{"title":"The Diagnosis and Treatment of Peripheral Lymphedema: 2023 Consensus Document of The International Society of Lymphology.","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>This International Society of Lymphology (ISL) Consensus Document is the latest revision of the 1995 Document for the evaluation and management of peripheral lymphedema (1). It is based upon modifications: [A] suggested and published following the 1997 XVI International Congress of Lymphology (ICL) in Madrid, Spain (2), discussed at the 1999 XVII ICL in Chennai, India (3), and considered confirmed at the 2000 (ISL) Executive Committee meeting in Hinterzarten, Germany (4); [B] derived from integration of discussions and written comments obtained during and following the 2001 XVIII ICL in Genoa, Italy as modified at the 2003 ISL Executive Committee meeting in Cordoba, Argentina (5); [C] suggested from comments, criticisms, and rebuttals as published in the December 2004 issue of Lymphology (6); [D] discussed in both the 2005 XX ICL in Salvador, Brazil and the 2007 XXI ICL in Shanghai, China and modified at the 2008 Executive Committee meeting in Naples, Italy (7,8); [E] modified from discussions and written comments from the 2009 XXII ICL in Sydney, Australia, the 2011 XXIII ICL in Malmo, Sweden, the 2012 Executive Committee Meetings (9); [F] discussions at the 2013 XXIV ICL in Rome, Italy, and the 2015 XXV ICL in San Francisco, USA, as well as multiple written comments and feedback from Executive Committee and other ISL members during the 2016 drafting (10); informal discussions at the XXVI ICL in Barcelona, Spain; [G] discussions at a dedicated, focused Post-Congress session at the XXVII ICL in Iguazu, Argentina (2019) followed by additional written comments from the Executive Committee and others (11); and [H] discussions and written comments from the XXVIII ICL in Athens, Greece (2021), and the XXIX ICL in Genoa, Italy (2023). The document attempts to amalgamate the broad spectrum of protocols and practices advocated worldwide for the diagnosis and treatment of peripheral lymphedema into a coordinated proclamation representing a \"Consensus\" of the international community based on various levels of evidence. The document is not meant to override individual clinical considerations for complex patients nor to impede clinical treatment or research progress. It is not meant to be a legal formulation from which variations could be used to describe or define medical malpractice. The Society understands that in some clinics the method of treatment derives from national standards while in others access to medical equipment, technical expertise, and supplies is limited; therefore, the suggested assessments and treatments might be impractical. Adaptability and inclusiveness do come at the price that members can rightly be critical of what they see as vagueness or imprecision in definitions, qualifiers in the choice of words ( e.g., the use of \"may ... perhaps ... unclear\", etc.) and mentions (albeit without endorsement) of treatment options supported by limited hard data (few randomized control trials). Most members are frustrated by the reality tha","PeriodicalId":94343,"journal":{"name":"Lymphology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142116796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Diagnostic Comparability of Ratio of Tissue Dielectric Constant (TDC) Between Patients with Lipedema and Those with Lower Limb Lymphedema (LLL): A Prospective Observational Study.","authors":"A Tugral, Y Bakar","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Lipedema is usually thought of as a dis-ease of women. Potentially diagnostic comparative data is needed between patients with lip-edema and those with lower limb lymphedema (LLL). Since there is no gold standard to diagnose lipedema, some promising modalities such as Tissue Dielectric Constant (TDC) need to be investigated among patients with lipedema and lymphedema. This study was completed with a total of 26 patients (14 lipedema, 12 LLL). Local tissue water was assessed with Moisture MeterD compact (DelfinTech, Kuopio, Finland) according to the TDC method at 300 MHz within a 2.5 mm tissue penetration depth via the following reference points: Thigh, calf (20 cm upper and lower point of knee level, respectively), and malleoli (5 cm upper point of medial malleolus). Patients with LLL showed significantly higher TDC values and interlimb TDC ratios in all affected points and unaffected malleolus points compared to patients with lipedema. No significant difference was achieved between genders with LLL in all reference points. The area under the curve (AUC) for thigh, calf, and malleolus reference points were found as 0.851 (95%CI .678-1.00), 0.801 (95% CI 0.612-0.989) and 0.786 (95%CI 0.596-0.976), respectively. Patients with LLL showed significantly higher TDC values compared to patients with lipedema, these differences should be carefully interpreted in patients with bilateral LLL and those with lipo-lymphedema.