Lymphaticovenous Anastomosis as Treatment for Lymphedema

NCT05441943 | Active Not Recruiting

• 2 other identifiers: 21/59848S-20210169
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

The primary aim of this study is to investigate and test whether the use of combined indocyanine green (ICG) lymphography and ultra high frequency ultrasonography can correctly identify lymphatic vessels and venoles in close proximity to each other, for identification prior to lymphovenous anastomosis (LVA) surgery.

Conditions

Breast Cancer Lymphedema; Secondary Lymphedema; Iatrogenic Lymphedema; Lymphedema; Lymphedema of Upper Limb; Lymphedema Arm; Lymphedema, Breast Cancer; Breast Neoplasm; Neoplasms; Breast Cancer; Breast Diseases; Lymphatic Diseases; Skin Diseases; Postoperative Complications; Pathologic Processes; Anastomose; Surgery; Surgical; Lymphedema, Postmastectomy; Postmastectomy Lymphedema; Postmastectomy Lymphedema Syndrome Left Upper Limb; Postmastectomy Lymphedema Syndrome Right Upper Limb; Postmastectomy Lymphedema Syndrome

Keywords

Lymphedema; Breast Cancer; Postmastectomy Lymphedema; Lymphoedema; Breast Cancer Lymphedema; Anastomose; Lymphovenous anastomosis; LVA; Surgery; Breast Neoplasm

Outcome Measures

Primary Outcomes (2)

• Number of vessels planned for surgery surgery

  The number of mapped lymphatics vessels and venoles.

  Preoperative

• Number of vessels found during surgery

  The number of vessels found during surgery. This number will be compared to the number of vessels planned for surgery.

  Perioprative

Secondary Outcomes (11)

• Changes of arm volume

  Baseline and 3 months follow-up

• Change of extracellular fluid (liters) relative to total body water (liters), measured in percentage.

  Baseline and 3 months follow-up

• Changes of intracellular fluid (liters) relative to total body water (liters), measured in percentage.

  Baseline and 3 months follow-up

• Changes of total body water (liters) relative to weight (kg), measured in percentage.

  Baseline and 3 months follow-up

• Changes of proteins and minerals (kg) relative to weight (kg), measured in percentage.

  Baseline and 3 months follow-up

Study Arms (1)

Lymphovenous anastomosis surgery

EXPERIMENTAL

Lymphovenous anastomosis surgery with pre-operative planning using ICG lymphography and ultra high frequency ultrasound.

Procedure: Lymphovenous anastomosis

Interventions

Lymphovenous anastomosis PROCEDURE

Pre-operative planning prior to lymphovenous anastomosis using ICG lymphography and ultra high frequency ultrasound for mapping of applicable vessels. During surgery, mapped vessels are freely dissected and anastomosed.

Also known as: LVA, Lymphaticovenous anastomosis, Lymphaticovenular anastomosis

Lymphovenous anastomosis surgery

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female
• Iatrogenic lymphedema following treatment for breast cancer in upper extremity
• Possible to obtain informed consent
• Age\>18

You may not qualify if:

• Duration of disease over 24 months
• Smoker
• Untreated or uncontrolled primary cancer
• No applicable lymphatic vessels identified, using ICG lymphangiography
• No applicable venous vessels identified using ultra high frequency ultrasound

Sponsors & Collaborators

• Odense University Hospital: lead
• Danish Cancer Society: collaborator

Study Sites (1)

Department of Plastic Surgery, Odense University Hospital

Odense, Region Syddanmark, 5000, Denmark

Location

Related Publications (32)

• Armer JM, Ballman KV, McCall L, Armer NC, Sun Y, Udmuangpia T, Hunt KK, Mittendorf EA, Byrd DR, Julian TB, Boughey JC. Lymphedema symptoms and limb measurement changes in breast cancer survivors treated with neoadjuvant chemotherapy and axillary dissection: results of American College of Surgeons Oncology Group (ACOSOG) Z1071 (Alliance) substudy. Support Care Cancer. 2019 Feb;27(2):495-503. doi: 10.1007/s00520-018-4334-7. Epub 2018 Jul 6.

  PMID: 29980907 BACKGROUND

• DiSipio T, Rye S, Newman B, Hayes S. Incidence of unilateral arm lymphoedema after breast cancer: a systematic review and meta-analysis. Lancet Oncol. 2013 May;14(6):500-15. doi: 10.1016/S1470-2045(13)70076-7. Epub 2013 Mar 27.

