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Hansen FG, Jørgensen MG, Thomsen JB, Sørensen JA. Topical tacrolimus for the amelioration of breast cancer-related lymphedema (TACLE Trial): a study protocol for a randomized, double-blind, placebo-controlled phase II/III trial. Trials 2025; 26:127. [PMID: 40200322 PMCID: PMC11977864 DOI: 10.1186/s13063-025-08829-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2024] [Accepted: 04/01/2025] [Indexed: 04/10/2025] Open
Abstract
BACKGROUND Breast cancer-related lymphedema is a chronic condition affecting 15-30% of breast cancer patients, resulting from treatment-related inflammation and fibrosis primarily mediated by CD4 + T-cells. Tacrolimus, an immunomodulator, has shown efficacy in reducing lymphedema in both animal models and an initial clinical trial. This study aims to validate these findings in a larger cohort, hypothesizing that tacrolimus will reduce lymphedema volume, fibrosis, and fluid retention while improving quality of life. METHODS This multicenter, double-blinded, randomized placebo-controlled trial will enroll 80 women with breast cancer-related lymphedema stages I and II. Participants will be randomized 1:1 to receive either 0.1% tacrolimus ointment or a placebo ointment for 12 months. Primary outcome will be the change in lymphedema volume measured at baseline, 6 months, and 12 months. Secondary outcomes include quality of life assessed via SF- 36, DASH, and LYMPH-Q Upper Extremity questionnaires; lymphedema index via bioimpedance spectroscopy; lymphatic function and flow via indocyanine green lymphangiography; and skin fibrosis measurement. Assessments will take place at baseline, 3, 6, 9, and 12 months. DISCUSSION This trial will provide robust data on the efficacy of topical tacrolimus in reducing BCRL volume and improving patient quality of life. Positive results could establish tacrolimus as a standard treatment for BCRL, potentially enhancing clinical outcomes for affected patients. The findings will also contribute to understanding the role of immunomodulation in lymphedema management. TRIAL REGISTRATION This trial is registered with the EU Clinical Trials Information System (CTIS) under EU CT Number: 2023-503644 - 13-00 (approved 16.05.2024) and ClinicalTrials.gov under identifier NCT06306274 (registered 12.03.2024).
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Affiliation(s)
- Frederik Gulmark Hansen
- Research Unit for Plastic Surgery, Odense University Hospital, Odense, Denmark.
- Clinical Institute, University of Southern Denmark, Odense, Denmark.
| | - Mads Gustaf Jørgensen
- Research Unit for Plastic Surgery, Odense University Hospital, Odense, Denmark
- Clinical Institute, University of Southern Denmark, Odense, Denmark
| | - Jørn Bo Thomsen
- Research Unit for Plastic Surgery, Odense University Hospital, Odense, Denmark
- Clinical Institute, University of Southern Denmark, Odense, Denmark
| | - Jens Ahm Sørensen
- Research Unit for Plastic Surgery, Odense University Hospital, Odense, Denmark
- Clinical Institute, University of Southern Denmark, Odense, Denmark
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Kappos EA, Fabi A, Halbeisen FS, Abu-Ghazaleh A, Stoffel J, Aufmesser-Freyhardt B, Bukowiecki J, Handschin TM, Andree C, Haug MD, Schaefer DJ, Fertsch S, Seidenstücker K. Vascularized lymph node transfer (VLNT) versus lymphaticovenous anastomosis (LVA) for chronic breast cancer-related lymphedema (BCRL): a retrospective cohort study of effectiveness over time. Breast Cancer Res Treat 2025; 210:319-327. [PMID: 39653884 PMCID: PMC11930869 DOI: 10.1007/s10549-024-07567-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2024] [Accepted: 11/19/2024] [Indexed: 03/25/2025]
Abstract
PURPOSE Microsurgical reconstruction, including vascularized lymph node transfer (VLNT) and lymphaticovenous anastomosis (LVA), have emerged as promising treatment options for chronic breast cancer-related lymphedema (BCRL). Despite their clinical relevance, the precise timelines for patient improvement following these interventions remain rather unexplored. Therefore, the goal of this study was to compare the long-term outcomes and improvement patterns over time of VLNT versus LVA to lay open potential differences and aid in personalized counseling of future patients. METHODS A prospectively maintained, encrypted database was analyzed for patients with chronic BCRL treated with either VLNT or LVA with a minimum follow-up of one year. Patient-specific variables, such as body weight and circumferential arm measurements at distinct locations on both arms were documented preoperatively and on regular postoperative outpatient follow-ups. RESULTS This study comprised 112 patients, of which 107 patients fully completed the one-year follow-up period. Both VLNT and LVA achieved significant arm size reductions. LVA showed an early peak in effectiveness within the first three months, followed by a subsequent decrease and eventual stabilization. Contrarily, VLNT exhibited a distinct pattern with two significant peaks at three and eighteen months. CONCLUSIONS VLNT and LVA are both effective in long-term lymphedema management, yet they demonstrate marked differences in the timing of improvement. VLNT shows a delayed but more durable response, in contrast to the greater but shorter-lasting surge in effectiveness achieved by LVA. Interestingly, VLNT demonstrates an earlier onset of therapeutic impact than previously understood.
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Affiliation(s)
- Elisabeth A Kappos
- Department of Plastic, Reconstructive, Aesthetic and Hand Surgery, University Hospital of Basel, Spitalstrasse 21, 4031, Basel, Switzerland.
- Faculty of Medicine, University of Basel, Basel, Switzerland.
- Breast Center, University Hospital of Basel, Basel, Switzerland.
| | - Adriano Fabi
- Department of Plastic, Reconstructive, Aesthetic and Hand Surgery, University Hospital of Basel, Spitalstrasse 21, 4031, Basel, Switzerland
- Faculty of Medicine, University of Zurich, Zurich, Switzerland
| | - Florian S Halbeisen
- Surgical Outcome Research Center, Department of Clinical Research, University Hospital Basel and University of Basel, Basel, Switzerland
| | - Alina Abu-Ghazaleh
- Department of Plastic, Reconstructive and Aesthetic Surgery, Sana Hospital Düsseldorf, Düsseldorf, Germany
| | - Julia Stoffel
- Department of Plastic, Reconstructive, Aesthetic and Hand Surgery, University Hospital of Basel, Spitalstrasse 21, 4031, Basel, Switzerland
- Faculty of Medicine, University of Basel, Basel, Switzerland
| | - Birgit Aufmesser-Freyhardt
- Department of Plastic, Reconstructive and Aesthetic Surgery, Sana Hospital Düsseldorf, Düsseldorf, Germany
| | - Julia Bukowiecki
- Department of Plastic, Reconstructive and Aesthetic Surgery, Sana Hospital Düsseldorf, Düsseldorf, Germany
- Faculty of Health, University Witten-Herdecke, Witten, Germany
| | - Tristan M Handschin
- Department of Plastic, Reconstructive, Aesthetic and Hand Surgery, University Hospital of Basel, Spitalstrasse 21, 4031, Basel, Switzerland
- Faculty of Medicine, University of Basel, Basel, Switzerland
| | - Christoph Andree
- Department of Plastic, Reconstructive and Aesthetic Surgery, Sana Hospital Düsseldorf, Düsseldorf, Germany
| | - Martin D Haug
- Department of Plastic, Reconstructive, Aesthetic and Hand Surgery, University Hospital of Basel, Spitalstrasse 21, 4031, Basel, Switzerland
- Faculty of Medicine, University of Basel, Basel, Switzerland
| | - Dirk J Schaefer
- Department of Plastic, Reconstructive, Aesthetic and Hand Surgery, University Hospital of Basel, Spitalstrasse 21, 4031, Basel, Switzerland
- Faculty of Medicine, University of Basel, Basel, Switzerland
| | - Sonia Fertsch
- Department of Plastic, Reconstructive and Aesthetic Surgery, Sana Hospital Düsseldorf, Düsseldorf, Germany
- Faculty of Health, University Witten-Herdecke, Witten, Germany
| | - Katrin Seidenstücker
- Department of Plastic, Reconstructive and Aesthetic Surgery, Sana Hospital Düsseldorf, Düsseldorf, Germany
- Breast Center, University Hospital Düsseldorf, Düsseldorf, Germany
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Schulz T, Lee Warg M, Kurow O, Langer S, Nuwayhid R. The burden of lymphedema on quality of life. VASA 2025; 54:124-132. [PMID: 39791212 DOI: 10.1024/0301-1526/a001173] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2025]
Abstract
Background: Due to a lack of validated methodologies, this study aimed to evaluate the quality of life (QoL) among individuals affected by lymphedema and to compare them with the general population and common diseases. Patients and methods: Patients were recruited from October 2023 till March 2024. The SF-36 and LYMQOL questionnaires were administered. The Robert Koch Institute provided data from the survey for secondary evaluations of the DEGS1 study. Descriptive analysis of the patient's data was conducted, followed by an analysis of risk factors, a comparison with common diseases and a pairs matched analyses with the general population based on the parameters sex, age and Body Mass Index (BMI). A p-value below 0.05 was considered significant. Results: Among the 273 patients, 18 had primary lymphedema and 255 had secondary lymphedema due to cancer history. Staging revealed 28 patients in stage I, 137 in stage II, and 75 in stage III. The majority of patients (83%) were female and mostly the lower extremity was affected. Age, International Society of Lymphology (ISL)-stage, and BMI were significantly correlated with reduced QoL in seven, six, and eleven out of thirteen subscales of the respective scores. The LYMQOL analysis revealed, that patients with upper limb lymphedema (ULL) demonstrated higher QoL compared to those with lower limb lymphedema (LLL). When compared to the general population, individuals with ULL exhibited reduced QoL in five out of eight SF-36 domains (p<0.05). Conversely, LLL patients showed decreased QoL across all eight SF-36 subscales (p<0.01). In comparison to diseases like myocardial infarction or malignant diseases, patients with lymphedema experience a significant, diminished QoL. Conclusions: By 2024, lymphedema patients continue to experience significantly lower QoL compared to the general population or common diseases in Germany. LLL patients exhibit a reduced QoL compared to individuals with ULL.
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Affiliation(s)
- Torsten Schulz
- Department of Orthopedic, Trauma and Plastic Surgery, University Hospital Leipzig, Germany
| | - Mary Lee Warg
- Department of Orthopedic, Trauma and Plastic Surgery, University Hospital Leipzig, Germany
| | - Olga Kurow
- Department of Orthopedic, Trauma and Plastic Surgery, University Hospital Leipzig, Germany
| | - Stefan Langer
- Department of Orthopedic, Trauma and Plastic Surgery, University Hospital Leipzig, Germany
| | - Rima Nuwayhid
- Department of Orthopedic, Trauma and Plastic Surgery, University Hospital Leipzig, Germany
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Dionyssiou D, Tsimponis A, Georgiadou E, Mamaligka K, Demiri E. Long-term results of lymphedema treatment with Combined lymph node transfer and collagen scaffolds: An Observational Study. JPRAS Open 2025; 43:328-339. [PMID: 39846030 PMCID: PMC11751497 DOI: 10.1016/j.jpra.2024.11.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2024] [Accepted: 11/17/2024] [Indexed: 01/24/2025] Open
Abstract
Aim Vascularized lymph node transfer (VLNT) accelerates growth factor secretion, lymphatic endothelial cell migration toward the interstitial flow and lymphagiogenesis in a multidirectional pattern. Our observational study aimed to examine the hypothesis that nanofibrillar collagen scaffolds (NCS) combined with VLNT can provide guided lymphagiogenesis creating long-lasting lymphatic pathways. Methods Twenty-four patients (21 female, 3 male) underwent a lymphatic microsurgery for upper (n = 11) or lower (n = 13) limb secondary lymphedema and completed at least 18 months follow-up were selected and equally divided in 2 groups; Group-A underwent VLNT, Group-B underwent combined VLNT and NCS procedure. Lymph node flap sizes, harvesting procedure, and implantation location were similar in both groups. Demographics, lymphedema etiology and staging, limb volumetry, and somatometric data were recorded. Pre- and post-operative data for limb-volume difference, infection episodes/year, and indocyanine-green (ICG) lymphography changes were documented in all patients. Results Mean follow-up was period was 42 months (24-60 months) in Group-A, and 27 months (18-48 months) in Group-B patients. Demographic data, lymphedema etiology, and staging were comparable in both groups. Pre- and post-operative edema volume difference for Group-A was 36 % and 25 % (p < 0.001), and 33 % and 14 % in Group-B (p = 0.001), respectively. The mean number of infection episodes decreased in Group-A and B from 1.75 to 0.33 and from 2.17 to 0.42 per patient/year, respectively. ICG mean stage in Group-A was 3.58 pre- and 3 post-operatively (p = 0.045), and 3.67 pre- and 2.08 post-operatively in Group-B (p = 0.506). A statistically significant difference was found in post-operative volume difference between the 2 groups (p = 0.008) and post-operative ICG changes (p < 0.001). ICG-lymphography demonstrated new lymphatic vessel formation at the NCS implantation location. Conclusions Long-term follow-up of the patients treated using combined VLNT-NCS approach revealed a statistically significant improvement regarding volume reduction, infection episodes per year, ICG downstaging, and new lymphatic vessel formation, compared to VLNT alone.
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Affiliation(s)
- Dimitrios Dionyssiou
- Department of Plastic Surgery, Aristotle University of Thessaloniki, School of Medicine, Papageorgiou General Hospital, Thessaloniki, 54603, Greece
| | - Antonios Tsimponis
- Department of Plastic Surgery, Aristotle University of Thessaloniki, School of Medicine, Papageorgiou General Hospital, Thessaloniki, 54603, Greece
| | - Eleni Georgiadou
- Department of Plastic Surgery, Aristotle University of Thessaloniki, School of Medicine, Papageorgiou General Hospital, Thessaloniki, 54603, Greece
| | - Konstantina Mamaligka
- Department of Plastic Surgery, Aristotle University of Thessaloniki, School of Medicine, Papageorgiou General Hospital, Thessaloniki, 54603, Greece
| | - Efterpi Demiri
- Department of Plastic Surgery, Aristotle University of Thessaloniki, School of Medicine, Papageorgiou General Hospital, Thessaloniki, 54603, Greece
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Chen L, Zheng Y, Zheng D, Li Z, Chen H, Chen C, Yu S. Research trends on lymphedema after mastectomy for breast cancer patients from 2000 to 2023: a scientometric analysis. Front Oncol 2025; 15:1440966. [PMID: 39968076 PMCID: PMC11832376 DOI: 10.3389/fonc.2025.1440966] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2024] [Accepted: 01/16/2025] [Indexed: 02/20/2025] Open
Abstract
Background Breast cancer-related lymphedema (BCRL) is a common and debilitating complication following breast cancer treatment. Despite its significant impact on patients' quality of life, bibliometric analyses focusing on BCRL are scarce. This study aims to explore global research trends on BCRL from 2000 to 2023, identify existing knowledge gaps, and highlight emerging focus areas through a bibliometric approach. Methods A comprehensive search was conducted using the Web of Science (WOS) database to retrieve literature published between January 2000 and November 2023. Bibliometric analyses and visualizations were performed using R Studio, CiteSpace, and VOSviewer. Key data extracted included publication trends, contributing countries and institutions, leading authors, journals, research categories, and keywords. Outcome measures for analysis included the number of publications, citation counts, author productivity, and keyword co-occurrence. Results A total of 919 eligible publications from 52 countries and regions, 1,163 institutions, and 3,550 authors were identified. These publications appeared in 255 journals, with "Lymphology" emerging as the journal with the highest citation count. The USA was the most prolific contributor to the field. The annual number of publications demonstrated a consistent upward trend. Keyword co-occurrence analysis revealed prominent research hotspots, including "lymphedema," "women," "breast cancer," "arm lymphedema," and "quality of life." Emerging keyword trends from 2021 to 2023 highlighted "prevention" and "validity" as pivotal research frontiers. Conclusions This bibliometric study highlights the growing interest in breast cancer-related lymphedema research and identifies key areas for future investigation, including prevention, diagnosis, and treatment strategies. The results underscore the need for further exploration of these emerging research areas to improve patient outcomes.
