Onset Of Lymphedema Research Articles

Navigating Lymphedema: The Impact of Indocyanine Green Lymphography on Personalized Therapy Outcomes in Breast Cancer Patients

AimTo evaluate the role of Indocyanine Green Lymphography (ICG_L) in the early diagnosis and personalized management of breast cancer-related lymphedema (BCRL) among high-risk breast cancer (BC) survivors. MethodsPatients who admitted to the UPMC Magee-Womens Hospital Lymphedema Program between October 2018 and December 2021 with episodic symptoms were enrolled into the study. Patient demographics, clinical characteristics, and outcomes were prospectively collected and retrospectively analysed. Lymphatic flow disruptions were identified and guided personalized therapeutic interventions were guided by ICG_L. ResultsAmong 154 BC survivors, 184 arms were evaluated. Initial ICG_L showed 57.1% had no lymphedema, while 42.9% were classified as stage 1 to 3 lymphedema. Early diagnosis and personalized interventions provided improved outcomes, with only 4.3% developing clinical lymphedema after a median follow-up of 27 months. Patients exhibited stable or improved symptoms with individualized treatments such as manual lymphatic drainage, compression therapies, and physiotherapy. ConclusionICG_L evaluation is essential for patients at high-risk of developing BCRL. Early diagnosis before clinical onset of lymphedema, and ICG_L guided therapy significantly enhances the clinical outcomes and improves lymphedema management.

New non-drug technologies for lymphedema associated with breast cancer: a review

INTRODUCTION. Breast Cancer-Related Lymphedema (BCRL) is the most common complication after radical treatment of breast cancer (BC). Currently, there are no molecular therapeutic targets whose pharmacologic action could prevent edema, making it necessary to study the efficacy of non-pharmacologic techniques. AIM. To study the effectiveness of non-medication technologies in BCRL to develop recommendations for practical application based on the analysis of systematic reviews and meta-analyses of randomized controlled trials (RCTs). MATERIALS AND METHODS. The search was conducted in the Physiotherapy Evidence-Based Database (PEDro, 2002–2024) using the keywords: “lymphedema”, “upper limbs”, “breast cancer”. A total of 203 sources were selected as of March 2024. RESULTS AND DISCUSSION. Numerous studies have found that the use of early postoperative physical exercise with a gradual expansion of the load in patients at risk of developing BCRL is a safe and effective method of rehabilitation. The effectiveness of early preventive use of manual lymphatic drainage (MLD) in 4 RCTs was studied in a Cochrane review. However, the clinical effectiveness of early prophylactic use of MLD to prevent BCRL remains insufficiently proven. In contrast, prophylactic use of compression sleeves has been shown to reduce and delay the onset of arm lymphedema in women at high risk of developing BCRL during the first year after breast cancer surgery. Studies have also confirmed the effectiveness of an early Prospective Surveillance Model using bioimpedance spectroscopy for early detection and immediate treatment of BCRL. It has been proven that in order to reduce the volume of a limb with BCRL, it is necessary to prescribe an intensive phase of complex decongestive therapy (CDT) for at least 3 weeks. Studies have also proven the effectiveness of using a standard or improved intermittent pneumatic compression device in the rehabilitation phases, including at home. CONCLUSION. To reduce the risk of development and progression of BCRL, modern exercise therapy techniques should be used to increase physical activity in order to control body weight, and educational techniques for self-massage and self-application of compression bandages should be actively used. The “golden” standard for conservative treatment of BCRL remains CDT, which is based on MLD. At the same time, the wider use and development of new methods of hardware lymphatic drainage that imitate MLD, which is a highly resourceful and costly method of treatment for BCRL, is justified. To confirm the clinical effectiveness of improved hardware pneumocompression, additional RCTs assessing long-term treatment results are required.

Lymphedema after regional nodal irradiation for breast cancer: a retrospective cohort study.

