Treatment Of Cancer-related Lymphedema Research Articles

Current Aspects of Medical Rehabilitation of Patients with Cancer Related Lymphedema of Extremities: a Narrative Review

INTRODUCTION. Over the past decades, in developed countries and in the Russian Federation, there has been an increase in the number of patients with secondary lymphedema who have undergone surgical treatment with dissection of regional lymph nodes and radiation therapy for various forms of gynecological cancer in women and prostate cancer in men, as well as breast cancer. AIM. Search and analysis of the results of previously published randomized controlled trials (RCTs) of the effectiveness of various non-drug rehabilitation methods in patients with lymphedema of the extremities who underwent radical treatment for cancer of various locations. MATERIALS AND METHODS. A search was conducted and studied publications in international scientific peer-reviewed publications (PEDro Database) on medical rehabilitation for cancer treatment-related lymphedema (LSPR) for the period from 1996 to December 2023 using the keywords “lymphedema”, “rehabilitation”. 145 RCTs focused on medical rehabilitation and conservative treatment of LSPR. DISCUSSION. Lifestyle correction and psychosocial interventions are recommended to improve the quality of life of patients. Studies have found that early activation, various physical exercises with a slow increase in loads under the supervision of a physical therapist are safe and help increase endurance, strength and range of motion in a limb with lymphatic edema. The clinical effectiveness of therapeutic exercises in the pool has been proven, manifested in the reduction of edema in patients with LSPR. The effectiveness of compression products with Velcro technology as an alternative to rigid low-stretch bandages in patients with LSPR has been confirmed. The anti-edematous and anti-inflammatory effects of low-intensity laser therapy and magnetic therapy in the rehabilitation of patients with LSLR have been proven. Alternating pneumatic compression (APC) is recommended as an adjuvant treatment in addition to comprehensive decongestant therapy. Preference should be given to the use of technologies of advanced hardware lymphatic drainage methods that imitate manual techniques. CONCLUSION. To improve the physical and socio-psychological functioning of patients with LSPR, an integrated approach is required, including lifestyle changes, psychological correction, compression therapy, modern exercise therapy techniques, and safe physiotherapeutic technologies. Conducted scientific research indicates the high effectiveness of the use of manual and hardware lymphatic drainage techniques, while the use of PPC is more economical and accessible, and does not require the involvement of specialists who know the expensive method of manual lymphatic drainage.

Supermicrosurgery lymphaticovenous and lymphaticolymphatic anastomosis: Technical detail and short-term follow-up for immediate lymphatic reconstruction in breast cancer treatment-related lymphedema prevention

ObjectiveWe describe the feasibility and short-term outcome of our surgical technique to repair the lymph vessel disruption directly after axillary lymph node dissection during breast cancer surgery. This procedure is called immediate lymphatic reconstruction to prevent breast cancer treatment-related lymphedema (BCRL), which frequently occurs after axillary lymph node dissection. The surgical technique consisted of lymphaticovenous anastomosis (LVA) or lymphaticolymphatic anastomosis. We named the procedure lymphatic bypass supermicrosurgery (LBS). MethodsThis study used a retrospective cohort design of patients with breast cancer between May 2020 and February 2023. LBS was performed by making an intima-to-intima coaptation between afferent lymph vessels and the recipient's veins (LVA) or efferent lymph vessels lymphaticolymphatic anastomosis. ResultsA total of 82 patients underwent lymphatic bypass. The mean age of patients was 50 ± 12 years, and most had stage III breast cancer (n = 59 [72%]). LVA was the most common type of lymphatic bypass (94.6%). The median number of LVA was 1 (range, 1-4) and 1 (range, 1-3) for lymphaticolymphatic anastomosis. The median follow-up time was 12.5 months (range, 1-33 months). The 50 patients who had postoperative indocyanine green lymphography described arm dermal backflow stage 0 in 20 (40%), stage 1 in 19 (38%), stage 2 in 2 (4%), and stage 3 in 9 (18%) cases. The proportion of BCRL was 11 (22%), and subclinical lymphedema was 19 (38%) in this period. Most cases were in stable subclinical lymphedema (10, 58.8%). The 1-year and 2-year BCRL rates were 14% (95% confidence interval, 4%-23.9%) and 22% (95% confidence interval, 10.1%-33.9%), respectively. ConclusionsAlong with the emerging immediate lymphatic reconstruction, LBS is a feasible supermicrosurgery technique that may have a potential role in BCRL prevention. A randomized controlled study would confirm the effectiveness of the technique.