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Affiliation(s)
- Ling Chen
- Breast Center, Cancer Hospital of Shantou University Medical College, Guangdong, Shantou, China
| | - Yuxian Zheng
- Nursing Department, Shantou University Medical College, Guangdong, Shantou, China
| | - Daitian Zheng
- Department of General Surgery, The Second Affiliated Hospital of Shantou University Medical College, Shantou, China
| | - Zhiyang Li
- Department of General Surgery, The Second Affiliated Hospital of Shantou University Medical College, Shantou, China
| | - Hongwu Chen
- Department of Neurosurgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, China
| | - Chujun Chen
- Breast Center, Cancer Hospital of Shantou University Medical College, Guangdong, Shantou, China
- Nursing Department, Cancer Hospital of Shantou University Medical College, Guangdong, Shantou, China
| | - Shuxian Yu
- Nursing Department, Cancer Hospital of Shantou University Medical College, Guangdong, Shantou, China
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Demirci M, Şanal C. Evaluation of the Treatment Process with Home Exercise Program and Telerehabilitation in Patients with Breast Cancer-Related Lymphedema: A Case-Control Study. Lymphat Res Biol 2025. [PMID: 39866130 DOI: 10.1089/lrb.2024.0038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2025] Open
Abstract
Background: This study aimed to evaluate and compare the effectiveness of telerehabilitation (TR) and home exercise program (HEP) in patients with breast cancer-related lymphedema and the patients' compliance with these treatment processes. Methods and Results: 23 patients were prospectively included in the HEP group and 22 patients in the TR group, who were followed up in the Lymphedema Outpatient Clinic of the Department of Physical Medicine and Rehabilitation of a University Hospital. These patients were randomized. The volume difference between the extremities of the patients was calculated with the truncated cone formula, before and after treatment. The patients' pain, tightness, heaviness, and stiffness symptoms associated with lymphedema were questioned using a numerical scale. The patients' functionality and participation in daily life activities were evaluated with disabilities of arm, shoulder, and hand Quick Questionnaire (Quick-DASH) and the Lymphedema Life Impact Scale (LLIS). Patients' treatment satisfaction and compliance with treatment were questioned using Likert scales. A total of 45 patients were included in the study. The mean age and body mass index were similar between the groups (p ≥ 0.05). In the evaluations performed, no significant differences were observed within groups or between groups in terms of volume difference, quick DASH, pain, tightness, heaviness, stiffness, and LLIS scores (p ≥ 0.05). Patient satisfaction was significantly higher in the TR group (p ≤ 0.001). During treatment follow-up, only one person from the TR group missed the 5th-week checkup (4.5%), whereas five patients from the HEP missed the 5th-week checkup and three missed the 8th-week checkup. Overall, eight patients discontinued treatment (34%). Conclusion: Although there were no significant differences in clinical assessments between TR and HEP groups, patient satisfaction, and treatment adherence were significantly higher in the TR group.
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Affiliation(s)
- Merve Demirci
- Department of Physical Medicine and Rehabilitation, Marmara University School of Medicine, Istanbul, Turkey
| | - Canan Şanal
- Department of Physical Medicine and Rehabilitation, Marmara University School of Medicine, Istanbul, Turkey
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Ren D, Zang L, Chen W, Huang H, Lin M, Li S, Lin N, Huang Q. A quality control circle to improve preventive care for lower limb lymphedema in gynecologic oncology surgery. Support Care Cancer 2024; 33:59. [PMID: 39733009 DOI: 10.1007/s00520-024-09106-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2024] [Accepted: 12/14/2024] [Indexed: 12/30/2024]
Abstract
OBJECTIVE This study aims to enhance compliance with lower limb lymphedema (LLL) prevention care measures post-gynecologic oncology surgery (GOS) through quality control circle (QCC) activity, aiming to improve patient recovery outcomes and reduce postoperative complications. METHODS A 6-month QCC activity was conducted within the hospital, employing the ten-step plan-do-check-act model for QCC activity. The root causes of inadequate implementation of LLL prevention care measures were analyzed, leading to the development of relevant strategies and protocols. Compliance rates of preventive care measures pre- and post-QCC activity were compared. RESULTS The focus of this improvement initiative was on "inadequate postoperative preventive measures" and "lack of standardized discharge preventive measures." Strategies included ensuring nurses proficiently assess LLL following gynecologic malignancy surgeries, enhancing standardized preventive measures for LLL post-GOS, and establishing personalized and diversified education models. Following the implementation of QCC activity, there was a significant improvement in the compliance rate of LLL prevention care measures. The compliance rate increased from 74.00% before the activity to 92.80%, surpassing the target rate by 119.00%, with an improvement rate of 25.40%. Comprehensive evaluations of circle members' abilities showed significant improvement, with notable increases in problem-solving abilities, initiative, and confidence. CONCLUSION Implementation of QCC activity resulted in a substantial improvement in compliance with LLL prevention care measures following GOS, ensuring safer and more effective patient care services.
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Affiliation(s)
- Danqing Ren
- Department of Gynecology, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, 350001, China
| | - Lele Zang
- Department of Gynecology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, 350014, China
| | - Wenyuan Chen
- Department of Gynecology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, 350014, China
| | - Hailian Huang
- Department of Gynecology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, 350014, China
| | - Mei Lin
- Department of Gynecology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, 350014, China
| | - Suyu Li
- Department of Gynecology, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, 350001, China
| | - Na Lin
- Department of Gynecology, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, 350001, China
| | - Qiuyuan Huang
- Department of Gynecology, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, 350001, China.
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Han CY, Choi SH, Chi SH, Hong JH, Cho YE, Kim J. Nano-fluorescence imaging: advancing lymphatic disease diagnosis and monitoring. NANO CONVERGENCE 2024; 11:53. [PMID: 39661218 PMCID: PMC11635084 DOI: 10.1186/s40580-024-00462-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Accepted: 11/30/2024] [Indexed: 12/12/2024]
Abstract
The lymphatic system plays a crucial role in maintaining physiological homeostasis and regulating immune responses. Traditional imaging modalities such as magnetic resonance imaging, computerized tomography, and positron emission tomography have been widely used to diagnose disorders in the lymphatic system, including lymphedema, lymphangioma, lymphatic metastasis, and Castleman disease. Nano-fluorescence technology has distinct advantages-including naked-eye visibility, operational simplicity, portability of the laser, and real-time visibility-and serves as an innovative alternative to traditional imaging techniques. This review explores recent advancements in nano-fluorescence imaging aimed at enhancing the resolution of lymphatic structure, function, and immunity. After delineating the fundamental characteristics of lymphatic systems, it elaborates on the development of various nano-fluorescence systems (including nanoparticles incorporating fluorescent dyes and those with intrinsic fluorescence) while addressing key challenges such as photobleaching, limited tissue penetration, biocompatibility, and signal interference from biomolecules. Furthermore, this review highlights the clinical applications of nano-fluorescence and its potential integration into standard diagnostic protocols. Ongoing advancements in nanoparticle technology underscore the potential of nano-fluorescence to revolutionize the diagnosis and treatment of lymphatic disease.
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Affiliation(s)
- Chae Yeon Han
- School of Integrative Engineering, Chung-Ang University, Seoul, 06974, South Korea
| | - Sang-Hun Choi
- School of Integrative Engineering, Chung-Ang University, Seoul, 06974, South Korea
| | - Soo-Hyang Chi
- School of Integrative Engineering, Chung-Ang University, Seoul, 06974, South Korea
| | - Ji Hyun Hong
- Department of Radiation Oncology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, 06591, South Korea
| | - Young-Eun Cho
- Department of Food and Nutrition, Andong National University, Andong, 36729, South Korea
| | - Jihoon Kim
- School of Integrative Engineering, Chung-Ang University, Seoul, 06974, South Korea.
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Jørgensen MG, Jensen CH, Hermann AP, Andersen DC, Toyserkani NM, Sheikh SP, Sørensen JA. No Clinical Efficacy of Adipose-Derived Regenerative Cells and Lipotransfer in Breast Cancer-Related Lymphedema: A Double-Blind Placebo-Controlled Phase II Trial. Plast Reconstr Surg 2024; 154:1172-1182. [PMID: 39591365 DOI: 10.1097/prs.0000000000011343] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/04/2024]
Abstract
BACKGROUND Breast cancer-related lymphedema (BCRL) is a debilitating sequela affecting up to 1 in 3 breast cancer survivors. Treatments are palliative and do not address the underlying lymphatic injury. Recent preclinical and nonrandomized studies have shown promising results using adipose-derived regenerative cells (ADRCs) and lipotransfer in alleviating BCRL through regeneration of lymphatic tissue. However, no randomized controlled trial has been performed in an attempt to eliminate a placebo effect. METHODS This randomized, double-blind, placebo-controlled trial included patients with no-option, persistent disabling unilateral BCRL. Patients were randomly assigned in a 1:1 ratio to receive either autologous ADRCs (4.20×10 7 ± 1.75×10 7 cells) and 30-cc lipotransfer or placebo (saline) to the axilla. The primary outcome was a change in BCRL volume 1 year after treatment. Secondary outcomes included changes in quality of life, indocyanine green lymphangiography stage, bioimpedance, and safety. RESULTS Eighty patients were included, of whom 39 were allocated to ADRCs and lipotransfer treatment and 41 to placebo treatment. Baseline characteristics were similar in the groups. One year after treatment, no objective improvements were observed in the treatment or placebo groups. In contrast, significant subjective improvements were noted for both the treatment and placebo groups. CONCLUSIONS This trial failed to confirm a benefit of ADRCs and lipotransfer in the treatment of BCRL. These nonconfirmatory results suggest that ADRC and lipotransfer should not be recommended for alleviating BCRL. However, the authors cannot exclude that repeated treatments or higher doses of ADRCs or lipotransfer could yield a clinical effect. CLINICAL QUESTION/LEVEL OF EVIDENCE Therapeutic, I.
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Affiliation(s)
- Mads Gustaf Jørgensen
- From the Departments of Plastic and Reconstructive Surgery
- Open Patient Data Explorative Network (OPEN), Odense University Hospital
- Clinical Institute, University of Southern Denmark
| | | | | | | | | | - Søren Paludan Sheikh
- Clinical Biochemistry and Pharmacology
- Clinical Institute, University of Southern Denmark
| | - Jens Ahm Sørensen
- From the Departments of Plastic and Reconstructive Surgery
- Clinical Institute, University of Southern Denmark
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Andersen DC, Bjerre FA, Jørgensen MG, Sørensen JA, Jensen CH. Clinical outcome is unlinked to injection of adipose-derived regenerative cells in the axilla of breast cancer-related lymphedema patients. Stem Cell Res Ther 2024; 15:426. [PMID: 39543743 PMCID: PMC11566835 DOI: 10.1186/s13287-024-04037-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2024] [Accepted: 11/01/2024] [Indexed: 11/17/2024] Open
Abstract
BACKGROUND Injection of autologous adipose-derived regenerative cells (ADRCs) combined with lipotransfer has been suggested to alleviate symptoms in diseases including breast cancer-related lymphedema (BCRL). We recently performed a randomized controlled trial injecting lipoaspirate with ADRCs into the axilla of BCRL patients, and here we aimed in the intervention group to define in an unbiased fashion whether ADRC injection was linked to the clinical outcome. METHODS 39 BCRL patients received lipotransfer assisted with autologous ADRCs (4.20 × 107 ± 1.75 × 107 cells) whereas 41 BCRL patients were included for placebo treatment. At 12 month follow-up, we assessed quality of life, lymphangiography, and bioimpedance enclosing 59 outcome parameters. Multifactorial analysis of clinical outcomes was used to define responders and non-responders to the intervention, and collected ADRCs from these patient groups were analyzed by single cell RNA sequencing (scRNAseq). RESULTS Unbiased multifactorial analysis ranked and defined the clinical outcomes (Sf36 physical change, L-Dex Lymph Change, ICG mdanderson change) with the highest effect on BCRL patients. The 10 patients with the highest- and lowest effect (five responders and five non-responders) were included in the study. No difference between non-responders and responders were observed for injected ADRC number/size/viability (p > 0.05). In scRNAseq, we did not find any major difference (p > 0.05) between groups in ADRC composition regarding adipose derived stem cells, endothelial-, smooth muscle-, T-, B-, mast cells as well as macrophages, which was verified by flow cytometry. Differential subcluster gene expression between groups were for 92.5% of genes, including those encoding secretory proteins, below the threshold of 1.5, and thus neglible. Together this suggested that the ADRC phenotype was indistinguishable between BCRL responders and non-responders to the intervention. CONCLUSION Our data suggest that the ADRC injection and ADRC phenotype or heterogeneity have no effect on the clinical outcomes on BCRL, and ADRC assisted lipotranfer for BCRL should therefore not be considered currently.
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Affiliation(s)
- Ditte Caroline Andersen
- Andersen-Group, University of Southern Denmark, Campusvej 55, 5230, Odense, Denmark
- Department of Clinical Biochemistry, Odense University Hospital, Odense, Denmark
- Clinical Institute, University of Southern Denmark, Odense, Denmark
| | - Frederik Adam Bjerre
- Andersen-Group, University of Southern Denmark, Campusvej 55, 5230, Odense, Denmark
- Clinical Institute, University of Southern Denmark, Odense, Denmark
| | - Mads Gustaf Jørgensen
- Department of Plastic and Reconstructive Surgery, Odense University Hospital, Odense, Denmark
- Clinical Institute, University of Southern Denmark, Odense, Denmark
| | - Jens Ahm Sørensen
- Department of Plastic and Reconstructive Surgery, Odense University Hospital, Odense, Denmark
- Clinical Institute, University of Southern Denmark, Odense, Denmark
| | - Charlotte Harken Jensen
- Andersen-Group, University of Southern Denmark, Campusvej 55, 5230, Odense, Denmark.
- Department of Clinical Biochemistry, Odense University Hospital, Odense, Denmark.
- Clinical Institute, University of Southern Denmark, Odense, Denmark.
