Mild Lymphedema Research Articles

Palpation of Increased Skin and Subcutaneous Thickness, Tissue Dielectric Constant, and Water Displacement Method for Diagnosis of Early Mild Arm Lymphedema.

Background: Early diagnosis of mild lymphedema and treatment are important to prevent its progress. The tissue dielectric constant (TDC), measuring local tissue water in the skin and upper subcutis, has neither been related to the water displacement method (WDM) nor been used to diagnose mild arm lymphedema in patients at risk. Our aims were to evaluate TDC and WDM in combination with palpation, examine the association between TDC and WDM measurements, and compare lymphedema-related factors. Methods and Results: Seventy-two women treated for breast cancer were diagnosed with mild arm lymphedema using skin palpation in combination with TDC from fixed measurement sites (threshold ratio for upper arm ≥1.45 and forearm ≥1.3) and/or WDM (lymphedema relative volume [LRV]: ≥5% to ≤8%). Results revealed that 32 (45%) women were diagnosed by TDC only, 19 (26%) by WDM only, and 21 (29%) by both TDC and WDM. TDC ratios exceeding the threshold were most frequently identified on the medial site of the arm, proximal and distal to the antecubital fossa. TDC and WDM were negatively associated; LRV (r = -0.545, p < 0.001). The women diagnosed by TDC only were diagnosed earlier after surgery (p = 0.003) and had a lower LRV (1.3%) than those diagnosed by WDM only (6.3%) or both TDC and WDM (6.2%; p < 0.001). Conclusions: TDC and WDM can be used together for early diagnosis of arm lymphedema, but TDC is the most valid method, determining the diagnosis earlier after surgery and at a lower arm volume than WDM.

Integrin binding site within the gC1q domain orchestrates EMILIN-1-induced lymphangiogenesis

Lymphatic vessels (LVs) play a pivotal role in the control of tissue homeostasis and also have emerged as important regulators of immunity, inflammation and tumor metastasis. EMILIN-1 is the first ECM protein identified as a structural modulator of the growth and maintenance of LV; accordingly, Emilin1−/− mice display lymphatic morphological alterations leading to functional defects as mild lymphedema, leakage and compromised lymph drainage. Many EMILIN-1 functions are exerted by the binding of its gC1q domain with the E933 residue of α4 and α9β1 integrins. To investigate the specific regulatory role of this domain on lymphangiogenesis, we generated a transgenic mouse model expressing an E933A-mutated EMILIN-1 (E1-E933A), unable to interact with α4 or α9 integrin. The mutant resulted in abnormal LV architecture with dense, tortuous and irregular networks; moreover, the number of anchoring filaments was reduced and collector valves had aberrant narrowed structures. E933A mutation also affected lymphatic function in lymphangiography assays and made the transgenic mice more prone to lymph node metastases. The finding that the gC1q/integrin interaction is crucial for a correct lymphangiogenesis response was confirmed and reinforced by functional in vitro tubulogenesis assays. In addition, ex vivo thoracic-duct ring assays revealed that E1-E933A-derived lymphatic endothelial cells had a severe reduction in sprouting capacity and were unable to organize into capillary-like structures. All these data provide evidence that the novel “regulatory structural” role of EMILIN-1 in the lymphangiogenic process is played by the integrin binding site within its gC1q domain.

The incidence and risk factors of related lymphedema for breast cancer survivors post-operation: a 2-year follow-up prospective cohort study.

