Contemporary Minimally Invasive Surgery for TASC-D Aorto-Iliac Lesions: Analysis of Outcomes and Risk Factors for Primary and Secondary Patency.

BACKGROUND: For complex extensive TASC-II D lesions, the standard of care remains conventional surgery. Nevertheless, guidelines tend to broaden endovascular surgery indications in expert centers for patients at high surgical risk with TASC-II D lesions. Due to the increasing use of endovascular surgery in this setting, we planned to evaluate the patency rate of this approach. METHODS: We conducted a retrospective study in a tertiary center. All patients treated for symptomatic peripheral arterial disease (PAD) with classified D lesions according to the TASC-II classification and requiring management of the aortoiliac bifurcation were retrospectively included between January 1, 2007 and December 31, 2017. The type of surgical approach was classified as a pure percutaneous approach or hybrid surgery. The main objective was to describe long-term patency results. The secondary objectives were to identify risk factors for loss of patency and long-term complications. The primary outcomes were primary patency, primary-assisted patency, and secondary patency at 5 years of follow-up. RESULTS: One hundred and thirty-six patients were included. For the overall population, the primary, primary-assisted, and secondary patency proportions at 5 years were 71.6% (95% confidence interval (CI) 63.2-81%), 82.1% (95% CI 74.9-89.3%), 96.3% (95% CI 92-100%), respectively. For primary patency, there was a significant difference in favor of the covered stent group at 36 months (P < 0.01) and 60 months (P = 0.037). In a multivariate model, only CS and age were associated with a better primary patency (hazard ratio (HR) 0.36, CI 95% [0.15-0.83], P = 0.0193 and an HR 0.07, 95% CI [0.05-0.09], P = 0.005, respectively). The overall rate of perioperative complications was 11%. CONCLUSIONS: We report that endovascular and hybrid surgery are safe and effective in the management of TASC-D complex aortoiliac lesions in mid to long-term follow-up. Short-term and long-term complications were all considered as minor.

A pan-cancer analysis of the human tumor coagulome and its link to the tumor immune microenvironment.

OBJECTIVE: Solid tumors often establish a procoagulable state that can lead to venous thromboembolism (VTE). Although some of the key genes involved in this process are known, no previous study has compared the "coagulome", i.e., the expression of coagulation/fibrinolysis genes, across different primary tumor types. It is also unclear whether the coagulome is associated with specific characteristics of the tumor microenvironment (TME). We aimed to address this question. METHODS: We analyzed the expression of the genes F3, PLAU, PLAT, PLAUR, SERPINB2, and SERPINE1 in 32 cancer types using data from The Cancer Genome Atlas (TCGA) and other freely available resources. RESULTS: We identified specific expression patterns of procoagulant and fibrinolytic genes. The expression of the Tissue Factor (F3) was found to be tumor type dependent, with the highest expression in glioblastoma (GBM), a highly procoagulable tumor type. Conversely, high expression of the fibrinolysis gene cluster PLAU, PLAUR, SERPINE1 was consistently linked to the characteristics of the TME (monocytic infiltration) and high expression of important checkpoints of the immune response, such as PD-L2 and CD276/B7-H3. CONCLUSION: These tumor-specific patterns of expression might partially explain the differences in VTE risk among tumor types. We propose that biomarkers of coagulation fibrinolysis might provide valuable information about the TME in cancer patients.

In vivo efficacy of endothelial growth medium stimulated mesenchymal stem cells derived from patients with critical limb ischemia.

