25 años del asunto di bella: ¿qué enseñanzas éticas nos deja? / 25 years from di bella affair: what ethical lessons does it leave us?

Hace 25 años, en 1998, ante la demanda de que la Sanidad Pública asumiera el coste del tratamiento alternativo del cáncer propuesto por el Profesor Luigi Di Bella -que incluía hormonas, vitaminas y, en ocasiones, quimioterapia- el Parlamento italiano aprobó realizar ensayos clínicos con pacientes oncológicos avanzados para conocer la eficacia de esta terapia. Aunque los estudios en fase II paralelos que se llevaron a cabo en diversos tumores demostraron la falta de actividad del esquema, algunos profesionales han seguido empleándolo desde entonces y han publicado unos resultados aparentemente prometedores en diversas revistas científicas. Este ejemplo real plantea tres escenarios éticos interesantes. El primero es el de la ética de los tratamientos alternativos propuestos por profesionales de la medicina o del ámbito académico que no consiguen distinguir entre hipótesis y eficacia real, algo que influye también en las ex pectativas que genera en pacientes y familiares que deben afrontar una patología potencialmente mortal con pocas o ninguna expectativa de curación con los tratamientos tradicionales. El segundo escenario es el del diseño de ensayos clínicos y la buena práctica para llevarlos a cabo, que fue también motivo de debate en relación con el método Di Bella. Y el último, la ética de las publicaciones científicas. Desde el año 2000, los seguidores de Di Bella han publicado 13 trabajos de calidad limitada con series de pacientes, la mayoría de ellos en una revista de pago por publicación en cuyo comité de editores se encuentra Giuseppe Di Bella, hijo del profesor Di Bella (AU)

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 pro fessionals 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 (AU)

[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.

¿Es necesario precisar el concepto de sedación? / Do we need a more precise definition of what sedation is?

La sedación paliativa se define como la disminución deliberada del nivel de conciencia del enfermo mediante la administración de los fármacos apropiados con el objeto de evitar un sufrimiento intenso causado por uno o más síntomas refractarios; la sedación en la agonía se asume como continua y tan profunda como sea necesario. La experiencia clínica muestra situaciones concretas donde es probable que exista una cierta confusión de términos. Así, se pueden entender de manera errónea como sedación paliativa los casos de tratamiento sintomático del delirium hiperactivo en la etapa de últimos días (una situación que se presenta a menudo como la primera causa de sedación en agonía) o aquellos en que se lleva a cabo un aumento progresivo de la medicación paliativa, que con frecuencia puede tener un efecto sedante, paralelo a la mayor intensidad de los síntomas en enfermos con un deterioro severo debido a la progresión de la enfermedad. En ambos casos se emplean fármacos con efecto sedante para aliviar las complicaciones clínicas y el sufrimiento en un enfermo que tiene la muerte cercana pero las circunstancias del enfermo, el objetivo de estos tratamientos y el modo en que se emplean no coinciden con la definición de sedación paliativa

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 sedatio

[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).

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

La enfermedad tromboembólica venosa (ETEV) es una complicación que se presenta con frecuencia en los pacientes con enfermedades neoplásicas; por ello se han desarrollado varios modelos para identificar subgrupos de pacientes diagnosticados de cáncer con riesgo aumentado de desarrollar ETEV. Las localizaciones más frecuentes de los episodios tromboembólicos son la trombosis venosa profunda en miembros inferiores y la tromboembolia pulmonar, sin olvidar que se diagnostican trombosis venosas en localizaciones atípicas. Apenas hay revisiones sobre trombosis venosas inusuales; en la mayoría de los casos, la localización más frecuente es en miembros superiores y en relación con la presencia de catéteres venosos centrales, marcapasos y desfibriladores. Presentamos el caso de una paciente diagnosticada de cáncer de mama y tratada con cirugía, quimioterapia y radioterapia que presentó una trombosis en miembros superiores (humeral y axilar) (AU)

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) (AU)

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.