Objective evaluation of skin stiffness in breast cancer-related lymphedema using MyotoPRO

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Skin stiffness is one of the symptoms of lymphedema; however, no objective method has been established to evaluate this symptom. We aimed to examine whether MyotonPRO, which is used to evaluate muscle and fascia stiffness, could evaluate skin stiffness in upper limb lymphedema. Methods Female patients with breast cancer-related lymphedema (BCRL) after unilateral breast cancer surgery were included. Stiffness by MyotonPRO and circumference were measured on both sides 5 and 10 cm from the elbow joint of the forearm and upper arm, respectively. Measurements were compared between the normal and lymphedema limbs. History of breast cancer, lymphedema and comorbidities were collected from medical records, and the relationship with skin stiffness was evaluated. Results The skin stiffness values of normal and lymphedema limbs were 249 ± 50 and 283 ± 56 N/m (p < 0.001) in the upper arm and 306 ± 44 and 353 ± 64 N/m (p < 0.001) in the forearm, respectively, and were significantly greater in the lymphedema limb. The circumferences of the normal and lymphedema limbs were 27.5 ± 3.6 and 29.1 ± 4.0 cm (p < 0.001) for the upper arm and 23.7 ± 2.4 and 25.1 ± 2.9 cm (p < 0.001) for the forearm, respectively, in which the lymphedema limb was significantly larger. In the multiple regression analysis, diabetes had the greatest effect on the lymphedema limb stiffness. Conclusion MyotonPRO can objectively assess chronic skin stiffness in BCRL. breast cancer-related lymphedema skin stiffness MyotonPRO measurement Figures Figure 1 Figure 2 Introduction Breast cancer is the most common malignant tumour in women [ 1 ], and breast cancer-related lymphedema (BCRL) is a complication of axillary dissection and radiation therapy in breast cancer [ 2 , 3 ]. The incidence of BCRL is approximately 20%. BCRL not only results in upper extremity disability, including decreased range of motion, muscle weakness and sensory abnormalities but also causes depression; anxiety; social, family, occupational and sexual difficulties; and financial and time burdens [ 4 – 6 ]. Therefore, early diagnosis and appropriate treatment is important, and complex physical therapy (CPT) is recommended as a treatment [ 7 ]. CPT consists of skin care, manual lymphatic drainage, compression and myolymphokinetic exercises [ 8 ]. BCRL symptoms include skin stiffness, and patients have reported subjective improvement in skin stiffness with manual lymphatic drainage [ 9 ]. Although skin stiffness is a symptom of BCRL, it is not indicated in the evaluation of the treatment efficacy of CPT. Because no method has been established for determining skin stiffness, evaluation relies on the subjectivity of the patient and skills of the evaluator [ 10 ]. A simple and objective evaluation of skin stiffness would be useful in evaluating BCRL and determining the efficacy of CPT. If skin stiffness could be evaluated objectively, BCRL could be detected earlier, and treatment could be initiated sooner. MyotonPRO, a tissue stiffness tester, is widely used for objective and non-invasive assessment of body surface skeletal muscles [ 11 , 12 ]. MyotonPRO is also useful in assessing skin stiffness [ 13 , 14 ]. In this study, we investigated whether MyotonPRO can be used to objectively assess skin stiffness in BCRL. In addition, the influence of patient factors such as lymphedema stage and history of cellulitis and diabetes on skin stiffness was statistically evaluated. Patients and methods Patients This study included female patients diagnosed with unilateral postoperative BCRL after breast cancer surgery with lymph node dissection who had attended Aichi Medical University Hospital as an outpatient for CPT between February and October 2023 and gave consent to participate in the study. Patients who were not living independently (patients with intervening care) were excluded. Patient data included age, height, weight, body mass index (BMI), comorbidities (diabetes, hypertension and hyperlipidaemia), direction of the dominant hand, side of the affected limbs, cancer type, operation type, presence of breast reconstruction, number of lymph nodes dissected, number of lymph nodes metastases, breast cancer staging, radiation therapy, chemotherapy, use of docetaxel, hormone therapy, International Society for Lymphology (ISL) classification stage, time from the operation to lymphedema onset, time from lymphedema onset to measurement and history of cellulitis and its frequency were identified from medical records. For breast cancer staging, patients on neoadjuvant chemotherapy adopted the stage at the start of treatment, and the pathologic stage obtained from the resected specimen was adopted for the others. BMI of ≥25 kg/m 2 was defined as obesity [15]. Staging of BCRL was based on the ISL: stage I, reversible pitting oedema; stage Ⅱ, pitting oedema that is not reduced by elevation; and late stage II, non-pitting oedema secondary to pronounced fibrosis. Diabetes was defined as a fasting blood glucose level of ≥126 mg/dL and HbA1c (National Glycohemoglobin Standardization Program) of ≥6.5% [16]. Hypertension was defined as an office blood pressure level of ≥140/90 mmHg [17] and hyperlipidaemia as low-density lipoprotein cholesterol ≥140 mg/dL, high-density lipoprotein cholesterol <40 mg/dL and triglycerides ≥150 mg/dL [18]. Cellulitis was diagnosed based on clinical findings of redness, swelling and tenderness of the affected extremity and high white blood cell and C-reactive protein levels in blood samples [19]. Measurements using MyotonPRO Circumference was measured on both sides at a site 10 cm from the elbow joint (medial epicondyle) on the upper arm and 5 cm from the elbow joint on the forearms [20], and skin stiffness was measured on the same area with MyotonPRO (Fig. 1). Measurements were taken while the patient was on bed, in a resting supine position with the shoulder joint in 90° of abduction and external rotation, and the elbow joint in 90° of flexion and mild forearm pronation. According to the manufacturer-recommended settings, MyotonPRO was measured using an L-shaped probe with an arm length of 20 mm, disc attachment (10 mm diameter) and a special adhesive seal so that the disc at the tip was level with the ground. MyotonPRO delivered a 7-ms impulse to the underlying tissue. Even with impulse duration of 15 ms, the minimal force was 0.6 N. Among the measurement items, stiffness was evaluated. Analysis of sarcopenia To evaluate the state of sarcopenia, CT images taken within 6 months before and after the measurement date of MyotonPRO were used, and the area of the bilateral iliopsoas muscles at the umbilical level was measured using the tracing method [21]. Measurements were made by two radiologists, and the average value was used. The sum of the bilateral iliopsoas muscle areas was divided by the square of the height to calculate the psoas major index (PMI). Based on the report of Hamaguchi et al., women with PMI of ≤3.92 cm 2 /m 2 were diagnosed as having sarcopenia. Statistical analysis Circumferential diameter and stiffness were compared between the normal and lymphedema limbs. The patients were divided into two groups based on the presence or absence of a history of cellulitis, and their BMIs were compared. Since stiffness was normally distributed, a t-test was performed, and Mann–Whitney U tests were performed for other factors. Correlations were evaluated using the Pearson correlation coefficient. To determine the factors that influence skin stiffness in the lymphedema limbs, a multivariate analysis was performed using multiple regression analysis. Age, BMI, history of diabetes, procedure (total mastectomy), number of onset of cellulitis, presence of radiotherapy, and days from lymphedema onset to measurement were explanatory variables. IBM SPSS Statistics version 28 (IBM Corp., Armonk, NY, USA) was used for all analyses, and a nominal two-sided p-value of <0.05 was considered significant. Ethical approval This study was conducted in accordance with the tenets of the Declaration of Helsinki and was approved by the ethics committees of Aichi Medical University (Permit No. 2022-140). Results Patient characteristics Seventy-one patients with BCRL were evaluated, and the mean age was 59.1 ± 10.8 years (Table 1). The mean BMI was 23.3 ± 4.4, and five patients (7.0%) had diabetes as comorbidity. Sarcopenia was found in 8 (11.3%) patients and obesity in 21 (29.6%). Thirteen patients (18.3%) had a history of cellulitis. By ISL staging, 1 (1.4%) case was in stage I, 65 (91.5%) in stage II and 5 (7.0%) in late stage II. The average time from after surgery to the lymphedema onset was 874 ± 1086 days, and the average time from lymphedema onset to the measurement of skin stiffness was 836 ± 715 days. In addition, 61 (85.9%) patients underwent total mastectomy with axillary lymph node dissection, of whom 8 underwent breast reconstruction (Table 2). Three patients underwent deep inferior epigastric perforator flap breast reconstruction, and five underwent breast reconstruction with tissue expander implantation. In total, 11.4 ± 4.6 lymph