BACKGROUND: Cell therapy has been proposed for patients with critical limb ischemia (CLI). Autologous bone marrow derived cells (BMCs) have been mostly used, mesenchymal stem cells (MSCs) being an alternative. The aim of this study was to characterize two types of MSCs and evaluate their efficacy. METHODS: MSCs were obtained from CLI-patients BMCs. Stimulated- (S-) MSCs were cultured in endothelial growth medium. Cells were characterized by the expression of cell surface markers, the relative expression of 6 genes, the secretion of 10 cytokines and the ability to form vessel-like structures. The cell proangiogenic properties was analysed in vivo, in a hindlimb ischemia model. Perfusion of lower limbs and functional tests were assessed for 28 days after cell infusion. Muscle histological analysis (neoangiogenesis, arteriogenesis and muscle repair) was performed. RESULTS: S-MSCs can be obtained from CLI-patients BMCs. They do not express endothelial specific markers but can be distinguished from MSCs by their secretome. S-MSCs have the ability to form tube-like structures and, in vivo, to induce blood flow recovery. No amputation was observed in S-MSCs treated mice. Functional tests showed improvement in treated groups with a superiority of MSCs and S-MSCs. In muscles, CD31+ and αSMA+ labelling were the highest in S-MSCs treated mice. S-MSCs induced the highest muscle repair. CONCLUSIONS: S-MSCs exert angiogenic potential probably mediated by a paracrine mechanism. Their administration is associated with flow recovery, limb salvage and muscle repair. The secretome from S-MSCs or secretome-derived products may have a strong potential in vessel regeneration and muscle repair. Trial registration NCT00533104.

Cell therapy in critical limb ischemia: A comprehensive analysis of two cell therapy products.

BACKGROUND: Cell therapy has been proposed as a salvage limb procedure in critical limb ischemia (CLI). In spite of the fact that clinical trials found some efficacy, the mechanism of action remains elusive. The objective of this study was to characterize two autologous cell therapy products (CTPs) obtained from patients with advanced peripheral arterial disease. METHODS: Bone marrow (BM-CTPs) (n = 20) and CTPs obtained by non-mobilized cytapheresis (peripheral blood [PB]-CTPs) (n = 20) were compared. CTPs were characterized by their cell composition, by the quantification of endothelial progenitor cells (EPCs) and mesenchymal stromal cells (MSCs) and by transcriptomic profiling. The angiogenic profile and the 6-month outcome of CLI patients are described. RESULTS: Patients presented inflammation syndrome and high levels of CXCL12, soluble stem cell factor and granulocyte colony-stimulating factor, whereas granulocyte macrophage colony-stimulating factor was low. Circulating CD34+ cells represented rare events. BM and PB-CTPs were heterogeneous. Mature cells and colony-forming unit-endothelial cells were in higher concentration in PB-CTPs, whereas CD34+ stem cells and EPCs were more abundant in BM-CTPs. MSCs were identified in both CTPs. Transcriptomic profiling revealed the strong angiogenic potential of BM-CTPs. Transcutaneous partial pressure of oxygen, C-reative protein and neutrophil content in CTPs are predictive of the clinical outcome at 6 months. DISCUSSION: Transcriptomic allows an accurate characterization of CTPs. BM-CTPs have the richest content in terms of stem cells and transcriptome. The high content of mature cells in PB-CTPs means that they work via a paracrine mechanism. The clinical outcome indicates the deleterious influence the patients' status and the limits of an autologous approach. In this respect, MSCs may allow an allogenic strategy.

Autologous Bone Marrow Mononuclear Cell Implantation and Its Impact on the Outcome of Patients With Critical Limb Ischemia　- Results of a Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Cell therapy is a therapeutic option for patients presenting with nonrevascularizable critical limb ischemia (CLI). However there is a lack of firm evidence on its efficacy because of the paucity of randomized controlled trials.Methods and Results:The BALI trial was a multicenter, randomized, controlled, double-blind clinical trial that included 38 patients. For all of them, 500 mL of bone marrow were collected for preparation of a BM-MNC product that was implanted in patients assigned to active treatment. For the placebo group, a placebo cell-free product was implanted. Within 6 months after inclusion, major amputations had to be performed in 5 of the 19 placebo-treated patients and in 3 of the 17 BM-MNC-treated patients. According to a classical logistic regression analysis there was no significant difference. However, when using the jackknife analysis, 6 months after inclusion BM-MNC implantation was associated with a lower risk of major amputation (odds ratio (OR): 0.55; 95% confidence interval (CI): 0.52-0.58; P<0.0001) and of occurrence of any event (major or minor amputation, or revascularization) (OR: 0.30; 95% CI: 0.29-0.31; P<0.0001). The secondary endpoints (i.e., pain, ulcers, TcPO2, and ankle-brachial index value) were not statistically different between groups. CONCLUSIONS: Our results suggested that cell therapy reduced the risk of major amputation in patients presenting with nonrevascularizable CLI.

