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Immediate lymphatic reconstruction (ILR) at the time of axillary lymph node dissection (ALND) has become increasingly utilized for the prevention of breast cancer related lymphedema. Preoperative indocyanine green (ICG) lymphography is routinely performed prior to an ILR procedure to characterize baseline lymphatic anatomy of the upper extremity. While most patients have linear lymphatic channels visualized on ICG, representing a non-diseased state, some patients demonstrate non-linear patterns. This study aims to determine potential inciting factors that help explain why some patients have non-linear patterns, and what these patterns represent regarding the relative risk of developing postoperative breast cancer related lymphedema in this population. A retrospective review was conducted to identify breast cancer patients who underwent successful ILR with preoperative ICG at our institution from November 2017—June 2022. Among the 248 patients who were identified, 13 (5%) had preoperative non-linear lymphatic anatomy. A history of trauma or surgery of the affected limb and an increasing number of sentinel lymph nodes removed prior to ALND appeared to be risk factors for non-linear lymphatic anatomy. Furthermore, non-linear anatomy in the limb of interest was associated with an increased risk of postoperative lymphedema development. Overall, non-linear lymphatic anatomy on pre-operative ICG lymphography appears to be a risk factor for developing ipsilateral breast cancer-related lymphedema. Guided by the study’s findings, when breast cancer patients present with baseline non-linear lymphatic anatomy, our institution has implemented a protocol of prophylactically prescribing compression sleeves immediately following ALND. [ABSTRACT FROM AUTHOR]

Enhancing our understanding of lymphatic anatomy from the microscopic to the anatomical scale is essential to discern how the structure and function of the lymphatic system interacts with different tissues and organs within the body and contributes to health and disease. The knowledge of molecular aspects of the lymphatic network is fundamental to understand the mechanisms of disease progression and prevention. Recent advances in mapping components of the lymphatic system using state of the art single cell technologies, the identification of novel biomarkers, new clinical imaging efforts, and computational tools which attempt to identify connections between these diverse technologies hold the potential to catalyze new strategies to address lymphatic diseases such as lymphedema and lipedema. This manuscript summarizes current knowledge of the lymphatic system and identifies prevailing challenges and opportunities to advance the field of lymphatic research as discussed by the experts in the workshop. [ABSTRACT FROM AUTHOR]

Enhancing our understanding of lymphatic anatomy from the microscopic to the anatomical scale is essential to discern how the structure and function of the lymphatic system interacts with different tissues and organs within the body and contributes to health and disease. The knowledge of molecular aspects of the lymphatic network is fundamental to understand the mechanisms of disease progression and prevention. Recent advances in mapping components of the lymphatic system using state of the art single cell technologies, the identification of novel biomarkers, new clinical imaging efforts, and computational tools which attempt to identify connections between these diverse technologies hold the potential to catalyze new strategies to address lymphatic diseases such as lymphedema and lipedema. This manuscript summarizes current knowledge of the lymphatic system and identifies prevailing challenges and opportunities to advance the field of lymphatic research as discussed by the experts in the workshop.

BackgroundConstructing a reliable animal model for preclinical treatment of secondary lymphedema is challenging because the anatomical characteristics near the lymph nodes are understudied. Therefore, this study examined the detailed anatomical relationship between the axillary lymph node flaps (ALNFs) and brachial lymph node flaps (BLNFs) in the forelimb of Sprague-Dawley (SD) rats.Materials and methodsTen male rats, weighing 250–300 g, were used. The ALNFs and BLNFs on either side of the rat forelimbs were dissected. The two lymph node flaps (LNFs) were immediately harvested to analyze their physical characteristics (via imaging process software) and microscopic structure (via histology examinations).ResultsA total of 20 ALNFs and BLNFs from 10 rats were harvested and analyzed. ALNF dissection was simpler and lasted a shorter time than BLNF dissection (p < 0.0001). The left LNFs were more difficult to dissect than the right LNFs (p < 0.0001). In physical characteristics of LNFs, the area (p < 0.001) of LNFs and the number of lymph nodes (p < 0.0001) associated with ALNFs were greater than those associated with BLNFs, but the pedicle lengths of ALNFs were shorter than that of BLNFs (p < 0.0001). No significant difference in the diameter of the venous and arterial pedicles was noted between the two LNFs (p > 0.05).ConclusionThis study reported detailed physical characteristics of ALNFs and BLNFs in SD rat forelimbs, assessing the respective area of LNFs, number of lymph nodes, and lengths and diameters of vascular pedicles. Moreover, this study suggested an efficient method to perform a study of LNFs by describing the operation process and repeatedly measuring the operation time.

