Lymphedema Research Articles

Breast Cancer-Related Lymphedema: The Primary/Secondary Conundrum

Lymphatic Research and BiologyVol. 21, No. 2 EditorialFree AccessBreast Cancer-Related Lymphedema: The Primary/Secondary ConundrumStanley G. RocksonStanley G. RocksonEditor-in-Chief, Stanford University School of Medicine, Stanford, California, USA.Search for more papers by this authorPublished Online:20 Apr 2023https://doi.org/10.1089/lrb.2023.29141.editorialAboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail For quite some time, within the pages of this journal1–3 and elsewhere,4,5 there has been a persistent theory that there might be systemic and other predispositions to the secondary (or acquired) lymphedema that is encountered frequently as a sequela of breast cancer therapeutics. In addition, it has recently been observed that the presence of a lymphatic disorder such as breast cancer-associated lymphedema can alter the patterns of associated systemic disease expression that exist as comorbidities.6 These phenomena help to blur the distinction between “primary” and “secondary” lymphedema.In the current issue of Lymphatic Research and Biology, we provide three additional sets of original observations that help to expand insights into this hypothesis.In the first of these, Kim and colleagues have explored rates of incidental subclinical lymphedema in the contralateral arm of patients with unilateral postsurgical secondary upper extremity lymphedema. In their study, magnetic resonance imaging of the upper extremities was utilized to examine patients with unilateral upper extremity clinical lymphedema. Axial STIR MR images of the symptomatic and contralateral arms were retrospectively reviewed and edema severity was graded by the investigators. In these 78 examined subjects, contralateral abnormalities were detected in 14.1%. Although the direct conclusion was to emphasize the importance of evaluation of the contralateral limb, the interpretation, by extension, is that there is a disturbance in lymphatic anatomy or function that extends beyond the direct lymphatic trauma of cancer therapeutics.The second investigation, by Furlan and colleagues, examines the phenomenon of blood flow abnormalities in the limb that precede the development of overt lymphedema. In a cohort of 200 subjects, Doppler ultrasound was utilized to examine the axillary and brachial arteries. In these patients, there was detection of higher mean flow velocity and end-diastolic velocity as early as 1 month after surgery. The end-diastolic velocity demonstrated a 73.7% sensitivity and 71.2% specificity as a predictor of long-term lymphedema, with a negative predictive value of 57.6%.The third of these three new investigations proposed a pilot investigation of abdominal fat ratio in subjects with breast cancer-related lymphedema. Here, Nakipoğlu and colleagues investigated the impact of central obesity to the occurrence of this lymphedema presentation. They investigated cohorts of postsurgical subjects with a matched control cohort that differed only in the distribution of BMI. The abdominal circumference measurement demonstrated a modest predictive utility, with a predictive specificity of 89%.In aggregate, these three newly published investigations continue to tantalize us with the increasingly tenable hypothesis that the appearance of acquired lymphedema (in this case following breast cancer therapies) may, and likely does, depend upon systemic factors that predict the likelihood of disease evolution. Continued exploration of these phenomena will, ideally, result in enhanced risk factor stratification, diagnostic evaluation, and, with good fortune, improved risk factor reduction strategies.

Primary angiosarcoma of the breast: a case report

Background: Angiosarcoma of the breast is a rare form of breast malignancy. Primary breast angiosarcoma occurs sporadically primarily in young women while secondary breast angiosarcoma most frequently develops in older patients with prior history of radiation therapy or chronic lymphedema. This aggressive malignant tumor of the vascular endothelium has a high risk of local recurrence and distant metastasis and the diagnosis carries a poor prognosis.

Phospholipase A2 (PLA2) injured lymphatic endothelial cells leading to progression of secondary lymphoedema

