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Hot off the Press October 2021

We have collated some great articles and material published over the last month. Click on the links below to read the  abstract or download the full paper.

Anatomy / Physiology /Pathophysiology

Current Understanding of Pathological Mechanisms of Lymphedema - click for abstract

Current Understanding of Pathological Mechanisms of Lymphedema

Cynthia J Sung, Sarah Xiao Wang, Jerry F Hsu, Roy P Yu, Alex K Wong. Adv Wound Care (New Rochelle). 2021 Sep 15.
SIGNIFICANCE: Lymphedema is a common disease that affects hundreds of millions of people worldwide with significant financial and social burdens. Despite increasing prevalence and associated morbidities, the mainstay treatment of lymphedema is largely palliative without an effective cure due to incomplete understanding of the disease. Recent Advances: Recent studies have described key histological and pathological processes that contribute to the progression of lymphedema including lymphatic stasis, inflammation, adipose tissue deposition, and fibrosis. This review aims to highlight cellular and molecular mechanisms involved in each of these pathological processes.
CRITICAL ISSUES: Despite recent advances in the understanding of the pathophysiology of lymphedema, cellular and molecular mechanisms underlying the disease remains elusive due to its complex nature.
FUTURE DIRECTIONS: Additional research is needed to gain a better insight into the cellular and molecular mechanisms underlying the pathophysiology of lymphedema, which will guide the development of therapeutic strategies that target specific pathology of the disease.

Prevalence and Risk Factors

Onset and burden of lower limb lymphedema after radical prostatectomy: a cross-sectional study - click for abstract

Onset and burden of lower limb lymphedema after radical prostatectomy: a cross-sectional study

Manuel Neuberger, Laura Schmidt, Frederik Wessels, Miriam Linke, Carina Müller, Niklas Westhoff, Philipp Nuhn, Jost von Hardenberg. Support Care Cancer. 2021 Sep 3.
OBJECTIVES: To explore men’s onset and burden of lower limb lymphedema (LLL) after radical prostatectomy (RP) with pelvic lymph node dissection (PLND).
PATIENTS AND METHODS: A cross-sectional survey-based study was conducted nation-wide and web-based in Germany. Part 1 included 15 multidisciplinary compiled questions with three questions from the Short Form 12 Health Survey (SF-12) and the WHO activity recommendation and part 2 included the validated German Lymph-ICF-Questionnaire (Lymph-ICF-LL). Subgroup comparisons and simple regression analyses were used to identify factors associated with therapy and burden of LLL, followed by multiple regression analyses to explain variance in impairment in the patients’ daily life.
RESULTS: Fifty-four patients completed the survey. Median time of LLL-onset was reported with 2.0 (0.5-9.75) months after RP. Nineteen patients (35.2%) reported bilateral lymphedema, 28 (51.9%) the use of individually fitted compression stockings (CS), 25 (46.3%) of manual lymphatic drainage (LD), and 26 (48.1%) complete regression. The Lymph-ICF-LL revealed a higher total burden for patients with an active LLL compared to complete regression (total score: 25.5 vs. 11.9, p = 0.01) especially for “physical function” (28.3 vs. 12.9, p < 0.01) and "mental function" (26.2 vs. 6.7, p < 0.01). In multiple linear regression analysis, a higher BMI (β = 0.28), lower subjective general health (β = -0.48), and active lymphedema (β = 0.28) were significant predictors of higher reported impairments in the Lymph-ICF-LL, accounting for 45.4% of variance.
CONCLUSION: Men with LLL after RP with PLND report a significant burden in daily life. Basic therapy needs to be offered early. Postoperative onset of LLL is variable, which should be considered when assessing complications after RP.

The Association Between the Number of Retrieved Pelvic Lymph Nodes and Ipsilateral Lower Limb Lymphedema in Patients With Gynecologic Cancer - click for abstract

The Association Between the Number of Retrieved Pelvic Lymph Nodes and Ipsilateral Lower Limb Lymphedema in Patients With Gynecologic Cancer

