Is axillary web syndrome a risk factor for breast cancer-related lymphedema of the upper extremity? A systematic review and meta-analysis.

PURPOSE: To systematically review the available literature to determine if axillary web syndrome (AWS) is a risk factor for breast cancer-related lymphedema (BCRL) of the upper extremity. METHODS: The study is Prospero-registered (ID CRD42024508169) and follows PRISMA guidelines. Ovid MEDLINE, PubMED, CINAHL, Embase, clinicaltrials.gov and the WHO International Clinical Trials Registry Platform were searched February 24, 2024. Original studies including a cohort of females > 18 years of age diagnosed with AWS after breast cancer surgery and assessing BCRL outcome were included. Scoping, mapping, systematic or qualitative reviews, dissertations without peer-review and conference abstracts were excluded. Methodological quality was assessed using the Modified Downs and Black Checklist and overall certainty in the body of evidence was assessed using Cochrane's GRADE criteria (Grading of Recommendations Assessment, Development and Evaluation). RESULTS: Nine cohort studies representing 3218 participants were included. The median incidence of AWS and BCRL was 31.79% (IQR 8.90%) and 14.29% (IQR 19.01%), respectively, across all studies. Pooled analysis indicated an odds ratio of 1.19 (95% confidence interval 0.60,2.37), with substantial heterogeneity across studies (Chi2 p < 0.0001, I2 = 82%). Methodological quality of the included studies was poor to fair, and there was very low certainty evidence indicating no difference in AWS for BCRL risk. The strongest study included, found that AWS more than doubles BCRL risk in the upper extremity. CONCLUSION: The available evidence base cannot definitively determine whether AWS imparts risk of BCRL. AWS should be considered a potential risk factor for BCRL, until definitive conclusions from future research are available.

Shoulder Kinematics of Axillary Web Syndrome in Women Treated for Breast Cancer.

OBJECTIVE: To better understand how the shoulder moves in breast cancer survivors with axillary web syndrome (AWS), we compared 3-dimensional (3D) shoulder kinematics during shoulder elevation among breast cancer survivors with and without AWS 5 years postoperatively. Although research consistently shows decreased shoulder range of motion with AWS, we do not understand the underlying biomechanics. DESIGN: Nested case control study. SETTING: University Academic Breast Center. PARTICIPANTS: Twenty-five women who had surgery 5 years previously for unilateral breast cancer with the removal of at least 1 lymph node participated in this study (N=25). Twelve participants had AWS; 13 women did not have AWS. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Three-dimensional shoulder kinematic data during shoulder forward flexion, scapular plane abduction, and coronal plane abduction were collected using 3D electromagnetic motion tracking. Kinematic data were extracted at 30°, 60°, 90°, and 120° of arm elevation for scapular upward rotation, internal rotation, and posterior tilt as well as for glenohumeral external rotation. RESULTS: Women with AWS demonstrated 15.2° less scapular upward rotation at 120° humerothoracic elevation (95% confidence interval [-25.2, -5.2], P=.005), regardless of plane. No significant between-group differences were found for any other angle of scapular upward rotation, nor for scapular internal rotation, scapular posterior tilt, or glenohumeral axial rotation at any angle. CONCLUSIONS: Five years after surgery for breast cancer, women diagnosed with AWS have altered scapulohumeral kinematics that may place them at an increased risk of shoulder pain based on existing kinematic literature in healthy cohorts. This information can help guide rehabilitation programs for breast cancer survivors to facilitate pain-free upper extremity function after treatment.

A high-throughput screening assay based on automated microscopy for monitoring antibiotic susceptibility of Mycobacterium tuberculosis phenotypes.

BACKGROUND: Efficient high-throughput drug screening assays are necessary to enable the discovery of new anti-mycobacterial drugs. The purpose of our work was to develop and validate an assay based on live-cell imaging which can monitor the growth of two distinct phenotypes of Mycobacterium tuberculosis and to test their susceptibility to commonly used TB drugs. RESULTS: Both planktonic and cording phenotypes were successfully monitored as fluorescent objects using the live-cell imaging system IncuCyte S3, allowing collection of data describing distinct characteristics of aggregate size and growth. The quantification of changes in total area of aggregates was used to define IC50 and MIC values of selected TB drugs which revealed that the cording phenotype grew more rapidly and displayed a higher susceptibility to rifampicin. In checkerboard approach, testing pair-wise combinations of sub-inhibitory concentrations of drugs, rifampicin, linezolid and pretomanid demonstrated superior growth inhibition of cording phenotype. CONCLUSIONS: Our results emphasize the efficiency of using automated live-cell imaging and its potential in high-throughput whole-cell screening to evaluate existing and search for novel antimycobacterial drugs.