ABSTRACT Secondary lymphoedema is one of the common complications after lymph node dissection for gynecologic malignancies and breast cancer. In this study, the relationship between PLA2 and postoperative lymphoedema in cancer at the molecular level has been explored through transcriptomics and metabolomic assays. Transcriptome sequencing technology, as well as metabolomic assays, were utilized to explore the expression of PLA2 in lymphoedema patients, and search for potential pathways in the pathogenesis and exacerbation mechanism of lymphoedema. The effect of sPLA2 on human lymphatic endothelial cells was investigated by culturing human lymphatic endothelial cells. Secretory phospholipases A2 (sPLA2) showed high expression levels in lymphoedema tissues, however, cytoplasmic phospholipases A2 (cPLA2), showed low expression in lymphoedema, as demonstrated by RT-qPCR. By culturing human lymphatic vascular endothelial cells, the study found that sPLA2 causes HLEC vacuolization and has an inhibitory effect on HLEC proliferation and migration. By detecting sPLA2 in the serum of lymphoedema patients and analyzing clinical data, it was found that sPLA2 was positively correlated with the severity of lymphoedema. Secretory Phospholipase A2 (sPLA2) is highly expressed in lymphoedema tissue, damages lymphatic vessel endothelial cells, is strongly associated with disease severity, and can be used as a potential predictor of disease severity. Abbreviations: PLA2: Phospholipase A2; DEGs: differentially expressed genes; DMP: differential metabolic production

The Prevalence of the Axillo-Inguinal Lymphatic Pathway in Lymphedema of the Extremities and Potential Therapeutic Implications.

Background: The axillo-inguinal (or inguino-axillary) is a compensatory lymphatic drainage pathway regularly utilized by lymphedema therapists when applying manual lymphatic drainage (MLD) for upper and lower extremity lymphedema. However, there is limited evidence of the frequency of this pathway and the characteristics of patients with lymphedema in which this pathway is present. Indocyanine green (ICG) lymphography is an imaging technique that has the capability to identify lymphatic drainage pathways in lymphedema when combined with MLD. In this study, we used ICG lymphography in patients with upper and lower extremity lymphedema to investigate the presence of this pathway and its clinical characteristics. Methods and Results: A retrospective cohort audit of 563 patients with lymphedema (285 with upper extremity and 278 with lower extremity) who underwent ICG lymphography was conducted in combination with MLD. Compensatory lymphatic drainage was investigated. Patients demonstrating the axillo-inguinal pathway were identified, and their clinical characteristics were recorded. The axillo-inguinal pathway was not demonstrated in any patient with upper extremity and only five patients with lower extremity lymphedema. Of these five patients, all were female with a history of secondary cancer-related lymphedema following gynecological cancer. The majority (four) had bilateral lymphedema extending to the lower abdomen and presented with a greater severity of lymphedema. Conclusions: These findings suggest that the axillo-inguinal pathway is an infrequent compensatory drainage pathway in lower extremity lymphedema and rare in upper extremity lymphedema. Our findings have clinical implications for lymphedema management, in particular, the sequence in which MLD is applied.

Early Detection of Breast Cancer-Related Lymphedema: Accuracy of Indocyanine Green Lymphography Compared with Bioimpedance Spectroscopy and Subclinical Lymphedema Symptoms.

Introduction: The reported incidences of breast cancer-related lymphedema (LE) affecting the arms vary greatly. Reason for this variability includes different diagnostic techniques used across studies. In the current study, we compared the accuracy of indocyanine green lymphography (ICG_L) and bioimpedance spectroscopy (BIS) in detecting LE before presentation of clinical signs. Methods and Results: Patients with no initial detectable signs of clinical LE of their arms after axillary lymph node dissection or removal of >5 lymph nodes on sentinel lymph node biopsy were included. Subclinical LE was defined as BIS values outside the normal range [(≥7 units (or >10 units)] or a 7-unit (or 10 unit) change between two measurements. We tracked ICG_L and BIS measurements for 133 potentially affected arms (n = 123). ICG_L detected signs of lymphatic flow disruption in 63 arms (47%). Based on the BIS value of 7 units, 60 arms (45%) had values outside the normal range. When using ICG_L-identified LE cases as true positives, BIS had a 54% accuracy (area under the curve [AUC] = 0.54) in detecting LE. Accuracy was 61% for subclinical LE symptoms when compared with ICG_L (AUC = 0.62). Both BIS and subclinical LE symptoms had <0.70 AUC-receiver characteristic operator curve, suggesting that BIS and development of subclinical LE symptoms are not adequate for identifying patients with subclinical LE. Conclusion: ICG_L is a reliable diagnostic tool for detecting early signs of lymphatic flow disruption in subclinical LE. Utilizing ICG_L to diagnose subclinical LE followed by a personalized treatment plan may provide patients the best chance of preventing disease progression.

