Lymphedema Of Upper Extremity Research Articles

Bioimpedance and upper limb lymphedema index in the diagnosis of lymphedema in post-mastectomy syndrome

Methods for assessing post-mastectomy edema: bioimpedance and upper extremity lymphedema index (UEL index) are non-invasive, highly sensitive and easily feasible diagnostic methods, suitable for predicting the prospects of surgical treatment and analyzing the dynamics of edema. The purpose of the study was to study UEL index indicators and bioimpedance data at different stages of upper extremity lymphedema. Material and methods. The study included 64 patients with post-mastectomy edema who underwent bioimpedance, measurement of the circumference of the upper extremity and calculation of the UEL index. Results. The upper extremity lymphedema index and bioimpedance parameters (fluid volume in the limb and the ratio of extracellular fluid to total fluid volume) characterizing the liquid component significantly increased at stages II and III of lymphedema in comparison with the control group. a statistically significant correlation was revealed between the upper limb lymphedema index and bioimpedance parameters (R=0.41) and (R=0.49), respectively. Conclusion. Bioimpedance parameters and values of the upper extremity lymphedema index can be interchangeable. The reliability and high sensitivity of these methods for assessing post-mastectomy edema allows us to obtain quantitative criteria for evaluating the liquid component at different stages of lymphedema.

Lymphovenous Bypass for Immediate Lymphatic Reconstruction in Breast Cancer Patients Undergoing Axillary Lymph Node Dissection: Minimizing the Risk of Upper Extremity Lymphedema.

Studies have shown a significant reduction in breast cancer-related lymphedema (BCRL) rates in patients undergoing complete axillary lymph node dissection (cALND) combined with immediate lymphatic reconstruction (ILR) using lymphovenous bypass (LVB).The purpose of this study was to determine if ILR with LVB at the time of cALND results in a decreased incidence of BCRL and its impact on patient quality of life (QOL). In this prospective cohort study, patients ≥ 18 years requiring cALND underwent ILR from 2019 to 2021. The primary outcome was bilateral upper limb volumes measured by Brørson's truncated cone formula and the Pero-System (3D Körper Scanner). The secondary outcome was QOL measured by the Lymphedema Quality of Life (LYMQOL) arm patient-reported outcome measurement. Forty-two patients consented to ILR using LVB. ILR was completed in 41 patients with a mean of 1.9 ± 0.9 lymphovenous anastomosis performed. Mean age of patients was 52.4 ± 10.5 years with a mean body mass index of 27.5 ± 4.9 kg/m2. All patients (n = 39, 100%) received adjuvant therapy after ILR. Mean follow-up was 15.2 ± 5.1 months. Five patients met criteria for lymphedema throughout the duration of the study (12.8%), with two patients having resolution, with an overall incidence of 7.7% by the end of the study period. Patients with lymphedema were found to have statistically significant lower total LYMQOL values at 18 months (8.44 ± 1.17 vs. 3.23 ± 0.56, p < 0.001). A mean increase of 0.73 ± 3.5 points was observed for overall QOL average for upper limb function at 18 months compared with 3 months (t = 0.823, p = 0.425). This study showed an incidence of 7.7% lymphedema development throughout the duration of study. We also showed that ILR has the potential to reduce the significant long-term adverse outcomes of lymphedema and improve QOL for patients undergoing cALND.

Alternative Lymphatic Drainage Pathways in the Trunk Following Oncologic Therapy.

Anatomic and functional descriptions of trunk and breast lymphedema following breast cancer treatment are emerging as indicators of lymphatic dysfunction. Indocyanine green-lymphangiography has been instrumental in characterizing this dysfunction in the extremity and can be applied to other regions. Previous work has established a validated Pittsburgh Trunk Lymphedema Staging System to characterize such affected areas. This study aims to identify risk and protective factors for the development of truncal and upper extremity lymphedema using alternative lymphatic drainage, providing implications for medical and surgical treatment. Patients undergoing revisional breast surgery with suspicion of upper extremity lymphedema between 12/2014 and 3/2020 were offered lymphangiography. The breast and lateral/anterior trunks were visualized and blindly evaluated for axillary and inguinal lymphatic flow. A linear-weighted Cohen's kappa statistic was calculated comparing alternative drainage evaluation. Binomial regression was used to compute relative risks (RRs). Significance was assessed at alpha = 0.05. Eighty-six sides (46 patients) were included. Twelve sides underwent no treatment and were considered controls. Eighty-eight percent of the noncontrols had alternative lymphatic flow to the ipsilateral axillae (64%), ipsilateral groins (57%), contralateral axillae (20.3%), and contralateral groins (9.3%). Cohen's kappa for alternative drainage was 0.631 ± 0.043. Ipsilateral axillary and contralateral inguinal drainage were associated with reduced risk of developing truncal lymphedema [RR 0.78, confidence interval (CI) 0.63-0.97, P = 0.04; RR 0.32, CI 0.13-0.79, P = 0.01, respectively]. Radiation therapy increased risk of truncal and upper extremity lymphedema (RR 3.69, CI 0.96-14.15, P = 0.02; RR 1.92, CI 1.09-3.39, P = 0.03, respectively). Contralateral axillary drainage and axillary lymph node dissection were associated with increased risk of upper extremity lymphedema (RR 4.25, CI 1.09-16.61, P = 0.01; RR 2.83, CI 1.23-6.52, P = 0.01, respectively). Building upon previous work, this study shows risk and protective factors for the development of truncal and upper extremity lymphedema. Most prevalent alternative channels drain to the ipsilateral axilla and groin. Ipsilateral axillary and contralateral inguinal drainage were associated with reduced risk of truncal lymphedema. Patients with radiation, axillary dissection, and contralateral axillary drainage were associated with increased risk of upper extremity lymphedema. These findings have important clinical implications for postoperative manual lymphatic drainage and for determining eligibility for lymphovenous bypass surgery.