nodes were dissected, and 3.4 ± 4.1 lymph nodes were positive. Measurement results The respective stiffness of the normal and lymphedema limbs were 249 ± 50 and 283 ± 56 N/m (p < 0.001) in the upper arm and 306 ± 44 and 353 ± 64 N/m (p < 0.001) in the forearm and were significantly greater in the lymphedema limb (Fig. 2). The circumferences of normal and lymphedema limbs were 27.5 ± 3.6 and 29.1 ± 4.0 cm (p < 0.001) for the upper arm and 23.7 ± 2.4 and 25.1 ± 2.9 cm (p < 0.001) for the forearm, in which the lymphedema limb was significantly larger. In the univariate analysis, a correlation was found between BMI and history of cellulitis (r = 0.358, p = 0.002, Table 3), and the BMI of the groups with and without a history of cellulitis were 22.6 ± 3.8 and 26.6 ± 5.3 kg/m 2 (p = 0.021), respectively. The history of diabetes showed a significant positive correlation with skin stiffness in the forearms (r = 0.231, p = 0.053), and the same trend was observed in the upper arms (r = 0.276, p = 0.033). Forearm and upper arm stiffness of the lymphedema limb was not significantly correlated with BMI, history of cellulitis or ISL stage. Multiple regression analysis on lymphedema limb stiffness showed that BMI (β = -0.317, p = 0.013) and diabetes (β = 0.325, p = 0.011) remained factors affecting skin stiffness in the upper arm (Table 3) and diabetes (β = 0.240, p = 0.064) in the forearm (Table 4). Discussion Herein, we measured skin stiffness on the upper arm and forearm of patients with unilateral BCRL using MyotonPRO and found that the lymphedema limb had considerable skin stiffness. To the best of our knowledge, this is the first report that demonstrates the utility of the MyotonPRO in assessing skin stiffness in BCRL. Herein, we demonstrated that the MyotonPRO can measure BCRL skin stiffness using an L-shaped probe with an arm length of 20 mm, disc attachment (10 mm diameter), and a special adhesive seal on the disc at the tip. BCRL is considered problematic because it limits upper extremity movement and sensation, thereby increasing psychosocial, economic and time burdens, and impairing quality of life [4-6]. Therefore, studies have been conducted to evaluate skin stiffness using MyotonPRO to properly evaluate and treat BCRL. In a study in which measurements were made with a 12-mm disc device attached to a regular stick probe, the stiffness of the upper limb with lymphedema was lower than that of the healthy limb [22]. The skin of the limbs with lymphedema is stiffer than the normal skin, and the longer the time elapsed from disease onset, the more hardening occurs [23]. Thus, the results could have been some kind of measurement error. One of the reasons for this was the use of a regular stick probe for skin stiffness evaluation. Because the vibration of a regular stick probe moves in a vertical direction, it may have measured biomechanical properties of the deep bone [13]. Conversely, skin stiffness can be properly measured when an L-shaped probe is used for measurement because the vibration direction is horizontal. Our patients had a median time since lymphedema onset of 836 days. Therefore, it is possible to quantify skin stiffness in chronic BCRL using the L-shaped probe with disc attachment on the MyotonPRO. This would help lymphedema therapists objectively assess what has been a subjective assessment of skin stiffness. This study is very important because the results show that skin stiffness in lymphedema can be evaluated objectively. In the future, measuring skin stiffness with MyotonPRO before the onset of subjective symptoms of lymphedema may allow for early detection of BCRL. As a result, CPT may be started at an early stage of lymphedema, thereby reducing exacerbations. In addition, objective evaluation of the effect of treatment may be possible by measuring the skin stiffness before and after CPT. In addition to lymphedema, other causes of oedema include disuse. Among other causes, disuse oedema is caused by reduced muscle pump action, although older adults with exercise habits are said to maintain muscle pump action [24]. Since the study participants were outpatients with independent activities of daily living and only a few patients had sarcopenia, the incidence of disuse oedema was considered low in the population. The usefulness of MyotonPRO in the evaluation of disuse oedema is unknown and needs further study. Obesity is a risk factor for BCRL development after breast cancer treatment [25]. Furthermore, obesity negatively affected the later development of secondary lymphedema [26]. Studies have also reported that obesity is positively correlated with the occurrence, recurrence, treatment failure and prolonged treatment of cellulitis [27-30]. In the present study, patients with a history of cellulitis had a significantly higher BMI than those without. Upper extremity cellulitis occurs less frequently than lower extremity cellulitis; however, when it does occur, the risk of recurrence is increased, and lymphedema is exacerbated [31, 32]. However, no association was demonstrated between the frequency of cellulitis onset and skin stiffness in this study. Patients in this study were on CPT, and CPT may have prevented BCRL worsening after cellulitis onset. Thus, appropriate CPT may be important to avoid exacerbating skin stiffness. Multiple regression analysis showed that diabetes affected skin stiffness in BCRL. The skin stiffness of the plantar feet in patients with diabetic neuropathy is harder than that of normal plantar feet [33]. Although whether this study patient had diabetic neuropathy is still unknown, diabetes may have negatively affected skin stiffness in the lymphedema limb. Further case accumulation will clarify the relationship between worsening skin stiffness in lymphedema and diabetes. The number of axillary lymph nodes dissected, lymph node metastases and docetaxel use have been associated with BCRL development [34-36]. Because this study included patients with BCRL, to what extent the aforementioned factors contributed to BCRL development is unclear; however, in patients who underwent axillary lymph node dissection at initial surgery, the number of days to BCRL development was not associated with the number of lymph nodes dissected, lymph node metastases or docetaxel use. In addition, no association was found between skin stiffness and the number of axillary lymph nodes dissected or the number of lymph nodes with metastases. Therefore, these are considered risk factors for BCRL development based on previous reports; however, whether these factors affect skin stiffness after BCRL development is unclear. Limitations This study has several limitations. First, many patients in this study were on CPT for chronic BCRL. Therefore, whether MyotonPRO can detect skin stiffness before starting CPT or mild cases early in the disease course is unclear. However, because CPT is thought to improve skin stiffness, MyotonPRO may detect skin stiffness even before starting CPT. If skin stiffness can be detected early in the disease onset or before symptoms appear, CPT can be performed at an early stage, and BCRL deterioration can be prevented. Second, measurements were taken in the supine position with the shoulder joint in 90° of abduction and external rotation and the elbow joint in 90° of flexion. Although skin stiffness may change with changes in limb position, because the lymphedema limb was compared with a healthy limb at the same limb position and site, the result that the skin of the lymphedema limb being significantly stiffer was not considered problematic. Conclusions MyotonPRO was able to objectively assess the skin stiffness of chronic BCRL. The skin of the lymphedema limb may harden when diabetes is present as a comorbidity. Further studies are required to determine whether MyotonPRO can be used to diagnose early onset BCRL and whether any changes are observed in skin stiffness with limb position. Declarations Acknowledgements We thank Junko Kousaka, Yukako Mouri, Takahito Ando, Manami Goto, Mirai Ido, Masayuki Saito, Hirona Banno, Yuki Orimoto and Yuki Maruyama. Author contributions: Study conception and design were conducted by Hiroki Mitsuoka, Takahiro Arima, Shun Ohtsuka, Xiyao Shan, Kimihito Fujii, Munekazu Naito, Shogo Nakano and Akio Kodama. Data collection was performed by Hiroki Mitsuoka, Yukie Ito, Miki Shima, Kensuke Takagi and Mitsuharu Osawa. Analysis was performed by Hiroki Mitsuoka, Takahiro Arima, Shun Ohtsuka and Kimihito Fujii. The first draft of the manuscript was written by Hiroki Mitsuoka and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. Funding: The authors did not receive support from any organisation for the submitted work. Data availability: The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Ethics approval: This study was conducted in accordance with the tenets of the Declaration of Helsinki and was approved by the ethics committees of Aichi Medical University (Permit Number: 2022-140). Consent to participate: Participants provided written informed consent. Conflict of interest: The authors declare no competing interests. References Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F (2021) Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. 