  PMID: 23540561 BACKGROUND

• Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249. doi: 10.3322/caac.21660. Epub 2021 Feb 4.

  PMID: 33538338 BACKGROUND

• Maajani K, Jalali A, Alipour S, Khodadost M, Tohidinik HR, Yazdani K. The Global and Regional Survival Rate of Women With Breast Cancer: A Systematic Review and Meta-analysis. Clin Breast Cancer. 2019 Jun;19(3):165-177. doi: 10.1016/j.clbc.2019.01.006. Epub 2019 Jan 29.

  PMID: 30952546 BACKGROUND

• Markkula SP, Leung N, Allen VB, Furniss D. Surgical interventions for the prevention or treatment of lymphoedema after breast cancer treatment. Cochrane Database Syst Rev. 2019 Feb 19;2(2):CD011433. doi: 10.1002/14651858.CD011433.pub2.

  PMID: 30779124 BACKGROUND

• Drobot A, Bez M, Abu Shakra I, Merei F, Khatib K, Bickel A, Ganam S, Bogouslavski G, Karra N, Mahran B, Kassis W, Kogan L, Drobot D, Weiss M, Koshima I, Kakiashvili E. Microsurgery for management of primary and secondary lymphedema. J Vasc Surg Venous Lymphat Disord. 2021 Jan;9(1):226-233.e1. doi: 10.1016/j.jvsv.2020.04.025. Epub 2020 May 21.

  PMID: 32446874 BACKGROUND

• Seki Y, Kajikawa A, Yamamoto T, Takeuchi T, Terashima T, Kurogi N. The dynamic-lymphaticovenular anastomosis method for breast cancer treatment-related lymphedema: Creation of functional lymphaticovenular anastomoses with use of preoperative dynamic ultrasonography. J Plast Reconstr Aesthet Surg. 2019 Jan;72(1):62-70. doi: 10.1016/j.bjps.2018.09.005. Epub 2018 Sep 20.

  PMID: 30292697 BACKGROUND

• Brahma B, Putri RI, Reuwpassa JO, Tuti Y, Alifian MF, Sofyan RF, Iskandar I, Yamamoto T. Lymphaticovenular Anastomosis in Breast Cancer Treatment-Related Lymphedema: A Short-Term Clinicopathological Analysis from Indonesia. J Reconstr Microsurg. 2021 Oct;37(8):643-654. doi: 10.1055/s-0041-1723940. Epub 2021 Mar 1.

  PMID: 33648010 BACKGROUND

• Wolfs JAGN, de Joode LGEH, van der Hulst RRWJ, Qiu SS. Correlation between patency and clinical improvement after lymphaticovenous anastomosis (LVA) in breast cancer-related lymphedema: 12-month follow-up. Breast Cancer Res Treat. 2020 Jan;179(1):131-138. doi: 10.1007/s10549-019-05450-2. Epub 2019 Sep 21.

  PMID: 31542874 BACKGROUND

• Jorgensen MG, Toyserkani NM, Hansen FG, Bygum A, Sorensen JA. The impact of lymphedema on health-related quality of life up to 10 years after breast cancer treatment. NPJ Breast Cancer. 2021 Jun 1;7(1):70. doi: 10.1038/s41523-021-00276-y.

  PMID: 34075045 BACKGROUND

• Kibar S, Dalyan Aras M, Unsal Delialioglu S. The risk factors and prevalence of upper extremity impairments and an analysis of effects of lymphoedema and other impairments on the quality of life of breast cancer patients. Eur J Cancer Care (Engl). 2017 Jul;26(4). doi: 10.1111/ecc.12433. Epub 2016 Jan 13.

  PMID: 26764197 BACKGROUND

• Ahmed RL, Prizment A, Lazovich D, Schmitz KH, Folsom AR. Lymphedema and quality of life in breast cancer survivors: the Iowa Women's Health Study. J Clin Oncol. 2008 Dec 10;26(35):5689-96. doi: 10.1200/JCO.2008.16.4731. Epub 2008 Nov 10.

  PMID: 19001331 BACKGROUND

• Gillespie TC, Sayegh HE, Brunelle CL, Daniell KM, Taghian AG. Breast cancer-related lymphedema: risk factors, precautionary measures, and treatments. Gland Surg. 2018 Aug;7(4):379-403. doi: 10.21037/gs.2017.11.04.

