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      Risk factors and a prediction model for lower limb lymphedema following lymphadenectomy in gynecologic cancer: a hospital-based retrospective cohort study

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          Abstract

          Background

          Lower limb lymphedema (LLL) is a chronic and incapacitating condition afflicting patients who undergo lymphadenectomy for gynecologic cancer. This study aimed to identify risk factors for LLL and to develop a prediction model for its occurrence.

          Methods

          Pelvic lymphadenectomy (PLA) with or without para-aortic lymphadenectomy (PALA) was performed on 366 patients with gynecologic malignancies at Yaizu City Hospital between April 2002 and July 2014; we retrospectively analyzed 264 eligible patients. The intervals between surgery and diagnosis of LLL were calculated; the prevalence and risk factors were evaluated using the Kaplan-Meier and Cox proportional hazards methods. We developed a prediction model with which patients were scored and classified as low-risk or high-risk.

          Results

          The cumulative incidence of LLL was 23.1% at 1 year, 32.8% at 3 years, and 47.7% at 10 years post-surgery. LLL developed after a median 13.5 months. Using regression analysis, body mass index (BMI) ≥25 kg/m 2 (hazard ratio [HR], 1.616; 95% confidence interval [CI], 1.030–2.535), PLA + PALA (HR, 2.323; 95% CI, 1.126–4.794), postoperative radiation therapy (HR, 2.469; 95% CI, 1.148–5.310), and lymphocyst formation (HR, 1.718; 95% CI, 1.120–2.635) were found to be independently associated with LLL; age, type of cancer, number of lymph nodes, retroperitoneal suture, chemotherapy, lymph node metastasis, herbal medicine, self-management education, or infection were not associated with LLL. The predictive score was based on the 4 associated variables; patients were classified as high-risk (scores 3–6) and low-risk (scores 0–2). LLL incidence was significantly greater in the high-risk group than in the low-risk group (HR, 2.19; 95% CI, 1.440–3.324). The cumulative incidence at 5 years was 52.1% [95% CI, 42.9–62.1%] for the high-risk group and 28.9% [95% CI, 21.1–38.7%] for the low-risk group. The area under the receiver operator characteristics curve for the prediction model was 0.631 at 1 year, 0.632 at 3 years, 0.640 at 5 years, and 0.637 at 10 years.

          Conclusion

          BMI ≥25 kg/m 2, PLA + PALA, lymphocyst formation, and postoperative radiation therapy are significant predictive factors for LLL. Our prediction model may be useful for identifying patients at risk of LLL following lymphadenectomy. Providing an intensive therapeutic strategy for high-risk patients may help reduce the incidence of LLL and conserve the quality of life.

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          Most cited references41

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          Detection rate and diagnostic accuracy of sentinel-node biopsy in early stage endometrial cancer: a prospective multicentre study (SENTI-ENDO).

          Retrospective single-centre series have shown the feasibility of sentinel lymph-node (SLN) identification in endometrial cancer. We did a prospective, multicentre cohort study to assess the detection rate and diagnostic accuracy of the SLN procedure in predicting the pathological pelvic-node status in patients with early stage endometrial cancer. Patients with International Federation of Gynecology and Obstetrics (FIGO) stage I-II endometrial cancer had pelvic SLN assessment via cervical dual injection (with technetium and patent blue), and systematic pelvic-node dissection. All lymph nodes were histopathologically examined and SLNs were serial sectioned and examined by immunochemistry. The primary endpoint was estimation of the negative predictive value (NPV) of sentinel-node biopsy per hemipelvis. This is an ongoing study for which recruitment has ended. The study is registered with ClinicalTrials.gov, number NCT00987051. From July 5, 2007, to Aug 4, 2009, 133 patients were enrolled at nine centres in France. No complications occurred after injection of technetium colloid and no anaphylactic reactions were noted after patent blue injection. No surgical complications were reported during SLN biopsy, including procedures that involved conversion to open surgery. At least one SLN was detected in 111 of the 125 eligible patients. 19 of 111 (17%) had pelvic-lymph-node metastases. Five of 111 patients (5%) had an associated SLN in the para-aortic area. Considering the hemipelvis as the unit of analysis, NPV was 100% (95% CI 95-100) and sensitivity 100% (63-100). Considering the patient as the unit of analysis, three patients had false-negative results (two had metastatic nodes in the contralateral pelvic area and one in the para-aortic area), giving an NPV of 97% (95% CI 91-99) and sensitivity of 84% (62-95). All three of these patients had type 2 endometrial cancer. Immunohistochemistry and serial sectioning detected metastases undiagnosed by conventional histology in nine of 111 (8%) patients with detected SLNs, representing nine of the 19 patients (47%) with metastases. SLN biopsy upstaged 10% of patients with low-risk and 15% of those with intermediate-risk endometrial cancer. SLN biopsy with cervical dual labelling could be a trade-off between systematic lymphadenectomy and no dissection at all in patients with endometrial cancer of low or intermediate risk. Moreover, our study suggests that SLN biopsy could provide important data to tailor adjuvant therapy. Direction Interrégionale de Recherche Clinique, Ile-de-France, Assistance Publique-Hôpitaux de Paris. Copyright © 2011 Elsevier Ltd. All rights reserved.
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            Effectiveness of early physiotherapy to prevent lymphoedema after surgery for breast cancer: randomised, single blinded, clinical trial

