May-thurner Syndrome

Recent Advances in the Diagnosis and Management of Pulmonary Embolism

Acute pulmonary embolism (PE) is a form of venous thromboembolism

(VTE) and has varied clinical manifestations with significant morbidity and mortality.

The general population's overall incidence is on the rise due to the increasing

availability of D-dimer and computed tomographic pulmonary angiography. The

incidence is higher in males than females (58 versus 48 per 100,000, respectively),

increasing with age. In the United States, PE accounts for approximately 100,000

deaths annually. Specific populations, including patients with malignancy, pregnant

females, hospitalized medical and surgical patients, or patients with total joint

replacement, or arthroplasty, are at a higher risk for PE. Patients presenting with

hemodynamic compromise due to PE need to be treated with intravenous thrombolytic

therapy unless contraindicated, followed by anticoagulation. For over six decades,

traditional anticoagulants like unfractionated heparin (UFH) are used for short-term

anticoagulation. For patients who require long-term anticoagulation, low molecular

weight heparin (LMWH) like enoxaparin and a vitamin K antagonist like warfarin are

used to achieve therapeutic anticoagulation. Options for anticoagulation have been

expanding steadily over the last decade with the introduction of the first direct oral

anticoagulant (DOAC). Since their introduction, DOACs have changed the landscape

of anticoagulation. This narrative review aims to summarize for clinicians managing

pulmonary embolism (PE) the main recent advances in patient care, including risk

stratification, current data regarding the use of thrombolytic treatment, and direct oral

anticoagulants.

T Cells in Gastrointestinal Cancers: Role and Therapeutic Strategies

Conventional treatments of gastrointestinal cancers based on surgical resection and chemotherapy are not enough to eradicate potentially relapsing tumor cells and can also impair the immune system functions. Immunotherapies aim to help the body to eradicate cancer and other diseases, by modulating the immune system. They can be performed by active approaches, usually orchestrated by dendritic cell vaccines that present a specific tumor associated antigen to T cells, or passive approaches, which have the T cells as protagonist, and are based on antitumor antibodies, or adoptive cell transfer. T lymphocyte subsets can exhibit different role face to a tumor scenario, varying from an effective cellular antitumor response to a regulatory participation. Although a lot of protocols to combat cancer progression have been proposed, T cell-based immunotherapies in gastrointestinal cancers are still not approved for clinical applications mainly because of their side effects. Nowadays, promising protocols combining two or more approaches, aiming to create an efficient therapy without or with fewer side effects. In this chapter, we made a review about the role of T cells on cancer, especially focusing on gastrointestinal cancer immunotherapeutic methods.

Targeted Cancer Therapy: The Roles Played by Antibody-Drug and Antibody-Toxin Conjugates

In recent years, antibody therapeutics have been widely and successfully used in treating cancer. Antibodies that specifically bind tumor surface antigens can also be used as therapeutics, and over 35 of them are in clinical use (e.g. trastuzumab, bevacizumab and cetuximab). However, some unmodified antibodies against tumorspecific antigens lack therapeutic activity. Conjugation to cytotoxic agents can increase the antibodies’ activity and, at the same time, enable extremely cytotoxic drugs to be used.

Antibody-delivered drugs and toxins are poised to become important classes of cancer therapeutics. These biopharmaceuticals have potential in this field, as they can selectively direct highly potent cytotoxic agents to cancer cells that present tumorassociated surface markers, thereby minimizing systemic toxicity. The activity of some conjugates is of particular interest receiving increasing attention, thanks to very promising clinical trial results in hematologic cancers. Over forty antibody-drug conjugates and six immunotoxins now in clinical trials, as well as some recently approved drugs, support the maturity of this approach.

This chapter focuses on recent advances in the development of these two classes of biopharmaceuticals: conventional toxins and anticancer drugs are described, together with their mechanisms of action. The processes of conjugation and purification, as reported in the literature and in several patents, are discussed and the most relevant results in clinical trials are listed. Innovative technologies and preliminary results on novel drugs and toxins, as reported in the literature and in recently-published patents (up to January 2015) are lastly examined.