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Cell May 2022For many solid malignancies, lymph node (LN) involvement represents a harbinger of distant metastatic disease and, therefore, an important prognostic factor. Beyond its...
For many solid malignancies, lymph node (LN) involvement represents a harbinger of distant metastatic disease and, therefore, an important prognostic factor. Beyond its utility as a biomarker, whether and how LN metastasis plays an active role in shaping distant metastasis remains an open question. Here, we develop a syngeneic melanoma mouse model of LN metastasis to investigate how tumors spread to LNs and whether LN colonization influences metastasis to distant tissues. We show that an epigenetically instilled tumor-intrinsic interferon response program confers enhanced LN metastatic potential by enabling the evasion of NK cells and promoting LN colonization. LN metastases resist T cell-mediated cytotoxicity, induce antigen-specific regulatory T cells, and generate tumor-specific immune tolerance that subsequently facilitates distant tumor colonization. These effects extend to human cancers and other murine cancer models, implicating a conserved systemic mechanism by which malignancies spread to distant organs.
Topics: Animals; Immune Tolerance; Immunotherapy; Lymph Nodes; Lymphatic Metastasis; Melanoma; Mice
PubMed: 35525247
DOI: 10.1016/j.cell.2022.04.019 -
BMJ (Clinical Research Ed.) Sep 2022To determine if margin involvement is associated with distant recurrence and to determine the required margin to minimise both local recurrence and distant recurrence in... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To determine if margin involvement is associated with distant recurrence and to determine the required margin to minimise both local recurrence and distant recurrence in early stage invasive breast cancer.
DESIGN
Prospectively registered systematic review and meta-analysis of literature.
DATA SOURCES
Medline (PubMed), Embase, and Proquest online databases. Unpublished data were sought from study authors.
ELIGIBILITY CRITERIA
Eligible studies reported on patients undergoing breast conserving surgery (for stages I-III breast cancer), allowed an estimation of outcomes in relation to margin status, and followed up patients for a minimum of 60 months. Patients with ductal carcinoma in situ only or treated with neoadjuvant chemotherapy or by mastectomy were excluded. Where applicable, margins were categorised as tumour on ink (involved), close margins (no tumour on ink but <2 mm), and negative margins (≥2 mm).
RESULTS
68 studies from 1 January 1980 to 31 December 2021, comprising 112 140 patients with breast cancer, were included. Across all studies, 9.4% (95% confidence interval 6.8% to 12.8%) of patients had involved (tumour on ink) margins and 17.8% (13.0% to 23.9%) had tumour on ink or a close margin. The rate of distant recurrence was 25.4% (14.5% to 40.6%) in patients with tumour on ink, 8.4% (4.4% to 15.5%) in patients with tumour on ink or close, and 7.4% (3.9% to 13.6%) in patients with negative margins. Compared with negative margins, tumour on ink margins were associated with increased distant recurrence (hazard ratio 2.10, 95% confidence interval 1.65 to 2.69, P<0.001) and local recurrence (1.98, 1.66 to 2.36, P<0.001). Close margins were associated with increased distant recurrence (1.38, 1.13 to 1.69, P<0.001) and local recurrence (2.09, 1.39 to 3.13, P<0.001) compared with negative margins, after adjusting for receipt of adjuvant chemotherapy and radiotherapy. In five studies published since 2010, tumour on ink margins were associated with increased distant recurrence (2.41, 1.81 to 3.21, P<0.001) as were tumour on ink and close margins (1.44, 1.22 to 1.71, P<0.001) compared with negative margins.
CONCLUSIONS
Involved or close pathological margins after breast conserving surgery for early stage, invasive breast cancer are associated with increased distant recurrence and local recurrence. Surgeons should aim to achieve a minimum clear margin of at least 1 mm. On the basis of current evidence, international guidelines should be revised.
SYSTEMATIC REVIEW REGISTRATION
CRD42021232115.
Topics: Breast; Breast Neoplasms; Female; Humans; Margins of Excision; Mastectomy; Mastectomy, Segmental; Neoplasm Recurrence, Local
PubMed: 36130770
DOI: 10.1136/bmj-2022-070346 -
International Journal of Biological... 2022Nasopharyngeal carcinoma (NPC) is a malignancy with high metastatic and invasive nature. Distant metastasis contributes substantially to treatment failure and mortality...