The 6 month interim analysis of a randomized controlled trial assessing the quality of life in patients with breast cancer related lymphedema undergoing lymphaticovenous anastomosis vs. conservative therapy

Breast cancer related lymphedema (BCRL) is a chronic condition with a detrimental impact on psychosocial and physical well-being. Lymphaticovenous anastomosis has shown promising results in alleviating physical symptoms and increasing quality of life in patients with BCRL. The aim of the study is to evaluate the effect on health related quality of life (HrQol) after LVA surgery versus conservative treatment in patients with BCRL. The study is a prospective, multicenter randomized controlled trial. Adult women with unilateral BCRL, with early stage lymphedema and viable lymphatic vessels were included. The primary outcome measure was HrQol measured by the lymphedema functioning disability and health (Lymph-ICF) questionnaire. The secondary outcomes were volume difference measured by the water displacement method; the Upper Extremity Lymphedema (UEL) index; and daily use of the compression garments after 3 and 6 months. For this interim analysis 46 patients per group were included. There was a significant improvement in the domains in physical and mental function in the Lymph-ICF questionnaire in the LVA group after 6 months, (− 16.46 ± 18.5, p < 0.05, − 10.12 ± 29.5, p < 0.05 respectively). However, there was no statistical difference in the total score of the Lymph-ICF after 6 months in both groups (LVA-group; − 8.57 ± 22.6, p > 0.05, CDT-group; − 2.65 ± 18.2, p < 0.05). Furthermore, there was no significant volume reduction in both groups (LVA-group: 20.04 ± 196.40, p = 0.497, CDT: 33.98 ± 189.87, p = 0.236). In the LVA group, 41% partially of completely stopped wearing the compression garments after six months whereas in the CDT group 0% discontinued to use of compression garments. LVA resulted in improvement of the domains physical and mental function of the Lymph-ICF. Limb volume did not significantly improve after 6 months. However, around 42% could completely or partially stopped with the use of compression garments in the LVA group. The current results are promising, however longer follow up is required to assess long term effect of LVA for secondary lymphedema. Clinical Trial Registration: NCT02790021 registered on 03/06/2016

Early lymphaticovenous anastomosis in lymphedema management: a pilot study

Aim: Lymphedema is a progressive degenerative disease that can cause severe swelling and recurrent infections. Conservative and surgical treatments, such as lymphaticovenous anastomosis (LVA), are available; however, the optimal timing for LVA after the initiation of complex decongestive therapy (CDT) remains unclear. This study aimed to evaluate the effect of CDT duration prior to LVA on the treatment outcomes of upper extremity lymphedema. Methods: Fifty patients with stage II upper extremity lymphedema who underwent LVA were retrospectively evaluated. Patients were divided into two groups based on the duration of CDT before LVA: &lt; 6 months (early group) and &gt; 6 months (non-early group). The primary outcome measures were percent excess volume (PEV) and reduction rate 12 months after LVA. Results: The early group (CDT &lt; 6 months) showed significantly better outcomes than the non-early group (CDT &gt; 6 months) . The early group had a lower PEV (4%) and a higher reduction rate (56%) than the non-early group (PEV of 10% and reduction rate of 25%) at 12 months after LVA. Conclusions: Early indication for LVA (within 6 months of CDT initiation) resulted in better treatment outcomes for stage II upper extremity lymphedema. This study highlights the potential benefits of early surgical intervention for improving the prognosis of lymphedema.

