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Journal of Cellular and Molecular... Aug 2023Hepatocellular carcinoma (HCC) is one of the most common and aggressive human malignancies worldwide. Portal vein tumour thrombus (PVTT) is considered one of most... (Review)
Review
Hepatocellular carcinoma (HCC) is one of the most common and aggressive human malignancies worldwide. Portal vein tumour thrombus (PVTT) is considered one of most fearful complications of HCC and is strongly associated with a poor prognosis. Clarification of the mechanisms underlying the formation and development of PVTT is crucial for developing novel therapeutic strategies for HCC patients. Several studies have been made to uncover that tumour microenvironment, stem cells, abnormal gene expression and non-coding RNAs deregulation are associated with PVTT in patients with HCC in the last decade. However, the exact molecular mechanisms of PVTT in patients with HCC are still largely unknown. In the present review, we briefly summarized the molecular mechanisms underlying the formation and development of PVTT in HCC.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Portal Vein; Thrombosis; Chemoembolization, Therapeutic; Retrospective Studies; Treatment Outcome; Tumor Microenvironment
PubMed: 37349905
DOI: 10.1111/jcmm.17808 -
Radiologic Clinics of North America May 2024The visceral vasculature is inextricably intertwined with abdominopelvic disease staging, spread, and management in routine and emergent cases. Comprehensive evaluation... (Review)
Review
The visceral vasculature is inextricably intertwined with abdominopelvic disease staging, spread, and management in routine and emergent cases. Comprehensive evaluation requires specialized imaging techniques for abnormality detection and characterization. Vascular pathology is often encountered on nondedicated routine imaging examinations, which may obscure, mimic, or confound many vascular diagnoses. This review highlights normal arterial, portal venous, and systemic venous anatomy and clinically relevant variants; diagnostic pitfalls related to image-acquisition technique and disease mimics; and characteristics of common and rare vascular diseases to empower radiologists to confidently interpret the vascular findings and avoid misdiagnosis.
Topics: Humans; Portal Vein; Diagnostic Imaging; Diagnostic Errors
PubMed: 38553185
DOI: 10.1016/j.rcl.2023.12.003 -
Hamostaseologie Aug 2023
Topics: Humans; Factor VIII; Portal Vein; Venous Thrombosis
PubMed: 37611604
DOI: 10.1055/s-0043-1774284 -
Hepatology International Oct 2023Baveno VII workshop recommends management of acute variceal bleeding (AVB) in cirrhotic patients with nonmalignant portal vein thrombosis (PVT) should be performed... (Observational Study)
Observational Study
BACKGROUND AND AIM
Baveno VII workshop recommends management of acute variceal bleeding (AVB) in cirrhotic patients with nonmalignant portal vein thrombosis (PVT) should be performed according to the guidelines for patients without PVT. Nevertheless, whether PVT affects the outcome of patients with cirrhosis and AVB remains unclear. The aim of this study was to assess the clinical impact of PVT on the outcomes in the pre-emptive TIPSS eligible patients with cirrhosis and AVB.
METHODS
From December 2010 to June 2016, 1219 consecutive cirrhotic patients admitted due to AVB with (n = 151; 12.4%) or without PVT (n = 1068; 87.6%), who received drug plus endoscopic treatment (a combination of vasoactive drugs, antibiotics, and endoscopic ligation for AVB, followed by beta-blockers plus variceal ligation for prevention of rebleeding) were retrospectively included. Fine and Gray competing risk regression models were taken to evaluate the impact of PVT on clinical outcomes after adjusting for potential confounders.
RESULTS
During follow-up, 211 patients (17.3%) died, 490 (40.2%) experienced further bleeding, and 78 (6.4%) experienced new or worsening ascites within 1 year. Compared with those without PVT, patients with PVT had a similar risk of mortality (PVT vs no-PVT: 19.9% vs 16.7% at 1 year; adjusted HR 0.88, 95%CI 0.51-1.52, p = 0.653), further bleeding (47.0% vs 39.2% at 1 year, adjusted HR 1.19, 95% CI 0.92-1.53, p = 183), and new or worsening ascites (7.9% vs 9.6%, adjusted HR 0.70, 95% CI 0.39-1.28, p = 0.253) after adjusting for confounders in multivariable models. These findings were consistent across different relevant subgroups and confirmed by propensity score matching analysis.