</p>","PeriodicalId":94343,"journal":{"name":"Lymphology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142116792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Aselli Award Winner 2023: The Life and Times of a Lymphomaniac.","authors":"D G Jackson","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Winning a scientific prize is always a welcome honor and receiving the Aselli Award in 2023 was a particularly pleasant surprise. The following text provides a brief summary of the research carried out by my group in Oxford that led to the discovery of the lymphatic endo-thelial marker LYVE-1 and its emerging role as a pivotal receptor controlling the entry of immune cells and metastatic tumor cells to lymphatic capillaries in peripheral tissues. As a basic scientist and relatively late comer to the field of lymphology, my hope is that a closer partnership of basic and clinical research will help explain the intricate workings of the lymphatics and improve the picture for patients suffering from much neglected lymphatic disorders.</p>","PeriodicalId":94343,"journal":{"name":"Lymphology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141428645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J K Kim, C Loo, J S Kim, C Pranskevich, O K Gordon
{"title":"Can Acupuncture be a Part of the Treatment for Breast Cancer-Related Lymphedema? A Systematic Review of the Safety and Proposed Model for Care.","authors":"J K Kim, C Loo, J S Kim, C Pranskevich, O K Gordon","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Acupuncture is a potential therapy for breast cancer-related lymphedema (BCRL). Despite a recent meta-analysis on efficacy, data on acupuncture safety in BCRL are lacking. Current clinical guidelines recommend avoiding needling in the upper extremity affected by lymph node dissection. We undertook a systematic review focusing on acupuncture safety and treatment protocols in clinical trials for BCRL. Literature searches were conducted in PubMed, Ovid, CINAHL, and Cochrane library. Eight clinical trials on acupuncture for BCRL were analyzed. The Standards of Acupuncture intervention (STRICTA 2010) and Cochrane risk of bias (RoB2 2019) were applied to assess methods for acupuncture interventions within Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework. Quantity and severity of adverse events (AE) were reviewed. A total of 189 subjects participated in 8 clinical trials with 2965 acupuncture treatments. No serious adverse events (SAE) were reported regardless of treatment laterality or protocol, with only a single grade 2 skin infection in 2,965 total treatments (0.034%), including 1,165 bilateral and 225 ipsilateral treatments. Our comprehensive review of clinical trials of acupuncture for BCRL demonstrated no significant adverse events in 2,965 treatments, including 1,390 in the affected limb. An approach for routine integration of acupuncture into BCRL maintenance therapy is proposed.</p>","PeriodicalId":94343,"journal":{"name":"Lymphology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138465358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M J Escobar-Domingo, V P Bustos, J E Fanning, J Foppiani, E Kim, A Hernandez-Alvarez, S J Lin, D Singhal, B T Lee
{"title":"Underreporting and Underrepresentation of Racial and Ethnic Minority Patients in Lymphedema Clinical Trials: A Systematic Review.","authors":"M J Escobar-Domingo, V P Bustos, J E Fanning, J Foppiani, E Kim, A Hernandez-Alvarez, S J Lin, D Singhal, B T Lee","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The generalizability of findings from Clinical Trials (CTs) investigating lymphedema treatment modalities requires an accurate representation of the target population. This study aims to evaluate racial and ethnic reporting and representation in lymphedema CTs. A comprehensive systematic literature search was conducted during May 2023 using multiple databases, following the PRISMA guidelines. All CTs published from 2018 to 2023 were included. A total of 84 articles were included in this review, from which 6,546 participants were included in the analysis. Seventy-four (88.1%) articles addressed secondary lymphedema, of which 60 (81.1%) were related to breast cancer. Only 12 (13%) of CTs reported at some extend race or ethnicity. Of these, five (41.6%) reported race and two (16.6%) reported ethnicity according to FDA guidelines. White race had the highest pooled prevalence (80%; 95% CI 72-86%; I2=90%), followed by Black (7%; 95% CI 2- 15%; I2= 94.3%) and Asian (4%; 95% CI 1-8%; I2= 89.9%). In studies reporting ethnicity, participants were predominantly non-Hispanic (92.1%; 95% CI 90 - 94%). There is an underreporting and underrepresentation of racial and ethnic minorities among lymphedema CTs, limiting their generalizability. It is imperative to future development of strategies to enhance diversity in the study sample.</p>","PeriodicalId":94343,"journal":{"name":"Lymphology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140857769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S Michelini, F Musa, M Vetrano, F Santoboni, S M Nusca, E Latini, D Trischitta, S Michelini, M Iosa, M C Vulpiani