Subcutaneous Adipose Tissue Edema in Lipedema Revealed by Noninvasive 3T MR Lymphangiography.

Lipedema exhibits excessive lower-extremity subcutaneous adipose tissue (SAT) deposition, which is frequently misidentified as obesity until lymphedema presents. MR lymphangiography may have relevance to distinguish lipedema from obesity or lymphedema. Hyperintensity profiles on 3T MR lymphangiography can identify distinct features consistent with SAT edema in participants with lipedema. Prospective cross-sectional study. Participants (48 females, matched for age [mean=44.8 years]) with lipedema (n=14), lipedema with lymphedema (LWL, n=12), cancer treatment-related lymphedema (lymphedema, n=8), and controls without these conditions (n=14). 3T MR lymphangiography (nontracer 3D turbo-spin-echo). Review of lymphangiograms in lower extremities by three radiologists was performed independently. Spatial patterns of hyperintense signal within the SAT were scored for extravascular (focal, diffuse, or not apparent) and vascular (linear, dilated, or not apparent) image features. Interreader reliability was computed using Fleiss Kappa. Fisher's exact test was used to evaluate the proportion of image features between study groups. Multinomial logistic regression was used to assess the relationship between image features and study groups. The odds ratio (OR) and 95% confidence interval (CI) of SAT extravascular and vascular features was reported in groups compared to lipedema. The threshold of statistical significance was P < 0.05. Reliable agreement was demonstrated between three independent, blinded reviewers (P < 0.001). The frequency of SAT hyperintensities in participants with lipedema (36% focal, 36% diffuse), LWL (42% focal, 33% diffuse), lymphedema (62% focal, 38% diffuse), and controls (43% focal, 0% diffuse) was significantly distinct. Compared with lipedema, SAT hyperintensities were less frequent in controls (focal: OR=0.63, CI=0.11-3.41; diffuse: OR=0.05, CI=0.00-1.27), similar in LWL (focal: OR=1.29, CI=0.19-8.89; diffuse: OR=1.05, CI=0.15-7.61), and more frequent in lymphedema (focal: OR=9.00, CI=0.30-274.12; diffuse: OR=5.73, CI=0.18-186.84). Noninvasive MR lymphangiography identifies distinct signal patterns indicating SAT edema and lymphatic load in participants with lipedema. 1 TECHNICAL EFFICACY: Stage 1.

The Breast Edema Enigma: Features, Diagnosis, Treatment, and Recommendations.

Breast edema most commonly occurs after breast cancer treatment involving breast-conserving therapy, although it may have a variety of other causes. As compared to research on breast cancer treatment-related lymphedema, breast edema and its objective measurement and diagnosis is far behind. Consequences of this disparity contribute to uncertainty and variability in its diagnosis, its treatment, and even the characterization of its incidence and morbidity. Moreover, consensus on a standardized definition, objective diagnostic method, and treatment techniques for breast edema has not yet been reached, making it difficult to provide appropriate guidelines with respect to its management. Given the recent rise in breast edema incidence as an outcome of the increasing use of breast-conserving therapy, this timely review examines the current state of breast edema assessment and makes a case for standardization in part via quantitative methods to diagnose and track breast edema.

The Effect of Exercise for the Prevention and Treatment of Cancer-Related Lymphedema: A Systematic Review with Meta-analysis.

The purpose of this systematic review and meta-analysis was to evaluate the effects of exercise on (i) the prevention of cancer-related lymphedema (CRL) and (ii) the treatment of CRL, lymphedema-associated symptoms, and other health outcomes among individuals with CRL. An electronic search was undertaken for exercise studies measuring lymphedema and involving individuals at risk of developing or with CRL. The Effective Public Health Practice Project Quality scale was used to assess study quality, and overall quality of evidence was assessed using the Grading of Recommendation, Assessment, Development and Evaluation approach. Meta-analyses were performed to evaluate effects of exercise on CRL incidence, existing CRL status, lymphedema-associated symptoms, and health outcomes. Twelve studies ( n = 1955; 75% moderate-high quality) and 36 studies ( n = 1741; 58% moderate-high quality) were included in the prevention and treatment aim, respectively. Relative risk of developing CRL for those in the exercise group compared with the nonexercise group was 0.90 (95% confidence interval (CI), 0.72 to 1.13) overall and 0.49 (95% CI, 0.28 to 0.85) for those with five or more lymph nodes removed. For those with CRL in the exercise group, the standardized mean difference (SMD) before to after exercise of CRL was -0.11 (95% CI, -0.22 to 0.01), and compared with usual care postintervention, the SMD was -0.10 (95% CI, -0.24 to 0.04). Improvements after intervention were observed for pain, upper-body function and strength, lower-body strength, fatigue, and quality of life for those in the exercise group (SMD, 0.3-0.8; P < 0.05). Findings support the application of exercise guidelines for the wider cancer population to those with or at risk of CRL. This includes promotion of aerobic and resistance exercise, and not just resistance exercise alone, as well as unsupervised exercise guided by symptom response.