Objective: The incidence of endometrial cancer is increasing in elderly people. Considering that aging progressively affects lymphatic draining function, we aimed to define its impact on IGC uptake during SLN mapping. Methods: A multicenter retrospective cohort of endometrial cancer patients with apparently early-stage endometrial cancer undergoing complete surgical staging with SLN dissection was identified in four referral cancer centers from May 2015 to March 2021. Patients were classified in Group 1 (<65 years old) and Group 2 (≥65 years old). The primary endpoint was the assessment of the overall, bilateral, and unsuccessful SLN mapping in the two groups. Secondary outcomes were the evaluation of SLN anatomical distribution and the identification of predictors for mapping failure applying a logistic regression. Results: A total of 844 patients were enrolled in the study (499 in Group 1 and 395 in Group 2). The overall detection rate, the successful bilateral mapping, and the mapping failure rate of the SLN were 93.8% vs. 87.6% (p = 0.002), 77.1% vs. 66.8% (p = 0.001), and 22.9% vs. 33.2% (p = 0.001), respectively, in Group 1 vs. Group 2. The advanced age affects the anatomical distribution of the SLN leading to a stepwise reduction of "unexpected" mapping sites (left hemipelvis: p < 0.001; right hemipelvis: p = 0.058). At multivariate analysis age ≥ 65 (OR: 1.495, 95% CI: 1.095–2.042, p = 0.011), BMI (OR: 1.023, 95% CI: 1.000–1.046, p = 0.047), non-endometrioid histotype (OR: 1.619, 95% CI: 1.067–2.458, p = 0.024), and LVSI (OR: 1.407, 95% CI: 1.010–1.961, p = 0.044) represent independent predictors of unsuccessful mapping. Applying binomial logistic regression analysis, there was a 1.280-fold increase in the risk of failed mapping for every 10-year-old increase in age (OR: 1.280, 95% CI: 1.108–1.479, p = 0.001). A higher rate of surgical under-staging (0.9% vs. 3.3%, p = 0.012) and adjuvant undertreatment (p = 0.018) was reported in Group 2. Conclusions: Old age represents a risk factor for SLN mapping failure both intrinsically and in relation to the greater incidence of other independent risk factors such as LVSI, non-endometrioid histotype, and BMI. Surgeons should target the usual uptake along UPP during the SLN dissection in this subgroup of patients to minimize mapping failure and the consequent risk of surgical under-staging and adjuvant undertreatment. [ABSTRACT FROM AUTHOR]

ObjectiveThe incidence of endometrial cancer is increasing in elderly people. Considering that aging progressively affects lymphatic draining function, we aimed to define its impact on IGC uptake during SLN mapping.MethodsA multicenter retrospective cohort of endometrial cancer patients with apparently early-stage endometrial cancer undergoing complete surgical staging with SLN dissection was identified in four referral cancer centers from May 2015 to March 2021. Patients were classified in Group 1 (

Tissue surrounding the superficial inferior epigastric vein (SIEV) can be harvested for vascularised lymph node transfer (vLNT) for the treatment of lymphoedema. The aim of this study is to define the anatomical relationship of lymph nodes surrounding the SIEV. Twenty-five fresh-frozen cadaveric groin specimens were harvested en bloc to the level of the deep fascia along the following anatomical boundaries, yielding quadrilateral tissue blocks: pubic tubercle (medial), anterior superior iliac spine (lateral), 5 cm superior and inferior to the inguinal ligament. The SIEV was marked at its entry point with the femoral vein. Specimens were oriented, secured and fixed in formaldehyde and analysed using longitudinal slices at 3 mm intervals. A total of 86 lymph nodes were identified. The average position of lymph nodes examined was 0.4 cm medial and 3.2 cm inferior to the mid-inguinal point. An improved understanding of the anatomical locations of lymph nodes surrounding the SIEV will allow a more purposeful harvest during vLNT, allowing a greater number of lymph nodes to be captured whilst limiting donor site morbidity. [ABSTRACT FROM AUTHOR]