Sang Geun Jung, Sang Hee Im, Migang Kim, Min Chul Choi, Won Duk Joo, Seung Hun Song, Chan Lee, Hyun Park. J Invest Surg. 2021 Sep 21:1-6.
PURPOSE: While the risk of lower limb lymphedema (LLE) after radical surgery for gynecologic malignancies is multifactorial, the limited assessment of lymph nodes (LNs), such as sentinel LN biopsy, has been incorporated into a standard procedure. We assessed the relationship between the number of LNs retrieved from the hemipelvis and the incidence of ipsilateral LLE (iLLE).
METHODS: This retrospective study included 103 women with gynecologic cancer who had LNs removed with minimally invasive surgery between January 2014 and December 2018. For early detection of LLE, the patients were followed up by a lymphedema specialist who complied with the International Society of Lymphedema criteria. Potential risk factors for LLE were collected, and the risk factors were further investigated according to the number of LNs removed in a side-specific manner.
RESULTS: LLE was diagnosed in 32 (31.1%) patients, and most of them were diagnosed with unilateral (n = 22) LLE rather than bilateral (n = 10). The number of pelvic LNs removed (p = 0.018), no lymphatic mapping (p = 0.034), and radiation (p = 0.020) were associated with the development of one or both LLEs. A side-specific analysis revealed that the incidence of iLLE increased significantly when four or more LNs were removed from the hemipelvis compared with three or fewer LNs (22.9% vs. 8.3%, p = 0.048).
CONCLUSIONS: The number of pelvic LNs retrieved was associated with the incidence of LLE in patients with early gynecologic cancer. We identified the cutoff number per hemipelvis through side-specific analysis that could minimize the risk of iLLE. Further studies are needed to validate our results.

Risk factors for lymphedema after breast surgery: A prospective cohort study in the era of sentinel lymph node biopsy - click for abstract

Risk factors for lymphedema after breast surgery: A prospective cohort study in the era of sentinel lymph node biopsy

S Salinas-Huertas, A Luzardo-González, S Vázquez-Gallego, S Pernas, C Falo, M J Pla, M Gil-Gil, M Beranuy-Rodriguez, H Pérez-Montero, M Gomila-Sancho, N Manent-Molina, A Arencibia-Domínguez, B Gonzalez-Pineda, F Tormo-Collado, M Ortí-Asencio, J Terra, E Martinez-Perez, A Mestre-Jane, I Campos-Varela, M Jaraba-Armas, A Benítez-Segura, M Campos-Delgado, M E Fernández-Montolí, Y Valverde-Alcántara, A Rodríguez, G Campos, A Guma, J Ponce-Sebastià, R Planas-Balagué, M Catasús-Clavé, A García-Tejedor. Breast Dis. 2021 Aug 23.
INTRODUCTION: The Objective was to investigate the incidence of lymphedema after breast cancer treatment and to analyze the risk factors involved in a tertiary level hospital.
METHODS: Prospective longitudinal observational study over 3 years post-breast surgery. 232 patients undergoing surgery for breast cancer at our institution between September 2013 and February 2018. Sentinel lymph node biopsy (SLNB) or axillary lymphadenectomy (ALND) were mandatory in this cohort. In total, 201 patients met the inclusion criteria and had a median follow-up of 31 months (range, 1-54 months). Lymphedema was diagnosed by circumferential measurements and truncated cone calculations. Patients and tumor characteristics, shoulder range of motion limitation and local and systemic therapies were analyzed as possible risk factors for lymphedema.
RESULTS: Most cases of lymphedema appeared in the first 2 years. 13.9% of patients developed lymphedema: 31% after ALND and 4.6% after SLNB (p < 0.01), and 46.7% after mastectomy and 11.3% after breast-conserving surgery (p < 0.01). The lymphedema rate increased when axillary radiotherapy (RT) was added to radical surgery: 4.3% for SLNB alone, 6.7% for SLNB + RT, 17.6% for ALND alone, and 35.2% for ALND + RT (p < 0.01). In the multivariate analysis, the only risk factors associated with the development of lymphedema were ALND and mastectomy, which had hazard ratios (95% confidence intervals) of 7.28 (2.92-18.16) and 3.9 (1.60-9.49) respectively.
CONCLUSIONS: The main risk factors for lymphedema were the more radical surgeries (ALND and mastectomy). The risk associated with these procedures appeared to be worsened by the addition of axillary radiotherapy. A follow-up protocol in patients with ALND lasting at least two years, in which special attention is paid to these risk factors, is necessary to guarantee a comprehensive control of lymphedema that provides early detection and treatment.