Epidemiological data on lower limb lymphedema

Objective: The aim of the present study was to evaluate epidemiological data of patients seen at a clinic specialized in the treatment of lymphedema. Methods: A retrospective, cross-sectional study was conducted involving data from 150 consecutive patients with lower limb lymphedema in clinical stages II and III treated at the Godoy Clinic in São Jose do Rio Preto. The follow data were collected: sex, age, type of lymphedema (primary or secondary), cause of secondary lymphedema (cancer, trauma, venous disease) and limb dominance. The diagnosis of lymphedema was based on the clinical history and physical examination; in cases of doubt, lymphoscintigraphy of the lower limbs was requested. Descriptive statistics were performed and results were expressed as percentages. Results: Twenty-five (16.66%) of the patients were male and 125 (83.33%) were female. Mean age was 42.52 years (41.8 years among the men and 42.67 years among the women). One hundred nine cases (72.66%) were primary lymphedema and 41 (27.33%) were secondary. Among the secondary cases, 27 (18%) were related to cancer treatment, 10 (6.6%) were linked to trauma and four (2.6%) were cases of phlebolymphedema. Mean age was 51.4 years among the patients with cancer treatment-related lymphedema, 41 years among those with trauma-related lymphedema and 64.25 years among those with phlebolymphedema. The left leg was affected in 61 cases (40.66%), the right leg was affected in 37 cases (24.66%) and lymphedema was bilateral in 52 cases (34.66%). Conclusion: Primary lymphedema was predominant and affected women more than men. Primary lymphedema occurred at an earlier age compared to cancer treatment-related lymphedema and phlebolymphedema. The left leg was affected more often, followed by bilateral lymphedema and, finally, the right leg alone.

Elevated magnetic resonance imaging measures of adipose tissue deposition in women with breast cancer treatment-related lymphedema.

Breast cancer treatment-related lymphedema (BCRL) is a common co-morbidity of breast cancer therapies, yet factors that contribute to BCRL progression remain incompletely characterized. We investigated whether magnetic resonance imaging (MRI) measures of subcutaneous adipose tissue were uniquely elevated in women with BCRL. MRI at 3.0T of upper extremity and torso anatomy, fat and muscle tissue composition, and T2 relaxometry were applied in left and right axillae of healthy control (n = 24) and symptomatic BCRL (n = 22) participants to test the primary hypothesis that fat-to-muscle volume fraction is elevated in symptomatic BCRL relative to healthy participants, and the secondary hypothesis that fat-to-muscle volume fraction is correlated with MR relaxometry of affected tissues and BCRL stage (significance criterion: two-sided p < 0.05). Fat-to-muscle volume fraction in healthy participants was symmetric in the right and left sides (p = 0.51); in BCRL participants matched for age, sex, and BMI, fat-to-muscle volume fraction was elevated on the affected side (fraction = 0.732 ± 0.184) versus right and left side in controls (fraction = 0.545 ± 0.221, p < 0.001). Fat-to-muscle volume fraction directly correlated with muscle T2 (p = 0.046) and increased with increasing level of BCRL stage (p = 0.041). Adiposity quantified by MRI is elevated in the affected upper extremity of women with BCRL and may provide a surrogate marker of condition onset or severity. NCT02611557.