To investigate the incidence rate, severity and risk factors of related lymphedema in breast cancer survivors. A 2-year follow-up prospective study of 387 women who had operation from four hospitals from January 1, to December 31, 2014 was conducted. Limb volume was measured by circumference and symptoms were measured using questionnaires pre-treatment and 1, 3, 6, 12, 18, 24months after surgery separately. The incidence rates and the severity of lymphedema were evaluated, respectively. Risk factors for the development of breast cancer-related lymphedema (BCRL) were analyzed using log-rank test and Cox regression. The incidences of BCRL were 4.4, 10.1, 15.2, 28.6, 31.2 and 32.5% at 1, 3, 6, 12, 18, 24months after surgery, respectively, measured by Norman questionnaire. The rates measured by arm circumference were 2.5, 6.7, 13.4, 21.4, 26.3 and 29.4%, respectively. About 114 (29.4% of 387) women were diagnosed with BCRL, and 78 of them got mild lymphedema. Axillary lymph node dissection (ALND) (HR=5.2, 95% CI 1.6-17.3), radiotherapy (HR=3.9, 95% CI 2.0-7.5), modified radical mastectomy (MRM) (HR=2.1, 95% CI 1.3-3.4), the number of positive lymph nodes (HR=1.1, 95% CI 1.0-1.2) and body mass index (BMI) (HR=1.1, 95% CI 1.0-1.1) were independent risk factors for BCRL. BCRL is a common complication for breast cancer patients after surgery. It can be fairly diagnosed only 1month post-operation and the cumulative incidence of BCRL seems to be increasing over time, especially in the first year after surgery. ALND, radiotherapy, MRM, the number of positive axillary lymph nodes and BMI were found to be independent risk factors in the development of BCRL in this study.

Circumference-Based Criteria for Detection of Secondary Arm Lymphedema for Chinese Women.

Detection of upper limb lymphedema following treatment for breast cancer typically relies on interlimb circumference-based differences. Normative-determined criteria from an Australian population have high sensitivity and specificity for detection of mild lymphedema in Australian women. It is unknown whether these criteria are applicable to Chinese women whose body habitus is different from Australian women. The aims of this study, therefore, were to determine the normative-based interlimb circumference and volume differences in a Chinese population and whether specific population-based thresholds are required. Arm circumferences at the wrist and at 10 cm intervals proximally to 40 cm were measured on both the dominant and nondominant limb in 484 healthy women, aged ≥20 years. Absolute interlimb differences and interlimb ratios were determined for the circumferences and derived 10 cm volume segments. Analysis of variance determined if the differences varied, depending on location. The absolute interlimb circumference difference from 10 to 30 cm did not vary significantly, enabling determination of a single threshold applicable to all three circumferences. The interlimb ratios varied less, requiring only a threshold for the wrist and one for 10-40 cm and one ratio for interlimb volume segments. The interlimb thresholds determined in the Chinese population were within 2 mm to that reported in the Australian study. Even though the habitus of Chinese women living in China differed to the women living in Australia, similar normative-based thresholds for the detection of lymphedema were identified.

INCIDENCE AND RISK FACTORS OF ARM OEDEMA FOLLOWING MODIFIED MASTECTTOMY OF BREAST CANCER

Background: Lymphoedema after curative mastectomy related breast cancer is a late complication with estimates of incidence ranging from 6-70%. Lymphoedema may present immediately or years after treatment, majority of cases occur during the first 18 months. Objective: Investigate the incidence arm lymphedema and relation of age, tumor size, axillary node status, chemotherapy, radiation therapy for breast cancer- related arm lymphedema. Patients and methods: From 1/2014 to 12/2016, eligible patients including 164 breast cancer patient, clinically stage I,II,III, have been treated with surgery, adjuvant chemotherapy, radiation therapy and hormonotherapy accoding to stage of disease and follow-up at Hue University Hospital. Method: Prospective, observational study, with arm-circumference measurement of pre-operatively and at regular intervals post-operatively. Results: The incidence of lymphedema post-operatively is 38.4% including: mild lymphedema 19.5%, moderate 13.4% and severe 5.5%. Related factors including tumor size, axillary node status, chemotherapy and radiation therapy were statistically significantly associated with lymphoedema. Conclusion: Lymphoedema was a late complication, affected of quality of life of breast cancer patients. More systematic surveillance for early detection and appropriate treatment. Key words: Breast cancer, lymphoedema, arm oedema

Does Lymphedema Severity Affect Quality of Life? Simple Question. Challenging Answers