Three-dimensional non-contrast magnetic resonance lymphography severity stage for upper extremity lymphedema

PurposesNon-contrast magnetic resonance lymphography (NMRL) has recently shown the capability of evaluating anatomical fluid distribution in upper extremity lymphedema (UEL). However, there is still a lack of knowledge about the correlation between the characteristic three-dimensional (3D) NMRL findings and the indocyanine green lymphography (ICG-L) findings. Our goal was to clarify the relationship between the 3D NMRL findings and the ICG-L findings. MethodsMedical charts of patients with secondary UEL who underwent NMRL and ICG-L between January 2018 to October 2021 were reviewed. The upper extremities were divided into 6 regions; the hand, elbow, and the radial and ulnar aspects of the forearm and the upper arm. We investigated the prevalence of characteristic 3D NMRL patterns (Mist/Spray/Inky) in each region based on the ICG-L stage. We also examined the association between the 3D NMRL stage which we proposed and the ICG-L stage, and other clinical factors. ResultsA total of 150 regions of 25 patients with upper extremities lymphedema were enrolled in the study. All of the characteristic patterns increased significantly as the ICG-L stage advanced (p < 0.001, < 0.001, and < 0.001, respectively). The predominant NMRL patterns changed significantly from the Early pattern (Mist pattern) to the Advanced pattern (Inky/Spray pattern) as the ICG-L stage progressed (p < 0.001). The higher Stage of 3D NMRL was significantly associated with the progression of the ICG-L stage (rs = 0.80, p < 0.001). ConclusionsCharacteristic 3D NMRL patterns and the 3D NMRL Stage had a significant relationship with the ICG-L stage and other clinical parameters. This information may be an efficient tool for a more precise and objective evaluation of various treatments for UEL patients.

Vascularized lymph node transfer with efferent lymphatico-lymphatic anastomosis for treatment of upper extremity lymphedema

Vascularized lymph node transfers (VLNT) are useful options for the surgical treatment of lymphedema. Conventional VLNT does not include the reconstruction of physiological lymphatic outflow, which may pose a risk of postoperative lymphatic vessel obstruction and lymph node sclerosis. We report a case of lymph flow bypass reconstruction using a superficial circumflex Iliac artery perforator (SCIP) flap, including VLNT with efferent lymphatico-lymphatic anastomosis. A 63-year-old female with severe right upper extremity lymphedema after mastectomy was reconstructed using a SCIP free flap, which included a vascularized lymph node elevated from the left groin area and transferred to the right axilla area. The SCIP vessels were anastomosed to the medial intercostal artery perforator vessels and the efferent lymphatic vessel from the vascularized lymph node was anastomosed to the internal mammary lymphatic vessels using supermicrosurgical technique. Indocyanine green lymphography showed the reconstructed lymphatic flow from the right hand to the right internal mammary lymphatics through the transferred flap. Postoperatively, lymphedema improved and there was no lymphedema at the donor site with a 2-year follow-up. Lymphatic flow bypass reconstruction using VLNT with efferent lymphatico-lymphatic anastomosis may provide a useful option for the treatment of severe lymphedema.

Toxicity and Efficacy of Hypofractionated Regional Nodal Irradiation

Hypofractionated whole-breast irradiation (HF-WBI) has been widely adopted. However, there are still limited data on whether hypofractionated regional nodal irradiation (HF-RNI) is safe and effective. We report toxicity and cancer outcomes with our HF-RNI approach. This retrospective study included 154 patients with node-positive or high-risk node-negative breast cancer treated with HF-RNI with curative intent at a single academic institution from 2008-2020. Median dose to the breast or chest wall/reconstructed breast was 40 Gy in 16 fractions (interquartile range [IQR], 40-45 Gy in 16-18 fractions). Median dose to the regional nodes was 40 Gy in 16 fractions (IQR, 40-40 Gy in 16-16 fractions). The primary end-point was the rate of chronic toxicity. Secondary endpoints were local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), disease-free survival (DFS), and overall survival (OS). Toxicities were scored using the Common Terminology Criteria for Adverse Events v5.0 and Radiation Therapy Oncology Group scale where appropriate. This study was approved by the Institutional Review Board. Median follow-up was 46 months (IQR 33-63 mo). Median age at diagnosis was 58 years. Sentinel lymph node biopsy (SLNB) was performed in 49% of patients, 16% underwent both SLNB and axillary lymph node dissection (ALND), 32% underwent ALND alone, and 3% had no axillary surgery; 79% had partial mastectomy and 21% had total mastectomy with or without reconstruction. The nodal target included the supraclavicular and axillary Level 1-3 nodes in 66% of patients and supraclavicular and Level 3 nodes in 34%. The crude incidence of grade 1 chronic brachial plexopathy was 2%, grade 1 chronic limited range of motion (LROM) of the upper extremity was 3%, and chronic upper extremity lymphedema was 8% (11 patients with grade 1 toxicity and 1 patient with grade 2 toxicity). The only grade 3+ chronic toxicity was hyperpigmentation (1%). The median time to the development of the highest-grade toxicity was 10 months for brachial plexopathy, 10 months for LROM, and 11 months for lymphedema, respectively. Five-year actuarial rates of LRFS, RRFS, DFS, and OS were 98%, 99%, 90%, and 88%, respectively. HF-RNI resulted in low rates of chronic toxicities and excellent disease control in this study. Results of randomized trials of HF-RNI are needed for definitive evidence, but these retrospective data support wider adoption of HF-RNI.