Therapeutic Targeting of PPAR Signaling in Cancer Treatment-Related Lymphedema

Lymphedema secondary to cancer treatment affects up to 1 in 5 cancer survivors. It is an irreversible late normal tissue toxicity characterized by swelling and scar formation (fibrosis) of the affected limb with physical and psychosocial health consequences for patients. Recent evidence reveals changes in peroxisome proliferator-activated receptor (PPAR) signaling as an underlying pathology of this disease. PPAR agonists have demonstrated therapeutic benefit in other fibrotic conditions; their role in lymphedema, however, remains unclear.In this study, RNA-sequencing of human and murine tissues with and without lymphedema was performed. Samples included: human lymphedema (n = 4), human normal tissue control (n = 5, matched for demographics and cancer history), murine lymphedema (n = 12), and murine control (n = 9). Pathway enrichment analysis was performed. An in vitro model of lymphedema fibrosis using cultured transforming growth factor beta (TGFβ)-stimulated fibroblasts and an in vivo model of lymphedema using a murine surgical model of tail lymphedema were utilized to evaluate the effects of PPAR agonists on gene expression and fibrotic protein expression (pro-collagen Iα1, collagen) in lymphedema compared to controls.RNA-sequencing of tissue from human and murine lymphedema and control subjects identified that suppression of PPAR signaling was a hallmark of lymphedema fibrosis on pathway enrichment analysis (FDR < 0.01). In the murine model, PPAR signaling gene expression changes co-occurred with fibrotic deposition beginning as early as two weeks after lymphedema development, and continued for at least 35 weeks. Treatment of TGFβ-stimulated fibroblasts with a PPAR agonist resulted in an increase in expression of PPAR genes and suppression of COL1α1 gene expression (n≥9 per group, q < 0.05) as well as reduction in the secretion of fibrotic proteins: pro-collagen Iα1 on ELISA (n≥8 per group, P < 0.0001) and collagen I on Western blotting. PPAR agonist treatment of the murine model of lymphedema resulted in a significant reduction in lymphedema fibrosis as measured by trichrome collagen staining (n≥4 per group, P < 0.05).These data, for the first time, demonstrated the value of upregulating PPAR signaling to treat lymphedema. For this condition, which to date, has no cure, repurposing PPAR agonists for lymphedema treatment is a highly promising therapeutic opportunity, which warrants further investigation.

Lymphaticovenular Anastomosis in Breast Cancer Treatment-Related Lymphedema: A Short-Term Clinicopathological Analysis from Indonesia.

Locally advanced breast cancer is commonly found in Indonesia. In this group of patients, aggressive treatment such as axillary lymph nodes dissection (ALND) with or without regional nodal irradiation (RNI) will increase the risk of breast cancer treatment-related lymphedema (BCRL) in our patients. Lymphaticovenular anastomosis (LVA) has been established as a minimally invasive approach in lymphedema surgery. In this study, we report our first experience of LVAs in BCRL patients. This was a cross-sectional study taken from breast cancer patients receiving ALND with or without RNI. From December 2018 until June 2020, we collected and described general patient information, tumor characteristics, diagnostic methods, and the outcome of LVA. Postoperative subjective symptoms scores (lymphedema quality-of-life score [LeQOLiS]) and lymphedematous volume (upper extremity lymphedema [UEL] index) were compared with preoperative ones. Seventy patients experienced BCRL with the mean age of 54.8 (9.4) years and mean body mass index of 28.1 (4.5). ALND was performed in 66 (97.1%) cases and RNI was given in 58 (82.9%) patients. Thirty-one (44.3%) patients were in the International Society of Lymphology stage 1, 24 (34.3%) in stage 2A, and 15 (21.4%) in stage 2B. The mean lymphatic vessel diameter was 0.5 (0.26) mm and 0.80 (0.54) mm for the vein. Lymphosclerosis severity was 7 (4%) in S0 type, 129 (74.1%) in S1 type, 37 (21.3%) in S2 type, and 1 (0.6%) in S3 type. In histopathology examination, S1 types were in lower grade injury, while S2 and S3 types were in the higher grade. Seven (53.8%) cases of S2 type showed severe fibrosis from trichrome staining. Postoperative LeQOLiSs were significantly lower than preoperative ones (5.6 ± 2.4 vs. 3.7 ± 2.6; p = 0.000). With the mean follow-up of 7.4 (3.7) months, the overall UEL index reduction was 9.2%; mean -11 (16.8). Postoperative UEL index was significantly lower than preoperative ones (117.7 ± 26.5 vs. 106.9 ± 18.5; p = 0.000). No complications were observed during this period. LVA reduced the subjective symptoms and UEL index in BCRL cases. Future studies using updated imaging technologies of the lymphatic system and longer follow-up time are needed to confirm our results.