We aimed to analyze the occurrence of lymphedema as a side effect in patients who underwent regional nodal irradiation (RNI) following surgery for breast cancer. This retrospective study was conducted on patients with breast cancer who underwent surgery from July 2014 to October 2020 at Inje University Busan Paik Hospital. The analysis included 113 cT1-3N1-3M0 breast cancer patients who underwent RNI as part of radiotherapy (RT). Mostly, surgeries were performed using breast-conserving surgery (n = 99, 87.6%), except for 14 patients with modified radical mastectomy. The total RT dose for RNI was 45-60 Gy, and the fraction size was 1.8-2.0 Gy. Most patients underwent chemotherapy (n = 98, 86.7%), including taxanes (n = 92, 81.4%). The median follow-up was 61.1 months (range, 5.0-110.5 months). Lymphedema occurred in 54 patients (47.8%) after surgery. Twenty of them (17.7%) developed a new onset of lymphedema after RT, while 34 (30.1%) detected lymphedema before the completion of RT. Over the follow-up, 16 patients (14.2%) experienced recurrence. High radiation dose (>50.4 Gy) for RNI (P = 0.003) and taxane use (P = 0.038) were related to lymphedema occurrence after RT. Moreover, lymphedema occurrence after RT was also related to recurrence after surgical resection (P = 0.026). Breast-conserving surgery was related to early-onset lymphedema before the completion of RT (P = 0.047). Furthermore, the degree of lymph node dissection (≤4) was related to the overall occurrence of lymphedema (P = 0.045). Considering a reduction in RNI dose may be beneficial in mitigating the incidence of lymphedema after RT in patients with breast cancer.

Changes in intracellular water volume after leg lymphedema onset and lymphaticovenular anastomosis as its surgical intervention

ObjectiveTo clarify the changes in the intracellular water (ICW) volume in lymphedema-affected legs after lymphedema onset and its surgical intervention (ie, lymphaticovenular anastomosis [LVA]), we investigated the changes in body water composition using bioelectrical impedance analysis. MethodsThis retrospective case series included 41 women with unilateral secondary leg lymphedema. The volume changes in the ICW and extracellular water (ECW) of the affected leg were measured using an InBody S10 (InBody Co, Ltd) multifrequency bioelectrical impedance analyzer, at both lymphedema onset and 1 year after LVA. ResultsThe volume increase with leg lymphedema onset was comparable between the ECW and ICW (0.59 L vs 0.56 L; 95% confidence interval [CI], −0.02 to 0.06; P = .27), and the increase rate was higher for ECW (35.3% vs 22.1%; 95% CI, 9.3%-17.2%; P < .001). The volume reduction at 1 year after LVA was comparable between ECW and ICW (0.23 L vs 0.27 L; 95% CI, −0.08 to 0.02; P = .20), and the reduction rate was higher for ECW (8.7% vs 7.0%, 95% CI, 0.04%-3.2%; P = .044). The volume difference between ICW and ECW remained constant throughout the six measurements before and after LVA (F[3.01, 120.20] = 1.85; P < .14). ConclusionsLeg LVA reduced ICW in the lymphedematous leg. The onset of leg lymphedema increased ECW and ICW in the affected limb, and LVA decreased both ECW and ICW. The volume change in the affected leg was comparable between ECW and ICW at both lymphedema onset and after LVA. However, the rate of change was higher for ECW. The volume difference between ICW and ECW remained constant. Using bioelectrical impedance analysis, alterations in ICW volume were detected in the legs affected by lymphedema, both after the onset of lymphedema and after LVA intervention.

Solid Facial Edema: A Rare Complication in Acne

Solid persistent facial edema is a rare and poorly understood condition that can be a serious complication of acne vulgaris and rosacea. It manifests as a slow onset of persistent lymphedema in the upper two-thirds of the face and can lead to significant cosmetic disfigurement affecting a patient's self-esteem and mental health. This article presents a case of persistent facial edema in a patient with severe acne and discusses the diagnosis and management of this rare condition.

