Recently, increased interest has focused on the phenomenon of lymphatic contractility. The thoracic duct and other lymph vessels appear to contract spontaneously to facilitate lymph flow with rate of contractions and their amplitude variable and dependent on different factors including fluid, concentration of ions or acidity, aging, drugs, or pathology. Not every lymph vessel remains contracting continuously with some seeming to completely stop their contractions due to various reasons. This may occur with no lymph flow within the vessel, or with very high flow, or it may be due to pathology or completely physiological conditions. Numerous studies have been conducted on this topic; however, their results may some-times seem contradictory. In this review, up-to-date publications have been collected and summarized to provide insights into the challenging topic of spontaneous lymphatic contractility and factors affecting it. This area remains of high research interest and newer techniques such as sonography may help to continue to shed light on the phenomenon of lymphatic contractility.
ICG lymphography is a lymphatic imaging tool that can inform lymphedema treatment, including self-management. Self-management requires patient engagement in a multimodal treatment program. However, lack of knowledge about lymphedema, challenges maintaining motivation, and lack of confidence in ability to perform self-management are barriers to engagement. This study aimed to determine if there was any change (immediate and/or delayed) to patient knowledge, motivation, confidence in lymphedema self-management, or lymphedema distress after undergoing ICG lymphography. A secondary aim was to observe health-related quality of life. A prospective observational repeated measures study followed 25 consecutive participants with limb lymphedema at three timepoints: pre; directly post; and, 12-months post ICG lymphography. A questionnaire exploring knowledge, motivation and confidence in self-management, along with lymphedema distress and a health-related quality of life tool were completed at each timepoint. Patients' knowledge about lymph-edema improved over all timepoints (p<0.001). Motivation for lymphedema self-management improvements trended toward significance directly post ICG lymphography (p=0.053), but was not maintained at 12-months. No other variables demonstrated significant change. Patients described the experience of undergoing ICG lymphography as positive and reported key learnings and changes to their self-management. ICG lymphography could be a useful tool to improve a person's knowledge of their lymphedema and may positively influence motivation to engage in self-management. Further exploration to sustaining motivation over time and potential im-pacts to lymphedema outcomes is necessary.
The primary study aim compared upper extremity (UE) functionality between breast cancer- related lymphedema (BCRL) patients and healthy controls. A secondary aim compared UE functionality based on lymphedema stage. The study included 50 women with unilateral BCRL and 50 healthy controls. UE functionality was assessed using the following measurement tools: the universal goniometer for range of motion (ROMs), digital inclinometer for proprioception, Semmes-Weinstein monofilament (SWM) test for light touch sensation, Upper Limb Functional Test (ULIFT) score for functionality and mobility, Disability of the Arm, Shoulder and Hand (DASH) for UE disability level, hand grip strength for peripheral muscle strength, and Upper Extremity Lymphedema Quality of Life questionnaire 27 (ULL-27) and Short Form 36-item Health Survey (SF-36) for quality of life (QoL). BCRL patients had reduced UE ROMs, UE functionality and mobility, hand grip strength, worse DASH score, impaired proprioception, light touch sensation and poorer quality of life compared to healthy controls (p<0.05). Significant between-group differences were detected in UE ROMs, ULIFT, DASH outcomes, proprioception, light touch sensation and physical and mental sub-scores of QoL assessments (p<0.05), while no significant differences were detected for hand grip strength, ULL-27 global score (p>0.05) according to lymphedema stage. Findings exhibited that patients with BCRL present with worse UE mobility, increased disability, loss of proprioception, impaired light touch sensation, and lower QoL compared to their healthy controls. UE functions and QoL may also vary between patients according to lymphedema severity.
