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Risk factors for lymphedema and method of assessment in endometrial cancer: a prospective longitudinal multicenter study
  1. Madelene Wedin1,
  2. Karin Stalberg2,
  3. Janusz Marcickiewicz3,
  4. Eva Ahlner4,
  5. Ulrika Ottander5,
  6. Åsa Åkesson6,
  7. Gabriel Lindahl7,
  8. Ninnie Borendal Wodlin8 and
  9. Preben Kjølhede8
  10. The LASEC study group
    1. 1 biomedical and clinical science, Linköping University, Linkoping, Sweden
    2. 2 Department of Women‘s and Children‘s Health, Uppsala University, Uppsala, Sweden
    3. 3 Department of Obstetrics and Gynecology, Varberg Hospital, Varberg, Sweden
    4. 4 Department of Oncology, and Department of Biomedical and Clinical Science, Linköping University Hospital, Linkoping, Sweden
    5. 5 Department of Clinical Sciences, Obstetrics and Gynecology, Umeå University, Umeå, Sweden
    6. 6 Department of Obstetrics and Gynecology, Sahlgrenska University Hospital, Institute of clinical sciences, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden
    7. 7 Department of Oncology, and Department of Biomedical and Clinical Scienses, Linköping University, Linköping, Sweden
    8. 8 Department of Obstetrics and Gynecology in Linköping and Department of Biomedical and Clinical Science, Linköping University, Linköping, Sweden
    1. Correspondence to Dr Madelene Wedin, Department of Obstetrics and Gynecology, and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, 581 83 Linköping, Sweden; madelene.wedin{at}regionostergotland.se

    Abstract

    Objective The aim of the study was to determine risk factors for lymphedema of the lower limbs, assessed by four methods, 1 year after surgery for endometrial cancer.

    Methods A prospective longitudinal multicenter study was conducted in 14 Swedish hospitals. 235 women with endometrial cancer were included; 116 underwent surgery including lymphadenectomy, and 119 had surgery without lymphadenectomy. Lymphedema was assessed preoperatively and 1 year postoperatively objectively by systematic circumferential measurements of the legs, enabling volume estimation addressed as (1) crude volume and (2) body mass index-standardized volume, or (3) clinical grading, and (4) subjectively by patient-reported perception of leg swelling. In volume estimation, lymphedema was defined as a volume increase ≥10%. Risk factors were analyzed using forward stepwise logistic regression models and presented as adjusted odds ratio (aOR) and 95% confidence interval (95% CI).

    Results Risk factors varied substantially, depending on the method of determining lymphedema. Lymphadenectomy was a risk factor for lymphedema when assessed by body mass index-standardized volume (aOR 14.42, 95% CI 3.49 to 59.62), clinical grading (aOR 2.11, 95% CI 1.04 to 4.29), and patient-perceived swelling (aOR 2.51, 95% CI 1.33 to 4.73), but not when evaluated by crude volume. Adjuvant radiotherapy was only a risk factor for lymphedema when assessed by body mass index-standardized volume (aOR 15.02, 95% CI 2.34 to 96.57). Aging was a risk factor for lymphedema when assessed by body mass index-standardized volume (aOR 1.07, 95% CI 1.00 to 1.15) and patient-perceived swelling (aOR 1.06, 95% CI 1.02 to 1.10), but not when assessed by crude volume or clinical grading. Increase in body mass index was a risk factor for lymphedema when estimated by crude volume (aOR 1.92, 95% CI 1.36 to 2.71) and patient-perceived swelling (aOR 1.36, 95% CI 1.11 to 1.66), but not by body mass index-standardized volume or clinical grading. The extent of lymphadenectomy was strongly predictive for the development of lymphedema when assessed by body mass index-standardized volume and patient-perceived swelling, but not by crude volume or clinical grading.

    Conclusion Apparent risk factors for lymphedema differed considerably depending on the method used to determine lymphedema. This highlights the need for a ‘gold standard’ method when addressing lymphedema for determining risk factors.