Effect of Yoga Among Women at Risk and With Breast Cancer–Related Lymphedema: A Systematic Review

Background: Participation in exercise improves function, restores fitness, and enhances quality of life in survivors of breast cancer. There is robust evidence regarding resistance and aerobic training for women at risk for and with breast cancer–related lymphedema; however, the effect of yoga on impairments and functional outcomes has not been well documented. The purpose of this systematic review is to examine the effect of yoga on arm volume, strength, range of motion, function, and quality of life among women at risk for and with breast cancer–related lymphedema and create evidence-based recommendations. Methods: This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (Prospero registration number: 42022311574). EMBASE, PubMed, CINAHL Complete, Web of Science, Scopus, and Google Scholar were searched from January 2010 through December 2021. Quality and bias of included studies were assessed using the American Physical Therapy Association's Critical Appraisal Tool for Experimental Intervention Studies. Results: A total of 132 articles were screened for eligibility and 9 studies met inclusion criteria. Based on 3 acceptable and 6 low-quality studies, this review found that participation in yoga demonstrated a positive effect on arm range of motion, strength, function, and quality of life among women at risk for and with breast cancer–related lymphedema. No safety issues, including new onset or exacerbation of lymphedema, were found in the reviewed studies. Conclusion: Integration of yoga into a therapeutic plan of care is supported. Variations in yoga type, mode, duration, and frequency currently make it challenging to generate specific guidelines. Adherence and an ongoing commitment to yoga practice may promote long-term effects.

The Risk of Lymphedema After Breast Cancer Surgery Should Not Restrict Necessary Hand Surgery Interventions.

The purpose of this study was to evaluate the incidence of lymphedema onset or exacerbation in patients undergoing upper extremity interventions, both nonoperative and operative, after breast cancer surgery. The study inclusion criteria were the following: (1) prior history of breast cancer surgery or lymphedema from the cancer; (2) upper extremity intervention, ipsilateral to the breast cancer side; and (3) follow-up of at least 1 month. Patients were evaluated for demographic information, type of breast cancer procedure and hand intervention, number of lymph nodes dissected, preexisting lymphedema, exacerbation of lymphedema, and new-onset lymphedema. A total of 161 patients undergoing 385 hand interventions (300 injections, 85 surgeries) were reviewed. Median follow-up was 31 months (range: 1-110). Nineteen patients had preexisting lymphedema ipsilateral to the hand procedure and none experienced an exacerbation of their lymphedema. Three patients developed new-onset lymphedema ipsilateral to their hand intervention at an average follow-up of 30 months (range: 4-67). One patient had a single injection and developed lymphedema over 5 years later. One had 2 injections in the same hand on the same date and developed lymphedema 3 months later. The third patient had 2 injections in the right hand, 1 injection and 1 surgery in the left hand, and developed either lymphedema or swelling due to rheumatoid arthritis in the right hand 1 year after the injections. Patients who have undergone breast cancer surgery can safely undergo upper extremity intervention with low risk of lymphedema exacerbation or onset.

A retrospective analysis of Stewart-Treves syndrome in the context of chronic lymphedema

BackgroundStewart-Treves syndrome (STS) is an angiosarcoma associated with chronic lymphedema. ObjectivesThis article analyses the characteristics of twenty-two patients and proposes active intervention in lymphedema and the early diagnosis of STS. MethodsTwenty-two patients with STS were diagnosed at the centre over an 11-year period. Clinical manifestations, a series of conventional analyses, and histopathology were used to study these cases retrospectively. ResultsThe age range of 22 patients with STS was 15 to 78 years. The main clinical manifestations included multiple skin and subcutaneous nodules and scattered red or purplish-red rashes in the lymphoedematous limbs. These patients often showed clinical symptoms such as lymphedema, weakness, emaciation, pain, mass, lymphadenopathy and so on. The positive rates of ultrasonography, MRI and radionuclide imaging were 66.7% (6/9), 92.3% (12/13) and 18.2% (2/11), respectively. The main points regarding active intervention in lymphedema and early diagnosis of STS were summarized. Study limitationsSince this was a retrospective study, the main points summarized by the author need to be further quantified in clinical work to guide the diagnosis of this kind of disease more conveniently. In addition, further clinical trials are needed to evaluate the role of lymphedema in the occurrence and development of malignant tumors. ConclusionsSTS can appear in lymphoedematous tissue many years after lymphedema onset. To avoid delays in the diagnosis and therapy of STS, physicians should actively look for signs or symptoms of malignant lymphedema during the follow-up period and promptly manage patients developing problems.