Statement for Doppler waveforms analysis.

Peripheral artery disease of the lower limbs (PAD) is a common disease. Evaluation of PAD is primarily based on non-invasive examinations with analysis of the arterial Doppler signal being a key element. However, the description of arterial Doppler waveforms morphologies varies considerably across medical schools and from country to country. In order to overcome this issue, the French College of Teachers for Vascular Medicine (Collège des Enseignants de Médecine Vasculaire; CEMV) has summarised the published data on Doppler waveforms analysis and proposes a new "Saint-Bonnet" classification system to describe Doppler waveforms morphologies. The simplified Saint-Bonnet classification comprises eight types and allows taking into account if the Doppler signal does not revert to baseline. This classification, which is based on previous classifications, could improve the descriptions of both physiological and pathological waveforms, recorded in lower limb arteries. According to the reviewed literature, recommendations about the use of Doppler waveforms are proposed. This statement is a preamble to reach an international consensus on the subject, which would standardize the description of arterial waveforms and improve the management of PAD patients.

Critical limb ischemia: thrombogenic evaluation of two autologous cell therapy products and biologic profile in treated patients.

BACKGROUND: Cell therapy has been proposed as a salvage limb procedure in critical limb ischemia (CLI). Autologous cell therapy products (CTP) are obtained from patients with advanced peripheral arterial disease to be injected at the site of ischemia. Thrombogenicity of CTPs has not yet been assessed. The objectives were: 1) to assess thrombotic risk in candidates for cell therapy, 2) to evaluate two different CTPs in terms of thrombogenic potential, and 3) to evaluate clinical thrombotic events. STUDY DESIGN AND METHODS: In this ancillary study of a Phase I and II clinical trial, bone marrow (BM)-CTPs (n = 20) and CTPs obtained by cytapheresis (peripheral blood [PB]-CTPs; n = 20) were compared. Inflammatory and coagulation markers were measured at baseline and 24 hours after CTP implantation. CTP cell content and tissue factor (TF) expression (mRNA and protein) were analyzed. Thrombin generation assessed CTP-related thrombogenicity. RESULTS: All patients presented cardiovascular risk factors. At baseline, the patients' biologic profile was characterized by high levels of fibrinogen, C-reactive protein (CRP), D-dimer, interleukin (IL)-6, and plasmatic TF, whereas IL-10 was low. Although different in terms of cell composition, both BM- and PB-CTPs support low thrombin generation. Twenty-four hours after implantation, biologic markers remained stable in the PB-CTP group, except for IL-6. In the BM-CTP group, a significant increase of IL-6 but also of CRP and D-dimer was observed. Clinically, one single patient developed deep vein thrombosis 24 hours after the implantation of autologous PB-CTP. CONCLUSION: CTPs supported low thrombin generation and were well tolerated after calf implantation.

Effect of a retrievable inferior vena cava filter plus anticoagulation vs anticoagulation alone on risk of recurrent pulmonary embolism: a randomized clinical trial.