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11
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Médor MC, Churchill IF, Pereira D, Roberts A, Cordeiro E, Findlay-Shirras L, Zhang J, Momtazi M. Lymphovenous Bypass for Immediate Lymphatic Reconstruction in Breast Cancer Patients Undergoing Axillary Lymph Node Dissection: Minimizing the Risk of Upper Extremity Lymphedema. J Reconstr Microsurg 2024; 40:713-721. [PMID: 38657631 DOI: 10.1055/s-0044-1785680] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/26/2024]
Abstract
BACKGROUND Studies have shown a significant reduction in breast cancer-related lymphedema (BCRL) rates in patients undergoing complete axillary lymph node dissection (cALND) combined with immediate lymphatic reconstruction (ILR) using lymphovenous bypass (LVB).The purpose of this study was to determine if ILR with LVB at the time of cALND results in a decreased incidence of BCRL and its impact on patient quality of life (QOL). METHODS In this prospective cohort study, patients ≥ 18 years requiring cALND underwent ILR from 2019 to 2021. The primary outcome was bilateral upper limb volumes measured by Brørson's truncated cone formula and the Pero-System (3D Körper Scanner). The secondary outcome was QOL measured by the Lymphedema Quality of Life (LYMQOL) arm patient-reported outcome measurement. RESULTS Forty-two patients consented to ILR using LVB. ILR was completed in 41 patients with a mean of 1.9 ± 0.9 lymphovenous anastomosis performed. Mean age of patients was 52.4 ± 10.5 years with a mean body mass index of 27.5 ± 4.9 kg/m2. All patients (n = 39, 100%) received adjuvant therapy after ILR. Mean follow-up was 15.2 ± 5.1 months. Five patients met criteria for lymphedema throughout the duration of the study (12.8%), with two patients having resolution, with an overall incidence of 7.7% by the end of the study period. Patients with lymphedema were found to have statistically significant lower total LYMQOL values at 18 months (8.44 ± 1.17 vs. 3.23 ± 0.56, p < 0.001). A mean increase of 0.73 ± 3.5 points was observed for overall QOL average for upper limb function at 18 months compared with 3 months (t = 0.823, p = 0.425). CONCLUSION This study showed an incidence of 7.7% lymphedema development throughout the duration of study. We also showed that ILR has the potential to reduce the significant long-term adverse outcomes of lymphedema and improve QOL for patients undergoing cALND.
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Affiliation(s)
- Maria C Médor
- Division of Plastic Surgery, University of Montreal, Montreal, Quebec, Canada
| | | | - Diego Pereira
- Division of Plastic Surgery, The Ottawa Hospital, Ottawa, Ontario, Canada
| | - Amanda Roberts
- Division of General Surgery, The Ottawa Hospital, Ottawa, Ontario, Canada
| | - Erin Cordeiro
- Division of General Surgery, The Ottawa Hospital, Ottawa, Ontario, Canada
| | | | - Jing Zhang
- Division of Plastic Surgery, The Ottawa Hospital, Ottawa, Ontario, Canada
| | - Moein Momtazi
- Division of Plastic Surgery, University of Alberta, Edmonton, Alberta, Canada
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12
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Sharifi N, Ahmad S. Breast cancer-related lymphedema: A critical review on recent progress. Surg Oncol 2024; 56:102124. [PMID: 39208532 DOI: 10.1016/j.suronc.2024.102124] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2024] [Revised: 08/06/2024] [Accepted: 08/21/2024] [Indexed: 09/04/2024]
Abstract
Lymphedema is a chronic and debilitating condition characterized by an abnormal buildup of protein-rich fluid in the interstitial tissue, leading to the development of edema and tissue structural alterations. Breast cancer-related lymphedema (BCRL) remains a significant healthcare burden because it can develop within days and up to 11-years after the surgery. Specifically, axillary lymph node dissection leads to 30-50 % upper limb lymphedema, which involves the accumulation of protein-rich fluid. In this article, we provide a comprehensive/critical overview of post-mastectomy lymphedema, focusing on key aspects as diagnosis, prevention, and treatment methods. Beginning with clinical condition, the article explores the pathophysiology and risk factors associated with post-mastectomy lymphedema. It further delves into various diagnostic modalities available, highlighting the importance of early detection for optimal management of BCRL. We also examine preventive strategies, emphasizing the role of patient education, lifestyle modifications, and proactive measures in reducing the risk of lymphedema development. In terms of treatment, the article covers a wide array of interventions ranging from conservative approaches like manual lymphatic drainage and compression therapy to surgical techniques such as lymph node transfer and lymphaticovenular anastomosis. Thus, through a comprehensive synthesis of current evidence and clinical practices updates, the review aims to guide healthcare professionals in delivering preventive and effective care while improving outcomes for individuals affected by post-mastectomy lymphedema.
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Affiliation(s)
- Nasrin Sharifi
- AdventHealth Cancer Institute, Gynecologic Oncology Program, Orlando, FL, 32804, USA; Valencia College, Department of Health Sciences, Section of Human Anatomy & Physiology, Orlando, FL, 32802, USA
| | - Sarfraz Ahmad
- AdventHealth Cancer Institute, Gynecologic Oncology Program, Orlando, FL, 32804, USA.
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13
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Ahari D, Wilkinson M, Ali N, Taxiarchi VP, Dave RV, Gandhi A. Abemaciclib Therapy Using the MonarchE Criteria Results in Large Numbers of Excess Axillary Node Clearances-Time to Pause and Reflect? Cancers (Basel) 2024; 16:3072. [PMID: 39272930 PMCID: PMC11394446 DOI: 10.3390/cancers16173072] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2024] [Revised: 08/31/2024] [Accepted: 09/02/2024] [Indexed: 09/15/2024] Open
Abstract
The monarchE study added the CDK4/6 inhibitor abemaciclib to the care of women with oestrogen-positive (ER+) breast cancers. Eligibility required meeting monarchE criteria-either >3 positive axillary nodes, or 1-3 positive sentinel nodes (SNB+) with tumour size >50 mm or grade 3 cancers. Women were advised to proceed to completion axillary node clearance (cANC) if size/grade criteria were not fulfilled for >3 positive nodes to be identified. However, cANC is associated with significant morbidity, conflicting with the potential benefits of abemaciclib. We analysed data of 229 consecutive women (2016-2022) with ER+ breast cancer and SNB+ who proceeded to cANC, keeping with contemporary treatment guidelines. We used this cohort to assess numbers that, under national guidance in place currently, would be advised to undergo cANC solely to check eligibility for abemaciclib treatment. Using monarchE criteria, 90 women (39%) would have accessed abemaciclib based on SNB+ and size/grade, without cANC. In total, 139 women would have been advised to proceed to cANC to check eligibility, with only 15/139 (11%) having >3 positive nodes after sentinel node biopsy and cANC. The remaining 124 (89%) would have undergone cANC but remained ineligible for abemaciclib. Size, age, grade, and Ki67 did not predict >3 nodes at cANC. Following cANC, a large majority of women with ER+, <50 mm, and grade 1-2 tumours remain ineligible for abemaciclib yet are subject to significant morbidity including lifelong lymphoedema risk. The monarchE authors state that 15 women need abemaciclib therapy for 1 to clinically benefit. Thus, in our cohort, 139 women undergoing cANC would lead to one woman benefitting.
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Affiliation(s)
- Daniel Ahari
- Wythenshawe Hospital and Nightingale Breast Cancer Centre, Manchester University Foundation Trust, Manchester M23 9LT, UK
| | - Mark Wilkinson
- Wythenshawe Hospital and Nightingale Breast Cancer Centre, Manchester University Foundation Trust, Manchester M23 9LT, UK
| | - Nisha Ali
- Wythenshawe Hospital and Nightingale Breast Cancer Centre, Manchester University Foundation Trust, Manchester M23 9LT, UK
| | - Vicky P Taxiarchi
- Centre for Women's Mental Health, Division of Psychology and Mental Health, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PL, UK
| | - Rajiv V Dave
- Wythenshawe Hospital and Nightingale Breast Cancer Centre, Manchester University Foundation Trust, Manchester M23 9LT, UK
- Division of Cancer Sciences, Faculty of Biology, Medicine & Health, University of Manchester, Manchester Academic Health Sciences Centre, Manchester University Foundation Trust, Manchester M13 9PL, UK
| | - Ashu Gandhi
- Wythenshawe Hospital and Nightingale Breast Cancer Centre, Manchester University Foundation Trust, Manchester M23 9LT, UK
- Division of Cancer Sciences, Faculty of Biology, Medicine & Health, University of Manchester, Manchester Academic Health Sciences Centre, Manchester University Foundation Trust, Manchester M13 9PL, UK
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14
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Ciudad P, Bolletta A, Kaciulyte J, Manrique OJ, Escandón JM. Primary LYmphedema Multidisciplinary Approach in Patients Affected by Primary Lower Extremity Lymphedema. J Clin Med 2024; 13:5161. [PMID: 39274373 PMCID: PMC11395934 DOI: 10.3390/jcm13175161] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2024] [Revised: 08/26/2024] [Accepted: 08/28/2024] [Indexed: 09/16/2024] Open
Abstract
Background: Primary lymphedema is a chronic condition caused by a developmental abnormality of the lymphatic system, leading to its malfunction. Various surgical options, including physiologic and excisional procedures, have been proposed. The aim of this study was to present a comprehensive algorithm for the treatment of primary lower extremity lymphedema: the Primary LYmphedema Multidisciplinary Approach (P-LYMA). Methods: Nineteen patients were treated following the P-LYMA protocol. Patients underwent pre- and postoperative complex decongestive therapy (CDT). A variety of physiologic and excisional procedures were performed, either independently or in combination. The primary outcome was to assess the circumferential reduction rate (CRR). The Lymphedema Quality of Life Score (LeQOLiS), reduction in the number of cellulitis episodes, and complications were recorded. Results: The mean CRR was 73 ± 20% at twelve months postoperatively. The frequency of cellulitis episodes per year decreased from a mean of 1.9 ± 0.8 preoperatively to 0.4 ± 0.6 during follow-up. Two patients experienced minor complications. The mean hospitalization time was 5 days. Patients' quality of life, as measured by the LeQOLiS, significantly improved from 70.4 ± 12 preoperatively to 24 ± 14 at twelve months postoperatively. Conclusions: The P-LYMA algorithm maximizes surgical outcomes and improves the quality of life in patients with primary lymphedema. CDT is essential for optimizing results.
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Affiliation(s)
- Pedro Ciudad
- Department of Plastic, Reconstructive and Burn Surgery, Arzobispo Loayza National Hospital, Lima 15082, Peru
- Academic Department of Surgery, Faculty of Medicine, Federico Villarreal National University, Lima 15084, Peru
| | - Alberto Bolletta
- Plastic Surgery Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56125 Pisa, Italy
| | - Juste Kaciulyte
- Unit of Plastic and Reconstructive Surgery, Department of Surgery "P.Valdoni", Sapienza University of Rome, Policlinico Umberto I, 00185 Rome, Italy
| | - Oscar J Manrique
- Department of Plastic, Reconstructive and Burn Surgery, Arzobispo Loayza National Hospital, Lima 15082, Peru
- Division of Plastic and Reconstructive Surgery, Strong Memorial Hospital, University of Rochester Medical Center, Rochester, NY 14642, USA
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15
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Kim DJ, Kim DS, Yu Y, Chung JH, Yoon ES. Cross-sectional analysis for lymphedema epidemiology in South Korea by HIRA data: An observational study. Medicine (Baltimore) 2024; 103:e38779. [PMID: 38968506 PMCID: PMC11224808 DOI: 10.1097/md.0000000000038779] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Accepted: 06/11/2024] [Indexed: 07/07/2024] Open
Abstract
Lymphedema is known to affect as many as 140 to 250 million people worldwide. Approximately 99% of lymphedemas are secondary cases after lymphadenectomy, radiation, or parasite infection. There has been no accurate estimate of the lymphedema population size in South Korea. This study aimed to quantify the epidemiology of lymphedema in South Korea and analyze the clinical characteristics of patients with lymphedema using a nationwide database. This large-scale cross-sectional study included patients who received one of the following three diagnostic codes - Q82.0 (hereditary lymphedema), I97.2 (breast cancer-related lymphedema), and I89.0 (unclassified lymphedema) from the Korean Health Insurance Review and Assessment service between January 2019 and July 2022 at tertiary hospitals, general hospitals, or other hospitals. The demographics of the lymphedema population, medication use, and medical characteristics were identified. Over the last 4 years, the annual incidence of lymphedema has steadily increased and peaked in 2021 with the number 1.85 out of 1000. Of all patients, 81% were located in the upper extremity, and 10.6% had previous cancer. Most patients were diagnosed in general hospitals (53.2%), at orthopedic surgery department (41.9%). On average, lymphedema patients spent 70.17 US dollar for medication and hospitalized for 16.9 days annually after diagnosis. Commonly prescribed medications were Entelon® (Vitis vinifera seed extract) (66.9%), steroids (40.5%), non-steroidal anti-inflammatory drugs (26.5%) and diuretics (21.8%). Only 5.7% of patients received surgery and 19.2% received herbal medicine. This is the first study in South Korea to quantify demographic and medical characteristics of lymphedema patients. These results will contribute to a comprehensive understanding of lymphedema diagnosis and treatment in our nation.
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Affiliation(s)
- Dong-Jin Kim
- Department of Plastic and Reconstructive Surgery, Korea University Anam Hospital, Seoul, Republic of Korea
| | - Da-Som Kim
- Department of Plastic and Reconstructive Surgery, Korea University Anam Hospital, Seoul, Republic of Korea
| | - Yeonju Yu
- Department of Biostatistics, Korea University College of Medicine, Seoul, Republic of Korea
| | - Jae-Ho Chung
- Department of Plastic and Reconstructive Surgery, Korea University Anam Hospital, Seoul, Republic of Korea
- Institute of Advanced Regeneration and Reconstruction, College of Medicine, Korea University, Seoul, Republic of Korea
| | - Eul-Sik Yoon
- Department of Plastic and Reconstructive Surgery, Korea University Anam Hospital, Seoul, Republic of Korea
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16
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Ahn HR, Jeong HE, Jeong C, Kang SY, Jung SH, Youn HJ, Kim JS. Incidence and risk factors of breast cancer-related lymphedema in Korea: a nationwide retrospective cohort study. Int J Surg 2024; 110:3518-3526. [PMID: 38477155 PMCID: PMC11175813 DOI: 10.1097/js9.0000000000001278] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2023] [Accepted: 02/22/2024] [Indexed: 03/14/2024]
Abstract
BACKGROUND Breast cancer-related lymphedema (BCRL) is a secondary lymphedema that occurs after breast cancer related treatments. BCRL develops from damage or dysfunction of the normally functioning lymphatic system due to surgery, radiation therapy, and rarely due to cancer recurrence. This nationwide, retrospective study was aimed at investigating the incidence and risk factors of BCRL using the database of the Korean National Health Insurance Service (NHIS). METHODS Patients with newly diagnosed breast cancer who underwent breast surgery from 1 January 2017 to 31 December 2020, were recruited. The incidence was compared by four groups according to the operation type of breast cancer [breast conserving surgery (BCS) with sentinel lymph node biopsy (S), BCS with axillary lymph node dissection (A), total mastectomy (TM) with S, modified radical mastectomy (MRM)]. The incidence rates of lymphedema were calculated by the number of incident events by the total follow-up period. Cox proportional hazard regression was used to calculate the risk of incidence of lymphedema based on a patients' characteristics, breast cancer treatment, and comorbidities. RESULTS The final cohort of operation subjects that satisfied the inclusion criteria was 34 676. BCRL occurred in 4242 patients (12.2%), and the median follow-up period was 695.4 days. The BCRL was diagnosed in the BCS with S (8.0%), BCS with A (23.5%), TM with S (10.7%), and MRM (28.5%) with an incidence of 40.8, 132.2, 55.8, and 171.8 per 1000 person-years, respectively. Young age, obesity, chemotherapy, radiotherapy, residence in metropolitan areas, and hyperlipidemia were identified as risk factors. CONCLUSION In Korea, the incidence of BCRL was found to be 12.2%, with the highest risk observed among patients who underwent MRM. Therefore, surgical oncologists should meticulously assess the appropriate surgical approach and consider providing education to patients with risk factors for BCRL, aiming to ensure effective prevention strategies.
