Breast metastasis and lung large-cell neuroendocrine carcinoma: first clinical observation.

BACKGROUND AND AIMS: The lung large-cell neuroendocrine carcinoma (LCNEC) is a very rare aggressive neuroendocrine tumor with a high propensity to metastasize and very poor prognosis. We report an atypical presentation of lung LCNEC was diagnosed from a metastatic nodule on the breast. METHODS: Our patient is a 59-years-old woman that presented in March 2014 nonproductive cough. A CT scan showed multiple brain, lung, adrenal gland and liver secondary lesions; moreover, it revealed a breast right nodule near the chest measuring 1.8 cm. The breast nodule and lung lesions were biopsied and their histology and molecular diagnosis were LCNEC of the lung. To our knowledge, this is the first documented case of breast metastasis from LCNEC of the lung. RESULTS: Furthermore, breast metastasis from extramammary malignancy is uncommon and its diagnosis is difficult but important for proper management and prediction of prognosis. Therefore, a careful clinical history with a thorough clinical examination is needed to make the correct diagnosis. Moreover, metastasis to the breast should be considered in any patient with a known primary malignant tumor history who presents with a breast lump. Anyhow, pathological examination should be performed to differentiate the primary breast cancer from metastatic tumor. CONCLUSION: Therefore, an accurate diagnosis of breast metastases may not only avoid unnecessary breast resection, more importantly it is crucial to determine an appropriate and systemic treatment.

Old Tyrosine Kinase Inhibitors and Newcomers in Gastrointestinal Cancer Treatment.

Gastrointestinal cancer treatment is based more on molecular biology that has provided increasing knowledge about cancer pathogenesis on which targeted therapy is being developed. Precisely, targeted therapy is defined as a "type of treatment that uses drugs, such as monoclonal antibodies or tyrosine kinase inhibitors, to identify and attack specific cancer cells". Nowadays, the United States Food and Drug Administration has approved many targeted therapies for gastrointestinal cancer treatment, as many are in various phases of development as well. In a previous review we discussed the main monoclonal antibodies used and studied in gastrointestinal cancer. In addition to monoclonal antibodies, tyrosine kinase inhibitors represent another class of targeted therapy and following the approval of imatinib for gastrointestinal stromal tumours, other tyrosine kinase inhibitors have been approved for gastrointestinal cancers treatment such as sunitinib, regoragenib, sorafenib and erlotinib. Moving forward, the purpose of this review is to focus on the efficacy data of main tyrosine kinase inhibitors commonly used in the personalized treatment of each gastrointestinal tumour and to provide a comprehensive overview about experimental targeted therapies ongoing in this setting.

Triple-negative breast cancer: new perspectives for targeted therapies.

Breast cancer is a heterogeneous disease, encompassing a large number of entities showing different morphological features and having clinical behaviors. It has became apparent that this diversity may be justified by distinct patterns of genetic, epigenetic, and transcriptomic aberrations. The identification of gene-expression microarray-based characteristics has led to the identification of at least five breast cancer subgroups: luminal A, luminal B, normal breast-like, human epidermal growth factor receptor 2, and basal-like. Triple-negative breast cancer is a complex disease diagnosed by immunohistochemistry, and it is characterized by malignant cells not expressing estrogen receptors or progesterone receptors at all, and human epidermal growth factor receptor 2. Along with this knowledge, recent data show that triple-negative breast cancer has specific molecular features that could be possible targets for new biological targeted drugs. The aim of this article is to explore the use of new drugs in this particular setting, which is still associated with poor prognosis and high risk of distant recurrence and death.

Clinical validation of a new algorithm for computerized dosing of vitamin K antagonist therapy: a retrospective simulation study.

The number of patients on oral anticoagulant therapy has increased in recent years, and this trend is expected to continue. The increased workload for physicians has led to the development of computerized systems to make organizational workflow more efficient. These programs may include algorithms to propose a weekly dosage and timing for the following visit. Before introducing a new algorithm in clinical practice, its safety and efficacy must be validated. We undertook a retrospective simulation study to test a new algorithm for the TAOnet system. The main outcome was the percentage of concordant and discordant proposals between manual- and algorithm-based prescriptions. Pairs of computerized and physician prescriptions were assessed. They were categorized as 0.1-5, 5.1-10 and >10% if the dose was different, and assigned as "algorithm better" or "manual better" dependent upon the subsequent international normalized ratio value. In 61.0% of cases, the manual and computerized weekly dosage assignments were identical; in 15.3% of cases, the difference was between 0.1 and 5%; in 14.7 of cases, it was between 5.1 and 10%; and in 9.0% of cases, it was >10%. The algorithm did better in 43.9% of discordant pairs, generally due to less frequent under-dosing. In conclusion, the new algorithm proved to consistently overlap with the manual method. The algorithm is useful but must be tested in a multi-center, prospective, interventional study.

Current approach in the treatment of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common malignant hepatobiliary disease; it is responsible for about 1 million deaths per year. Risk factors include hepatitis B and C, hepatic cirrhosis, including alcohol related hepatitis, metabolic and nutritional hepatic damage. The main modality of diffusion is intrahepatic in the natural course of the disease. There are two leading types of treatment: local and systemic. Surgical resection and liver transplantation constitute the most appropriate local treatments and are considered the only real possibility for recovery. Other local approaches include: radiofrequency ablation, percutaneous ethanol ablation, hepatic endoarterial chemoembolization and intrahepatic radiotherapy (SIRT: selective internal radiation therapy). These last treatments are used to control the disease when surgery or transplantation is not achievable; in some cases they are able to prolong survival while they constitute mainly a palliative treatment. Systemic treatments include: chemotherapy, immunological and hormonal therapies and, more recently, the introduction of new specific molecular target drugs. At the moment, in this group, the only drug that has given positive results during phase III trials (SHARP study) is Sorafenib. Sorafenib represents the only primary systemic therapy that has demonstrated, unlike the other treatments previously described, an increase in survival rate in patients affected with advanced HCC. Currently, other studies are taking place that are further developing the potential of this drug. These studies, including phase III trials, are directed in order to test the activity and safety of new emerging drugs with targeted activity. Examples of these new agents are: Sunitinib, Gefitinib, Cetuximab, Bevacizumab and Erlotinib.