Lymphedema can have a negative impact on the function and quality of life (QOL) of patients, but most studies have examined lymphedema as a binary variable, rather than a multidimensional disease that ranges in severity. This study explored the potential impact of lymphedema severity on function and overall QOL. Of the 54 lymphedema patients recruited, 40 reported their most severe swelling to be in a limb. These participants underwent bioimpedance measurement (L-Dex®) and completed either the disabilities of the arm, shoulder, and hand (DASH) questionnaire or the lower extremity functional scale (LEFS). All participants completed the lymphedema quality of life questionnaire (LYMQOL) and were categorized for severity using International Society of Lymphology (ISL) stage. Mild (Stage 0-I), moderate (Stage IIa), and severe (Stage IIb-III) lymphedema accounted for 22%, 50%, and 28% of the participants, respectively. The median [inter-quartile range (IQR)] L-Dex score was 17.8 (6.6-52.7) for arm participants and 36.4 (15.9-93.5) for leg participants. Apart from a mild difference in LYMQOL ARM Appearance domain (p = 0.046), ISL staging did not have any relationship with DASH, LEFS, and LYMQOL domains, or overall QOL. Higher L-Dex was related to poorer function (DASH p = 0.015; LEFS p = 0.019), but was not related to overall QOL of limb lymphedema participants (p > 0.05). Lymphedema severity did not appear to impact QOL. ISL staging may not be used alone to describe lymphedema severity. Other methods such as bioimpedance, imaging, and self-report of symptoms are required to fully evaluate the impact of lymphedema severity on function and QOL.

Effect of Arm Position on Circumference Measurement of Upper Arms in Healthy and in Women With Breast Cancer–Related Lymphedema

Background: Arm circumference measurement for women with breast cancer–related lymphedema (BCRL) using a tape measure is reliable, valid, and widespread in clinical practice. Arm position for measurement varies among therapists and lacks uniformity in the literature. Objective: To examine the effect of arm position on total arm and segment volume for both arms in healthy women and women with BCRL. Design: Case-control study. Methods: Fourteen women in the maintenance phase of treatment of unilateral BCRL and 16 healthy women matched for age and body mass index. Three sequential circumferential measurements were performed in 2 different resting arm positions (90° supported forward flexion, dependent alongside the body) in both arms during 1 session. Arm volume was calculated using the summed truncated cone formula. Results: A nonsignificant interaction effect of arm (small vs large), position (horizontal vs vertical), and group (women with BCRL vs healthy women) on limb volume was noted (F 1,28 = 3.30, P = .08). While among women with BCRL (study group), the mean percentage volume change in the large arm between positions was lower than in the small arm (1.37% ± 1.97%) vs 1.61% ± 1.99%, respectively), the opposite was noted among healthy women (control group) (3.36% ± 1.45% vs 2.46% ± 1.59%, respectively). Limitations: Participants with BCRL presented with nonpitting mild lymphedema, and 2 specific positions that were selected limit the external validity to this stage of lymphedema and to these positions. Conclusions: Measurements should be performed in the same position; if not, according to the findings of this study, testing for systematic bias between positions should be performed.

Real-Time Direct Evidence of the Superficial Lymphatic Drainage Effect of Intermittent Pneumatic Compression Treatment for Lower Limb Lymphedema.

Intermittent pneumatic compression (IPC) is a widely used lymph drainage therapy that can be performed at home. However, the effectiveness of IPC for lymph drainage remains unclear. The aim of this study is to investigate the real-time change in the lymph flow velocity during IPC and consider which mode and pressure are best for treating lower limb lymphedema. Eight lower left limbs of 8 healthy volunteers and 17 lower limbs of 15 secondary lymphedema patients were investigated. Indocyanine green lymphography was performed with the subject covered with a transparent six-chambered IPC garment. The IPC treatment was administered in several modes (sequential or nonsequential inflation mode, sequential or interrupted deflation mode, and under high or low pressure). Using a brightness intensity analysis software program, the real-time change in the fluorescence intensity during the treatment was recorded and graphed. The maximum inclination of the graph between 2 seconds in the inflation phase (SLOPE) and the mean SLOPE value of all subjects (average SLOPE) were calculated. The average SLOPEs of each mode of treatment were then compared. The average SLOPEs were also compared between patients with mild and moderate lymphedema. There were no significant differences among the SLOPEs in the healthy group. However, in the patient group, the average SLOPE was significantly higher in the sequential inflation mode as well as under high pressure than in the nonsequential inflation mode. On comparing the mild and moderate lymphedema groups, the average SLOPE tended to be higher in the mild group; however, the difference was not statistically significant. Sequential programs and high pressure resulted in a faster lymphatic flow than other modes. These results suggest that a greater treatment effect could be obtained by adjusting the mode of treatment and the pressure of IPC.