This study assessed responsiveness of the Lymphedema Life Impact Scale (LLIS), Upper Limb Functional Index (ULFI), and Shoulder Pain and Disability Index (SPADI) instruments in patients with upper limb lymphedema undergoing complete decongestive therapy (CDT). The prospective cohort study was conducted from March 2024 to May 2025. Participants were patients with unilateral upper limb lymphedema secondary to breast cancer. All patients completed the LLIS, ULFI, and SPADI at baseline and again after 10 sessions of physiotherapy delivered over a 20-day period. Additionally, a 7-point Global Rating of Change scale (GRC) was administered as an external anchor. Paired t-tests or Wilcoxon tests were utilized to examine differences between pre- and post-intervention scores. A total of 110 patients were enrolled. The ULFI, LLIS, and SPADI demonstrated acceptable responsiveness, as indicated by an area under the curve (AUC) exceeding 0.70. Furthermore, the change scores for all three instruments exhibited strong correlations with patients' GRC scales, with Spearman correlation coefficients greater than 0.60. The results support the use of the LLIS, ULFI, and SPADI as reliable tools to monitor treatment outcomes in patients with upper limb lymphedema due to breast cancer.
Early detection of early-stage lymphedema resulting from breast cancer treatment enables prompt intervention and can potentially slow disease progression. To support this, various methods have been developed that use quantitative criteria sensitive to excess tissue fluid, which is a hallmark of lymphedema. One such method involves measuring the dielectric constant (TDC) of arm tissue in both the at-risk and contralateral arms to calculate their ratio. This communication aims to estimate what constitutes an interarm TDC ratio likely to serve as a threshold for arm lymphedema. Data from 403 healthy women were used to calculate the ratio of the highest to the lowest forearm TDC values (β). The distribution of β was analyzed, and estimated lymphedema thresholds were calculated as the mean β plus 2.0, 2.5, and 3.0 standard deviations, producing less and more conservative thresholds. Values ranged from approximately 1.15 to 1.20, with only 0.74% of cases exceed-ing a β value of 1.20. The β values were not affected by age, which ranged from 18 to 87, or body mass index, ranging from 14.7 to 49.9 kg/m². These data represent the most comprehensive reference values available to help physicians and therapists determine appropriate thresholds.
Bioimpedance analysis constitutes noninvasive, low-cost intervention for early diagnosis and evaluation of breast cancer-related lymphedema (BCRL). In this study, we investigated the frequency dependence of capacitance, a marker of disease progression, in patients with BRCL. Pseudo membrane capacitance of the affected and unaffected sides of upper limbs was calculated from reactance values obtained at 5, 50, and 250 kHz. At all frequencies, pseudo membrane capacitance differed significantly between affected and unaffected limbs, with the most pronounced difference observed at 5 kHz. The Weibull analysis of the 5 kHz data demonstrated linear distributions for both limbs, with high correlation coefficients (affected: r = 0.97; unaffected: r = 0.98). The shape parameter derived from the Weibull plot indicated that pseudo membrane capacitance on the unaffected side followed a Gaussian-like distribution (α = 3.90), whereas that on the affected side was characterized by a Rayleigh distribution (α = 2.04). These distributional differences suggest distinct underlying tissue characteristics between affected and unaffected limbs. These findings indicate that capacitance measured using commonly available bioimpedance devices can differentiate affected from unaffected limbs and may provide clinically relevant information for identifying early or subclinical lymphedema prior to the development of overt clinical edema.
This study evaluated the quality and readability of responses provided by ChatGPT and Gemini to frequently asked questions related to lymphedema. Ten frequently asked questions about lymphedema were selected by expert therapists for submission to ChatGPT and Gemini. The initial responses from ChatGPT and Gemini were recorded without follow-up queries. Five independent experts (therapists) specialized in this field evaluated responses from ChatGPT and Gemini using a four-point rating scale. Readability levels were analyzed using the Flesch-Kincaid Grade Level through WordCalc software. Results indicated that except for questions 3 and 6, ChatGPT and Gemini provided similar responses, with significant differences observed in those two questions (p = 0.014). ChatGPT's answers to questions 1, 2, 3, 4, 8, 9, and 10 were found to be more readable than Gemini's, while Gemini's answers to questions 5, 6, and 7 were more readable. Overall, approximately 70% of ChatGPT's responses were found to be easier to read compared to Gemini. The results of this study indicate that both AI search engines offer comparable responses to research questions. However, when evaluating clarity and accessibility of the answers, ChatGPT was found to be more understandable and user-friendly than Gemini.
