The lymphedema patient experience within the healthcare system: a cross-sectional epidemiologic assessment.

Lymphedema is a progressive lymphatic disease that potentiates physical and psychosocial distress. Despite its impact, patients reportedly encounter lymphatic ignorance throughout the healthcare system. This cross-sectional study aims to summarize clinical characteristics and interactions of lymphedema patients within the healthcare system. Two lymphedema patient cohorts were included: The Global Registry Analysis Cohort included lymphedema patients who contributed to an international digital lymphatic registry and the Interactions Cohort included patients who initiated a questionnaire about interactions with the medical system. The global registry was used to obtain demographic and clinical characteristics from affiliated lymphedema patients. A 23-item online questionnaire on healthcare experiences and satisfaction with lymphatic healthcare was then distributed to the Interactions Cohort. Complete responses were obtained from 2474 participants. Participants were a mean age of 57.5 ± 16.1 years and 51.4% had a cancer history. Participants reported substantial delays in diagnosis and treatment. Cancer-related and non-cancer-related lymphedema patients reported similar levels of perceived physician disinterest in their lymphedema; however, non-cancer-related lymphedema patients reported more care dissatisfaction. Ultimately, patients continue to face delays in lymphedema diagnosis and treatment. We developed an evidence-based model highlighting areas of reform needed to improve lymphatic education and healthcare.

Longitudinal assessment of health-related quality of life and clinical outcomes with at home advanced pneumatic compression treatment of lower extremity lymphedema.

OBJECTIVE: This prospective, longitudinal, pragmatic study describes at home treatment with a proprietary advanced pneumatic compression device (APCD) for patients with lower extremity lymphedema (LED). METHODS: Following institutiona review board approval, four participating Veterans Affairs centers enrolled LED patients from 2016 to 2022. The primary outcome measures were health-related quality of life (HR-QoL) questionnaires (lymphedema quality of life-leg and the generic SF-36v2) obtained at baseline and 12, 24, and 52 weeks. The secondary outcome measures were limb circumference, cellulitis events, skin quality, and compliance with APCD and other compression therapies. RESULTS: Because a portion of the trial was conducted during the coronavirus disease 2019 pandemic, 179 patients had 52 weeks of follow-up, and 143 had complete measurements at all time points. The baseline characteristics were a mean age of 66.9 ± 10.8 years, 91% were men, and the mean body mass index was 33.8 ± 6.9 kg/m2. LED was bilateral in 92.2% of the patients. Chronic venous insufficiency or phlebolymphedema was the most common etiology of LED (112 patients; 62.6%), followed by trauma or surgery (20 patients; 11.2%). Cancer treatment as a cause was low (4 patients; 2.3%). Patients were classified as having International Society for Lymphology (ISL) stage I (68.4%), II (27.6%), or III (4.1%). Of the primary outcome measures, significant improvements were observed in all lymphedema quality of life-leg domains of function, appearance, symptoms, and emotion and the overall score after 12 weeks of treatment (P < .0001) and through 52 weeks of follow-up. The SF-36v2 demonstrated significant improvement in three domains at 12 weeks and in the six domains of physical function, bodily pain, physical component (P < .0001), social functioning (P = .0181), role-physical (P < .0005), and mental health (P < .0334) at 52 weeks. An SF-36v2 score <40 indicates a substantial reduction in HR-QoL in LED patients compared with U.S. norms. Regarding the secondary outcome measures at 52 weeks, compared with baseline, the mean limb girth decreased by 1.4 cm (P < .0001). The maximal reduction in mean limb girth was 1.9 cm (6.0%) at 12 weeks in ISL stage II and III limbs. New episodes of cellulitis in patients with previous episodes (21.4% vs 6.1%, P = .001) were reduced. The 75% of patients with skin hyperpigmentation at baseline decreased to 40% (P < .01) at 52 weeks. At 52 weeks, compliance, defined as use for 5 to 7 days per week, was reported for the APCD by 72% and for elastic stockings by 74%. CONCLUSIONS: This longitudinal study of Veterans Affairs patients with LED demonstrated improved generic and disease-specific HR-QoL through 52 weeks with at home use of an APCD. Limb girth, cellulitis episodes, and skin discoloration were reduced, with excellent compliance.

The N-LVA Study: effectiveness and cost-effectiveness of lymphaticovenous anastomosis (LVA) for patients with cancer who suffer from chronic peripheral lymphoedema - study protocol of a multicentre, randomised sham-controlled trial.