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Affiliation(s)
- Ha Rim Ahn
- Department of Surgery, Jeonbuk National University Medical School
- Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, South Korea
| | - Hyeong Eun Jeong
- Department of Surgery, Jeonbuk National University Medical School
- Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, South Korea
| | - Choyun Jeong
- Department of Medical Informatics, Jeonbuk National University Medical School
| | - Sang Yull Kang
- Department of Surgery, Jeonbuk National University Medical School
- Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, South Korea
| | - Sung Hoo Jung
- Department of Surgery, Jeonbuk National University Medical School
- Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, South Korea
| | - Hyun Jo Youn
- Department of Surgery, Jeonbuk National University Medical School
- Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, South Korea
| | - Jong Seung Kim
- Department of Otorhinolaryngology, Jeonbuk National University Medical School
- Department of Medical Informatics, Jeonbuk National University Medical School
- Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, South Korea
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17
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Seidenstuecker K, Fertsch S, Ghazaleh AA, Fabi A, Stoffel J, Bukowiecki J, Wolter A, Aghlmandi S, Nadella A, Halbeisen FS, Andree C, Haug MD, Schaefer DJ, Handschin TM, Kappos EA. Improving quality of life after breast cancer: a comparison of two microsurgical treatment options for breast cancer-related lymphedema (BCRL). Clin Exp Med 2024; 24:82. [PMID: 38653874 PMCID: PMC11039536 DOI: 10.1007/s10238-024-01344-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2024] [Accepted: 04/02/2024] [Indexed: 04/25/2024]
Abstract
PURPOSE Vascularized lymph node transfer (VLNT) entails the autologous relocation of lymph nodes to a lymphedematous region of the body, whereas lymphaticovenous anastomosis (LVA) creates a direct bypass between the lymphatic and venous system. Both techniques are meant to lastingly bolster the local lymphatic drainage capacity. This study compared safety and effectiveness of VLNT and LVA in patients with chronic breast cancer related lymphedema (BCRL). METHODS A retrospective cohort study was conducted using data from our encrypted database composed of patients with chronic BCRL who were treated with either VLNT or LVA and had a minimum follow-up of two years. Patient-specific variables analyzed included pre- and postoperative arm circumferences, lymphedema stages and postoperative complications. RESULTS A total of 105 patients met the inclusion criteria, of which 96 patients demonstrated a complete follow-up period of two years. The VLNT group displayed larger preoperative circumferential measurements, evident in both in the isolated examination of the affected arm, as well as when adjusted for the contralateral unaffected arm. Significant reduction in arm volume was achieved by both groups. However, VLNT demonstrated superior relative reduction rates than LVA, neutralizing any significant arm size disparities after 24 months. Surgery duration was slightly longer for VLNT than LVA. Postoperative complications, predominantly minor, were exclusively observed in the VLNT group. CONCLUSIONS Both VLNT and LVA offer significant improvement for patients suffering from chronic BCRL. VLNT shows an even greater potential for improvement in more severe cases of BCRL, but involves a higher risk for (mostly minor) complications.
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Affiliation(s)
- Katrin Seidenstuecker
- Department of Plastic, Reconstructive and Aesthetic Surgery, Sana Hospital Düsseldorf, Düsseldorf, Germany
- Breast Center, University Hospital Düsseldorf, Düsseldorf, Germany
| | - Sonia Fertsch
- Department of Plastic, Reconstructive and Aesthetic Surgery, Sana Hospital Düsseldorf, Düsseldorf, Germany
- Faculty of Health, University Witten-Herdecke, Witten, Germany
| | - Alina A Ghazaleh
- Department of Plastic, Reconstructive and Aesthetic Surgery, Sana Hospital Düsseldorf, Düsseldorf, Germany
| | - Adriano Fabi
- Department of Plastic, Reconstructive, Aesthetic and Hand Surgery, University Hospital of Basel, Spitalstrasse 21, 4031, Basel, Switzerland
- Faculty of Medicine, University of Zurich, Zurich, Switzerland
| | - Julia Stoffel
- Department of Plastic, Reconstructive, Aesthetic and Hand Surgery, University Hospital of Basel, Spitalstrasse 21, 4031, Basel, Switzerland
- Faculty of Medicine, University of Basel, Basel, Switzerland
| | - Julia Bukowiecki
- Department of Plastic, Reconstructive and Aesthetic Surgery, Sana Hospital Düsseldorf, Düsseldorf, Germany
| | - Andreas Wolter
- Department of Plastic, Reconstructive and Aesthetic Surgery, Sana Hospital Düsseldorf, Düsseldorf, Germany
- Faculty of Health, University Witten-Herdecke, Witten, Germany
| | - Soheila Aghlmandi
- Surgical Outcome Research Center, Department of Clinical Research, University Hospital Basel and University of Basel, Basel, Switzerland
| | - Anshoo Nadella
- Surgical Outcome Research Center, Department of Clinical Research, University Hospital Basel and University of Basel, Basel, Switzerland
| | - Florian S Halbeisen
- Surgical Outcome Research Center, Department of Clinical Research, University Hospital Basel and University of Basel, Basel, Switzerland
| | - Christoph Andree
- Department of Plastic, Reconstructive and Aesthetic Surgery, Sana Hospital Düsseldorf, Düsseldorf, Germany
| | - Martin D Haug
- Department of Plastic, Reconstructive, Aesthetic and Hand Surgery, University Hospital of Basel, Spitalstrasse 21, 4031, Basel, Switzerland
- Faculty of Medicine, University of Basel, Basel, Switzerland
| | - Dirk J Schaefer
- Department of Plastic, Reconstructive, Aesthetic and Hand Surgery, University Hospital of Basel, Spitalstrasse 21, 4031, Basel, Switzerland
- Faculty of Medicine, University of Basel, Basel, Switzerland
| | - Tristan M Handschin
- Department of Plastic, Reconstructive, Aesthetic and Hand Surgery, University Hospital of Basel, Spitalstrasse 21, 4031, Basel, Switzerland
- Faculty of Medicine, University of Basel, Basel, Switzerland
| | - Elisabeth A Kappos
- Department of Plastic, Reconstructive, Aesthetic and Hand Surgery, University Hospital of Basel, Spitalstrasse 21, 4031, Basel, Switzerland.
- Faculty of Medicine, University of Basel, Basel, Switzerland.
- Breast Center, University Hospital of Basel, Basel, Switzerland.
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Cai ZM, Li ZZ, Zhong NN, Cao LM, Xiao Y, Li JQ, Huo FY, Liu B, Xu C, Zhao Y, Rao L, Bu LL. Revolutionizing lymph node metastasis imaging: the role of drug delivery systems and future perspectives. J Nanobiotechnology 2024; 22:135. [PMID: 38553735 PMCID: PMC10979629 DOI: 10.1186/s12951-024-02408-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2023] [Accepted: 03/18/2024] [Indexed: 04/02/2024] Open
Abstract
The deployment of imaging examinations has evolved into a robust approach for the diagnosis of lymph node metastasis (LNM). The advancement of technology, coupled with the introduction of innovative imaging drugs, has led to the incorporation of an increasingly diverse array of imaging techniques into clinical practice. Nonetheless, conventional methods of administering imaging agents persist in presenting certain drawbacks and side effects. The employment of controlled drug delivery systems (DDSs) as a conduit for transporting imaging agents offers a promising solution to ameliorate these limitations intrinsic to metastatic lymph node (LN) imaging, thereby augmenting diagnostic precision. Within the scope of this review, we elucidate the historical context of LN imaging and encapsulate the frequently employed DDSs in conjunction with a variety of imaging techniques, specifically for metastatic LN imaging. Moreover, we engage in a discourse on the conceptualization and practical application of fusing diagnosis and treatment by employing DDSs. Finally, we venture into prospective applications of DDSs in the realm of LNM imaging and share our perspective on the potential trajectory of DDS development.
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Affiliation(s)
- Ze-Min Cai
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, 430072, China
| | - Zi-Zhan Li
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, 430072, China
| | - Nian-Nian Zhong
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, 430072, China
| | - Lei-Ming Cao
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, 430072, China
| | - Yao Xiao
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, 430072, China
| | - Jia-Qi Li
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, 430072, China
| | - Fang-Yi Huo
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, 430072, China
| | - Bing Liu
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, 430072, China
- Department of Oral & Maxillofacial Head Neck Oncology, School & Hospital of Stomatology, Wuhan University, Wuhan, 430079, Hubei, China
| | - Chun Xu
- School of Dentistry, The University of Queensland, Brisbane, QLD, 4066, Australia
| | - Yi Zhao
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, 430072, China
- Department of Prosthodontics, School and Hospital of Stomatology, Wuhan University, Wuhan, China
| | - Lang Rao
- Institute of Biomedical Health Technology and Engineering, Shenzhen Bay Laboratory, Shenzhen, 518132, China.
| | - Lin-Lin Bu
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, 430072, China.
- Department of Oral & Maxillofacial Head Neck Oncology, School & Hospital of Stomatology, Wuhan University, Wuhan, 430079, Hubei, China.
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19
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Esmer M, Schingale FJ. Effect of Physical Therapy on Circumference Measurement and Extremity Volume in Patients Suffering from Lipedema with Secondary Lymphedema. Lymphat Res Biol 2024; 22:8-11. [PMID: 37787957 DOI: 10.1089/lrb.2023.0013] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/04/2023] Open
Abstract
Background: Lipedema is a chronic and progressive disease. Many complications can occur if the disease is not treated. The most important of these complications is lipedema with secondary lymphedema. There are very few publications about lipedema with secondary lymphedema. The aim of this study is to investigate the effect of physical therapy on lower extremity circumference and volume in patients suffering from lipedema with secondary lymphedema. Methods and Results: All patients received pneumatic compression and complex decongestive therapy (CDT). Perometer measurement was made at five distinct points. Fifteen patients were included in the study. It was seen that significant reduction was found in the circumference of three of the five points of measurements performed in the left leg, whereas significant reduction was found in the circumference of four of the five points of measurements performed in the right leg. Also, there was a decrease in the extremity volume in both legs. Conclusion: Combined application of CDT and pneumatic compression in patients suffering from lipedema with secondary lymphedema is an effective treatment method in reducing lower extremity volume and circumference measurement.
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Affiliation(s)
- Murat Esmer
- Department of Physiotherapy and Rehabilitation, Faculty of Health Sciences, Gazi University, Ankara, Turkey
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20
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Shimbo K, Kawamoto H, Koshima I. Comparative study of conservative treatment and lymphaticovenular anastomosis with compression therapy for early-stage breast cancer-related lymphoedema. J Plast Reconstr Aesthet Surg 2024; 88:390-396. [PMID: 38086324 DOI: 10.1016/j.bjps.2023.11.035] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Revised: 11/11/2023] [Accepted: 11/22/2023] [Indexed: 01/02/2024]
Abstract
This single-centre retrospective cohort study aimed to clarify the superiority of treatment by comparing the outcomes of lymphaticovenular anastomosis with compression therapy and conservative treatment centred on compression therapy in the early stage of breast cancer-related lymphoedema. Data were collected from all patients treated for breast cancer-related lymphoedema between January 2015 and December 2022. The patients were classified into conservative treatment and surgical treatment groups. The upper extremity lymphoedema index value was calculated, based on five circumference values of the upper extremity and body mass index, to compare the 6-, 12-, 18- and 24-month outcomes between the groups. Of 101 patients with breast cancer-related lymphoedema, 81 (conservative treatment: 52; surgical treatment: 29) were included in the analysis. The therapeutic effect was significantly higher in the surgical treatment group than in the conservative treatment group, when comparing the rate of change in oedema at 6 (-6.6% ± 7.3% vs. 0.9% ± 7.5%; p < 0.001), 12 (-7.3% ± 6.2% vs. 2.9% ± 8.6%; p < 0.001), 18 (-7.6% ± 8.0% vs. 3.9% ± 9.2%; p < 0.001) and 24 (-5.6% ± 6.0% vs. 4.4% ± 10.7%; p < 0.001) months. The incidence of cellulitis increased in the conservative treatment group (from 9.6% to 15.4%), whereas it was suppressed in the surgical treatment group (from 13.8% to 0%). Conservative treatment centred on compression therapy increased oedema over time; however, lymphaticovenular anastomosis with compression therapy effectively reduced oedema.
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Affiliation(s)
- Keisuke Shimbo
- Department of Plastic and Reconstructive Surgery, Hiroshima Prefectural Hospital, Hiroshima, Japan.
| | - Haruka Kawamoto
- Department of Plastic and Reconstructive Surgery, Hiroshima Prefectural Hospital, Hiroshima, Japan.
| | - Isao Koshima
- Department of Plastic and Reconstructive Surgery, Hiroshima University Hospital, Hiroshima, Japan; International Center for Lymphedema, Hiroshima University Hospital, Hiroshima, Japan.
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21
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Shimbo K, Kawamoto H, Koshima I. Conservative treatment versus lymphaticovenular anastomosis for early-stage lower extremity lymphedema. J Vasc Surg Venous Lymphat Disord 2023; 11:1231-1240. [PMID: 37454902 DOI: 10.1016/j.jvsv.2023.06.013] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2023] [Revised: 06/01/2023] [Accepted: 06/04/2023] [Indexed: 07/18/2023]
Abstract
OBJECTIVE Several options for the treatment of lower extremity lymphedema (LEL) can be broadly classified into conservative treatment, such as compression garments and decongestive lymphatic therapy, and surgical treatment, such as lymphaticovenular anastomosis (LVA). The purpose of our study was to clarify the superiority of these treatments by comparing the outcomes of LVA with those of conservative treatment for early-stage LEL. METHODS We performed a single-center, retrospective cohort study. The patients with LEL who presented to our department between January 2015 and December 2022 were identified and classified into two groups: conservative treatment and surgical treatment. The LEL indexes, calculated from the four lower extremity circumferences and the body mass index, were compared at the 6-, 12-, and 24-month follow-up between the two groups. RESULTS Of the 101 patients with LEL, 53 with 72 affected limbs (conservative treatment, 39 patients and 53 affected limbs; surgical treatment, 15 patients and 19 affected limbs) were included in the present analysis. The therapeutic effect for reducing edema, as determined by comparing the corrected LEL index at 12 months (103.7 ± 12.7 vs 91.9 ± 10.7; P = .005) and 24 months (103.1 ± 12.9 vs 83.8 ± 7.2; P < .001), was significantly higher in the surgical treatment group than that in the conservative treatment group. The conservative treatment group showed little change in the corrected LEL index at ≤24 months of follow-up (+3.1%; P = .299). In contrast, the surgical treatment group showed a significant reduction in edema at 24 months according to the corrected LEL index (-16.2%; P = .019). CONCLUSIONS In early-stage LEL, conservative treatment centered on compression therapy alone only maintained edema (ie, edema did not worsen or improve). In contrast, LVA with compression therapy reduced edema.