Lymphovenous anastomosis (LVA) and stellate ganglion block (SGB) have been reported as effective treatments for breast cancer-related lymphedema (BCRL). However, no studies have evaluated the efficacy of ultrasound-guided SGB in patients undergoing LVA. This study aimed to assess whether adding SGB to LVA improves outcomes in BCRL patients. Thirty BCRL patients were randomly assigned to either the control (LVA only, n = 15) or SGB group (n = 15). The SGB group received ultrasound-guided SGBs at 2 days, 2 weeks, and 4 weeks postoperatively. Arm circumferences were measured at four points (5 cm and 10 cm above and below the elbow) at baseline and at 1-, 3-, and 6-months post-surgery. Treatment-related variables were also analyzed to identify potential predictors of success. Repeated-measures analysis of variance showed no significant differences in circumferential changes between groups over time, although a decreasing trend was observed within groups. However, significant reductions in circumferential differences compared with baseline were observed at several measurement sites in the SGB group. Logistic regression analysis revealed no significant predictors of treatment success. In conclusion, ultrasound-guided SGB performed postoperatively may enhance the therapeutic effect of LVA in BCRL, further reducing arm circumferential differences.
Prox-1 (prospero homeobox protein 1) is a master control gene for lymphatic vessel development and it has been widely used as a marker to detect lymphatic vessels inside and outside the eye. We herein report a novel finding of Prox-1 expression on the astrocytes of the optic nerve, a critical structure that conveys visual information from the retina to the brain. We identified that Prox-1 expressing cells were widely distributed inside the optic nerve. These cells co-expressed both GFAP (glial fibrillary acidic protein) and AQP4 (aquaporin-4) which are typical markers for astrocytes. Interestingly, some of the Prox-1+ cells ensheath CD31+ blood vessels inside the optic nerve and these cells are part of the glymphatic system utilized for ocular fluid circulation. This study not only reveals a novel expression pattern of Prox-1 in the optic nerve but also identifies a new marker for the glymphatic system in this critical structure. Further exploration on this novel phenomenon may re-veal new mechanisms and therapeutic targets for optic nerve-related diseases that affect many patients worldwide.
ISL CONSENSUS 2020 DOCUMENT UPDATE A discussion will take place at the next International Congress of Lymphology (September 2019) concerning updates to the ISL Consensus Document on the diagnosis and treatment of peripheral lymphedema. Please send any comments or suggestions for changes, deletions, additions, or clarifications to the Central Office for inclusion of items for discussion.
Lymphedema is a chronic and multifaceted condition characterized not only by abnormal lymphatic fluid accumulation but also by fibrosis, adipose tissue hypertrophy, impaired immune and skin barrier function, and tissue remodeling. Despite its complexity, clinical management typically focuses on physical interventions, often neglecting psychobiological aspects such as the placebo and nocebo effects. The placebo effect-mediated by positive expectations-activates pathways involving dopamine, endogenous opioids, and forebrain-limbic system interactions, while the nocebo effect-driven by negative expectations-amplifies symptoms via HPA axis activation and cortisol release. This Lymphspiration explores how contextual and emotional fac-tors, including communication, empathy, and even friendship, modulate these effects in lymphedema care. Emphasizing these factors could improve long-term adherence, symptom relief, and overall quality of life. A holistic framework that includes neurophysiological mechanisms, emotional support, and personalized care is essential for optimizing treatment outcomes in lymphedema.
This study aimed to determine the mini-mal clinically important differences (MCID) for the Lymphedema Quality of Life Questionnaire (LYMQOL) in breast cancer-related lymphedema (BCRL). LYMQOL was used to evaluate quality of life (QoL) with four do-mains: function, body image, symptoms, and mood. All patients received a standardized three-week program of combined complex de-congestive therapy. An anchored-based (response to a satisfaction question at post treatment) method was used to estimate MCIDs. The optimal cut-off points were calculated. The study included 67 patients with a mean age of 54.3±9.73 years and a BMI of 32.6±6.80 kg/m². Significant statistical improvements were observed in all domains of the LYMQOL after treatment, including function (p=0.001), body image (p=0.001), symptoms (p<0.001), and mood (p=0.012) with the overall QoL score increasing from 6.31±1.93 to 6.81±1.45 (p=0.004). The MCID values for LYMQOL were 0.31 for function, 0.5 for body image, 0.31 for symptoms, and 0.33 for mood, with corresponding MCID change percentages of 10.33%, 16.66%,10.33%, and 11%, respectively. This study's MCID values for QoL provide valuable insights to enhance clinical decision- making and improve patient outcomes in BCRL.