The Early Detection of Breast Cancer Treatment-Related Lymphedema of the Arm.

Background: It is recognized that the early detection of breast cancer treatment related lymphedema (BCRL) leading to earlier intervention may improve long-term outcomes. This study aimed to determine whether limb volume measurement or bioimpedance spectroscopy (BIS) was the better tool for the early detection of BCRL. It also aimed to identify factors, which may be used to assess the risk of development of BCRL for individual patients. Methods and Results: This was a large prospective multicenter study of 1100 patients, who had had axillary node clearance for breast cancer, carried out in the United Kingdom. Limb volumes (by Perometer) and BIS (L-Dex by Impedimed U400) measurements were taken preoperatively and postsurgery with a follow-up period of 5 years. Details of the cancer, its treatment, body mass index (BMI), and age were recorded. BCRL was defined by relative arm volume increase (RAVI) ≥10%. At 24 months, the incidence of BCRL defined by RAVI was 22.8% and that defined by L-Dex >10 was 45.6%. Independent risk factors for the development of BCRL at 36 months were RAVI ≥5%-<10%, at 1 month, 10 or more positive nodes, BMI >30 and taxane chemotherapy. A risk assessment tool based on these was developed. Conclusions: Limb volume measurements performed better than BIS in the early detection of BCRL. Pre- and postoperative monitoring of limb volume measurements is useful in the early detection of, and prediction of those likely to develop, BCRL and allow early intervention.

ONS Guidelines™ for Cancer Treatment-Related Lymphedema.

Lymphedema is a chronic condition that may result from cancer-related surgery. The incidence of lymphedema varies greatly; however, patients remain at risk for life and may experience decreased quality of life and functional capacity. Providing recommendations for an evidence-based guideline for care of cancer treatment-related lymphedema will help to improve outcomes for patients with this chronic condition. A panel of healthcare professionals with patient representation convened to develop a national clinical practice guideline on prospective surveillance, risk reduction, and conservative treatment of lymphedema. Systematic reviews of the literature were conducted and the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) methodology approach was used to assess the evidence. The panel made multiple recommendations for patients who are at risk for or experiencing lymphedema. Early diagnosis and treatment of lymphedema may mitigate symptoms. This evidence-based guideline supports patients, clinicians, and other healthcare professionals in clinical decision making. //onf.ons.org/supplementary-material-ons-guidelines-cancer-treatment-related-lymphedema.

Use of magnetic resonance imaging for evaluation of therapeutic response in breast cancer-related lymphedema: A systematic review.

Breast cancer treatment-related lymphedema (BCRL) is a common comorbidity in breast cancer survivors. Although magnetic resonance imaging (MRI) is widely used to evaluate therapeutic response of patients with various medical conditions, it is not routinely used to evaluate lymphedema patients. We conducted a systematic review of the literature to identify studies on the use of MRI to evaluate therapy for BCRL. We hypothesized that MRI could provide information otherwise not possible through other examinations. On October 21, 2019, we conducted a systematic review on the PubMed/MEDLINE and Scopus databases, without time frame or language limitations, to identify studies on the use of MRI to evaluate therapy for BCRL. We excluded studies that investigated other applications of MRI, such as lymphedema diagnosis and surgical planning. Of 63 potential articles identified with the search, three case series fulfilled the eligibility criteria. In total, 53 patients with BCRL were included and quantitatively evaluated with MRI before and after manual lymphatic drainage. Authors used MRI or MR lymphagiography to investigate factors such as lymphatic vessel cross-sectional area, tissue water relaxation time (T2), and chemical exchange saturation transfer. The only study that compared MRI measurement with standard examinations reported that MRI added information to the therapy evaluation. MRI seems to be a promising tool for quantitative measurement of therapeutic response in patients with BCRL. However, the identified studies focused on only manual lymphatic drainage and were limited by the small numbers of patients. More studies are necessary to shed light on the topic.

Magnetic resonance imaging and bioimpedance evaluation of lymphatic abnormalities in patients with breast cancer treatment-related lymphedema.