Prevalence of Chronic Progressive Lymphedema in the Rhenish German Draught Horse

Chronic progressive lymphedema (CPL) is a common disease in Rhenisch German draught horses. The objective of our study was to evaluate the prevalence of this disease and its progression with age in 493 Rhenish German draught horses from different regions in Germany. We employed generalized linear models with binomial, multinomial, and normal distributions to analyse the effects of breeding association, coat colour, sex and age within sex, time of examination, limb on which CPL was recorded, and farm-related factors on disease scores. The occurrence and severity of CPL were significantly influenced by breeding area, sex, coat colour, and interaction of age by sex. Males had significantly higher CPL-scores than geldings (1.92-fold) and females (5.02-fold) as well as a faster (1.85-fold) disease progression per year of life than females (1.44-fold) and geldings (1.25-fold). Regression on age within sex was still significant when age was restricted to a minimum of 7 years in the analysis. Bay horses exhibited 1.77-fold and 2.19-fold higher CPL-scores than chestnut and black horses. Keeping horses on pasture and keeping bedding clean reduced CPL-scores, whereas feeding of hay silage and concentrates during winter increased CPL-scores. Our analysis revealed significant regression coefficients of cannon bone circumference on CPL-scores. Relationships with hoof measures and skinfold diameter at the neck were not found. In conclusion, differences among breeding districts and sexes by age had the largest impact on CPL prevalence and scores. Disease progression was evident up to a mean age of 16 years in males and 20 years in females. The identification of risk factors and their effects on CPL should help to reduce the occurrence and progression of CPL.

Extracellular vesicles from adipose-derived stem cells relieve extremity lymphedema in mouse models.

Transplantation of adipose-derived mesenchymal stem cells (ADSCs) has been reported to improve the severity of chronic lymphedema. Extracellular vesicles (EVs) derived from mesenchymal stem cells have been reported to exert effects such as the promotion of angiogenesis, suppression of inflammation, and regeneration of damaged organs. In this study, we showed that lymphangiogenesis was induced by EVs derived from ADSCs and revealed the therapeutic potential of these EVs for the treatment of lymphedema. We examined in vitro effects of ADSC-EVs to lymphatic endothelial cells (LECs). Next, we conducted in vivo analysis of ADSC-EVs to mouse lymphedema models. Furthermore, Bioinformatics analysis was also performed to evaluate the implications of the altered miRNA expression. We showed that ADSC-EVs promoted the proliferation, migration, and tube formation of LECs, and the gene expression of lymphatic markers was elevated in the ADSC-EV-treated group. Notably, a mouse lymphedema model revealed that legs treated with ADSC-EVs had markedly improved edema with increased numbers of capillary vessels and lymphatic channels. Bioinformatics analysis revealed that ADSC-EV-associated microRNAs, such as miR-199a-3p, miR-145-5p, miR-143-3p, miR-377-3p, miR-100-3p, miR-29a-3p, miR-495-3p, and miR-29c-3p, targeted MDM2, which contributed to the stability of HIF1 and resulted in angiogenesis and lymphangiogenesis in LECs. The present study showed lymphangiogenic effects of ADSC-EVs, which will lead to new treatment options for chronic lymphedema. Cell-free therapy with EVs has fewer potential risks, such as poor engraftment efficiency and potential tumor formation, than stem cell transplantation and could be a promising tool for patients suffering from lymphedema.

Current concepts of lymphedema treatment for the breast cancer patient: a clinical practice review

: Lymphedema is a progressive disease caused by insufficient lymphatic drainage leading to abnormal accumulation of interstitial fluid within soft tissues. The most common cause for secondary lymphedema in the developed world is treatment for breast cancer. In the past, almost a forgotten disease, frequently overlooked, nowadays we can provide patients with treatment and relief. We discuss the current approach to lymphedema treatment for the breast cancer patient from clinical diagnosis through different imaging modalities with their advantages and disadvantages. Possible conservative and operational treatments aimed to restore lymphatic function and reduce adipose hypertrophy are described. From reductive techniques such as resection or liposuction to physiologic techniques involving reconstructive microsurgery such as lymphatico-venous anastomosis (LVA), vascularized lymph node transfer (VLNT) and other lymphatic free flaps. A review of our constructed approach and guidelines for managing secondary lymphedema in the breast cancer patient from 2005 to present days is presented. It is based on our growing experience and evolving techniques. Management of lymphedema in the breast cancer patient is multi-disciplinary and involves both the general and plastic surgeons, oncologists, physical therapists, social workers and many more. A holistic approach to the patient is advocated. This is best performed by adjusting and tailoring the appropriate treatment for each patient.