IMPORTANCE: Although retrievable inferior vena cava filters are frequently used in addition to anticoagulation in patients with acute venous thromboembolism, their benefit-risk ratio is unclear. OBJECTIVE: To evaluate the efficacy and safety of retrievable vena cava filters plus anticoagulation vs anticoagulation alone for preventing pulmonary embolism recurrence in patients presenting with acute pulmonary embolism and a high risk of recurrence. DESIGN, SETTING, AND PARTICIPANTS: Randomized, open-label, blinded end point trial (PREPIC2) with 6-month follow-up conducted from August 2006 to January 2013. Hospitalized patients with acute, symptomatic pulmonary embolism associated with lower-limb vein thrombosis and at least 1 criterion for severity were assigned to retrievable inferior vena cava filter implantation plus anticoagulation (filter group; n = 200) or anticoagulation alone with no filter implantation (control group; n = 199). Initial hospitalization with ambulatory follow-up occurred in 17 French centers. INTERVENTIONS: Full-dose anticoagulation for at least 6 months in all patients. Insertion of a retrievable inferior vena cava filter in patients randomized to the filter group. Filter retrieval was planned at 3 months from placement. MAIN OUTCOMES AND MEASURES: Primary efficacy outcome was symptomatic recurrent pulmonary embolism at 3 months. Secondary outcomes were recurrent pulmonary embolism at 6 months, symptomatic deep vein thrombosis, major bleeding, death at 3 and 6 months, and filter complications. RESULTS: In the filter group, the filter was successfully inserted in 193 patients and was retrieved as planned in 153 of the 164 patients in whom retrieval was attempted. By 3 months, recurrent pulmonary embolism had occurred in 6 patients (3.0%; all fatal) in the filter group and in 3 patients (1.5%; 2 fatal) in the control group (relative risk with filter, 2.00 [95% CI, 0.51-7.89]; P = .50). Results were similar at 6 months. No difference was observed between the 2 groups regarding the other outcomes. Filter thrombosis occurred in 3 patients. CONCLUSIONS AND RELEVANCE: Among hospitalized patients with severe acute pulmonary embolism, the use of a retrievable inferior vena cava filter plus anticoagulation compared with anticoagulation alone did not reduce the risk of symptomatic recurrent pulmonary embolism at 3 months. These findings do not support the use of this type of filter in patients who can be treated with anticoagulation. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00457158.

Pilot safety study of perivascular injection of tissue-engineered allogeneic aortic endothelial cells in patients undergoing minimally invasive peripheral revascularization.

OBJECTIVE: Restenosis is a limitation of endovascular interventions performed in the superficial femoral artery (SFA). Preclinical studies have demonstrated that the perivascular delivery of tissue-engineered allogeneic aortic endothelial cells (PVS-10200) reduced stenosis in porcine models of SFA revascularization. The purpose of this study was to investigate the safety and feasibility of percutaneous PVS-10200 delivery after angioplasty and stenting in the SFA of patients with peripheral artery disease. METHODS: In this phase I open-label trial, 21 patients (average lesion length of 10.10 ± 2.36 cm and ≥70% stenosis) were treated with PVS-10200: 11 in a low-dose cohort (cohort A) and 10 in a high-dose cohort (cohort B). The primary objective was to demonstrate the safety (incidence of major adverse events) of PVS-10200 within 4 weeks after surgery. Secondary end points included assessments of resting ankle-brachial index (ABI) in the treated leg, Fontaine class, and time to target lesion revascularization (TLR). RESULTS: No patient had a major adverse event within 4 weeks. One patient required a limb amputation at 30 weeks. At 48 weeks, cohort A and cohort B patients maintained a 37% and 62% increase in ABI compared with baseline, respectively; 70% of cohort A and 78% of cohort B improved by ≥1 Fontaine classification stage, and the TLR rate was 39% for cohort A and 20% for cohort B. CONCLUSIONS: Percutaneous local delivery of PVS-10200 is a well-tolerated and novel therapeutic approach that may be a suitable treatment for patients after endovascular intervention of the SFA. Larger randomized trials are needed to determine if PVS-10200 can improve ABI and reduce TLR rates.

Treatment of cancer-associated venous thromboembolism in patients under palliative care.

Many patients with cancer require palliative care at some stage and the vast majority of people followed in palliative care are cancer patients. Patients with cancer are at high risk of venous thromboembolism (VTE), and this is particularly true during the advanced palliative phase when mobility is limited or absent. Patients with cancer in palliative cancer are at higher bleeding risk compared to non-cancer patients. Decisions to treat VTE or withhold anticoagulation for these patients have proven to be difficult and depend largely on an individual clinician's judgment. For this reason, we have developed a consensus proposal for appropriate management of cancer-associated thromboembolism (CAT) in patients in palliative care, which is presented in this article. The proposal was informed by the recent scientific literature retrieved through a systematic literature review. In cancer patients in advanced palliative care, the benefit-risk ratio of anticoagulation seems unfavourable with a higher haemorrhagic risk than the benefit associated with prevention of CAT recurrence and, above all, in the absence of any benefit on quality of life. For this reason, we recommend that patients should be prescribed anticoagulants on a case-by-case basis. The choice of whether to treat, and with which type of treatment, should take into account anticipated life expectancy and patient preferences, as well as clinical factors such as the estimated bleeding risk, the type of VTE experienced and the time since the VTE event.

