Search Results (1,561)

Background: Fluorescence-guided surgery based on near-infrared imaging, most often using indocyanine green (ICG), is increasingly used in colorectal cancer (CRC) surgery. This narrative review integrates current evidence across four clinically relevant domains-anastomotic perfusion, lymphatic mapping, tumor localization, and metastasis detection and emphasizes the technical and translational factors that will determine broader implementation. Methods: We performed a structured narrative review of clinical and translational studies identified through PubMed and citation tracking, with emphasis on ICG-based workflows and emerging targeted tracers. Because the literature spans heterogeneous interventions, imaging platforms, and endpoints, no de novo meta-analysis or formal risk-of-bias assessment was undertaken. Results: ICG fluorescence angiography is the most mature application and can refine transection-line selection, although its effect on anastomotic leak appears protocol dependent. In lymphatic mapping, ICG improves visualization of drainage pathways and nodal basins but does not reliably distinguish benign from metastatic nodes. For tumor localization, ICG supports lesion marking and dynamic tissue characterization, while targeted probes and contrast-free adjuncts may improve oncologic specificity. For metastatic disease, ICG is most useful for liver margin guidance and for excluding residual disease, whereas CEA-targeted and multimodal approaches appear particularly promising for peritoneal metastases. Conclusions: The added value of this review lies in linking current clinical maturity to the translational steps still required for routine adoption. In CRC surgery, fluorescence imaging is already useful in selected settings, but broader implementation will depend on standardized protocols, objective real-time quantification, and multicenter validation of targeted tracers against clinically meaningful outcomes. Full article

Bone metastasis is a devastating complication of advanced osteotropic malignancies, notably breast, prostate, lung carcinomas, and malignant melanoma, and remains a primary driver of mortality. Historical paradigms have conceptualized skeletal dissemination almost exclusively as a hematogenous process wherein circulating tumor cells colonize receptive bone marrow niches. However, this model fails to reconcile why lymph node metastasis consistently serves as a potent predictor of bone involvement even though therapeutic lymphadenectomy rarely prevents distant spread. This discordance suggests that lymph nodes function not merely as passive reservoirs but as active ‘evolutionary gateways’ that sculpt bone-tropic metastatic clones. In this review, we introduce the Lymphatic–Bone Axis, a framework integrating lymphatic biology into models of bone metastasis. We synthesize emerging evidence elucidating how the lymph node microenvironment primes tumor cells through CCR7-CXCR4 switching, induction of osteomimicry programs, and metabolic reprogramming that favors survival within the bone marrow. We also discuss preclinical data demonstrating direct intranodal intravasation via high endothelial venules (HEVs), providing a rapid route into the systemic circulation that bypasses the thoracic duct. Beyond consolidating current knowledge, we outline a research agenda for dissecting this axis, including longitudinal single-cell transcriptomic mapping and functional assessments of lymph node-derived tumor cells. Finally, we consider translational implications, highlighting why bone-targeted agents alone may prove insufficient once cells are conditioned within lymphatic niches. By mechanistically linking lymphatic priming to skeletal colonization, this review informs the rational design of multimodal therapeutic approaches that jointly target lymphatic transit and the bone microenvironment. Full article

Etrasimod is an oral selective sphingosine-1 phosphate receptor modulator, and its anti-inflammatory mechanism of action in inflammatory bowel diseases is not completely understood. It targets pro-inflammatory immune cells expressing sphingosine-1-phosphate receptors during their migration from the lymphatic system to the circulation and intestinal mucosa. Reductions in certain lymphocyte subsets in the peripheral blood have been reported, but its effects in lymph nodes remain unknown. This study investigated changes in leukocyte subpopulations in peripheral lymph nodes and blood in Crohn’s disease patients treated with etrasimod. Moderate-to-severe Crohn’s disease patients participated in this randomized, double-blind study, within the phase 2 CULTIVATE clinical trial. At baseline and after 14 weeks of etrasimod treatment, peripheral blood and inguinal lymph node biopsies were obtained. Isolated peripheral blood mononuclear cells and lymph node leukocyte populations were analyzed at single cell level using mass cytometry at both timepoints. The immunophenotyping revealed 15 innate and adaptive major immune cell populations, as well as 14 subpopulations of CD4+ and CD8+ T-cells. In peripheral lymph nodes, etrasimod resulted in significant accumulation of naïve, central memory, and effector memory CD4+ T-cells (+10.7%, +4.2%, and +2.3%, respectively; all p = 0.03), as well as naïve CD8+ T-cells (+4.2%; p = 0.03). Conversely, these subsets were reduced in peripheral blood (−6.2%, −6.0%, −2.0%, and −2.2%, respectively; all p = 0.03). Naïve and memory B-cells decreased in the circulation (−1.7%, p = 0.057; −0.6%, p = 0.03, respectively) but were unchanged in the lymph nodes. Innate immune cell populations remained mostly unaffected in both compartments. Our data indicate that etrasimod’s pharmacodynamic effect is related primarily with the attenuation of the T-cell mediated inflammation with minor changes in B-cells. However, additional follow-up studies are needed for the validation of these observations in the context of Crohn’s disease. Full article