INTRODUCTION: Cancer-related lymphoedema is one of the most debilitating side-effects of cancer treatment with an overall incidence of 15.5%. Patients may suffer from a variety of symptoms, possibly resulting in a diminished health-related quality of life (HRQoL). A microsurgical technique known as lymphaticovenous anastomosis (LVA) might be a promising treatment option. The objective of this study is to evaluate whether LVA is effective and cost-effective compared with sham surgery in improving the HRQoL. METHODS AND ANALYSIS: A multicentre, double-blind, randomised sham-controlled trial conducted in three university hospitals in the Netherlands. The study population comprises 110 patients over the age of 18 years with unilateral, peripheral cancer-related lymphoedema, including 70 patients with upper limb lymphoedema and 40 patients with lower limb lymphoedema. A total of 55 patients will undergo the LVA operation, while the remaining 55 will undergo sham surgery. The follow-up will be at least 24 months. Patients are encouraged to complete the follow-up by explaining the importance of the study. Furthermore, patients may benefit from regular monitoring moments for their lymphoedema. The primary outcome is the HRQoL. The secondary outcomes are the limb circumference, excess limb volume, changes in conservative therapy, postoperative complications, patency of the LVA and incremental cost-effectiveness. ETHICS AND DISSEMINATION: The study was approved by the Medical Ethical Committee of Maastricht University Medical Center on 20 September 2023 (NL84169.068.23). The results will be presented at scientific conferences and published in peer-reviewed medical journals. TRIAL REGISTRATION NUMBER: NCT06082349.

The assessment and management of foot and toe oedema as part of holistic lower limb care.

Toe and foot swelling can manifest as lymphoedema or chronic oedema but can also be a complication of the treatment of these conditions. In this article, the authors discuss the assessment and treatment options for toe and foot swelling, highlighting the importance of prevention in the first instance.

The clinical and economic impact of chronic venous insufficiency-associated lymphedema and the prevalence of persistent edema after venous intervention.

OBJECTIVES: To determine the demographics, outcomes, and healthcare utilization of patients with chronic venous insufficiency-associated lymphedema (CVI-LED) and the prevalence of lymphedema-specific therapy use after venous intervention. METHODS: The IBM MarketScan Commercial and Medicare Claims Databases were examined for patients with CVI-LED. Patient demographics and the use of lymphedema-specific therapy before and after venous intervention were collected. RESULTS: Of 85,601 LED patients identified, 8,406 also had a diagnosis of CVI. In the CVI-LED group, 1051 underwent endovenous ablation or venous stent placement. The use of lymphedema-specific therapy before and after venous intervention was 52% and 39%, respectively (p < .05). The mean time of initiation of LED-specific therapy following venous intervention was 265 days after ablation and 347 days after stent placement. CONCLUSION: Treating venous hypertension improves certain venous-related signs and symptoms of CVI. However, a significant proportion of patients have persistent edema which may reflect underlying, sub-optimally treated LED.

Development of a head and neck lymphoedema specific quality of life tool: The Comprehensive Assessment of Lymphoedema Impact in the Head and Neck.

PURPOSE: To develop a head and neck lymphoedema (HNL) specific quality of life (QoL) instrument to assess physical, functional, and social/emotional impacts of HNL. METHODS: Instrument candidate items were reviewed by patients with HNL and clinicians and rated for importance, clarity, and invasiveness. The Content Validity Ratio was applied for item reduction. Three-step cognitive interviews were conducted with HNL patients to validate the items, survey format, and instructions. RESULTS: Initially, 130 candidate questions were developed. Following item reduction, 52 items progressed to three-step cognitive interviews. Following cognitive interviews, the Comprehensive Assessment of Lymphoedema Impact in Head and Neck (CALI-HaN) included 33 items; 1 global, 10 physical, 7 functional, and 15 emotional. CONCLUSIONS: Physical, functional, and socioemotional effects need to be considered when measuring QoL in patients with HNL. This study describes initial development of the CALI-HaN, an instrument that shows promise for clinical and research applications following future validation.

Lymphedema self-assessment among endometrial cancer survivors.

