Venous thromboembolism in colorectal cancer patients with central venous catheters for 5-FU infusion-based pharmacokinetic modulating chemotherapy

Colorectal cancer patients with central venous catheters (CVC) for pharmacokinetic modulating chemotherapy (PMC) have a substantial risk of venous thromboembolism (VTE). PMC, designed as a hybrid of lower metronomic and higher shorter plasma 5-FU concentrations, has been clinically successful. To determine the effectiveness and safety of D-dimer tests and multidetector-row CT (MDCT) for diagnosis in cancer patients with suspected VTE, we carried out a clinical outcome study on PMC outpatients. Patients received a D-dimer test before and after commencing the PMC regimen. MDCT was performed additionally if the D-dimer test appeared positive or showed signs of VTE. When CT results were positive for thromboembolism, anticoagulation was started. The overall prevalence of VTE in PMC patients was 2.0% (7 of 350 patients). In this study, 34 out of 102 colorectal cancer patients gave a positive D-dimer test (33.3%). CT identified venous thrombi in 2 of the 102 patients (2.0%), mural thrombosis on catheterized veins in another 3 patients (2.9%), and endothelial hyperplasia on catheterized veins in 8 patients (7.8%). The catheters of these patients did not show any significant abnormalities. Patients with negative D-dimer tests showed no signs or symptoms of VTE. In colorectal cancer patients receiving continuous 5-FU infusion via CVC, a D-dimer test can be safely used as the primary diagnostic test for ruling out VTE. We suggest 7.0 microg/ml as the D-dimer cut-off value. Thromboprophylaxis should be considered in the patients showing values >7.0 microg/ml.     

Thrombotic complications of central venous catheters in cancer patients

Central venous catheters (CVCs), such as the tunneled catheters and the totally implanted ports, play a major role in general medicine and oncology. Aside from the complications (pneumothorax, hemorrhage) associated with their initial insertion, all of these CVCs are associated with the long-term risks of infection and thrombosis. Despite routine flushing with heparin or saline, 41% of CVCs result in thrombosis of the blood vessel, and this markedly increases the risk of infection. Only one-third of these clots are symptomatic. Within days of insertion, almost all CVCs are coated with a fibrin sheath, and within 30 days, most CVC-related thrombi arise. Aside from reducing the function of the catheter, these CVC-related thrombi can cause postphlebitic syndrome in 15%-30% of cases and pulmonary embolism in 11% (only half of which are symptomatic). Risk factors for CVC thrombosis include the type of malignancy, type of chemotherapy, type of CVC, and locations of insertion site and catheter tip, but not inherited thrombophilic risk factors. Efforts to reduce CVC thrombosis with systemic prophylactic anticoagulation with low-molecular-weight heparin have failed. Low-dose warfarin prophylaxis remains controversial; all studies are flawed, with older studies, but not newer ones, showing benefit. Currently, less than 10% of patients with CVCs receive any systemic prophylaxis. Although its general use cannot be recommended, low-dose warfarin may be a low-risk treatment in patients with good nutrition and adequate hepatic function. Clearly, additional studies are required to substantiate the prophylactic use of low-dose warfarin. Newer anticoagulant treatments, such as pentasaccharide and direct thrombin inhibitors, need to be explored to address this major medical problem.     

Local infusion of urokinase for the lysis of thrombosis associated with permanent central venous catheters in cancer patients

We assessed the efficacy of local fibrinolytic therapy in 35 axillary-subclavian vein thromboses (SVT) that occurred in cancer patients with percutaneous central venous catheters (CVC). These catheters were indwelling for a median of 1 month (range, one day to 10 months) before thrombosis developed. Urokinase was administered at a dose of 500 to 2,000 U/kg/h. Complete lysis occurred in 25 of 30 thrombi that were directly infused, after a median of four days. Complete lysis occurred in one of 12 thrombi that could not be directly infused with urokinase and in two of six with associated phlebitis. Eighty-one percent of the thrombi that were symptomatic for less than 1 week before treatment resolved, compared with 56% present for longer than 1 week. Sixteen patients who had complete (12) or partial (four) thrombolysis did not have their CVCs removed. All four patients with partial thrombolysis had recurrent thrombosis at a median of eight days (range, one to 90). Only two patients who had complete thrombolysis had recurrent thrombosis, at 8 and 16 months. Only minor hemorrhagic toxicity was seen.     

