between leptin, adiponectin, IL-1β, and/or VEGF in normal human breast tissue in vivo and to elucidate the role of adipocytes in the regulation of these factors.

Design and methods: Microdialysis was used to sample proteins of normal human breast tissue and abdominal subcutaneous (s.c.) fat in situ in pre-and postmenopausal women. An in vitro co-culture model of breast cancer cells and primary mature human adipocytes was used.

Results: In vivo, in normal breast tissue, significant positive correlations between VEGF and leptin, and VEGF and leptin/adiponectin ratio were detected. No correlations were found in s.c. abdominal fat tissue. Co-culture of adipocytes and breast cancer cells per se increased the secretion of VEGF and leptin and enhanced the effects of estradiol compared to culture of either cell type alone. In vitro, inhibition of VEGF diminished the release of leptin while inhibition of leptin had no influence on VEGF secretion. In breast tissue, significant correlations between IL-1β and leptin and VEGF were revealed.

Conclusions: Our results suggest that VEGF regulates leptin in normal human breast tissue. Moreover, physical contact between adipocytes and breast cancer cells, induces phenotypic changes and enhances the effects of estradiol. These mechanisms may be involved in breast cancer progression.

National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-117982 (URN)
Available from: 2015-05-19 Created: 2015-05-19 Last updated: 2015-05-19Bibliographically approved
Kjölhede, P., Dahm-Kähler, P., Tholander, B. & Åvall Lundqvist, E. (2015). Individualiserad behandling vid ovarialcancer kan bli möjlig. Läkartidningen, 112(50), 2281-3
Open this publication in new window or tab >>Individualiserad behandling vid ovarialcancer kan bli möjlig
2015 (Swedish)In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 112, no 50, p. 2281-3Article in journal (Refereed) Published
Abstract [en]

Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy in developed countries. Several promising steps toward individualized therapy have been taken recently due to increased knowledge of molecular biology. Multidisciplinary conferences for treatment planning and the centralization to tertiary surgical centers improve quality of surgery and survival. The primary treatment of EOC is radical surgery followed by adjuvant chemotherapy with carboplatin and paclitaxel. Bevacizumab added to the chemotherapy and used as maintenance treatment is standard in the primary treatment of patients with residual tumor or inoperable patients. The PARP inhibitor olaparib is recommended as maintenance treatment of women with platinum sensitive relapsed BRCA mutated high-grade serous EOC who have responded to platinum-based chemotherapy. BRCA testing should be offered to women with EOC. In platinum-resistant recurrence addition of bevacizumab to chemotherapy should be considered.

Abstract [sv]

Ovarialcancer har högst mortalitet bland gynekologiska cancersjukdomar. I Sverige insjuknar årligen ca 700 patienter. Överlevnaden är bland de högsta i Europa, men på en låg nivå, 46 procent.Nästan 90 procent av kvinnor-na har symtom även i tidigt stadium.Symtom som ska väcka misstanke om ovarialcancer är ihållande utspänd buk, tidig mättnadskänsla, bäcken- eller buksmärta, ökande urinträngningar och postmenopausal blödning.Kvinnors benägenhet att söka sjukvård och sjukvårdens organisation bidrar till canceröverlevnad.Ovarialcancer sammanfattarflera sjukdomar med skilda tumörkarakteristika och prognos. Individualiserad behandling och preventiva åtgärder utifrån denna nyvunna kunskap kan komma att inverka positivt på överlevnaden.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:liu:diva-125273 (URN)26646960 (PubMedID)
Available from: 2016-02-18 Created: 2016-02-18 Last updated: 2017-05-12Bibliographically approved
Kjölhede, P., Persson, P. & Brynhildsen, J. (2014). Authors' reply: Pelvic organ prolapse after subtotal and total hysterectomy: a long-term follow-up of an open randomised controlled multicentre study [Letter to the editor]. British Journal of Obstetrics and Gynecology, 121(12), 1579-1579
Open this publication in new window or tab >>Authors' reply: Pelvic organ prolapse after subtotal and total hysterectomy: a long-term follow-up of an open randomised controlled multicentre study
2014 (English)In: British Journal of Obstetrics and Gynecology, ISSN 1470-0328, E-ISSN 1471-0528, Vol. 121, no 12, p. 1579-1579Article in journal, Letter (Other academic) Published
Abstract [en]