The Lymphatic Endothelium in the Context of Radioimmuno-Oncology

The study of lymphatic tumor vasculature has been gaining interest in the context of cancer immunotherapy. These vessels constitute conduits for immune cells' transit toward the lymph nodes, and they endow tumors with routes to metastasize to the lymph nodes and, from them, toward distant sites. In addition, this vasculature participates in the modulation of the immune response directly through the interaction with tumor-infiltrating leukocytes and indirectly through the secretion of cytokines and chemokines that attract leukocytes and tumor cells. Radiotherapy constitutes the therapeutic option for more than 50% of solid tumors. Besides impacting transformed cells, RT affects stromal cells such as endothelial and immune cells. Mature lymphatic endothelial cells are resistant to RT, but we do not know to what extent RT may affect tumor-aberrant lymphatics. RT compromises lymphatic integrity and functionality, and it is a risk factor to the onset of lymphedema, a condition characterized by deficient lymphatic drainage and compromised tissue homeostasis. This review aims to provide evidence of RT's effects on tumor vessels, particularly on lymphatic endothelial cell physiology and immune properties. We will also explore the therapeutic options available so far to modulate signaling through lymphatic endothelial cell receptors and their repercussions on tumor immune cells in the context of cancer. There is a need for careful consideration of the RT dosage to come to terms with the participation of the lymphatic vasculature in anti-tumor response. Here, we provide new approaches to enhance the contribution of the lymphatic endothelium to radioimmuno-oncology.

Paediatric lymphoedema: An audit of patients seen by the paediatric and primary lymphoedema group of vascular European Reference Network (VASCERN)

Little is known about the overall prevalence of lymphoedema in children and the types of paediatric lymphoedema seen by specialist centres. Therefore, this study was aimed to provide a profile of children with primary or secondary lymphoedema seen by the expert centres of the paediatric and primary lymphoedema working group (PPL-WG) of VASCERN and to compare the profile between the different countries.A retrospective review of all children (aged up to 18 years) seen for the first time by the expert centres over one year (2019) was carried out. Lymphoedema-, patient- and genetics-related data was collected and described for the whole group and compared between the different European countries/UK.In 2019, a total of 181 new children were seen by eight expert centres. For primary lymphoedema, the phenotype was based on the St George's classification of lymphatic anomalies. The percentages diagnosed according to each category were: 7.2% for syndromic lymphoedema, 2.8% for systemic/visceral involvement, 30.4% for congenital, 35.9% for late-onset lymphoedema and 19.3% for vascular/lymphatic malformations. 4.4% had secondary lymphoedema. Nearly 10% of all children had had at least one episode of cellulitis. The median delay from onset of symptoms to being seen by an expert centre was 2.4 years. In 44.4% of the children with primary lymphoedema a genetic test was performed, of which 35.8% resulted in a molecular diagnosis. Across the different centres, there was a wide variety in distribution of the different categories of paediatric lymphoedema diagnosed and the frequency of genetic testing.In conclusion, this paper has demonstrated that there is a large delay between the onset of paediatric lymphoedema and the first visit in the expert centres and that an episode of cellulitis is a relatively common complication. Diagnostic variation across the centres may reflect different referral criteria. Access to genetic testing was limited in some centres. It is recommended that these issues are addressed in the future work of the PPL-WG to improve the referral to the expert centres and the consistency in service provision for paediatric lymphoedema in Europe.

Evaluation of Circulating MicroRNAs and Adipokines in Breast Cancer Survivors with Arm Lymphedema.

