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RoFo : Fortschritte Auf Dem Gebiete Der... Apr 2023Hematogenous osteomyelitis has increased over the past quarter century in frequency, virulence, and degree of soft-tissue involvement, bringing about changes in clinical... (Review)
Review
BACKGROUND
Hematogenous osteomyelitis has increased over the past quarter century in frequency, virulence, and degree of soft-tissue involvement, bringing about changes in clinical manifestations and management of the disease especially in children that should be reflected in the current imaging approach. Likewise, the global disease burden of diabetes has increased greatly in the same period, compounding the problem of ascertaining osteomyelitis in diabetic foot.
METHOD
This article provides an updated overview of imaging findings in hematogenous and contiguous osteomyelitis based on the literature and our institutional experience, along with salient features of recent recommendations from expert groups on the diagnostic algorithms and reporting terminology.
RESULTS AND CONCLUSION
Findings on radiography and especially magnetic resonance imaging (MRI) closely reflect pathophysiology in osteomyelitis, whereby the characteristic involvement of the metaphysis or metaphyseal-equivalents, the formation and subperiosteal extension of intramedullary pus collection, and the development of cloaca, sequestrum, and involucrum are all diagnostic clues. Non-enhancing foci within the medullary bone, the penumbra sign, intra- or extramedullary fat globules, and surrounding soft tissue inflammation or abscesses are among key MRI findings. Diabetic foot is a special condition with characteristic pathophysiologic and imaging features that suggest the likelihood of osteomyelitis and the main differential diagnostic consideration of acute on chronic neuropathic osteoarthropathy with or without osteomyelitis.
KEY POINTS
· Imaging closely reflects pathophysiology in hematogenous osteomyelitis.. · Acute hematogenous osteomyelitis predominantly involves metaphyses and metaphyseal equivalent sites.. · MRI clues for hematogenous osteomyelitis include central marrow non-enhancement, intra- or extramedullary fat globules, and the "penumbra" sign.. · An increased fluid-sensitive MRI bone signal abutting a soft tissue ulcer, abscess, or sinus tract suggests a high probability of contact osteomyelitis..
CITATION FORMAT
· Aydingoz U, Imaging Osteomyelitis: An Update. Fortschr Röntgenstr 2023; 195: 297 - 308.
Topics: Child; Humans; Diabetic Foot; Osteomyelitis; Bone Marrow; Magnetic Resonance Imaging; Radiography
PubMed: 36724804
DOI: 10.1055/a-1949-7641 -
Gut Apr 2023Haematogenous dissemination is a prevalent route of colorectal cancer (CRC) metastasis. However, as the gatekeeper of vessels, the role of tumour pericytes (TPCs) in...
OBJECTIVE
Haematogenous dissemination is a prevalent route of colorectal cancer (CRC) metastasis. However, as the gatekeeper of vessels, the role of tumour pericytes (TPCs) in haematogenous metastasis remains largely unknown. Here, we aimed to investigate the heterogeneity of TPCs and their effects on CRC metastasis.
DESIGN
TPCs were isolated from patients with CRC with or without liver metastases and analysed by single-cell RNA sequencing (scRNA-seq). Clinical CRC specimens were collected to analyse the association between the molecular profiling of TPCs and CRC metastasis. RNA-sequencing, chromatin immunoprecipitation-sequencing and bisulfite-sequencing were performed to investigate the TCF21-regulated genes and mechanisms underlying integrin α5 on DNA hypermethylation. Pericyte-conditional -knockout mice were constructed to investigate the effects of TCF21 in TPCs on CRC metastasis. Masson staining, atomic force microscopy, second-harmonic generation and two-photon fluorescence microscopy were employed to observe perivascular extracellular matrix (ECM) remodelling.
RESULTS
Thirteen TPC subpopulations were identified by scRNA-seq. A novel subset of TCF21 TPCs, termed 'matrix-pericytes', was associated with liver metastasis in patients with CRC. TCF21 in TPCs increased perivascular ECM stiffness, collagen rearrangement and basement membrane degradation, establishing a perivascular metastatic microenvironment to instigate colorectal cancer liver metastasis (CRCLM). depletion in TPCs mitigated perivascular ECM remodelling and CRCLM, whereas the coinjection of TCF21 TPCs and CRC cells markedly promoted CRCLM. Mechanistically, loss of integrin α5 inhibited the FAK/PI3K/AKT/DNMT1 axis to impair DNA hypermethylation in TCF21 TPCs.
