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Current Oncology Reports Sep 2023Breast cancer-related lymphedema (BCRL) is a debilitating progressive disease resulting in various impairments and dysfunctions. Complete decongestive therapy embodies... (Review)
Review
PURPOSE OF REVIEW
Breast cancer-related lymphedema (BCRL) is a debilitating progressive disease resulting in various impairments and dysfunctions. Complete decongestive therapy embodies conservative rehabilitation treatments for BCRL. Surgical procedures performed by plastic and reconstructive microsurgeons are available when conservative treatment fails. The purpose of this systematic review was to investigate which rehabilitation interventions contribute to the highest level of pre- and post-microsurgical outcomes.
RECENT FINDINGS
Studies published between 2002 and 2022 were grouped for analysis. This review was registered with PROSPERO (CRD42022341650) and followed the PRISMA guidelines. Levels of evidence were based upon study design and quality. The initial literature search yielded 296 results, of which, 13 studies met all inclusion criteria. Lymphovenous bypass anastomoses (LVB/A) and vascularized lymph node transplant (VLNT) emerged as dominant surgical procedures. Peri-operative outcome measures varied greatly and were used inconsistently. There is a dearth of high quality literature leading to a gap in knowledge as to how BCRL microsurgical and conservative interventions complement each other. Peri-operative guidelines are needed to bridge the knowledge and care gap between lymphedema surgeons and therapists. A core set of outcome measures for BCRL is vital to unify terminological differences in the multidisciplinary care of BCRL. Complete decongestive therapy embodies conservative rehabilitation treatments for breast cancer-related lymphedema (BCRL). Surgical procedures performed by microsurgeons are available when conservative treatment fails. This systematic review investigated which rehabilitation interventions contribute to the highest level of pre- and post-microsurgical outcomes. Thirteen studies met all inclusion criteria and revealed that there is a dearth of high quality literature leading to a gap in knowledge as to how BCRL microsurgical and conservative interventions complement each other. Furthermore, peri-operative outcome measures were inconsistent. Peri-operative guidelines are needed to bridge the knowledge and care gap between lymphedema surgeons and therapists.
Topics: Humans; Female; Breast Neoplasms; Lymphedema; Outcome Assessment, Health Care
PubMed: 37402044
DOI: 10.1007/s11912-023-01439-9 -
Journal de Medecine Vasculaire 2023Kaposi sarcoma (KS), due to HHV-8 infection is classified in 4 subtypes: epidemic, endemic, HIV-related and iatrogenic essentially after organ transplant. Lymphedema is... (Review)
Review
BACKGROUND
Kaposi sarcoma (KS), due to HHV-8 infection is classified in 4 subtypes: epidemic, endemic, HIV-related and iatrogenic essentially after organ transplant. Lymphedema is a complication of KS. We reviewed the interactions between HHV-8 infection and lymphedema according an analysis of the literature.
MAIN BODY
HHV-8 can infect different types of cells, among them a privileged tropism for lymphatic endothelial cells. It induces multi-centric endothelial proliferation leading to the occlusion of lymphatic vascular lumen. Lymphatic obstruction progressively lead to the blockage of lymphatic drainage, lymph stasis and lymphedema. Lymphedema mostly involved the lower limb affected by KS. It can then develop simultaneously or after the appearance of KS lesions but also be the first sign of KS, a long time before KS skin lesion onset. Lymphedema diagnosis is clinical and lymphoscintigraphy can confirm it if necessary. Lymphedema may be associated with active lesions of KS or non-evolutive, with only cicatricial lesions. KS should be treated according to the KS subtype, aggressive form, with local or systemic treatments associating with causal treatment, such as HIV infection or reducing immuno-suppressive drugs in transplant patients. In most of the cases, KS treatment may slightly reduce (or not) lymphedema volume which remains a chronic disease. Lymphedema management should be associated in order to reduce the volume and then stabilizing it. Low-stretch bandage, elastic garments and skin care are the cornerstone of treatment.
CONCLUSION
Lymphedema is a frequent complication of KS, and may reveal KS or occurs throughout its course. Association of KS and lymphedema must be known because lymphedema is a chronic disease affecting the quality of life. Beyond the treatment of KS, its management must be specific including a long follow-up to optimize the patient's observance required to maintain the best lymphedema control.
Topics: Humans; Sarcoma, Kaposi; HIV Infections; Endothelial Cells; Quality of Life; Lymphedema; Chronic Disease
PubMed: 38035924
DOI: 10.1016/j.jdmv.2023.10.007 -
Journal of Hepatology Oct 2023Lymphedema cholestasis syndrome 1 or Aagenaes syndrome is a condition characterized by neonatal cholestasis, lymphedema, and giant cell hepatitis. The genetic background...
BACKGROUND & AIMS
Lymphedema cholestasis syndrome 1 or Aagenaes syndrome is a condition characterized by neonatal cholestasis, lymphedema, and giant cell hepatitis. The genetic background of this autosomal recessive disease was unknown up to now.