Abstract P5-08-09: Does Breast Inflammation Contribute to Lymphedema Risk in Patients Treated with Axillary Lymph Node Dissection?

Abstract Background Chronic inflammatory responses initiated by lymphatic injury play a key role in the pathophysiology of secondary lymphedema. However, it is unclear if baseline inflammation or ethnic/racial variability in inflammatory responses increase lymphedema risk. Crown-like structures of the breast (CLS-B), consisting of macrophages engulfing necrotic adipocytes, are a marker of systemic inflammation and have been implicated in the pathogenesis of breast cancer, but their role in lymphedema development is unknown. Here we determine whether baseline differences in inflammation, characterized by the presence of CLS-B, contributed to lymphedema risk in a diverse cohort of patients treated with ALND. Methods Patients ≥ 18 years undergoing ALND were enrolled in a prospective lymphedema screening study. Body mass index (BMI) and volumetric arm measurements (perometer) were performed at baseline, postoperatively, and every 6 months. Breast tissue obtained at definitive surgery was assessed for CLS-B with CD-68 IHC stain in non-tumor breast tissue. Inflammation severity was determined by number of CLS-B/cm2, with the median used to differentiate between mild and severe inflammation. Lymphedema was defined as a relative arm volume change of ≥10%. Lymphedema incidence was assessed using competing risk analysis and compared between patients with and without CLS-B. Uni- and multivariable analysis was performed to identify factors associated with lymphedema development. Results Between 11/2016-03/2020, 304 ALND patients were enrolled; 281 had at least 6 months of follow-up and were included in the study. Eleven percent self-identified as Asian, 20% Black, 6% Hispanic, and 60% White. Median age was 48 years; median BMI was 26.3 kg/m2, with higher BMI observed in Black and Hispanic women compared to Asian and White women (p &amp;lt; 0.001). Overall, 54% had CLS-B, with severe inflammation (&amp;gt; 0.4 CLS-B/cm2) identified in 71 (25%) patients. CLS-B presence correlated with BMI (36% [BMI &amp;lt; 25], 63% [BMI 25-30], 70% [BMI &amp;gt; 30], p &amp;lt; 0.001) and varied across racial/ethnic groups, with a higher prevalence in Black and Hispanic women (68% [Black], 69% [Hispanic] vs 59% [Asian], 46% [White], p = 0.03) (Table). Inflammation severity did not differ by race/ethnicity (p = 0.11). At 2.1 years median follow-up (IQR 1.6-3.1), 66 women developed lymphedema, with a 2-year lymphedema rate of 21.3% (95% CI 16.4-26.8). Lymphedema incidence was higher among Black and Hispanic women, compared to Asian and White women (2-year rate: 33.8% [Black], 31% [Hispanic], 17.4% [Asian], 18.2% [White], p = 0.002), and was higher among women with CLS-B (2-year rate: 28.2% [CLS-B] vs 12.9% [no CLS-B], p = 0.02). On multivariable analysis, Black race (White [referent]: HR 2.85, 95% CI 1.4-5.8; p = 0.03), receipt of NAC (upfront surgery [referent]: HR 2.46, 95% CI 1.04-5.8, p = 0.04) and older age (HR 1.03, 95% CI 1.01-1.06 per 1-year increase; p = 0.009) were independently associated with lymphedema development, while CLS-B was not (HR 1.37, 95% CI 0.81-2.34, p = 0.2). Conclusions In a prospective cohort of patients treated with ALND, Black race, receipt of NAC, and increasing age, but not CLS-B, were independently associated with lymphedema risk. However, the higher CLS-B prevalence in Black women suggests that they may have a propensity for increased inflammation, which may in part be contributing to the higher lymphedema risk observed, but is likely not the only inflammatory mechanism that modulates risk. Table. Clinical characteristics of study cohort stratified by the presence of CLS-B Citation Format: Andrea V. Barrio, Giacomo Montagna, Varadan Sevilimedu, Ethan Gomez, Dilip Giri, Babak Mehrara, Monica Morrow. Does Breast Inflammation Contribute to Lymphedema Risk in Patients Treated with Axillary Lymph Node Dissection? [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-08-09.