CONCLUSIONS
Our study showed no evidence that the PVT was associated with an improved or worsened outcome among cirrhotic patients with AVB who received standard treatment.
Topics: Humans; Esophageal and Gastric Varices; Portal Vein; Retrospective Studies; Ascites; Gastrointestinal Hemorrhage; Liver Cirrhosis; Fibrosis; Portasystemic Shunt, Transjugular Intrahepatic; Venous Thrombosis; Treatment Outcome
PubMed: 37258989
DOI: 10.1007/s12072-023-10493-1 -
Theranostics 2023: Hepatocellular carcinoma (HCC) is primarily characterized by a high incidence of vascular invasion. However, the specific mechanism underlying portal vein tumor...
: Hepatocellular carcinoma (HCC) is primarily characterized by a high incidence of vascular invasion. However, the specific mechanism underlying portal vein tumor thrombus (PVTT) in HCC remains unclear. As a consequence of myeloid cell developmental arrest, CD71 erythroid progenitor cells (EPCs) and myeloid-derived suppressor cells play important roles in HCC; however, their roles in PVTT remain unclear. The role of CD71 EPCs in the HCC tumor microenvironment (TME) was evaluated via morphological, RNA-sequencing, enzyme-linked immunosorbent assay, and flow cytometric analyses. Co-culture techniques were employed to assess the CD45 EPCs and their vascular compromising effect. Additionally, the PVTT-promoting function of CD45 EPCs was explored in a murine model. The CD45EPCs in HCC tissues exhibited increased myeloid cell features, including morphology, surface markers, transforming growth factor (TGF)-β generation, and gene expression, compared with those in circulation. Hence, a large proportion of CD45EPCs, particularly those in TMEs, comprise erythroid-transdifferentiated myeloid cells (EDMCs). Additionally, the expression of C-C chemokine receptor type 2 (CCR2) mRNA was upregulated in CD45EPCs within the TME. Tumor macrophages from HCC tissues induced substantial migration of CD45EPCs in a dose-dependent manner. Meanwhile, results from immunofluorescence analyses revealed that these two cell types are positively associated in the TME and circulation. That is, EDMCs are chemoattracted by HCC macrophages mainly via CCR2 from CD45 EPCs in the circulation. Additionally, the expressions of FX, FVII, FGB, C4b, CFB, and CFH were elevated in CD45EPCs within the TME compared with those in the spleen. The CD45EPCs from the HCC TME promoted vessel endothelial cell migration and compromised tube formation through TGF-β and FGB, respectively. Additionally, CD45EPCs from the TME induced HCC cell migration. HCC macrophage-induced CD45EPCs to exhibit higher levels of FX, FVII, FGB, and TGF-β. Meanwhile, upregulation of CCAAT/enhancer binding protein beta expression induced FGB and TGF-β generation in CD45EPCs in the TME. WTAP, a major RNA mA writer, stabilized and mRNA and enhanced their nuclear export in CD45EPCs from the TME. CD45EPCs from the TME were positively associated with PVTT and poor prognosis. Splenectomy reduced the level of CD45EPCs in the circulation and TME, as well as the incidence of microvascular invasion. The incidence of microvascular invasion increased following the transfer of HCC tissue CD45EPCs to splenectomized HCC-bearing mice. The CD45EPCs enriched in the HCC microenvironment are EDMCs, which are induced by HCC macrophages to migrate from the circulation to the TME. Subsequently, EDMCs promote PVTT by compromising the blood vessel endothelium, aggravating coagulation, and promoting HCC cell migration.