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Breast Cancer 27:929-937. 10.1007/s12282-020-01088-x Tables Table 1: Patient characteristics Characteristic n 71 Right-handed 70 (98.6%) Age 59.1 ± 10.8 Height (m) 1.58 ± 0.05 Weight (kg) 58.1 ± 12.3 BMI 23.3 ± 4.4 Comorbidities DM 5 (7.0%) HT 20 (28.2%) HL 15 (21.1%) History of cellulitis 13 (18.3%) Number of times cellulitis 0.7 ± 2.7 Values are listed as mean ± SD. BMI, body mass index; DM, diabetes mellitus; HL, hyperlipemia; HT, hypertension Table 2: Breast cancer-related characteristics Breast cancer-related characteristics Affected side (right/left) 29/42 Procedure Bp+Ax 10 (14.1%) Bt+Ax 53 (74.6%) Bt+Ax+breast reconstruction 8 (11.3%) Cancer type IDC 62 (87.3%) ILC 7 (9.9%) Others 2 (2.8%) Positive for lymph node metastasis 60 (84.5%) Number of lymph nodes Dissected 11.4 ± 4.6 Positive for metastases 3.4 ± 4.1 Stage Ⅰ 0 (0%) Ⅱ 44 (62.0%) Ⅲ 27 (38.0%) Ⅳ 0 (0%) Hormone therapy 59 (83.1%) Chemotherapy 62 (87.3%) Radiotherapy 66 (93.0%) Ax, axillary lymph node dissection; Bp, partial mastectomy; Bt, total mastectomy; IDC, invasive ductal carcinoma; ILC, invasive lobular carcinoma. Table 3: Multiple regression analysis of factors that affect skin stiffness of the upper arm in patients with lymphedema Variables B β p 95% CI Age 0.928 0.179 0.127 −0.272 to 2.129 BMI −4.037 −0.317 0.013 −7.176 to −0.898 Diabetes 70.206 0.325 0.011 16.869 to 123.543 Total mastectomy 7.568 0.048 0.683 −29.237 to 44.373 Cellulitis −1.209 −0.059 0.622 −6.089 to 3.671 Radiotherapy 0.648 0.003 0.980 −49.983 to 51.279 Days from onset to measurement 0.008 0.101 0.399 −0.011 to 0.026 BMI, body mass index; DM, diabetes mellitus Table 4: Multiple regression analysis of factors that affect skin stiffness of the forearm in patients with lymphedema Variables B β p 95% CI Age 1.011 0.171 0.157 −0.399 to 2.421 BMI 0.223 0.015 0.904 −3.466 to 3.911 Diabetes 59.234 0.240 0.064 −3.436 to 121.903 Total mastectomy 3.982 0.022 0.855 −39.263 to 47.227 Cellulitis 0.505 0.021 0.861 −5.229 to 6.239 Radiotherapy 48.104 0.195 0.111 −11.386 to 107.594 Days from onset to measurement −0.012 −0.133 0.278 −0.034 to 0.01 BMI, body mass index; DM, diabetes mellitus Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4352290","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":314655380,"identity":"4936f8df-d2d9-4c6a-bb07-e66719068fb4","order_by":0,"name":"Hiroki Mitsuoka","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABFElEQVRIie3QsUrDQBzH8V84uCxXuslJBF/hQqFGqORBXFICcWnQyalDQIhLoWseI+ALRA4y6lrRIaHQWRfpoGDOdCh4qbqJ3Hf6c8eH+yeAyfQHEwSwEtFMhBQIUDB1yje3wTeEBj8kUORzZGousE20Hdm9us4ucAqbvTxX06cD7MnbhZXisJ9gVWnI8ZU9cHOBOCG9Gx6UKwYnCr2GuFmBM6FbTFK6X7Uk5+NEMv9xMnTeU1g5EOk23CJsuVYEzvkrb17xd5J2MUZ5SyZUkfEOQtxM8DgldOgFpSLRwMMdDzPZ8S33pVXP3kbxvC+XD+up9OGE9QKXo5P59SzS/bFNHPTLCQiLukVHdvlrYjKZTP+xDz16VjZmbEEbAAAAAElFTkSuQmCC","orcid":"","institution":"Aichi Medical University","correspondingAuthor":true,"prefix":"","firstName":"Hiroki","middleName":"","lastName":"Mitsuoka","suffix":""},{"id":314655382,"identity":"b521c331-34b9-42b8-9eb5-53371e593cc7","order_by":1,"name":"Takahiro Arima","email":"","orcid":"","institution":"Aichi Medical University","correspondingAuthor":false,"prefix":"","firstName":"Takahiro","middleName":"","lastName":"Arima","suffix":""},{"id":314655383,"identity":"55b3e964-bbb7-48b9-ade6-9bf0fd621f45","order_by":2,"name":"Yukie Ito","email":"","orcid":"","institution":"Aichi Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yukie","middleName":"","lastName":"Ito","suffix":""},{"id":314655386,"identity":"fdd1381b-04b6-4c7b-a3ad-fb6aaf5d5ef8","order_by":3,"name":"Kimihito Fujii","email":"","orcid":"","institution":"Aichi Medical University","correspondingAuthor":false,"prefix":"","firstName":"Kimihito","middleName":"","lastName":"Fujii","suffix":""},{"id":314655390,"identity":"0461c786-8578-402c-86eb-6596513705d8","order_by":4,"name":"Shun Otsuka","email":"","orcid":"","institution":"Aichi Medical University","correspondingAuthor":false,"prefix":"","firstName":"Shun","middleName":"","lastName":"Otsuka","suffix":""},{"id":314655394,"identity":"fd2fa288-b747-41f6-a31b-a81a08b46a41","order_by":5,"name":"Xiyao Shan","email":"","orcid":"","institution":"Aichi Medical University","correspondingAuthor":false,"prefix":"","firstName":"Xiyao","middleName":"","lastName":"Shan","suffix":""},{"id":314655397,"identity":"87df2044-776c-41e9-b455-fb7c36ed61f5","order_by":6,"name":"Miki Shima","email":"","orcid":"","institution":"Aichi Medical University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Miki","middleName":"","lastName":"Shima","suffix":""},{"id":314655399,"identity":"5e85c329-3fa4-46ff-9099-9b1bdfa32cc4","order_by":7,"name":"Kensuke Takagi","email":"","orcid":"","institution":"Aichi Medical University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Kensuke","middleName":"","lastName":"Takagi","suffix":""},{"id":314655400,"identity":"76054fd0-3eca-4844-a63b-b662bb533d9d","order_by":8,"name":"Mitsuharu Osawa","email":"","orcid":"","institution":"Aichi Medical University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Mitsuharu","middleName":"","lastName":"Osawa","suffix":""},{"id":314655401,"identity":"1e749839-8f16-44ae-bfc3-f4de92afd186","order_by":9,"name":"Munekazu Naito","email":"","orcid":"","institution":"Aichi Medical University","correspondingAuthor":false,"prefix":"","firstName":"Munekazu","middleName":"","lastName":"Naito","suffix":""},{"id":314655405,"identity":"c873d2f1-e4d3-413e-9030-210c1cba643d","order_by":10,"name":"Shogo Nakano","email":"","orcid":"","institution":"Aichi Medical University","correspondingAuthor":false,"prefix":"","firstName":"Shogo","middleName":"","lastName":"Nakano","suffix":""},{"id":314655406,"identity":"bd77fbd0-544e-46a0-b004-efc8afa197d1","order_by":11,"name":"Akio Kodama","email":"","orcid":"","institution":"Aichi Medical University","correspondingAuthor":false,"prefix":"","firstName":"Akio","middleName":"","lastName":"Kodama","suffix":""}],"badges":[],"createdAt":"2024-05-01 04:08:15","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4352290/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4352290/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":58746840,"identity":"edaa0ec3-51f3-40e8-9b6c-8c70337a49d9","added_by":"auto","created_at":"2024-06-20 15:11:59","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":3048485,"visible":true,"origin":"","legend":"\u003cp\u003eMeasurement methods\u003c/p\u003e\n\u003cp\u003eA clinical example of the right upper limb. (a) On the upper arm, the circumference and stiffness by MyotonPRO were measured at a site 10 cm from the elbow joint (medial epicondyle). (b) On the forearm, circumference and stiffness by MyotonPRO were measured at a site 5 cm from the elbow joint.\u003c/p\u003e","description":"","filename":"Fig1.png","url":"https://assets-eu.researchsquare.com/files/rs-4352290/v1/46ed9462d72443ada76512a7.png"},{"id":58747958,"identity":"f2ae563c-f1bf-465d-a8c3-d01b532bdded","added_by":"auto","created_at":"2024-06-20 15:19:59","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":301993,"visible":true,"origin":"","legend":"\u003cp\u003eSkin stiffness and circumference of the normal and lymphedema limbs\u003c/p\u003e\n\u003cp\u003e(a) Stiffness of the upper arm in normal and lymphedema limbs. (b) Stiffness of the forearm in normal and lymphedema limbs. (c) Circumference of the upper arm in the normal and lymphedema limbs. (d) Circumference on forearm of the normal and lymphedema limbs.* p \u0026lt; 0.001.\u003c/p\u003e","description":"","filename":"Fig2.png","url":"https://assets-eu.researchsquare.com/files/rs-4352290/v1/69e6820ddcc125213ce583f6.png"},{"id":79029591,"identity":"0e39dcc1-a4b5-4bf3-b102-287b75b4c739","added_by":"auto","created_at":"2025-03-23 02:46:34","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":5227025,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4352290/v1/ab236c40-da96-4548-b73e-d4b76a58d416.pdf"},{"id":58746838,"identity":"b9007ee3-20a5-4de5-860e-385e4d443c66","added_by":"auto","created_at":"2024-06-20 15:11:59","extension":"xlsx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":15324,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementalTable1.