Breast cancer-related lymphedema (BCRL) is a form of secondary lymphedema that is characterized by abnormal swelling of one or both arms due to the accumulation of lymph fluid in the interstitial tissue spaces, resulting from obstruction of the lymphatic vessels due to surgery insults, radiotherapy, or chemotherapy. Due to the multifactorial nature of this condition, the pathogenesis of secondary lymphedema remains unclear and the search for molecular factors associated with the condition is ongoing. This study aimed to identify serum microRNAs and adipokines associated with BCRL. Blood was collected from 113 breast cancer survivors and processed to obtain serum for small RNA-sequencing (BCRL vs. non-BCRL, n = 7 per group). MicroRNAs that were differentially expressed (fold change >1.5, p < 0.05) between lymphedema cases and those without lymphedema were further quantified in a validation cohort through quantitative reverse transcription PCR (BCRL n = 16, non-BCRL, n = 83). Leptin and adiponectin levels were measured in a combined cohort (BCRL n = 23, non-BCRL n = 90) using enzyme-linked immunosorbent assays. Two of the most significantly upregulated microRNAs, miR-199a-3p and miR-151a-3p, were strongly correlated with the onset of lymphedema and diabetes mellitus in the BCRL group. Leptin levels were higher in the BCRL cohort compared to the non-BCRL cohort (p < 0.05). A metabolic syndrome biomarker, the adiponectin/leptin ratio, was found to be lower in the BCRL group than in the non-BCRL group (median: 0.28 vs. 0.41, p < 0.05). Extensive studies on the mechanisms of the identified microRNAs and association of leptin with arm lymphedema may provide new insights on the potential biomarkers for lymphedema that should be followed up in a prospective cohort study.

RISK FACTORS FOR DEVELOPING UPPER LIMB CELLULITIS AFTER BREAST CANCER TREATMENT

Cellulitis is one of the most important troubling complications of breast cancer treatment. Therefore, elucidating the risk factors for cellulitis in patients that have undergone breast cancer treatment is crucial. This is a retrospective medical record study among 523 patients who had received breast cancer treatment and were referred to the Lymphedema Clinic. Data on age, height, weight, BMI (body mass index), education level, arm dominance, history of previous surgery, axillary lymph node dissection, radiotherapy, and chemotherapy were noted. The time between operation and onset of lymphedema, duration of lymphedema, history of cellulitis, and number of cellulitis attacks were recorded. Circumference measurements were taken at four points on the upper limb. Univariate analysis showed that longer duration of lymphedema, larger circumference of the unaffected arm and larger circumference of the arm with lymphedema were associated with higher risk of cellulitis (p=0.008, p=0.007, p< 0.001, respectively). The incidence of cellulitis was higher in patients with lymphedema than patients who had no lymphedema (p< 0.001). Moreover, the frequency of cellulitis was higher in patients with lower education level (p=0.015). It was deter-mined that patients with cellulitis needed more compression garments (p< 0.001) and multi-layered bandage therapy (p< 0.001) than those without. Regression analysis revealed that presence of lymphedema (p=0.036), duration of lymphedema (p=0.048), radiotherapy (p=0.01) and educational level (0.019) are significantly associated with developing upper extremity cellulitis. It is important to consider these risk factors for the prevention and management of cellulitis in patients who undergo treatment for breast cancer. Early detection and treatment of lymphedema also remains essential for these patients.

Early Blood Flow Abnormalities in Axillary and Brachial Arteries Precede the Onset of Persistent Lymphedema in Women Treated Surgically for Breast Cancer.

Background: surgery to treat breast cancer (BC) is associated with upper limb (UL) lymphedema, which in some cases may become permanent. It is uncertain whether lymphedema results from injury to either lymphatic or blood vessels, or to both. Methods and Results: a cohort of 200 BC patients was examined 1, 3, 6, 12, and 24 months after surgery. Axillary and brachial blood vessels were evaluated using Doppler Ultrasound, and patients had their UL examined for lymphedema at each visit. Patients who developed lymphedema 24 months after surgery presented with higher mean flow velocity (MFV) and end diastolic velocity (EDV) in both axillary (MFV = 13.57 vs. 10.7 cm/s, p = 0.02; EDV = 5.62 vs. 3.47 cm/s; p = 0.004) and brachial (MFV = 11.44 vs. 8.74 cm/s; p = 0.03; EDV = 5.08 vs. 3.04; p = 0.04) arteries as early as 1 month after surgery. Similar associations were found 3, 6, and 12 months after surgery. Early abnormalities of the resistive and pulsatility indexes were also significantly associated with persistent lymphedema. EDV measured 1 month after surgery had the best performance to detect patients who will later develop long-term lymphedema, (sensitivity = 73.7%; specificity = 71.2%; negative predictive value = 57.6%). Conclusion: vascular abnormalities precede and are possible causal factors for UL lymphedema in BC patients.