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Affiliation(s)
- Keisuke Shimbo
- Department of Plastic and Reconstructive Surgery, Hiroshima Prefectural Hospital, Hiroshima, Japan.
| | - Haruka Kawamoto
- Department of Plastic and Reconstructive Surgery, Hiroshima Prefectural Hospital, Hiroshima, Japan
| | - Isao Koshima
- Department of Plastic and Reconstructive Surgery, Hiroshima University Hospital, Hiroshima, Japan; International Center for Lymphedema, Hiroshima University Hospital, Hiroshima, Japan
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22
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Jeffers EJ, Wagner JL, Korentager SS, Larson KE, Balanoff CR, Baker J, Chollet-Hinton L, Kilgore LJ. Breast Cancer-Related Lymphedema (BCRL) and Bioimpedance Spectroscopy: Long-Term Follow-Up, Surveillance Recommendations, and Multidisciplinary Risk Factors. Ann Surg Oncol 2023; 30:6258-6265. [PMID: 37535267 DOI: 10.1245/s10434-023-13956-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2023] [Accepted: 07/06/2023] [Indexed: 08/04/2023]
Abstract
BACKGROUND Early detection and intervention for breast cancer-related lymphedema (BCRL) significantly decreases progression to persistent BCRL (pBCRL). We aimed to provide long-term follow-up on our early detection with bioimpedance spectroscopy (BIS) and early home intervention demonstrating reduced pBCRL to guide surveillance recommendations. PATIENTS AND METHODS In total, 148 female patients with breast cancer who had axillary lymph node dissection (ALND) from November 2014 to December 2017 were analyzed. Baseline BIS measurements and postoperative follow-up occurred every 3 months for 1 year, biannual for 1 year, and then annually. An elevated BIS triggered evaluation and initiation of at-home interventions with reassessment for resolution versus persistent BCRL (pBCRL). High-risk factors and timing were analyzed. RESULTS Mean follow-up was 55 months, and 65 (44%) patients had an abnormal BIS. Of these, 54 (82%) resolved with home intervention. The overall pBCRL rate was 8%. Average time to first abnormal BIS was 11.7 months. None of the stage 0 patients (0/34) and only 5/25 (20%) of stage 1 patients had pBCRL. All of stage 2 and stage 3 patients (7/7) had pBCRL. pBCRL correlated with number of positive nodes, percentage of positive nodes, stage of lymphedema at diagnosis, and recurring abnormal BIS measurements (p < 0.05). CONCLUSIONS We have shown that patients undergoing ALND with early BCRL identified by BIS who performed home interventions had an 8% pBCRL rate. Patients at high risk for pBCRL should have routine surveillance starting at 9 months postoperatively to identify an opportunity for early intervention.
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Affiliation(s)
- Elizabeth J Jeffers
- Division of Breast Surgical Oncology, Department of Surgery, University of Kansas Cancer Center, Kansas City, KS, USA
| | - Jamie L Wagner
- Division of Breast Surgical Oncology, Department of Surgery, University of Kansas Cancer Center, Kansas City, KS, USA
| | - Sabrina S Korentager
- Division of Breast Surgical Oncology, Department of Surgery, University of Kansas Cancer Center, Kansas City, KS, USA
| | - Kelsey E Larson
- Division of Breast Surgical Oncology, Department of Surgery, University of Kansas Cancer Center, Kansas City, KS, USA
| | - Christa R Balanoff
- Division of Breast Surgical Oncology, Department of Surgery, University of Kansas Cancer Center, Kansas City, KS, USA
| | - Jordan Baker
- Department of Biostatistics & Data Science, University of Kansas Medical Center, Kansas City, KS, USA
| | - Lynn Chollet-Hinton
- Department of Biostatistics & Data Science, University of Kansas Medical Center, Kansas City, KS, USA
| | - Lyndsey J Kilgore
- Division of Breast Surgical Oncology, Department of Surgery, University of Kansas Cancer Center, Kansas City, KS, USA.
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23
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Ji H, Hu C, Yang X, Liu Y, Ji G, Ge S, Wang X, Wang M. Lymph node metastasis in cancer progression: molecular mechanisms, clinical significance and therapeutic interventions. Signal Transduct Target Ther 2023; 8:367. [PMID: 37752146 PMCID: PMC10522642 DOI: 10.1038/s41392-023-01576-4] [Citation(s) in RCA: 64] [Impact Index Per Article: 32.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2022] [Revised: 07/04/2023] [Accepted: 07/26/2023] [Indexed: 09/28/2023] Open
Abstract
Lymph nodes (LNs) are important hubs for metastatic cell arrest and growth, immune modulation, and secondary dissemination to distant sites through a series of mechanisms, and it has been proved that lymph node metastasis (LNM) is an essential prognostic indicator in many different types of cancer. Therefore, it is important for oncologists to understand the mechanisms of tumor cells to metastasize to LNs, as well as how LNM affects the prognosis and therapy of patients with cancer in order to provide patients with accurate disease assessment and effective treatment strategies. In recent years, with the updates in both basic and clinical studies on LNM and the application of advanced medical technologies, much progress has been made in the understanding of the mechanisms of LNM and the strategies for diagnosis and treatment of LNM. In this review, current knowledge of the anatomical and physiological characteristics of LNs, as well as the molecular mechanisms of LNM, are described. The clinical significance of LNM in different anatomical sites is summarized, including the roles of LNM playing in staging, prognostic prediction, and treatment selection for patients with various types of cancers. And the novel exploration and academic disputes of strategies for recognition, diagnosis, and therapeutic interventions of metastatic LNs are also discussed.
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Affiliation(s)
- Haoran Ji
- Department of Thoracic Surgery, Shanghai Key Laboratory of Tissue Engineering, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China
| | - Chuang Hu
- Department of Thoracic Surgery, Shanghai Key Laboratory of Tissue Engineering, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China
| | - Xuhui Yang
- Department of Thoracic Surgery, Shanghai Key Laboratory of Tissue Engineering, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China
| | - Yuanhao Liu
- Department of Thoracic Surgery, Shanghai Key Laboratory of Tissue Engineering, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China
| | - Guangyu Ji
- Department of Thoracic Surgery, Shanghai Key Laboratory of Tissue Engineering, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China
| | - Shengfang Ge
- Department of Ophthalmology, Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Xiansong Wang
- Department of Thoracic Surgery, Shanghai Key Laboratory of Tissue Engineering, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
| | - Mingsong Wang
- Department of Thoracic Surgery, Shanghai Key Laboratory of Tissue Engineering, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
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24
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Anik AR, Hasan K, Islam MM, Hasan MM, Ali MF, Das SK. Non-Invasive Portable Technologies for Monitoring Breast Cancer Related Lymphedema to Facilitate Telehealth: A Scoping Review. IEEE J Biomed Health Inform 2023; 27:4524-4535. [PMID: 37247315 DOI: 10.1109/jbhi.2023.3280196] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/31/2023]
Abstract
Breast cancer related lymphedema (BCRL) is a common, debilitating condition that can affect up to one in five breast cancer surviving patients (BCSP). BCRL can significantly reduce the quality of life (QOL) of patients and poses a significant challenge to healthcare providers. Early detection and continuous monitoring of lymphedema is crucial for the development of client-centered treatment plans for post-cancer surgery patients. Therefore, this comprehensive scoping review aimed to investigate the current technology methods used for the remote monitoring of BCRL and their potential to facilitate telehealth in the treatment of lymphedema. Initially, five electronic databases were systematically searched and analyzed following the PRISMA flow diagram. Studies were included, specifically if they provided data on the effectiveness of the intervention and were designed for the remote monitoring of BCRL. A total of 25 included studies reported 18 technological solutions to remotely monitor BCRL with significant methodological variation. Additionally, the technologies were categorized by method of detection and wearability. The findings of this comprehensive scoping review indicate that state-of-the-art commercial technologies were found to be more appropriate for clinical use than home monitoring, with portable 3D imaging tools being popular (SD 53.40) and accurate (correlation 0.9, p 0.05) for evaluating lymphedema in both clinic and home settings with expert practitioners and therapists. However, wearable technologies showed the most future potential for accessible and clinical long-term lymphedema management with positive telehealth outcomes. In conclusion, the absence of a viable telehealth device highlights the need for urgent research to develop a wearable device that can effectively track BCRL and facilitate remote monitoring, ultimately improving the quality of life for patients following post-cancer treatment.
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25
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Soran A, Bengur FB, Rodriguez W, Chroneos MZ, Sezgin E. Early Detection of Breast Cancer-Related Lymphedema: Accuracy of Indocyanine Green Lymphography Compared with Bioimpedance Spectroscopy and Subclinical Lymphedema Symptoms. Lymphat Res Biol 2023; 21:359-365. [PMID: 36946918 DOI: 10.1089/lrb.2022.0066] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/23/2023] Open
Abstract
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.
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Affiliation(s)
- Atilla Soran
- Comprehensive Lymphedema Program, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
- Department of Surgery and University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Fuat Baris Bengur
- Department of Plastic and Reconstructive Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Wendy Rodriguez
- Comprehensive Lymphedema Program, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Maria Z Chroneos
- Department of Surgery and University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Efe Sezgin
- Department of Food Engineering, Izmir Institute of Technology, Izmir, Turkey
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26
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Donahue PMC, MacKenzie A, Filipovic A, Koelmeyer L. Advances in the prevention and treatment of breast cancer-related lymphedema. Breast Cancer Res Treat 2023; 200:1-14. [PMID: 37103598 DOI: 10.1007/s10549-023-06947-7] [Citation(s) in RCA: 42] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Accepted: 04/06/2023] [Indexed: 04/28/2023]
Abstract
PURPOSE Breast cancer-related lymphedema (BCRL) represents a lifelong risk for breast cancer survivors and once acquired becomes a lifelong burden. This review summarizes current BCRL prevention and treatment strategies. FINDINGS Risk factors for BCRL have been extensively studied and their identification has affected breast cancer treatment practice, with sentinel lymph node removal now standard of care for patients with early stage breast cancer without sentinel lymph node metastases. Early surveillance and timely management aim to reduce BCRL incidence and progression, and are further facilitated by patient education, which many breast cancer survivors report not having adequately received. Surgical approaches to BCRL prevention include axillary reverse mapping, lymphatic microsurgical preventative healing (LYMPHA) and Simplified LYMPHA (SLYMPHA). Complete decongestive therapy (CDT) remains the standard of care for patients with BCRL. Among CDT components, facilitating manual lymphatic drainage (MLD) using indocyanine green fluorescence lymphography has been proposed. Intermittent pneumatic compression, nonpneumatic active compression devices, and low-level laser therapy appear promising in lymphedema management. Reconstructive microsurgical techniques such as lymphovenous anastomosis and vascular lymph node transfer are growing surgical considerations for patients as well as liposuction-based procedures for addressing fatty fibrosis formation from chronic lymphedema. Long-term self-management adherence remains problematic, and lack of diagnosis and measurement consensus precludes a comparison of outcomes. Currently, no pharmacological approaches have proven successful. CONCLUSION Progress in prevention and treatment of BCRL continues, requiring advances in early diagnosis, patient education, expert consensus and novel treatments designed for lymphatic rehabilitation following insults.
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Affiliation(s)
- Paula M C Donahue
- Physical Medicine and Rehabilitation, Vanderbilt University Medical Center, 2201 21St Children's Way, Suite 1218, Nashville, TN, 37212, USA.
- Dayani Center for Health and Wellness, Vanderbilt University Medical Center, Nashville, TN, USA.
| | - Adrien MacKenzie
- Osher Center for Integrative Health, Vanderbilt University Medical Center, Nashville, TN, USA
| | | | - Louise Koelmeyer
- Faculty of Medicine, Health, and Human Sciences, Australian Lymphoedema Education, Research, and Treatment (ALERT), Macquarie University, Sydney, Australia
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27
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Perdomo M, Davies C, Levenhagen K, Ryans K, Gilchrist L. Patient education for breast cancer-related lymphedema: a systematic review. J Cancer Surviv 2023; 17:384-398. [PMID: 36207626 PMCID: PMC9546750 DOI: 10.1007/s11764-022-01262-4] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Accepted: 09/22/2022] [Indexed: 11/19/2022]
Abstract
PURPOSE The aim was to identify the impact of the (a) components of breast cancer-related lymphedema (BCRL) educational content, (b) modes of education, and (c) timing of education on arm volume, quality of life, function, complications associated with BCRL, adherence to interventions, and knowledge acquisition in individuals diagnosed with breast cancer (BC). METHODS This review followed the Preferred Reported Items for Systematic Review and Meta-analysis (PRISMA) guidelines (PROSPERO CRD42021253084). Databases searched included PubMed, CINAHL, Web of Science, Google Scholar, and Scopus from January 2010 to December 2021. Study quality and bias were assessed using the American Physical Therapy Association's Critical Appraisal Tool for Experimental Intervention Studies. RESULTS Forty-five studies were eligible, and 15 met the inclusion criteria (4 acceptable and 11 low quality). This review was unable to determine the optimal content, mode, and timing for BCRL education across survivorship. Content included a brief overview of BCRL, early signs and symptoms, risk reduction practices, and a point of contact. Delivery was multi-modal, and knowledge acquisition was rarely assessed. Education was provided pre/post operatively and after BCRL developed. CONCLUSIONS Individualized BCRL education via a multi-modal approach, repeated at multiple time points, and assessment of survivors' knowledge acquisition is recommended. Consideration of the survivors' phase of treatment, content volume, and time required to complete the program is advised when developing the educational intervention. IMPLICATIONS FOR CANCER SURVIVORS Survivors of BC may need to advocate for BCRL education based on their individual risk and needs, request a point of contact for questions/follow up, and express their preferred style of learning.
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Affiliation(s)
- Marisa Perdomo
- Division of Biokinesiology and Physical Therapy @ the Ostrow School of Dentistry, University of Southern California, 1540 Alcazar Street CHP 155, Los Angeles, CA, 90089, USA.
| | - Claire Davies
- Nursing and Allied Health Research Office, Baptist Health Lexington, 1740 Nicholasville Road, Lexington, KY, 40503, USA
| | - Kimberly Levenhagen
- Saint Louis University Program in Physical Therapy, 3437 Caroline Street Suite 1026, St Louis, MO, 63104, USA
| | - Kathryn Ryans
- Mercy College Doctor of Physical Therapy Program, 555 Broadway, , Dobbs Ferry, NY, 10522, USA
| | - Laura Gilchrist
- St. Catherine Univeristy, Doctor of Physical Therapy Program, 2004 Randolph Ave, St. Paul, MN, 55105, USA
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28
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Shah C, Asha W, Vicini F. Current Diagnostic Tools for Breast Cancer-Related Lymphedema. Curr Oncol Rep 2023; 25:151-154. [PMID: 36696076 DOI: 10.1007/s11912-023-01357-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/25/2022] [Indexed: 01/26/2023]
Abstract
PURPOSE OF REVIEW Breast cancer-related lymphedema (BCRL) can have a significant impact on breast cancer survivors quality of life. The purpose of this review is to evaluate diagnostic tools for the assessment of BCRL. RECENT FINDINGS Multiple BCRL diagnostic tools are available, though older diagnostic tools have low sensitivity, limiting the ability for sub-clinical BCRL diagnosis while BIS and perometry have increased sensitivity and the ability to diagnose BCRL sub-clinically. Prospective studies have demonstrated such an approach coupled to early intervention is associated with low rates of chronic BCRL while a recently published randomized trial demonstrated that prospective surveillance with BIS coupled with early intervention reduced rates of chronic BCRL as compared to circumference measurements with compression garments. Prospective and randomized data support the use of prospective surveillance for BCRL. The strongest data available comes from the PREVENT trial and supports prospective BCRL surveillance with bioimpedance spectroscopy coupled to early intervention with a compression sleeve.
