Showing papers by "Stanley G. Rockson published in 2023"
TL;DR: In this paper , the authors examined the safety and feasibility of an acupuncture randomized control trial (RCT) in this patient cohort, utilizing a battery of standardized clinical and patient-centered outcome measures, including circumferential measurements, bioimpedance spectroscopy, perometry, cytokine levels and patient quality of life.
Abstract: Background: Methods of conservative management for breast cancer-related lymphedema (BCRL) are burdensome in terms of time, cost, and convenience. In addition, many patients are not candidates for surgical treatment. Preliminary results have demonstrated possible beneficial effects of acupuncture for patients with BCRL. In this small pilot study, we examined the safety and feasibility of an acupuncture randomized control trial (RCT) in this patient cohort, utilizing a battery of standardized clinical and patient-centered outcome measures. Methods and Results: Patients with BCRL were randomized 2:1 to the acupuncture (n = 10) or the control (n = 4) group. Patients received acupuncture to the unaffected extremity biweekly for 6 weeks. Feasibility was defined as enrollment ≥80%, completion of ≥9 of 12 acupuncture sessions per person, and ≥75% completion of three of three measurement visits. To inform a future adequately powered RCT, we describe within-group changes in patient-centered outcomes, including circumferential measurements, bioimpedance spectroscopy, perometry, cytokine levels, and patient quality of life. Adverse events were systematically tracked. Fourteen patients completed the study. Of those who received acupuncture (n = 10), 8 completed all 12 acupuncture sessions, and 2 patients completed 11 sessions. Ninety-three percent of all participants completed all three measurement visits. There was no consistent improvement in arm volumes. Inflammatory marker levels had inconclusive fluctuations among both groups. All patients receiving acupuncture demonstrated an improvement in their functional quality-of-life score. No severe adverse events occurred. Conclusions: A randomized controlled study of acupuncture for BCRL is feasible. The acupuncture intervention is acceptable in this population, without safety concerns in a small sample and warrants further investigation.
1 citations
TL;DR: In this article , a rat hindlimb model of secondary lymphedema was developed and characterised using micro computed tomography imaging for limb volume measurements and visualization of lymph drainage with near infrared imaging.
Abstract: Secondary lymphedema is a common condition among cancer survivors, and treatment strategies to prevent or treat lymphedema are in high demand. The development of novel strategies to diagnose or treat lymphedema would benefit from a robust experimental animal model of secondary lymphedema. The purpose of this methods paper is to describe and summarize our experience in developing and characterizing a rat hindlimb model of lymphedema. Here we describe a protocol to induce secondary lymphedema that takes advantage of micro computed tomography imaging for limb volume measurements and visualization of lymph drainage with near infrared imaging. To demonstrate the utility of this preclinical model for studying the therapeutic benefit of novel devices, we apply this animal model to test the efficacy of a biomaterials-based implantable medical device.
TL;DR: In this article , the authors present a compelling review of this problem with consideration for future endeavors to more adequately address the medical needs of the patients, emphasizing the importance of fat and scar to our understanding of the natural history and biology of lymphedema.
Abstract: Lymphatic Research and BiologyVol. 21, No. 1 EditorialFree AccessLymphedema: A Symphony of Fat and ScarStanley G. Rockson Editor-in-ChiefStanley G. Rockson Editor-in-ChiefStanford University School of Medicine, Stanford, California, USA.Search for more papers by this authorPublished Online:16 Feb 2023https://doi.org/10.1089/lrb.2023.29138.editorialAboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail As commonly conceived, lymphedema is a disorder of impaired fluid transport that leads to regional fluid accumulation that manifests as perceptible edema. However, the phenomenon of adipose deposition is central to the presentation of well-established lymphedema, and represents one of the most challenging aspects of the disease for long-term medical management. As of this date, nonsurgical interventions have failed to reduce the excess adipose volume that typifies chronic lymphedema; this phenomenon embodies the failure of conservative management to adequately address the problems encountered by these patients.In the current issue of Lymphatic Research and Biology, Burton and colleagues present a compelling review of this problem with consideration for future endeavors to more adequately address the medical needs of the patients.In a parallel consideration, here Meng and Zhang explore the clinical significance of serum collagen type IV and procollagen type III N-peptide levels in these patients. Recognizing that lymphedema is typified by substantial deposition of collagen in the affected tissues, the authors have addressed the possibility that circulating collagen products might serve as meaningful biomarkers for the disease.For their study, they enrolled 44 subjects, distributed among clinical categories of primary lymphedema, secondary lymphedema, and venous edema, along with 15 healthy control subjects. Through chemiluminescence immunoassay, the authors measured a variety of relevant molecules (hyaluronic acid, laminin, procollagen type III-N peptide, and collagen type IV). Of note is the fact that analysis of receiver operating characteristics supports the ability of the serum assays of both procollagen III-N peptide and collagen type to accurately differentially discriminate the presentation of lymphedema.Taken together, these two articles underscore the importance of fat and scar to our understanding of the natural history and biology of lymphedema. Refinement in our comprehension of these phenomena will help us to better meet the needs of the lymphedema patient.FiguresReferencesRelatedDetails Volume 21Issue 1Feb 2023 InformationCopyright 2023, Mary Ann Liebert, Inc., publishersTo cite this article:Stanley G. Rockson Editor-in-Chief.Lymphedema: A Symphony of Fat and Scar.Lymphatic Research and Biology.Feb 2023.1-1.http://doi.org/10.1089/lrb.2023.29138.editorialPublished in Volume: 21 Issue 1: February 16, 2023PDF download
TL;DR: Rockson et al. as discussed by the authors investigated the impact of central obesity on the occurrence of secondary lymphedema in patients with unilateral upper extremity clinical lymphoma and found that central obesity was associated with higher mean flow velocity and end-diastolic velocity as early as 1 month after surgery.