{"title":"Defocused and Radial Shock Wave Therapy, Mesotherapy, and Kinesio Taping Effects in Patients with Lipedema: A Pilot Study.","authors":"S Michelini, F Musa, M Vetrano, F Santoboni, S M Nusca, E Latini, D Trischitta, S Michelini, M Iosa, M C Vulpiani","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The aim of this pilot study was to investigate the effects of defocused and radial shock wave therapy, mesotherapy, and kinesio taping on pain, circumferences of lower limbs, echographic/ elastosonographic pattern of subcutaneous adipose tissue (SAT), and quality of life in patients with lipedema. Fifteen women affected by lower limb lipedema in stage II were treated with shock wave therapy, mesotherapy, and kinesio taping on thighs and legs (eight sessions, twice a week). The primary outcome was pain, as assessed by Numeric Rating Scale (NRS). Secondary outcomes included the limb circumferences measurements, the SF-12 Health Survey for quality of life, the International Classification of Functioning (ICF) for disability, and echographic/ elastosonographic changes of SAT. Significant reductions of pain and circumference measurements were seen in patients at each follow up. This was associated with significant reduction of thickness, echographic pattern improvement, and increased elasticity of SAT, with consequent positive impact on the quality of life and disability reported by the patients. The results demonstrate improved clinical and functional ultrasound findings in patients affected by lipedema in the early stages of lower limbs, and this combination therapy needs to be investigated in larger populations at multiple centers to confirm the findings.</p>","PeriodicalId":94343,"journal":{"name":"Lymphology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138465359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
K Dalci, S Gumus, A G Saritas, H B Onan, A T Akeam, A Ulku, G Sakman
{"title":"Multimodal Treatment of Chylous Fistula: A Retrospective Case-Control Study.","authors":"K Dalci, S Gumus, A G Saritas, H B Onan, A T Akeam, A Ulku, G Sakman","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Chylous fistulas (CF) are rare surgical complications and there is no standard treatment. This study presents the treatment modalities performed on patients who developed CF over a 10-year period. During the observation period, CF developed in 29 patients, 16 of whom were women. The mean age was 55.76± 13.48. Lymphatic duct injury was mostly seen in the abdomen (58.6%) and the most common reason was nephrectomy (20.7%). Extended lymphatic dissection due to malignancy was performed in 82.7% of all cases. Chylous leakage started postoperatively on 3.78±3.94 days (range: 1-19 days). Fasting, total parenteral nutrition (TPN), and somatostatin treatment were applied to all patients, and 75.8% of the fistulas were resolved completely with medical treatment. Surgical ligation of the lymphatic canal was performed in 7 patients. One was not successful and underwent percutaneous embolization of the thoracic lymphatic leakage cavity. All fistulas were resolved in 18.18±10.4 days. The resolution time and hospital stay were significantly higher in thoracic fistulas (p=0.017; p=0.003, respectively). In addition, malignant cases had longer resolution time (32.40±28.72 vs 16.27±11.25, p=0.036) and hospital stay (35.0±29.74 vs 16.25±14.05p= 0.002 respectively) than non-malignant. There was no chylothorax, chylous ascites, or recurrence at 20.55±22.88 months follow-up. Treatment of CF with fasting, TPN, and somatostatin analogs are effective. Other interventions such as surgical ligation with or without fibrin glue and interventional radiology treatments may be considered when conservative treatments fail.</p>","PeriodicalId":94343,"journal":{"name":"Lymphology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140874346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M S Dundar, I Belanova, G Bonetti, V Gelanova, R Kozacikova, D Veselenyiova, A Macchia, C Micheletti, C Medori, K Donato, M Ricci, M Cestari, B Amato, C Micheletti, F Boccardo, M Dundar, M Bertelli, S Michelini