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Affiliation(s)
- Chirag Shah
- Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, 10201 Carnegie Avenue, Cleveland, OH, 44106, USA.
| | - Wafa Asha
- Department of Radiation Oncology, King Hussein Cancer Center, Amman, Jordan
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29
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Kim Y, Park EY, Lee H. The effect of myofascial release in patients with breast cancer-related lymphedema: a cross-over randomized controlled trial. Eur J Phys Rehabil Med 2023; 59:85-93. [PMID: 36637800 PMCID: PMC10035446 DOI: 10.23736/s1973-9087.22.07698-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
AIM This study aimed to compare the effects of myofascial release (MFR) on upper extremity volume in patients with breast cancer-related lymphedema (BCRL). DESIGN A randomized, single-blinded, cross-over, controlled trial. SETTING An outpatient rehabilitation clinical setting. POPULATION Thirty patients with BCRL. METHODS Within a crossover design with randomized treatment sequences, fifteen subjects received MFR for 4 weeks, followed by 4 weeks of washout period, and then received placebo MFR and the other fifteen subjects received interventions in the reverse order. Each session had a 60 min process including either MFR or placebo MFR for 30 min, followed by complete decongestive therapy for 30 min twice a week. Upper limb volume as the primary outcome and subjective pain, shoulder range of motion (ROM), chest mobility, shoulder function, and quality of life as secondary outcomes were assessed before and at the end of each intervention period. RESULTS There were significant differences in upper limb volume after both MFR and placebo MFR (P<0.05) while no significant difference between MFR and placebo MFR treatments was found (P>0.05). MFR-based treatment also achieved a greater improvement than placebo MFR-based treatment in subjective pain and shoulder ROM (P<0.05), except for internal rotation, and shoulder function. CONCLUSIONS MFR-based treatment showed clinical improvement in shoulder function, induced by decreased edema volume and pain, and improved ROM and chest mobility. However, a further study with parallel randomized controlled trials to confirm what was achieved in the present study. CLINICAL REHABILITATION IMPACT MFR-based treatment is considered an important part of BCRL rehabilitation. Moreover, MFR-based treatment may be safe for patients with BCRL.
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Affiliation(s)
- Yena Kim
- Department of Physical Therapy, College of Health Science, Gachon University, Incheon, South Korea
| | - Eun Y Park
- College of Nursing, Gachon University, Incheon, South Korea
| | - Haneul Lee
- Department of Physical Therapy, College of Health Science, Gachon University, Incheon, South Korea -
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Gulmark Hansen FC, Jørgensen MG, Sørensen JA. Treatment of Breast Cancer-Related Lymphedema With Topical Tacrolimus: A Prospective, Open-Label, Single-Arm, Phase II Pilot Trial. J Breast Cancer 2023; 26:46-59. [PMID: 36762782 PMCID: PMC9981991 DOI: 10.4048/jbc.2023.26.e2] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Revised: 11/23/2022] [Accepted: 12/13/2022] [Indexed: 02/05/2023] Open
Abstract
PURPOSE Breast cancer-related lymphedema (BCRL) is a chronic, progressive side effect of breast cancer treatment, occurring in one-third of patients treated with axillary lymph node dissection and nodal radiotherapy. Cluster of differentiation 4-positive (CD4+) cells plays a key role in BCRL by facilitating inflammation and inhibiting lymphangiogenesis. Tacrolimus is an anti-inflammatory and immunosuppressive macrolide that targets CD4+ cells. Treatment of lymphedema with topical tacrolimus has revealed promising results in preclinical trials. This clinical trial was aimed at evaluating the feasibility, safety, and effect of tacrolimus in women with stage I or II BCRL, according to the International Society of Lymphology. METHODS We conducted this open-label, single-arm, phase II pilot trial from September 2020 to April 2021. Eighteen women with BCRL stage I or II BCRL were treated with topical tacrolimus for 6 months and followed up at 3 and 6 months. The primary outcome was arm volume, and secondary outcomes were the lymphedema index (L-Dex), health-related quality of life (HRQoL), lymph flow and function, and safety and feasibility of the trial design. RESULTS The mean lymphedema arm volume and L-Dex reduced significantly by 130.44 ± 210.13 mL (p < 0.05; relative reduction: 3.6%) and 3.54 ± 4.98 (p < 0.05), respectively, and health-related quality of life scores was improved significantly (p < 0.05). According to the MD Anderson scale, in terms of lymph flow and function, three patients (16.7%) showed improvement, while none showed worsening. Lymph flow or function showed no change according to the Arm Dermal Backflow scale. CONCLUSION In this trial, treatment with tacrolimus was safe and feasible in women with stage I or II BCRL. Tacrolimus alleviated BCRL in terms of improved arm volume, L-Dex, and HRQoL. Assessments of lymph flow and function were positive, although inconclusive. Larger randomized controlled trials are required to verify these findings. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT04541290.
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Affiliation(s)
- Frederik C. Gulmark Hansen
- Research Unit for Plastic Surgery, Odense University Hospital, Odense, Denmark.,Clinical Institute, University of Southern Denmark, Odense, Denmark
| | - Mads Gustaf Jørgensen
- Research Unit for Plastic Surgery, Odense University Hospital, Odense, Denmark.,Clinical Institute, University of Southern Denmark, Odense, Denmark
| | - Jens Ahm Sørensen
- Research Unit for Plastic Surgery, Odense University Hospital, Odense, Denmark.,Clinical Institute, University of Southern Denmark, Odense, Denmark
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31
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Tolaymat B, Bye M, Lee D, McMackin KK, Lombardi JV, Batista PM. Postamputation diagnosis of squamous cell carcinoma in a patient with lymphedema. J Vasc Surg Cases Innov Tech 2023; 9:101100. [PMID: 36852314 PMCID: PMC9958079 DOI: 10.1016/j.jvscit.2023.101100] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2022] [Revised: 12/13/2022] [Accepted: 12/20/2022] [Indexed: 01/15/2023] Open
Abstract
Chronic lymphedema is fraught with morbidity, including tissue loss. We present the case of a woman with long-standing lymphedema suffering from nonhealing ulcerations despite multiple interventions, who underwent below-knee amputation. Surgical pathology yielded a diagnosis of invasive squamous cell carcinoma. We highlight the uncommon association between lymphedema and squamous cell carcinoma, and the importance of routine pathological testing with lower extremity amputations.
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Affiliation(s)
- Besher Tolaymat
- Correspondence: Besher Tolaymat, MD, Divsion of Vascular Surgery, Department of Surgery, Cooper University Hospital, 3 Cooper Plaza, Suite 411, Camden, NJ 08103
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Sung C, Jiao W, Park SY, Cooper M, Bouz A, Choi D, Jung E, Kim G, Hong YK, Wong AK. Lymphatic endothelial cell RXRα is critical for 9-cis-retinoic acid-mediated lymphangiogenesis and prevention of secondary lymphedema. FASEB J 2023; 37:e22674. [PMID: 36520015 DOI: 10.1096/fj.202200146rr] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2022] [Revised: 11/11/2022] [Accepted: 11/16/2022] [Indexed: 12/23/2022]
Abstract
Secondary lymphedema is a debilitating disease characterized by abnormal soft tissue swelling and caused by lymphatic system dysfunction. Despite a high prevalence of secondary lymphedema after cancer treatments, current management is supportive and there are no approved therapeutic agents that can thwart disease progression. We have previously demonstrated that 9-cis-retinoic acid (9-cisRA) has the potential to be repurposed for lymphedema as it mitigates disease by promoting lymphangiogenesis at the site of lymphatic injury. Although the efficacy of 9-cisRA has been demonstrated in previous studies, the mechanism of action is not completely understood. In this study, we demonstrate that when RXRα is specifically deleted in lymphatic endothelial cells, 9-cisRA fails to induce lymphangiogenesis in vitro and prevent pathologic progression of postsurgical lymphedema in vivo. These findings demonstrate that downstream nuclear receptor RXRα plays a critical role in the therapeutic efficacy of 9-cisRA in postsurgical lymphedema.
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Affiliation(s)
- Cynthia Sung
- Division of Plastic Surgery, City of Hope National Medical Center, Duarte, California, USA.,Keck School of Medicine of USC, Los Angeles, California, USA
| | - Wan Jiao
- Division of Plastic and Reconstructive Surgery, Keck School of Medicine of USC, Los Angeles, California, USA
| | - Sun Young Park
- Division of Plastic Surgery, City of Hope National Medical Center, Duarte, California, USA.,Division of Plastic and Reconstructive Surgery, Keck School of Medicine of USC, Los Angeles, California, USA
| | - Michael Cooper
- Division of Plastic and Reconstructive Surgery, Keck School of Medicine of USC, Los Angeles, California, USA
| | - Antoun Bouz
- Herbert Wertheim College of Medicine of FIU, Miami, Florida, USA
| | - Dahae Choi
- Department of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, Los Angeles, California, USA
| | - Eunson Jung
- Department of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, Los Angeles, California, USA
| | - Gene Kim
- Keck School of Medicine of USC, Los Angeles, California, USA
| | - Young Kwon Hong
- Keck School of Medicine of USC, Los Angeles, California, USA.,Department of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, Los Angeles, California, USA
| | - Alex K Wong
- Division of Plastic Surgery, City of Hope National Medical Center, Duarte, California, USA.,Division of Plastic and Reconstructive Surgery, Keck School of Medicine of USC, Los Angeles, California, USA
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What do we know about treating breast-cancer-related lymphedema? Review of the current knowledge about therapeutic options. Breast Cancer 2023; 30:187-199. [PMID: 36571707 PMCID: PMC9950281 DOI: 10.1007/s12282-022-01428-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Accepted: 12/16/2022] [Indexed: 12/27/2022]
Abstract
Breast-cancer-related lymphedema (BCRL) is a common consequence of oncological treatment. Its management is a complicated, chronic, and arduous process. Therapeutic options can be divided on non-surgical and surgical methods, although there is still no clear consensus about their effectiveness in preventing or stopping the disease. That brings problems in everyday practice, as there are no guidelines about proper time for starting therapy and no agreement about which management will be beneficial for each patient. The aim of this review is to summarize current knowledge about possible treatment choices, non-surgical so as surgical, indicate knowledge gaps, and try to direct pathways for future studies.
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Shah C, Whitworth P, Valente S, Schwarz GS, Kruse M, Kohli M, Brownson K, Lawson L, Dupree B, Vicini FA. Bioimpedance spectroscopy for breast cancer-related lymphedema assessment: clinical practice guidelines. Breast Cancer Res Treat 2023; 198:1-9. [PMID: 36566297 PMCID: PMC9883343 DOI: 10.1007/s10549-022-06850-7] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2022] [Accepted: 11/30/2022] [Indexed: 12/25/2022]
Abstract
PURPOSE Breast cancer-related lymphedema (BCRL) represents a significant concern for patients following breast cancer treatment, and assessment for BCRL represents a key component of survivorship efforts. Growing data has demonstrated the benefits of early detection and treatment of BCRL. Traditional diagnostic modalities are less able to detect reversible subclinical BCRL while newer techniques such as bioimpedance spectroscopy (BIS) have shown the ability to detect subclinical BCRL, allowing for early intervention and low rates of chronic BCRL with level I evidence. We present updated clinical practice guidelines for BIS utilization to assess for BCRL. METHODS AND RESULTS Review of the literature identified a randomized controlled trial and other published data which form the basis for the recommendations made. The final results of the PREVENT trial, with 3-year follow-up, demonstrated an absolute reduction of 11.3% and relative reduction of 59% in chronic BCRL (through utilization of compression garment therapy) with BIS as compared to tape measurement. This is in keeping with real-world data demonstrating the effectiveness of BIS in a prospective surveillance model. For optimal outcomes patients should receive an initial pre-treatment measurement and subsequently be followed at a minimum quarterly for first 3 years then biannually for years 4-5, then annually as appropriate, consistent with previous guidelines; the target for intervention has been changed from a change in L-Dex of 10 to 6.5. The lack of pre-operative measure does not preclude inclusion in the prospective surveillance model of care. CONCLUSION The updated clinical practice guidelines present a standardized approach for a prospective model of care using BIS for BCRL assessment and supported by evidence from a randomized controlled trial as well as real-world data.
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Affiliation(s)
- Chirag Shah
- Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH USA
| | | | - Stephanie Valente
- Department of Breast Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, OH USA
| | - Graham S. Schwarz
- Deparment of Plastic Surgery, Dermatology and Plastic Surgery Institute, Cleveland Clinic, Cleveland, OH USA
| | - Megan Kruse
- Department of Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH USA
| | - Manpreet Kohli
- Department of General Surgery, RWJ Barnabas Health, West Long Beach, NJ USA
| | - Kirstyn Brownson
- Department of General Surgery, University of Utah, Salt Lake City, UT USA
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Erdinç Gündüz N, Şahin E, Dilek B, Ellidokuz H, Akalın E. Adherence to Compression Garment Wear and Associated Factors Among Patients with Breast Cancer-Related Lymphedema: A Pilot Study from a Turkish Tertiary Center. Lymphat Res Biol 2022; 20:665-670. [PMID: 35245100 DOI: 10.1089/lrb.2021.0091] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
Background: Compression garments are the basis of the maintenance phase of the breast cancer-related lymphedema (BCRL) treatment. The aim of this study is to investigate the adherence to compression garment wear and the associated factors among patients with BCRL. Methods and Results: Patients who received standard therapy and training on compression garment wear from a single center were asked to fill out a 28-item questionnaire on compression garment wear. Adherence to compression garment wear and the associated factors were examined. These factors were compared between patients who were wearing and who were not wearing compression garments as recommended. The study was completed with 60 patients. Twenty-five percent of the patients used custom-made compression garment. The rate of patients wearing compression garments as per recommendation was 51.7% (n = 31). The most common reasons for not wearing/discontinuation included functional difficulties in daily life (33%) and discomfort (28.8%). Compared according to the factors with potential impact on wearing, the rate of garment wear as per recommendation was statistically significantly higher in patients who had modified radical mastectomy than in those who had breast-conserving surgery (p = 0.038). Conclusion: Although standard information was provided to the patients, the adherence to compression garments was nonoptimal. The economic status of the patients is one of the main factors affecting the choice of compression garments and thus their adherence. To improve the adherence to this method, which is the basis of maintenance treatment of lymphedema, training programs to reduce patient beliefs and anxiety that are tailored to individual needs can be useful. Clinical trial registration number: NCT04832386.