Central venous catheter associated upper extremity deep vein thrombosis in cancer patients: Diagnosis and therapeutic management.

Catheter-related thrombosis (CRT) is a relatively frequent and potentially fatal complication arising in patients with cancer who require a central catheter placement for intravenous treatment. In everyday practice, CRT remains a challenge for management; despite its frequency and its negative clinical impact, few data are available concerning diagnosis and treatment of CRT. In particular, no diagnostic studies or clinical trials have been published that included exclusively patients with cancer and a central venous catheter (CVC). For this reason, many questions regarding optimal management of CRT remain unanswered. Due to the paucity of high-grade evidence regarding CRT in cancer patients, guidelines are derived from upper extremity DVT studies for diagnosis, and from those for lower limb DVT for treatment. This article addresses the issues of diagnosis and management of CRT through a review of the available literature and makes a number of proposals based on the available evidence. In symptomatic patients, venous ultrasound is the most appropriate choice for first-line diagnostic imaging of CRT because it is noninvasive, and its diagnostic performance is high (which is not the case in asymptomatic patients). In the absence of direct comparative clinical trials, we suggest treating patients with CRT with a therapeutic dose of either a LMWH or a direct oral factor Xa inhibitor, with or without a loading dose. These anticoagulants should be given for a total of at least three months, including at least one month after catheter removal following initiation of therapy.

An MRI Radiomics Approach to Predict the Hypercoagulable Status of Gliomas.

Venous thromboembolic events are frequent complications of Glioblastoma Multiforme (GBM) and low-grade gliomas (LGGs). The overexpression of tissue factor (TF) plays an essential role in the local hypercoagulable phenotype that underlies these complications. Our aim was to build an MRI radiomics model for the non-invasive exploration of the hypercoagulable status of LGG/GBM. Radiogenomics data from The Cancer Genome Atlas (TCGA) and REMBRANDT (Repository for molecular BRAin Neoplasia DaTa) cohorts were used. A logistic regression model (Radscore) was built in order to identify the top 20% TF-expressing tumors, considered to be at high thromboembolic risk. The most contributive MRI radiomics features from LGG/GBM linked to high TF were identified in TCGA using Least Absolute Shrinkage and Selection Operator (LASSO) regression. A logistic regression model was built, whose performance was analyzed with ROC in the TCGA/training and REMBRANDT/validation cohorts: AUC = 0.87 [CI95: 0.81-0.94, p < 0.0001] and AUC = 0.78 [CI95: 0.56-1.00, p = 0.02], respectively. In agreement with the key role of the coagulation cascade in gliomas, LGG patients with a high Radscore had lower overall and disease-free survival. The Radscore was linked to the presence of specific genomic alterations, the composition of the tumor coagulome and the tumor immune infiltrate. Our findings suggest that a non-invasive assessment of the hypercoagulable status of LGG/GBM is possible with MRI radiomics.

Care pathways for patients with cancer-associated thrombosis: From diagnosis to long-term follow-up.

Venous thromboembolism (VTE) in patients with cancer is associated with a high risk of bleeding complications and hospitalisation, as well as with increased mortality. Good practice recommendations for diagnosis and treatment of VTE in patients with cancer have been developed by a number of professional bodies. Although these guidelines provide consistent recommendations on what treatment should be offered to patients presenting with cancer-associated thromboembolism (CAT), many questions remain unanswered, in particular about the modalities of management (Who? When? Where?) and, for this reason, we have developed a consensus proposal for an appropriate multidisciplinary care pathway for patients with CAT, which is presented in this article. The proposal was informed by the recent scientific literature retrieved through a systematic literature review. This proposal is centred on the development of a shared care plan individualised to each patient's needs and expectations, patient information and shared decision-making to promote adherence, involvement of all relevant hospital- and community- based healthcare providers in the development and implementation of the care plan, and regular re-evaluation of the treatment strategy.