CONCLUSION
This study uncovers a previously unidentified role of TPCs in haematogenous metastasis and provides a potential diagnostic marker and therapeutic target for CRC metastasis.
Topics: Animals; Mice; Cell Line, Tumor; Colorectal Neoplasms; DNA; Gene Expression Regulation, Neoplastic; Integrin alpha5; Liver Neoplasms; Neoplasm Metastasis; Pericytes; Phosphatidylinositol 3-Kinases; Tumor Microenvironment
PubMed: 36805487
DOI: 10.1136/gutjnl-2022-327913 -
Nature Communications Jul 2021Little is known about the transcriptomic plasticity and adaptive mechanisms of circulating tumor cells (CTCs) during hematogeneous dissemination. Here we interrogate the...
Little is known about the transcriptomic plasticity and adaptive mechanisms of circulating tumor cells (CTCs) during hematogeneous dissemination. Here we interrogate the transcriptome of 113 single CTCs from 4 different vascular sites, including hepatic vein (HV), peripheral artery (PA), peripheral vein (PV) and portal vein (PoV) using single-cell full-length RNA sequencing in hepatocellular carcinoma (HCC) patients. We reveal that the transcriptional dynamics of CTCs were associated with stress response, cell cycle and immune-evasion signaling during hematogeneous transportation. Besides, we identify chemokine CCL5 as an important mediator for CTC immune evasion. Mechanistically, overexpression of CCL5 in CTCs is transcriptionally regulated by p38-MAX signaling, which recruites regulatory T cells (Tregs) to facilitate immune escape and metastatic seeding of CTCs. Collectively, our results reveal a previously unappreciated spatial heterogeneity and an immune-escape mechanism of CTC, which may aid in designing new anti-metastasis therapeutic strategies in HCC.
Topics: Aged; Animals; Biomarkers, Tumor; Carcinoma, Hepatocellular; Cell Cycle; Cell Line, Tumor; Chemokine CCL5; Gene Expression Regulation, Neoplastic; Genetic Heterogeneity; Humans; Immune Evasion; Liver Neoplasms; Male; Mice; Mice, Inbred C57BL; Middle Aged; Neoplasm Metastasis; Neoplastic Cells, Circulating; Prognosis; RNA-Seq; Transcriptome; Tumor Microenvironment
PubMed: 34215748
DOI: 10.1038/s41467-021-24386-0 -
Nature Communications Feb 2023It is critical to understand factors associated with nasopharyngeal carcinoma (NPC) metastasis. To track the evolutionary route of metastasis, here we perform an...
It is critical to understand factors associated with nasopharyngeal carcinoma (NPC) metastasis. To track the evolutionary route of metastasis, here we perform an integrative genomic analysis of 163 matched blood and primary, regional lymph node metastasis and distant metastasis tumour samples, combined with single-cell RNA-seq on 11 samples from two patients. The mutation burden, gene mutation frequency, mutation signature, and copy number frequency are similar between metastatic tumours and primary and regional lymph node tumours. There are two distinct evolutionary routes of metastasis, including metastases evolved from regional lymph nodes (lymphatic route, 61.5%, 8/13) and from primary tumours (hematogenous route, 38.5%, 5/13). The hematogenous route is characterised by higher IFN-γ response gene expression and a higher fraction of exhausted CD8 T cells. Based on a radiomics model, we find that the hematogenous group has significantly better progression-free survival and PD-1 immunotherapy response, while the lymphatic group has a better response to locoregional radiotherapy.