Background: Tailored axillary surgery (TAS) and axillary reverse mapping (ARM)-guided axillary lymph node dissection (ALND) have been developed to avoid arm lymphedema without increasing a risk of axillary recurrence. However, the oncological feasibility of TAS and ARM-guided ALND remains a crucial consideration. Methods: This article reviewed the oncological feasibility of TAS and ARM-guided ALND based on the current literature. Results: For ALND performed after TAS, additional involved nodes were found in 70% of upfront surgery patients and 60% of neoadjuvant chemotherapy (NAC) patients. ARM nodes were also involved in up to 64.7% of patients after ALND. However, it is not necessary to preserve all ARM nodes and lymphatics because multiple ARM lymphatic pathways exist. Selective preservation of ARM nodes closest to the axillary vein significantly reduced the incidence of involved ARM nodes (from 64.7% to 15.7%). Conclusions: TAS and ARM-guided ALND remain much less radical than ALND. However, residual nodal disease after TAS or ARM-guided ALND does not always develop axillary recurrence. Postoperative irradiation is effective in achieving local control in patients with low-volume (microscopic) residual nodal disease after TAS or ARM-guided ALND. We await the long-term results of prospective randomized clinical trials comparing TAS and ARM-guided ALND with conventional ALND. Full article

Isolated pelvic nodal metastasis from carcinoma of unknown primary origin (CUP) is rare. Evaluation should prioritize gynecological and anorectal sites based on pelvic lymphatic drainage. Although spontaneous regression of these primary lesions is exceptional, regressed lesions can present as CUP, necessitating diagnostic caution. Here, we report the case of a 40-year-old woman with a solitary, intensely fluorodeoxyglucose F-18 avid left obturator lymph node and a subtle endocervical abnormality on pelvic magnetic resonance imaging. Loop electrosurgical excision revealed a Nabothian cyst only. Excisional nodal biopsy by polymerase chain reaction revealed metastatic squamous cell carcinoma with diffuse block-type p16 and human papillomavirus (HPV) 16. Considering the potential for a primary cervical tumor along the obturator drainage pathway, the patient underwent hysterectomy with pelvic lymph node dissection. No residual invasive carcinoma was found; however, HPV16 was detected in the cervix with a low-grade squamous intraepithelial lesion, supporting a regressed cervical focus. She received adjuvant cisplatin-based chemoradiotherapy and has remained disease-free for 56 months. This case highlights the diagnostic value of integrating lymphatic anatomy with the molecular profile of HPV. Cervical squamous cell carcinoma rarely regresses and presents solely as an isolated nodal disease. Full article

Objective: An important characteristic of Hepatocellular carcinoma (HCC) is that it features multicentric recurrences that can recur after curative treatment. Current recommended curative treatments for HCC include liver transplantation (LT), and prognostic evaluation and appropriate treatment selection are crucial in the management of HCC patients. Factors considered tend to include tumor size and number, lobar distribution, multinodularity, α-fetoprotein (AFP) level, degree of tumor differentiation, vascular invasion, and satellite nodules. However, the prognostic value of intrahepatic lymphatic vessel invasion (LVI) has rarely been reported for liver cancers. Methods: From January 2012 to December 2020, a total of 178 HCC patients who underwent liver transplantation consecutively were retrospectively enrolled. Those who underwent liver transplantation were divided into two groups based on the presence or absence of lymphatic vessel invasion. The primary aim was to compare the two groups for overall survival (OS), disease free survival (DFS), and recurrence rates, as well as to evaluate the prognostic effect of LVI after transplantation. Results: Poor tumor characteristics such as high tumor differentiation grade and MVI were significantly higher in the patient group with LI. Tumor recurrence and mortality rates were significantly higher in LI-positive recipients. Conclusions: The lymphatic invasion (LI) group displayed higher rates of recurrence and mortality. The findings emphasize the need to incorporate LI assessment into prognostic evaluations to enhance the management and outcomes of individuals with Hepatocellular carcinoma. Full article

