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Seminars in Nuclear Medicine Sep 2022Breast cancer is the most frequent cancer diagnosed in women worldwide. Accurate lymph node staging is essential for both prognosis (of early-stage disease) and... (Review)
Review
Breast cancer is the most frequent cancer diagnosed in women worldwide. Accurate lymph node staging is essential for both prognosis (of early-stage disease) and treatment (for regional control of disease) in patients with breast cancer. The sentinel lymph nodes are the regional nodes that directly drain lymph from the primary tumor. No imaging modality is accurate enough to detect lymph node metastases when a primary breast cancer is at an early stage (I or II), but sentinel lymph node biopsy is a highly reliable method for screening axillary nodes and for identifying metastatic (including micro-metastatic) disease in regional lymph nodes. Despite the widespread use of sentinel lymph node biopsy for early-stage breast cancer, relevant variations have been described regarding practical aspects of the procedure, and some variability has initially been reported regarding the rates of intraoperative sentinel lymph node identification and of false-negative findings, most likely because of differences in the size of the populations being investigated and in lymphatic mapping techniques. Nevertheless, using adequate learning curves and once a multidisciplinary team is experienced with the procedure, improved levels of accuracy are achieved.
Topics: Axilla; Breast Neoplasms; Female; Humans; Neoplasm Staging; Sentinel Lymph Node; Sentinel Lymph Node Biopsy
PubMed: 35241267
DOI: 10.1053/j.semnuclmed.2022.01.006 -
Cancer Cell Dec 2022The lack of T cell infiltrates is a major obstacle to effective immunotherapy in cancer. Conversely, the formation of tumor-associated tertiary-lymphoid-like structures...
The lack of T cell infiltrates is a major obstacle to effective immunotherapy in cancer. Conversely, the formation of tumor-associated tertiary-lymphoid-like structures (TA-TLLSs), which are the local site of humoral and cellular immune responses against cancers, is associated with good prognosis, and they have recently been detected in immune checkpoint blockade (ICB)-responding patients. However, how these lymphoid aggregates develop remains poorly understood. By employing single-cell transcriptomics, endothelial fate mapping, and functional multiplex immune profiling, we demonstrate that antiangiogenic immune-modulating therapies evoke transdifferentiation of postcapillary venules into inflamed high-endothelial venules (HEVs) via lymphotoxin/lymphotoxin beta receptor (LT/LTβR) signaling. In turn, tumor HEVs boost intratumoral lymphocyte influx and foster permissive lymphocyte niches for PD1 and PD1TCF1 CD8 T cell progenitors that differentiate into GrzBPD1 CD8 T effector cells. Tumor-HEVs require continuous CD8 and NK cell-derived signals revealing that tumor HEV maintenance is actively sculpted by the adaptive immune system through a feed-forward loop.
Topics: Humans; Venules; Endothelial Cells; Immunotherapy; Lymph Nodes; Neoplasms
PubMed: 36423635
DOI: 10.1016/j.ccell.2022.11.002 -
Immunity Apr 2022Lymph node (LN) stromal cells play a crucial role in LN development and in supporting adaptive immune responses. However, their origin, differentiation pathways, and...
Lymph node (LN) stromal cells play a crucial role in LN development and in supporting adaptive immune responses. However, their origin, differentiation pathways, and transcriptional programs are still elusive. Here, we used lineage-tracing approaches and single-cell transcriptome analyses to determine origin, transcriptional profile, and composition of LN stromal and endothelial progenitors. Our results showed that all major stromal cell subsets and a large proportion of blood endothelial cells originate from embryonic Hoxb6 progenitors of the lateral plate mesoderm (LPM), whereas lymphatic endothelial cells arise from Pax3 progenitors of the paraxial mesoderm (PXM). Single-cell RNA sequencing revealed the existence of different Cd34 and Cxcl13 stromal cell subsets and showed that embryonic LNs contain proliferating progenitors possibly representing the amplifying populations for terminally differentiated cells. Taken together, our work identifies the earliest embryonic sources of LN stromal and endothelial cells and demonstrates that stromal diversity begins already during LN development.
Topics: Endothelial Cells; Lymph Nodes; Sequence Analysis, RNA; Single-Cell Analysis; Stromal Cells; Transcription Factors
PubMed: 35358427
DOI: 10.1016/j.immuni.2022.03.002 -
International Journal of Gynecological... Mar 2020Many tracers have been introduced into current medical practice with the purpose of improving lymphatic mapping techniques, anatomic visualization, and organ/tissue... (Review)
Review
Many tracers have been introduced into current medical practice with the purpose of improving lymphatic mapping techniques, anatomic visualization, and organ/tissue perfusion assessment. Among them, three tracers have dominated the field: indocyanine green, technetium-99m radiocolloid (Tc99), and blue dye. Tc99 and blue dye are used individually or in combination; however, given particular challenges with these tracers, such as the need for a preoperative procedure by nuclear medicine and cost, other options have been sought. Indocyanine green has proven to be a promising alternative for certain procedures, as it is easy to use and has quick uptake. Its use in the management of gynecologic cancers was first described for sentinel lymph node mapping in cervical cancer, and later for endometrial and vulvar cancers. This review provides an in-depth look at these mapping substances, their uses, and the potential for new discoveries.