  PMID: 30175055 BACKGROUND

• Chang EI, Skoracki RJ, Chang DW. Lymphovenous Anastomosis Bypass Surgery. Semin Plast Surg. 2018 Feb;32(1):22-27. doi: 10.1055/s-0038-1636510. Epub 2018 Apr 9.

  PMID: 29636650 BACKGROUND

• Mihara M, Hara H, Araki J, Kikuchi K, Narushima M, Yamamoto T, Iida T, Yoshimatsu H, Murai N, Mitsui K, Okitsu T, Koshima I. Indocyanine green (ICG) lymphography is superior to lymphoscintigraphy for diagnostic imaging of early lymphedema of the upper limbs. PLoS One. 2012;7(6):e38182. doi: 10.1371/journal.pone.0038182. Epub 2012 Jun 4.

  PMID: 22675520 BACKGROUND

• Hayashi A, Giacalone G, Yamamoto T, Belva F, Visconti G, Hayashi N, Handa M, Yoshimatsu H, Salgarello M. Ultra High-frequency Ultrasonographic Imaging with 70 MHz Scanner for Visualization of the Lymphatic Vessels. Plast Reconstr Surg Glob Open. 2019 Jan 22;7(1):e2086. doi: 10.1097/GOX.0000000000002086. eCollection 2019 Jan.

  PMID: 30859043 BACKGROUND

• Visconti G, Bianchi A, Hayashi A, Salgarello M. Ultra-high frequency ultrasound preoperative planning of the rerouting method for lymphaticovenular anastomosis in incisions devoid of vein. Microsurgery. 2020 Sep;40(6):717-718. doi: 10.1002/micr.30600. Epub 2020 May 5. No abstract available.

  PMID: 32369213 BACKGROUND

• Hayashi A, Visconti G, Giacalone G, Hayashi N, Yoshimatsu H. Recent Advances in Ultrasound Technology: Ultra-High Frequency Ultrasound for Reconstructive Supermicrosurgery. J Reconstr Microsurg. 2022 Mar;38(3):193-199. doi: 10.1055/s-0041-1740129. Epub 2021 Dec 17.

  PMID: 34921372 BACKGROUND

• Jorgensen MG, Toyserkani NM, Hansen FCG, Thomsen JB, Sorensen JA. Prospective Validation of Indocyanine Green Lymphangiography Staging of Breast Cancer-Related Lymphedema. Cancers (Basel). 2021 Mar 26;13(7):1540. doi: 10.3390/cancers13071540.

  PMID: 33810570 BACKGROUND

• Jorgensen MG, Hermann AP, Madsen AR, Christensen S, Sorensen JA. Indocyanine green lymphangiography is superior to clinical staging in breast cancer-related lymphedema. Sci Rep. 2021 Oct 26;11(1):21103. doi: 10.1038/s41598-021-00396-2.

  PMID: 34702877 BACKGROUND

• Gupta N, Verhey EM, Torres-Guzman RA, Avila FR, Jorge Forte A, Rebecca AM, Teven CM. Outcomes of Lymphovenous Anastomosis for Upper Extremity Lymphedema: A Systematic Review. Plast Reconstr Surg Glob Open. 2021 Aug 25;9(8):e3770. doi: 10.1097/GOX.0000000000003770. eCollection 2021 Aug.

  PMID: 34476159 BACKGROUND

• Visconti G, Hayashi A, Tartaglione G, Yamamoto T, Bianchi A, Salgarello M. Preoperative planning of lymphaticovenular anastomosis in patients with iodine allergy: A multicentric experience. J Plast Reconstr Aesthet Surg. 2020 Apr;73(4):783-808. doi: 10.1016/j.bjps.2019.11.020. Epub 2019 Nov 29. No abstract available.

  PMID: 31813793 BACKGROUND

• Gallagher KK, Lopez M, Iles K, Kugar M. Surgical Approach to Lymphedema Reduction. Curr Oncol Rep. 2020 Jul 28;22(10):97. doi: 10.1007/s11912-020-00961-4.

  PMID: 32720071 BACKGROUND

• Ogata F, Narushima M, Mihara M, Azuma R, Morimoto Y, Koshima I. Intraoperative lymphography using indocyanine green dye for near-infrared fluorescence labeling in lymphedema. Ann Plast Surg. 2007 Aug;59(2):180-4. doi: 10.1097/01.sap.0000253341.70866.54.