Assessment

Developing and validating a prediction model for lymphedema detection in breast cancer survivors - click for abstract

Developing and validating a prediction model for lymphedema detection in breast cancer survivors

Xiaoxia Wei, Qian Lu, Sanli Jin, Fenglian Li, Quanping Zhao, Ying Cui, Shuai Jin, Yiwei Cao, Mei R. Fu
Eur J Oncol Nurs. 2021 Aug 31;54:102023
PURPOSE: Early detection and intervention of lymphedema is essential for improving the quality of life of breast cancer survivors. Previous studies have shown that patients have symptoms such as arm tightness and arm heaviness before experiencing obvious limb swelling. Thus, this study aimed to develop a symptom-warning model for the early detection of breast cancer-related lymphedema.
METHODS: A cross-sectional study was conducted at a tertiary hospital in Beijing between April 2017 and December 2018. A total of 24 lymphedema-associated symptoms were identified as candidate predictors. Circumferential measurements were used to diagnose lymphedema. The data were randomly split into training and validation sets with a 7:3 ratio to derive and evaluate six machine learning models. Both the discrimination and calibration of each model were assessed on the validation set.
RESULTS: A total of 533 patients were included in the study. The logistic regression model showed the best performance for early detection of lymphedema, with AUC = 0.889 (0.840-0.938), sensitivity = 0.771, specificity = 0.883, accuracy = 0.825, and Brier scores = 0.141. Calibration was also acceptable. It has been deployed as an open-access web application, allowing users to estimate the probability of lymphedema individually in real time. The application can be found at https://apredictiontoolforlymphedema.shinyapps.io/dynnomapp/.
CONCLUSION: The symptom-warning model developed by logistic regression performed well in the early detection of lymphedema. Integrating this model into an open-access web application is beneficial to patients and healthcare providers to monitor lymphedema status in real-time.

Diagnostic Criteria for Breast Cancer-Related Lymphedema of the Upper Extremity: The Need for Universal Agreement- click for abstract

Diagnostic Criteria for Breast Cancer-Related Lymphedema of the Upper Extremity: The Need for Universal Agreement

Yara W Kassamani, Cheryl L Brunelle, Tessa C Gillespie, Madison C Bernstein, Loryn K Bucci, Tracy Nassif, Alphonse G Taghian. Ann Surg Oncol. 2021 Sep 9.

With advances in breast cancer treatments and resultant increased survival rates, emphasis has been placed on post-treatment complications such as breast cancer-related lymphedema (BCRL), a chronic, negative sequela of breast cancer treatment. Accurate BCRL diagnosis necessitates longitudinal screening beginning at preoperative baseline. Prospective screening programs incorporating symptoms, objective measurements and clinical examination allow for early detection, early intervention, and improved BCRL prognosis. Currently, varied diagnostic criteria for BCRL exist, and this lack of consensus leads to variation in diagnostic and screening practices across institutions. This review outlines current diagnostic tools, including subjective and objective measurement methods and clinical examination. The merits of different criteria are evaluated and recommendations are made regarding measurement tools and diagnostic criteria for BCRL. Ultimately, the BCRL diagnostic process should be universalized and combine objective measurements, clinical evaluation, and symptoms assessment, and adhere to the best practices of the measurement tools used.

Comparison of perometry-based volumetric arm measurements and bioimpedance spectroscopy for early identification of lymphedema in a prospectively-screened cohort of breast cancer patients - click for abstract

Comparison of perometry-based volumetric arm measurements and bioimpedance spectroscopy for early identification of lymphedema in a prospectively-screened cohort of breast cancer patients

T C Gillespie, S A Roberts, C L Brunelle, L K Bucci, M C Bernstein, K M Daniell, G N Naoum, C L Miller, A G Taghian. Lymphology. 2021;54(1):1-11.
Breast cancer-related lymphedema (BCRL) affects more than one in five women treated for breast cancer, and women remain at lifelong risk. Screening for BCRL is recommended by several national and international organizations for women at risk of BCRL, and multiple methods of objective screening measurement exist. The goal of this study was to compare the use of perometry and bioimpedance spectroscopy (BIS) for early identification of BCRL in a cohort of 138 prospectivelyscreened patients. At each screening visit, a patient’s relative volume change (RVC) from perometer measurements and change in L-Dex from baseline (ΔL-Dex) using BIS was calculated. There was a negligible correlation between RVC and ΔL-Dex (r=0.195). Multiple thresholds of BCRL were examined: RVC ≥5% and ≥10% as well as and ΔL-Dex ≥6.5 and ≥10. While some patients developed an elevated RVC and ΔL-Dex, many demonstrated elevations in only one threshold category. Moreover, the majority of patients with RVC ≥5%, ΔL-Dex ≥6.5, or ΔL-Dex ≥10 regressed to non-elevated measurements without intervention. These findings suggest a role for combining multiple screening methods for early identification of BCRL; furthermore, BCRL diagnosis must incorporate patient symptoms and clinical evaluation with objective measurements obtained from techniques such as perometry and bioimpedance spectroscopy.