Prevalence and associations of axillary web syndrome in Asian women after breast cancer surgery undergoing a community-based cancer rehabilitation program.

BACKGROUND: Patients who have breast cancer surgery are at risk of axillary web syndrome (AWS), an under-recognized postsurgical complication which can result in shoulder morbidity and functional impairment. Emerging studies have indicated that AWS may persist beyond the first few months after surgery, although few studies have assessed the prevalence and association of AWS beyond a year after diagnosis. Therefore, the aim of this study was to investigate the prevalence and associations for AWS in post-operative breast cancer patients up to 3 years after surgery. METHODS: This cross sectional observational study was conducted at a community-based cancer rehabilitation center. Patients were evaluated for the presence of AWS via physical examination. Disease-related data was obtained from clinical review and medical records. Descriptive statistics were utilized to illustrate patient demographics and clinical characteristics. Logistic regression analyses were used to determine associations of AWS. RESULTS: There were 111 Asian women who were recruited, who had undergone breast surgery and were referred to a national outpatient rehabilitation center. The prevalence of AWS in this population was 28.9%. In the multivariate regression model, significant factors were age < 50 years (OR = 3.51; 95% CI = 1.12-11.0; p = 0.031) and ALND (OR = 6.54; 95% CI = 1.36-31.3; p = 0.019). There was reduced shoulder flexion ROM (p < 0.001) in patients with AWS compared to patients without AWS. CONCLUSIONS: A high prevalence of AWS was reported in breast cancer survivors even at 3 years after breast surgery. Our findings highlight the need to identify breast cancer survivors with AWS even in the survivorship phase, and develop strategies to raise awareness and minimize functional impairment in these patients.

Patients who report cording after breast cancer surgery are at higher risk of lymphedema: Results from a large prospective screening cohort.

OBJECTIVES: To identify the association between cording and breast cancer-related lymphedema (BCRL); describe time course, location, symptoms and functional impairments. METHODS: A total of 1181 patients were prospectively screened for BCRL after breast cancer (BC) surgery, including patient-reported outcome measures (4193) and perometric arm volume measurements (BCRL defined as relative or weight-adjusted volume change [RVC or WAC] ≥10% ≥3 months postoperatively). RESULTS: A total of 374/1181 patients (31.7%) reported cording first a median of 4.5 months postoperatively, and were more likely to: have body mass index less than 30 kg/m2 ; be less than 55 years of age; have had mastectomy, axillary lymph node dissection, regional lymph node radiation, neoadjuvant chemotherapy (all P < .001), or RVC/WAC ≥10% (P = .002). Patients who reported cording had 2.4 times the odds of developing BCRL compared to those who did not (odds ratio = 2.40; 95% confidence interval = 1.40-4.11; P = .002), and most frequently reported these symptoms: tenderness (61.2%), aching (60.7%), and firmness/tightness (59.8%). On multivariable analysis, cording was significantly correlated with functional difficulty for 17 actions. CONCLUSIONS: Patients frequently present with cording, potentially months after BC surgery. Risk factors for and symptoms of cording are identified, and treatment is recommended. Patients reporting cording are at higher risk of BCRL, therefore, cording should be incorporated into BCRL risk stratification.

Axillary web syndrome among Chilean women with breast cancer: incidence and possible predisposing factors.