Topics: Animals; Mice; Carcinoma, Hepatocellular; Portal Vein; Liver Neoplasms; Myeloid Cells; Thrombosis; Tumor Microenvironment
PubMed: 37649603
DOI: 10.7150/thno.82907 -
The Lancet. Gastroenterology &... Nov 2023Ectopic variceal bleeding is a rare cause of gastrointestinal bleeding that can occur in settings of cirrhotic and non-cirrhotic portal hypertension and is characterised... (Review)
Review
Ectopic variceal bleeding is a rare cause of gastrointestinal bleeding that can occur in settings of cirrhotic and non-cirrhotic portal hypertension and is characterised by its development at locations remote from the oesophagus and stomach. Ectopic varices can be difficult to identify and access, and, although a relatively uncommon cause of portal hypertensive bleeding, can represent a difficult diagnostic and therapeutic challenge associated with considerable mortality. Low incidence and variance in variceal anatomy preclude large randomised controlled trials, and clinical practice is based on experience from case reports, case series, and specialist centre expertise. Optimisation of survival outcomes relies on understanding a patient's portal venous anatomy and functional hepatic reserve to guide timely and targeted endoscopic and endovascular interventions to facilitate the rapid control of ectopic variceal bleeding.
Topics: Humans; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Hypertension, Portal; Varicose Veins; Portal Vein
PubMed: 37683687
DOI: 10.1016/S2468-1253(23)00209-1 -
Liver International : Official Journal... Sep 2023PIEZO1 and TRPV4 are mechanically and osmotically regulated calcium-permeable channels. The aim of this study was to determine the relevance and relationship of these...
BACKGROUND & AIMS
PIEZO1 and TRPV4 are mechanically and osmotically regulated calcium-permeable channels. The aim of this study was to determine the relevance and relationship of these channels in the contractile tone of the hepatic portal vein, which experiences mechanical and osmotic variations as it delivers blood to the liver from the intestines, gallbladder, pancreas and spleen.
METHODS
Wall tension was measured in freshly dissected portal veins from adult male mice, which were genetically unmodified or modified for either a non-disruptive tag in native PIEZO1 or endothelial-specific PIEZO1 deletion. Pharmacological agents were used to activate or inhibit PIEZO1, TRPV4 and associated pathways, including Yoda1 and Yoda2 for PIEZO1 and GSK1016790A for TRPV4 agonism, respectively.
RESULTS
PIEZO1 activation leads to nitric oxide synthase- and endothelium-dependent relaxation of the portal vein. TRPV4 activation causes contraction, which is also endothelium-dependent but independent of nitric oxide synthase. The TRPV4-mediated contraction is suppressed by inhibitors of phospholipase A and cyclooxygenases and mimicked by prostaglandin E , suggesting mediation by arachidonic acid metabolism. TRPV4 antagonism inhibits the effect of agonising TRPV4 but not PIEZO1. Increased wall stretch and hypo-osmolality inhibit TRPV4 responses while lacking effects on or amplifying PIEZO1 responses.
CONCLUSIONS
The portal vein contains independently functioning PIEZO1 channels and TRPV4 channels in the endothelium, the pharmacological activation of which leads to opposing effects of vessel relaxation (PIEZO1) and contraction (TRPV4). In mechanical and osmotic strain, the PIEZO1 mechanism dominates. Modulators of these channels could present important new opportunities for manipulating liver perfusion and regeneration in disease and surgical procedures.
Topics: Animals; Male; Mice; Endothelium; Nitric Oxide; Nitric Oxide Synthase; Osmotic Pressure; Portal Vein; TRPV Cation Channels; Vasodilation; Ion Channels
PubMed: 37349903
DOI: 10.1111/liv.15646 -
Medicina Clinica May 2024The term portosinusoidal vascular disorder (PSVD) refers to a clinical-pathological entity that encompasses those patients with intrahepatic vascular damage without... (Review)
Review
The term portosinusoidal vascular disorder (PSVD) refers to a clinical-pathological entity that encompasses those patients with intrahepatic vascular damage without cirrhosis at risk of developing severe complications of portal hypertension. Numerous systemic diseases, genetic disorders, and toxic agents have been associated with this pathology, making its diagnosis an important clinical challenge. The recent description of uniform diagnostic criteria and a better understanding of its pathophysiology will allow for better identification of patients, even in early stages of the disease. Although there is currently no effective etiological treatment available, early diagnosis allows for the development of preventive strategies for some severe complications of portal hypertension.
Topics: Humans; Hypertension, Portal; Portal Vein; Vascular Diseases
PubMed: 38302397
DOI: 10.1016/j.medcli.2023.11.018 -
BMJ Open Jul 2023Portal vein obstruction (PVO) consists of anastomotic stenosis and thrombosis, which occurs due to a progression of the former. The aim of this large-scale international...