            Objective To determine the effectiveness of early physiotherapy in reducing the risk of secondary lymphoedema after surgery for breast cancer. Design Randomised, single blinded, clinical trial. Setting University hospital in Alcalá de Henares, Madrid, Spain. Participants 120 women who had breast surgery involving dissection of axillary lymph nodes between May 2005 and June 2007. Intervention The early physiotherapy group was treated by a physiotherapist with a physiotherapy programme including manual lymph drainage, massage of scar tissue, and progressive active and action assisted shoulder exercises. This group also received an educational strategy. The control group received the educational strategy only. Main outcome measure Incidence of clinically significant secondary lymphoedema (>2 cm increase in arm circumference measured at two adjacent points compared with the non-affected arm). Results 116 women completed the one year follow-up. Of these, 18 developed secondary lymphoedema (16%): 14 in the control group (25%) and four in the intervention group (7%). The difference was significant (P=0.01); risk ratio 0.28 (95% confidence interval 0.10 to 0.79). A survival analysis showed a significant difference, with secondary lymphoedema being diagnosed four times earlier in the control group than in the intervention group (intervention/control, hazard ratio 0.26, 95% confidence interval 0.09 to 0.79). Conclusion Early physiotherapy could be an effective intervention in the prevention of secondary lymphoedema in women for at least one year after surgery for breast cancer involving dissection of axillary lymph nodes. Trial registration Current controlled trials ISRCTN95870846.
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              Weight lifting for women at risk for breast cancer-related lymphedema: a randomized trial.

              Clinical guidelines for breast cancer survivors without lymphedema advise against upper body exercise, preventing them from obtaining established health benefits of weight lifting. To evaluate lymphedema onset after a 1-year weight lifting intervention vs no exercise (control) among survivors at risk for breast cancer-related lymphedema (BCRL). A randomized controlled equivalence trial (Physical Activity and Lymphedema trial) in the Philadelphia metropolitan area of 154 breast cancer survivors 1 to 5 years postunilateral breast cancer, with at least 2 lymph nodes removed and without clinical signs of BCRL at study entry. Participants were recruited between October 1, 2005, and February 2007, with data collection ending in August 2008. Weight lifting intervention included a gym membership and 13 weeks of supervised instruction, with the remaining 9 months unsupervised, vs no exercise. Incident BCRL determined by increased arm swelling during 12 months (≥5% increase in interlimb difference). Clinician-defined BCRL onset was also evaluated. Equivalence margin was defined as doubling of lymphedema incidence. A total of 134 participants completed follow-up measures at 1 year. The proportion of women who experienced incident BCRL onset was 11% (8 of 72) in the weight lifting intervention group and 17% (13 of 75) in the control group (cumulative incidence difference [CID], -6.0%; 95% confidence interval [CI], -17.2% to 5.2%; P for equivalence = .04). Among women with 5 or more lymph nodes removed, the proportion who experienced incident BCRL onset was 7% (3 of 45) in the weight lifting intervention group and 22% (11 of 49) in the control group (CID, -15.0%; 95% CI, -18.6% to -11.4%; P for equivalence = .003). Clinician-defined BCRL onset occurred in 1 woman in the weight lifting intervention group and 3 women in the control group (1.5% vs 4.4%, P for equivalence = .12). In breast cancer survivors at risk for lymphedema, a program of slowly progressive weight lifting compared with no exercise did not result in increased incidence of lymphedema. clinicaltrials.gov Identifier: NCT00194363.
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                Author and article information

                Contributors
                +81-54-623-3111 , kenji.kuroda@hospital.yaizu.shizuoka.jp
                yamamotoyasuhiro77@gmail.com
                manami.yanagisawa@hospital.yaizu.shizuoka.jp
                akira.kawata@hospital.yaizu.shizuoka.jp
                naoya.akiba@hospital.yaizu.shizuoka.jp
                kensuke.suzuki@hospital.yaizu.shizuoka.jp
                kazutoshi.naritaka@hospital.yaizu.shizuoka.jp
                Journal
                BMC Womens Health
                BMC Womens Health
                BMC Women's Health
                BioMed Central (London )
                1472-6874
                25 July 2017
                25 July 2017
                2017
                : 17
                : 50
                Affiliations
                Department of Obstetrics and Gynecology, Yaizu City Hospital, 1000, Dobara, Yaizu-shi, 425-8505 Japan
                Author information
                http://orcid.org/0000-0001-9960-9673
                Article
                403
                10.1186/s12905-017-0403-1
                5526302
                28743274
                b91c14e6-e0a4-4892-81d6-58f488d7955e
                © The Author(s). 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 2 May 2016
                : 19 July 2017
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2017

                Obstetrics & Gynecology
                lower limb lymphedema,lymph node dissection,lymphocyst,body mass index,prediction model

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