Posterior Neck Coverage in Patients Receiving Regional Nodal Irradiation for Breast Cancer

Patterns-of-failure studies suggest the posterior neck (PN) may harbor microscopic disease in patients with locally advanced breast cancer. We compared target coverage, lung dose, and toxic effects in patients treated with either an anterior oblique field (AO) or opposed oblique fields (OO) to address the superior axillary and supraclavicular nodal (SCV) regions. We identified 119 consecutively treated patients who received regional nodal irradiation, including a "third field," to address the superior axillary and supraclavicular nodal regions with a monoisocentric technique in our institution. Coverage of the axillary clinical target volume (CTV), SCV CTV and PN CTV was determined based on the delivered treatment plan. Wilcoxon rank-sum test and Fisher's exact test were used to compare coverage of the axillary, SCV, and PN CTVs, lung dosimetry, and toxic effects (graded by the Common Terminology Criteria for Adverse Events v4.0) between patients receiving an AO or OO. There were 29 patients in the AO group and 80 in the OO group. All patients in the AO group received conventionally fractionated radiation versus 61% in the OO group. Modestly hypofractionated plans were delivered to 39% of the OO group. The body mass index and anterior-posterior separation at the matchline (measured at the center of the carotid artery) were similar in both groups. The median volume (%) of the SCV CTV receiving at least 90% of the prescription dose (V90%) was 91% (85, 99) in the AO group and 93% (91, 95) in the OO group (P = 0.2). The median V90% of the PN CTV was 30% (12, 49) in the AO group and 100% (100, 100) in the OO group (P<0.001). The median V90% in the axillary levels I, II and III CTVs were 98%, 95% and 90%, respectively, in the AO group and all 100% in the OO group (P<0.001). Maximum dose and heterogeneity in the SCV CTV were similar in both groups. Including only patients who received conventionally fractionated plans, the mean lung dose (cGy) was 1216 in the AO group and 1328 in the OO group (P = 0045). The lung V5 Gy, V10 Gy and V20 Gy were similar in both groups. Ipsilateral upper extremity lymphedema (all grade 1) was 3.4% in the AO group and 2.5% in the OO group (p>0.9). Moist desquamation in the neck was 0% in the AO group and 1.2% in the OO group (p>0.9). Pneumonitis (all grade 1) was 0% in the AO group and 1.2% in the OO group (p>0.9). Compared to a single anterior field, opposed oblique fields provide superior axillary and posterior neck coverage without increasing toxicity.

Assessment of proprioception, muscle strength and endurance during dynamic isokinetic test in patients with breast cancer-related lymphedema

BackgroundBreast cancer-related lymphedema is a common complication after breast cancer treatment.This study examined isokinetic proprioception, muscular strength, and endurance by comparing extremity with lymphedema and the extremity without lymphedema in women with breast cancer-related lymphedema. MethodsA total of 15 individuals aged between 35 and 70 years participated in this study. Cybex Humac NORM Isokinetic dynamometer (CSMi, Stoughton, MA) were used to assess upper extremity passive proprioception, active proprioception, kinesthesia, muscle strength, and muscle endurance. The upper extremity lymphedema was measured with the water displacement arm volumetry test using a volumeter. FindingsAll isokinetic measurements demonstrated a statistically significant difference between the extremity with lymphedema and the extremity without lymphedema, suggesting lower scores in the extremity with lymphedema (p < .05). There was a positive correlation between passive internal rotation in the extremity with lymphedema and the time after mastectomy (r= 0.628, p = .012) and a moderate positive relationship was found between the time after lymphedema and passive internal rotation (r = 0.577; p = .024), and active external rotation position sense (r = 0.540; p = .038) in the extremity with lymphedema. Also, a unidirectional positive moderate (r = 0.594; p = .020) relationship was found between the lymphedema stage and passive external rotation in the extremity with lymphedema. InterpretationThe difference in proprioception, muscle strength, and endurance between the extremity with lymphedema and the extremity without lymphedema in women with breast cancer-related lymphedema will provide valuable information in terms of prioritizing these parameters in treatment.