PURPOSE: Breast cancer (BC) is the most common cancer in women worldwide. The main treatment for BC is surgery, which involves an axillary procedure that associates with the development of axillary web syndrome (AWS). The incidence of AWS among Chilean women with BC and its possible predisposing factors are currently unknown. Thus, we aimed to (1) determine the incidence of AWS among Chilean women with BC after surgery and (2) identify possible predisposing factors. METHODS: Within 90 days post-surgery, patients were assessed for AWS, i.e., palpable or visible axillary cords in the axillary region extending down from the mid-axilla to the ipsilateral arm. We then computed the odds ratio with 95% confidence interval (OR [95% CI]) for having AWS considering the following predisposing factors: age, body mass index (BMI), number of lymph nodes removed, axillary procedure, days from surgery to the physical therapy assessment, hospital for the surgery, type of breast surgery, and neoadyuvant chemotherapy. RESULTS: AWS was present in 49 out of 107 patients (45.8%). Younger age and lower BMI appeared as the sole predisposing factors for AWS (age, 0.95 [0.91-0.99]; BMI, normal weight 1.00, overweight 0.35 [0.11-1.12], obesity 0.28 [0.08-0.97]). CONCLUSION: The incidence of AWS among Chilean women with BC was 45.8%. Our study also confirms data from previous reports showing that younger age and low BMI are associated with the development of AWS.

Incidence and predictors of axillary web syndrome and its association with lymphedema in women following breast cancer treatment: a retrospective study.

PURPOSE: Axillary web syndrome (AWS) presents as a common postsurgical complication in individuals with breast cancer. Breast cancer-related lymphedema (BCRL) contributes to the shoulder and arm morbidity common in breast cancer survivors and often associated to cancer treatment. A paucity of literature exists evaluating the risk factors for developing AWS and the association between AWS and BCRL. The purposes of this study were (1) to identify risk factors for AWS in individuals with breast cancer, (2) to examine the association between BCRL and AWS, and (3) to determine if AWS increases the risk for developing BCRL. METHODS: A retrospective study of 354 women who underwent breast cancer treatment and received physical therapy was included. RESULTS: Axillary web syndrome developed in a third of women and predominately occurred in the first 8 postoperative weeks. The odds of AWS development were 73% greater for participants over the age of 60 (OR = 1.73, CI 95% 1.05-2.84). Women with AWS had 44% greater risk to develop lymphedema during the first postoperative year (RR = 1.44, CI 95% 1.12-1.84, p = 0.002). If AWS developed within the first postoperative month, women were almost 3 times more likely to develop lymphedema within the first 3 postoperative months compared with other women with AWS (RR = 2.75, CI 95% 1.199-6.310, p = 0.007). CONCLUSIONS: Our findings suggest that 30% of breast cancer survivors will have AWS during the first year of survivorship. As institutions prioritize screening efforts, early postoperative prospective surveillance is needed for women over 60 due to high risk for AWS development and any women with AWS for increased risk of lymphedema development based on our findings.

Deletion of a dehydratase important for intracellular growth and cording renders rough Mycobacterium abscessus avirulent.

Mycobacterium abscessus (Mabs) is a rapidly growing Mycobacterium and an emerging pathogen in humans. Transitioning from a smooth (S) high-glycopeptidolipid (GPL) producer to a rough (R) low-GPL producer is associated with increased virulence in zebrafish, which involves the formation of massive serpentine cords, abscesses, and rapid larval death. Generating a cord-deficient Mabs mutant would allow us to address the contribution of cording in the physiopathological signs of the R variant. Herein, a deletion mutant of MAB_4780, encoding a dehydratase, distinct from the ß-hydroxyacyl-ACP dehydratase HadABC complex, was constructed in the R morphotype. This mutant exhibited an alteration of the mycolic acid composition and a pronounced defect in cording. This correlated with an extremely attenuated phenotype not only in wild-type but also in immunocompromised zebrafish embryos lacking either macrophages or neutrophils. The abolition of granuloma formation in embryos infected with the dehydratase mutant was associated with a failure to replicate in macrophages, presumably due to limited inhibition of the phagolysosomal fusion. Overall, these results indicate that MAB_4780 is required for Mabs to successfully establish acute and lethal infections. Therefore, targeting MAB_4780 may represent an attractive antivirulence strategy to control Mabs infections, refractory to most standard chemotherapeutic interventions. The combination of a dehydratase assay with a high-resolution crystal structure of MAB_4780 opens the way to identify such specific inhibitors.

Mucispirillum schaedleri: Biofilm Architecture and Age-Dependent Pleomorphy.

