Imaging of the lymphatic system: new horizons

The lymphatic system is a complex network of lymph vessels, lymphatic organs and lymph nodes. Traditionally, imaging of the lymphatic system has been based on conventional imaging methods like computed tomography (CT) and magnetic resonance imaging (MRI), whereby enlargement of lymph nodes is considered the primary diagnostic criterion for disease. This is particularly true in oncology, where nodal enlargement can be indicative of nodal metastases or lymphoma. CT and MRI on their own are, however, anatomical imaging methods. Newer imaging methods such as positron emission tomography (PET), dynamic contrast‐enhanced MRI (DCE‐MRI) and color Doppler ultrasound (CDUS) provide a functional assessment of node status. None of these techniques is capable of detecting flow within the lymphatics and, thus, several intra‐lymphatic imaging methods have been developed. Direct lymphangiography is an all‐but‐extinct method of visualizing the lymphatic drainage from an extremity using oil‐based iodine contrast agents. More recently, interstitially injected intra‐lymphatic imaging, such as lymphoscintigraphy, has been used for lymphedema assessment and sentinel node detection. Nevertheless, radionuclide‐based imaging has the disadvantage of poor resolution. This has lead to the development of novel systemic and interstitial imaging techniques which are minimally invasive and have the potential to provide both structural and functional information; this is a particular advantage for cancer imaging, where anatomical depiction alone often provides insufficient information. At present the respective role each modality plays remains to be determined. Indeed, multi‐modal imaging may be more appropriate for certain lymphatic disorders. The field of lymphatic imaging is ever evolving, and technological advances, combined with the development of new contrast agents, continue to improve diagnostic accuracy. Published in 2006 by John Wiley & Sons, Ltd.     

循环肿瘤细胞的“旧语新说”

循环肿瘤细胞(CTC)是指游离在循环体液中的肿瘤细胞;CTC检测避免了侵入性组织活检的局限性,取材便捷、无创,在动态反映肿瘤状态、疗效监测与预后评估中有重要作用。目前,应用于临床的CTC计数是评估乳腺癌、前列腺癌和结直肠癌预后的有效指标;CTC携带的肿瘤特异性抗原与核酸分析的转化研究,将有助于提高CTC的捕获效率与诊断性能。虽然CTC检测技术的临床应用仍然面临着诸多挑战,但是其在肿瘤诊疗上的潜力不容小觑,具有广阔的应用前景。     

Extracorporeal methods of therapy in lymphatic tumors

The paper is concerned with the use of plasmapheresis, lymphocytapheresis, lymphocytaplasmapheresis and plasma perfusion in patients with tumors of the lymphoid tissue. Based on 976 plasmapheresis sessions given to 161 patients the authors demonstrate its efficacy in the treatment of patients with tumors of the lymphoid tissue associated with secretion of paraprotein whose presence gives rise to such complications as the syndrome of high viscosity, cryoglobulinemia, chronic renal failure, amyloidosis, cold hemolytic disease and other paraproteinemia-induced complications. On abundant material (535 sessions given to 98 patients) the authors review situations in which lymphocytapheresis, lymphocytaplasmapheresis and plasma perfusion may be indicated. Consider approaches to their performance as well as the clinical efficacy of the methods.     

Old and new anticoagulants

Vitamin-K-antagonists (VKA) and heparins have been complementary anticoagulants for prevention and treatment of thrombosis for almost 70 years. In contrast to heparins, VKA have not been modified pharmacologically, however treatment surveillance has improved by introducing INR and self-monitoring/management. Disclosure of the molecular basis of interaction with VKORC1, the target enzyme of VKA, has helped to better understand coumarin sensitivity and resistance. New oral anticoagulants have now been approved and stimulated expectations in patients and physicians to get rid of the burdening frequent controls of VKA without loss of efficacy and safety. This review will summarize the development and profile of the new substances. Main difference compared to VKA is their direct mode of action against one clotting factor which is factor IIa in dabigatran and factor Xa in rivaroxaban and other "xabanes" currently under intensive investigation. Half lifes of the new anticoagulants are much shorter than that of the mainly used coumarins (phenprocoumon, warfarin), making "anticoagulation bridging" unnecessary before surgery. Therapeutic width of direct thrombin inhibitors and factor Xa inhibitors is broader and they are given at fixed doses. Clinical studies in thromboprophylaxis, thromboembolism and atrial fibrillation indicate at least non-inferiority or even superior efficacy compared with enoxaparin and VKA at comparable safety outcomes. Limitations of the new substances may arise from gastrointestinal side effects, mode of metabolism and route of elimination. Specific antidots are not available for none of them. Undoubtedly, the new oral anticoagulants are very promising. But, although thousands of study patients already have been treated, there are questions to be answered such as treatment adherence in absence of monitoring, safety and efficacy in risk patients, dosage adjustment and interactions with other drugs, before conclusions can be drawn towards their potential to replace VKA.     