The use of novel oral anticoagulants in cancer patients with venous thromboembolism

Venous thromboembolism (VTE) is not uncommon among patients with cancer and is one of the major causes of mortality and morbidity. Treatment with low-molecular-weight heparin (LMWH) is effective, yet accompanied by the need for daily administration of injections for a prolonged time and (even rarely) thrombocytopenia. The discovery of novel oral anticoagulants (NOACs) was based on an effort to improve the pharmacodynamic and pharmacokinetic properties of previous generation anticoagulants while maintaining efficacy without the need for daily subcutaneous administration and frequent laboratory monitoring. The MEDLINE database was searched using PubMed in order to find relevant studies on the use of NOACs in patients with active malignancy and VTE. Furthermore, critical reading of references in recently published studies and reviews was performed. NOACs appear to be at least equivalent to coumarin anticoagulants in terms of efficacy and safety and their administration is easier, but data specifically concerning patients with active malignancy or comparing them to LMWH in this specific clinical setting are not yet available. Furthermore, patients with active cancer present several unique characteristics and drawing conclusions from studies involving other patient groups may not be appropriate. Specific studies in cancer patients are still pending that will help decide if NOACs will be the drugs of choice in this group of patients in need of efficient and simple to administer treatments.     

Complications from long-term indwelling central venous catheters in hematologic patients with special reference to infection

Forty-three evaluable patients with hematologic malignancies, mainly acute leukemia, were prospectively randomized to receive a double lumen central venous catheter or a totally implantable venous access system. The mean catheter stay was 166 days (median, 104 days) for the 23 double lumen catheters and 164 days (median, 65 days) for implanted systems. Exit site infections were not encountered in double lumen catheters, but there were two proven infections around the injection port of implanted devices. Tunnel infections did not occur. Seven double lumen catheters and four implanted systems were removed because of infection. Staphylococcus epidermidis was the predominant microorganism cultured from these catheters. Five of nine patients with double lumen catheters and catheter-related S. epidermidis infection and the two patients with implanted systems in whom S. epidermidis was cultured were on selective gut decontamination. The pattern of infection did not seem to be influenced by this regimen. Totally implantable systems proved to be as safe as double lumen central venous lines.     

肺癌术后并发静脉血栓栓塞症的临床分析

目的:分析肺癌术后发生静脉血栓栓塞(venous thromboembolism,VTE)的高危因素及其预后.方法:对1001例有完整临床随访资料的肺癌手术患者进行回顾性分析.应用螺旋CT、肺动脉造影和彩色多普勒超声诊断VTE.寿命表法绘制血栓发生曲线,COX多因素分析VTE高危因素.Kaplan-Meier法及log-rank检验绘制并比较高危因素血栓发生曲线及生存曲线.结果:术后1、3、5、11和30个月的VTE累积发生率分别为2.0％、3.0％、4.0％、5.0％和5.3％.COX多因素回归分析显示,接受不完全切除术患者发生VTE的风险比(hazard ratio,HR)为9.867(95％可信区间为5.275～18.459),P=0.000;术后接受化疗联合重组人血管内皮抑制素治疗患者的HR为3.472 (95％可信区间为1.761～6.845),P=0.000;术后接受表皮生长因子受体酪氨酸激酶抑制剂治疗患者的HR为2.808 (95％可信区间为1.439～5.479),P=0.002;术前基线血浆D-二聚体水平升高者的HR为7.520(95％可信区间为3.968～14.250),P=0.000.肺癌术后伴VTE患者的生存时间明显短于无VTE的患者(P=0.000).结论:不完全切除术、术后化疗联合重组人血管内皮抑制素治疗、表皮生长因子受体酪氨酸激酶抑制剂治疗和术前基线血浆D-二聚体水平升高是肺癌手术患者术后并发VTE的高危因素.肺癌术后伴VTE患者的生存时间明显短于无VTE的患者.     

Thrombotic and infectious complications of central venous catheters in patients with hematological malignancies.