Topics: Humans; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Clinical Relevance; CD8-Positive T-Lymphocytes; Lymphatic Metastasis; Carcinoma; Lymph Nodes
PubMed: 36739462
DOI: 10.1038/s41467-023-35995-2 -
Journal of Oncology 2019Metastasis is the major cause of death in patients with colorectal carcinoma (CRC). The most common sites of metastasis are the liver and the peritoneum. Peritoneal... (Review)
Review
Metastasis is the major cause of death in patients with colorectal carcinoma (CRC). The most common sites of metastasis are the liver and the peritoneum. Peritoneal carcinomatosis is often considered the end stage of the disease after the tumor has spread to the liver. However, almost half of CRC patients with peritoneal carcinomatosis do not present with liver metastasis. This brings up the question of whether peritoneal spread can still be considered as the end stage of a metastasized CRC or whether it should just be interpreted as a site of metastasis alternative to the liver. This review tries to discuss this question and summarize the current status of literature on potential characteristics in tumor biology in the primary tumor, i.e., factors (transcription factors and direct and indirect E-cadherin repressors) and pathways (WNT, TGF-, and RAS) modulating EMT, regulation of EMT on a posttranscriptional and posttranslational level (miRNAs), and angiogenesis. In addition to tumor-specific characteristics, factors in the tumor microenvironment, immunological markers, ways of transport of tumor cells, and adhesion molecules appear to differ between hematogenous and peritoneal spread. Factors such as integrins and exosomal integrins, cancer stem cell phenotype, and miRNA expression appear to contribute in determining the metastatic route. We went through each step of the metastasis process comparing hematogenous to peritoneal spread. We identified differences with respect to organotropism, epithelial-mesenchymal transition, angiogenesis and inflammation, and tumor microenvironment which will be further elucidated in this review. A better understanding of the underlying mechanisms and contributing factors of metastasis development in CRC has huge relevance as it is the foundation to help find specific targets for treatment of CRC.
PubMed: 31641356
DOI: 10.1155/2019/7407190 -
Acta Otorhinolaryngologica Italica :... Jun 2021
Review
Topics: Carcinoma, Adenoid Cystic; Humans; Salivary Gland Neoplasms
PubMed: 34264913
DOI: 10.14639/0392-100X-N1379 -
Frontiers in Oncology 2020Tumor-associated macrophages (TAMs) are major innate immune cells that constitute up to 50% of the cell mass of human tumors. TAMs are highly heterogeneous cells that... (Review)
Review
Tumor-associated macrophages (TAMs) are major innate immune cells that constitute up to 50% of the cell mass of human tumors. TAMs are highly heterogeneous cells that originate from resident tissue-specific macrophages and from newly recruited monocytes. TAMs' variability strongly depends on cancer type, stage, and intratumor heterogeneity. Majority of TAMs are programmed by tumor microenvironment to support primary tumor growth and metastatic spread. However, TAMs can also restrict tumor growth and metastasis. In this review, we summarized the knowledge about the role of TAMs in tumor growth, metastasis and in the response to cancer therapy in patients with five aggressive types of cancer: breast, colorectal, lung, ovarian, and prostate cancers that are frequently metastasize into distant organs resulting in high mortality of the patients. Two major TAM parameters are applied for the evaluation of TAM correlation with the cancer progression: total amount of TAMs and specific phenotype of TAMs identified by functional biomarkers. We summarized the data generated in the wide range of international patient cohorts on the correlation of TAMs with clinical and pathological parameters of tumor progression including lymphatic and hematogenous metastasis, recurrence, survival, therapy efficiency. We described currently available biomarkers for TAMs that can be measured in patients' samples (tumor tissue and blood). CD68 is the major biomarker for the quantification of total TAM amounts, while transmembrane receptors (stabilin-1, CD163, CD206, CD204, MARCO) and secreted chitinase-like proteins (YKL-39, YKL-40) are used as biomarkers for the functional TAM polarization. We also considered that specific role of TAMs in tumor progression can depend on the localization in the intratumoral compartments. We have made the conclusion for the role of TAMs in primary tumor growth, metastasis, and therapy sensitivity for breast, colorectal, lung, ovarian, and prostate cancers. In contrast to other cancer types, majority of clinical studies indicate that TAMs in colorectal cancer have protective role for the patient and interfere with primary tumor growth and metastasis. The accumulated data are essential for using TAMs as biomarkers and therapeutic targets to develop cancer-specific immunotherapy and to design efficient combinations of traditional therapy and new immunomodulatory approaches.
PubMed: 33194645
DOI: 10.3389/fonc.2020.566511