Tissue Dielectric Constant and Water Displacement Method Can Detect Changes of Mild Breast Cancer-Related Arm Lymphedema- click for abstract

Tissue Dielectric Constant and Water Displacement Method Can Detect Changes of Mild Breast Cancer-Related Arm Lymphedema

Katarina Karlsson, Karin Johansson, Lena Nilsson-Wikmar, Christina Brogårdh. Lymphat Res Biol. 2021 Sep 22
Background:Most commonly, volume measurements are used to evaluate the effect of lymphedema treatment, but as the accumulation of lymph fluid can be local, this method may not always be the best. Tissue dielectric constant (TDC) can be applied to identify local lymphedema changes, but has not been used before when evaluating treatment in mild arm lymphedema. Thus, the overall aim of this study was to examine if TDC and water displacement method (WDM) can measure changes in mild breast cancer-related lymphedema during the 6-month standard treatment. More specifically, we examined changes within and between three defined groups based on lymphedema thresholds of TDC and WDM at start of treatment, as well as changes of the highest TDC ratio and site.   
Methods and Results: Forty-six women with mild arm lymphedema, received treatment with compression sleeves, mostly ccl 1, and instructions about self-care. Local tissue water was measured by TDC at six defined sites and lymphedema relative volume (LRV) by WDM before treatment and at first, second, third, and sixth month. There was a significant decrease in the site with the highest TDC ratio, as well as LRV at all follow-up visits. At 6 months, TDC ratio had decreased mean 0.26 (p < 0.001) and LRV mean - 3.3% (p < 0.001). There was a significant difference between the groups in change of TDC ratio, but not in LRV. Sixty percent changed the overall highest TDC ratio to another site during 6 months.
Conclusion: Both TDC and WDM could detect changes in mild arm lymphedema but should be interpreted separately.

Efficient and precise Ultra-QuickDASH scale measuring lymphedema impact developed using computerized adaptive testing - click for abstract

Efficient and precise Ultra-QuickDASH scale measuring lymphedema impact developed using computerized adaptive testing

Cai Xu, Mark V Schaverien, Joani M Christensen, Chris J Sidey-Gibbons. Qual Life Res. 2021 Sep 29.
PURPOSE: This study aimed to evaluate and improve the accuracy and efficiency of the QuickDASH for use in assessment of limb function in patients with upper extremity lymphedema using modern psychometric techniques.
METHOD: We conducted confirmative factor analysis (CFA) and Mokken analysis to examine the assumption of unidimensionality for IRT model on data from 285 patients who completed the QuickDASH, and then fit the data to Samejima’s graded response model (GRM) and assessed the assumption of local independence of items and calibrated the item responses for CAT simulation.
RESULTS: Initial CFA and Mokken analyses demonstrated good scalability of items and unidimensionality. However, the local independence of items assumption was violated between items 9 (severity of pain) and 11 (sleeping difficulty due to pain) (Yen’s Q3 = 0.46) and disordered thresholds were evident for item 5 (cutting food). After addressing these breaches of assumptions, the re-analyzed GRM with the remaining 10 items achieved an improved fit. Simulation of CAT administration demonstrated a high correlation between scores on the CAT and the QuickDash (r = 0.98). Items 2 (doing heavy chores) and 8 (limiting work or daily activities) were the most frequently used. The correlation among factor scores derived from the QuickDASH version with 11 items and the Ultra-QuickDASH version with items 2 and 8 was as high as 0.91.
CONCLUSION: By administering just these two best performing QuickDash items we can obtain estimates that are very similar to those obtained from the full-length QuickDash without the need for CAT technology.

A phase III, multicenter, single-arm study to assess the utility of indocyanine green fluorescent lymphography in the treatment of secondary lymphedema- click for abstract