{"title":"Genetic Variants in Genes Correlated to the PI3K/AKT Pathway: The Role of <i>ARAP3, CDH5, KIF11</i> and <i>RELN</i> in Primary Lymphedema.","authors":"M S Dundar, I Belanova, G Bonetti, V Gelanova, R Kozacikova, D Veselenyiova, A Macchia, C Micheletti, C Medori, K Donato, M Ricci, M Cestari, B Amato, C Micheletti, F Boccardo, M Dundar, M Bertelli, S Michelini","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Genetic anomalies affecting lymphatic development and function can lead to lymphatic dysfunction, which could manifest as lymphedema. Understanding the signaling pathways governing lymphatics function is crucial for developing targeted diagnostic and therapeutic interventions. This study aims to characterize genetic variants in genes involved in the PI3K/AKT signaling pathway, which plays a critical role in lymphangiogenesis. 408 patients diagnosed with primary lymphedema were sequenced using a next-generation sequencing (NGS) gene panel composed of 28 diagnostic genes and 71 candidate genes. The analysis revealed six variants in genes <i>RELN, ARAP3, CDH5</i>, and <i>KIF11</i>. Five of these variants have never been reported in the literature. All these genes have been correlated to lymphatic activity and are involved in the PI3K/ AKT pathway. As the PI3K/AKT signaling pathway plays an essential role in lymphangiogenesis and lymphatic function, genetic variants in genes correlated to this pathway could lead to lymphedema. Our findings underscore the potential of the PI3K/AKT pathway in lymphedema pathogenesis, supporting the role of <i>RELN, ARAP3, CDH5,</i>, and <i>KIF11</i> as diagnostic and therapeutic targets.</p>","PeriodicalId":94343,"journal":{"name":"Lymphology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142116793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Does Liposuction for Lymphedema Worsen Lymphatic Injury?","authors":"W F Chen, S K Pandey, J N Lensing","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Liposuction for treatment of lymphedema is an effective and time-tested treatment. However, as there is a fear regarding further lymphatic damage caused by liposuction, we objectively compared lymphatic function pre- and post-liposuction. All patients with solid-predominant lymphedema who were treated during the study period of June 2014 and November 2018 were included. Patients were assessed using patient-reported baselines/outcomes, lymphedema- specific quality of life scale (LYMQOL), limb circumference/volume measurements, and indocyanine green lymphography (ICGL) preoperatively and at predefined postoperative time intervals. Fifty-seven limbs from 41 patients were included. Mean lipoaspirate volumes were 2035 mL, 5385 mL, and 3106 mL for the arm, thigh, and leg, respectively with a mean adipose fraction of the lipoaspirate of 71%. All patients underwent redundant skin excision with the \"flying squirrel\" technique. The mean follow-up was 10.7 months (range 3 - 48 months) with a mean limb volume reduction of 32.2% and all patients reporting satisfactory relief of symptoms. All showed statistically significant improvement in LYMQOL in symptoms, appearance, and function. On ICGL, none showed worsened lymphatic drainage, rather, all showed improved lymph drainage. Furthermore, the improved lymph drainage was found to be progressive during the study period in all patients. Our study results demonstrate that treating extremity lymphedema with liposuction does not worsen lymphatic function and in fact, paradoxically, it induces progressive improvement in lymph drainage.</p>","PeriodicalId":94343,"journal":{"name":"Lymphology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138465360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Re-Discovery of Dural (Meningeal) Lymphatics: Amnesia or Ambition?","authors":"R P Erickson","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>In 2015 the discovery of meningeal (dural) lymphatics was announced to much fanfare. The journal Science named this the second most important discovery of the year! Yet, they had actually been well described two and a quarter centuries earlier, in Italy, England, and Holland. However, there was controversy about their existence because of the difficulties in studying them, also addressed two and a quarter centuries earlier. Their study had generated a very large literature and they were \"textbook\" knowledge. The reasons for this neglect are discussed emphasizing the current scientific milieu and the changing modes of evaluating scientists.</p>","PeriodicalId":94343,"journal":{"name":"Lymphology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141428649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}