Nasopharyngeal carcinoma (NPC) is a malignancy with high metastatic and invasive nature. Distant metastasis contributes substantially to treatment failure and mortality in NPC. Platelets are versatile blood cells and the number of platelets is positively associated with the distant metastasis of tumor cells. However, the role and underlying mechanism of platelets responsible for the metastasis of NPC cells remain unclear. Here we found that the distant metastasis of NPC patients was positively correlated with the expression levels of integrin β3 (ITGB3) in platelet-derived extracellular vesicles (EVs) from NPC patients (P-EVs). We further revealed that EVs transfer occurred from platelets to NPC cells, mediating cell-cell communication and inducing the metastasis of NPC cells by upregulating ITGB3 expression. Mechanistically, P-EVs-upregulated ITGB3 increased SLC7A11 expression by enhancing protein stability and activating the MAPK/ERK/ATF4/Nrf2 axis, which suppressed ferroptosis, thereby facilitating the metastasis of NPC cells. NPC xenografts in mouse models further confirmed that P-EVs inhibited the ferroptosis of circulating NPC cells and promoted the distant metastasis of NPC cells. Thus, these findings elucidate a novel role of platelet-derived EVs in NPC metastasis, which not only improves our understanding of platelet-mediated tumor distant metastasis, but also has important implications in diagnosis and treatment of NPC.
Topics: Mice; Animals; Humans; Nasopharyngeal Carcinoma; Integrin beta3; NF-E2-Related Factor 2; Ferroptosis; Cell Line, Tumor; Extracellular Vesicles; Nasopharyngeal Neoplasms; Neoplasm Metastasis; Gene Expression Regulation, Neoplastic
PubMed: 36263165
DOI: 10.7150/ijbs.76162 -
Current Opinion in Immunology Oct 2023Delivery of vaccines via the mucosal route is regarded as the most effective mode of immunization to counteract infectious diseases that enter via mucosal tissues,... (Review)
Review
Delivery of vaccines via the mucosal route is regarded as the most effective mode of immunization to counteract infectious diseases that enter via mucosal tissues, including oral, nasal, pulmonary, intestinal, and urogenital surfaces. Mucosal vaccines not only induce local immune effector elements, such as secretory Immunoglobulin A (IgA) reaching the luminal site of the mucosa, but also systemic immunity. Moreover, mucosal vaccines may trigger immunity in distant mucosal tissues because of the homing of primed antigen-specific immune cells toward local and distant mucosal tissue via the common mucosal immune system. While most licensed intramuscular vaccines induce only systemic immunity, next-generation mucosal vaccines may outperform parenteral vaccination strategies by also eliciting protective mucosal immune responses that block infection and/or transmission. Especially the nasal route of vaccination, targeting the nasal-associated lymphoid tissue, is attractive for local and distant mucosal immunization. In numerous studies, bacterial outer membrane vesicles (OMVs) have proved attractive as vaccine platform for homologous bacterial strains, but also as antigen delivery platform for heterologous antigens of nonbacterial diseases, including viruses, parasites, and cancer. Their application has also been extended to mucosal delivery. Here, we will summarize the characteristics and clinical potential of (engineered) OMVs as vaccine platform for mucosal, especially intranasal delivery.
Topics: Humans; Vaccines; Administration, Intranasal; Immunization; Vaccination; Immunity, Mucosal; Mucous Membrane
PubMed: 37598549
DOI: 10.1016/j.coi.2023.102376 -
International Journal of Nursing Studies Mar 2024Patients who are suffering may be commonly encountered in health care. The growing use of telehealth implies that encounters with patients who are suffering may...
BACKGROUND
Patients who are suffering may be commonly encountered in health care. The growing use of telehealth implies that encounters with patients who are suffering may increasingly take place at a distance. "Distant suffering" is a concept coined within sociology to describe the suffering of far-away others. It is conceptualized as a paradox, as distance changes the relation between the witness of suffering and the suffering encountered. Impacts may include a potential detriment to the sufferer and ethical implications for the witness.
OBJECTIVE
To explore the concept of distant suffering and any relevance, implications, or important avenues for potential research within the healthcare sciences.
DESIGN
Rodgers' evolutionary concept analysis.
DATA SOURCES
Databases of Web of Science, Medline, CINAHL and PsycInfo were searched for the terms "distant suffering" or "mediated suffering".
REVIEW METHOD
Attributes, surrogate or related terms, antecedents, consequences, and uses of the concept were extracted and synthesized.
RESULTS
Thirty articles published within the past ten years were selected for review from the search results. "Distant suffering" was characterized as comprising 1) mediated far-away suffering, 2) a "recognizer" or witness, and 3) a potential role of a moderator. Antecedents include shared understandings and socially-influenced responses. Consequences include responses like empathy, compassion, pity, also indifference, cynicism and compassion fatigue.