Inflammatory mammary carcinoma (IMC) is an aggressive mammary carcinoma phenotype characterized by tumor emboli within superficial dermal lymphatic vessels and early metastasis. A captive Bengal tiger (Panthera tigris tigris) presented with large abdominal mammary masses and regional lymphadenopathy; contrast-enhanced computed tomography also revealed a pulmonary nodule. Postmortem examination and histopathology confirmed mammary carcinoma with dermal lymphatic tumor emboli and metastases to regional lymph nodes and the lung. Tumor emboli were cytokeratin positive, supporting epithelial origin and an IMC diagnosis, and neoplastic cells were immunopositive for cytokeratin with concurrent vimentin immunoreactivity. This case highlights the clinicopathologic basis of IMC and the diagnostic importance of including full-thickness skin and adjacent subcutis in the sampling plan. Full article

Alzheimer’s disease (AD) is a serious medical challenge, representing an incurable and insidious disease. Current treatments can slow AD progression but cannot cure it. Promising new methods for AD therapy are essential for addressing the growing number of people with dementia, especially after the COVID-19 pandemic. The review highlights pioneering approaches to AD treatment based on innovative methods for the stimulation of brain drainage and clearance, in which the meningeal lymphatic vessels (MLVs) play a key role. Clinically promising noninvasive technologies using photobiomodulation for the effective clearance of metabolites, including amyloid beta (Aβ), and for the improvement of cognitive impairment during AD progression are discussed. An interesting part of the review is its analysis of innovative methods of improving the efficacy of anti-Aβ immunotherapy by stimulating MLV growth. The review is also focused on lifestyle, including sleep and physical exercises, discussing their support for the efficient lymphatic removal of waste products from the brain. Overall, the review provides an important, informative platform to excite the interest of a wide range of readers in the development of promising and clinically significant strategies for the treatment of AD, based on new strategies for the stimulation of brain drainage and clearance. Full article

Background: Acalabrutinib is a selective Bruton tyrosine kinase inhibitor widely used for chronic lymphocytic leukemia and mantle cell lymphoma. Real-world safety evidence from Latin America remains limited, which restricts local benchmarking and pharmacovigilance planning. In this study we aimed to assess exposure-adjusted adverse events in routine care in Mexico. Methods: We analyzed postmarketing surveillance datasets and spontaneous reports from March 2020 to August 2024, classifying events with MedDRA and summarizing seriousness, severity, and incidence per 100 patient-years. Results: A total of 266 patients were registered; 193 had evaluable exposure and safety data, contributing 242.73 patient-years. The overall adverse event incidence was 24.71 per 100 patient-years. Twenty-eight individual case safety reports documented 60 events. Forty-four events were serious. Among 33 events with reported severity, 14 were severe, 14 moderate, and five mild. Frequently affected system organ classes were blood and lymphatic, vascular, and infections. Seven deaths were reported; most were associated with COVID-19 complications or disease progression. Conclusions: The adverse event profile observed aligns with published trial experience and supports the tolerability of acalabrutinib in Mexican practice. These country-level, exposure-adjusted estimates provide actionable context for clinicians, institutional pharmacists and pharmacovigilance teams and point to the value of strengthening report completeness to improve signal detection in routine oncology care. Full article