Editorial- Botulism, Botulinus Toxin, Byheart Baby Formula: Life-Saving Thoracic Duct Lymph Drainage?
Tyrosine kinase inhibitors (TKIs) are widely used in oncology and hematology. While chylous pleural and pericardial effusion have been described, peripheral lymphedema with administration of acalabrutinib has not been documented. Clinical and imaging data were retrospectively collected from the medical record of an 80-year-old patient with a prior history of radical prostatectomy and pelvic lymphadenectomy who was treated with acalabrutinib for chronic lymphocytic leukemia (CLL). A Medline review (from data-base creation to October 2025) and pharmaco-vigilance database searches were conducted to identify TKI-related lymphatic complications. The patient developed progressive peno-scrotal lymphedema after acalabrutinib initiation. Cardiac and venous evaluations were normal. MR-lymphography showed patent central lymphatic pathways and superficial peno-scrotal edema. Dynamic lymphangiography revealed no obstruction or leak, suggesting functional impairment of lymphatic drainage. Literature review identified 28 relevant articles, including 20 cases of chylothorax, mainly under dasatinib, and additional cases of chylous ascites and chylopericardium. To our knowledge, no previous case of TKI-induced lymphedema has been published. Pharmacovigilance databases identified few lymphatic adverse events, including 24 cases of lymphedema in the FAERS database. This first report of TKI-induced lymphedema broadens the spectrum of lymphatic complications associated with these agents and high-lights the potential concept of functional rather than obstructive lymphatic impairment.
In the field of interventional radiology, transvascular routes of access to adjacent structures have led to shorter procedure times and fewer complications. No transvenous approach to intervene on the lymphatic ducts currently exists, nor do any standard measurements of the inferior vena cava (IVC) and cisterna chyli (CC). This retrospective review of cross-sectional imaging studies consisted of 150 adults (age 57±17.8) who obtained a magnetic resonance pancreatography (MRCP) for a variety of clinical indications. Of those, 8 patients had poor image quality and 28 did not have an identifiable CC. The remaining 114 images were evaluated for size, caliber, and orientation of anatomic structures of interest using a PACS workstation. The average distance between the center of the IVC to the center of the CC was found to be 24.3 mm (11.1-50.5 mm). The angle relative to anterior-posterior as determined by the spine ranged from 21.0° anterior to 103.0° posterior. Important intervening structures included the renal artery (19.30%), liver (7.02%), and aorta (4.39%). The short spatial approximation of the IVC and CC and the rarity of intervening structures support further development of transvascular CC access techniques.
Lymphedema is a chronic inflammatory disease caused by defective lymphatic system function or development that proceeds in ab-normal fluid drainage and edema of the peripheral tissues. This retrospective study evaluates the potential role of transcription factors in the development of primary lymphedema. We analyzed 408 Italian primary lymphedema patients for pathogenic variants in genes related to the transcription factor network. Eighteen likely pathogenic genetic variants were identified in 5 genes - FOXC1, FOXC2, NOTCH1, RORC, and SOX18 - most of which have not been previously reported in the literature. Although majority of these genetic variants resulted in premature termination of the proteins, a single missense variant was identified in FOXC2 and analyzed in this study using molecular modeling approaches to evaluate its structural changes. These results suggested possible deleterious effects of the analyzed variant and supported its potential pathogenicity. Our findings provide additional evidence that associates variants in transcription factors to the onset of lymphedema and support the addition of the candidate genes FOXC1, NOTCH1, and RORC in primary lymphedema diagnostic practice.