  PMID: 17667413 BACKGROUND

• Klassen AF, Tsangaris E, Kaur MN, Poulsen L, Beelen LM, Jacobsen AL, Jorgensen MG, Sorensen JA, Vasilic D, Dayan J, Mehrara B, Pusic AL. Development and Psychometric Validation of a Patient-Reported Outcome Measure for Arm Lymphedema: The LYMPH-Q Upper Extremity Module. Ann Surg Oncol. 2021 Sep;28(9):5166-5182. doi: 10.1245/s10434-021-09887-y. Epub 2021 Jul 5.

  PMID: 34224044 BACKGROUND

• Coroneos CJ, Wong FC, DeSnyder SM, Shaitelman SF, Schaverien MV. Correlation of L-Dex Bioimpedance Spectroscopy with Limb Volume and Lymphatic Function in Lymphedema. Lymphat Res Biol. 2019 Jun;17(3):301-307. doi: 10.1089/lrb.2018.0028. Epub 2018 Nov 2.

  PMID: 30388062 BACKGROUND

• Mastick J, Smoot BJ, Paul SM, Kober KM, Hamolsky D, Madden LK, Conley YP, Dixit N, Hammer MJ, Fu MR, Miaskowski C. A Comparison of Supine Versus Stand-on Bioimpedance Devices to Assess Breast Cancer-Related Lymphedema. Lymphat Res Biol. 2021 Dec;19(6):553-561. doi: 10.1089/lrb.2020.0058. Epub 2021 Feb 9.

  PMID: 33567232 BACKGROUND

• Tang NSJ, Ramakrishnan A, Shayan R. Quality-of-life outcomes after operative management of primary and secondary lymphoedema: a systematic review. ANZ J Surg. 2021 Dec;91(12):2624-2636. doi: 10.1111/ans.16764. Epub 2021 Apr 6.

  PMID: 33825306 BACKGROUND

• Karafa M, Karafova A, Szuba A. The effect of different compression pressure in therapy of secondary upper extremity lymphedema in women after breast cancer surgery. Lymphology. 2018;51(1):28-37.

  PMID: 30248729 BACKGROUND

• Gasteratos K, Morsi-Yeroyannis A, Vlachopoulos NC, Spyropoulou GA, Del Corral G, Chaiyasate K. Microsurgical techniques in the treatment of breast cancer-related lymphedema: a systematic review of efficacy and patient outcomes. Breast Cancer. 2021 Sep;28(5):1002-1015. doi: 10.1007/s12282-021-01274-5. Epub 2021 Jul 12.

  PMID: 34254232 BACKGROUND

• Carl HM, Walia G, Bello R, Clarke-Pearson E, Hassanein AH, Cho B, Pedreira R, Sacks JM. Systematic Review of the Surgical Treatment of Extremity Lymphedema. J Reconstr Microsurg. 2017 Jul;33(6):412-425. doi: 10.1055/s-0037-1599100. Epub 2017 Feb 24.

  PMID: 28235214 BACKGROUND

• Fu MR, Cleland CM, Guth AA, Kayal M, Haber J, Cartwright F, Kleinman R, Kang Y, Scagliola J, Axelrod D. L-dex ratio in detecting breast cancer-related lymphedema: reliability, sensitivity, and specificity. Lymphology. 2013 Jun;46(2):85-96.

  PMID: 24354107 RESULT

Related Links

• Will, P.A., Wan, Z., Seide, S.E. et al. Supermicrosurgical treatment for lymphedema: a systematic review and network meta-analysis protocol. Syst Rev 11, 18 (2022). https://doi.org/10.1186/s13643-022-01885-9

MeSH Terms

Conditions

Breast Cancer Lymphedema; Lymphedema; Breast Neoplasms; Neoplasms; Breast Diseases; Lymphatic Diseases; Skin Diseases; Postoperative Complications; Pathologic Processes

Condition Hierarchy (Ancestors)

Hemic and Lymphatic Diseases; Pathological Conditions, Signs and Symptoms; Neoplasms by Site; Skin and Connective Tissue Diseases

Study Officials

• Caroline Lilja, MD

  Department of Plastic Surgery at Odense University Hospital

  PRINCIPAL INVESTIGATOR

• Jens Ahm Sørensen, MD, Prof, PhD

  Department of Plastic Surgery at Odense University Hospital

  STUDY CHAIR

• Jørn Bo Thomsen, MD, Prof, PhD

  Department of Plastic Surgery at Odense University Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 7, 2022
• First Posted: July 1, 2022
• Study Start: May 11, 2022
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: March 5, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)