PURPOSE: Lower extremity lymphedema (LEL), which causes ankle, leg, and feet swelling, poses a significant challenge for endometrial cancer survivors, impacting physical functioning and psychological well-being. Inconsistent LEL diagnostic methods result in wide-ranging LEL incidence estimates. METHODS: We calculated the cumulative incidence of LEL based on survivor-reported Gynecologic Cancer Lymphedema Questionnaire (GCLQ) responses in addition to survivor- and nurse-reported leg circumference measurements among a pilot sample of 50 endometrial cancer survivors (27 White, 23 Black) enrolled in the ongoing population-based Carolina Endometrial Cancer Study. RESULTS: Self-leg circumference measurements were perceived to be difficult and were completed by only 17 survivors. Diagnostic accuracy testing measures (sensitivity, specificity, positive and negative predictive value) compared the standard nurse-measured ≥ 10% difference in leg circumference measurements to GCLQ responses. At a mean of ~11 months post-diagnosis, 54% of survivors met established criteria for LEL based on ≥ 4 GCLQ cutpoint while 24% had LEL based on nurse-measurement. Percent agreement, sensitivity, and specificity approximated 60% at a threshold of ≥ 5 GCLQ symptoms. However, Cohen's kappa, a measure of reliability that corrects for agreement by chance, was highest at ≥ 4 GCLQ symptoms (κ = 0.27). CONCLUSION: Our findings emphasize the need for high quality measurements of LEL that are feasible for epidemiologic study designs among endometrial cancer survivors. Future studies should use patient-reported survey measures to assess lymphedema burden and quality of life outcomes among endometrial cancer survivors.

Surgical lymphedema models in the mice hindlimb-A systematic review and quality assessment.

BACKGROUND: Lymphedema constitutes a major unsolved problem in plastic surgery. To identify novel lymphedema treatments, preclinical studies are vital. The surgical mouse lymphedema model is popular and cost-effective; nonetheless, a synthesis and overview of the literature with evidence-based guidelines is needed. The aim of this review was to perform a systematic review to establish best practice and support future high-quality animal studies exploring lymphedema treatments. METHODS: We performed a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, searching four databases (PubMed, Embase, Web of Science, and Scopus) from inception-September 2022. The Animals in Research Reporting In Vivo Experiments 2.0 (ARRIVE 2.0) guidelines were used to evaluate reporting quality. Studies claiming to surgically induce lymphedema in the hindlimb of mice were included. RESULTS: Thirty-seven studies were included. Four main models were used. (1) Irradiation+surgery. (2) A variation of the surgery used by (1) + irradiation. (3) Surgery only (SPDF-model). (4) Surgery only (PLND-model). Remaining studies used other techniques. The most common measurement modality was the caliper. Mean quality coefficient was 0.57. Eighteen studies (49%) successfully induced sustained lymphedema. Combination of methods seemed to yield the best results, with an overrepresentation of irradiation, the removal of two lymph nodes, and the disruption of both the deep and superficial lymph vessels in the 18 studies. CONCLUSION: Surgical mouse hindlimb lymphedema models are challenged by two related problems: (1) retaining lymphedema for an extended period, that is, establishing a (chronic) lymphedema model (2) distinguishing lymphedema from post-operative edema. Most studies failed to induce lymphedema and used error-prone measurements. We provide an overview of studies claiming to induce lymphedema and advocate improved research via five evidence-based recommendations to use: (1) a proven lymphedema model; (2) sufficient follow-up time, (3) validated measurement methods; (4) ARRIVE-guidelines; (5) contralateral hindlimb as control.

Test-Retest Reliability of a Protocol for Assessment of Local Tissue Water in the Head and Neck Area.

Background: Lymphedema measurement is vital to select appropriate treatment and monitor its progress. Quantifying lymphedema in the head and neck area is challenging. The use of tissue dielectric constant (TDC) measurements has shown promising results in other body areas. This study aims to determine the test-retest reliability of a TDC measurement protocol developed for the head and neck area. Methods and Results: A detailed measurement protocol, including eight measurement points per side, was developed. Subsequently, the reliability of the protocol was tested in a sample of healthy participants (n = 50, 28 males). Using the LymphScanner (Delfin, Finland), participants were subjected to two measurement sessions. Each measurement point was measured three times per session. Test-retest reliability for each point was evaluated using intraclass correlation coefficients (ICCs) and standard errors of measurement (SEMs). Using the average of three measurements, reliability was good to excellent for all points (ICCs 0.81-0.95), with small measurement errors (SEMs 1.51-2.86). The reliability of a single measurement was moderate to excellent for all measurement points (ICCs 0.58-0.87), with larger, but still small, measurement errors (SEMs 1.65-3.39). When using single measurements, the lowest ICCs were found for the temporal (left 0.73 and right 0.67) and submandibular (left 0.58 and right 0.77) locations. Conclusion: Measurements with the LymphScanner, taken according to the developed protocol, are reliable in healthy participants. We recommend using the average of three measurements to optimize reliability. The protocol is fit for further testing in patient populations and for determining normal values in a larger scale study with healthy subjects.