Skin lesions on a man's face and scalp

An 87-year-old male patient was admitted to our Clinic for diagnostic evaluation and treatment of extensive, confluent erythematous-livid areas that affected almost the entire skin of his face, scalp, and neck Figure (1). The patient also showed left eyelid ectropion and a palpable subcutaneous, painless nodule in the left mandibular region the size of an apple that bled easily. The patient had been treated for undiagnosed erythematous papules on his left cheek 2 years before and reported that his condition had dramatically worsened over the last few weeks. The patient was otherwise healthy and was only being treated for hypertension and hyperlipemia. Multiple computed tomography (CT) scans were performed which showed an extensive disease affecting the skin and subcutaneous tissue of almost the entire face, scalp and neck, with occasional involvement of muscle tissue as well. Numerous secondarily altered lymph nodes of the neck and multiple tumour infiltrates in the liver were also seen. A skin biopsy from the scalp was performed Figure (2). Histopathology showed a tumoral lesion composed of irregular, anastomosing vascular spaces and an increased number of surrounding endothelial cells with hyperchromatic, atypical nuclei. The clinical and pathological features corresponded to a typical presentation of angiosarcoma (AS). The patient had an inoperable disseminated disease and palliative chemotherapy with paclitaxel was initiated. After three cycles of therapy, the patient's general condition worsened, and was admitted to a palliative care facility. cAS is a rare vascular malignant tumour that has a high risk of both local and distant metastatic dissemination despite aggressive therapy. It is classified into primary AS that occurs sporadically, usually in the scalp or face, and secondary AS that is most often related to a history of radiation treatment and chronic lymphedema.1 This malignant tumour resembles a “spreading bruise” that varies from blue to red in colour. The diagnosis of cAS is often delayed due to its subtle initial clinical appearance as it is often mistaken for an ecchymosis or haematoma, especially in elderly patients on anticoagulants. Most patients are asymptomatic although some may present with bleeding, oedema, and/or ulceration. Diagnosis is based on clinical examination and histopathological and immunohistochemical analysis. The extent of the disease may be assessed with magnetic resonance imaging or CT.1, 2 AS represents less than 0.1% of all head and neck malignancies but is associated with the highest rate of lymphatic dissemination among all head and neck soft tissue sarcomas.3, 4 AS shows aggressive behaviour and carries a poor prognosis, thus early diagnosis is crucial. The optimal treatment is surgery followed by wide-field radiotherapy. Clear surgical margins are of paramount importance and correlate with better outcome, but the disease is often so extensive at the time of diagnosis that it is not possible to excise.5, 6 Despite inconsistent data regarding chemotherapy, this is usually employed for patients with metastatic or inoperable disease. Doxorubicin-based regimens are most recommended, but recent use of paclitaxel has shown better efficacy compared with doxorubicin.6, 7 Though involvement of the face and scalp is common in cAS, the extent of disease in our case was striking. AS should be considered in the differential diagnosis of violaceous or ecchymotic lesions on the head or scalp in the elderly. All authors contributed to the manuscript conception, design, and writing. All authors read and approved the final manuscript. The authors have not declared a specific grant from any funding agency in the public, commercial or not-for-profit sectors. The authors declare no conflict of interest. This article did not require the approval of the Ethics committee. The patient in this manuscript has given written informed consent to the publication of his case details. Due to privacy and ethical concerns, neither the data nor the source of the data can be made available.

Fluid Distribution Patterns in Early-Stage Upper Extremity Lymphedema.

Magnetic resonance imaging (MRI) stage 1 (early stage) upper extremity lymphedema is characterized by fluid infiltration in the subcutaneous tissues that does not exceed 50% of the extremity circumference at any level. The spatial fluid distribution in these cases has not been detailed and may be important to help determine the presence and location of compensatory lymphatic channels. The aim of this study is to determine whether there was a pattern of distribution of fluid infiltration in patients with early-stage lymphedema that could correspond to known lymphatic pathways in the upper extremity. A retrospective review identified all patients with MRI stage 1 upper extremity lymphedema who were evaluated at a single lymphatic center. Using a standardized scoring system, a radiologist graded the severity of fluid infiltration at 18 anatomical locations. A cumulative spatial histogram was then created to map out regions where fluid accumulation occurred most and least frequently. Eleven patients with MRI stage 1 upper extremity lymphedema were identified between January 2017 and January 2022. The mean age was 58 years and the mean BMI was 30 m/kg2. One patient had primary lymphedema and the remaining 10 had secondary lymphedema. The forearm was affected in nine cases, and fluid infiltration was predominantly concentrated along the ulnar aspect, followed by the volar aspect, while the radial aspect was completely spared. Within the upper arm, fluid was primarily concentrated distally and posteriorly, and occasionally medially. In patients with early-stage lymphedema, fluid infiltration is concentrated along the ulnar forearm and the posterior distal upper arm, which aligns with the tricipital lymphatic pathway. There is also sparing of fluid accumulation along the radial forearm in these patients, suggesting a more robust lymphatic drainage along this region, possibly due to a connection to the lateral upper arm pathway.