n/a

Place, publisher, year, edition, pages
Wiley-Blackwell, 2014
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-112618 (URN)10.1111/1471-0528.12701 (DOI)000344372600032 ()25348452 (PubMedID)
Available from: 2014-12-08 Created: 2014-12-05 Last updated: 2017-12-05Bibliographically approved
Blomberg, M., Birch Tyrberg, R. & Kjölhede, P. (2014). Impact of maternal age on obstetric and neonatal outcome with emphasis on primiparous adolescents and older women: a Swedish Medical Birth Register Study. BMJ Open, 4(11), e005840
Open this publication in new window or tab >>Impact of maternal age on obstetric and neonatal outcome with emphasis on primiparous adolescents and older women: a Swedish Medical Birth Register Study
2014 (English)In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 4, no 11, p. e005840-Article in journal (Refereed) Published
Abstract [en]

Objectives: To evaluate the associations between maternal age and obstetric and neonatal outcomes in primiparous women with emphasis on teenagers and older women. Design: A population-based cohort study. Setting: The Swedish Medical Birth Register. Participants: Primiparous women with singleton births from 1992 through 2010 (N=798 674) were divided into seven age groups: less than17 years, 17-19 years and an additional five 5-year classes. The reference group consisted of the women aged 25-29 years. Primary outcome: Obstetric and neonatal outcome. Results: The teenager groups had significantly more vaginal births (adjusted OR (aOR) 2.04 (1.79 to 2.32) and 1.95 (1.88 to 2.02) for age less than17 years and 1719 years, respectively); fewer caesarean sections (aOR 0.57 (0.48 to 0.67) and 0.55 (0.53 to 0.58)), and instrumental vaginal births (aOR 0.43 (0.36 to 0.52) and 0.50 (0.48 to 0.53)) compared with the reference group. The opposite was found among older women reaching a fourfold increased OR for caesarean section. The teenagers showed no increased risk of adverse neonatal outcome but presented an increased risk of prematurity less than32 weeks (aOR 1.66 (1.10 to 2.51) and 1.20 (1.04 to 1.38)). Women with advancing age (greater than= 30 years) revealed significantly increased risk of prematurity, perineal lacerations, preeclampsia, abruption, placenta previa, postpartum haemorrhage and unfavourable neonatal outcomes compared with the reference group. Conclusions: For clinicians counselling young women it is of importance to highlight the obstetrically positive consequences that fewer maternal complications and favourable neonatal outcomes are expected. The results imply that there is a need for individualising antenatal surveillance programmes and obstetric care based on age grouping in order to attempt to improve the outcomes in the age groups with less favourable obstetric and neonatal outcomes. Such changes in surveillance programmes and obstetric interventions need to be evaluated in further studies.

Place, publisher, year, edition, pages
BMJ Publishing Group: Open Access / BMJ Journals, 2014
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:liu:diva-113224 (URN)10.1136/bmjopen-2014-005840 (DOI)000345762300028 ()25387756 (PubMedID)
Note

Funding Agencies|County Council of Ostergotland; Linkoping University

Available from: 2015-01-12 Created: 2015-01-12 Last updated: 2017-12-05
Lundin, E. S., Johansson, T., Zachrisson, H., Leandersson, U., Backman, F., Falknas, L. & Kjölhede, P. (2014). Single-dose tranexamic acid in advanced ovarian cancer surgery reduces blood loss and transfusions: double-blind placebo-controlled randomized multicenter study. Acta Obstetricia et Gynecologica Scandinavica, 93(4), 335-344
Open this publication in new window or tab >>Single-dose tranexamic acid in advanced ovarian cancer surgery reduces blood loss and transfusions: double-blind placebo-controlled randomized multicenter study
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2014 (English)In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 93, no 4, p. 335-344Article in journal (Refereed) Published
Abstract [en]