The mechanisms underlying meningeal lymphatic vessel (mLV)-mediated immune cell clearance after stroke remain unclear. Using a mouse middle cerebral artery occlusion model, we performed single-cell RNA sequencing to analyze post-ischemic meningeal macrophages. In vitro co-culture and CCR2 inhibition (RS504393) validated the CCL2-CCR2 axis between lymphatic endothelial cells and macrophages. Macrophage trafficking to mLVs and cervical lymph nodes was assessed by Evans Blue tracing and F4/80 immunofluorescence. We utilized VEGF-C to enhance meningeal lymphatic vessel function and concomitantly evaluated neurological deficits, brain edema, and neuroinflammation. Ischemia expanded meningeal macrophages, whose crosstalk with lymphatic endothelial cells relied on CCL2-CCR2 axis. CCR2 inhibition impaired macrophage trafficking to mLVs and cervical lymph nodes, worsening edema, motor deficits, and inflammation, whereas VEGF-C enhanced mLV drainage and improved outcomes. We identify a novel mechanism where in mLVs recruit macrophages via CCL2 for perivascular clearance post-ischemia. Combining VEGF-C with modulation of the CCL2-CCR2 axis presents a promising synergistic therapeutic strategy for stroke. Full article

Background/Objectives: The use of near-infrared fluorescence (NIRF) imaging with indocyanine green (ICG) has gained increasing attention in the management of vascular malformations, offering real-time visualization of vascular and lymphatic structures that may improve surgical precision and outcomes. Methods: A systematic review was conducted in accordance with PRISMA guidelines, searching PubMed, Web of Science, CINAHL, and EMBASE databases for studies evaluating the intraoperative use of ICG in vascular malformations, which was prospectively registered in PROSPERO (CRD420251131951). Two independent reviewers screened all records based on predefined eligibility criteria. Extracted data included study design, patient characteristics, ICG administration protocols, clinical applications, and perioperative outcomes. Results: A total of 33 studies comprising 433 patients treated between 2014 and 2025 were included for qualitative synthesis. Nineteen (57.6%) were case reports, seven (21.2%) retrospective descriptive studies, two (6.1%) retrospective comparative studies, three (9.1%) prospective comparative trials, and two (6.1%) prospective descriptive studies. Clinical indications for ICG included capillary and venous malformations (5 studies), arteriovenous malformations (9 studies), and lymphatic malformations (19 studies). Quality assessment with the MINORS tool showed that most studies scored < 17, while only seven reached 18–24, reflecting higher methodological quality. Conclusions: Intraoperative ICG fluorescence imaging represents a promising adjunct in the treatment of vascular malformations, providing real-time visualization that may facilitate lesion delineation, guide resection, and support minimally invasive techniques such as lymphaticovenous anastomosis. However, current evidence is largely descriptive, with very limited comparative outcome data, and high-quality studies are needed to determine whether these technical advantages translate into improved long-term clinical outcomes. Full article

The compatibility of economic efficiency and animal welfare is a major challenge given the increasing demand for animal-based foods. Various studies have shown that it is possible to promote the resistance and robustness of commercial poultry (primarily broilers) by modifying incubation temperatures. Focused on the histology of the Bursa fabricii, an important lymphatic organ in birds, the investigations in this paper aim to show whether short-term temperature changes during final incubation (+1 °C, 2 h/incubation day 17–20) could have an influence on the robustness of broilers compared to conventionally incubated ones. Overall, however, the temperature stimulation during final embryonic development did not result in any statistically significant morphological changes in the bursa or in the heterophil-to-lymphocyte ratio (HLR) that would clearly indicate improved immune function. However, there are obvious sex-specific differences. For instance, a sexual dimorphism could be seen in the parameters of follicle number, follicle density and in the HLR when looking at the absolute numbers. Calculation of the effect size using Cohen’s d showed that there was an effect on the relative weight of the Bursa fabricii (d = −0.28, d ♂ = −0.25, d ♀ = −0.35) cell density (d ♀ = −0.32), follicle density (d ♀ = 0.37) and the HLR (d = 0.24, d ♂ = 0.43), so that further investigations should be encouraged. Full article