Elective Hand Surgery in Patients With History of Axillary Node Dissection: Risks and Patient Education.

Objective: To determine if patients with a prior history of axillary lymph node dissection (ALND) secondary to breast cancer surgery and other procedures are at an increased risk of postoperative complications including lymphedema and infection following elective upper extremity surgery. Furthermore, the study aimed to evaluate the extent of patient education regarding lymphedema as a possible complication of upper extremity surgery.Methods: A review of 312 patients presenting to the clinic with upper extremity pathologies was performed of which 15 patients had a history of surgeries secondary to breast cancer and 297 had no prior history of breast cancer. Nine out of 15 patients with prior breast procedures and 66 out of 297 patients with no such history underwent elective hand surgeries, with 22 out of the 75 patients having a history of ALND. Incidences of postoperative complications including lymphedema and infection were recorded. Afterward, a survey inquiring about patient education was conducted to assess whether the patients were educated regarding lymphedema and if so, when and from whom they received the counseling.Results: No patients with a prior history of ALND secondary to breast cancer or other surgeries developed a postoperative infection or onset of lymphedema, and no patients with preoperative lymphedema had any worsening of lymphedema or infection postoperatively. The survey conducted afterward revealed that 61% of the patients with a prior history of breast cancer-related procedures including lymph node dissection were never counseled regarding lymphedema as a possible complication of hand surgery. Furthermore, 75% of the survey participants wished they were given more information about possible causes and complications of, and ways to prevent or minimize the possibility of lymphedema developing postoperatively.Conclusion: Prior history of ALND did not make patients more susceptible to postoperative complications, thus a history of isolated ALND or breast cancer surgery including ALND should not preclude elective hand surgical procedures from being performed ipsilaterally. Additionally, improvements in the degree of patient counseling regarding postoperative complications following hand surgery are needed as increased patient education is shown to be associated with a lower rate of complications and faster recovery times.

Pediatric Lymphedema: Study of 180 Patients Referred to a Tertiary Lymphedema Clinic.

Lymphedema is due to dysfunction of the lymphatic system. It can be primary or secondary. Pediatric lymphedema is more often primary and is a chronic disease with a heavy burden on quality of life. Medical records of patients under 18 years of age referred between 1996 and 2021 to the specialized lymphedema clinic at the Sainte-Justine University Hospital Center were reviewed. Demographic data, sex, age at presentation, location of the lymphedema, clinical features, genetic testing, symptoms, complications, investigations, and treatment were collected. Of 180 referred patients, lymphedema was confirmed in 151, and 137 were primary lymphedema. Median age of apparition of primary lymphedema was 7.00 years and was significantly lower in boys than in girls. Primary congenital lymphedema was more frequent in boys (51.0%, 27.3% in girls, P = .007), and onset of primary lymphedema during adolescence was more frequent in girls (53.4%, 25.0% in boys, P = .001). Lower limbs were the most impacted (88.3%). Sixty patients had genetic testing, and 38 (63.3%) of them were discovered to have a pertinent genetic mutation. The most common mutated gene was the FLT4 gene (in 9 patients). Seven patients (5.1%) had associated extensive/central lymphatic malformation and 24 (17.6%) had a polymalformative syndrome/syndromic lymphedema. Pediatric lymphedema is more frequent in girls, usually involves lower limb, and is most often sporadic, but often associated with a genetic mutation, and genetic testing should be performed.

COVID-19 Vaccination in Patients with Cancer.