Prevalence, management and efficacy of treatment in portal vein obstruction after paediatric liver transplantation: protocol of the retrospective international multicentre PORTAL registry.
INTRODUCTION
Portal vein obstruction (PVO) consists of anastomotic stenosis and thrombosis, which occurs due to a progression of the former. The aim of this large-scale international study is to assess the prevalence, current management practices and efficacy of treatment in patients with PVO.
METHODS AND ANALYSIS
The Portal vein Obstruction Revascularisation Therapy After Liver transplantation registry will facilitate an international, retrospective, multicentre, observational study, with 25 centres around the world already actively involved. Paediatric patients (aged <18 years) with a diagnosed PVO between 1 January 2001 and 1 January 2021 after liver transplantation will be eligible for inclusion. The primary endpoints are the prevalence of PVO, primary and secondary patency after PVO intervention and current management practices. Secondary endpoints are patient and graft survival, severe complications of PVO and technical success of revascularisation techniques.
ETHICS AND DISSEMINATION
Medical Ethics Review Board of the University Medical Center Groningen has approved the study (METc 2021/072). The results of this study will be disseminated via peer-reviewed publications and scientific presentations at national and international conferences.
TRIAL REGISTRATION NUMBER
Netherlands Trial Register (NL9261).
Topics: Humans; Child; Liver Transplantation; Portal Vein; Retrospective Studies; Prevalence; Liver Diseases; Vascular Diseases; Registries; Observational Studies as Topic; Multicenter Studies as Topic
PubMed: 37500271
DOI: 10.1136/bmjopen-2022-066343 -
Radiology Sep 2023Background Percutaneous transhepatic portal vein (PV) embolization (PVE) is a standard preoperative procedure for advanced biliary cancer when the future liver remnant...
Background Percutaneous transhepatic portal vein (PV) embolization (PVE) is a standard preoperative procedure for advanced biliary cancer when the future liver remnant (FLR) is insufficient, yet the effect of this procedure on portal hemodynamics is still unclear. Purpose To assess whether four-dimensional (4D) MRI flowmetry can be used to estimate FLR volume and to identify the optimal time for this measurement. Materials and Methods This prospective single-center study enrolled consecutive adult patients with biliary cancer who underwent percutaneous transhepatic PVE for the right liver between June 2020 and November 2022. Portal hemodynamics were assessed using 4D flow MRI before PVE and within 1 day (0-day group) or 3-4 days (3-day group) after PVE. FLR volume was measured using CT before PVE and after PVE but before surgery. Blood flow changes were analyzed with the Wilcoxon signed rank test, and correlations with Spearman rank correlation. Results The 0-day group included 24 participants (median age, 72 years [IQR, 69-77 years]; 17 male participants), and the 3-day group included 13 participants (median age, 71 years [IQR, 68-78 years]; eight male participants). Both groups showed increased left PV (LPV) flow rate after PVE (0-day group: from median 3.72 mL/sec [IQR, 2.83-4.55 mL/sec] to 9.48 mL/sec [IQR, 8.12-10.7 mL/sec], < .001; 3-day group: from median 3.65 mL/sec [IQR, 2.14-3.79 mL/sec] to 8.16 mL/sec [IQR, 6.82-8.98 mL/sec], < .001). LPV flow change correlated with FLR volume change relative to the number of days from PVE to presurgery CT only in the 3-day group (ρ = 0.62, = .02; 0-day group, = .11). The output of the regression equation for estimating presurgery FLR volume correlated with CT-measured volume (ρ = 0.78; = .002). Conclusion Four-dimensional flow MRI demonstrated increased blood flow in residual portal branches 3-4 days after PVE, offering insights for estimating presurgery FLR volume. Published under a CC BY 4.0 license. See also the editorial by Roldán-Alzate and Oechtering in this issue.
Topics: Adult; Humans; Male; Aged; Portal Vein; Liver Neoplasms; Prospective Studies; Retrospective Studies; Liver; Embolization, Therapeutic; Biliary Tract Neoplasms; Magnetic Resonance Imaging; Hemodynamics; Hepatectomy; Treatment Outcome
PubMed: 37750777
DOI: 10.1148/radiol.230709