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-4352290/v1/6f701ff54c0cf9db1043b217.xlsx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Objective evaluation of skin stiffness in breast cancer-related lymphedema using MyotoPRO","fulltext":[{"header":"Introduction","content":"\u003cp\u003eBreast cancer is the most common malignant tumour in women [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e], and breast cancer-related lymphedema (BCRL) is a complication of axillary dissection and radiation therapy in breast cancer [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. The incidence of BCRL is approximately 20%. BCRL not only results in upper extremity disability, including decreased range of motion, muscle weakness and sensory abnormalities but also causes depression; anxiety; social, family, occupational and sexual difficulties; and financial and time burdens [\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Therefore, early diagnosis and appropriate treatment is important, and complex physical therapy (CPT) is recommended as a treatment [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. CPT consists of skin care, manual lymphatic drainage, compression and myolymphokinetic exercises [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. BCRL symptoms include skin stiffness, and patients have reported subjective improvement in skin stiffness with manual lymphatic drainage [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Although skin stiffness is a symptom of BCRL, it is not indicated in the evaluation of the treatment efficacy of CPT. Because no method has been established for determining skin stiffness, evaluation relies on the subjectivity of the patient and skills of the evaluator [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. A simple and objective evaluation of skin stiffness would be useful in evaluating BCRL and determining the efficacy of CPT. If skin stiffness could be evaluated objectively, BCRL could be detected earlier, and treatment could be initiated sooner. MyotonPRO, a tissue stiffness tester, is widely used for objective and non-invasive assessment of body surface skeletal muscles [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. MyotonPRO is also useful in assessing skin stiffness [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. In this study, we investigated whether MyotonPRO can be used to objectively assess skin stiffness in BCRL. In addition, the influence of patient factors such as lymphedema stage and history of cellulitis and diabetes on skin stiffness was statistically evaluated.\u003c/p\u003e"},{"header":"Patients and methods","content":"\u003cp\u003ePatients\u003c/p\u003e\n\u003cp\u003eThis study included female patients diagnosed with unilateral postoperative BCRL after breast cancer surgery with lymph node dissection who had attended Aichi Medical University Hospital as an outpatient for CPT between February and October 2023 and gave consent to participate in the study. Patients who were not living independently (patients with intervening care) were excluded. Patient data included age, height, weight, body mass index (BMI), comorbidities (diabetes, hypertension and hyperlipidaemia), direction of the dominant hand, side of the affected limbs, cancer type, operation type, presence of breast reconstruction, number of lymph nodes dissected, number of lymph nodes metastases, breast cancer staging, radiation therapy, chemotherapy, use of docetaxel, hormone therapy, International Society for Lymphology (ISL) classification stage, time from the operation to lymphedema onset, time from lymphedema onset to measurement and history of cellulitis and its frequency were identified from medical records. For breast cancer staging, patients on neoadjuvant chemotherapy adopted the stage at the start of treatment, and the pathologic stage obtained from the resected specimen was adopted for the others. BMI of ≥25 kg/m\u003csup\u003e2\u003c/sup\u003e was defined as obesity [15]. Staging of BCRL was based on the ISL: stage I, reversible pitting oedema; stage Ⅱ, pitting oedema that is not reduced by elevation; and late stage II, non-pitting oedema secondary to pronounced fibrosis. Diabetes was defined as a fasting blood glucose level of ≥126 mg/dL and HbA1c (National Glycohemoglobin Standardization Program) of ≥6.5% [16]. Hypertension was defined as an office blood pressure level of ≥140/90 mmHg [17] and hyperlipidaemia as low-density lipoprotein cholesterol ≥140 mg/dL, high-density lipoprotein cholesterol \u0026lt;40 mg/dL and triglycerides ≥150 mg/dL [18]. Cellulitis was diagnosed based on clinical findings of redness, swelling and tenderness of the affected extremity and high white blood cell and C-reactive protein levels in blood samples [19].\u003c/p\u003e\n\u003cp\u003eMeasurements using MyotonPRO\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCircumference was measured on both sides at a site 10 cm from the elbow joint (medial epicondyle) on the upper arm and 5 cm from the elbow joint on the forearms [20], and skin stiffness was measured on the same area with MyotonPRO (Fig. 1). Measurements were taken while the patient was on bed, in a resting supine position with the shoulder joint in 90° of abduction and external rotation, and the elbow joint in 90° of flexion and mild forearm pronation. According to the manufacturer-recommended settings, MyotonPRO was measured using an L-shaped probe with an arm length of 20 mm, disc attachment (10 mm diameter) and a special adhesive seal so that the disc at the tip was level with the ground. MyotonPRO delivered a 7-ms impulse to the underlying tissue. Even with impulse duration of 15 ms, the minimal force was 0.6 N. Among the measurement items, stiffness was evaluated.\u003c/p\u003e\n\u003cp\u003eAnalysis of sarcopenia\u003c/p\u003e\n\u003cp\u003eTo evaluate the state of sarcopenia, CT images taken within 6 months before and after the measurement date of MyotonPRO were used, and the area of the bilateral iliopsoas muscles at the umbilical level was measured using the tracing method [21]. Measurements were made by two radiologists, and the average value was used. The sum of the bilateral iliopsoas muscle areas was divided by the square of the height to calculate the psoas major index (PMI). Based on the report of Hamaguchi et al., women with PMI of ≤3.92 cm\u003csup\u003e2\u003c/sup\u003e /m\u003csup\u003e2\u003c/sup\u003e were diagnosed as having sarcopenia.\u003c/p\u003e\n\u003cp\u003eStatistical analysis\u003c/p\u003e\n\u003cp\u003eCircumferential diameter and stiffness were compared between the normal and lymphedema limbs. The patients were divided into two groups based on the presence or absence of a history of cellulitis, and their BMIs were compared. Since stiffness was normally distributed, a t-test was performed, and Mann–Whitney U tests were performed for other factors. Correlations were evaluated using the Pearson correlation coefficient. To determine the factors that influence skin stiffness in the lymphedema limbs, a multivariate analysis was performed using multiple regression analysis. Age, BMI, history of diabetes, procedure (total mastectomy), number of onset of cellulitis, presence of radiotherapy, and days from lymphedema onset to measurement were explanatory variables. IBM SPSS Statistics version 28 (IBM Corp., Armonk, NY, USA) was used for all analyses, and a nominal two-sided p-value of \u0026lt;0.05 was considered significant.\u003c/p\u003e\n\u003cp\u003eEthical approval\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis study was conducted in accordance with the tenets of the Declaration of Helsinki and was approved by the ethics committees of Aichi Medical University (Permit No. 2022-140).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003ePatient characteristics\u003c/p\u003e\n\u003cp\u003eSeventy-one patients with BCRL were evaluated, and the mean age was 59.1 \u0026plusmn; 10.8 years (Table 1). The mean BMI was 23.3 \u0026plusmn; 4.4, and five patients (7.0%) had diabetes as comorbidity. Sarcopenia was found in 8 (11.3%) patients and obesity in 21 (29.6%). Thirteen patients (18.3%) had a history of cellulitis. By ISL staging, 1 (1.4%) case was in stage I, 65 (91.5%) in stage II and 5 (7.0%) in late stage II. The average time from after surgery to the lymphedema onset was 874 \u0026plusmn; 1086 days, and the average time from lymphedema onset to the measurement of skin stiffness was 836 \u0026plusmn; 715 days. In addition, 61 (85.9%) patients underwent total mastectomy with axillary lymph node dissection, of whom 8 underwent breast reconstruction (Table 2). Three patients underwent deep inferior epigastric perforator flap breast reconstruction, and five underwent breast reconstruction with tissue expander implantation. In total, 11.4 \u0026plusmn; 4.6 lymph nodes were dissected, and 3.4 \u0026plusmn; 4.1 lymph nodes were positive.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMeasurement results\u003c/p\u003e\n\u003cp\u003eThe respective stiffness of the normal and lymphedema limbs were 249 \u0026plusmn; 50 and 283 \u0026plusmn; 56 N/m (p \u0026lt; 0.001) in the upper arm and 306 \u0026plusmn; 44 and 353 \u0026plusmn; 64 N/m (p \u0026lt; 0.001) in the forearm and were significantly greater in the lymphedema limb (Fig. 2). The circumferences of normal and lymphedema limbs were 27.5 \u0026plusmn; 3.6 and 29.1 \u0026plusmn; 4.0 cm (p \u0026lt; 0.001) for the upper arm and 23.7 \u0026plusmn; 2.4 and 25.1 \u0026plusmn; 2.9 cm (p \u0026lt; 0.001) for the forearm, in which the lymphedema limb was significantly larger. In the univariate analysis, a correlation was found between BMI and history of cellulitis (r = 0.358, p = 0.002, Table 3), and the BMI of the groups with and without a history of cellulitis were 22.6 \u0026plusmn; 3.8 and 26.6 \u0026plusmn; 5.3 kg/m\u003csup\u003e2\u003c/sup\u003e (p = 0.021), respectively. The history of diabetes showed a significant positive correlation with skin stiffness in the forearms (r = 0.231, p = 0.053), and the same trend was observed in the upper arms (r = 0.276, p = 0.033). Forearm and upper arm stiffness of the lymphedema limb was not significantly correlated with BMI, history of cellulitis or ISL stage. Multiple regression analysis on lymphedema limb stiffness showed that BMI (\u0026beta; = -0.317, p = 0.013) and diabetes (\u0026beta; = 0.325, p = 0.011) remained factors affecting skin stiffness in the upper arm (Table 3) and diabetes (\u0026beta; = 0.240, p = 0.064) in the forearm (Table 4).