The critical role of phlebolymphedema in cellulitis associated with lymphedema: Its incidence and economic impact in a large real-world population.

OBJECTIVE: The aims of this study were: to define the incidence of cellulitis in patients with lymphedema (LED) overall and relate this to the etiology of LED; to determine how this rate might be affected by recurrence of cellulitis; and to quantify the contemporary economic burden of treatment. Understanding these factors is essential in developing targeted cellulitis prevention strategies and reducing health care costs. METHODS: The IBM MarketScan Research Database was examined from April 2013 to March 2019 for patients with a new diagnosis of LED (n = 85,601). Based on International Classification of Diseases (ICD)-9/ICD-10 diagnosis codes, the incidence and cost of cellulitis were ascertained during the 3-year follow-up period. Incidence rates (per 100 patient-years [PYs]) and cost (per patient per year) of cellulitis were evaluated among all patients with LED and within subgroups of LED etiologies. RESULTS: Among the three most common morbidities associated with LED (breast cancer-related lymphedema [BCRL], n = 17,954 [20.97%]; gynecological cancer-related LED [GCRL], n = 1256 [1.47%]; and phlebolymphedema [PLED], n = 8406 [9.82%]), rates of cellulitis were markedly lower for BCRL (8.9; 95% confidence interval [CI], 8.7-9.2) and GCRL (14.8; 95% CI, 13.4-16.4) vs PLED (47.7; 95% CI, 46.7-48.8). Patients with a history of cellulitis had markedly higher cellulitis rates during follow-up than those without-overall, 74.0% vs 16.4%; BCRL, 42.9%; 95% CI, 39.7%-46.3% vs 7.6%; 95% CI, 7.3%-7.9%; GCRL, 67.5%; 95% CI, 56.4%-80.8% vs 11.0%; 95% CI, 9.8%-12.4%; and PLED, 81.7%; 95% CI, 79.4%-84.1% vs 30.4%; 95% CI, 29.4%-31.4%, respectively. The mean $/patient/year of cellulitis-related costs for a patient with PLED ($2836; 95% CI, $2395-$3471) was significantly greater than that for BCRL ($503; 95% CI, $212-$1387) and GCRL ($609; 95% CI, $244-$1314). CONCLUSIONS: The incidence of cellulitis associated with LED varies by the etiology of LED. PLED has the highest rates of both an initial cellulitis episode and recurrent cellulitis events. Additionally, PLED has one of the largest cellulitis-related total costs per patient per year. Prevention, as well as early identification and treatment of PLED-associated cellulitis, could significantly decrease health care costs and improve patient quality of life.

Commercial Insurance Rates and Coding for Lymphedema Procedures: The Current State of Confusion and Need for Consensus.

BACKGROUND: Surgical treatment of lymphedema has outpaced coding paradigms. In the setting of ambiguity regarding coding for physiologic procedures [lymphovenous bypass (LVB) and vascularized lymph node transplant (VLNT)], we hypothesized that there would be variation in commercial reimbursement based on coding pattern. METHODS: The authors performed a cross-sectional analysis of 2021 nationwide hospital pricing data for 21 CPT codes encompassing excisional (direct excision, liposuction), physiologic (LVB, VLNT), and ancillary (lymphangiography) procedures. Within-hospital ratios (WHRs) and across-hospital ratios (AHRs) for adjusted commercial rates per CPT code quantified price variation. Mixed effects linear regression modeled associations of commercial rate with public payer (Medicare and Medicaid), self-pay, and chargemaster rates. RESULTS: A total of 270,254 commercial rates, including 95,774 rates for physiologic procedures, were extracted from 2863 hospitals. Lymphangiography codes varied most in commercial price (WHR, 1.76 to 3.89; AHR, 8.12 to 44.38). For physiologic codes, WHRs ranged from 1.01 (VLNT; free omental flap) to 3.03 (LVB; unlisted lymphatic procedure), and AHRs ranged from 5.23 (LVB; lymphatic channel incision) to 10.36 (LVB; unlisted lymphatic procedure). Median adjusted commercial rates for excisional procedures ($3635.84) were higher than for physiologic procedures ($2560.40; P < 0.001). Commercial rate positively correlated with Medicare rate for all physiologic codes combined, although regression coefficients varied by code. CONCLUSIONS: Commercial payer-negotiated rates for physiologic procedures were highly variable both within and across hospitals, reflective of variation in CPT codes. Physiologic procedures may be undervalued relative to excisional procedures. Consistent coding nomenclature should be developed for physiologic and ancillary procedures.