Home treatment for patients with cancer-associated venous thromboembolism.

Patients hospitalised with acute venous thromboembolism (VTE), and notably patients with pulmonary embolism, often remain in hospital for extended periods due to the perceived risk of complications. However, several studies have shown that home treatment of selected patients is feasible and safe, with a low incidence of adverse events. This may offer clear benefits for patients' quality of life, hospital planning and cost to the health service. Nonetheless, there is a need for a VTE risk-stratification tool specifically addressing prognosis in patients with cancer. This may aid in the selection of low-risk patients with cancer and VTE who are suitable for outpatient treatment. Although several prognostic scores have been proposed, we suggest using a pragmatic clinical decision-making tool such as the Hestia criteria for selecting patients for home care in everyday clinical practice. Once patients have been discharged, it is mandatory to monitor patients regularly (we suggest after 3 days, 10 days, 1 month and 3 months, or more frequently if needed) with the involvement of a multidisciplinary team, so that appropriate and timely remedial action can be taken in case of warning signs of complications. If patients are selected carefully and monitored effectively, many patients who experience acute VTE can be cared for safely at home.

[Translation into French and republication of: "Home treatment for patients with cancer-associated venous thromboembolism"]. / Traduction et republication de : « Traitement à domicile des patients atteints de maladie veineuse thromboembolique associée au cancer ¼.

Patients hospitalised with acute venous thromboembolism (VTE), and notably patients with pulmonary embolism, often remain in hospital for extended periods due to the perceived risk of complications. However, several studies have shown that home treatment of selected patients is feasible and safe, with a low incidence of adverse events. This may offer clear benefits for patients' quality of life, hospital planning and cost to the health service. Nonetheless, there is a need for a VTE risk-stratification tool specifically addressing prognosis in patients with cancer. This may aid in the selection of low-risk patients with cancer and VTE who are suitable for outpatient treatment. Although several prognostic scores have been proposed, we suggest using a pragmatic clinical decision-making tool such as the Hestia criteria for selecting patients for home care in everyday clinical practice. Once patients have been discharged, it is mandatory to monitor patients regularly (we suggest after 3 days, 10 days, 1 month and 3 months, or more frequently if needed) with the involvement of a multidisciplinary team, so that appropriate and timely remedial action can be taken in case of warning signs of complications. If patients are selected carefully and monitored effectively, many patients who experience acute VTE can be cared for safely at home.

Cancer-associated thrombosis: How many patients seen in clinical practice would be eligible for a direct oral anticoagulant randomized controlled trial?

Based on the results of randomized clinical trials (RCT) assessing direct oral anticoagulants (DOACs) for the treatment of patients with cancer-associated thrombosis (CAT), DOACs have been proposed as alternative to low molecular weight heparin by several international guidelines. However, the proportion of CAT patients who would have not been eligible for such trials is currently unknown. Our primary aim was to assess the proportion of patients seen in clinical practice for acute CAT who would not have been eligible for CARAVAGGIO or HOKUSAI-VTE RCT. Secondary aim was to describe patients outcomes according to eligibility. In a multicenter, observational study, all patients consecutively admitted from January 2017 to December 2019 for an acute CAT event were retrospectively analyzed. Patients were classified according to the presence or absence of non-inclusion criteria for CARAVAGGIO or HOKUSAI-VTE RCT. Event free survival during a 6-month follow-up were analyzed as secondary endpoints. Among the 302 patients (women: 53 %, mean age: 67.9 ± 13.2) analyzed, 138 (46 %) for HOKUSAI-VTE cancer and 161 (53 %) for CARAVAGGIO met one or more non-inclusion criteria. Main criteria were upper limb and unsual site thrombosis (n = 63, 18.5 %), anemia/thrombopenia (n = 43, 14.2 %), brain tumors (n = 33, 10.9 %), ECOG PS >2 (n = 28, 9.3 %), severe renal failure (n = 16, 5.3 %). At 6 months, the event-free survival rate was not statistically different between the two groups. Almost half of CAT patients would have not been able to participate to a modern DOAC RCT. Evaluation of DOACs safety and efficacy in this subset of patients deserves further research.