Simple SummaryPatients with cancer are concerned about the effects of the COVID-19 vaccination while authorities search for ways to encourage vaccination; however, many points are still unclear. To remedy this situation, we conducted an online survey of 1182 female patients with cancer. The results showed that 768 were concerned about the vaccine, and 726 consulted with their attending physicians about the vaccination. The results also showed significantly higher vaccination rates among the patients who had consulted with their physicians. We found that consulting with attending physicians appeared to be linked to reduced anxiety, decisions about the timing of the vaccination, and higher vaccination rates. This was corroborated by the result of the cross-analysis of vaccination status and information sources about the vaccination. Therefore, we concluded that consulting with a physician about vaccination alleviates the concerns of patients with cancer and encourages them to get vaccinated.Patients with cancer are concerned about the effects of the COVID-19 vaccination. We conducted an online survey on the COVID-19 vaccination status and side effects among patients with cancer in Japan between 8 and 14 August 2021. We included 1182 female patients with cancer aged 20–70 years and registered on an online patient website. Of the patients, 944 had breast cancer, 216 had gynecological cancer, 798 were undergoing drug/radiation therapy, and 370 were in follow-up. At the time of the survey, 885 patients had already received at least one dose. Of these, 580 had also received their second dose. The incidence rate of side effects was equivalent to previous reports. In patients with breast cancer, problems such as the onset or worsening of lymphedema or axillary lymphadenopathy metastasis requiring differential diagnosis were encountered following vaccination. A total of 768 patients were concerned about the vaccine at some point, and 726 consulted with their attending physicians about the timing or side effects of the vaccination. Of the 110 patients undergoing chemotherapy or radiation therapy, 75 adjusted the timing of the vaccination based on their therapy. The cross-analysis revealed that 81% of those who consulted their physician had received at least one dose of the COVID-19 vaccination compared with 65% of those who had not consulted their physician. Consulting with a physician about the COVID-19 vaccination was found to alleviate the concerns of patients with cancer and encourage them to get vaccinated.

CDH5, a Possible New Candidate Gene for Genetic Testing of Lymphedema.

Background: Expressed by endothelial cells, CDH5 is a cadherin involved in vascular morphogenesis and in the maintenance of vascular integrity and lymphatic function. The main purpose of our study was to identify distinct variants of the CDH5 gene that could be associated with lymphatic malformations and predisposition for lymphedema. Methods and Results: We performed Next Generation Sequencing of the CDH5 gene in 235 Italian patients diagnosed with lymphedema but who tested negative for variants in known lymphedema genes. We detected six different variants in CDH5 five missense and one nonsense. We also tested available family members of the probands. For family members who carried the same variant as the proband, we performed lymphoscintigraphy to detect any lymphatic system abnormalities. Variants were modeled in silico. The results showed that CDH5 variants may contribute to the onset of lymphedema, although further in vitro studies are needed to confirm this hypothesis. Conclusions: Based on our findings, we propose CDH5 as a new gene that could be screened in patients with lymphedema to gather additional evidence.

Adipocytes are larger in lymphedematous extremities than in controls

Lymphedema is caused by dysfunctional lymph vessels or as a complication of cancer treatment leading to edema and adipose tissue deposition. One hypothesis is that adipocyte hypertrophy contributes to the volume increase in lymphedema. The aim of the study was to compare adipocyte size in arm and leg lymphedema and controls. The adipocyte size difference was also compared between the arms and legs. Furthermore, any link between adipocyte size difference and gender, lymphedema onset, duration, previous radio- and chemotherapy was studied, as well as any relationship to total excess volume increase in the extremities, body mass index (BMI) and body weight. Adipose tissue biopsies from the lymphedematous and non-affected extremities were taken from 47 patients. The adipocytes sizes were measured using an Olympus PROVIS microscope, Olympus DP50 camera (Olympus, Tokyo, Japan) and ImageJ program (NIH, Bethesda, MD). Additional information was obtained from the Lymphedema Center database. The data were assembled in Excel and statistics was calculated in SPSS® Statistics 23 (IBM®, Armonk, NY). The adipocyte size (mean ± SEM) in the lymphedematous extremities was significantly larger, 8880 ± 291 μm2, compared to the adipocyte size in the non-affected extremities, where it was 7143 ± 280 μm2, i.e. 24% larger (p < .001). The adipocyte size increase was larger in arm than in leg lymphedema. No correlation was found between adipocyte size and gender or onset. However, a negative correlation was found between adipocyte size difference and duration. No correlation was found between adipocyte size and previous chemo- or radiotherapy. There was a positive correlation between adipocyte size and BMI. Hypertrophy of adipocytes was seen in the lymphedematous extremities versus control and contributes to the excess volume.