Breast cancer treatment-related lymphedema (BCRL) evaluation is frequently performed using portable measures of limb volume and bioimpedance asymmetry. Here quantitative magnetic resonance imaging (MRI) is applied to evaluate deep and superficial tissue impairment, in both surgical and contralateral quadrants, to test the hypothesis that BCRL impairment is frequently bilateral and extends beyond regions commonly evaluated with portable external devices. 3-T MRI was applied to investigate BCRL topographical impairment. Female BCRL (n = 33; age = 54.1 ± 11.2years; stage = 1.5 ± 0.8) and healthy (n = 33; age = 49.4 ± 11.0years) participants underwent quantitative upper limb MRI relaxometry (T2), bioimpedance asymmetry, arm volume asymmetry, and physical evaluation. Parametric tests were applied to evaluate study measurements (i) between BCRL and healthy participants, (ii) between surgical and contralateral limbs, and (iii) in relation to clinical indicators of disease severity. Two-sided p-value < 0.05 was required for significance. Bioimpedance asymmetry was significantly correlated with MRI-measured water relaxation (T2) in superficial tissue. Deep muscle (T2 = 37.6 ± 3.5ms) and superficial tissue (T2 = 49.8 ± 13.2ms) relaxation times were symmetric in healthy participants. In the surgical limbs of BCRL participants, deep muscle (T2 = 40.5 ± 4.9ms) and superficial tissue (T2 = 56.0 ± 14.8ms) relaxation times were elevated compared to healthy participants, consistent with an edematous micro-environment. This elevation was also observed in contralateral limbs of BCRL participants (deep muscle T2 = 40.3 ± 5.7ms; superficial T2 = 56.6 ± 13.8ms). Regional MRI measures substantiate a growing literature speculating that superficial and deep tissue, in surgical and contralateral quadrants, is affected in BCRL. The implications of these findings in the context of titrating treatment regimens and understanding malignancy recurrence are discussed.

Oncologists and COVID-19 in Indonesia: What can we learn and must do?

Oncologists and COVID-19 in Indonesia: What can we learn and must do?

Indocyanine green lymphangiography-guided liposuction in breast cancer-related lymphedema treatment - patient selection and technique

Indocyanine green lymphangiography-guided liposuction in breast cancer-related lymphedema treatment - patient selection and technique

Feasibility of Bioimpedance Analysis to Assess the Outcome of Complex Decongestive Therapy in Cancer Treatment-Related Lymphedema.

Background: Cancer treatment-related lymphedema (CTRL) affects patients physically, psychologically and emotionally, and remains a significant quality of life issue among patients with cancer. Reliable methods to measure changes in lymphedema are required for early detection, acute intensive treatment, and long-term management. Here, we evaluated the use of bioimpedance analysis (BIA) as a tool to measure lymphedema before and after treatment.Patients and Methods: Patients with CTRL who were admitted to a secondary university hospital between October 2017 and July 2018 for complex decongestive therapy (CDT) were eligible for this prospective cohort study. Circumferential measure (CM) and BIA were used to evaluate lymphedema at admission (initial) and before discharge (follow-up, FU). Volume was calculated from the CM using the truncated cone formula. The inter-limb ratios (ILRs) of the circumference, volume, and impedance were also calculated as the unaffected limb to affected limb. Each parameter before and after treatment and correlations between parameters also were analyzed.Results: A total of 29 patients (12 upper- and 17 lower-extremity CTRL) completed were included in this analysis. Absolute value and the ILRs of circumference, volume or impedance, and extracellular water/total body water (ECW/TBW) were significantly improved at FU (p < 0.01, p < 0.05). The initial and FU absolute values, ILRs, ECW/TBW correlated significantly with each other (p < 0.01, p < 0.05). The cutoff values of ECW/TBW for moderate and severe degree of CTRL were 0.3855 and 0.3955, respectively. The changes of ILRs between initial and FU assessments were significantly different among three groups according to lymphedema severity (p < 0.01, p < 0.05).Conclusions: BIA data correlates significantly with clinical measurement, and therefore can be a practical tool in monitoring outcome measure after lymphedema treatment. In addition, BIA is more sensitive to subtle changes in lymphedema, and therefore can be useful for the long-term maintenance of lymphedema.