Anticoagulants. Old and new

Anticoagulants are effective in the prevention and treatment of a variety of arterial and venous thrombotic disorders but are associated with an increased risk of serious bleeding complications. Based on well documented studies of patients using vitamin K antagonists the incidence of major bleeding is 0.5%/year and the incidence of intracranial bleeding is 0.2%/year, however, in real life practice this incidence may be even higher. Risk factors for bleeding are the intensity of anticoagulation, the management strategy to keep the anticoagulant effect in the desired range, and patient characteristics. Recently, a new generation of anticoagulants have been developed and is currently evaluated in clinical trials. Initial results show a similar or superior efficacy over conventional anticoagulant agents with a good safety profile. In case of serious bleeding complications in a patient who uses vitamin K antagonists, this anticoagulant treatment can be quickly reversed by administration of vitamin K or coagulation factor concentrates. For the newer anticoagulants, quick reversal strategies are more cumbersome, although some interventions, including prothrombin complex concentrates, show promising results in initial experimental studies.     

Old and new inotropic drugs

An ideal cardiotonic agent should improve cardiac contractility and increase the oxygen supply to various tissues without inducing tachycardia, arrhythmias, decrease in coronary blood flow or increment in oxygen requirements of the myocardium. It should also be safe and orally active and have a persistent action. The aim of this paper is to describe various positive inotropic drugs at our disposal. The hemodynamic effects and the indications of adrenaline, noradrenaline, isoprenaline, dopamine, dobutamine and cardiac glycosides are presented first. Then several new promising orally active compounds are discussed.     

Role of the lymphatic circulatory system in shock

That the lymphatic vessel participates in the regulation of interstitial dynamics through its ability to contract and propel fluid and protein from the extravascular tissues back to the bloodstream has not been fully appreciated. The "lymph pump" appears to be regulated by local physiologic forces as well as neurogenic and humoral factors. We have assessed the effects of hemorrhage and endotoxin on the ability of the lymph vessel to propel fluid in sheep using a model system that permits the quantitation of lymphatic pumping in vivo without the complication of variable lymph inputs. A major blood loss was found to enhance lymphatic contractile activity and fluid pumping. Considering the large reservoir of fluid and protein in the interstitium and lymph, we speculate that stimulation of the "lymph pump" after hemorrhage might help to re-expand the vascular space. On the other hand, the intravenous administration of endotoxin inhibited lymphatic pumping, suggesting that impaired lymph propulsion in sepsis may contribute to edema by reducing the ability of the lymphatic vessel to remove extravasated protein from the tissues.     

Lymphoedema 1: components and function of the lymphatic system

Lymphoedema is an incurable and debilitating condition which has a negative impact on the quality of life of the sufferer and his/her family. Information with regards to diagnosis and treatment is often scarce and conflicting in nature. The following series of articles should enable nurses to recognize the condition, provide basic information to a patient and instigate treatment though referral. The first article describes the anatomy, physiology and functions of the lymphatic system. The focus is on the parts of the lymphatic system which are specific to the condition of lymphoedema and aims to place subsequent articles in context. The following articles describe the different types of lymphoedema and the four main elements of treatment that are central to the management of the condition.     

表观遗传学在淋巴系统肿瘤研究中的新进展

表观遗传学是研究不涉及DNA序列改变的基因表达和调控的可遗传修饰,即探索从基因演绎为表型的过程和机制的一门新兴学科。近年来诸多证据显示,表观遗传学改变在淋巴系统肿瘤发生发展过程中起重要作用。例如,近期多个实验室的资料显示,参与许多重要分子信号通路的基因在急性淋巴细胞白血病中是表观抑制的;一组甲基化标志可被用作慢性淋巴细胞白血病患者额外的危险分层因素;基于表观遗传学甲基化谱研究中间性(灰区)B细胞淋巴瘤类别划分模型;多发性骨髓瘤中mciroRNA介导的表观遗传学沉默与P53功能联系密切;表观遗传修饰治疗赋予免疫治疗更广的内涵,其可能是极富潜力的免疫治疗策略之一。本文就淋巴系统肿瘤中表观遗传学改变的最新研究进展及通过干预表观遗传修饰治疗的相关研究和应用前景做一综述。