Central venous catheters (CVCs) have considerably improved the management of patients with hematological malignancies, by facilitating chemotherapy, supportive therapy and blood sampling. Complications of insertion of CVCs include mechanical (arterial puncture, pneumothorax), thrombotic and infectious complications. CVC-related thrombosis and infections are frequently occurring complications and may cause significant morbidity in patients with hematological malignancies. CVC-related thrombosis and infections are related and can therefore not be seen as separate entities. The incidence of symptomatic CVC-related thrombosis had been reported to vary between 1.2 and 13.0% of patients with hematological malignancy. The incidence of CVC-related bloodstream infections varies between 0.0 and 20.8%. There is need for a specific approach regarding diagnosis and treatment of CVC-related thrombosis and infection with specific attention to the preservation of the catheter. Since data on CVC-related infections and thrombosis in hematological patients have been obtained mainly from retrospective studies of small sample size, prospective, randomized studies of prophylactic measures concerning CVC-related thrombosis and infection are warranted.     

Management of venous thromboembolism in cancer patients

Venous thromboembolism is a common complication in patients with cancer. The management of deep-vein thrombosis and pulmonary embolism can be a considerable challenge in these patients. Diagnosing venous thrombosis requires objective testing, and noninvasive investigations may be less accurate in patients who have cancer than in those who do not. Treatment of acute venous thrombosis at home with low-molecular-weight heparin is an attractive option in patients with malignant disease, in whom quality of life is especially important. Comorbid conditions, warfarin resistance, difficult venous access, and a potentially high bleeding risk are some of the factors that often complicate the prolonged course of anticoagulant therapy needed in this group. In addition, the use of central venous catheters is increasing, but the optimal treatment of catheter-related thrombosis remains controversial. This article reviews the current diagnostic and treatment approaches to venous thromboembolism in patients with cancer and provides several clinical scenarios to illustrate and discuss some common management problems.     

Enoxaparin for the prevention of venous thromboembolism associated with central vein catheter: a double-blind, placebo-controlled, randomized study in cancer patients.

PURPOSE: The extent of venous thromboembolism (VTE) associated with central vein catheters (CVC) in cancer patients remains unclear. The aim of this study was to evaluate the efficacy and safety of the low molecular weight heparin, enoxaparin, in the prevention of VTE. PATIENTS AND METHODS: In a multicenter, double-blind study, consecutive cancer patients scheduled for CVC insertion were randomly assigned to receive either subcutaneous enoxaparin 40 mg once a day or placebo. Treatment was started 2 hours before CVC insertion and continued for 6 weeks. The primary end points of the study were deep vein thrombosis (DVT), confirmed by venography of the CVC limb performed 6 weeks after randomization, or clinically overt pulmonary embolism, confirmed by objective testing during the study drug administration. Patients were assessed for bleeding complications. RESULTS: Three hundred eighty-five patients were randomized, of which 321 (83.4%) underwent venography. A venography was adequate for adjudication in 155 patients in each treatment group. A DVT was observed in 22 patients (14.1%) treated with enoxaparin and in 28 patients (18.0%) treated with placebo, corresponding to a relative risk of 0.78 (95% CI, 0.47 to 1.31). No major bleeding occurred. Five patients (2.6%) in the enoxaparin group and two patients (1.0%) in the placebo group died during the treatment period. CONCLUSION: In this study, no difference in the rate of CVC-related VTE was detected between patients receiving enoxaparin and patients receiving placebo. The dose of enoxaparin used in this study proved to be safe. Clinical trials evaluating higher enoxaparin doses could optimize the efficacy of this agent for this indication.     

Venous thromboembolism predicts poor prognosis in irresectable pancreatic cancer patients.

BACKGROUND: The aim was to investigate the outcomes associated with venous thromboembolism (VTE) among irresectable pancreatic cancer patients. METHODS: This is a follow-up study of consecutive irresectable cancer patients, treated and followed up in clinical trials between December 2001 and December 2004 in order to evaluate the prognostic impact of symptomatic VTE on clinical outcomes, such as response to treatment, progression-free survival (PFS) and overall survival (OS). RESULTS: Among 227 irresectable pancreatic cancer patients, with Eastern Cooperative Oncology Group performance status (ECOG-PS) < or = 2, 59 (26.0%) patients developed a VTE. A synchronous VTE occurred in 28 (12.3%) patients, while a VTE during chemotherapy was observed in 15 (6.6%) patients, and 16 (7.0%) patients experienced both events. Presence of synchronous VTE was associated with a higher probability of not responding to treatment (odds ratio 2.98, 95% CI 1.42-6.27, P = 0.004), but showed no effect on both PFS and OS at least at multivariate analysis. Occurrence of a VTE during chemotherapy showed a statistically significant effect on PFS (hazard ratio [HR] 2.59, 95% CI 1.69-3.97, P < 0.0001) and OS (HR 1.64, 95%CI 1.04-2.58, P = 0.032). CONCLUSIONS: Our data suggest that the occurrence of VTE may be associated with a reduced response rate and a shorter PFS and OS among patients with irresectable pancreatic cancer. In these patients the development of VTE may reflect the presence of a biologically more aggressive cancer that in turn leads to a worse prognosis.     