Venous Thrombosis Recurrence After Catheter-Related Upper Extremity Deep Venous Thrombosis in Cancer Patients: A Retrospective Analysis.

Long-term indwelling central venous catheters (CVC) are frequently used to secure vascular access to deliver injectable treatment. Catheter-related thrombosis (CRT) occurs in approximately 2-6% of cancer patients. We conducted a single-center retrospective study to assess the rate of venous thromboembolism (VTE) recurrence in cancer patients; 200 patients were included. Mean age was 56 ± 15.15 years, median follow-up duration was 16.5 [range: 10-36] months. The incidence of recurrence was estimated using Gray's method for competing risk with death as the competing event of VTE. Recurrent VTE occurred in 25.5% of patients with a median occurrence time of 6.5 [range: 5-11.25] months. In case of recurrence, 94.6% of patients were treated for cancer and 80.4% of them received anticoagulants; 4 major bleeds and 17 non-major bleeds occurred during follow-up. In multivariate analysis, previous VTE (Hazard Ratio (HR) 2.48 (95% CI 1.42-4.32) and presence of CVC (HR 5.56 (95% CI 1.96-15.75) were significant recurrence risk factors. After a first episode of CRT, 25.5% of patients experienced VTE recurrence as UEDVT in 30 cases (55.5%), PE in 17 cases (31.5%), and DVT in 7 cases (13%), mostly during anticoagulation therapy. Anticoagulation therapy does not avoid CRT in case of cancer and must be balanced with hemorrhagic risk.

The coagulome of oral squamous cell carcinoma: examining the role and regulation of coagulation in oral cancers using a systems approach.

PURPOSE OF REVIEW: Solid tumors often establish a locally hypercoagulant state that promotes vascular complications, such as venous thromboembolism (VTE). Oral squamous cell carcinoma (OSCC) is associated with a broad range of hemostatic complications. Although VTE rarely occurs in ambulatory patients with OSCC, the coagulation cascade is typically activated by surgical resection and local hemorrhage. We present the recent progress in the understanding of the role and regulation of coagulation in OSCC. RECENT FINDINGS: Application of systems biology, using bulk tumor and single cell genomic analyses, unveiled the landscape of the tumor coagulome. Of all tumor types, OSCC express the highest mRNA levels of F3 and PLAU, the genes that encode the tissue factor (TF) and urokinase-type plasminogen activator (uPA), the key regulators of coagulation and fibrinolysis, respectively. It also brought to light the intimate and reciprocal regulation between coagulation/fibrinolysis and the tumor microenvironment (TME). SUMMARY: OSCC have a specific coagulome, with consequences that likely extend beyond the vascular risk. We discuss the attractive possibility that biomarkers of the coagulation cascade might reflect some important characteristics of the TME, offering new opportunities to better understand the impact of surgical procedures, better predict their oncological outcome and improve current therapeutic approaches.

Preliminary results of the European multicentric phase III trial regarding sirolimus in slow-flow vascular malformations.