METHODS
A total of 26 patients with Aagenaes syndrome and 17 parents were investigated with whole-genome sequencing and/or Sanger sequencing. PCR and western blot analyses were used to assess levels of mRNA and protein, respectively. CRISPR/Cas9 was used to generate the variant in HEK293T cells. Light microscopy, transmission electron microscopy and immunohistochemistry for biliary transport proteins were performed in liver biopsies.
RESULTS
One specific variant (c.-98G>T) in the 5'-untranslated region of Unc-45 myosin chaperone A (UNC45A) was identified in all tested patients with Aagenaes syndrome. Nineteen were homozygous for the c.-98G>T variant and seven were compound heterozygous for the variant in the 5'-untranslated region and an exonic loss-of-function variant in UNC45A. Patients with Aagenaes syndrome exhibited lower expression of UNC45A mRNA and protein than controls, and this was reproduced in a CRISPR/Cas9-created cell model. Liver biopsies from the neonatal period demonstrated cholestasis, paucity of bile ducts and pronounced formation of multinucleated giant cells. Immunohistochemistry revealed mislocalization of the hepatobiliary transport proteins BSEP (bile salt export pump) and MRP2 (multidrug resistance-associated protein 2).
CONCLUSIONS
c.-98G>T in the 5'-untranslated region of UNC45A is the causative genetic variant in Aagenaes syndrome.
IMPACT AND IMPLICATIONS
The genetic background of Aagenaes syndrome, a disease presenting with cholestasis and lymphedema in childhood, was unknown until now. A variant in the 5'-untranslated region of the Unc-45 myosin chaperone A (UNC45A) was identified in all tested patients with Aagenaes syndrome, providing evidence of the genetic background of the disease. Identification of the genetic background provides a tool for diagnosis of patients with Aagenaes syndrome before lymphedema is evident.
Topics: Humans; Infant, Newborn; 5' Untranslated Regions; Carrier Proteins; Cholestasis; HEK293 Cells; Intracellular Signaling Peptides and Proteins; Lymphedema; Myosins
PubMed: 37328071
DOI: 10.1016/j.jhep.2023.05.037 -
Lymphatic Research and Biology Apr 2024
Topics: Humans; Lipedema; Lymphedema; Diagnosis, Differential
PubMed: 38630992
DOI: 10.1089/lrb.2024.29161.editorial -
Surgical Oncology Clinics of North... Oct 2023In the setting where breast cancer-related lymphedema (BCRL) remains a feared and common complication of breast cancer, here we review important factors for the... (Review)
Review
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.
Topics: Humans; Female; Lymphedema; Morbidity; Breast Neoplasms; Risk Assessment; Upper Extremity
PubMed: 37714638
DOI: 10.1016/j.soc.2023.05.004 -
Annals of Surgical Oncology Jan 2024Identification of risk factors facilitates the prevention of breast cancer-related lymphedema (BCRL). Several published systematic reviews have already addressed the... (Review)
Review
BACKGROUND
Identification of risk factors facilitates the prevention of breast cancer-related lymphedema (BCRL). Several published systematic reviews have already addressed the risk factors for BCRL. This study aimed to systematically identify potential risk factors for BCRL and evaluate the quality of evidence.
METHODS
The study followed methodologic guidance from the Joanna Briggs Institute, and the Cochrane Handbook. The following electronic databases were systematically searched from inception to 15 November 2022: PubMed, Embase, CINAHL, Web of Science, Scopus, CNKI, SinoMed, Wanfang, JBI Database, Cochrane Database, ProQuest, and PROSPERO. Two authors independently screened studies, extracted data, and assessed methodologic quality using AMSTAR2, risk of bias using ROBIS, and evidence quality using GRADE. The study evaluated overlap, assessed the small-study effect, and calculated the I statistic and Egger's P value as needed.
RESULTS
The study included 14 publications comprising 10 meta-analyses and 4 systematic reviews. The authors identified 39 factors and 30 unique meta-analyses. In the study, 13 innate personal trait-related risk factors, such as higher body mass index (BMI) and axillary lymph nodes dissection, showed statistically significant associations with BCRL incidence. Breast reconstruction was found to be a protective factor. The methodologic quality was low or critically low. The majority of the systematic reviews and/or meta-analyses were rated as having a high risk of bias. Evidence quality was low for 22 associations and moderate for 8 associations.
CONCLUSIONS
The currently identified risk factors for BCRL all are innate personal trait-related factors. Future well-designed studies and robust meta-analyses are needed to explore potential associations between behavioral-, interpersonal-, and environmental-related factors and BCRL, as well as the role of genetic variations and pathophysiologic factors.
Topics: Female; Humans; Breast Cancer Lymphedema; Breast Neoplasms; Lymph Node Excision; Lymphedema; Risk Factors; Systematic Reviews as Topic; Meta-Analysis as Topic
PubMed: 37725224
DOI: 10.1245/s10434-023-14277-7 -
Psycho-oncology Oct 2023Cancer-related lymphoedema is a common side effect of cancer, affecting 24%-49% of people with cancer. Body image contributes to the well-being of individuals with this... (Review)
Review
OBJECTIVE
Cancer-related lymphoedema is a common side effect of cancer, affecting 24%-49% of people with cancer. Body image contributes to the well-being of individuals with this condition. This systematic review aimed to explore, for the first time, the state of the science concerning body image in cancer-related lymphoedema, including how body image is measured and variables associated with body image concerns.