CONCLUSIONS
Further research to explore distant suffering from healthcare sciences' perspective could uncover valuable insights for those suffering, for healthcare workers, and any who are exposed to it. An improved understanding of how distant suffering is conveyed and moderated could enable targeted reduction of exposure or improve response to distant suffering. Such knowledge could help diminish negative consequences for those suffering, for healthcare workers who are caring at a distance for those suffering, or for others who encounter distant suffering in their occupations or in daily life via media, social media, or digital communications.
TWEETABLE ABSTRACT
New analysis finds that exposure to distant suffering may have important implications for health and health care.
Topics: Humans; Empathy; Health Personnel; Compassion Fatigue; Delivery of Health Care; Telemedicine
PubMed: 38184919
DOI: 10.1016/j.ijnurstu.2023.104672 -
Acta Otorhinolaryngologica Italica :... Apr 2020
Review
Topics: Drug Therapy; Epstein-Barr Virus Infections; Female; Frailty; Head and Neck Neoplasms; Herpesvirus 4, Human; Humans; Immunotherapy; Male; Nanomedicine; Neoplasms, Second Primary; Papillomavirus Infections; Prognosis; Radiotherapy; Socioeconomic Factors; Squamous Cell Carcinoma of Head and Neck; Tumor Microenvironment
PubMed: 32469009
DOI: 10.14639/0392-100X-suppl.1-40-2020 -
Molecular Cancer Nov 2023Current research has demonstrated that extracellular vesicles (EVs) and circulating tumor cells (CTCs) are very closely related in the process of distant tumor... (Review)
Review
Current research has demonstrated that extracellular vesicles (EVs) and circulating tumor cells (CTCs) are very closely related in the process of distant tumor metastasis. Primary tumors are shed and released into the bloodstream to form CTCs that are referred to as seeds to colonize and grow in soil-like distant target organs, while EVs of tumor and nontumor origin act as fertilizers in the process of tumor metastasis. There is no previous text that provides a comprehensive review of the role of EVs on CTCs during tumor metastasis. In this paper, we reviewed the mechanisms of EVs on CTCs during tumor metastasis, including the ability of EVs to enhance the shedding of CTCs, protect CTCs in circulation and determine the direction of CTC metastasis, thus affecting the distant metastasis of tumors.
Topics: Humans; Neoplastic Cells, Circulating; Extracellular Vesicles; Neoplasm Metastasis; Biomarkers, Tumor
PubMed: 38037077
DOI: 10.1186/s12943-023-01909-5 -
Frontiers in Oncology 2023Distant metastasis from rectal cancer usually results in poorer survival and quality of life, so early identification of patients at high risk of distant metastasis from...
BACKGROUND
Distant metastasis from rectal cancer usually results in poorer survival and quality of life, so early identification of patients at high risk of distant metastasis from rectal cancer is essential.
METHOD
The study used eight machine-learning algorithms to construct a machine-learning model for the risk of distant metastasis from rectal cancer. We developed the models using 23867 patients with rectal cancer from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2017. Meanwhile, 1178 rectal cancer patients from Chinese hospitals were selected to validate the model performance and extrapolation. We tuned the hyperparameters by random search and tenfold cross-validation to construct the machine-learning models. We evaluated the models using the area under the receiver operating characteristic curves (AUC), the area under the precision-recall curve (AUPRC), decision curve analysis, calibration curves, and the precision and accuracy of the internal test set and external validation cohorts. In addition, Shapley's Additive explanations (SHAP) were used to interpret the machine-learning models. Finally, the best model was applied to develop a web calculator for predicting the risk of distant metastasis in rectal cancer.
RESULT
The study included 23,867 rectal cancer patients and 2,840 patients with distant metastasis. Multiple logistic regression analysis showed that age, differentiation grade, T-stage, N-stage, preoperative carcinoembryonic antigen (CEA), tumor deposits, perineural invasion, tumor size, radiation, and chemotherapy were-independent risk factors for distant metastasis in rectal cancer. The mean AUC value of the extreme gradient boosting (XGB) model in ten-fold cross-validation in the training set was 0.859. The XGB model performed best in the internal test set and external validation set. The XGB model in the internal test set had an AUC was 0.855, AUPRC was 0.510, accuracy was 0.900, and precision was 0.880. The metric AUC for the external validation set of the XGB model was 0.814, AUPRC was 0.609, accuracy was 0.800, and precision was 0.810. Finally, we constructed a web calculator using the XGB model for distant metastasis of rectal cancer.