A phase III, multicenter, single-arm study to assess the utility of indocyanine green fluorescent lymphography in the treatment of secondary lymphedema
Shinsuke Akita, Naoki Unno, Jiro Maegawa, Yoshihiro Kimata, Yusuke Ota, Yuichiro Yabuki, Akira Shinaoka, Masaki Sano, Fumio Ohnishi, Hisashi Sakuma, Takashi Nuri, Yoshihito Ozawa, Yuki Shiko, Yohei KawasakI, Michiko Hanawa, Yasuhisa Fujii, Eri Imanishi, Tadami Fujiwara, Hideki Hanaoka, Nobuyuki Mitsukawa. J Vasc Surg Venous Lymphat Disord. 2021 Sep 27:S2213-333X(21)00488-1.
OBJECTIVE: Indocyanine green fluorescent lymphography may be useful in patients undergoing lymphatic surgery for secondary lymphedema. This clinical trial aimed to confirm whether indocyanine green fluorescent lymphography is useful for evaluating lymphedema, identifying lymphatic vessels suitable for anastomosis, and confirming patency of a lymphaticovenular anastomosis in patients with secondary lymphedema.
METHODS: This phase III, multicenter, single-arm, open-label clinical trial (HAMAMATSU-ICG study) investigated the accuracy of lymphedema diagnosis via indocyanine green fluorescent lymphography compared with lymphoscintigraphy, the identification rate of lymphatic vessels at the incision site, and the efficacy for confirming patency of a lymphaticovenular anastomosis. The external diameter of the identified lymphatic vessels and the distance from the skin surface to the lymphatic vessels based on preoperative indocyanine green fluorescent lymphography were measured intraoperatively under surgical microscopy.
RESULTS: When the clinical decision for surgical indication at each research site was made, the standard diagnosis of lymphedema was considered to be correct. In 26 upper extremities, a central judgment committee blinded to the clinical presentation confirmed the imaging diagnosis as accurate in 100.0% of cases, whether assessments were made via lymphoscintigraphy or indocyanine green lymphography. In contrast, in 88 lower extremities, the accuracy rates of diagnosis based on those made by the central judgment committee were 70.5% and 88.2% for lymphoscintigraphy and indocyanine green lymphography, respectively. The external diameter of the identified lymphatic vessels was significantly greater in the lower extremities than in the upper extremities (0.54 ± 0.21 mm vs. 0.42 ± 0.14 mm, p < 0.0001), and the distance from the skin surface to the lymphatic vessels was significantly longer in the lower extremities than in the upper extremities (5.8 ± 3.5 mm vs. 4.4 ± 2.6 mm, p = 0.01). In 263 skin incisions determined using indocyanine green fluorescent lymphography findings, the identification rate of lymphatics vessels suitable for anastomosis was 97.7% (95% confidence interval: 95.1-99.2). In total, 267 lymphaticovenular anastomoses were performed. Indocyanine green fluorescent lymphography was judged as "useful" in confirming patency after anastomosis in 95.1% of cases.
CONCLUSIONS: Indocyanine green fluorescent lymphography may be useful for improving the management of patients with secondary lymphedema from the outpatient setting to the operating room.

Management Strategies

Manual Lymphedema Drainage for Reducing Risk for and Managing Breast Cancer-Related Lymphedema After Breast Surgery: A Systematic Review - click for abstract

Manual Lymphedema Drainage for Reducing Risk for and Managing Breast Cancer-Related Lymphedema After Breast Surgery: A Systematic Review

Ausanee Wanchai, Jane M Armer Jane M. Armer, Nurs Womens Health. 2021 Aug 27:S1751-4851(21)00165-3
OBJECTIVE: To examine the effects of manual lymphatic drainage (MLD) on reducing the risk of and managing breast cancer-related lymphedema (BCRL).
DATA SOURCES: The electronic databases ScienceDirect, Scopus, PubMed, and CINAHL were searched for articles published in the English language from January 2000 to June 2020.
STUDY SELECTION: A total of 518 articles were retrieved. After the removal of duplicates, 472 articles remained, 433 of which were excluded based on title and abstract consideration. Thereafter, 39 studies were further inspected, and 27 articles were excluded because they were not randomized controlled trials, did not measure BCRL, and/or were an incomplete study. Ten studies were included for the final review.
DATA EXTRACTION: Data from the 10 studies were extracted and compiled into a summary table.
DATA SYNTHESIS: Based on the results of this systematic review, it cannot be concluded that MLD helps reduce the risk of BCRL for women after breast surgery. Regarding the effect of MLD on managing BCRL, the findings indicate that MLD alone or MLD combined with other treatments was likely to give similar benefits in terms of reducing arm volume for women diagnosed with BCRL.
CONCLUSION: Scientific evidence to support the benefits of MLD on preventing or reducing BCRL remains unclear. More rigorous studies to confirm findings on the effectiveness of MLD are needed.

Compression Therapy for the Patients With Breast Cancer: A Meta-analysis of Randomized Controlled Trials - click for abstract

Compression Therapy for the Patients With Breast Cancer: A Meta-analysis of Randomized Controlled Trials