Round bodies in spirochete cultures have been a controversial subject since their description seven decades ago. We report the existence of round bodies (spherical cells) in cultures of Mucispirillum schaedleri, a spiral bacterium phylogenetically distant from spirochetes. Furthermore, when grown in biofilms, M. schaedleri demonstrates a unique morphology known as cording, which has been previously described only in mycobacteria. Thus, M. schaedleri has two distinct features, each previously thought to be unique to two different phylogenetically distant groups of bacteria.

Occurrence of axillary web syndrome without surgical intervention: a case report.

Axillary web syndrome (AWS) is characterized by the formation of cords in the axilla. Classically, it develops after surgical biopsy or removal of axillary lymph nodes for breast cancer. It can cause a limited range of motion and may contribute to abnormal shoulder movements or patterns that can cause pain. In this report, an atypical case of AWS presented in a 38-year-old male after physical activity but with no surgical history or breast cancer. This case report highlights that AWS can appear in healthy individuals with no history of breast cancer and/or surgical intervention. It also emphasizes the need to consider AWS in clinical practice as a differential diagnosis of painful shoulder movement and restricted range of motion.

Lymphoscintigraphic Investigations for Axillary Web Syndromes.

Background: Axillary web syndrome (AWS) is a frequent complication after surgery for breast cancer, but its lymphatic involvement is not definitively established. Here we report the results of lymphoscintigraphic investigations in patients with AWS. Methods and Results: We conducted a retrospective, single-center review of lymphoscintigraphic investigations performed in 46 patients with AWS that was either clinically obvious or suspected. Of this group, 23 patients had two investigations with a mean interval of 19 weeks between them (range, 6-98 weeks). Results of the lymphoscintigraphic investigations, which were performed according to a well-standardized protocol, were classified into four patterns: normal; functional lymphatic insufficiency only (no lymphatic vascular morphologic abnormality); lymphovascular blockade without collateralization; and vascular collateralization and/or dermal backflow. Of the 46 patients, on the first lymphoscintigraphic investigation, four (8.6%) had a normal pattern, seven (15.2%) had functional lymphatic insufficiency only, four (8.6%) had lymphovascular blockade without collateralization, and 31 (67.3%) had vascular collateralization and/or dermal backflow. Among patients who underwent two investigations, four of the five who had only functional lymphatic insufficiency at the first investigation had developed vascular collateralization and/or dermal backflow by the second. The three patients who had lymphovascular blockade without collateralization at the first examination had also progressed to collateralization and/or dermal backflow at the second. None of the 15 patients who initially had vascular collateralization and/or dermal backflow showed any reversal at the second examination. Conclusions: Our analysis confirms the lymphatic nature of AWS and shows the lymphoscintigraphic patterns and evolutions of the lymphatic lesions with potential therapeutic implications. The retrospective review of our database is approved by the institutional ethics committee under number 2048.

Cording in Disseminated Mycobacterium chelonae Infection in an Immunocompromised Patient.

Cording is a phenomenon in which acid fast bacilli grow in parallel and was previously used as a means of presumptive microscopic identification of Mycobacterium tuberculosis (TB). However, this process has been shown in multiple other nontuberculous mycobacterial (NTM) species. Here we present the case of an immunocompromised adult who presented with wrist pain, weight loss, and cough. A positron emission tomography scan showed uptake in the right ulna, multiple soft tissue sites, and the left lung. Biopsies and cultures were obtained from multiple sites, and the patient was ultimately diagnosed with disseminated Mycobacterium chelonae infection. The organism showed cording in culture. As seen in this patient, cording may occur in multiple NTM species and is not reliable as the sole indicator of the presence of TB.

CFTR Depletion Confers Hypersusceptibility to Mycobacterium fortuitum in a Zebrafish Model.