Meme Kanseri Tedavisiyle İlişkili Lenfödemi Olan Hastalarda Lenfödem Şiddetinin Yaşam Kalitesi, Üst Ekstremite Fonksiyonu ve Fiziksel Aktivite Düzeyi Üzerindeki Etkileri

Amaç: Bu çalışmanın amacı, meme kanseri tedavisi ile ilişkili hafif, orta ve şiddetli lenfödemi olan hasta grupları arasında yaşam kalitesi, üst ekstremitenin fonksiyonel durumu ve fiziksel aktivite düzeyindeki karşılaştırmaktı. Gereç ve Yöntemler: Bu çalışmaya, meme kanseri tedavisi ile ilişkili lenfödem tanısı olan 83 kadın (% 24 hafif, % 41 orta, % 35 şiddetli) katıldı. Lenfödemin varlığı ve şiddeti çevre ölçümü ile belirlendi. Lenfödem Yaşam Kalite Ölçeği (LYKÖ), Kol, Omuz ve El Sorunları Anketi’nin kısa versiyonu (DASH) ve Uluslararası Fiziksel Aktivite Anketi’nin kısa formu (UFAA-KF), sırasıyla yaşam kalitesi, üst ekstremitenin fonksiyonel durumu ve fiziksel aktivite düzeyinin değerlendirilmesi için kullanıldı. Bulgular: Hafif, orta ve şiddetli lenfödemi olan hastalar arasında yaşam kalitesi ve üst ekstremitenin fonksiyonel durumu açısından istatistiksel olarak anlamlı fark vardı (p&amp;lt;0.05). Ancak, fiziksel aktivite düzeyinden üç grup arasında anlamlı fark yoktu (p&amp;gt;0.05). İkili analizlerin sonuçlarına göre, şiddetli lenfödemi olan hastalarda, yaşam kalitesinin fonksiyon, görünüm ve semptom alt alanlarının ve üst ekstremitenin fonksiyonel durumunun hafif derecede lenfödemi olan hastalara göre daha fazla etkilendiği bulundu (p&amp;lt;0.016). Lenfödem şiddeti ile LYKÖ fonksiyon, görünüm ve semptom alt alanları ve DASH arasında istatistiksel olarak anlamlı ancak zayıf bir ilişki bulundu (p≤0.01). Tartışma ve Sonuç: Şiddetli lenfödemi olan hastalarda yaşam kalitesinin ve üst ekstremitenin fonksiyonel durumunun hafif lenfödemi olan hastalara göre daha fazla etkilendiği bulundu. Bu sonuçlar, meme kanseri cerrahisi geçiren bireylerde lenfödem hafif düzeyden ileri düzeye geçtiğinde yaşam kalitesi ve üst ekstremite fonksiyonelliğinin etkilenebileceğini göstermektedir. Dolayısıyla bu etkilenimi önlemek veya azaltmak için lenfödemin erken dönemde belirlenmesi ve tedavi edilmesi önemlidir.

CEST MRI quantification procedures for breast cancer treatment-related lymphedema therapy evaluation.

To quantify chemical exchange saturation transfer contrast in upper extremities of participants with lymphedema before and after standardized lymphatic mobilization therapy using correction procedures for B0 and B1 heterogeneity, and T1 relaxation. Females with (n = 12) and without (n = 17) breast cancer treatment-related lymphedema (BCRL) matched for age and body mass index were scanned at 3.0T MRI. B1 efficiency and T1 were calculated in series with chemical exchange saturation transfer in bilateral axilla (B1 amplitude = 2µT, Δω = ±5.5 ppm, slices = 9, spatial resolution = 1.8 × 1.47 × 5.5 mm3 ). B1 dispersion measurements (B1 = 1-3 µT; increment = 0.5 µT) were performed in controls (n = 6 arms in 3 subjects). BCRL participants were scanned pre- and post-manual lymphatic drainage(MLD) therapy. Chemical exchange saturation transfer amide proton transfer(APT) and nuclear Overhauser effect (NOE) metrics corrected for B1 efficiency were calculated, including proton transfer ratio(PTR'), magnetization transfer ratio asymmetry , and apparent exchange-dependent relaxation (AREX'). Nonparametric tests were used to evaluate relationships between metrics in BCRL participants pre- versus post-MLD (two-sided P < 0.05 required for significance). B1 dispersion experiments showed nonlinear dependence of Z-values on B1 efficiency in the upper extremities; PTR' showed < 1% mean fractional difference between subject-specific and group-level correction procedures. PTR'APT significantly correlated with T1 (Spearman's rho = 0.57, P < 0.001) and body mass index (Spearman's rho = -0.37, P = 0.029) in controls and with lymphedema stage (Spearman's rho = 0.48, P = 0.017) in BCRL participants. Following MLD therapy, PTR'APT significantly increased in the affected arm of BCRL participants (pre- vs. post-MLD: 0.41 ± 0.05 vs. 0.43 ± 0.03, P = 0.02), consistent with treatment effects from mobilized lymphatic fluid. Chemical exchange saturation transfer metrics, following appropriate correction procedures, respond to lymphatic mobilization therapies and may have potential for evaluating treatments in participants with secondary lymphedema.