CONCLUSION
The study developed and validated an XGB model based on clinicopathological information for predicting the risk of distant metastasis in patients with rectal cancer, which may help physicians make clinical decisions. rectal cancer, distant metastasis, web calculator, machine learning algorithm, external validation.
PubMed: 37655097
DOI: 10.3389/fonc.2023.1235121 -
Oncology Letters May 2023The present study aimed to investigate the factors affecting the cardiac uptake of 18F-fluorodeoxyglucose (18F-FDG) during 18F-FDG positron emission tomography (PET) for...
The present study aimed to investigate the factors affecting the cardiac uptake of 18F-fluorodeoxyglucose (18F-FDG) during 18F-FDG positron emission tomography (PET) for new-onset rectal cancer and new-onset colon cancer (ascending, transverse, descending, sigmoid colon cancer) and to examine the association between the cardiac uptake of 18F-FDG and prognosis. The participants were diagnosed with new-onset rectal cancer and new-onset colon cancer (ascending, transverse, descending, sigmoid cancer) at the Iga City General Hospital (Iga, Japan) between January 1, 2013, and March 31, 2018, and underwent an 18F-FDG PET scan for pretreatment staging. The relationship between cardiac maximum standard uptake value (SUVmax), the presence/absence of distant metastasis and prognosis was examined. A total of 26 patients (14 men and 12 women) aged 72.0±10 years with new-onset rectal cancer were selected for the study. No patients had multiple simultaneous cancers. The median cardiac SUVmax was 3.8 and 2.5 in patients with no distant metastasis and distant metastasis, respectively, revealing a statistically significant difference (P<0.01). The median tumor volume on PET-computed tomography (CT) images was 7,815 cm and was 66,248 cm in patients with no distant metastasis and distant metastasis, respectively, revealing a statistically significant difference (P<0.01). Echocardiography findings revealed no significant difference between patients with and without distant metastasis. The correlation coefficient between cardiac SUVmax and total tumor volume on PET/CT images (primary + lymph + distant metastases) was statistically significant (r=-0.42, P=0.03). Analysis of the association between the occurrence of distance metastasis and cardiac SUVmax as a continuous variable gave a statistically significant result [hazard ratio (HR): 0.30, 95% confidence interval (CI): 0.09-0.98, P=0.045]. Receiver operating characteristic analysis showed a cardiac SUVmax of 2.6 with an area under the curve of 0.86 for determining the presence of distant metastasis (95% CI: 0.70-1.00). The median observation time was 56 months, and nine patients died during observation. Analysis of the association between the overall survival and cardiac SUVmax (cutoff: 2.6) showed 95% CI: 0.01-0.45 and HR: 0.06 (P<0.01); that between the overall survival and total tumor volume on PET images showed 95% CI: 1.00-1.00 and HR: 1.00 (P<0.01); and that between the overall survival and presence of distant metastasis showed 95% CI: 1.72-116.4 and HR: 14.1 (P<0.01). Furthermore, 25 patients (16 men and nine women) aged 71.4±14.2 years with new-onset colon cancer were selected for the study. Analysis of new-onset colon cancer revealed no statistically significance between the cardiac SUVmax and distant metastasis.
PubMed: 37113403
DOI: 10.3892/ol.2023.13783 -
Frontiers in Oncology 2022Breast cancer with distant metastases is a systemic disease. While systemic therapies are the main treatment strategy, locoregional therapy for metastatic breast cancer... (Review)
Review
Breast cancer with distant metastases is a systemic disease. While systemic therapies are the main treatment strategy, locoregional therapy for metastatic breast cancer (MBC) is generally palliative only. However, recent progress in systemic and local therapies has improved the prognosis of patients with MBC and some may expect long-term survival. More vigorous local therapies for MBC may, therefore, be clinically justified in selected patients. A number of clinical trials and studies have investigated the clinical significance of surgical therapy for primary tumors and distant metastases in patients with MBC. Four prospective randomized trials and multiple retrospective studies have investigated the benefit of surgical resection of primary lesions in patients with MBC, with conflicting results. There have been a number of case-control studies examining the impact of surgical resection of distant metastases, but the benefit of this approach in terms of survival is controversial because selection bias is unavoidable in retrospective studies. The present review discusses the state of the literature relating to local management of the primary breast cancer through surgical resection and surgical management of distant metastatic lesions including pulmonary and liver metastases with future perspectives.
PubMed: 35600412
DOI: 10.3389/fonc.2022.910544