Lymphoscintigraphic Indications in the Diagnosis, Management and Prevention of Secondary Lymphedema

Secondary lymphedema is caused by damage to the lymphatic system, often following an oncological tumor removal intervention, or even by an accident. The diagnosis of lymphedema is not easy, because the disease can also be confused with other clinical manifestations (for example, venous insufficiency edema), though an experienced Lymphologist is usually able to diagnose it with good accuracy. To confirm the diagnosis, it is often necessary to resort to specialist imaging tests for an anatomo-functional definition of the pathology. Among these, lymphoscintigraphy is confirmed as the “gold standard” procedure for the diagnosis of lymphedema. Lymphoscintigraphy has been included in the Italian Guidelines by the Ministry of Health.

Single-Stage Free Flap Reconstruction Following Extremity Sarcoma Resection: a Regional Cancer Center Experience.

Surgery remains mainstay modality of treatment of STS of extremity. In majority of patients, primary closure is possible following surgical resection of the tumor. Primary closure of wound may not be feasible in tumors with large area of skin involvement and sometimes following a whoopsprocedure. We analyzed postoperative complications and oncological outcomes in patients who underwent free flap reconstruction. Thirty-seven patients who required a free flap for reconstruction of the defect following resection of the STS were included in the study. There were 26 men and 11 women with a mean age of 40years. Seventy-three percent tumors were in lower limb; 62% patients had undergone a whoops procedure elsewhere. Flaps were fasciocutaneous in 19, myocutaneous in 15, and free muscle transfers in 3 patients. Seventeen patients had early surgical site complications. Nine patients had early flap failures. Of the 9, 6 patients had total loss of flap and in 3 the flaps were salvaged. Two patients had partial loss (< 50% of total area) of flap. Four patients had edge necrosis and two had suture diastasis. Nine patients had late surgical site complications. Four had post-radiotherapy wound dehiscence. Late SSI was noted in two. Late joint contracture and chronic lymphedema was seen in one patient each. One died due to sepsis. Statistically significant association was not found between patient, tumor or treatment-related factors and complications or flap failures. Mean duration of surgery was 7.73h. Twenty-three patients required multiple surgeries due to complications. Mean time to initiate adjuvant therapy from the date of surgery was 47days. Mean OS of the group was 67 ± 7.3months. Mean RFS was 58 ± 7.8months. Single-stage free flap reconstruction following surgical resection of extremity sarcoma is a viable option of reconstruction while salvaging the limb. Though associated with high rate of early surgical site complications, they are manageable.

The efficacy of stenting in the iliofemoral vein of patients with venous obstruction and secondary lymphedema from malignancy

ObjectiveTo investigate the safety and effectiveness of venous stenting in patients with chronic iliofemoral venous obstruction and secondary lymphedema from malignancy. MethodsFrom July 2012 to December 2020, patients with iliofemoral venous obstruction and secondary lymphedema who underwent venous stenting in our institution were reviewed retrospectively. Clinical characteristics, surgical complications, and symptom relief were assessed. Stent patency was evaluated with duplex ultrasound or computed tomographic venography. Twelve-month outcomes were reported. ResultsFifty-three patients with concurrent secondary lymphedema who had stents placed for iliofemoral venous obstruction were included. There were 42 females, and the mean age was 56.9 years. Nonthrombotic iliac vein lesions were identified in 16 patients (30.1%). Immediate technical success was 100%, with an average of two stents implanted. The median Villalta score, and Chronic Venous Disease Quality of Life quality of life questionnaire scores decreased from 12 (IQR, 10-15) and 58 (IQR, 50-66) at baseline, respectively, to 5 (interquartile range [IQR], 4-6) and 28 (IQR, 22-45) at 12 months after the procedure (P < .05), showing significant improvement in the quality of life. At the end of a median follow-up of 12 months (range, 3-25 months), the cumulative primary, assisted primary, and secondary patency rates were 70.8%, 76.9%, and 90.1%, respectively. ConclusionsIn patients with secondary lymphedema from malignancy, venous stent placement is safe and effective for iliofemoral venous obstruction.