\u0026nbsp;\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eHerein, we measured skin stiffness on the upper arm and forearm of patients with unilateral BCRL using MyotonPRO and found that the lymphedema limb had considerable skin stiffness. To the best of our knowledge, this is the first report that demonstrates the utility of the MyotonPRO in assessing skin stiffness in BCRL.\u003c/p\u003e\n\u003cp\u003eHerein, we demonstrated that the MyotonPRO can measure BCRL skin stiffness using an L-shaped probe with an arm length of 20 mm, disc attachment (10 mm diameter), and a special adhesive seal on the disc at the tip. BCRL is considered problematic because it limits upper extremity movement and sensation, thereby increasing psychosocial, economic and time burdens, and impairing quality of life [4-6]. Therefore, studies have been conducted to evaluate skin stiffness using MyotonPRO to properly evaluate and treat BCRL. In a study in which measurements were made with a 12-mm disc device attached to a regular stick probe, the stiffness of the upper limb with lymphedema was lower than that of the healthy limb [22]. The skin of the limbs with lymphedema is stiffer than the normal skin, and the longer the time elapsed from disease onset, the more hardening occurs [23]. Thus, the results could have been some kind of measurement error. One of the reasons for this was the use of a regular stick probe for skin stiffness evaluation. Because the vibration of a regular stick probe moves in a vertical direction, it may have measured biomechanical properties of the deep bone [13]. Conversely, skin stiffness can be properly measured when an L-shaped probe is used for measurement because the vibration direction is horizontal.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOur patients had a median time since lymphedema onset of 836 days. Therefore, it is possible to quantify skin stiffness in chronic BCRL using the L-shaped probe with disc attachment on the MyotonPRO. This would help lymphedema therapists objectively assess what has been a subjective assessment of skin stiffness. This study is very important because the results show that skin stiffness in lymphedema can be evaluated objectively. In the future, measuring skin stiffness with MyotonPRO before the onset of subjective symptoms of lymphedema may allow for early detection of BCRL. As a result, CPT may be started at an early stage of lymphedema, thereby reducing exacerbations. In addition, objective evaluation of the effect of treatment may be possible by measuring the skin stiffness before and after CPT.\u003c/p\u003e\n\u003cp\u003eIn addition to lymphedema, other causes of oedema include disuse. Among other causes, disuse oedema is caused by reduced muscle pump action, although older adults with exercise habits are said to maintain muscle pump action [24]. Since the study participants were outpatients with independent activities of daily living and only a few patients had sarcopenia, the incidence of disuse oedema was considered low in the population. The usefulness of MyotonPRO in the evaluation of disuse oedema is unknown and needs further study.\u003c/p\u003e\n\u003cp\u003eObesity is a risk factor for BCRL development after breast cancer treatment\u0026nbsp;[25].\u0026nbsp;Furthermore, obesity negatively affected the later development of secondary lymphedema [26]. Studies have also reported that obesity is positively correlated with the occurrence, recurrence, treatment failure and prolonged treatment of cellulitis [27-30]. In the present study, patients with a history of cellulitis had a significantly higher BMI than those without. Upper extremity cellulitis occurs less frequently than lower extremity cellulitis; however, when it does occur, the risk of recurrence is increased, and lymphedema is exacerbated [31, 32]. However, no association was demonstrated between the frequency of cellulitis onset and skin stiffness in this study. Patients in this study were on CPT, and CPT may have prevented BCRL worsening after cellulitis onset. Thus, appropriate CPT may be important to avoid exacerbating skin stiffness. Multiple regression analysis showed that diabetes affected skin stiffness in BCRL. The skin stiffness of the plantar feet in patients with diabetic neuropathy is harder than that of normal plantar feet [33]. Although whether this study patient had diabetic neuropathy is still unknown, diabetes may have negatively affected skin stiffness in the lymphedema limb. Further case accumulation will clarify the relationship between worsening skin stiffness in lymphedema and diabetes.\u003c/p\u003e\n\u003cp\u003eThe number of axillary lymph nodes dissected, lymph node metastases and docetaxel use have been associated with BCRL development [34-36]. Because this study included patients with BCRL, to what extent the aforementioned factors contributed to BCRL development is unclear; however, in patients who underwent axillary lymph node dissection at initial surgery, the number of days to BCRL development was not associated with the number of lymph nodes dissected, lymph node metastases or docetaxel use. In addition, no association was found between skin stiffness and the number of axillary lymph nodes dissected or the number of lymph nodes with metastases. Therefore, these are considered risk factors for BCRL development based on previous reports; however, whether these factors affect skin stiffness after BCRL development is unclear.\u003c/p\u003e\n\u003cp\u003eLimitations\u003c/p\u003e\n\u003cp\u003eThis study has several limitations. First, many patients in this study were on CPT for chronic BCRL. Therefore, whether MyotonPRO can detect skin stiffness before starting CPT or mild cases early in the disease course is unclear. However, because CPT is thought to improve skin stiffness, MyotonPRO may detect skin stiffness even before starting CPT. If skin stiffness can be detected early in the disease onset or before symptoms appear, CPT can be performed at an early stage, and BCRL deterioration can be prevented. Second, measurements were taken in the supine position with the shoulder joint in 90° of abduction and external rotation and the elbow joint in 90° of flexion. Although skin stiffness may change with changes in limb position, because the lymphedema limb was compared with a healthy limb at the same limb position and site, the result that the skin of the lymphedema limb being significantly stiffer was not considered problematic.\u0026nbsp;\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eMyotonPRO was able to objectively assess the skin stiffness of chronic BCRL. The skin of the lymphedema limb may harden when diabetes is present as a comorbidity. Further studies are required to determine whether MyotonPRO can be used to diagnose early onset BCRL and whether any changes are observed in skin stiffness with limb position.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank Junko Kousaka, Yukako Mouri, Takahito Ando, Manami Goto, Mirai Ido, Masayuki Saito, Hirona Banno, Yuki Orimoto and Yuki Maruyama.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions:\u003c/strong\u003e Study conception and design were conducted by Hiroki Mitsuoka, Takahiro Arima, Shun Ohtsuka, Xiyao Shan, Kimihito Fujii, Munekazu Naito, Shogo Nakano and Akio Kodama. Data collection was performed by Hiroki Mitsuoka, Yukie Ito, Miki Shima, Kensuke Takagi and Mitsuharu Osawa. Analysis was performed by Hiroki Mitsuoka, Takahiro Arima, Shun Ohtsuka and Kimihito Fujii. The first draft of the manuscript was written by Hiroki Mitsuoka and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003eThe authors did not receive support from any organisation for the submitted work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability:\u003c/strong\u003e The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval:\u003c/strong\u003e This study was conducted in accordance with the tenets of the Declaration of Helsinki and was approved by the ethics committees of Aichi Medical University (Permit Number: 2022-140).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate:\u003c/strong\u003e Participants provided written informed consent.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest:\u003c/strong\u003e The authors declare no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F (2021)\u003cem\u003e \u003c/em\u003eGlobal cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 71:209-249. https://doi.org/10.3322/caac.21660\u003c/li\u003e\n\u003cli\u003eDiSipio T, Rye S, Newman B, Hayes S (2013) Incidence of unilateral arm lymphoedema after breast cancer: A systematic review and meta-analysis. Lancet Oncol 14:500-515. https://doi.org/10.1002/cncr.34489\u003c/li\u003e\n\u003cli\u003eRen Yumeng, Kebede MA, Ogunleye AA, Emerson MA, Evenson KR, Carey LA, Hayes SC, Troester MA (2022) Burden of lymphedema in long-term breast cancer survivors by race and age. Cancer 128:4119-4128. https://doi.org/10.1007/s12609-020-00376-x\u003c/li\u003e\n\u003cli\u003ePinto M, Gimigliano F, Tatangelo F, Megna M, Izzo F, Gimigliano R, Iolascon G (2013) Upper limb function and quality of life in breast cancer related lymphedema: A cross-sectional study. Eur J Phys Rehabil Med 49:665-673. \u003c/li\u003e\n\u003cli\u003eEaton LH, Narkthong N, Hulett JM (2020) Psychosocial issues associated with breast cancer-related lymphedema: A literature review. 