Topics: Female; Genital Neoplasms, Female; Humans; Lymph Nodes; Lymphatic Metastasis; Neoplasm Staging; Prognosis; Randomized Controlled Trials as Topic; Sentinel Lymph Node; Sentinel Lymph Node Biopsy
PubMed: 31953349
DOI: 10.1136/ijgc-2019-001078 -
Gland Surgery Apr 2020Lymphedema is a chronic, progressive disease caused by primary or secondary reasons. It is currently uncurable and conservative compression therapy is generally applied.... (Review)
Review
Lymphedema is a chronic, progressive disease caused by primary or secondary reasons. It is currently uncurable and conservative compression therapy is generally applied. Lymphovenous anastomosis and vascularized lymph node transfer (VLNT) are two main surgical treatment that are used in addition to conservative therapy. Lymphovenous anastomosis involves the anastomosing remaining functional lymphatic vessels to vein. When the lymphatic vessels are greatly damaged and in no case can they be used for anastomosis, VLNT provide the affected area with lymph nodes from elsewhere to restore the drainage function. During all these procedures, a clear image to identify related lymphatic structures and venous vessels can be greatly useful for preoperative planning, intraoperative navigation, and postoperative evaluation. Lymphoscintigraphy used to be the gold standard in evaluating lymphedema and mapping lymphatic systems. But due to the downside of radiation, invasive operation and complication, other modalities are gaining attention. In this article, we reviewed the application of Indocyanine green (ICG) lymphography, ultrasound, magnetic resonance lymphography (MRL), and single-photon emission computed tomography-computed tomography (SPECT-CT) in the field of surgical therapy in lymphedema.
PubMed: 32420293
DOI: 10.21037/gs.2020.03.24 -
Theranostics 2015In view of the importance of sentinel lymph nodes (SLNs) in tumor staging and patient management, sensitive and accurate imaging of SLNs has been intensively explored.... (Review)
Review
In view of the importance of sentinel lymph nodes (SLNs) in tumor staging and patient management, sensitive and accurate imaging of SLNs has been intensively explored. Along with the advance of the imaging technology, various contrast agents have been developed for lymphatic imaging. In this review, the lymph node imaging agents were summarized into three groups: tumor targeting agents, lymphatic targeting agents and lymphatic mapping agents. Tumor targeting agents are used to detect metastatic tumor tissue within LNs, lymphatic targeting agents aim to visualize lymphatic vessels and lymphangionesis, while lymphatic mapping agents are mainly for SLN detection during surgery after local administration. Coupled with various signal emitters, these imaging agents work with single or multiple imaging modalities to provide a valuable way to evaluate the location and metastatic status of SLNs.
Topics: Animals; Contrast Media; Fluorescent Dyes; Humans; Lymphatic Metastasis; Magnetic Resonance Imaging; Positron-Emission Tomography; Radiopharmaceuticals; Spectroscopy, Near-Infrared; Tomography, X-Ray Computed
PubMed: 25897334
DOI: 10.7150/thno.11862 -
Chinese Clinical Oncology Apr 2021Lymph node removal as a part of surgical management is a standard of care in vulvar cancer patients. Due to patient morbidities and difficulties in treatment of inguinal... (Review)
Review
Lymph node removal as a part of surgical management is a standard of care in vulvar cancer patients. Due to patient morbidities and difficulties in treatment of inguinal healing after lymph nodes removal, lymphatic mapping has emerged as an increasingly popular option over the past few years. At this time several different techniques have been described and variety of different dyes were used. In addition, an important aspect of the use of the sentinel lymph node (SLN) technique is the removal of a limited number of lymph nodes, which allows more detailed pathological examination. Moreover, the interpretation of pathological ultra-staging of SLNs, which can identify low-volume metastases for which the clinical significance and the ideal management, remain uncertain. Despite differences in techniques and dyes used, this minimally invasive procedure is currently recommended as an alternative to full inguinofemoral lymph node dissection in selected cases by all major international societies. As for now SLN concept became a standard of care in vulvar cancer. This technique, though simple as a concept, requires a learning curve and should only be used in expert centers. This article provides a review on literature on SLN technique in vulvar cancer, current recommendations and future lines of investigation.
Topics: Female; Humans; Lymphatic Metastasis; Sentinel Lymph Node; Sentinel Lymph Node Biopsy; Vulvar Neoplasms
PubMed: 33353362
DOI: 10.21037/cco-20-202