The Dynamic Lymphaticovenular Anastomosis for Breast Cancer-related Lymphedema without Compression: Salvaging Lymphedema Patients Who Lost Conservative Treatment Opportunity.

The study involved 17 BCRL patients, 18 limbs. All patients had International Society of Lymphology stage-2 lymphedema, but they had no compression: six patients had difficulty by other diseases to undergo compression, and other 11 patients refused any compression usage because of the burden of the treatment itself. Three dynamic LVAs were performed in each patient. Patients' mean age was 60.4 ± 10.1, and mean body mass index was 24.0 ± 3.3. The mean follow-up period was 25.5 ± 9.2 months. The volume of the lymphedematous limb, according to the upper extremity lymphedema (UEL) index, was reduced in all 18 limbs postoperatively (postoperative UEL index 101.8 ± 9.4 versus preoperative UEL index 116.0 ± 20.1; P < 0.01). Twelve of the 18 limbs were cured without edema. Even without compression therapy, International Society of Lymphology stage-2 BCRL patients can be treated by the dynamic LVA method.

Pneumatic Compression-Assisted Lymphoscintigraphy for Quantitative Evaluation of Breast Cancer-Related Lymphedema.

Acquired lymphedema of upper extremity is a chronic pathologic status that frequently occurs after breast cancer treatment. Reliable and quantitative evaluation of lymphedema is crucial for successful management of patients. Although lymphoscintigraphy is the primary investigation for the confirmation and evaluation of lymphedema, the specific protocol of stress intervention is not well established. This study aims to introduce intermittent pneumatic compression (IPC) as a part of stress lymphoscintigraphy and compare the effectiveness of conventional stress lymphoscintigraphy (CSL) and pneumatic compression-assisted lymphoscintigraphy (PCAL). Our study was designed as a retrospective analysis of 85 breast cancer patients with lymphedema who underwent lymphoscintigraphy utilizing either IPC device or conventional stress maneuver and received complex decongestive therapy. The flow extent of the lymphatic fluid (FE) was evaluated using a 0- to 4-point scale based on lymphoscintigraphic images. The visualization of lymph nodes was also assessed. The clinical outcomes were evaluated by changes in side-to-side circumferential and volume differences of upper extremities and compared between groups. Of 85 patients, 47 underwent CSL, and 38 underwent PCAL. Participants with relatively preserved flow extent of the lymphatic fluid (FE 3) showed a significant difference in percentage reduction of volume (PRV) between CSL and PCAL groups ( P = 0.036). In the other groups, CSL and PCAL demonstrated comparable differences in PRV without statistical significance. Our study suggests that participants in the PCAL group with relatively preserved lymphatic flow extent (FE 3) had better PRV compared with those in the CSL group. The use of IPC devices in lymphoscintigraphy with the novel stress maneuver can help in the quantitative description of lymphedema status and the selection of an appropriate treatment method.

Efficacy of Lymphaticovenular Anastomosis for Secondary Upper Extremity Lymphedema: Treatment Strategies with Effects of Compression Therapy Discontinuation and Site-Specific Evaluation of the Upper Extremity.

Background: Lymphaticovenular anastomosis (LVA) has recently become a mainstream surgical treatment for lymphedema and is a useful treatment option in addition to conservative therapies such as compression therapy, exercise therapy, and lymphatic drainage. We performed LVA with the goal of stopping compression therapy and report the effect of LVA on secondary lymphedema of the upper extremities. Methods and Results: The participants were 20 patients with secondary lymphedema of the upper extremities categorized as stage 2 or 3 according to the International Society of Lymphology classification. We measured and compared the upper limb circumference at six locations before and 6 months after LVA. Significant decreases in circumference after surgery were observed at 8 cm proximal to the elbow, the elbow joint, 5 cm distal to the elbow, and the wrist joints, but not at 2 cm distal to the axilla or the dorsum of the hand. At more than 6 months postoperatively, eight patients who had been wearing compression gloves were no longer required to wear them, and three patients who had been wearing both sleeves and gloves were no longer required to wear them. Conclusions: LVA is effective in the treatment of secondary lymphedema of the upper extremities, particularly in improving elbow circumference, and is one of the treatments that contributes significantly to the improvement of quality of life. For severe cases with limited range of motion of the elbow joint, LVA should be performed first. Based on these results, we present an algorithm for upper extremity lymphedema treatment.