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.

Skincare for chronic oedema and lymphoedema patients

British Journal of Community NursingVol. 28, No. 2 ProfessionalSkincare for chronic oedema and lymphoedema patientsSarah Jane PalmerSarah Jane PalmerE-mail Address: [email protected]Registered nurse and freelance writer, based at the Department of Work and Pensions as a disability analystSearch for more papers by this authorSarah Jane PalmerPublished Online:3 Feb 2023https://doi.org/10.12968/bjcn.2023.28.2.84AboutSectionsView articleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareShare onFacebookTwitterLinked InEmail View article References Fife CE, Farrow W, Hebert AA, Armer NC, Stewart BR, Cormier JN, Armer JM. Skin and Wound Care in Lymphedema Patients: A Taxonomy, Primer, and Literature Review. Adv Skin Wound Care. 2017; 30(7):305-318. https://doi.org/10.1097/01.asw.0000520501.23702.82 Crossref, Medline, Google ScholarLymphodema Scotland. Management of chronic oedema and lymphoedema. 2020. https://www.lymphoedema-scotland.org/community-nurses/management-of-chronic-oedema/ (accessed 9 February 2022) Google ScholarMarie Curie. Fluid build-up: oedema, lymphoedema and ascites. 2021. https://www.mariecurie.org.uk/professionals/palliative-care-knowledge-zone/symptom-control/lymphoedema#cellulitis (accessed 9 February 2022) Google ScholarThe British Medical Journal. Best practice lymphoedema. 2022. https://bestpractice.bmj.com/topics/en-gb/610#:~:text=Summary,disruption%20of%20the%20lymphatic%20system (accessed 9 February 2022) Google Scholar FiguresReferencesRelatedDetails 2 February 2023Volume 28Issue 2ISSN (print): 1462-4753ISSN (online): 2052-2215 Metrics History Published online 3 February 2023 Published in print 2 February 2023 Information© MA Healthcare LimitedPDF download

Comparison of Lymphatic Drainage of the Lower Limbs After Soft Tissue Reconstruction by Microvascular Muscle Flap Versus Fasciocutaneous Flaps.

Complex traumatic injuries of the lower limb are increasingly being salvaged. The common long-term morbidity includes secondary lymphedema. The role of microvascular flaps is often discussed for lymph flow restoration. However, the differential effect of using muscle flap versus fasciocutaneous flap in the lower-limb trauma to avoid secondary lymphedema is not studied. Forty patients who underwent microvascular flap reconstruction were reviewed retrospectively to obtain data regarding clinical demographics and surgical procedure. Assessment for presence of clinical lymphedema was done. The lymphatic drainage in all these patients was assessed by 99mTc lymphoscintigraphy. Of the 40 patients included in the study, group A (n = 23) underwent muscle-based free flap reconstruction, and group B (n = 17) had fasciocutaneous flaps. Clinical lymphedema was present in 21 patients, of which 18 were of group A and 3 of group B. On lymphoscintigraphy, 14 patients had either partial or complete obstruction in the reconstructed lower limb, 11 in group A and 3 in group B. All of them (n = 14) were found to have associated clinical lymphedema. The association of clinical lymphedema (P < 0.001) and obstructive pattern on lymphoscintigraphy (P < 0.05) with muscle flaps was found to be statistically significant. With the advancement in surgery and techniques, not only salvageability but also stable and morbidity free outcomes are the goals. Fasciocutaneous flaps may have better lymphatic outcomes than the muscle-based flaps, and the criteria for lower-limb reconstruction can be reformed to include simultaneous soft tissue and lymphatic reconstruction.