ObjectiveTo determine whether single-dose tranexamic acid given intravenously immediately before surgery for presumed advanced ovarian cancer reduces perioperative blood loss and blood transfusions. DesignA randomized double-blind, placebo-controlled multicenter study. SettingTwo university hospitals and two central hospitals in the southeast health region of Sweden. PopulationOne hundred women with presumed advanced ovarian cancer scheduled for radical debulking surgery between March 2008 and May 2012 who complied with inclusion/exclusion criteria were randomized; 50 were allocated to receive tranexamic acid and 50 to receive placebo. Analysis was performed according to intention-to-treat principles. MethodsThe volume of tranexamic acid (15mg/kg body weight, 100mg/mL tranexamic acid) or the same volume of placebo (0.9% NaCl) was added to a 100-mL saline solution plastic bag. The study medication was given immediately before the start of surgery. Data were analyzed by means of non-parametric statistics and multivariate models adjusted for confounding factors. Main outcome measuresBlood loss and red blood cell transfusions. ResultsThe total blood loss volume and transfusion rate were significantly lower in the tranexamic acid group compared with the placebo group. Median total blood loss was 520 and 730mL, respectively (p=0.03). Fifteen (30%) and 22 (44%), respectively received transfusions (odds ratio 0.44; upper 95% CI 0.97; p=0.02). ConclusionA single dose of tranexamic acid given immediately before surgery reduces blood loss and transfusion rates significantly in advanced ovarian cancer surgery. Tranexamic acid may be recommended as standard prophylactic treatment in advanced ovarian cancer surgery.

Place, publisher, year, edition, pages
Informa Healthcare / Wiley, 2014
Keywords
Blood loss; ovarian cancer; randomized trial; surgery; tranexamic acid; transfusion
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-106118 (URN)10.1111/aogs.12333 (DOI)000333150700003 ()
Available from: 2014-04-25 Created: 2014-04-24 Last updated: 2017-12-05
Borendal Wodlin, N., Nilsson, L. & Kjölhede, P. (2014). Snabbspår har fördelar vid elektiv gynekologisk kirurgi.. Läkartidningen, 111(25-26), 2-7
Open this publication in new window or tab >>Snabbspår har fördelar vid elektiv gynekologisk kirurgi.
2014 (Swedish)In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 111, no 25-26, p. 2-7Article in journal (Refereed) Published
Abstract [sv]

Principerna för snabbspår i samband med elektiv kirurgi har visat sig förbättra och påskynda postoperativ återhämtning.

Snabbspår bygger på en kombination av evidensbaserade åtgärder och förhållningssätt pre-, per- och postoperativt.

Översikten ger stöd för uppfattningen att snabbspår ska användas i samband med elektiv benign gynekologisk kirurgi för att optimera patientens återhämtning.

Trots övertygande evidens behövs ytterligare studier, information och utbildning för att förbättra införandet av principer för snabbspår i samband med gynekologisk kirurgi. 

Engagemang från alla inblandade personalkategorier är avgörande för möjligheten till implementering.

Abstract [en]

Fast-track is a multimodal strategy aimed at achieving an improved and accelerated postoperative recovery. The strategy combines unimodal evidence-based interventions concerning preoperative preparation, peroperative principles and postoperative care. There is substantial evidence for the benefits of following fast-track concepts in general elective surgery to enhance postoperative recovery. The main findings of this review are that there are benefits likewise within elective gynecological surgery, but studies of quality of life, patient satisfaction and health economics are needed. Studies of fast-track within non-elective surgery and gynaecological oncology surgery are lacking. Widespread information and education is needed to improve the rate of implementation of fast-track. Comprehensive involvement of the entire staff dealing with the patient in the perioperative period is crucial to ensure implementation and development of surgical care aiming for enhanced postoperative recovery.

National Category
Other Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-115279 (URN)25072075 (PubMedID)
Available from: 2015-03-12 Created: 2015-03-12 Last updated: 2017-12-04Bibliographically approved
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