Jia-Xin Li, Jie Gao, Jiang-Yan Song, Hui-Ping Li, Wen-Juan Yang, Dong-Tong Tong, Yang Zou. Cancer Nurs. 2021 Aug 30.
BACKGROUND: Compression therapy is a common method for treating breast cancer-related lymphedema. However, no specific evidence exists to guide practitioners on the morbidity of lymphedema, limb volume, and range of motion.
OBJECTIVE: The aims of this study were to compare the effects of compression therapy and routine nursing during the treatment of breast cancer-related lymphedema and to provide a basis for better clinical decision-making.
METHODS: The PubMed, Cochrane Library, EMBASE, Web of Science, CBM, CNKI, Wanfang, and VIP databases were searched through January 21, 2021. Meta-analysis and description of the outcomes were performed by using the RevMan 5.3 software.
RESULTS: A total of 17 studies were included. A meta-analysis of 13 studies was conducted. The experimental group had a lower morbidity of lymphedema, the difference was significant, and there was no heterogeneity (P < .05; odds ratio, 0.35, I2 = 31%). There was no significant difference between the experimental group and control group in limb volume, and there was significant heterogeneity (P = .44, mean difference = 4.51, I2 = 85%). Regarding range of motion, the standardized mean difference of shoulder adduction, shoulder lift, shoulder abduction, and shoulder extension were 1.37, 0.69, 0.56, and 0.87, respectively, and the differences were significant; there was heterogeneity (P < .05, I2 = 92%).CONCLUSIONS: Compression therapy can reduce the morbidity of lymphedema and improve limb movement, but the effect on limb volume needs to be further explored.
IMPLICATION FOR PRACTICE: In terms of therapeutic effectiveness and limb function, the results provide evidence that physicians can reduce the morbidity of lymphedema, reduce the degree of limb, and increase limb mobility by applying compression therapy.

Treatment Outcomes of Manual Lymphatic Drainage in Pediatric Lymphedema: Pediatric Lymphedema Manual Lymphatic Drainage - click for abstract

Treatment Outcomes of Manual Lymphatic Drainage in Pediatric Lymphedema: Pediatric Lymphedema Manual Lymphatic Drainage

Kausar Ali, Rami Dibbs, Catherine Dougherty, Ionela Iacobas, Renata Maricevich. Ann Vasc Surg. 2021 Sep 1:S0890-5096(21)00563-X.
BACKGROUND: Pediatric lymphedema can result in irreversible, debilitating limb swelling, tissue fibrosis, skin ulcers, infection, and impaired limb function in children at an early age. Manual lymphatic drainage (MLD) is a noninvasive technique, which is a part of intensive decongestive therapy to reroute lymphatic flow to healthy channels used to manage lymphedema. Outcomes of this treatment option in children have not been studied. We evaluated the effect of decongestive therapy involving MLD in pediatric patients with complex lymphatic anomalies by measuring treatment progress and functional outcomes via changes in limb circumference, limb functionality, dexterity, skin quality, and pain.
METHODS: A single-institution retrospective study on a cohort of eight pediatric patients with lymphatic anomalies who completed a course of MLD was conducted from 2015 to 2017 to investigate the role MLD plays in their lymphedema reduction. Pain scores were measured on a scale of 0-10, with 0 being no pain and 10 being the worst pain imaginable. The functional performance was measured by the Canadian Occupational Performance Measurement questionnaire.
RESULTS: Among all patients, there were four cases affecting the upper extremities, four affecting the lower extremities, and three affecting the truncal region. 5 of 8 patients demonstrated a reduction in lymphedema with an average girth reduction of 8.2% in the lower extremities, 3.0% in the upper extremities, and 7.4% in the truncal regions. In unilateral cases, the difference in limb circumference between the affected and normal extremity decreased by an average of 25.6%. Four patients completed the Canadian Occupational Performance Measurement questionnaire with an average improvement of 30% in daily task performance. Three patients reported complete resolution of pain.
CONCLUSIONS: MLD can be used as a reliable noninvasive method for decongestion and analgesia to delay the onset of lymphedema-associated fibrosis and long-term disability in children with complex lymphatic malformations.

Physical therapies in the decongestive treatment of lymphedema: A randomized, non-inferiority controlled study - click for abstract

Physical therapies in the decongestive treatment of lymphedema: A randomized, non-inferiority controlled study

Isabel Forner-Cordero, José Muñoz-Langa, Juan María DeMiguel-Jimeno, Pilar Rel-Monzó. Clin Rehabil. 2021 Sep 13:2692155211032651.
OBJECTIVE: To assess whether the treatment with intermittent pneumatic compression plus multilayer bandages is not inferior to classical trimodal therapy with manual lymphatic drainage in the decongestive lymphedema treatment.
STUDY DESIGN: Randomized, non-inferiority, controlled study to compare the efficacy of three physical therapies’ regimens in the Decongestive Lymphatic Therapy.
PARTICIPANTS: 194 lymphedema patients, stage II-III with excess volume > 10% were stratified within upper and lower limb and then randomized to one of the three treatment groups. Baseline characteristics were comparable between the groups.
INTERVENTION: all patients were prescribed 20 sessions of the following regimens: Group A (control group): manual lymphatic drainage + Intermittent Pneumatic Compression + Bandages; Group B: pneumatic lymphatic drainage + Intermittent Pneumatic Compression + Bandages; and Group C: only Intermittent Pneumatic Compression + Bandages.
END-POINT: Percentage reduction in excess volume (PREV).
RESULTS: All patients improved after treatment. Global mean of PREV was 63.9%, without significant differences between the groups. The lower confidence interval of the mean difference in PREV between group B and group A, and between group C and group A were below 15%, thus meeting the non-inferiority criterion. Most frequent adverse events were discomfort and lymphangitis, without differences between groups. A greater baseline edema, an upper-limb lymphedema and a history of dermatolymphangitis were independent predictive factors of worse response in the multivariate analysis.
CONCLUSIONS: Decongestive lymphatic therapy performed only with intermittent pneumatic compression plus bandages is not inferior to the traditional trimodal therapy with manual lymphatic drainage. This approach did not increase adverse events