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Affiliation(s)
- Nihan Erdinç Gündüz
- Department of Physical Medicine and Rehabilitation, Izmir Tepecik Training and Research Hospital, Health Science University, Izmir, Turkey
| | - Ebru Şahin
- Department of Physical Medicine and Rehabilitation, Faculty of Medicine, Dokuz Eylul University, Izmir, Turkey
| | - Banu Dilek
- Department of Physical Medicine and Rehabilitation, Faculty of Medicine, Dokuz Eylul University, Izmir, Turkey
| | - Hülya Ellidokuz
- Department of Biostatistics and Medical Informatics, Faculty of Medicine, Dokuz Eylul University, Izmir, Turkey
| | - Elif Akalın
- Department of Physical Medicine and Rehabilitation, Faculty of Medicine, Dokuz Eylul University, Izmir, Turkey
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Deban M, Vallance P, Jost E, McKinnon JG, Temple-Oberle C. Higher Rate of Lymphedema with Inguinal versus Axillary Complete Lymph Node Dissection for Melanoma: A Potential Target for Immediate Lymphatic Reconstruction? Curr Oncol 2022; 29:5655-5663. [PMID: 36005184 PMCID: PMC9406378 DOI: 10.3390/curroncol29080446] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Revised: 08/05/2022] [Accepted: 08/08/2022] [Indexed: 11/16/2022] Open
Abstract
Background: The present study was conducted to define the lymphedema rate at our institution in patients undergoing axillary (ALND) or inguinal (ILND) lymph node dissection (LND) for melanoma. It aimed to examine risk factors predisposing patients to a higher rate of lymphedema, highlighting which patients could be targeted for immediate lymphatic reconstruction (ILR). Methods: A retrospective chart review was conducted between October 2015 and July 2020 to identify patients who had undergone ALND or ILND for melanoma. The main outcome measures were rates of transient and permanent lymphedema. Univariate and multivariate analyses were performed to assess the relationship between lymphedema rate and factors related to patient characteristics, surgical procedure, pathology findings, and adjuvant treatment. Results: Between October 2015 and July 2020, 66 patients underwent LND for melanoma: 34 patients underwent ALND and 32 patients underwent ILND. At a median follow-up of 29 months, 85.3% (n = 29) of patients having had an ALND did not experience lymphedema, versus 50.0% (n = 16) of ILND (p = 0.0019). The rates of permanent lymphedema for patients having undergone ALND and ILND were 11.8% (n = 4) and 37.5% (n = 12) respectively (p = 0.016, NS). The rate of transient lymphedema was 2.9% (n = 1) for ALND and 12.5% (n = 4) for ILND (p = 0.13, NS). On univariate analysis, the location of LND and wound infection were found to be significant factors for lymphedema. On multivariate analysis, only the location of LND remained a significant predictor, with the inguinal location predisposing to lymphedema. Conclusion: This study highlights the high rate of lymphedema following ILND for melanoma and is a potential target for future patients to be considered for ILR.
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Affiliation(s)
- Melina Deban
- Surgical Oncology, Tom Baker Cancer Center, Calgary, AB T2N 4N2, Canada
- Correspondence:
| | - Patrick Vallance
- Surgical Oncology, Tom Baker Cancer Center, Calgary, AB T2N 4N2, Canada
| | - Evan Jost
- Surgical Oncology, Tom Baker Cancer Center, Calgary, AB T2N 4N2, Canada
| | | | - Claire Temple-Oberle
- Plastic and Reconstructive Surgery, Tom Baker Cancer Center, Calgary, AB T2N 4N2, Canada
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Hsu JF, Yu RP, Stanton EW, Wang J, Wong AK. Current Advancements in Animal Models of Postsurgical Lymphedema: A Systematic Review. Adv Wound Care (New Rochelle) 2022; 11:399-418. [PMID: 34128396 PMCID: PMC9142133 DOI: 10.1089/wound.2021.0033] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023] Open
Abstract
Significance: Secondary lymphedema is a debilitating disease caused by lymphatic dysfunction characterized by chronic swelling, dysregulated inflammation, disfigurement, and compromised wound healing. Since there is no effective cure, animal model systems that support basic science research into the mechanisms of secondary lymphedema are critical to advancing the field. Recent Advances: Over the last decade, lymphatic research has led to the improvement of existing animal lymphedema models and the establishment of new models. Although an ideal model does not exist, it is important to consider the strengths and limitations of currently available options. In a systematic review adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we present recent developments in the field of animal lymphedema models and provide a concise comparison of ease, cost, reliability, and clinical translatability. Critical Issues: The incidence of secondary lymphedema is increasing, and there is no gold standard of treatment or cure for secondary lymphedema. Future Directions: As we iterate and create animal models that more closely characterize human lymphedema, we can achieve a deeper understanding of the pathophysiology and potentially develop effective therapeutics for patients.
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Affiliation(s)
- Jerry F. Hsu
- Division of Plastic and Reconstructive Surgery, Keck School of Medicine of USC, Los Angeles, California, USA.,Division of Plastic Surgery, City of Hope National Medical Center, Duarte, California, USA.,Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
| | - Roy P. Yu
- Division of Plastic and Reconstructive Surgery, Keck School of Medicine of USC, Los Angeles, California, USA
| | - Eloise W. Stanton
- Division of Plastic and Reconstructive Surgery, Keck School of Medicine of USC, Los Angeles, California, USA
| | - Jin Wang
- Division of Plastic and Reconstructive Surgery, Keck School of Medicine of USC, Los Angeles, California, USA.,Division of Plastic Surgery, City of Hope National Medical Center, Duarte, California, USA
| | - Alex K. Wong
- Division of Plastic and Reconstructive Surgery, Keck School of Medicine of USC, Los Angeles, California, USA.,Division of Plastic Surgery, City of Hope National Medical Center, Duarte, California, USA.,Correspondence: Division of Plastic Surgery, City of Hope National Medical Center, 1500 E. Duarte Road, Pavillion 2216, Duarte, CA 91010, USA.
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Single-cell RNA sequencing of subcutaneous adipose tissues identifies therapeutic targets for cancer-associated lymphedema. Cell Discov 2022; 8:58. [PMID: 35725971 PMCID: PMC9209506 DOI: 10.1038/s41421-022-00402-5] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2021] [Accepted: 03/09/2022] [Indexed: 12/14/2022] Open
Abstract
Cancer-associated lymphedema frequently occurs following lymph node resection for cancer treatment. However, we still lack effective targeted medical therapies for the treatment or prevention of this complication. An in-depth elucidation of the cellular alterations in subcutaneous adipose tissues of lymphedema is essential for medical development. We performed single-cell RNA sequencing of 70,209 cells of the stromal vascular fraction of adipose tissues from lymphedema patients and healthy donors. Four subpopulations of adipose-derived stromal cells (ASCs) were identified. Among them, the PRG4+/CLEC3B+ ASC subpopulation c3 was significantly expanded in lymphedema and related to adipose tissue fibrosis. Knockdown of CLEC3B in vitro could significantly attenuate the fibrogenesis of ASCs from patients. Adipose tissues of lymphedema displayed a striking depletion of LYVE+ anti-inflammatory macrophages and exhibited a pro-inflammatory microenvironment. Pharmacological blockage of Trem1, an immune receptor predominantly expressed by the pro-inflammatory macrophages, using murine LR12, a dodecapeptide, could significantly alleviate lymphedema in a mouse tail model. Cell–cell communication analysis uncovered a perivascular ligand-receptor interaction module among ASCs, macrophages, and vascular endothelial cells. We provided a comprehensive analysis of the lineage–specific changes in the adipose tissues from lymphedema patients at a single-cell resolution. CLEC3B was found to be a potential target for alleviating adipose tissue fibrosis. Pharmacological blockage of TREM1 using LR12 could serve as a promising medical therapy for treating lymphedema.
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Winters H, Tielemans H, Hummelink S, Slater N, Ulrich D. DIEP flap breast reconstruction combined with vascularized lymph node transfer for patients with breast cancer-related lymphedema. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2022; 48:1718-1722. [DOI: 10.1016/j.ejso.2022.05.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2021] [Revised: 05/06/2022] [Accepted: 05/09/2022] [Indexed: 11/29/2022]
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Perez CS, Mestriner C, Ribeiro LTN, Grillo FW, Lemos TW, Carneiro AA, Guirro RRDJ, Guirro ECO. Relationship between lymphedema after breast cancer treatment and biophysical characteristics of the affected tissue. PLoS One 2022; 17:e0264160. [PMID: 35442985 PMCID: PMC9020674 DOI: 10.1371/journal.pone.0264160] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2020] [Accepted: 02/04/2022] [Indexed: 12/24/2022] Open
Abstract
The treatment of breast cancer is often complicated by lymphedema of the upper limbs. Standard lymphedema evaluation methodologies are not able to measure tissue fibrosis. The ultrasound aspects related to tissue microstructures of lymphedema are neglected in clinical evaluations. The objective of this study was to identify and measure the degree of impairment, topography, and biophysical alterations of subcutaneous lymphedema tissue secondary to the treatment of breast cancer by ultrasonography. Forty-two women at a mean age of 58 (±9.7) years, with unilateral lymphedema due to breast cancer treatment, were evaluated. The upper limbs were divided into affected (affected by lymphedema) and control (contralateral limb). Each limb was subdivided into seven areas, defined by perimetry, evaluated in pairs. The biophysical characteristics thickness, entropy, and echogenicity were evaluated by ultrasonography. The results showed a significant difference in the echogenicity and thickness variables between the affected and unaffected upper limb, in all the extent of the upper limb, while entropy showed no significant difference. The findings indicate that the data presented were consistent both in identifying and measuring the degree of impairment and biophysical changes in the subcutaneous tissue of lymphedema secondary to the treatment of breast cancer.
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Affiliation(s)
- Carla S. Perez
- Programa de Pós-Graduação em Reabilitação e Desempenho Funcional, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brasil
- Departamento de Ciências das Saúde, Faculdade de Medicina de Ribeirão Preto, Universidade de são Paulo, Ribeirão Preto, São Paulo, Brasil
- * E-mail: , (CSP); (ECOG)
| | - Carolina Mestriner
- Programa de Pós-Graduação em Reabilitação e Desempenho Funcional, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brasil
| | - Leticia T. N. Ribeiro
- Departamento de Física, Faculdade de Filosofia, ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brasil
| | - Felipe W. Grillo
- Departamento de Física, Faculdade de Filosofia, ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brasil
| | - Tenysson W. Lemos
- Departamento de Ciências das Saúde, Faculdade de Medicina de Ribeirão Preto, Universidade de são Paulo, Ribeirão Preto, São Paulo, Brasil
| | - Antônio A. Carneiro
- Departamento de Física, Faculdade de Filosofia, ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brasil
| | - Rinaldo Roberto de Jesus Guirro
- Programa de Pós-Graduação em Reabilitação e Desempenho Funcional, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brasil
- Departamento de Ciências das Saúde, Faculdade de Medicina de Ribeirão Preto, Universidade de são Paulo, Ribeirão Preto, São Paulo, Brasil
| | - Elaine C. O. Guirro
- Programa de Pós-Graduação em Reabilitação e Desempenho Funcional, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brasil
- Departamento de Ciências das Saúde, Faculdade de Medicina de Ribeirão Preto, Universidade de são Paulo, Ribeirão Preto, São Paulo, Brasil
- * E-mail: , (CSP); (ECOG)
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Küçükakkaş O, İnce B. Can YouTube be used as an educational tool in lymphedema rehabilitation? Arch Physiother 2022; 12:5. [PMID: 35236412 PMCID: PMC8890817 DOI: 10.1186/s40945-022-00130-9] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Accepted: 01/11/2022] [Indexed: 11/10/2022] Open
Abstract
Background Lymphedema is defined as the abnormal accumulation of interstitial fluid and fibro-adipose tissues resulting from injury, infection, or congenital abnormalities of the lymphatic system. The gold standard approach in the treatment of lymphedema is Complete Decongestive Therapy and it has many components that require practical knowledge and skills. YouTube can be a useful tool to provide these skills to healthcare professionals and patients. The aim of this study was to examine the videos about lymphedema rehabilitation on YouTube and analyze their technical features, sources, contents, educational value and reliability. Methods The YouTube database was searched using the “lymphedema rehabilitation”, “lymphedema treatment”, “complete decongestive therapy”, “lymphedema massage”, and “lymphedema exercises” keywords. Two reviewers (Physical medicine and rehabilitation specialist) assessed videos for educational quality using a Global Quality Scale (GQS). To evaluate the reliability the 5-point Discern scale was used. Results A total of 90 videos, which met the inclusion criteria were included in the analysis. The mean duration of the videos was 8.9 ± 10.5 min. The mean number of daily views was 22.7 ± 47.1 for a day. The majority of the videos were created to inform patients (57.8%).The uploaders were mostly private healthcare institutions or healthcare professionals (65.6%). Information providers were lymphedema therapists mostly (63.3%). Manual lymphatic drainage was observed to stand out as the most mentioned lymphedema rehabilitation component on YouTube. The mean of reliability and GQS scores of the videos were 2.2 ± 1.0 and 2.7 ± 1.0, respectively. Conclusions The biggest obstacle for YouTube to be an excellent source of information is that it hosts large volumes of uncontrolled and low-quality data. When Youtube content related to lymphedema rehabilitation was examined, it was observed that many videos were quite insufficient and incomplete even though there were useful videos. If careful controlling measures are implemented and if medical videos aim to meet reliability and GQS criteria, YouTube can become an effective and useful source of information for lymphedema rehabilitation.
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Affiliation(s)
- Okan Küçükakkaş
- Department of Physical Medicine and Rehabilitation, Faculty of Medicine, Bezmialem Vakıf University, 34093, Istanbul, Turkey.
| | - Buğra İnce
- Department of Physical Medicine and Rehabilitation, Faculty of Medicine, Bezmialem Vakıf University, 34093, Istanbul, Turkey
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Psychometric Properties of Quality of Life Questionnaires for Patients with Breast Cancer-Related Lymphedema: A Systematic Review. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:ijerph19052519. [PMID: 35270209 PMCID: PMC8909332 DOI: 10.3390/ijerph19052519] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/19/2022] [Revised: 02/18/2022] [Accepted: 02/19/2022] [Indexed: 02/04/2023]
Abstract
Backgrounds: Assessing quality of life (QoL) using a well-developed and validated questionnaire is an essential part of a breast cancer-related lymphedema (BCRL) treatment. However, a QoL questionnaire with the best psychometric properties is so far unknown. The aim of this systematic review is to evaluate the psychometric properties of the questionnaires measuring the QoL of patients with BCRL. Methods: A thorough search was performed to identify published studies in electronic databases such as Medline (via Ovid), EBSCOhost, PubMed, Scopus, and Web of Science, on 8 February 2022, by using search terms as follows: ‘quality of life’; ‘breast cancer’; ‘upper limb’; ‘lymphedema’; ‘questionnaire’; and ‘measurement properties.’ Two reviewers conducted article selection, data extraction, and quality assessment independently. The third reviewer helped solve any possible disagreements between the two reviewers. The COSMIN checklist and manual were used to assess the quality of included studies. Results: A total of nineteen articles with nine questionnaires were included and assessed using the COSMIN Risk of Bias checklist. Most studies only assessed content validity, structural validity, internal consistency, reliability, and construct validity. Lymph-ICF-UL showed the most ‘sufficient’ and ‘high’ quality of evidence ratings for its measurement properties. Conclusion: The most appropriate questionnaire for use based on our assessment is Lymph-ICF-UL.
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A Prospective Observational Pilot Study of Young Women Undergoing Initial Breast Cancer Treatment and Their Biopsychosocial Profile. REHABILITATION ONCOLOGY 2022. [DOI: 10.1097/01.reo.0000000000000298] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Pina Moreno J, Ortega Abad V, Perez Corral A, Garcia‐Tizon Larroca S. Maternal mirror syndrome with foetal hydrops due to isoimunization by anti-KPa antibodies: A case report and narrative literature review. Clin Case Rep 2022; 10:e05484. [PMID: 35223025 PMCID: PMC8850394 DOI: 10.1002/ccr3.5484] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Accepted: 01/11/2022] [Indexed: 11/12/2022] Open
Abstract
We present a rare case of mirror syndrome due to anti-Kpa antibodies, which can be difficult to identify with routine screening tests.