Prefabricated Cervical Skin Flaps for Hemi-Facial Resurfacing: Elucidating the Natural History of Postoperative Edema Using Indocyanine Green.

The increases in capillary wall permeability and capillary hydrostatic pressure are considered to be the causes for the acute swelling seen in flaps; however, disruption of the circulating flap lymphatics could be another contributory factor. In this study we monitor the development of flap edema in a series of 18 prefabricated flaps and aim to delineate the natural history of this phenomenon by use of lymphography. Postoperative swelling was monitored in a series of 18 pre-expanded prefabricated cervical skin flaps used for hemi-facial burns-scar resurfacing. Time to spontaneous resolution, presence or absence of venous congestion, and clinical outcome were recorded. In two cases, indocyanine-green (ICG) lymphography was used to monitor the dermal backflow pattern until swelling had completely resolved. Average moving velocity of ICG after injection as well as flap thickness was also recorded over the follow-up period. The average moving velocity of ICG in the flap lymphatics improved from 0.48 cm/min to 1.5 cm/min in the first 12 days after flap transfer. The dermal backflow pattern was stardust in the first 12 days, indicating moderate lymphedema, transforming to splash from week three, and a robust collecting lymphatic vessel occurring from the fifth month, indicating mild lymphedema and lymphatic channel recovery, respectively. Transient swelling was observed in all prefabricated flaps in our series. We postulate that this is mostly secondary to lymphatic disruption that subsides as lymphangiogenesis takes place. ICG lymphography is an inexpensive, safe, and easy-to-use imaging technology that could be used in the monitoring of postoperative lymphedema seen in prefabricated flaps.

English

This study aims to determine health-related quality of life (HRQOL) of breast cancer patients with unilateral arm lymphedema one year after completion of treatment at Cancer Diseases Hospital. The study design comprises of a cross sectional study, where we assessed the HRQoL controlling for patient demographics, cancer stages and treatment types. Short form of 36 interview schedule was used to assess HRQol and to determine relationships among HRQoL components. The physical and functional well-being was significantly associated with lymphedema. Patients with moderate lymphedema were 10 times more likely to have physical impairment and 3 times more likely to have mild functionality impairment compared to patients with mild lymphedema. While patients with severe lymphedema were 25 times more likely to have mild functionality impairment compared to patients with mild lymphedema. The study showed that &nbsp;the physical and functional well-being were significantly affected by the presence of lymphedema after breast cancer &nbsp;treatment, lymphedema has an impact on long-term health related quality of life in survivors of breast cancer and its effects should not be underestimated. &nbsp; Key words: Health related quality of life, breast cancer, patients, arm lymphedema.

Financial cost of lymphedema borne by women with breast cancer.

ObjectiveOur study examines the financial cost of lymphedema following a diagnosis of breast cancer and addresses a significant knowledge gap regarding the additional impact of lymphedema on breast cancer survivors.MethodsAn online national survey was conducted with 361 women who had either breast cancer without lymphedema (BC) (group 1, n = 209) or breast cancer with lymphedema (BC+LE) (group 2, n = 152). Participant recruitment was supported by the Breast Cancer Network Australia and the Australasian Lymphology Association.ResultsBoth breast cancer and lymphedema result in significant out‐of‐pocket financial costs borne by women. Of patients with BC+LE, 80% indicated that their breast cancer diagnosis had affected them financially compared with 67% in the BC group (P < .020). For patients with lymphedema, over half (56%) indicated that this specific additional diagnosis to their breast cancer affected them financially and that costs increased with lymphedema severity. The cost of compression garments formed a large proportion of these costs (40.1%). The average number of attendances to a therapist each year was 5.8 (range, 0‐45). Twenty‐five patients (16.4%) had an episode of cellulitis in the past year. The incidence of cellulitis was 7.7% in 91 patients with subclinical or mild lymphedema compared with 29.5% of 61 patients with more extensive lymphedema (P < .001). The average out‐of‐pocket financial cost of lymphedema care borne by women was A$977 per annum, ranging from A$207 for subclinical lymphedema to over A$1400 for moderate or severe lymphedema.ConclusionsThis study identifies an additional detrimental effect of lymphedema on women in terms of financial costs.