The Ketogenic Diet (KD) is currently the most widely studied nutritional approach for patients with lipedema, although its use may cause important drawbacks especially in case of comorbidities. A Modified Mediterranean Diet (MMed) is more easily adaptable, better tolerated, and can be temporarily replaced by a ketogenic diet for a short period of time if necessary using a sort of "sandwich" approach. We report 10 clinical cases with lipedema and comorbidities subjected to a hypocaloric MMed for 6 months. All patients were properly assessed by anthropometric measurements and body composition before and at the end of nutritional treatment. Only 2 patients needed a short period of KD due to poor response to MMed. At the end of 6-month follow-up, patients showed weight loss with reduction in body circumferences and improvement in body composition. In the two cases where it was necessary to resort to a period of KD, good results were achieved allowing a return to the MMed for the maintenance. In patients suffering from lipedema with associated comorbidities and concomitant pharmacological treatments, the use of MMed as first line treatment allows achievement of better metabolic balance, greater compliance, and improved body composition.
This study explored differences in morphology and distribution of myocardial lymphatic drainage ducts in patients with dilated cardiomyopathy (DCM), ischemic cardiomyopathy (ICM), and hypertrophic cardiomyopathy (HCM) in end-stage heart failure to reveal the relationship between the morphological distribution characteristics of myocardial lymphatic drainage ducts and different etiologies and these disease courses. Hearts of 24 patients (transplant recipients) who underwent heart transplantation and 1 normal heart were collected. Myocardial tissue from the anterior wall of the ventricle was taken and quickly frozen. Immunohistochemical and Western blotting techniques were used to detect the expression of LYVE-1, Podoplanin, and VEGFR-3 in cardiac tissue. Ink injection, immunohistochemical staining, and immunofluorescence double labeling techniques were used to detect the co-localization of three antibodies in hu-man heart tissue. Masson staining was used to observe the distribution and content of collagen fibers in the heart tissue of transplant recipients. Compared with the normal group, expression levels of LYVE-1 (p<0.05) and VEGFR-3 (p<0.001) in the DCM group were significantly increased. Expression level of LYVE-1 (p<0.05) was significantly increased in the ICM and HCM groups, but there was no significant change in the expression level of VEGFR-3. The expression level of Podoplanin in the normal group was higher than that in the heart failure groups, but the protein ex-pression results were the opposite. The expression levels of LYVE-1 and VEGFR-3 in the DCM and ICM groups showed an increasing trend with the progression of the disease, while the expression levels of Podoplanin showed a decreasing trend. The immunofluorescence results showed that on larger lymphatic vessels, LYVE-1 and VEGFR-3 were expressed on the inner side of the lymphatic lumen, while Podoplanin was expressed on the outer side, and there was co-localization between the two layers. Masson's staining results showed that the degree of myocardial fibrosis in the DCM group (p<0.01) and HCM group (p<0.001) increased, while there was no significant change in the ICM group (p<0.05). Positive expression intensity of LYVE-1, Podoplanin, and VEGFR-3 does not have a consistent quantitative relationship with different types of heart failure and the duration of the disease. The expression of three biomarkers confirms that DCM, ICM, and HCM have increased lymphatic vessel architecture compared to normal hearts, and the number of lymphatic vessels increases with prolongation of disease course.
Lymphedema is a chronic, progressive impairment of the lymphatic system that can impact activities and quality of life. Research regarding conservative management of lymphedema primarily consists of complete decongestive therapy (CDT) and compression devices intended to promote lymphatic and venous return. Advanced pneumatic compression devices (APCDs) contain multiple programmable sleeves designed to mimic manual lymph drainage at home. This study aims to determine the effectiveness of APCDs in the treatment of lymphedema through the completion of a systematic review and meta-analysis. A systematic search of five databases was conducted, spanning the years 2010-2021. Only experimental designs of moderate or strong quality were chosen and final review set consists of twelve articles. APCDs are found to be effective for lymphedema treatment based on differences in pre- and post-intervention limb volumes and patient-reported outcomes. Two meta-analyses evaluated the impact of APCDs on both rates of cellulitis and manual therapy. Both analyses demonstrated significant decreases in rates after the APCD interventions. The data showed consistent reduction of limb volume and improved patient-reported outcomes, indicating that APCDs are generally effective as a complementary intervention to CDT in the maintenance phase of lymphedema treatment.
