Lymphatic Research and Biology

Lymphedema is a common breast cancer side effect, with an average incidence of 30%. The gold standard conservative treatment for lymphedema is complex decongestive therapy (CDT), which includes manual lymphatic drainage, compression therapy, skin care, and exercise. Lymphovenular anastomosis (LVA) is a microsurgical technique that intends to redirect excess lymphatic fluid to the venous circulation; this procedure is usually performed when conservative treatment fails. Therefore, the objective of this study is to evaluate the effectiveness of LVA and CDT for the treatment of breast cancer-related lymphedema (BCRL).

The search was performed in CENTRAL, MEDLINE, Embase, PsycINFO, SCOPUS, and LILACS. Inclusion criteria were (1) population: women with BCRL; (2) intervention: treated with LVA and CDT; and (3) outcome: primary outcome was lymphedema reduction. Secondary outcome was quality of life. Risk of bias and quality of study reporting were also assessed. The search found 3872 articles, with 5 articles meeting the PICO (population, intervention, comparison, outcomes) criteria, 4 pre–post studies, and one observational cohort study. The total sample included 2763 patients. Follow-up was variable. The follow-up varies from 7.8 to 120 months, with an average of 35 months. Lymphedema reduction was obtained in the five studies.

The present systematic review suggests that for patients with lymphedema secondary to breast cancer, the combination of both treatments is effective in reducing the size of the limb and improving quality of life. Low-quality evidence was found for both limb circumference reduction and quality of life. Additional research effort is needed to reduce bias and improve the quality of evidence, in order to better inform clinical practice and enhance the care and well-being of patients with BCRL.

Complex decongestive therapy (CDT) is being used in breast cancer-related lymphedema (BCRL). The degree of initial edema and bioimpedance analysis (BIA) are known to be related with the therapeutic effect of CDT. D-dimer can indirectly reflect lymphangiogenesis because IL-6 regulates D-dimer and vascular endothelial growth factor, which is the most important lymphangiogenic factor. We assessed whether D-dimer could be used for the prediction of therapeutic effect of CDT, as well as BIA and initial edema.

The participants were patients who took inpatient treatment for BCRL from July 2016 to May 2020. Percent excess volume (PEV) was calculated by dividing the difference in volume of both arms by the edema arm, and the difference in PEV before and after 2 weeks of CDT was defined as the CDT effect. BIA and D-dimer tests were performed before treatment.

The single frequency bioimpedance analysis (SFBIA) ratio and D-dimer showed significant correlations with β coefficients of 0.581 and 0.402 (p < 0.01), respectively, and the explanatory power of these models was confirmed to be 0.704.The areas under the curve of initial PEV, SFBIA ratio, D-dimer for determining the CDT effect were identified as 0.849, 0.795, and 0.725, respectively.

Initial PEV, SFBIA ratio, and blood D-dimer levels could be used as predictors for CDT treatment effect. Their usefulness order was in the order of initial PEV, SFBIA ratio, and D-dimer. These factors could be used as predictors to establish therapeutic plan in patients with mild lymphedema.

Breast cancer-related lymphedema (BCRL) is a disabling and frequently occurring condition after treatment for breast cancer. Studying lymph anatomy by means of indocyanine green (ICG) lymphography is a promising tool to help better understand BCRL. The aim of this study is to investigate the relation between ICG lymphography characteristics and the risk of developing BCRL.

Patients scheduled for breast surgery with either unilateral axillary lymph node dissection or sentinel lymph node biopsy between November 2017 and May 2019 were included. Patients were assessed at baseline and up to 36 months postsurgery. BCRL was defined as an increase of ≥5% relative arm volume difference compared with the presurgical difference. In total, 128 patients were included. During 36 months of follow-up, 45 patients (35.2%) developed BCRL. The number of lymph vessels before surgery was not a statistically significant risk factor for developing BCRL (p = 0.8485). However, an increase in the number of lymph vessels compared with baseline was a significant protective factor for developing BCRL (odds ratio = 0.8). An increase of one lymph vessel corresponds to a 19% relative risk reduction of developing BCRL. The presence of lymph nodes at baseline and the change in the presence of lymph nodes compared with baseline were no predictors for the development of BCRL (p = 0.0986 and p = 0.8910, respectively).

An increase in the number of lymph vessels visualized by ICG lymphography compared with baseline is a protective factor for developing BCRL. Therapies with the ability to increase the number of lymph vessels can thus possibly decrease the risk of developing BCRL.

Among super-microsurgical techniques, the anastomosis of vessels smaller than 0.5 mm is very difficult to perform due to the small diameter and thinness of the blood and lymphatic vessel walls. In this article, we report on the main points of super microsurgery, particularly on the anastomosis of veins and lymphatic vessels with diameters smaller than 0.5 mm.

Details of anastomosis of vessels smaller than 0.5 mm.

(1) The outer wall of the first blood vessel near the abrupt end hook with the tip of the needle in the needle holder. The entire abrupt end of the first blood vessel was supported by forceps in the surgeon’s left-hand.

(2) The surgeon decided the entry point and angle of the needle while moving the tip. After the needle was fixed, a force was applied so that the needle could pass through to the vascular wall.

(3) After the needle passed through, the tip was confirmed to be located in the lumen of the first blood vessel.

(4) The tip of the needle was inserted into the lumen of the second blood vessel, and the bite was adjusted while touching the second blood vessel through the endometrium.

(5) Once the tip was properly positioned, counter-traction was applied by holding the entire outer wall with a left-hand forceps.

(6) The needle was held near the tip and pulled out along its curvature.

The anastomosis time was 11.35 minutes on average (9 to 14 minutes). The patency rate for all 20 anastomosis procedures was also 100%.

The important points of LVA for lymphatic vessels and veins smaller than 0.5 mm were reported. Once the surgeons are familiarized with this anastomosis procedure, they can typically perform one anastomosis in about 10 minutes.