The Mycobacterium fortuitum complex comprises several closely related species, causing pulmonary and extra-pulmonary infections. However, there is very limited knowledge about the disease pathogenesis involved in M. fortuitum infections, particularly due to the lack of suitable animal models. Using the zebrafish model, we show that embryos are susceptible to M. fortuitum infection in a dose-dependent manner. Furthermore, zebrafish embryos form granulomas from as early as 2 days post-infection, recapitulating critical aspects of mycobacterial pathogenesis observed in other pathogenic species. The formation of extracellular cords in infected embryos highlights a previously unknown pathogenic feature of M. fortuitum. The formation of large corded structures occurs also during in vitro growth, suggesting that this is not a host-adapted stress mechanism deployed during infection. Moreover, transient macrophage depletion led to rapid embryo death with increased extracellular cords, indicating that macrophages are essential determinants of M. fortuitum infection control. Importantly, morpholino depletion of the cystic fibrosis transmembrane conductance regulator (cftr) significantly increased embryo death, bacterial burden, bacterial cords and abscesses. There was a noticeable decrease in the number of cftr-deficient infected embryos with granulomas as compared to infected controls, suggesting that loss of CFTR leads to impaired host immune responses and confers hypersusceptiblity to M. fortuitum infection. Overall, these findings highlight the application of the zebrafish embryo to study M. fortuitum and emphasizes previously unexplored aspects of disease pathogenesis of this significant mycobacterial species.

Cording Mycobacterium tuberculosis Bacilli Have a Key Role in the Progression towards Active Tuberculosis, Which is Stopped by Previous Immune Response.

Cording was the first virulence factor identified in Mycobacterium tuberculosis (Mtb). We aimed to ascertain its role in the induction of active tuberculosis (TB) in the mouse strain C3HeB/FeJ by testing the immunopathogenic capacity of the H37Rv strain. We have obtained two batches of the same strain by stopping their growth in Proskauer Beck liquid medium once the mid-log phase was reached, in the noncording Mtb (NCMtb) batch, and two days later in the cording Mtb (CMtb) batch, when cording could be detected by microscopic analysis. Mice were challenged with each batch intravenously and followed-up for 24 days. CMtb caused a significant increase in the bacillary load at an early stage post-challenge (day 17), when a granulomatous response started, generating exudative lesions characterized by neutrophilic infiltration, which promoted extracellular bacillary growth together with cording formation, as shown for the first time in vivo. In contrast, NCMtb experienced slight or no bacillary growth and lesions could barely be detected. Previous Bacillus Calmette-Guérin (BCG) vaccination or low dose aerosol (LDA) Mtb infection were able to delay the progression towards active TB after CMtb challenge. While BCG vaccination also reduced bacillary load when NCMtb was challenged, LDA did not, and its proliferative lesions experienced neutrophil infiltration. Analysis of lung cytokine and chemokine profiles points to their capacity to block the production of CXCL-1 and further amplification of IL-1ß, IL-17 and neutrophilic extracellular trap formation, all of which are essential for TB progression. These data highlight the key role of cording formation in the induction of active TB.

Axillary web syndrome following breast cancer surgery: symptoms, complications, and management strategies.

Axillary web syndrome (AWS) is a common condition occurring in up to 86% of patients following breast cancer surgery with ipsilateral lymphadenectomy of one or more nodes. AWS presents as a single cord or multiple thin cords in the subcutaneous tissues of the ipsilateral axilla. The cords may extend variable distances "down" the ipsilateral arm and/or chest wall. The cords frequently result in painful shoulder abduction and limited shoulder range of motion. AWS most frequently becomes symptomatic between 2 and 8 weeks postoperatively but can also develop and recur months to years after surgery. Education about and increased awareness of AWS should be promoted for patients and caregivers. Assessments for AWS should be performed on a regular basis following breast cancer surgery especially if there has been associated lymphadenectomy. Physical therapy, which consists of manual therapy, exercise, education, and other rehabilitation modalities to improve range of motion and decrease pain, is recommended in the treatment of AWS.

Review of axillary web syndrome: What the radiologist should know.

Axillary web syndrome is common after axillary surgery, frequently affecting breast cancer patients. In this condition, patients develop one or more linear bands of firm tissue, also known as "cords", in the axilla and arm, associated with pain and limited range of motion of the shoulder and arm. Radiologists may encounter this syndrome in patients referred for axillary or upper extremity ultrasound, and should be aware of the physical examination and ultrasound findings for accurate diagnosis. However, there are currently limited articles about this syndrome published in radiology journals, suggesting that radiologists may be unaware of this entity. In this work, axillary web syndrome will be discussed, including background knowledge, incidence, clinical presentation, possible etiology, and ultrasound appearance.