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JSES Int 7:25-29. https://doi.org/10.1016/j.jseint.2022.08.017\u003c/li\u003e\n\u003cli\u003eLiu CL, Feng YN, Zhang HQ, Li YP, Zhu Y, Zhang ZJ (2018) Assessing the viscoelastic properties of upper trapezius muscle: Intra- and inter-tester reliability and the effect of shoulder elevation. J Electromyogr Kinesiol 43:226-229. https://doi.org/10.1016/j.jelekin.2017.09.007\u003c/li\u003e\n\u003cli\u003eRosicka K, Mierzejewska-Krzyżowska B, Mr\u0026oacute;wczyński W (2021) Comparison of different MyotonPRO probes for skin stiffness evaluation in young women. Skin Res Technol 26:1-8. https://doi.org/10.1111/srt.12946. Epub 2020 Oct 20.\u003c/li\u003e\n\u003cli\u003eRosicka K, Mierzejewska-Krzyżowska B, Mr\u0026oacute;wczyński W (2022) Skin biomechanical and viscoelastic properties measured with MyotonPRO in different areas of human body. Skin Res Technol 28:236-245. https://doi.org/10.1111/srt.13116\u003c/li\u003e\n\u003cli\u003eJapan Society for the Study of Obesity (2016). Guidelines for the management of obesity disease 2016, Japan Society for the Study of Obesity, Tokyo, 4-11.\u003c/li\u003e\n\u003cli\u003eAraki E, Goto A, Kondo T, Noda M, Noto H, Origasa H, Osawa H, Taguchi A, Tanizawa Y, Tobe K, Yoshioka N (2020) Japanese clinical practice guideline for diabetes 2019. Diabetol Int 11:165-223. https://doi.org/10.1007/s13340-020-00439-5\u003c/li\u003e\n\u003cli\u003eUmemura S, Arima H, Arima S, Asayama K, Dohi Y, Hirooka Y, Horio T, Hoshide S, Ikeda S, Ishimitsu T, Ito M, Ito S, Iwashima Y, Kai H, Kamide K, Kanno Y, Kashihara N, Kawano Y, Kikuchi T, Kitamura K, Kitazono T, Kohara K, Kudo M, Kumagai H, Matsumura K, Matsuura H, Miura K, Mukoyama M, Nakamura S, Ohkubo T, Ohya Y, Okura T, Rakugi H, Saitoh S, Shibata H, Shimosawa T, Suzuki H, Takahashi S, Tamura K, Tomiyama H, Tsuchihashi T, Ueda S, Uehara Y, Urata H, Hirawa N (2019) The Japanese Society of Hypertension guidelines for the management of hypertension (JSH 2019). Hypertens Res 42:1235-1481. https://doi.org/10.1038/s41440-019-0284-9\u003c/li\u003e\n\u003cli\u003eJapan Atherosclerosis Society guidelines for prevention of atherosclerotic cardiovascular diseases 2022 (2022), Japan atherosclerosis society, Tokyo, 19-25.\u003c/li\u003e\n\u003cli\u003eStevens DL, Bisno AL, Chambers HF, Dellinger EP, Goldstein EJC, Gorbach SL, Hirschmann JV, Kaplan SL, Montoya JG, Wade JC (2014) Executive summary: Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clin Infect Dis 59:147-159. https://doi.org/10.1093/cid/ciu444\u003c/li\u003e\n\u003cli\u003eKojima M, Yamauchi C, Oyamada S, Hojo T, Iwase S, Naito A, Yamano K, Takahashi S, Ochiai A (2020) Assessment of upper limb physiological features in patients with lymphedema after breast surgery using multiple instruments. 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J Biomech 49:94-99. https://doi.org/10.1016/j.jbiomech.2015.11.043\u003c/li\u003e\n\u003cli\u003eFujii T, Ohno N, Sawazaki T, Ogura K, Miyati T, Sugama J (2021) Gravity magnetic resonance imaging measurement of muscle pump change accompanied by aging and posture. Jpn J Nurs Sci 18:e12407. https://doi.org/10.1111/jjns.12407\u003c/li\u003e\n\u003cli\u003eHelyer LK, Varnic M, Le LW, Leong W, McCready D (2010) Obesity is a risk factor for developing postoperative lymphedema in breast cancer patients. Breast J 16:48-54. https://doi.org/10.1111/j.1524-4741.2009.00855.x\u003c/li\u003e\n\u003cli\u003eGreene AK, Zurakowski D, Goss JA (2020) Body mass index and lymphedema morbidity: comparison of obese versus normal-weight patients. Plast Reconstr Surg 146:402-407. https://doi.org/10.1097/PRS.0000000000007021\u003c/li\u003e\n\u003cli\u003eConway EL, Sellick JA, Kurtzhalts K, Mergenhagen KA (2017) Obesity and heart failure as predictors of failure in outpatient skin and soft tissue infections. Antimicrob Agents\u003cem\u003e \u003c/em\u003eChemother 61:1-7. https://doi.org/10.1128/AAC.02389-16\u003c/li\u003e\n\u003cli\u003eZhang J, Moore E, Bousfield R (2016) OPAT for cellulitis: Its benefits and the factors that predispose to longer treatment. Eur J Clin Microbiol Infect Dis 35:1013-1015. https://doi.org/10.1007/s10096-016-2631-y\u003c/li\u003e\n\u003cli\u003eDupuy A, Benchikhi H, Roujeau JC, Bernard P, Vaillant L, Chosidow O, Sassolas B, Guillaume JC, Grob JJ, Bastuji-Garin S (1999) Risk factors for erysipelas of the leg (cellulitis): Case-control study. BMJ 318:1591-1594. https://doi.org/10.1136/bmj.318.7198.1591\u003c/li\u003e\n\u003cli\u003eNjim T, Aminde LN, Agbor VN, Toukam LD, Kashaf SS, Ohuma EO\u003cem\u003e \u003c/em\u003e(2017) Risk factors of lower limb cellulitis in a level-two healthcare facility in Cameroon: A case-control study. BMC Infect Dis 17:418. https://doi.org/10.1186/s12879-017-2519-1\u003c/li\u003e\n\u003cli\u003ePavlotsky F, Amrani S, Trau H (2004) Recurrent erysipelas: Risk factors. J Dtsch Dermatol Ges 2:89-95. 10.1046/j.1439-0353.2004.03028.x\u003c/li\u003e\n\u003cli\u003eChlebicki MP, Oh CC (2014) Recurrent cellulitis: Risk factors, etiology, pathogenesis and treatment. Curr Infect Dis Rep 16:422. https://doi.org/10.1007/s11908-014-0422-0\u003c/li\u003e\n\u003cli\u003eKlaesner JW, Hastings MK, Zou D, Lewis C, Mueller MJ (2002) Plantar tissue stiffness in patients with diabetes mellitus and peripheral neuropathy. Arch Phys Med Rehabil 83:1796-1801. https://doi.org/10.1053/apmr.2002.35661\u003c/li\u003e\n\u003cli\u003eZou L, Liu FH, Shen PP, Hu Y, Liu XQ, Xu YY, Pen QL, Wang B, Zhu YQ, Tian Y (2018) The incidence and risk factors of related lymphedema for breast cancer survivors post-operation: A 2-year follow-up prospective cohort study. Breast Cancer 25:309-314. https://doi.org/10.1007/s12282-018-0830-3\u003c/li\u003e\n\u003cli\u003eVieira RA, da Costa AM, de Souza JL, Coelho RR, de Oliveira CZ, Sarri AJ, Junior RJ, Zucca-Matthes G (2016) Risk factors for arm lymphedema in a cohort of breast cancer patients followed up for 10 years.\u003cem\u003e \u003c/em\u003eBreast Care (Basel) 11:45-50. doi: 10.1159/000442489\u003c/li\u003e\n\u003cli\u003eAoishi Y, Oura S, Nishiguchi H, Hirai Y, Miyasaka M, Kawaji M, Shima A, Nishimura Y (2020) Risk factors for breast cancer-related lymphedema: Correlation with docetaxel administration. Breast Cancer 27:929-937. 10.1007/s12282-020-01088-x\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1: Patient characteristics\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"264\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"67.42424242424242%\"\u003e\n \u003cp\u003eCharacteristic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.57575757575758%\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"67.42424242424242%\"\u003e\n \u003cp\u003e\u0026nbsp; n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.57575757575758%\"\u003e\n \u003cp\u003e71\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"67.42424242424242%\"\u003e\n \u003cp\u003e\u0026nbsp; Right-handed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.57575757575758%\"\u003e\n \u003cp\u003e70\u0026nbsp;(98.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"67.42424242424242%\"\u003e\n \u003cp\u003e\u0026nbsp; Age\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.57575757575758%\"\u003e\n \u003cp\u003e59.1 \u0026plusmn; 10.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"67.42424242424242%\"\u003e\n \u003cp\u003e\u0026nbsp; Height (m)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.57575757575758%\"\u003e\n \u003cp\u003e1.58 \u0026plusmn; 0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"67.42424242424242%\"\u003e\n \u003cp\u003e\u0026nbsp; Weight (kg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.57575757575758%\"\u003e\n \u003cp\u003e58.1 \u0026plusmn; 12.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"67.42424242424242%\"\u003e\n \u003cp\u003e\u0026nbsp; BMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.57575757575758%\"\u003e\n \u003cp\u003e23.3 \u0026plusmn; 4.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"67.42424242424242%\"\u003e\n \u003cp\u003e\u0026nbsp; Comorbidities\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.57575757575758%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"67.42424242424242%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;DM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.57575757575758%\"\u003e\n \u003cp\u003e5\u0026nbsp;(7.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"67.42424242424242%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;HT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.57575757575758%\"\u003e\n \u003cp\u003e20\u0026nbsp;(28.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"67.42424242424242%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;HL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.57575757575758%\"\u003e\n \u003cp\u003e15\u0026nbsp;(21.