SP33. Optimizing Patient Selection for Lympha in Patients with Inflammatory Breast Cancer

PURPOSE: Patients with inflammatory breast cancer (IBC) are at high risk for lymphedema due to their need for axillary lymph node dissection (ALND) and high-dose regional nodal radiation. LYMPHA (Lymphatic Microsurgical Preventive Healing Approach) is increasingly offered for prevention of upper extremity lymphedema after breast cancer treatment. Prior studies focus on intraoperative and postoperative lymphedema risk factors, some of which are unknown preoperatively when the decision to perform LYMPHA is made. This study aimed to identify preoperative lymphedema risk factors in the high-risk IBC population. METHODS: Retrospective review of our institution’s IBC program database was conducted. All patients with IBC who underwent neoadjuvant chemotherapy (NAC) and modified radical mastectomy (MRM) with adjuvant radiation were reviewed. The primary outcome was self-reported lymphedema development. Secondary endpoints were time from IBC diagnosis, mastectomy, or radiation completion to lymphedema diagnosis. Multivariable logistic regression analysis was used to identify preoperative lymphedema risk factors, while controlling for number of lymph nodes removed during ALND, number of positive lymph nodes, presence of residual disease on final pathology, and need for adjuvant systemic therapy. Additionally, the subset of patients who underwent breast reconstruction was reviewed and descriptive statistics of reconstructive techniques performed. RESULTS: Of 356 patients (86% Stage 3, 14% Stage 4) who underwent NAC, MRM and radiation, complete data on risk factors were available for 134 (37.6%). Mean age at diagnosis was 51 years (range 22-89 years). Forty-seven percent of patients developed lymphedema during treatment and 87% had ≥5 lymph nodes removed. Four percent developed lymphedema preoperatively (mean 138 days, median 149 days after IBC diagnosis), 14.6% developed lymphedema after surgery and before radiation (mean 51 days, median 45 days postoperatively), and 81.7% developed lymphedema after radiation (mean 470 days, median 271 days after radiation). Obesity (BMI > 30) (OR 2.7, CI 1.2-6.4, p = 0.02) and non-white race (OR 4.5, CI 1.2-23, p = 0.04) were preoperative risk factors for lymphedema. Reconstruction data was available for 91.3% of patients (n=325). Of these, 78.5% (n=255) did not receive reconstruction. Among those who underwent reconstruction (n=70, 21.5%), most patients were younger than 50 years (n=41, 58.6%). Most who underwent reconstruction were white (n=63, 90.0% versus n=2, 2.86% black and n=5, 7.14% other). Ethnicity data was available for 48 patients (68.6%). The majority of patients were non-Hispanic (n=46, 95.83%). BMI data was available for 48 patients and the majority had BMI <30 (n=29, 60.42%). CONCLUSION: Patients with IBC are at high risk of lymphedema, with 47% of patients in our study developing self-reported lymphedema. While need for NAC, ALND, and PMRT are known risk factors, we identified obesity and non-white race as additional lymphedema risk factors in this population. Given this high prevalence, LYMPHA should be considered for all patients with IBC. Larger, prospective studies are needed to further evaluate potential racial disparities in lymphedema development.

Skin microbiome alterations in upper extremity secondary lymphedema.

Lymphedema is a chronic condition that commonly occur from lymphatic injury following surgical resection of solid malignancies. While many studies have centered on the molecular and immune pathways that perpetuate lymphatic dysfunction, the role of the skin microbiome in lymphedema development remains unclear. In this study, skin swabs collected from normal and lymphedema forearms of 30 patients with unilateral upper extremity lymphedema were analyzed by 16S ribosomal RNA sequencing. Statistical models for microbiome data were utilized to correlate clinical variables with microbial profiles. Overall, 872 bacterial taxa were identified. There were no significant differences in microbial alpha diversity of the colonizing bacteria between normal and lymphedema skin samples (p = 0.25). Notably, for patients without a history of infection, a one-fold change in relative limb volume was significantly associated with a 0.58-unit increase in Bray-Curtis microbial distance between paired limbs (95%CI = 0.11,1.05, p = 0.02). Additionally, several genera, including Propionibacterium and Streptococcus, demonstrated high variability between paired samples. In summary, we demonstrate high compositional heterogeneity in the skin microbiome in upper extremity secondary lymphedema, supporting future studies into the role of host-microbe interactions on lymphedema pathophysiology.