Association between Bioimpedance Spectroscopy and Magnetic Resonance Lymphangiography in the Diagnosis and Assessment of Lymphedema.

BACKGROUND: This study assesses associations between bioimpedance spectroscopy (BIS) and magnetic resonance lymphangiography (MRL) in the staging and assessment of lymphedema. METHODS: Adults who received MRL and BIS between 2020 and 2022 were included. We collected fluid, fat, and lymphedema severity ratings, and measured fluid stripe thickness, subcutaneous fat width, and lymphatic diameter on MRL. BIS lymphedema index (L-Dex) scores were collected from patient charts. We assessed sensitivity and specificity of L-Dex scores to detect MRL-identified lymphedema, and examined associations between L-Dex scores and MRL imaging measures. RESULTS: Forty-eight limbs across 40 patients were included. L-Dex scores had 72.5% sensitivity and 87.5% specificity for detecting MRL-defined lymphedema, with a 96.7% estimated positive predictive value and 38.9% negative predictive value. L-Dex scores were associated with MRL fluid and fat content scores (p ≤ 0.05), and lymphedema severity (p = 0.01), with better discrimination between fluid than fat content levels on pairwise analysis, and poor discrimination between adjacent severity levels. L-Dex scores were correlated with distal and proximal limb fluid stripe thickness (distal: rho = 0.57, p < 0.01; proximal: rho = 0.58, p < 0.01), partially correlated with distal subcutaneous fat thickness when accounting for body mass index (rho = 0.34, p = 0.02), and were not correlated with lymphatic diameter (p = 0.25). CONCLUSION: L-Dex scores have high sensitivity, specificity, and positive predictive value for the identification of MRL-detected lymphedema. L-Dex has difficulty distinguishing between adjacent severity levels of lymphedema and a high false negative rate, explained in part by reduced discrimination between levels of fat accumulation.

The added value of SPECT/CT lymphoscintigraphy in the initial assessment of secondary extremity lymphedema patients.

An added value of SPECT/CT over planar lymphoscintigraphy for initial staging in patients with secondary extremity lymphedema was investigated. Furthermore, we developed a hybrid SPECT/CT classification combining dermal backflow (DBF) of SPECT and honeycomb pattern (HP) of CT, correlated it with lymphoscintigraphic staging and clinical severity. Forty-one patients with secondary extremity lymphedema who underwent lymphoscintigraphy with SPECT/CT were included retrospectively. The severity of extremity lymphedema was assessed using CT volumetry. Lymphoscintigraphic findings were evaluated using the Taiwan Lymphoscintigraphy Staging (TLS), and CT-based and SPECT-based quantitative analysis were performed. TLS was performed by planar scintigraphy only and with SPECT/CT, respectively. The SPECT/CT findings were classified into DBF-/HP-, DBF+/HP-, DBF+/HP+, and DBF-/HP+. Based on these findings, patients were categorized into five classes: Class 1 = DBF-HP- entire limb, Class 2 = DBF+/HP- proximal/distal limb without DBF+/HP+ or DBF-/HP+, Class 3 = DBF+/HP+ proximal/distal limb without DBF-/HP+, Class 4 = Mixed DBF+/HP+ and DBF-/HP+ in proximal/distal limb, Class 5 = DBF-/HP+ entire limb. Adding SPECT/CT to planar scintigraphy showed a 15.4% modification rate in lymphoscintigraphic staging. HP volume ratio significantly increased as clinical severity and lymphoscintigraphic staging increased, while DBF volume ratio increased with severity and followed expected patterns according to lymphoscintigraphic staging. Hybrid SPECT/CT lymphoscintigraphic classification showed strong positive correlation with clinical severity and TLS. Our results demonstrated substantial modification of lymphoscintigraphic staging by adding SPECT/CT to a conventional planar scintigraphy. In addition, a hybrid SPECT/CT is expected to provide new indicators reflecting lymphoscintigraphic staging and clinical severity by providing both of functional DBF and anatomical HP information.

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

BACKGROUND: Breast 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. METHODS: A 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. FINDINGS: All 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. INTERPRETATION: The 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.

Managing the Morbidity: Individualizing Risk Assessment, Diagnosis, and Treatment Options for Upper Extremity Lymphedema.