胰腺癌相关静脉血栓文献复习

恶性肿瘤患者是静脉血栓栓塞症的高危人群,而血栓栓塞在胰腺癌患者的发生率更高,且早期发生往往提示预后不良.本文对国内外既往胰腺癌相关静脉血栓文献进行回顾,并对胰腺癌相关静脉血栓的发生机制,预防、诊断、治疗胰腺癌相关静脉血栓的重要性,胰腺癌相关静脉血栓的风险评估,通过对胰腺癌相关静脉血栓的诊断以及胰腺癌相关静脉血栓的治疗及安全性等方面进行探讨,旨在提高对于胰腺癌相关静脉血栓疾病的认识和重视程度,并提高患者生存质量、延长生存时间.     

Complication rates among cancer patients with peripherally inserted central catheters.

PURPOSE: Peripherally inserted central catheters (PICCs) are frequently used to deliver outpatient courses of intravenous therapy. However, the rates and risks of complication for this device have not been well-studied. Our objective was to determine the incidence and risk factors of PICC-related complications with a 1-year prospective observational study. PATIENTS AND METHODS: All PICCs inserted in adult and pediatric patients at Memorial Sloan-Kettering Cancer Center (MSKCC) were followed prospectively. The device insertion team, inpatient nurses, and various home-care companies and outside institutions collected longitudinal data. RESULTS: Three hundred fifty-one PICCs were inserted during the study period and followed for a total of 10,562 catheter-days (median placement, 15 days; range, 1 to 487 days). Two hundred five PICCs (58%) were managed by home-care companies and outside institutions, and 146 PICCs (42%) were managed exclusively at MSKCC. For these 205 PICCs, 131 nurses from 74 home-care companies and institutions were contacted for follow-up clinical information. In all, 115 (32.8%) of 351 PICCs were removed as a result of a complication, for a rate of 10.9 per 1,000 catheter-days. Patients with hematologic malignancy or bone marrow transplant were more likely to develop a complication, whereas those with metastatic disease were less likely. CONCLUSION: Complications occur frequently among cancer patients with PICCs, and long-term follow-up is onerous. Despite a high complication rate, the ease of insertion and removal argues for continued PICC use in the cancer population.     

肺癌合并静脉血栓栓塞症89例临床分析

目的:本研究旨在探讨肺癌合并静脉血栓栓塞症(venous thromboembolism,VTE)患者的临床相关因素,为肺癌合并VTE的预防及治疗提供依据。方法:对2008年7月-2010年6月收治的经细胞学或病理学确诊的2053例肺癌病例进行回顾性分析。采用螺旋CT、肺动脉造影及彩色多普勒超声检查明确VTE诊断。将年龄、性别、病理类型、肺癌分期、手术、体质量指数、基础疾病、治疗前血小板计数、D-二聚体、白细胞介素1和肿瘤坏死因子作为临床相关因素。结果:2053例肺癌患者中,89例(4.34%)患者合并VTE。腺癌患者的VTE发生率为5.65%(58/1027),非腺癌患者为3.02%(31/1026),差异有统计学意义(P=0.003);Ⅰ～ⅢA期患者的VTE发生率为1.48%(10/677),ⅢB～Ⅳ期患者的VTE发生率为5.74%(79/1376),差异有统计学意义(P<0.001);Ⅰ～ⅢA期接受手术治疗患者的VTE发生率为1.55%(10/645),未行手术治疗患者的VTE发生率为0%(0/32),差异有统计学意义(P=0.044);无基础疾病患者的VTE发生率为2.70%(33/1221),伴随基础疾病患者的VTE发生率为6.73%(56/832),差异有统计学意义(P<0.001)。治疗前,血小板计数、D-二聚体、白细胞介素1和肿瘤坏死因子水平正常者的VTE发生率分别为3.72%、0.31%、2.44%和3.27%,而水平升高者的VTE发生率分别为6.26%、19.91%、10.26%和7.74%,差异均有统计学意义(P<0.05)。Logistic多因素回归分析显示,腺癌、手术、基础疾病以及D-二聚体、白细胞介素1和肿瘤坏死因子水平升高是肺癌患者发生VTE的相关临床因素(P<0.05)。结论:肺癌合并VTE患者中,腺癌是最常见的病理类型。手术、基础疾病以及D-二聚体、白细胞介素1和肿瘤坏死因子水平升高是肺癌患者发生VTE的危险因素。     