Central lymphatic disorders of the lung have not received intense investigation. Lymphatic system physiology is presented in the context of historical developments and basic lung lymphatic anatomy is reviewed followed by emerging characteristics of primary and secondary pathophysiological disturbances of lymphatic involvement in a number of pulmonary diseases including Gorham-Stout disease, pulmonary edema and infections and inflammatory conditions including lymphangioleiomyomatosis (LAM). The future includes potential molecular targeting of lymphangiogenesis or lymphatic vessels for interventional occlusion. This article is an amalgamation of presentations at the 2023 ISL International Congress of Lymphology, Genoa, Italy in a special symposium on central and regional lymphatic system in health and disease and as part of a Special Symposium on the Lymphatic system of the Heart and Lung in Health and Disease at the 26th International Congress of Lymphology meeting held in Barcelona, Spain, September 2017, which has been updated to 2024., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright by International Society of Lymphology.)

Discovery of the lymphatic system is documented in numerous sources and can be attributed to a variety of persons. Like many other important developments in medicine, the recognition of the lymphatic system starts with Hippocrates (ca. 460-370 BC), who described a disease course consistent with metastasis to lymph nodes. Until the 17th century, knowledge about the anatomy and pathophysiology of the lymphatic system was limited, probably because of the difficulty of visualizing lymph vessels in animals and humans. Frederik Ruysch (1638-1731), a "praelector anatomiae" of the Amsterdam Guild of Surgeons, must be considered one of the pioneers in lymphatic research. His contribution relied on meticulous anatomical dissection of lymph vessels, and with his innovative preservation techniques, he was the first to visualize lymphatic valves. This major step provided a better understanding of lymphatic anatomy and the circulation of lymph. The German pathologist Rudolf Virchow (1821-1902) suggested that lymph nodes function as filters in the lymphatic system and could therefore contain cancer. He was the first to propose that lymph fluid from any given area of the body drains through lymphatics to a specific lymph node and subsequently to other lymph nodes. Consequently, clinicians began to recommend that local therapy of cancer should be supplemented with regional lymph node treatment to improve the cure rate. Subsequently, lymph node surgery became an essential element of surgical oncology. Lymphatic mapping and sentinel lymph node biopsy were developed several decades ago by Donald Morton (1934-2014) to stage melanoma accurately and to avoid unnecessary lymph node dissection. In a way, history is now repeating itself, as today there is renewed interest in imaging lymph vessels and lymph nodes from an oncological perspective, more than 300 years since Ruysch committed himself to visualizing the lymphatic system. From this perspective, it is important to acknowledge early contributions of Ruysch in providing the foundations to our knowledge of lymphatic anatomy. [ABSTRACT FROM AUTHOR]

Purpose: Pancreatic cancer is the fourth cause of death by cancer worldwide. Lymph node (LN) involvement is known to be the main prognostic factor. However, lymphatic anatomy is complex and only partially characterized. The aim of the study was to study the pancreatic lymphatic system using computer-assisted anatomic dissection (CAAD) technique and also to update CAAD technique by automatizing slice alignment.Methods: We dissected three human fetuses aged from 18 to 34 WA. 5-µm serial sections of duodeno-pancreas and spleen blocks were stained (hematoxylin-eosin, hematoxylin of Mayer and Masson trichrome), scanned, aligned and modeled in three dimensions.Results: We observed a rich, diffuse but not systematized lymphatic network in the peri-pancreatic region. There was an equal distribution of LNs between the cephalic and body-tail portions. The lymphatic vascularization appeared in continuity from the celiac trunk to the distal ends of its hepatic and splenic arterial branches parallel to the nerve ramifications of the celiac plexus. We also observed a continuity between the drainage of the pancreatic head and the para-aortic region posteriorly.Conclusion: In view of the wealth of peri-pancreatic LNs, the number of LNs to harvest could be increased to improve nodal staging and prognostic evaluation. Pancreatic anatomy as described does not seem to be compatible with the sentinel LN procedure in pancreatic surgery. Finally, we are now able to offer an alternative to manual alignment with a semi-automated alignment. [ABSTRACT FROM AUTHOR]