Lymphatic filariasis (LF) is a mosquito-borne neglected tropical disease that causes substantial morbidity and social exclusion. Global efforts under the World Health Organization’s Global Programme to Eliminate Lymphatic Filariasis have markedly reduced prevalence, and several Pacific Island Countries and Territories (PICTs) have achieved elimination of the disease as a public health problem. However, post-validation surveillance (PVS), essential for detecting resurgence and enabling early response, has rarely been implemented, and barriers to its delivery remain poorly understood. We used two complementary qualitative approaches to identify systemic barriers and enablers to LF PVS in PICTs. First, we conducted a Nominal Group Technique followed by a structured expert elicitation involving program managers and technical staff. Data were analysed thematically and triangulated across sources. Participants identified 70 challenges which were consolidated into ten thematic domains. Pertinent barriers relate to limited leadership understanding of LF and surveillance options, inconsistent technical and financial support, and a lack of context-appropriate operational guidance. Additional challenges included limited field-ready diagnostics, procurement delays, the absence of formal mandates, and low community engagement. Enablers included embedding PVS within existing health services, leveraging trusted community networks, strengthening regional frameworks, and co-developing practical tools with countries. Sustaining LF elimination in the Pacific will require political commitment, regional collaboration, and integrated, programmatic approaches informed by recent PVS experience. Full article

Cervical lymph node metastases are major prognostic determinants in head and neck squamous cell carcinoma (HNSCC), and neck dissection (ND) has long been central to regional control. As ND has evolved from radical to selective procedures, immune checkpoint inhibitors (ICIs) have emerged as a fourth treatment pillar, reframing tumor-draining lymph nodes (TDLNs) as active immune organs rather than passive conduits of metastatic spread. This narrative review synthesizes surgical, immunologic, and translational evidence on how ND and cervical irradiation interact with immunotherapy. It also examines the historical development of ND, the immunologic structure and function of cervical TDLNs, and the use of neoadjuvant, perioperative, and recurrent/metastatic immunotherapy in HNSCC. Preclinical and early clinical observations suggest that ablating or heavily irradiating non-involved nodal basins may attenuate ICI efficacy by disrupting antigen presentation, progenitor exhausted CD8⁺ T (Tpex) cell pools, and effector recirculation, supporting the conceptual model of an “immune desert neck.” The review critically appraises timing (pre- versus post-immunotherapy ND), response-adapted or de-escalated surgery, and imaging, tissue-based, and circulating biomarkers to guide individualized management. Current evidence does not support abandoning elective or therapeutic ND, but does highlight the need for biomarker-driven, lymphatic-sparing trials to redefine when ND is essential, modifiable, or potentially avoidable in immunotherapy-treated HNSCC. Full article

Introduction: Implant-based breast reconstruction is associated with an increased risk of ischemic complications, which may result in implant loss, suboptimal aesthetic outcomes, and delays in adjuvant oncological treatment. Additionally, axillary surgery carries a risk of upper-limb lymphedema. Indocyanine green (ICG) angiography enables more accurate real-time assessment of tissue perfusion than clinical evaluation alone, while axillary reverse mapping (ARM) facilitates the preservation of upper-limb lymphatics. The integration of these techniques reduces complications and improves both functional and aesthetic outcomes. Materials and methods: A total of 208 breast cancer patients who underwent mastectomy followed by immediate implant-based breast reconstruction were enrolled in this case–control study. The prospective intervention group received intraoperative ICG angiography at three time points and underwent ARM with ICG. Conventional surgical techniques were applied in the retrospective control group. Results: ICG angiography showed excellent diagnostic accuracy for predicting postoperative ischemic complications (AUC = 0.93, 95% CI 0.82–0.99, p < 0.001). Compared with the control group, patients in the ICG group had significantly lower rates of mastectomy skin flap necrosis (11.5% vs. 30.8%, p = 0.001), seroma (4.8% vs. 14.4%, p = 0.032), hematoma (1.9% vs. 9.6%, p = 0.033), and lymphedema (2.9% vs. 17.3%, p < 0.001). They also experienced shorter hospitalization (6.2 ± 1.9 vs. 8.0 ± 2.8 days, p < 0.001), fewer delays in adjuvant treatment initiation (16.3% vs. 32.7%, p = 0.010), and higher aesthetic satisfaction scores (81.41 ± 10.12 vs. 76.03 ± 9.74, p <0.001). Conclusions: Intraoperative indocyanine green angiography is a valuable tool for predicting ischemic complications in alloplastic breast reconstruction and is associated with reduced morbidity, fewer delays in adjuvant treatment, and improved aesthetic outcomes. Preliminary evidence suggests that axillary reverse mapping is associated with lower rates of upper-limb lymphedema. Full article