Venous thromboembolism in cervical cancer

Venous thromboembolism (VTE) is common in malignant disease and is associated with substantial morbidity and mortality. Recently, VTE has received increased attention as a result of the use of newer drugs, such as erythropoietin-stimulating agents or antiangiogenic drugs, which increase the risk of this condition. Several reviews have been published on VTE in cancer, but none have specifically focused on cervical cancer. In this review, we focus on the incidence of VTE, patient, tumour, and treatment-related risk factors for VTE, and treatment and prevention of VTE in the setting of cervical cancer.     

Long-term therapy of venous thromboembolism in cancer patients

Venous thromboembolism (VTE) is a common complication in cancer patients that results in significant morbidity and mortality. Long-term treatment options for cancer patients who experience VTE include vitamin K antagonists (VKAs), low molecular weight heparins (LMWHs), and inferior vena caval (IVC) filters. Cancer patients have a two- to fourfold higher risk for experiencing recurrent VTE and major bleeding during chronic VKA therapy than patients without malignancies. Recent randomized clinical trials have shown that LMWHs rather than oral VKAs are preferred for initial chronic treatment of VTE in patients with advanced cancer. One factor potentially limiting the broader use of LMWH for chronic therapy in the United States is its higher acquisition cost. Efficacy, cost, drug availability, patient comorbidities, and concomitant medications all need to be considered when selecting chronic VTE therapy. Cancer patients with VTE should be treated for as long as their disease is active to minimize the incidence of recurrence. Use of IVC filters should generally be reserved for patients at high risk for recurrent VTE who have contraindications to anticoagulation. Several new anticoagulants are being investigated that promise greater therapeutic choices and potentially better outcomes for cancer patients with VTE.     

Circulating tumour cells are associated with increased risk of venous thromboembolism in metastatic breast cancer patients

Background:

Cancer is a risk factor for venous thromboembolism (VTE). Circulating tumour cells (CTCs) are an independent predictor of survival in metastatic breast cancer (MBC) patients. The aim of this study was to test the hypothesis that CTCs are associated with the risk of VTE in MBC patients.

Methods:

This retrospective study included 290 MBC patients treated in the MD Anderson Cancer Center from January 2004 to December 2007. Circulating tumour cells were detected and enumerated using the CellSearch system before starting new lines of therapy.

Results:

At a median follow-up of 12.5 months, 25 patients experienced VTE and 53 patients died without experiencing thrombosis. Cumulative incidence of thrombosis at 12 months was 8.5% (95% confidence interval (CI)=5.5%, 12.4%). Patients with CTCs ⩾1 and ⩾5 had a higher incidence of VTE compared with patients with 0 and <5 CTCs (12-month estimate, 11.7 and 11.6% vs 3 and 6.6%; P=0.006 and P=0.076, respectively). In the multivariate model, patients with CTCs⩾1 had a hazard ratio of VTE of 5.29 (95% CI=1.58, 17.7, P=0.007) compared with patients with no CTCs.

Conclusion:

These results suggest that CTCs in MBC patients are associated with increased risk of VTE. These patients should be followed up more closely for the risk of VTE.     

Molecular and clinical conditions associated with venous thromboembolism in oncological patients

The association between cancer and thrombophilia has been known since 1865 since Trousseau described it. However in the last three decades an increased interest has been raised on this issue related to several molecular and condition that are involved in the daily management of oncological patients. This brief review has been focused on molecular conditions underlying cancer acquired thrombophilia then to further clinical aspects inducing thrombophilia in oncological patients such as surgery, chemotherapy, concomitant medical illness and inherited thrombophilia.