Lymphedema after surgical treatment for breast cancer: a 2-year follow-up study of incidence and risk factors

Objective To identify the incidence and risk factors for upper extremity lymphedema within 2 years after surgery in patients with breast cancer. Methods A follow-up study was performed among 157 patients who newly received surgical treatment for breast cancer. Norman questionnaire and circumference measurement were used to evaluate the volume of the upper limb before treatment and at 1, 3, 6, 12, 18, and 24 months after treatment. The incidence of lymphedema was calculated. Based on the results of circumference measurement, the log-rank test and Cox regression were used to analyze the risk factors for lymphedema. Results A total of 141 patients were finally enrolled as subjects. The incidence rates of lymphedema at 1, 3, 6, 12, 18, and 24 months after surgery were 3.5%, 9.2%, 13.5%, 24.8%, 28.4%, and 30.5% by Norman questionnaire, and 1.4%, 3.5%, 9.2%, 20.6%, 27.0%, and 27.7% by circumference measurement. At 24 months after surgery, 31(22.0%) out of 39 patients with lymphedema had mild lymphedema. Axillary lymph node dissection (ALND), radiotherapy, modified radical mastectomy (MRM), and the number of removed axillary lymph nodes were independent risk factors for lymphedema (HR=13.58, 95% CI: 2.17-85.00; HR=3.54, 95% CI: 1.13-11.07; HR=2.19, 95% CI: 1.07-4.49; HR=1.11, 95% CI: 1.05-1.16). Conclusions The incidence of lymphedema associated with breast cancer increases gradually within 2 years after surgery, especially fast in the first year. ALND, radiotherapy, MRM, and the number of removed axillary lymph nodes are independent risk factors for lymphedema. Key words: Breast neoplasms; Lymphedema; Incidence; Risk factor

Initiating a lymphedema screening program for breast cancer patients: Determining variability as a first step towards standardization.

267 Background: Breast cancer-related lymphedema (BCRL) is a known morbidity from treatment, and yet published estimates of its incidence are highly variable. Typically, a single volume measurement is recorded and the degree of intra-rater variability undefined. A threshold 5% limb volume change over time is used to define “mild lymphedema.” Therefore, small variations in volume measurements could substantially lead to over or under-diagnosis of BRCL. Gage R&amp;R is a measurement systems analysis tool that quantifies the amount of variability induced in measurements by the measurement system itself and compares this to the total variability observed. The objective of this study was to define the degree of variability in perometer arm volume measurements and factors contributing to this. Methods: A medical assistant (MA) was trained by a certified lymphedema therapist (CLT) to perform perometer-based lymphedema screening in the MD Anderson Nellie B. Connally Breast Center. Three measurements of each arm were taken and intra-rater variability against the mean calculated. Gage R&amp;R testing was performed by the MA and CLT, to determine the degree of repeatability and reproducibility variation. As a part of this analysis, 30 patients had both their left and right arm volume measured 3 times by each measurer. Results: Over 6 months, 565 breast cancer patients had preoperative BCRL screening by the MA, with an overall intra-rater variability of 2.2%. Among the 30 patients in the Gage R&amp;R study, median body mass index (BMI) was 27.7 (range 19.7-38.3), median height 1.61m (range 1.52-1.73m), intrarater variability of the MA was 2.07% and of the CLT was 1.21%. Gage R&amp;R accounted for 4.77% of total variability, 1.26% repeatability and 3.51% reproducibility. Regression analysis demonstrated that patient BMI and height impacted variability in measurements (R2= 16.27). Conclusions: Intra-rater variability for perometer arm measurements diminishes with experience. Gage R&amp;R variability is acceptable per industry standards, but there is room for improvement. Our findings suggest a role for targeted interventions to minimize variability in the diagnosis of BCRL based on patient characteristics.