D25. Alternative Patterns of Superficial Lymphatic Drainage in the Breast and Trunk after Breast Cancer Surgery

PURPOSE: Changes in superficial lymphatic drainage from the chest wall/trunk after breast cancer treatment are not well described. This study examines alternative lymphatic flow in the post-mastectomy lymphedema population to identify risks associated with truncal and upper extremity lymphedema. METHODS: Patients undergoing revision breast surgery with suspicion of lymphedema from 2014-2020 were offered lymphangiography. Breasts and trunks were visualized and blindly evaluated for alternative drainage. Summary statistics were computed, and linear Cohen’s Kappa statistic was used to compare rater agreement. Binomial regression was used to compute relative risks (RR). RESULTS: 86 sides (46 patients) were included. 12 sides underwent no treatment and were considered controls. 88% of the non-controls had alternative lymphatic flow. This was seen in ipsilateral axillae (64%), ipsilateral groins (57%), contralateral axillae (20.3%), and contralateral groins (9.3%). Cohen’s Kappa for alternative drainage was 0.631 ± 0.043. Ipsilateral axillary and contralateral inguinal drainage reduced risk of truncal lymphedema (RR 0.78, CI 0.63-0.97, p=0.04; RR 0.32, CI 0.13-0.79, p=0.01, respectively). Radiation therapy increased risk of truncal and upper extremity lymphedema (RR 3.69, CI 0.96-14.15, p=0.02; RR 1.92, CI 1.09-3.39, p=0.03, respectively). Contralateral axillary drainage and axillary lymph node dissection increased risk of upper extremity lymphedema (RR 4.25, CI 1.09-16.61, p=0.01; RR 2.83, CI 1.23-6.52, p=0.01, respectively). CONCLUSION: This study highlights several risk/protective factors for truncal and upper extremity lymphedema. Ipsilateral axillary and contralateral inguinal drainage are protective against truncal lymphedema. Patients with radiation, axillary lymph node dissection and contralateral axillary drainage are at highest risk of upper extremity lymphedema.

D84. Pre-operative Lymphedema Risk Factors in Patients with Inflammatory Breast Cancer: Optimizing Patient Selection for LYMPHA

PURPOSE: LYMPHA (Lymphatic Microsurgical Preventive Healing Approach) is increasingly offered for prevention of upper extremity lymphedema after breast cancer treatment, which develops in up to 47% of breast cancer patients. Prior studies have focused on intraoperative and postoperative lymphedema risk factors. This study aimed to identify preoperative risk factors, when the decision to perform LYMPHA must be made. METHODS: Retrospective review of a dedicated inflammatory breast cancer (IBC) program database was conducted. The primary outcome was self-reported lymphedema development. Multivariable logistic regression analysis was performed to identify preoperative lymphedema risk factors, while controlling for number of lymph nodes removed during axillary lymph node dissection (ALND), number of positive lymph nodes, residual disease on final pathology, and need for adjuvant chemotherapy. RESULTS: Of 356 patients with IBC, 134 (mean age 51 years, range 22-89 years) had complete data. Forty-seven percent developed lymphedema. Obesity (BMI>30) (OR 2.7, CI 1.2-6.4, p=0.02) and non-white race (OR 4.5, CI 1.2-23, p=0.04) were preoperative risk factors for lymphedema development. CONCLUSION: Patients with IBC are at high risk for developing lymphedema, due to their need for ALND, radiation, and neoadjuvant chemotherapy. This study identified non-white race and obesity as additional risk factors. Due to the high prevalence of lymphedema, LYMPHA should be considered for all patients with inflammatory breast cancer. Larger prospective studies should evaluate potential racial disparities in lymphedema development.

Ensuring patient centeredness in upper extremity lymphedema research: Identifying patient-prioritized agenda and preferences

To elicit a patient-prioritized agenda and preferences for upper extremity lymphedema (LE) research. Focus group sessions (FGs) were conducted with English-speaking, adult women (18 years and older) with breast cancer-related LE (BCRL) seeking conservative or surgical care at two tertiary cancer centers in Ontario, Canada. An interview guide was used; women were asked to describe health-related quality of life (HRQL) outcomes that mattered the most to them, followed by their preferences for research study design and for providing patient-reported outcomes measure (PROM) data. Inductive content analysis was used to identify themes and subthemes. A total of 16 women participated in 4 FG sessions (55±9.5 years) and described the impact of LE on their appearance, physical, psychosocial, and sexual well-being. Women emphasized that psychosocial well-being was often not discussed in clinical care and that they were poorly informed of LE risk and care options. Most women said that they would not be willing to be randomized to surgical versus conservative management of LE. They also expressed a preference to complete PROM data electronically. All women emphasized the value of having an open text option alongside PROMs to expand on their concerns. Patient centeredness is key to generating meaningful data and ensuring ongoing engagement in clinical research. In LE, comprehensive PROMs that measure a range of HRQL concerns, especially psychosocial well-being, should be considered. Women with BCRL are reluctant to be randomized to conservative care when a surgical option is available, resulting in implications for planning trial sample size and recruitment.