Topical captopril: a promising treatment for secondary lymphedema

Transforming growth factor-beta 1 (TGF-β1)-mediated tissue fibrosis is an important regulator of lymphatic dysfunction in secondary lymphedema. However, TGF-β1 targeting can cause toxicity and autoimmune complications, limiting clinical utility. Angiotensin II (Ang II) modulates intracellular TGF-β1 signaling, and inhibition of Ang II production using angiotensin-converting enzyme (ACE) inhibitors, such as captopril, has antifibrotic efficacy in some pathological settings. Therefore, we analyzed the expression of ACE and Ang II in clinical lymphedema biopsy specimens from patients with unilateral breast cancer-related lymphedema (BCRL) and mouse models, and found that cutaneous ACE expression is increased in lymphedematous tissues. Furthermore, topical captopril decreases fibrosis, activation of intracellular TGF-β1 signaling pathways, inflammation, and swelling in mouse models of lymphedema. Captopril treatment also improves lymphatic function and immune cell trafficking by increasing collecting lymphatic pumping. Our results show that the renin-angiotensin system in the skin plays an important role in the regulation of fibrosis in lymphedema, and inhibition of this signaling pathway may hold merit for treating lymphedema.

Surgical lymphology. Therapy option for lymphoedema and lipohyperplasia dolorosa.

The typical therapy in lymphology is conservative. However, reconstructive and resective treatments for primary and secondary lymphoedema as well as resective procedures for lipohyperplasia dolorosa (LiDo) "lipedema" have been available for several decades. Each of these procedures has its clear indication and decades of successful history. These therapies represent a paradigm shift in lymphology. In reconstruction, the basic idea is to restore lymph flow, to bypass the obstacle to drainage in the vascular system. The combination procedures of two-stage application of resection and reconstruction in lymphoedema are just as much a "work in progress" as the concept of prophylactic lymphatic venous anastomosis (LVA). In the case of resective procedures, the focus is not only on improving the silhouette, but also on reducing the complex decongestion therapy (CDT) and - in the case of LiDo - freedom from pain by improving imaging procedures and the early use of surgical therapy options, the development of higher stages of lymphoedema should be a thing of the past. For LiDo, the application of surgical procedures avoids lifelong CDT and achieves painlessness. All surgical procedures, but especially the resection procedures, are now possible in a way that is gentle on the lymphatic vessels and should be offered to patients with lymphoedema or lipohyperplasia dolorosa without reservation if the goals - reduction in circumference, avoidance of lifelong CDT and, in the case of LiDo, painlessness - cannot be achieved by other means.

Adjustable compression wraps: stretch, interface pressures and static stiffness indices.

Adjustable compression wraps (ACWs) may represent the future of compression for the treatment of the most severe stages of chronic venous diseases and lymphedema. We tested in five healthy subjects: Coolflex® from Sigvaris®; Juzo wrap 6000®, Readywrap® from Lohmann Rauscher®; Juxtafit® and Juxtalite® from Medi®, Compreflex® from Sigvaris®. The objective of this pilot study was to study the stretch, interface pressures, and Static Stiffness Index (SSI) of the six ACWs applied to the leg. The stretch was evaluated by stretching the ACWs to their maximum length. Interface pressure measurements were performed using a PicoPress® transducer and a probe placed at point B1. Interface pressures were measured in the supine resting position and in the standing position. We calculated the SSI. We started the measurements at 20 mmHg in the supine position and increased the pressures by 5 mmHg to 5 mmHg. Coolflex® (inelastic ACW) cannot exceed a maximum pressure of 30 mmHg at rest with a maximum SSI of approximately 30 mmHg. Juzo wrap 6000® (a 50% stretch) and Readywrap® (a 60% stretch) have a profile of stiffness very near one to the other. The optimal stiffness for Juzo is from 16 mmHg to of 30 mmHg for a resting pressure between 25 mmHg and 40 mmHg. For Readywrap, the optimal stiffness is from 17 mmHg to 30 mmHg with a maximum SSI of 35mmHg. The optimal application zone of this wrap at rest is 30 to 45 mmHg. Juxtafit®, Juxtalite® and Compreflex® (respectively 70%, 80%, 124% stretch) can be applied with pressures above 60 mmHg but with maximum SSI of 20 mmHg for Circaid® and>30 mmHg for Compreflex®. This pilot study allows us to propose a classification of wraps according to their stretch: inelastic ACW and short or long stretch ACW (50-60% and 70%, 80%, and 124% stretch). Their stretch and stiffness could help to better determine what could be expected of ACWs in clinical practice.