Sentinel Lymph Node Biopsy, Lymph Node Dissection, and Lymphedema Management Options in Melanoma - click for abstract

Sentinel Lymph Node Biopsy, Lymph Node Dissection, and Lymphedema Management Options in Melanoma

Brian A Mailey, Ghaith Alrahawan, Amanda Brown, Maki Yamamoto, Aladdin H Hassanein. Clin Plast Surg. 2021 Oct;48(4):607-616.
Melanoma tumor thickness and ulceration are the strongest predictors of nodal spread. The recommendations for sentinel lymph node biopsy (SLNB) have been updated in recent American Joint Committee on Cancer and National Comprehensive Cancer Network guidelines to include tumor thickness ≥0.8 mm or any ulcerated melanoma. Mitotic rate is no longer considered an indicator for determining T category. Improvements in disease-specific survival conferred from SLNB were demonstrated through level I data in the Multicenter Selective Lymphadenectomy Trial (MSLT) I. The role for completion lymph node dissection has evolved to less surgery in lieu of recent domestic (MSLT II) and international (Dermatologic Cooperative Oncology Group Selective Lymphadenectomy Trial [DeCOG-SLT]) level I data having similar melanoma-specific survival. Treatment options for the prevention of treatment of lymphedema have progressed to include immediate lymphatic reconstruction, lymphovenous anastomosis, and vascularized lymph node transfer.

Comparison of complete decongestive therapy and kinesiology taping for unilateral upper limb breast cancer-related lymphedema: A randomized controlled trial - click for abstract

Comparison of complete decongestive therapy and kinesiology taping for unilateral upper limb breast cancer-related lymphedema: A randomized controlled trial

C Basoglu, D Sindel, M Corum, A Oral. Lymphology. 2021;54(1):41-51.
We designed a study to compare effects of complete decongestive therapy (CDT) and kinesiology taping (KT) (with exercise and skin care) on limb circumference, lymphedema volume, grip strength, functional status, and quality of life in patients with unilateral breast cancer-related lymphedema (BCRL). Forty patients with unilateral stage 2 BCRL were randomized to either the CDT group (n=20) or the KT group (n=20). Patients in the CDT group underwent 30-min manual lymphatic drainage (MLD) and multi-layer, short-stretch bandaging once a week for four weeks. Patients in the KT group underwent taping once a week for four weeks. In addition, all patients were informed about skin care and given an exercise program throughout the treatment. Upper extremity circumference and volume differences as primary outcomes and grip strength, Quick-Disabilities of the Arm, Shoulder and Hand (Q-DASH), and Functional Assessment of Cancer Therapy-Breast (FACT-B) scores as secondary outcomes were assessed initially, after treatment (4 weeks), and at the 1st month follow-up. Limb circumference and volume differences were significantly reduced in the CDT group after the 4-week treatment compared with the KT group (p=0.012 and p=0.015, respectively), but there was no difference between the groups in the 1st month follow-up (p>0.05). There was no difference between the groups in terms of grip strength, Q-DASH, and FACT-B scores after treatment and at the 1st month follow-up (p>0.05). Our results show that both KT and CDT were found to significantly reduce limb volume and circumference individually at 4-weeks and the one-month follow-up in patients with BCRL and that CDT significantly reduced both limb volume and circumference compared to KT at the 4- week time point, but not at the follow-up. Further randomized controlled trials with patients at different stages of BCRL are needed to confirm and expand these results.