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"67.42424242424242%\"\u003e\n \u003cp\u003e\u0026nbsp; History of cellulitis \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.57575757575758%\"\u003e\n \u003cp\u003e13\u0026nbsp;(18.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"67.42424242424242%\"\u003e\n \u003cp\u003e\u0026nbsp; Number of times cellulitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.57575757575758%\"\u003e\n \u003cp\u003e0.7 \u0026plusmn; 2.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eValues are listed as mean \u0026plusmn; SD. BMI, body mass index; DM, diabetes mellitus; HL, hyperlipemia; HT, hypertension\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 2: Breast cancer-related characteristics\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"310\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"72.58064516129032%\"\u003e\n \u003cp\u003eBreast cancer-related characteristics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.419354838709676%\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"72.58064516129032%\"\u003e\n \u003cp\u003e\u0026nbsp; Affected side (right/left)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.419354838709676%\"\u003e\n \u003cp\u003e29/42\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"72.58064516129032%\"\u003e\n \u003cp\u003e\u0026nbsp; Procedure\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.419354838709676%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"72.58064516129032%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Bp+Ax\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.419354838709676%\"\u003e\n \u003cp\u003e10\u0026nbsp;(14.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"72.58064516129032%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Bt+Ax\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.419354838709676%\"\u003e\n \u003cp\u003e53\u0026nbsp;(74.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"72.58064516129032%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Bt+Ax+breast reconstruction\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.419354838709676%\"\u003e\n \u003cp\u003e8\u0026nbsp;(11.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"72.58064516129032%\"\u003e\n \u003cp\u003e\u0026nbsp; Cancer type\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.419354838709676%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"72.58064516129032%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;IDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.419354838709676%\"\u003e\n \u003cp\u003e62\u0026nbsp;(87.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"72.58064516129032%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;ILC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.419354838709676%\"\u003e\n \u003cp\u003e7\u0026nbsp;(9.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"72.58064516129032%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Others\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.419354838709676%\"\u003e\n \u003cp\u003e2\u0026nbsp;(2.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"72.58064516129032%\"\u003e\n \u003cp\u003e\u0026nbsp; Positive for lymph node metastasis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.419354838709676%\"\u003e\n \u003cp\u003e60\u0026nbsp;(84.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"72.58064516129032%\"\u003e\n \u003cp\u003e\u0026nbsp; Number of lymph nodes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.419354838709676%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"72.58064516129032%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Dissected\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.419354838709676%\"\u003e\n \u003cp\u003e11.4 \u0026plusmn; 4.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"72.58064516129032%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Positive for metastases\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.419354838709676%\"\u003e\n \u003cp\u003e3.4 \u0026plusmn; 4.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"72.58064516129032%\"\u003e\n \u003cp\u003e\u0026nbsp; Stage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.419354838709676%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"72.58064516129032%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Ⅰ\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.419354838709676%\"\u003e\n \u003cp\u003e0\u0026nbsp;(0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"72.58064516129032%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Ⅱ\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.419354838709676%\"\u003e\n \u003cp\u003e44\u0026nbsp;(62.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"72.58064516129032%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Ⅲ\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.419354838709676%\"\u003e\n \u003cp\u003e27\u0026nbsp;(38.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"72.58064516129032%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Ⅳ\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.419354838709676%\"\u003e\n \u003cp\u003e0\u0026nbsp;(0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"72.58064516129032%\"\u003e\n \u003cp\u003e\u0026nbsp; Hormone therapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.419354838709676%\"\u003e\n \u003cp\u003e59\u0026nbsp;(83.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"72.58064516129032%\"\u003e\n \u003cp\u003e\u0026nbsp; Chemotherapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.419354838709676%\"\u003e\n \u003cp\u003e62\u0026nbsp;(87.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"72.58064516129032%\"\u003e\n \u003cp\u003e\u0026nbsp; Radiotherapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.419354838709676%\"\u003e\n \u003cp\u003e66\u0026nbsp;(93.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAx, axillary lymph node dissection; Bp, partial mastectomy; Bt, total mastectomy; IDC, invasive ductal carcinoma; ILC, invasive lobular carcinoma. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 3: Multiple regression analysis of factors that affect skin stiffness of the upper arm in patients with lymphedema\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"492\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"43.6105476673428%\"\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.344827586206897%\"\u003e\n \u003cp\u003eB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.344827586206897%\"\u003e\n \u003cp\u003e\u0026beta;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.72210953346856%\"\u003e\n \u003cp\u003ep\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.97768762677485%\"\u003e\n \u003cp\u003e\u0026nbsp;95% CI\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"43.6105476673428%\"\u003e\n \u003cp\u003e\u0026nbsp; Age\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.344827586206897%\"\u003e\n \u003cp\u003e0.928\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.344827586206897%\"\u003e\n \u003cp\u003e0.179\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.72210953346856%\"\u003e\n \u003cp\u003e0.127\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.97768762677485%\"\u003e\n \u003cp\u003e\u0026minus;0.272 to 2.129\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"43.6105476673428%\"\u003e\n \u003cp\u003e\u0026nbsp; BMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.344827586206897%\"\u003e\n \u003cp\u003e\u0026minus;4.037\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.344827586206897%\"\u003e\n \u003cp\u003e\u0026minus;0.317\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.72210953346856%\"\u003e\n \u003cp\u003e0.013\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.97768762677485%\"\u003e\n \u003cp\u003e\u0026minus;7.176 to \u0026minus;0.898\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"43.6105476673428%\"\u003e\n \u003cp\u003e\u0026nbsp; Diabetes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.344827586206897%\"\u003e\n \u003cp\u003e70.206\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.344827586206897%\"\u003e\n \u003cp\u003e0.325\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.72210953346856%\"\u003e\n \u003cp\u003e0.011\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.97768762677485%\"\u003e\n \u003cp\u003e16.869\u0026nbsp;to\u0026nbsp;123.543\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"43.6105476673428%\"\u003e\n \u003cp\u003e\u0026nbsp; Total mastectomy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.344827586206897%\"\u003e\n \u003cp\u003e7.568\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.344827586206897%\"\u003e\n \u003cp\u003e0.048\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.72210953346856%\"\u003e\n \u003cp\u003e0.683\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.97768762677485%\"\u003e\n \u003cp\u003e\u0026minus;29.237 to 44.373\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"43.6105476673428%\"\u003e\n \u003cp\u003e\u0026nbsp; Cellulitis\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.344827586206897%\"\u003e\n \u003cp\u003e\u0026minus;1.209\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.344827586206897%\"\u003e\n \u003cp\u003e\u0026minus;0.059\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.72210953346856%\"\u003e\n \u003cp\u003e0.622\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.97768762677485%\"\u003e\n \u003cp\u003e\u0026minus;6.089 to 3.671\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"43.6105476673428%\"\u003e\n \u003cp\u003e\u0026nbsp; Radiotherapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.344827586206897%\"\u003e\n \u003cp\u003e0.648\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.344827586206897%\"\u003e\n \u003cp\u003e0.003\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.72210953346856%\"\u003e\n \u003cp\u003e0.980\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.97768762677485%\"\u003e\n \u003cp\u003e\u0026minus;49.983 to 51.279\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"43.6105476673428%\"\u003e\n \u003cp\u003e\u0026nbsp; Days from onset to measurement\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.344827586206897%\"\u003e\n \u003cp\u003e0.008\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.344827586206897%\"\u003e\n \u003cp\u003e0.101\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.72210953346856%\"\u003e\n \u003cp\u003e0.399\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.97768762677485%\"\u003e\n \u003cp\u003e\u0026minus;0.011 to 0.026\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eBMI, body mass index; DM, diabetes mellitus\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 4: Multiple regression analysis of factors that affect skin stiffness of the forearm in patients with lymphedema \u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"499\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"43.08617234468938%\"\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.220440881763528%\"\u003e\n \u003cp\u003eB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.220440881763528%\"\u003e\n \u003cp\u003e\u0026beta;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.617234468937875%\"\u003e\n \u003cp\u003ep\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.85571142284569%\"\u003e\n \u003cp\u003e\u0026nbsp;95% CI\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"43.08617234468938%\"\u003e\n \u003cp\u003e\u0026nbsp; Age\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.220440881763528%\"\u003e\n \u003cp\u003e1.011\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.220440881763528%\"\u003e\n \u003cp\u003e0.171\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.617234468937875%\"\u003e\n \u003cp\u003e0.157\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.85571142284569%\"\u003e\n \u003cp\u003e\u0026minus;0.399 to 2.421\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"43.08617234468938%\"\u003e\n \u003cp\u003e\u0026nbsp; BMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.220440881763528%\"\u003e\n \u003cp\u003e0.223\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.220440881763528%\"\u003e\n \u003cp\u003e0.015\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.617234468937875%\"\u003e\n \u003cp\u003e0.904\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.85571142284569%\"\u003e\n \u003cp\u003e\u0026minus;3.466 to 3.911\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"43.08617234468938%\"\u003e\n \u003cp\u003e\u0026nbsp; Diabetes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.220440881763528%\"\u003e\n \u003cp\u003e59.234\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.220440881763528%\"\u003e\n \u003cp\u003e0.240\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.617234468937875%\"\u003e\n \u003cp\u003e0.064\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.85571142284569%\"\u003e\n \u003cp\u003e\u0026minus;3.436 to 121.903\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"43.08617234468938%\"\u003e\n \u003cp\u003e\u0026nbsp; Total mastectomy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.220440881763528%\"\u003e\n \u003cp\u003e3.982\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.220440881763528%\"\u003e\n \u003cp\u003e0.022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.617234468937875%\"\u003e\n \u003cp\u003e0.855\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.85571142284569%\"\u003e\n \u003cp\u003e\u0026minus;39.263 to 47.227\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"43.08617234468938%\"\u003e\n \u003cp\u003e\u0026nbsp; Cellulitis\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.220440881763528%\"\u003e\n \u003cp\u003e0.505\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.220440881763528%\"\u003e\n \u003cp\u003e0.021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.617234468937875%\"\u003e\n \u003cp\u003e0.861\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.85571142284569%\"\u003e\n \u003cp\u003e\u0026minus;5.229 to 6.239\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"43.08617234468938%\"\u003e\n \u003cp\u003e\u0026nbsp; Radiotherapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.220440881763528%\"\u003e\n \u003cp\u003e48.104\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.220440881763528%\"\u003e\n \u003cp\u003e0.195\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.617234468937875%\"\u003e\n \u003cp\u003e0.111\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.85571142284569%\"\u003e\n \u003cp\u003e\u0026minus;11.386 to 107.594\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"43.08617234468938%\"\u003e\n \u003cp\u003e\u0026nbsp; Days from onset to measurement\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.220440881763528%\"\u003e\n \u003cp\u003e\u0026minus;0.012\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.220440881763528%\"\u003e\n \u003cp\u003e\u0026minus;0.133\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.617234468937875%\"\u003e\n \u003cp\u003e0.278\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.85571142284569%\"\u003e\n \u003cp\u003e\u0026minus;0.034 to 0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eBMI, body mass index; DM, diabetes mellitus\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"breast cancer-related lymphedema, skin stiffness, MyotonPRO, measurement","lastPublishedDoi":"10.21203/rs.3.rs-4352290/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4352290/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eSevere lymphedema leads to a decline in quality of life. Skin stiffness is one of the symptoms of lymphedema; however, no objective method has been established to evaluate this symptom. We aimed to examine whether MyotonPRO, which is used to evaluate muscle and fascia stiffness, could evaluate skin stiffness in upper limb lymphedema.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eFemale patients with breast cancer-related lymphedema (BCRL) after unilateral breast cancer surgery were included. Stiffness by MyotonPRO and circumference were measured on both sides 5 and 10 cm from the elbow joint of the forearm and upper arm, respectively. Measurements were compared between the normal and lymphedema limbs. History of breast cancer, lymphedema and comorbidities were collected from medical records, and the relationship with skin stiffness was evaluated.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe skin stiffness values of normal and lymphedema limbs were 249\u0026thinsp;\u0026plusmn;\u0026thinsp;50 and 283\u0026thinsp;\u0026plusmn;\u0026thinsp;56 N/m (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) in the upper arm and 306\u0026thinsp;\u0026plusmn;\u0026thinsp;44 and 353\u0026thinsp;\u0026plusmn;\u0026thinsp;64 N/m (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) in the forearm, respectively, and were significantly greater in the lymphedema limb. The circumferences of the normal and lymphedema limbs were 27.5\u0026thinsp;\u0026plusmn;\u0026thinsp;3.6 and 29.1\u0026thinsp;\u0026plusmn;\u0026thinsp;4.0 cm (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) for the upper arm and 23.7\u0026thinsp;\u0026plusmn;\u0026thinsp;2.4 and 25.1\u0026thinsp;\u0026plusmn;\u0026thinsp;2.9 cm (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) for the forearm, respectively, in which the lymphedema limb was significantly larger. In the multiple regression analysis, diabetes had the greatest effect on the lymphedema limb stiffness.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eMyotonPRO can objectively assess chronic skin stiffness in BCRL.\u003c/p\u003e","manuscriptTitle":"Objective evaluation of skin stiffness in breast cancer-related lymphedema using MyotoPRO","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-06-20 15:11:54","doi":"10.21203/rs.3.rs-4352290/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"c11b3c65-b654-4574-8222-7d6344a3209b","owner":[],"postedDate":"June 20th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-03-23T02:38:25+00:00","versionOfRecord":[],"versionCreatedAt":"2024-06-20 15:11:54","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4352290","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4352290","identity":"rs-4352290","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}