Implementation of Single-Tab Electrodes for Bioimpedance Spectroscopy Measures

Background: Bioimpedance spectroscopy (BIS) demonstrates proficiency in early identification of breast cancer treatment-related lymphedema (BCRL) development. Dual-tab electrodes were designed for consistent and easy electrode placement, however, single-tab electrodes positioned to mimic dual-tab placement on the body may make BIS technology more accessible in community hospitals and outpatient settings. The purpose of this study is to evaluate use of single-tab electrodes for BIS measurements and assess whether single-tab electrodes provide consistent BIS measurements in controls and patients with BCRL. Methods and Results: Upper limb BIS ratios were obtained using ImpediMed L-Dex® U400 in controls (n = 13; age = 23-75 years; 9 repeated measurements) using dual-tab and single-tab electrodes. BCRL patients (n = 17; Stage = 1.65 ± 0.49; number nodes removed = 16.3 ± 7.7; age = 50.9 ± 10.6 years; age range = 33-77 years) and healthy controls (n = 19) were evaluated to determine if single-tab electrodes provided discriminatory capacity for detecting BCRL. Intraclass correlation coefficients (ICC), linear mixed-effects models, Wilcoxon rank-sum tests, and linear regression with two-sided p-values <0.05 required for significance were applied. Single-tab electrodes were found to be statistically interchangeable with dual-tab electrodes (ICC = 0.966; 95% confidence interval = 0.937-0.982). No evidence of differences in single-tab versus dual-tab measurements were found for L-Dex ratios (p = 0.74) from the linear mixed-effects model. Repeated trials involving reuse of the same electrodes revealed a trend toward increases in L-Dex ratio for both styles of electrodes. Single-tab electrodes were significant (p < 0.0001) for discriminating between BCRL and control subjects. Conclusion: Findings expand upon the potential use of BIS in clinic and research settings and suggest that readily available single-tab electrodes provide similar results as dual-tab electrodes for BIS measurements.

3.0T relaxation time measurements of human lymph nodes in adults with and without lymphatic insufficiency: Implications for magnetic resonance lymphatic imaging.

The purpose of this work was to quantify 3.0T (i) T1 and T2 relaxation times of in vivo human lymph nodes (LNs) and (ii) LN relaxometry differences between healthy LNs and LNs from patients with lymphatic insufficiency secondary to breast cancer treatment-related lymphedema (BCRL). MR relaxometry was performed over bilateral axillary regions at 3.0T in healthy female controls (105 LNs from 20 participants) and patients with BCRL (108 LNs from 20 participants). Quantitative T1 maps were calculated using a multi-flip-angle (20, 40, 60°) method with B1 correction (dual-TR method, TR1 /TR2 =30/130ms), and T2 maps using a multi-echo (TE =9-189ms; 12ms intervals) method. T1 and T2 were quantified in the LN cortex and hilum. A Mann-Whitney U-test was applied to compare LN relaxometry values between patients and controls (significance, two sided, p<0.05). Linear regression was applied to evaluate how LN relaxometry varied with age, BMI, and clinical indicators of disease. LN substructure relaxation times (mean±standard deviation) in healthy controls were T1 cortex, 1435±391ms; T1 hilum, 714±123ms; T2 cortex, 102±12ms, and T2 hilum, 119±21ms. T1 of the LN cortex was significantly reduced in the contralateral axilla of BCRL patients compared with the axilla on the surgical side (p<0.001) and compared with bilateral control values (p<0.01). The LN cortex T1 asymmetry discriminated cases from controls (p=0.004) in a multiple linear regression, accounting for age and BMI. Human 3.0TT1 and T2 relaxation times in axillary LNs were quantified for the first time in vivo. Measured values are relevant for optimizing acquisition parameters in anatomical lymphatic imaging sequences, and can serve as a reference for novel functional and molecular LN imaging methods that require quantitative knowledge of LN relaxation times.