Lower Limb Lymphedema: An Exploration of Various Treatment Methods - click for abstract

 Lower Limb Lymphedema: An Exploration of Various Treatment Methods
Adam Abboud, Jared Blum, Zarnab Butta, Elizabeth Ferber Lindvig, Nishani Kuruppu, Sonya Wali, Tracey C Vlahovic. Clin Podiatr Med Surg. 2021 Oct;38(4):589-593.
Unilateral or bilateral lower limb lymphedema is a chronic and progressive phenomenon that occurs for several reasons. From a podiatric perspective, this condition may result after a trauma, a surgical procedure, a neoplasm, or a primary condition that impairs lymph vessel function. Even though no gold standard exists, early intervention and management of lower limb lymphedema with active exercise and compression than with compression therapy alone.

Exercise: A Treatment That Should Be Prescribed With Radiation Therapy - click for abstract

Exercise: A Treatment That Should Be Prescribed With Radiation Therapy

Nicholas G Zaorsky, Sara Garrett, Daniel E Spratt, Paul L Nguyen, Chris Sciamanna, Kathryn H. Schmitz. Int J Radiat Oncol Biol Phys. 2021 Sep 18:S0360-3016(21)02644-4.
Schumacher et al 1 performed a systematic review and meta-analysis on the effects of exercise therapy during radiation therapy on physical function and treatment-related side effects in men with prostate cancer. The authors highlighted that exercise therapy improved physical function and mitigated urinary toxicity in 6 randomized controlled trials including 391 patients with prostate cancer. The meta-analysis had several major findings from exercise therapy (vs control): (1) improved cardiorespiratory fitness, (2) improved muscle function (eg, upper and lower body muscle strength, flexibility), and (3) decreased urinary toxicity. This is an important piece of work, highlighting the ability of exercise therapy to address multiple side effects for patients we manage in radiation oncology. In this editorial, we summarize the major problems that patients and physicians face in radiation therapy for prostate cancer, the possible solution from exercise therapy (based on the article by Schumacher et al), and unresolved questions related to exercise oncology.

A systematic review of pharmacological and cell-based therapies for the treatment of lymphoedema (2010-2021) - click for abstract

A systematic review of pharmacological and cell-based therapies for the treatment of lymphoedema (2010-2021)

James Walker, Sameera Tanna, Justin Roake, Oliver Lyons. J Vasc Surg Venous Lymphat Disord. 2021 Sep 26:S2213-333X(21)00486-8.
BACKGROUND: Lymphoedema describes accumulation of interstitial fluid resulting from lymphatic failure and can be of primary or secondary origin, and is estimated to affect 200 million people worldwide. Secondary lymphoedema is commonly due to damage of lymphatic vessels following surgical procedures. Treatments include compression bandaging and exercise regimes, but currently no pharmacological therapy has been approved. We aimed to perform a systematic review of randomised controlled trials (RCTs) investigating pharmacological and cell-based therapies for secondary lymphoedema.
METHODS: We searched the databases Medline, Embase and clinicaltrials.gov, from January 2010 to May 2021. Only RCTs investigating pharmacological and/or cell-based therapies for secondary lymphoedema were eligible for inclusion, and studies examining only active filarial infection were excluded. Two reviewers independently screened studies for eligibility.
RESULTS: 8 RCTs were identified that met the inclusion criteria. Overall, studies were of poor quality with high risk of bias. Ketoprofen demonstrated promising improvements in skin thickness and tissue histopathology score. There was some evidence to suggest doxycycline may be beneficial in non-filarial secondary lymphoedema, and a single small RCT demonstrated selenium may also confer some benefit. Neither synbiotics nor platelet-rich plasma resulted in reduced lymphoedema volumes or symptom severity, and although bone marrow-derived stem cells resulted in improved symptom scores, no significant volume reduction was detected. Although positive results were demonstrated in trials investigating benzopyrones, previous meta-analyses cast doubt on their efficacy. No two studies assessed the same intervention so meta-analysis could not be performed.
CONCLUSIONS: Although some studies appear promising, there is currently insufficient evidence for any pharmacological or cell based therapy for the use in patients with secondary lymphoedema. Further, large high-quality RCTs are required before treatment recommendations can be made.

Intensive Treatment for Upper Limb Lymphedema

Ana Carolina Pereira de Godoy, Maria de Fatima Guerreiro Godoy, Lívia Maria Pereira de Godoy, Henrique Jose Pereira de Godoy, Jose Maria Pereira de Godoy. Cureus. 2021 Sep 16;13(9):e18026

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Quality of Life and Costs Within Decongestive Lymphatic Therapy in Patients with Leg Lymphedema: A Multicountry, Open-Label, Prospective Study

Peter J Franks, Isabelle Quéré, Vaughan L. Keeley, Andrea Tilley, Max Liebl, Susie Murray, Ewa A Burian, Christine J Moffatt. Lymphat Res Biol. 2021 Sep 28.

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