Re-examining content validity of the BREAST-Q more than a decade later to determine relevance and comprehensiveness

PurposeThe BREAST-Q is the most used patient-reported outcome measure (PROM) in breast cancer surgery. The purposes of this study were to re-examine the content validity of BREAST-Q cancer modules (mastectomy, lumpectomy and reconstruction) and to determine the need for new scales.MethodsInterviews were conducted with women with breast cancer (Stage 0–4, any treatment), and were audio-recorded and transcribed verbatim. Deductive (based on original BREAST-Q conceptual framework) and inductive (new codes from the data) content analysis approaches were used to analyze the data. The number of codes that mapped to BREAST-Q were recorded.ResultsDataset included 3948 codes from 58 participants. Most of the breast (n = 659, 96%) and all psychosocial (n = 127, 100%), sexual (n = 179, 100%) and radiation-related (n = 79, 100%) codes mapped to BREAST-Q Satisfaction with Breast, Psychosocial Wellbeing, Sexual Wellbeing and Adverse Effects of Radiation scales, respectively. For the physical wellbeing codes (n = 939) for breast/chest and arm, 34% (n = 321) mapped to the Physical Wellbeing-Chest scale. Most of the abdomen codes (n = 311) mapped to Satisfaction with Abdomen (n = 90, 76%) and Physical Wellbeing-Abdomen (n = 171, 89%) scales. Codes that did not map (n = 697, 30%) covered breast sensation and lymphedema. Concerns related to fatigue, cancer worry, and work impact were most reported and did not map to BREAST-Q.ConclusionThe BREAST-Q, which was developed using extensive patient input more than a decade ago, is still relevant. To ensure the BREAST-Q remains comprehensive, new scales for upper extremity lymphedema, breast sensation, fatigue, cancer worry, and work impact were developed.

Breast Cancer-Related Lymphedema: The Primary/Secondary Conundrum

Lymphatic Research and BiologyVol. 21, No. 2 EditorialFree AccessBreast Cancer-Related Lymphedema: The Primary/Secondary ConundrumStanley G. RocksonStanley G. RocksonEditor-in-Chief, Stanford University School of Medicine, Stanford, California, USA.Search for more papers by this authorPublished Online:20 Apr 2023https://doi.org/10.1089/lrb.2023.29141.editorialAboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail For quite some time, within the pages of this journal1–3 and elsewhere,4,5 there has been a persistent theory that there might be systemic and other predispositions to the secondary (or acquired) lymphedema that is encountered frequently as a sequela of breast cancer therapeutics. In addition, it has recently been observed that the presence of a lymphatic disorder such as breast cancer-associated lymphedema can alter the patterns of associated systemic disease expression that exist as comorbidities.6 These phenomena help to blur the distinction between “primary” and “secondary” lymphedema.In the current issue of Lymphatic Research and Biology, we provide three additional sets of original observations that help to expand insights into this hypothesis.In the first of these, Kim and colleagues have explored rates of incidental subclinical lymphedema in the contralateral arm of patients with unilateral postsurgical secondary upper extremity lymphedema. In their study, magnetic resonance imaging of the upper extremities was utilized to examine patients with unilateral upper extremity clinical lymphedema. Axial STIR MR images of the symptomatic and contralateral arms were retrospectively reviewed and edema severity was graded by the investigators. In these 78 examined subjects, contralateral abnormalities were detected in 14.1%. Although the direct conclusion was to emphasize the importance of evaluation of the contralateral limb, the interpretation, by extension, is that there is a disturbance in lymphatic anatomy or function that extends beyond the direct lymphatic trauma of cancer therapeutics.The second investigation, by Furlan and colleagues, examines the phenomenon of blood flow abnormalities in the limb that precede the development of overt lymphedema. In a cohort of 200 subjects, Doppler ultrasound was utilized to examine the axillary and brachial arteries. In these patients, there was detection of higher mean flow velocity and end-diastolic velocity as early as 1 month after surgery. The end-diastolic velocity demonstrated a 73.7% sensitivity and 71.2% specificity as a predictor of long-term lymphedema, with a negative predictive value of 57.6%.The third of these three new investigations proposed a pilot investigation of abdominal fat ratio in subjects with breast cancer-related lymphedema. Here, Nakipoğlu and colleagues investigated the impact of central obesity to the occurrence of this lymphedema presentation. They investigated cohorts of postsurgical subjects with a matched control cohort that differed only in the distribution of BMI. The abdominal circumference measurement demonstrated a modest predictive utility, with a predictive specificity of 89%.In aggregate, these three newly published investigations continue to tantalize us with the increasingly tenable hypothesis that the appearance of acquired lymphedema (in this case following breast cancer therapies) may, and likely does, depend upon systemic factors that predict the likelihood of disease evolution. Continued exploration of these phenomena will, ideally, result in enhanced risk factor stratification, diagnostic evaluation, and, with good fortune, improved risk factor reduction strategies.