Stewart-Treves syndrome and other cutaneous malignancies in the context of chronic lymphedema: a systematic review.

Angiosarcoma developing in chronically lymphedematous tissue, or Stewart-Treves syndrome (STS), is a rare and lethal complication of lymphedema. This systematic review summarizes characteristics and outcomes of STS and other cutaneous malignancies arising in chronic lymphedema. MEDLINE and EMBASE databases were searched on February 19th, 2021, to identify 200 articles included in the analysis. Of 369 included patients, 89.7% (n = 331/369) had STS and 10.3% (n = 38/369) had other associated malignancies. Mean age of onset was 61.2 years, and 85.9% (n = 317/369) of cases were female. Common risk factors were previous cancer history (69.8%, n = 258/369) and radiation history (53.7%, n = 198/369). Lymphedema was most commonly attributed to surgical causes (68.3%, n = 252/369). STS begins on average 14.9 years after lymphedema with mortality of 53.9% (n = 178/331) and remission rate of 16.1% (n = 53/331). Other malignancies begin on average 23.7 years after lymphedema, with mortality of 10.5% (n = 4/38) and remission rate of 31.6% (n = 12/38). STS and other malignancies had 5-year survivals of 22.4% and 65.2%, respectively (P = 0.00145). For all patients, patients initially treated with excision had the best survival (median: 48 months, 5-year survival: 43.3%) and radiotherapy had the worst survival (median: 10 months, 5-year survival: 6.5%) (P = 0.0141). Malignancy can appear in lymphedematous tissue many years after lymphedema onset. STS has poorer prognosis compared to other malignancies. Further research should be conducted to better understand the causes, risk factors, and management of this phenomenon.

Cellulitis risk factors for patients with primary or secondary lymphedema

BackgroundLimb lymphedema is a chronic disease with primary and secondary forms, with the latter occurring essentially after cancer treatment. In the present study, we retrospectively analyzed the cellulitis frequency and its associated risk factors for patients with primary or secondary limb lymphedema. MethodsInformation from all 1991 patients referred to a specialized lymphedema center from January to June 2018 was collected, including previous cellulitis episodes and the clinical and lymphedema characteristics. ResultsOf the 1846 patients whose information could be analyzed, 695 (37.6%) had experienced one or more cellulitis episodes, and 23.3% had had recurrent cellulitis. Cellulitis occurred in 39.5%, 30.5%, and 38.6% (P = .02) of the patients with secondary upper limb, secondary lower limb, and primary lower limb lymphedema, respectively. The corresponding duration of lymphedema was 106.5, 97, and 243.1 months. For secondary upper limb lymphedema, a long interval from lymphedema onset to the first consultation at our specialized center, younger age at lymphedema onset, and the use of radiotherapy were independently associated with cellulitis. However, axillary lymph node excision, the use of chemotherapy, and segmentation of the upper limb lymphedema were not associated with cellulitis. A longer interval from lymphedema onset to the first consultation and lymph node excision were associated with cellulitis in those with lower limb secondary lymphedema but higher body mass index and younger age at lymphedema onset were not. For primary lower limb lymphedema, male sex, greater body mass index, and younger age at lymphedema onset were associated with cellulitis. ConclusionsDifferent risk factors for cellulitis were identified for patients with lymphedema at risk. Awareness of those factors is important for physicians to recognize lymphedema promptly and refer patients to specialized centers to optimize treatment.