The Patient’s Perspective on the Effect of Autologous Breast Reconstruction on Lymphedema

Lymphedema is a well-documented complication of the treatment for breast cancer. Although the onset of lymphedema is rare after delayed autologous breast reconstruction, no studies have surveyed a patient's perspective on the effects of reconstruction on lymphedema. The design of this study was a retrospective review of delayed unilateral breast reconstruction performed by the senior authors between 2005 and 2009 combined with the use of a well-validated survey instrument that can be used to diagnose lymphedema. Patients were mailed a series of questions to determine if they had lymphedema. In addition, they were asked separate questions about reconstruction's effect on arm symptoms. During this period, 90 patients underwent delayed unilateral breast reconstruction with an autologous free flap. After 2 mailings, 68.8% (n = 62) of patients returned the survey and were included in data analysis. Of the 62 respondents, 11.3% (n = 7) had been diagnosed and documented as having lymphedema in the medical record. This is in stark contrast to the survey that reported 48.3% (n = 30) with lymphedema (P < 0.01), which is more consistent with previous reports of lymphedema after mastectomy. Overall, 29.0% (n = 18) reported mild lymphedema and 20.0% (n = 12) reported moderate/severe lymphedema. Of those diagnosed by survey, 51.7% thought there was no change, 27.6% were worse, and 20.7% were better after reconstruction. Although not necessarily indicative of a diagnosis of lymphedema, when asked questions about arm symptoms, 38.4% thought their symptoms were worse, 30.8% reported no change, and 30.8% stated they were better. Of those patients with lymphedema by survey, only 18.5% reported discussing this with their plastic surgeon. Overall, the prevalence of lymphedema was similar to published reports in the cancer literature, but much more common than reported in our plastic surgery clinic or recent plastic surgery literature. On the whole, delayed reconstruction seems to have no effect on lymphedema. Although more prospective study is necessary to answer this question conclusively, as part of a multidisciplinary team, plastic surgeons should be aware that lymphedema is common; patients may not volunteer their symptoms and may in fact benefit from specific questioning to aid in diagnosis and treatment.

Abstract P1-09-09: Determination of the first evidence-based diagnosis of secondary upper limb lymphedema

Abstract Background: The incidence of secondary upper limb lymphedema after treatment for breast cancer is unclear due to the wide variety of measurement tools and diagnostic thresholds that are used in both the literature and clinical practice. Furthermore, this lack of clarity in what constitutes lymphedema or not has prevented the progression of the field of lymphedema. Many of the thresholds have been chosen for ease of use only and have no evidence base to support them. The aim of this study, therefore, was to determine which clinical diagnostic threshold for unilateral upper limb lymphedema has the best sensitivity and specificity when compared to diagnosis by lymphoscintigraphy. Methods: Women with and without a history of secondary upper limb lymphedema were assessed using lymphoscintigraphy, bioimpedance spectroscopy (BIS) as well as volume and circumference measurements using the perometer. Dermal backflow score was determined as the diagnostic criteria for the lymphoscintigraphy and was assessed by an experienced nuclear medicine physician. Determination of the presence of lymphedema by lymphoscintigraphy was compared with diagnosis by both commonly-used and normatively-determined diagnostic thresholds for circumference, volume and bioimpedance. Normatively-and commonly-used diagnostic thresholds examinedWhole arm volumeCircumferenceWhole arm BISNormatively-determined thresholds examined3SD perometry threshold*Single elevated circ (3SD threshold)*3SD Cornish, 20012SD perometry threshold*Adjacent raised circ (3SD threshold)*2SD Cornish, 20013SD frustrum threshold*Single raised threshold (2 SD)*3SD, Ward 20112SD frustum threshold*Adjacent raised circ (2SD threshold)*2SD, Ward 2011 3SD SOAC* 2SD SOAC* Commonly-used thresholds examined200 ml interlimb difference2 cm single interlimb difference 10% differenceAdjacent 2 cm interlimb difference 5 cm SOAC * Dylke et al, 2012; Sum of arm circumferences (SOAC); Circumference measure (Circ) Results: For those with widespread dermal backflow, any clinical diagnostic criteria could differentiate between those with and without lymphedema. In contrast, for those with mild to moderate dermal backflow, only the normatively-determined threshold, set at 2 standard deviations above the norm, for arm circumference and full arm bioimpedance (Cornish et al 2001) had adequate sensitivity and specificity. Both of these thresholds had clinically relevant positive (23 and 10 respectively) and negative (0.2 and 0.3) likelihood ratios. Conclusion: Evidence-based diagnostic thresholds have been established for the diagnosis of secondary upper limb lymphedema. In determining if lymphoedema is present in those with mild lymphedema, normatively-determined circumference and bioimpedance thresholds that account for limb dominance should be used. Adoption of these evidence-based criteria will allow, for the first time, comparison between studies, clarifying the incidence and risk factors for lymphedema, allowing the field to make meaningful progress forward in determining who is at-risk for lymphedema and how to prevent it from developing. Acknowledgements: Cancer Australia and National Breast Cancer Foundation. Citation Format: Sharon L Kilbreath, Elizabeth S Dylke, Geoff P Schembri, Leigh C Ward, Dale L Bailey, Deborah Black, Elizabeth A Bailey, Jane M Beith, Kathryn M Refshauge. Determination of the first evidence-based diagnosis of secondary upper limb lymphedema [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-09-09.