In the setting where breast cancer-related lymphedema (BCRL) remains a feared and common complication of breast cancer, here we review important factors for the development, diagnosis, prevention, and treatment of BCRL. We find that race/ethnicity affect BCRL development risk, that future studies should focus on understanding the biological reasons behind the increased susceptibility of certain racial minorities to BCRL, that surveillance, early detection, exercise programs, and arm compression can reduce the risk of BCRL, and that surgical techniques to preserve and restore lymphatic drainage being evaluated in randomized trials may become transformative in reducing BCRL risk for high-risk patients.

Assessment and management of upper limb lymphoedema in advanced disease: a case study.

Lymphoedema is thought to affect around 200 000 people in the UK (NHS England, 2023). Secondary lymphoedema is a relatively common complication of cancer and cancer treatment, and in advanced disease it may present a challenging issue for community nursing staff caring for patients approaching the end of their lives. In this article, a case study considers the assessment and treatment of upper limb lymphoedema in a patient with advanced metastatic breast cancer. Management of this complex and distressing condition requires holistic assessment and collaborative care planning with the patient and their wider care team, including onward referral to specialist lymphoedema and palliative care services. The case study considers the typical presentation of lymphoedema in an upper limb, exclusion of reversible causes for oedema, awareness of palliative care emergencies such as superior vena cava obstruction, and the provision of supportive therapeutic interventions in context of the patient's expressed wishes for her ongoing care.

Effect of illness perception on predicting breast cancer-related lymphedema risk management behaviours among breast cancer patients: A comparison between dimensions and profiles.

AIM: This study aimed to explore the utility of latent profile analysis of illness perception, in comparison to treating illness perception as several dimensions, to predict breast cancer-related lymphedema risk management behaviours among Chinese breast cancer patients. METHODS: This is a 3-month longitudinal study. From August 2019 to January 2021, patients who recently underwent breast cancer surgery including axillary lymphadenectomy were recruited. Illness perception and risk management behaviours were measured by breast cancer-related lymphedema specific questionnaires before discharge following surgery (n = 268) and at 3 months postsurgery (n = 213), respectively. RESULTS: Treating illness perception as several dimensions, 'illness coherence' and 'timeline (cyclical)' dimensions were found to be significantly associated with breast cancer-related lymphedema risk management behaviours. Using the latent profile analysis, two illness perception profiles were identified and significant differences were revealed in breast cancer-related lymphedema risk management behaviours between them. Overall, illness perception profiles explained smaller amounts of variability in breast cancer-related lymphedema risk management behaviours than illness perception dimensions. CONCLUSION: Future studies could combine these two different perspectives of illness perception regarding breast cancer-related lymphedema into the design of interventions to improve breast cancer-related lymphedema risk management behaviours.

In-silico assessment of high-risk non-synonymous SNPs in ADAMTS3 gene associated with Hennekam syndrome and their impact on protein stability and function.

Hennekam Lymphangiectasia-Lymphedema Syndrome 3 (HKLLS3) is a rare genetical disorder caused by mutations in a few genes including ADAMTS3. It is characterized by lymphatic dysplasia, intestinal lymphangiectasia, severe lymphedema and distinctive facial appearance. Up till now, no extensive studies have been conducted to elucidate the mechanism of the disease caused by various mutations. As a preliminary investigation of HKLLS3, we sorted out the most deleterious nonsynonymous single nucleotide polymorphisms (nsSNPs) that might affect the structure and function of ADAMTS3 protein by using a variety of in silico tools. A total of 919 nsSNPs in the ADAMTS3 gene were identified. 50 nsSNPs were predicted to be deleterious by multiple computational tools. 5 nsSNPs (G298R, C567Y, A370T, C567R and G374S) were found to be the most dangerous and can be associated with the disease as predicted by different bioinformatics tools. Modelling of the protein shows it can be divided into segments 1, 2 and 3, which are connected by short loops. Segment 3 mainly consists of loops without substantial secondary structures. With prediction tools and molecular dynamics simulation, some SNPs were found to significantly destabilize the protein structure and disrupt the secondary structures, especially in segment 2. The deleterious effects of mutations in segment 1 are possibly not from destabilization but from other factors such as the change in phosphorylation as suggested by post-translational modification (PTM) studies. This is the first-ever study of ADAMTS3 gene polymorphism, and the predicted nsSNPs in ADAMST3, some of which have not been reported yet in patients, will serve for diagnostic purposes and further therapeutic implications in Hennekam syndrome, contributing to better diagnosis and treatment.