BACKGROUNDSlow-flow vascular malformations frequently harbor activating mutations in the PI3K/AKT/mTOR cascade. Phase II trials pinpointed sirolimus effectiveness as a drug therapy. Efficacy and safety of sirolimus thus need to be evaluated in large prospective phase III trials.METHODSThe Vascular Anomaly-Sirolimus-Europe (VASE) trial, initiated in 2016, is a large multicentric prospective phase III trial (EudraCT 2015-001703-32), which evaluates efficacy and safety of sirolimus for 2 years in pediatric and adult patients with symptomatic slow-flow vascular malformations. In this interim analysis, we studied all patients enrolled up to October 2021 who received sirolimus for 12 or more months or who prematurely stopped the treatment.RESULTSThirty-one pediatric and 101 adult patients were included in this analysis; 107 completed 12 or more months of sirolimus, including 61 who were treated for the whole 2-year period. Sirolimus resulted in a clinical improvement in 85% of patients. The efficacy appeared within the first month for the majority of them. Grade 3-4 adverse events were observed in 24 (18%) patients; all resolved after treatment interruption/arrest. Sirolimus increased feasibility of surgery or sclerotherapy in 20 (15%) patients initially deemed unsuitable for intervention. Among the 61 patients who completed the 2-year treatment, 33 (54%) reported a recurrence of symptoms after a median follow-up of 13 months after sirolimus arrest. While there was no difference in efficacy, clinical improvement was faster but subsided more rapidly in PIK3CA-mutated (n = 24) compared with TIE2-mutated (n = 19) patients.CONCLUSIONSirolimus has a high efficacy and good tolerance in treatment of slow-flow vascular malformations in children and adults.TRIAL REGISTRATIONClinicalTrials.gov NCT02638389 and EudraCT 2015-001703-32.FUNDINGThe Fonds de la Recherche Scientifique (FNRS grants T.0247.19, P.C005.22, T.0146.16, and P.C013.20), the Fund Generet managed by the King Baudouin Foundation (grant 2018-J1810250-211305), the Walloon Region through the FRFS-WELBIO strategic research programme (WELBIO-CR-2019C-06), the MSCA-ITN network V.A. Cure no. 814316, the Leducq Foundation Networks of Excellence Program grant "ReVAMP" (LFCR grant 21CVD03), the European Union's Horizon 2020 research and innovation programme under grant agreement no. 874708 (Theralymph), the Swiss National Science Foundation under the Sinergia project no. CRSII5_193694, and a Pierre M. fellowship.

[Screening for cancer in case of venous thromboembolism: when and how?] / Quand et comment rechercher un cancer en cas de maladie thromboembolique veineuse ?

Screening for cancer in case of venous thromboembolism: when and how? Cancer associated thrombosis (cat) is an important challenge. When venous thromboembolism (vte) occurs without any identified risk factors, the risk of cat raises the question of a hidden cancer and the need for an extensive screening or not. Several series have shown a prevalence between 5% and 10% of cancer when non provoqued vte is diagnosed. Most of cancers occur during the following year of vte. If we consider diagnosing the cancer in early stage, we might improve the patient outcome and reduce cancer mortality. A simple screening, including clinical examina¬tion, personal and familial history of cancer, basic laboratory tests and recommended age and sex testing is mandatory. Other exams are considered as useless at present time. Whether a tep-scan, prescribed in patients older than 50, brings a clinical benefit, is still unresolved. Screening for cancer in case of venous thromboembolism: when and how? Cancer associated thrombosis (cat) is an important challenge. When venous thromboembolism (vte) occurs without any identified risk factors, the risk of cat raises the question of a hidden cancer and the need for an extensive screening or not. Several series have shown a prevalence between 5% and 10% of cancer when non provoqued vte is diagnosed. Most of cancers occur during the following year of vte. If we consider diagnosing the cancer in early stage, we might improve the patient outcome and reduce cancer mortality. A simple screening, including clinical examina¬tion, personal and familial history of cancer, basic laboratory tests and recommended age and sex testing is mandatory. Other exams are considered as useless at present time. Whether a tep-scan, prescribed in patients older than 50, brings a clinical benefit, is still unresolved.

Quand et comment rechercher un cancer en cas de maladie thromboembolique veineuse ? L'association thrombose et cancer est connue depuis longtemps et pose des problèmes diagnostiques et thérapeutiques spécifiques. La maladie thromboembolique veineuse (mtev) peut précéder le cancer et servir de signe d'alerte. Plusieurs publications font état d'une prévalence comprise entre 5 et 10 % de cancer occulte en cas de mtev non provoquée. La plupart des cancers apparaissent dans l'année qui suit le diagnostic de mtev. Dépister un cancer au stade infraclinique, au moment du diagnostic de la thrombose, permettrait de diminuer le risque d'extension du cancer et d'améliorer le pronostic des patients. Une recherche de cancer, simple, incluant interrogatoire, examen clinique et bilan biologique minimal, sans examens complémentaires inutiles et adaptée aux facteurs de risque, doit donc être effectuée. La question est aujourd'hui de savoir si une stratégie plus extensive, comprenant un tep-scan, notamment chez les patients de plus de 50 ans, apporte un bénéfice clinique.