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Affiliation(s)
| | | | - Ana Perez Corral
- HematologyHospital General Universitario Gregorio MarañonMadridSpain
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Rafn BS, Christensen J, Larsen A, Bloomquist K. Prospective Surveillance for Breast Cancer-Related Arm Lymphedema: A Systematic Review and Meta-Analysis. J Clin Oncol 2022; 40:1009-1026. [PMID: 35077194 DOI: 10.1200/jco.21.01681] [Citation(s) in RCA: 46] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
PURPOSE The call to integrate prospective surveillance for lymphedema into cancer care pathways is building momentum to enable early intervention and prevent the progression of the condition. We offer a critical evaluation of the literature on prospective surveillance and early management for cancer-related lymphedema and evaluate the effect of such programs in preventing chronic lymphedema (CRD42019137965). METHODS Five databases and two registries were searched for randomized controlled trials or observational studies that assessed the incidence or prevalence of lymphedema associated with participation in a prospective surveillance program, published until February 26, 2021. Numbers triggered for early lymphedema management, resolved, and chronic lymphedema were extracted. Pooled relative risk (trials) and pooled rate (cumulative incidence; observational studies) of chronic lymphedema was calculated. Subgroup analyses assessed the effect of study design, length of follow-up, and extent of axillary surgery. RESULTS Twenty-three studies were included, of which 21 studies evaluated breast cancer-related arm lymphedema (BCRaL). Participation in prospective surveillance with early management reduced the risk of chronic BCRaL versus usual care (relative risk 0.31; 95% CI, 0.10 to 0.95; two randomized controlled trials; N = 106). The pooled rate of chronic BCRaL was 4% (95% CI, 3 to 6; 15 observational studies; N = 3,545), and 6% (95% CI, 4 to 9) when restricted to participants with axillary lymph node dissection (12 studies; N = 1,527). CONCLUSION The findings suggest that participation in prospective surveillance with early management reduces the risk of chronic BCRaL. Only a minority of patients at high risk of lymphedema because of axillary surgery developed chronic lymphedema. More robust research is needed to determine whether prospective surveillance with early management can reduce the risk of chronic lymphedema, particularly among cancer survivors other than breast cancer.
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Affiliation(s)
- Bolette S Rafn
- Cancer Survivorship and Treatment Late Effects Research Unit (CASTLE), Department of Oncology, Copenhagen University Hospital, Rigshospitalet, Denmark
| | - Jan Christensen
- Department of Occupational Therapy and Physiotherapy, Copenhagen University Hospital, Rigshospitalet, Denmark
| | - Anders Larsen
- University Hospitals Centre for Health Research (UCSF), Copenhagen University Hospital, Rigshospitalet, Denmark
| | - Kira Bloomquist
- University Hospitals Centre for Health Research (UCSF), Copenhagen University Hospital, Rigshospitalet, Denmark
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46
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Yoshihara M, Kitamura K, Tsuru S, Shimono R, Sakuda H, Mayama M, Tano S, Uno K, Ukai MO, Kishigami Y, Oguchi H, Hirota A. Factors associated with response to compression-based physical therapy for secondary lower limb lymphedema after gynecologic cancer treatment: a multicenter retrospective study. BMC Cancer 2022; 22:25. [PMID: 34980013 PMCID: PMC8722292 DOI: 10.1186/s12885-021-09163-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2021] [Accepted: 11/30/2021] [Indexed: 11/30/2022] Open
Abstract
Background Lower limb lymphedema (LLL) is one of the most refractory and debilitating complications related to gynecological cancer treatment. We investigated factors associated with response to compression-based physical therapy (CPT) for secondary LLL after gynecologic cancer treatment. Methods We performed a multicenter retrospective study using the records of seven medical institutions from 2002 and 2014. Patients who developed LLL after gynecological cancer treatment were included. Limb volumes were calculated from the lengths of the limb circumferences at four points. All participants underwent compression-based physical therapy for LLL. Factors, including MLD, indicative of circumference reductions in LLL were determined. Results In total, 1,034 LLL met the required criteria of for the study. A multivariate linear regression analysis identified age; body mass index (BMI); endometrial cancer; radiotherapy; and initial limb circumference as significant independent prognostic factors related to improvement in LLL. In analysis of covariance for improvement in LLL adjusted by the initial limb circumference and stratified by BMI and radiotherapy, patients with BMI 28 kg/m2 or higher and receiving radiation rarely responded to CPT. Conclusions Improvements in the lower limb circumference correlated with clinical histories and physical characteristics, which may be used as independent prognostic factors for successful CPT for LLL after gynecological cancer treatment.
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Affiliation(s)
- Masato Yoshihara
- Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan.,Obstetrics and Gynecology, TOYOTA Memorial Hospital, 1-1 Heiwa-cho, Toyota, Aichi, 471-8513, Japan
| | - Kaoru Kitamura
- Department of Breast Surgery, Kaizuka Hospital, 7-7-27 Hakozaki, Higashi-ku, Fukuoka, Fukuoka, 812-0053, Japan
| | - Satoko Tsuru
- School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan.
| | - Ryoko Shimono
- Organization for Interdisciplinary Research Project, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan
| | - Hiromi Sakuda
- Graduate School of Nursing, Osaka City University, 3-3-138, Sugimoto, Sumiyoshi-ku, Osaka-shi, 558-8585, Japan
| | - Michinori Mayama
- Obstetrics and Gynecology, TOYOTA Memorial Hospital, 1-1 Heiwa-cho, Toyota, Aichi, 471-8513, Japan.,Obstetrics and Gynecology, Hokkaido University Graduate School of Medicine, Kita 8, Nishi 5, Kita-ku, Sapporo, Hokkaido, 060-0808, Japan
| | - Sho Tano
- Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan.,Obstetrics and Gynecology, TOYOTA Memorial Hospital, 1-1 Heiwa-cho, Toyota, Aichi, 471-8513, Japan
| | - Kaname Uno
- Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan.,Obstetrics and Gynecology, TOYOTA Memorial Hospital, 1-1 Heiwa-cho, Toyota, Aichi, 471-8513, Japan
| | - Mayu Ohno Ukai
- Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan.,Obstetrics and Gynecology, TOYOTA Memorial Hospital, 1-1 Heiwa-cho, Toyota, Aichi, 471-8513, Japan
| | - Yasuyuki Kishigami
- Obstetrics and Gynecology, TOYOTA Memorial Hospital, 1-1 Heiwa-cho, Toyota, Aichi, 471-8513, Japan
| | - Hidenori Oguchi
- Obstetrics and Gynecology, TOYOTA Memorial Hospital, 1-1 Heiwa-cho, Toyota, Aichi, 471-8513, Japan
| | - Akio Hirota
- Hirota Internal Medicine Clinic, 5-19-10 Minami-karasuyama, Setagaya-ku, Tokyo, 157-0062, Japan
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47
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Al-Sakkaf AM, Masia J, Auladell-Rispau A, Shamardal AI, Vasconcello-Castillo L, Sola I, Bonfill X. Evidence Mapping of the Treatments for Breast Cancer-related Lymphedema. PLASTIC AND RECONSTRUCTIVE SURGERY-GLOBAL OPEN 2022; 10:e4045. [PMID: 35070599 PMCID: PMC8769095 DOI: 10.1097/gox.0000000000004045] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Accepted: 11/16/2021] [Indexed: 02/07/2023]
Abstract
Women treated for breast cancer are facing a lifetime risk of developing lymphedema, which occurs in up to 40% of this population. There is a lack of evidence and limited knowledge regarding the treatment of breast cancer-related lymphedema (BCRL). The aim of this study was to identify, describe, and organize the currently available evidence in the treatment of BCRL. METHODS We conducted an evidence mapping review study according to the methodology proposed by Global Evidence Mapping. We performed a systematic search in Medline, Embase, Central (Cochrane), and Epistemonikos, from 2000-2020. We included studies about all treatment types for BCRL, including surgical and nonsurgical treatment. Results were summarized in narrative and tabular forms. RESULTS A total of 240 studies were included in this mapping review, distributed as follows: 147 experimental studies [102 randomized clinical trials (RCTs) and 45 quasi-experimental clinical trials], 48 observational studies (34 prospective and 14 retrospective studies), and 45 systematic reviews (17 of them with metanalysis). Most of the RCTs were on nonsurgical interventions. Only two RCTs addressed surgical intervention. CONCLUSIONS In the last 20 years, there were an average of 12 publications per year on the treatment of BCRL. Recently this lack of attention has been partially corrected, as the majority were published in the past 5 years. However, most of them were on nonsurgical interventions. Well-designed RCTs on surgery are needed to measure the effectiveness of the applied interventions.
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Affiliation(s)
- Ali M. Al-Sakkaf
- From Department of Plastic Surgery, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Jaume Masia
- From Department of Plastic Surgery, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain
| | | | | | - Luis Vasconcello-Castillo
- Department of Physical Therapy, Faculty of Medicine, University of Chile, Santiago, Chile
- International Physiotherapy Research Network (PhysioEvidence)
| | - Ivan Sola
- Health Education England-East Midlands, London, UK
- International Physiotherapy Research Network (PhysioEvidence)
| | - Xavier Bonfill
- Health Education England-East Midlands, London, UK
- Iberoamerican Cochrane Centre, Biomedical Research Institute Sant Pau (IIB Sant Pau), CIBERESP, Universitat Autònoma de Barcelona, Barcelona, Spain
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Laustsen-Kiel CM, Lauritzen E, Langhans L, Engberg Damsgaard T. Study protocol for a 10-year prospective observational study, examining lymphoedema and patient-reported outcome after breast reconstruction. BMJ Open 2021; 11:e052676. [PMID: 34873005 PMCID: PMC8650483 DOI: 10.1136/bmjopen-2021-052676] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
INTRODUCTION Over the last decades, treatment of breast cancer has become increasingly more effective. Consequently, an increasing number of women are living with late effects of breast cancer treatment, including disfiguring scars, deformity or asymmetry of the breast, secondary lymphoedema and other physical and psychosocial late effects. Data from this study will provide knowledge on how to guide breast reconstruction in the future towards outcomes with fewer complications, higher long-term quality of life (QoL) and satisfaction with the aesthetic outcome. The development of secondary lymphoedema, for which the effect of breast reconstruction has yet to be established, will be thoroughly examined. METHODS AND ANALYSIS Women receiving breast reconstruction (autologous and implant based) at the Department of Plastic Surgery and Burns Treatment, Rigshospitalet, will be invited to participate. The patients will be followed for 10 years postoperatively. Demographic, health-related, oncological characteristics and treatment data will be registered. Validated assessment tools, such as the BREAST-Q and Beck Depression Inventory, will be used to measure an extensive range of clinical outcomes, including QoL, life and aesthetic satisfaction and depression. Arm range of motion will be measured with a goniometer and lymphoedema by bioimpedance spectroscopy, compared with circular arm measurements. ETHICS AND DISSEMINATION This study will be conducted according to the 5th version of the Helsinki Declaration. The regional ethical committee for Capital Region Denmark did not find the study notifiable, according to the law of the committee § 1, part 4. All data will be anonymised before its publication. This study will be conducted according to the Danish data protection regulation and is catalogued and approved by the Capital Region Head of Knowledge Centre. According to the Danish health law § 46, part 2, this study does not need the Danish Patient Safety Authority's approval. The findings of this study will be submitted to international peer-reviewed journals.
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Affiliation(s)
| | - Elisabeth Lauritzen
- Department of Plastic Surgery and Burns Treatment, Rigshospitalet, Copenhagen, Denmark
| | - Linnea Langhans
- Department of Plastic Surgery and Burns Treatment, Rigshospitalet, Copenhagen, Denmark
| | - Tine Engberg Damsgaard
- Department of Plastic Surgery and Burns Treatment, Rigshospitalet, Copenhagen, Denmark
- Institute of Clinical Medicine, University of Copenhagen Faculty of Health and Medical Sciences, Copenhagen, Denmark
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Hou G, Zhang Y, Chen L, Li F, Jing H. The relationship between the drainage function of inguinal lymph nodes and unilateral pelvic cancer-related lymphedema: A retrospective analysis. Medicine (Baltimore) 2021; 100:e28051. [PMID: 35049221 PMCID: PMC9191291 DOI: 10.1097/md.0000000000028051] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2021] [Accepted: 11/10/2021] [Indexed: 11/29/2022] Open
Abstract
The aim of this study was to investigate the relationship between iliolumbar lymph nodes (LNs), inguinal LNs, and unilateral pelvic cancer-related lymphedema by retrospective analysis of lymphoscintigraphy data.Ninety-six patients (3 men and 93 women; mean age, 53.3 ± 11.3 years) with pelvic cancer-related lymphedema were enrolled in this retrospective study. Lymphoscintigraphy was performed at 1 hour and 4 to 6 hours after injection. The visualization of inguinal LNs and iliolumbar LNs were recorded.According to statistical analysis, the display of inguinal LNs in lymphoscintigraphy has a significant negative correlation with ipsilateral lower limb lymphedema (P < .01, r = -0.561). However, there is no correlation between the show of iliolumbar LNs and ipsilateral lower extremity lymphedema (P = .056, r = -0.138). When lymphoscintigraphy was performed at 1 hour after injection, there were 13 out of 96 patients without inguinal LNs revealed on imaging, but at 4 to 6 hours after injection, inguinal LNs were seen in lymphoscintigraphy.The drainage function of inguinal LNs has a significant negative correlation with ipsilateral pelvic cancer-related lymphedema. Treatment dedicated to restoring the drainage function of LNs in the inguinal region may effectively relieve lymphedema. The image acquisition at 4 to 6 hours after injection is necessary for significant additional information.
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Affiliation(s)
- Guozhu Hou
- Department of Nuclear Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Beijing, China
| | - Yuwei Zhang
- Department of Nuclear Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Beijing, China
| | - Libo Chen
- Department of Nuclear Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Beijing, China
| | - Fang Li
- Department of Nuclear Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Beijing, China
| | - Hongli Jing
- Department of Nuclear Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Beijing, China
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50
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Use of adipose-derived stem cells in lymphatic tissue engineering and regeneration. Arch Plast Surg 2021; 48:559-567. [PMID: 34583446 PMCID: PMC8490113 DOI: 10.5999/aps.2021.00339] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2021] [Accepted: 06/16/2021] [Indexed: 12/11/2022] Open
Abstract
The potential to differentiate into different cell lines, added to the easy and cost-effective method of extraction, makes adipose-derived stem cells (ADSCs) an object of interest in lymphedema treatment. Our study’s goal was to conduct a comprehensive systematic review of the use of ADSCs in lymphatic tissue engineering and regeneration. On July 23, 2019, using PubMed/MEDLINE, Cochrane Clinical Answers, Cochrane Central Register of Controlled Trials, and Embase databases, we conducted a systematic review of published literature on the use of ADSCs in lymphatic tissue engineering and regeneration. There were no language or time frame limitations, and the following search strategy was applied: ((Adipose stem cell) OR Adipose-derived stem cell)) AND ((Lymphedema) OR Breast Cancer Lymphedema). Only original research manuscripts were included. Fourteen studies fulfilled the inclusion criteria. Eleven studies were experimental (in vitro or in vivo in animals), and only three were clinical. Publications on the topic demonstrated that ADSCs promote lymphangiogenesis, and its effect could be enhanced by modulation of vascular endothelial growth factor-C, interleukin-7, prospero homeobox protein 1, and transforming growth factor-β1. Pilot clinical studies included 11 patients with breast cancer-related lymphedema, and no significant side effects were present at 12-month follow-up. Literature on the use of ADSCs in lymphatic tissue engineering and regeneration demonstrated promising data. Clinical evidence is still in its infancy, but the scientific community agrees that ADSCs can be useful in regenerative lymphangiogenesis. Data collected in this review indicate that unprecedented advances in lymphedema treatment can be anticipated in the upcoming years.
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