Vascularized groin lymph node transfer (VGLNT) has been successfully used to treat lymphedema. However, lack of familiarity with the inguinal node anatomy and concerns regarding donor site morbidity have limited its widespread use. The purpose of this study was to use magnetic resonance angiography (MRA) to clarify the inguinal anatomy and provide a reliable method for identifying the location of the superficial transverse inguinal lymph nodes. In this study MRA was used to evaluate the superficial inguinal lymph nodes in 117 patients. Coordinates of lymph nodes were plotted relative to an axis from the anterior superior iliac spine (ASIS) to the pubic tubercle (PT). The nodes were also plotted relative to the superficial circumflex iliac vein (SCIV) and superficial inferior epigastric vein (SIEV). A total of 1,938 lymph nodes were identified. These lymph nodes were concentrated on one-third the distance from the PT toward the ASIS and 3 cm perpendicularly below this line. About 67% of the superficial inguinal nodes were located within the bifurcation of the SIEV and SCIV. The results from this study provide useful guidelines for locating lymph nodes targeted for VGLNT. [ABSTRACT FROM AUTHOR]

Summary: Background: The recent advent in the surgical treatment of lymphedema necessitates a more detailed understanding of the anatomy of the lymphatic system. Lymphovenous anastomosis (LVA) requires a precise knowledge of the anatomy of the superficial lymphatic collectors in relation to the superficial veins. In vascularized lymph node transfer (VLNT), donor site lymphatic function must be preserved. Methods: Using the previously described technique, the superficial lymphatic drainage of 8 anterior hemi-abdomen/upper thigh specimens from 4 fresh human cadavers was investigated. Results: The upper and lower abdominal collectors were found above Scarpa's fascia immediately below the subdermal venules. They were thin-walled and translucent and their diameter ranged between 0.2 and 0.8 mm. In the upper thigh two distinct groups of superficial collectors were found. The collectors of the ventromedial bundle constituted the majority of the superficial collectors, were deep in the subcutaneous fat, measured 0.6–1 mm in diameter, had thick walls, and consistently drained into two large nodes inferolateral to the saphenous bulb. The local collectors of the thigh were immediately deep to the subdermal venules, measured 0.3–0.5 mm, had thin walls, and drained into the superolateral group of the superficial inguinal nodes which also drained the lower abdomen, the lower back and the upper gluteal region. Conclusions: When raising the groin lymphatic flap for VLNT, the medial extent of the dissection should be limited to the lateral border of femoral artery. When following up patients after VLNT with a groin donor site, circumference measurements must include the upper thigh. [Copyright &y& Elsevier]

Background: Constructing a reliable animal model for preclinical treatment of secondary lymphedema is challenging because the anatomical characteristics near the lymph nodes are understudied. Therefore, this study examined the detailed anatomical relationship between the axillary lymph node flaps (ALNFs) and brachial lymph node flaps (BLNFs) in the forelimb of Sprague-Dawley (SD) rats., Materials and Methods: Ten male rats, weighing 250-300 g, were used. The ALNFs and BLNFs on either side of the rat forelimbs were dissected. The two lymph node flaps (LNFs) were immediately harvested to analyze their physical characteristics (via imaging process software) and microscopic structure (via histology examinations)., Results: A total of 20 ALNFs and BLNFs from 10 rats were harvested and analyzed. ALNF dissection was simpler and lasted a shorter time than BLNF dissection ( p < 0.0001). The left LNFs were more difficult to dissect than the right LNFs ( p < 0.0001). In physical characteristics of LNFs, the area ( p < 0.001) of LNFs and the number of lymph nodes ( p < 0.0001) associated with ALNFs were greater than those associated with BLNFs, but the pedicle lengths of ALNFs were shorter than that of BLNFs ( p < 0.0001). No significant difference in the diameter of the venous and arterial pedicles was noted between the two LNFs ( p > 0.05)., Conclusion: This study reported detailed physical characteristics of ALNFs and BLNFs in SD rat forelimbs, assessing the respective area of LNFs, number of lymph nodes, and lengths and diameters of vascular pedicles. Moreover, this study suggested an efficient method to perform a study of LNFs by describing the operation process and repeatedly measuring the operation time., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chen, Yang, Kim, Gelvosa, Wei, Jeon and Cheon.)