The effectiveness of decongestive treatments provided within 12 months of developing a swollen arm for women with breast cancer-related lymphedema: a systematic review protocol of quantitative evidence

REVIEW QUESTION/OBJECTIVE The objective of this review is to identify the effectiveness of decongestive lymphedema treatment to reduce excess limb volume or improve patient-centered outcomes for women presenting within 12 months of developing a swollen arm due to breast cancer-related lymphedema. More specifically, the objectives are to identify: 1) The most effective combination of treatment elements 2) The optimal duration of treatment. INCLUSION CRITERIA Types of participants This review will consider studies that include women with unilateral breast cancer-related lymphedema of the arm, who have received lymphedema treatment within 12 months of developing arm swelling. As many studies have included participants with chronic swelling, this review will consider studies where the average duration of swelling is no more than nine months. It is believed that this will maximize the inclusion of relevant studies while limiting the number of participants with chronic lymphedema (i.e. > 12 months duration). Studies which include participants with other forms of lymphedema (e.g. leg lymphedema) will be included only where data is separately reported for breast cancer-related lymphedema of the arm. Studies which include truncal/breast lymphedema, bilateral lymphedema, individuals who are “at risk” of developing breast cancer-related lymphedema or receiving concurrent cancer treatment will be excluded from the review. Types of intervention(s) This review will consider studies that evaluate any decongestive lymphedema treatment delivered with the purpose of reducing arm lymphedema, within 12 months of development of arm swelling, whether as lymphedema therapist-treatment or patient self-management. This will include, but not be TRUNCATED AT 250 WORDS

Axillary reverse mapping in breast cancer: a Canadian experience.

The aim of this study was to evaluate the axillary reverse lymphatic mapping (ARM) procedure for reducing the risk of arm lymphedema after breast cancer surgery. The ARM procedure was carried out with a subareolar injection of technetium-99 sulfur colloid the morning of surgery, and a patent blue dye injection into the upper inner arm after anesthesia. Fifty-two women made up our study population. Thirty-seven patients underwent sentinel lymph node biopsy (SLNB) and 15 patients underwent an axillary lymph node dissection (ALND) for known nodal metastasis. The sentinel lymph node was identified in 36 of the 37 cases who underwent SLNB alone and in 12 of 15 patients who underwent on ALND. In 13 patients, both blue and radioactive lymph nodes or lymphatics were clearly identified (25%) and 5 patients had a clear crossover with nodes being both blue and hot. Only a single patient with crossover lymphatics had metastases present in their sentinel node. The ARM technique did not prevent identification of the SLN and we identified much greater crossover than reported. We had a single patient, who underwent a sentinel node biopsy, with mild arm lymphedema (1.9%) after 2 years of follow up.

Yellow nail syndrome presenting with postpartum massive pleural effusion

Yellow nail syndrome (YNS) is an uncommon clinical syndrome characterized by yellow-green discoloration of nails and recurrent respiratory tract lesions, pleural effusions and lymphedema. A 38-year-old woman was referred to the emergency complaining of chronic cough and increasing dyspnea within last 2 weeks. She had given birth 1 month ago. On examination, the patient exhibited dystrophic yellowish nails and mild peripheral lymphedema. A chest roentgenogram revealed a large right pleural effusion and a small left pleural effusion. YNS is a rare clinical entity but should be taken into consideration in patients with massive pleural effusions and persistent lymphedemas on the postpartum period.