METHODS
Six databases were systematically searched for peer-reviewed articles describing empirical quantitative studies where body image was measured with a reliable and valid measurement tool in adults with cancer-related lymphoedema.
RESULTS
Nine studies with 977 participants were included. The studies involved individuals who had experienced breast, head and neck, melanoma, and urogenital cancers and developed lymphoedema. There was considerable heterogeneity in body image measures used, precluding meta-analysis. The following variables were associated with increased body image concern: higher body integrity beliefs, experience of physical changes (e.g. pain) and differences in sensation and function, including changes in appearance related thoughts, feelings and emotions. Several studies described behavioural and psychological interventions which positively impacted body image outcomes in individuals with lymphoedema relating to specific cancers.
CONCLUSION
Regular screening for body image concerns could encourage more positive body image awareness in individuals with cancer-related lymphoedema and lessen some of its associated negative consequences. Future longitudinal and individual differences research in this area is important to inform intervention development. There is also need for a more standardised approach to the study and measurement of body image in people with cancer-related lymphoedema.
Topics: Adult; Humans; Body Image; Emotions; Lymphedema; Melanoma; Quality of Life
PubMed: 37681525
DOI: 10.1002/pon.6215 -
Proceedings of the National Academy of... Oct 2023Impaired lymphatic drainage and lymphedema are major morbidities whose mechanisms have remained obscure. To study lymphatic drainage and its impairment, we engineered a...
Impaired lymphatic drainage and lymphedema are major morbidities whose mechanisms have remained obscure. To study lymphatic drainage and its impairment, we engineered a microfluidic culture model of lymphatic vessels draining interstitial fluid. This lymphatic drainage-on-chip revealed that inflammatory cytokines that are known to disrupt blood vessel junctions instead tightened lymphatic cell-cell junctions and impeded lymphatic drainage. This opposing response was further demonstrated when inhibition of rho-associated protein kinase (ROCK) was found to normalize fluid drainage under cytokine challenge by simultaneously loosening lymphatic junctions and tightening blood vessel junctions. Studies also revealed a previously undescribed shift in ROCK isoforms in lymphatic endothelial cells, wherein a ROCK2/junctional adhesion molecule-A (JAM-A) complex emerges that is responsible for the cytokine-induced lymphatic junction zippering. To validate these in vitro findings, we further demonstrated in a genetic mouse model that lymphatic-specific knockout of ROCK2 reversed lymphedema in vivo. These studies provide a unique platform to generate interstitial fluid pressure and measure the drainage of interstitial fluid into lymphatics and reveal a previously unappreciated ROCK2-mediated mechanism in regulating lymphatic drainage.
Topics: Animals; Mice; Biomimetics; Cytokines; Endothelial Cells; Intercellular Junctions; Junctional Adhesion Molecule A; Lymphatic Vessels; Lymphedema; rho-Associated Kinases
PubMed: 37782785
DOI: 10.1073/pnas.2308941120 -
Vascular Medicine (London, England) Feb 2024Lymphedema has traditionally been underappreciated by the healthcare community. Understanding of the underlying pathophysiology and treatments beyond compression have... (Review)
Review
Lymphedema has traditionally been underappreciated by the healthcare community. Understanding of the underlying pathophysiology and treatments beyond compression have been limited until recently. Increased investigation has demonstrated the key role of inflammation and resultant fibrosis and adipose deposition leading to the clinical sequelae and associated reduction in quality of life with lymphedema. New imaging techniques including magnetic resonance imaging (MRI), indocyanine green lymphography, and high-frequency ultrasound offer improved resolution and understanding of lymphatic anatomy and flow. Nonsurgical therapy with compression, exercise, and weight loss remains the mainstay of therapy, but growing surgical options show promise. Physiologic procedures (lymphovenous anastomosis and vascularized lymph node transfers) improve lymphatic flow in the diseased limb and may reduce edema and the burden of compression. Debulking, primarily with liposuction to remove the adipose deposition that has accumulated, results in a dramatic decrease in limb girth in appropriately selected patients. Though early, there are also exciting developments of potential therapeutic targets tackling the underlying drivers of the disease. Multidisciplinary teams have developed to offer the full breadth of evaluation and current management, but the development of a greater understanding and availability of therapies is needed to ensure patients with lymphedema have greater opportunity for optimal care.
Topics: Humans; Quality of Life; Lymphedema; Lymphatic Vessels; Lymphography; Vascular Surgical Procedures
PubMed: 38166534
DOI: 10.1177/1358863X231215329 -
Vascular Medicine (London, England) Feb 2024
Topics: Humans; Lipedema; Lymphedema; Extremities
PubMed: 38334093
DOI: 10.1177/1358863X231222016