[25 Years from Di Bella affair: what ethical lessons does it leave us?] / 25 Años del asunto Di Bella: ¿qué enseñanzas éticas nos deja?

Twenty-five years ago, in 1998, the Italian Parliament approved to implement clinical trials in patients with advanced cancer to know the efficacy of an alternative cancer treatment that associated hormones, vitamins and, occasionally, chemotherapy proposed by Professor Luigi Di Bella. It was the answer to people demanding Public Health assume the cost of this therapy. Although parallel phase II trials in various tumors demonstrated the lack of activity, some professionals have continued to use this method since then and have published apparently promising results a few various scientific journals. This real example raises three interesting ethical scenarios. The first one is the ethics of alternative treatments proposed by medical professionals or from the academic field. In these cases, the difficulty in differentiating between hypothesis and real efficacy. This problem impacts on patients and relatives' expectations who must face a potentially fatal disease with little or no hope of a cure with traditional treatments. The second scenario is the design and good practice in the development of clinical trials, which was also the subject of debate in relation to the Di Bella method. And the last one, the ethics of scientific publications. Di Bella's followers published since 2000 12 papers with limited quality on series of patients treated with his method, the majority in a pay-per-publication journal of which Giuseppe Di Bella, son of Professor Di Bella, is included in the board of editors.

Development of psoriatic arthritis during nivolumab therapy for metastatic non-small cell lung cancer, clinical outcome analysis and review of the literature.

Lung cancer is the leading cause of cancer-related death worldwide. The most common type, non-small cell lung cancer (NSCLC), is further divided into two main types, squamous cell and non-squamous cell (which includes adenocarcinoma). Nivolumab, a fully human IgG4 programmed death-1 immune checkpoint inhibitor antibody, has shown not only an overall survival advantage when compared to docetaxel, but also a relatively good side-effect profile among patients with previously treated advanced squamous and non-squamous NSCLC. Psoriatic arthritis (PsA), a heterogeneous chronic inflammatory disease, has a wide clinical spectrum and a variable clinical course that affects mainly musculoskeletal structures, skin and nails. Here we report the second case to the best of our knowledge of PsA development during nivolumab therapy. It is important to note that arthritis activity decreased without nivolumab discontinuation with the use of naproxen and a low dose of corticosteroid. Furthermore, a minimal disease activity was achieved adding methotrexate to the treatment and antitumor therapy efficacy was not influenced (a partial response was documented after eight and 39 cycles of nivolumab). Rheumatic immune-related adverse events management is a challenge and a coordinated multidisciplinary management by medical oncologists, rheumatologists and immunologists will be mandatory in the near future.

[Do we need a more precise definition of what sedation is?]. / ¿Es Necesario Precisar el Concepto de Sedación?

Palliative sedation in defined as the deliberate reduction in the level of consciousness of the patient by administering the appropriate drugs in order to avoid intense suffering caused by one or more refractory symptoms; sedation in the patient who is in his last days or hours of life is assumed to be continuous and as deep as needed. Clinical experience shows specific situations where it is likely that there is some confusion of terms. We could erroneously understand as palliative sedation the cases of symptomatic treatment of hyperactive delirium in a patient in its last days (a situation that sometimes is presented as the first cause of palliative sedation) or those in which it is carried out a progressive increase in the palliative treatment that often have a sedative effect, parallel to the increased severity of symptoms because of disease progression in severe ill patients. In both scenarios, sedating drugs are used to relieve end-of-life clinical complications and suffering but the circumstances of the patient, the goal of these treatments, and the way they are used do not match the definition of sedation.

[Venous thrombosis of atypical location in patients with cancer]. / Trombosis venosa de localización atípica en pacientes con cáncer.

Venous thromboembolism (VTE) is a complication that frequently occurs in patients with neoplastic diseases. Several models have therefore been developed to identify patient subgroups diagnosed with cancer who are at increased risk of developing VTE. The most common forms of thromboembolic episodes are deep vein thrombosis in the lower limbs and pulmonary thromboembolism. However, venous thrombosis is also diagnosed in atypical locations. There are few revisions of unusual cases of venous thrombosis. In most cases, VTE occurs in the upper limbs and in the presence of central venous catheters, pacemakers and defibrillators. We present the case of a patient diagnosed with breast cancer and treated with surgery, chemotherapy and radiation therapy who developed a thrombosis in the upper limbs (brachial and axillary).

Signet-ring cell carcinoma presenting in the uterine cervix: report of a primary and 2 metastatic cases.

Signet-ring cell carcinoma presenting in the uterine cervix is an uncommon neoplasm. It is usually a metastasis from a primary gastric tumor; only rarely, cervical involvement is the first manifestation of the disease. Primary signet-ring carcinoma of the cervix is extremely unusual, and it is always necessary to rule out a metastatic neoplasm. We report 3 cases of signet-ring cell carcinoma diagnosed in cervical biopsies. All cases were initially considered as metastatic, but a primary site other than the cervix could be confirmed in only 2 cases. Although autopsy was not authorized, a very comprehensive clinical workup and the evolution of the disease support the interpretation of the third case as a primary neoplasm. Primary signet-ring cell carcinoma of the cervix is an extraordinary event-the diagnosis of which requires excluding a metastasis from the gastrointestinal tract (usually the stomach), the ovary, or the breast.