Abstract: 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.References1. Rockson SG. Secondary lymphedema: Is it a primary disease? Lymphat Res Biol 2008;6(2):63–64. Link, Google Scholar2. Rockson SG. Cancer-related lymphedema: Primary or secondary? Lymphat Res Biol 2022;20(6):579. Link, Google Scholar3. Kapellas N, Demiri E, Lampropoulos A, et al. Genetic predisposition in cancer-related lymphedema: A systematic review. Lymphat Res Biol 2022;20(5):478–487. Abstract, Google Scholar4. DiSipio T, Rye S, Newman B, et al. Incidence of unilateral arm lymphoedema after breast cancer: A systematic review and meta-analysis. Lancet Oncol 2013;14:500–515. Crossref, Medline, Google Scholar5. Cormier JN, Askew RL, Mungovan KS, et al. Lymphedema beyond breast cancer. Cancer 2010;15:5138–5149. Crossref, Google Scholar6. Rockson SG, Zhou X, Zhao L, et al. Exploring disease interrelationships in patients with lymphatic disorders: A single center retrospective experience. Clin Transl Med 2022;12(4):e760. Crossref, Medline, Google ScholarFiguresReferencesRelatedDetails Volume 21Issue 2Apr 2023 InformationCopyright 2023, Mary Ann Liebert, Inc., publishersTo cite this article:Stanley G. Rockson.Breast Cancer-Related Lymphedema: The Primary/Secondary Conundrum.Lymphatic Research and Biology.Apr 2023.99-100.http://doi.org/10.1089/lrb.2023.29141.editorialPublished in Volume: 21 Issue 2: April 20, 2023PDF download
TL;DR: In this article , the role of altered S1P signaling effects in lymphatic cells was investigated in human and mouse lymphedema, and P-selectin inhibitors were suggested as a possible treatment for this pervasive condition.
Abstract: BACKGROUND: Lymphedema is a global health problem with no effective drug treatment. Enhanced T cell immunity and abnormal lymphatic endothelial cell (LEC) signaling are promising therapeutic targets for this condition. Sphingosine-1-phosphate (S1P) mediates a key signaling pathway required for normal LEC function, and altered S1P signaling in LECs could lead to lymphatic disease and pathogenic T cell activation. Characterizing this biology is relevant for developing much-needed therapies. METHODS: Human and mouse lymphedema was studied. Lymphedema was induced in mice by surgically ligating the tail lymphatics. Lymphedematous dermal tissue was assessed for S1P signaling. To verify the role of altered S1P signaling effects in lymphatic cells, LEC-specific S1pr1-deficient (S1pr1LECKO) mice were generated. Disease progression was quantified by tail-volumetric and -histopathological measurements over time. LECs from mice and humans, with S1P signaling inhibition, were then co-cultured with CD4 T cells, followed by an analysis of CD4 T cell activation and pathway signaling. Finally, animals were treated with a monoclonal antibody specific to P-selectin to assess its efficacy in reducing lymphedema and T cell activation. RESULTS: Human and experimental lymphedema tissues exhibited decreased LEC S1P signaling through S1PR1. LEC S1pr1 loss-of-function exacerbated lymphatic vascular insufficiency, tail swelling, and increased CD4 T cell infiltration in mouse lymphedema. LECs, isolated from S1pr1LECKO mice and co-cultured with CD4 T cells, resulted in augmented lymphocyte differentiation. Inhibiting S1PR1 signaling in human dermal LECs (HDLECs) promoted T helper type 1 and 2 (Th1 and Th2) cell differentiation through direct cell contact with lymphocytes. HDLECs with dampened S1P signaling exhibited enhanced P-selectin, an important cell adhesion molecule expressed on activated vascular cells. In vitro, P-selectin blockade reduced the activation and differentiation of Th cells co-cultured with shS1PR1-treated HDLECs. P-selectin-directed antibody treatment improved tail swelling and reduced Th1/Th2 immune responses in mouse lymphedema CONCLUSION: This study suggests that reduction of the LEC S1P signaling aggravates lymphedema by enhancing LEC adhesion and amplifying pathogenic CD4 T cell responses. P-selectin inhibitors are suggested as a possible treatment for this pervasive condition.
TL;DR: In this article , the authors present the results of a scientific and educational endeavor by a worldwide group of top experts who selected and analyzed the major issues and related evidence-based facts on vein and lymphatic management.
Abstract: Published scientific evidence demonstrate the current spread of healthcare misinformation in the most popular social networks and unofficial communication channels. Up to 40% of the medical websites were identified reporting inappropriate information, moreover being shared more than 450,000 times in a 5-year-time frame. The phenomenon is particularly spread in infective diseases medicine, oncology and cardiovascular medicine. The present document is the result of a scientific and educational endeavor by a worldwide group of top experts who selected and analyzed the major issues and related evidence-based facts on vein and lymphatic management. A section of this work is entirely dedicated to the patients and therefore written in layman terms, with the aim of improving public vein-lymphatic awareness. The part dedicated to the medical professionals includes a revision of the current literature, summing up the statements that are fully evidence-based in venous and lymphatic disease management, and suggesting future lines of research to fulfill the still unmet needs. The document has been written following an intense digital interaction among dedicated working groups, leading to an institutional project presentation during the Universal Expo in Dubai, in the occasion of the v-WINter 2022 meeting.