    • surgery
    • endometrial neoplasms
    • sln and lympadenectomy

    Data availability statement

    Data are available upon reasonable request. Data are available upon reasonable request and in accordance with Swedish legislation. In accordance with the journal’s guidelines, we will provide our data in de-identified form for the reproducibility of this study in other centers if such is requested.

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    Data availability statement

    Data are available upon reasonable request. Data are available upon reasonable request and in accordance with Swedish legislation. In accordance with the journal’s guidelines, we will provide our data in de-identified form for the reproducibility of this study in other centers if such is requested.

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    Footnotes

    • Collaborators The LASEC trial group consisted of (in alphabetic order of the hospitals): Eva Rundqvist, MD, Sarah Karlsson, RNM (Blekinge Hospital, Karlskrona), Lisbeth Liest, MD, Liselotte Roos, RN, Karin Norin Andersson, RPT (Eksjö Highland Hospital), Åsa Nyberg, MD, PhD, Karin Ervard, RN, Helena Johansson, RPT (Falun Hospital). Peter Smith, MD, PhD, Anette Henriksson, RN, Lena Larsson, Ulrika Ehn, RPT (Gävle Hospital). Margareta Lood, MD, Lena Hermansson, RN, Eva Satherberg RN, Eva Eliasson RPT (Karlstad Central Hospital). Eva Blank, MD, PhD, Inga-Lill Martinsson, RN, Marie de-France Westerling, RPT, Eva Mattsson RPT (NÄL Hospital, Trollhättan). Åsa Åkesson, MD, Eva Rosén, RN, Birgitta Bååthe, RPT, Elisabeth Brodin, RPT, Matilda Möller, RPT (Sahlgrenska University Hospital, Gothenburg). Lars Hogström, MD, Maarten Buimer, MD, PhD, Agneta Johansson, RN, Eva Andersson RN, Johanna Tallbacka, RPT, Sofie Eriksson, RPT (Skaraborg Hospital, Skövde). Lotta Andrèen, MD, PhD, Christine Näslund, RN, Ylva Vidgren, RPT (Sundsvall Regional Hospital). Preben Kjølhede, MD, PhD, Madelene Wedin, MD, Per Rosenberg, MD, PhD, Gabriel Lindahl, MD, PhD, Ninnie Borendal Wodlin, MD, PhD, Linda Shosholli, RN, Åsa Rydmark Kersley, RN, MScN, Eva Ahlner, RPT (University Hospital, Linköping). Ulrika Ottander, MD, PhD, Jenny Eklund, RN, Åsa Sandström, Annika Falk, RPT (University Hospital of Umeå). Karin Glimskär Stålberg, MD, PhD, Charlotte Eklind, RN, Petra Strandh, RPT, Nicola Ingvast, RPT (Uppsala University Hospital). Janusz Marcickiewicz, MD, PhD, Pia Andersson, RN Lotti Källman, RN, Viveka Grant-Pedersen, RPT (Varberg Hospital). Anders Rosenmüller, MD, Carina Bergsten, RN, Camilla Dahlberg, RPT (Västervik Hospital). Lars Henning, MD, Andres Hess Engström, RPT (Västmanland Hospital, Västerås).

    • Contributors PK conceptualized the study and wrote the study protocol together with EA, KS, and JM. MW is the main author of the manuscript. PK and MW conducted the statistical analyses. All authors participated actively in conducting the study, evaluating the analyses and critically revised the manuscript, approved the final version, and are accountable for all aspects of the work.

    • Funding The work was supported by The Swedish Cancer Society (Cancerfonden) (grant number CAN2013/620; recipient: PK), The Medical Research Council of Southeast Sweden (grant numbers FORSS-308611, FORSS-391311, FORSS-662141 and FORSS-858611; recipient: PK), Uppsala-Örebro Regional Research Council (grant number LUL-349271; recipient: KS) and unrestricted grants from the Scientific Council of the Region Halland (recipient: JM), the County Council of Östergötland (recipient: PK), and Linköping University (recipient: PK).

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.

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