Abstract OT2-5-01: The PREDICT study (prospective, randomized early detection and intervention after breast cancer - Treatment, for women at risk of lymphedema)

Abstract Introduction: It is well-documented that lymphedema is one of the most feared long-term side effects of breast cancer (BC) treatment. However, to date, a standardized approach for the quantification and treatment of breast cancer-related lymphedema (BCRL) has yet to be established. Aims: We propose a screening and intervention trial to assess the efficacy of early detection and intervention with various treatment strategies for BCRL. Intervention comprises the use of compression garments for mild lymphedema and compression garments +/- nighttime bandaging for moderate lymphedema. Other factors to be evaluated include: symptom clusters, treatment adherence, fear avoidance behavior, quality of life (QOL), upper extremity function, and risk factors for BCRL. Eligibility Criteria: Women 18 years + with a confirmed BC diagnosis, no history of BC, no known metastatic or locally advanced disease, no history of primary lymphedema, sentinel lymph node biopsy or axillary lymph node dissection as part of definitive breast surgery. Study Design: A two-stage study which includes a Screening and an Intervention trial. The screening trial will evaluate arm volume change during and after BC treatment with target accrual of 8000. Currently, 1286 participants have been enrolled among three sites including MGH, MD Anderson and Brigham and Women's Hospital. Patients will undergo perometer measurements and complete the MGH Lymphedema Evaluation Following Treatment for Breast Cancer (LEFT-BC) survey at each screening assessment to evaluate changes in functionality, upper extremity utilization, fear avoidance behaviors, and QOL. Screening visits will occur pre- and post-operatively, at the conclusion of chemotherapy and/or radiation therapy and every 3-8 months thereafter. Patients will become eligible for intervention trial enrollment if, during the course of screening, unilaterally affected patients develop a relative arm volume change (RVC) of ≥ 5% or bilaterally affected patients develop a weight adjusted change (WAC) of ≥ 5% which persists at a verification measurement within 4-8 weeks. Eligible subjects will be enrolled into one of two groups based on verification RVC/WAC: Group I – Mild Lymphedema (5-10% RVC/WAC) or Group II – Moderate Lymphedema (11-20% RVC/WAC). Subjects are then randomized within each group. Group I subjects are randomized to one of two arms: I-A – Observation, I-B – Compression, and Group II subjects are randomized to one of two arms: II-A – Compression, II-B – Compression + Night Compression Bandaging. Target accrual for the intervention trial is 336 subjects (Group I: 208, Group II: 128). Clinical Relevance: The results of this study will yield Level I evidence on the effectiveness of early detection and intervention for BCRL. Findings may shape clinical practice in diagnosis and treatment, as well as provide insight regarding the risk factors, symptoms, upper extremity function, and QOL associated with BCRL.*Funding by award #s R01CA139118 &amp;3P5OCA089393, AGT. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr OT2-5-01.

One-Year Postoperative Morbidity Associated With Near-Infrared–Guided Indocyanine Green (ICG) or ICG in Conjugation With Human Serum Albumin (ICG:HSA) Sentinel Lymph Node Biopsy

Sentinel lymph node biopsy (SLNB) is a standard staging procedure in breast cancer and skin melanoma patients. Radioactive colloid (RC) and blue dye are the routinely used markers for staining. The new dye used in this procedure, indocyanine green (ICG), seems to have true potential in near-infrared-guided SLNB. The aim of this study was to analyze 1-year morbidity after SLNB using RC and ICG or RC and ICG conjugated to human serum albumin (ICG:HSA) in breast cancer and skin melanoma patients. Forty-nine patients diagnosed with breast cancer and 10 patients with skin melanoma underwent SLNB using ICG with RC and ICG:HSA with RC. A total of 47 SLNB patients without the need for additional lymphadenectomy were evaluated approximately 1 year (11-13 months) for the presence of tattoo, extremity swelling, nerve dysfunction/pain, range of motion, and stiffness. From the 47 patients examined, long-term morbidity was present in 3 (6.4%). In 1 patient, tattoo persisted for 11 months. Mild lymphedema was seen in 1 patient, and 1 patient exhibited minor functional deficit. Using ICG or ICG:HSA seems to be safe, and long-term morbidity in SLNB patients is low. However, skin discoloration may appear as it does after the use of blue dye, and an increased number of harvested nodes might be associated with an increased number of iatrogenic lymphedema.