Abstract: The lymphatic system was first described centuries ago. The recent discovery of various molecular markers has allowed for more in-depth research of the lymphatic system and its role in health and disease. The lymphatic system has recently been elucidated as playing an active role in cancer metastasis. The knowledge of the active processes involved in lymphatic metastasis provides novel treatment targets for various malignancies. [Copyright &y& Elsevier]

Current understanding of the lymphatics draining the breast is controversial, despite its known importance in the spread of breast cancer. Similarly, knowledge regarding the spatial distribution of primary tumours in the breast is limited. This study sought to test commonly held assumptions in this field, including: (i) that breast lymphatic drainage and tumour prevalence are symmetric between the left and right sides of the body, (ii) that males and females have the same drainage patterns and tumour prevalences, and (iii) that lymphatic drainage in the breast occurs independently to different node fields. This study has used lymphoscintigraphy data from 2304 breast cancer patients treated at the RPAH Medical Centre, Sydney, Australia. Symmetry of lymphatic drainage and tumour distribution as well as gender differences were tested using Fisher's exact test. Drainage independence was assessed using Fisher's exact test, and a multivariate probit model was used to test for drainage correlations. Results showed that the breasts are likely to have symmetric lymphatic drainage and tumour prevalence, and that there is no significant difference between males and females. Furthermore, results showed that direct lymphatic drainage of the breasts is likely to be independent between node fields. Collectively, these results serve to further our understanding of lymphatic anatomy and the distribution of tumours in the breast. [ABSTRACT FROM AUTHOR]

Relatively little is known about the functional anatomy of the lymphatic vessels draining the skin. To address this issue, we previously created a three-dimensional computer model of skin lymphatic drainage, using melanoma lymphoscintigraphy (LS) data from 5232 patients. In this study we sought to extend our model by performing a detailed statistical analysis of the mapped LS data to characterize the functional anatomy of the superficial lymphatics without any a-priori spatial bias. We investigated the commonly held assumption that lymphatic drainage is symmetric between the two sides of the body. Results indicated that, with the exception of the lower anterior torso, posterior leg and a small section of the posterior torso, most skin regions with sufficient data showed symmetric drainage. LS data from each symmetric skin region were then reflected to the opposite side of the body to provide an increased LS dataset for subsequent analysis. Cluster analysis was then applied to this reflected LS dataset to group regions of skin that drained in a similar manner. Results defined nine large clusters of skin, largely draining to the dominant axillary, groin, cervical level II and preauricular node fields. Each of the four axillary and groin node fields defined large clusters of skin on the torso, dividing it into regions similar to the historical ‘Sappey’s lines’, although a fifth region of highly ambiguous drainage was also shown in the anterior and posterior center of the torso. Collectively, these results provide important new insights into skin lymphatic drainage, both improving and quantifying our understanding of functional lymphatic anatomy. [ABSTRACT FROM AUTHOR]

Managing lymphoedema of the male genitals is challenging, distressing and potentially life-threatening if not managed appropriately. Consideration is made of the classification, clinical presentation, lymphatic anatomy and management of genital lymphoedema in clinical practice. The article addresses the issues raised when caring for patients suffering from this condition. A case history demonstrates the use of a novel innovation. The Whitaker Pouch, which can relieve and manage symptoms facilitating self-management and appropriate best practice. [ABSTRACT FROM AUTHOR]

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Background: Anatomic variations in lymphatic drainage pathways of the upper arm may have an important role in the pathophysiology of lymphedema development. The Mascagni–Sappey (M–S) pathway, initially described in 1787 by Mascagni and then again in 1874 by Sappey, is a lymphatic drainage pathway of the upper arm that normally bypasses the axilla. Utilizing modern lymphatic imaging modalities, there is an opportunity to better visualize this pathway and its potential clinical implications. Methods: A retrospective review of preoperative indocyanine green (ICG) lymphangiograms of consecutive node-positive breast cancer patients undergoing nodal resection was performed. Lymphography targeted the M-S pathway with an ICG injection over the cephalic vein in the lateral upper arm. Results: In our experience, the M-S pathway was not visualized in 22% (n = 5) of patients. In the 78% (n = 18) of patients where the pathway was visualized, the most frequent anatomic destination of the channel was the deltopectoral groove in 83% of patients and the axilla in the remaining 17%. Conclusion: Our study supports that ICG injections over the cephalic vein reliably visualizes the M-S pathway when present. Further study to characterize this pathway may help elucidate its potential role in the prevention or development of upper extremity lymphedema. [ABSTRACT FROM AUTHOR]

This study describes a new alternative route for lymphatic drainage of the arm to the cervical region. This provides a new possibility of manual lymphatic drainage in patients with lymphedema due to dissection of the axillary lymph node chain [ABSTRACT FROM AUTHOR]