Axillary Web Syndrome in Breast Cancer: A Prevalent But Under-Recognized Postoperative Complication.

The purpose of this review is to define axillary web syndrome (AWS) and describe its diagnosis and management. The following databases were searched through July 2017: PubMed, EMBASE (OvidSP), Cumulative Index for Nursing and Allied Health Literature, Physiotherapy Evidence Database, and Cochrane Database of Systematic Reviews. Search terms included 'axillary web syndrome', 'axillary cording', and 'lymphatic cording'. 49 articles were identified; 8 did not relate to breast cancer, and 3 were not in English. Of the remaining articles, the majority were case reports, case series, or descriptive reviews. 2 systematic reviews were located as well as 1 randomized trial, 6 prospective cohort studies, and 2 retrospective cohort studies. Although a common sequela after axillary surgery for breast cancer staging, AWS has been poorly described in the medical literature as to the underlying pathophysiology, diagnosis, and management. Interventions range from patient education and simple reassurance that the syndrome will resolve spontaneously to active physical or manual therapies to maintain upper extremity range-of-motion, especially adequate motion for undergoing radiation therapy. Oncologists, breast surgeons, family physicians, and oncology nurse practitioners that work with patients with breast cancer should educate them about this prevalent complication and inform them preoperatively about what to anticipate.

Quantifying coordination among the rearfoot, midfoot, and forefoot segments during running.

Because previous studies have suggested that there is a relationship between injury risk and inter-segment coordination, quantifying coordination between the segments is essential. Even though the midfoot and forefoot segments play important roles in dynamic tasks, previous studies have mostly focused on coordination between the shank and rearfoot segments. This study aimed to quantify coordination among rearfoot, midfoot, and forefoot segments during running. Eleven healthy young men ran on a treadmill. The coupling angle, representing inter-segment coordination, was calculated using a modified vector coding technique. The coupling angle was categorised into four coordination patterns. During the absorption phase, rearfoot-midfoot coordination in the frontal planes was mostly in-phase (rearfoot and midfoot eversion with similar amplitudes). The present study found that the eversion of the midfoot with respect to the rearfoot was comparable in magnitude to the eversion of the rearfoot with respect to the shank. A previous study has suggested that disruption of the coordination between the internal rotation of the shank and eversion of the rearfoot leads to running injuries such as anterior knee pain. Thus, these data might be used in the future to compare to individuals with foot deformities or running injuries.

Mycobacterium abscessus: Shapeshifter of the Mycobacterial World.

In this review we will focus on unique aspects of Mycobacterium abscessus (MABS) which we feel earn it the designation of "shapeshifter of the mycobacterial world." We will review its emergence as a distinct species, the recognition and description of MABS subspecies which are only now being clearly defined in terms of pathogenicity, its ability to exist in different forms favoring a saprophytic lifestyle or one more suitable to invasion of mammalian hosts, as well as current challenges in terms of antimicrobial therapy and future directions for research. One can see in the various phases of MABS, a species transitioning from a free living saprophyte to a host-adapted pathogen.

Mycobacterium tuberculosis cording in alveolar macrophages of patients with pulmonary tuberculosis is likely associated with increased mycobacterial virulence.

Mycobacterium tuberculosis (Mtb) is an infectious agent that causes tuberculosis (TB) in humans. A study of the volume of Mtb population and the detection of Mtb virulence in the lungs of patients with pulmonary TB are of great importance for understanding the infectious process and the outcome of the disease. We analyzed the functional state of Mtb and their number in alveolar macrophages obtained from the resected lungs of patients with TB in ex vivo culture and determined that the number of Mtb, referred mainly to the Beijing genotype family (A0 and B0/W148 clusters), were significantly different in cells between different patients. Only single Mtb were found in alveolar macrophages of some patients, while Mtb were actively replicated in colonies in alveolar macrophages of other patients, including cord morphology of Mtb growth (the indicator of Mtb virulence). Our data demonstrated association between the formation of Mtb cording in alveolar macrophages of patients and increased virulence of Mtb from the lungs of these patients in guinea pig TB model. The find of cording formation by replicating Mtb in human alveolar macrophages may be used for preliminary quick estimation of increased Mtb virulence in individual patients with pulmonary TB.