Review of imaging techniques for evaluating morphological and functional responses to the treatment of bone metastases in prostate and breast cancer

Bone metastases are very common complications associated with certain types of cancers that frequently negatively impact the quality of life and functional status of patients; thus, early detection is necessary for the implementation of immediate therapeutic measures to reduce the risk of skeletal complications and improve survival and quality of life. There is no consensus or universal standard approach for the detection of bone metastases in cancer patients based on imaging. Endorsed by the Spanish Society of Medical Oncology (SEOM), the Spanish Society of Medical Radiology (SERAM), and the Spanish Society of Nuclear Medicine and Molecular Imaging (SEMNIM) a group of experts met to discuss and provide an up-to-date review of our current understanding of the biological mechanisms through which tumors spread to the bone and describe the imaging methods available to diagnose bone metastasis and monitor their response to oncological treatment, focusing on patients with breast and prostate cancer. According to current available data, the use of next-generation imaging techniques, including whole-body diffusion-weighted MRI, PET/CT, and PET/MRI with novel radiopharmaceuticals, is recommended instead of the classical combination of CT and bone scan in detection, staging and response assessment of bone metastases from prostate and breast cancer.

Review of imaging techniques for evaluating morphological and functional responses to the treatment of bone metastases in prostate and breast cancer.

Bone metastases are very common complications associated with certain types of cancers that frequently negatively impact the quality of life and functional status of patients; thus, early detection is necessary for the implementation of immediate therapeutic measures to reduce the risk of skeletal complications and improve survival and quality of life. There is no consensus or universal standard approach for the detection of bone metastases in cancer patients based on imaging. Endorsed by the Spanish Society of Medical Oncology (SEOM), the Spanish Society of Medical Radiology (SERAM), and the Spanish Society of Nuclear Medicine and Molecular Imaging (SEMNIM) a group of experts met to discuss and provide an up-to-date review of our current understanding of the biological mechanisms through which tumors spread to the bone and describe the imaging methods available to diagnose bone metastasis and monitor their response to oncological treatment, focusing on patients with breast and prostate cancer. According to current available data, the use of next-generation imaging techniques, including whole-body diffusion-weighted MRI, PET/CT, and PET/MRI with novel radiopharmaceuticals, is recommended instead of the classical combination of CT and bone scan in detection, staging and response assessment of bone metastases from prostate and breast cancer.Clinical trial registration: Not applicable.

Pneumatosis intestinalis in a radioactive iodine-refractory metastasic thyroid papillary carcinoma with BRAFV600E mutation treated with dabrafenib-trametinib: a case report.

BACKGROUND: Pneumatosis intestinalis (PI) is a rare entity which refers to the presence of gas within the wall of the small bowel or colon which is a radiographic sign. The etiology and clinical presentation are variable. Patients with PI may present either with chronic mild non-specific symptoms or with acute abdominal pain with peritonitis. Some cases of intestinal pneumatosis have been reported as adverse events of new oncological treatments such as targeted therapies that are widely used in multiple tumors. CASE PRESENTATION: A 59-year-old caucasian female with radioactive iodine-refractory metastatic thyroid papillary carcinoma with BRAFV600E mutation was treated with dabrafenib and trametinib as a compassionate use. After 4 months treatment, positron emission tomography-computed tomography (PET-CT) showed PI. At the time of diagnosis, the patient was asymptomatic without signs of peritonitis. The initial treatment was conservative and no specific treatment for PI was needed. Unfortunately, after dabrafenib-trametinib withdrawal, the patient developed tumor progression with significant clinical worsening. CONCLUSIONS: This case report is, in our knowledge, the first description of PI in a patient treated with dabrafenib-trametinib. Conservative treatment is feasible if there are no abdominal symptoms.

[How does one die from SARS-CoV-2 infection? Analysis of the death process in patients admitted to an acute hospital]. / ¿Cómo se fallece por infección por SARS-CoV-2?: Análisis del proceso de muerte en pacientes ingresados en un hospital de agudos.

INTRODUCTION: The SARS-CoV-2 pandemic has generated a mortality rate 10times higher than normal influenza according to the World Health Organization (WHO), yet they do not mention palliative care in their action guidelines on maintaining essential health services during this crisis. The aim of this study was to analyse the death process of patients who died from SARS-CoV-2 at the Hospital Costa del Sol. MATERIAL AND METHODS: Descriptive cross-sectional study of the period in which all patients who died of SARS-CoV-2 from February to April 2020 were analysed. Sociodemographic characteristics, sample characterization and a set of variables related to the death process were collected in the death event. RESULTS: A total of 16 deaths were recorded out of a total of 103 admissions positive for SARS-CoV-2. Limitation of therapeutic effort was decided in 68.8% of the patients, and admission to the intensive care unit was refused in 56.3%. Support devices had not been removed in any of the cases on the day of death, 43.8% had palliative sedation, and 18.8% were in induced coma. CONCLUSIONS: Quality standards were maintained in the death process in patients who died from SARS-CoV-2, although there were aspects that could be improved. Palliative care is an essential component of the response to SARS-CoV-2 that must be incorporated into all health care settings.

Correlation of radiological and immunochemical parameters with clinical outcome in patients with recurrent glioblastoma treated with Bevacizumab.

BACKGROUND: Some phase 2 trials had reported encouraging progression-free survival with Bevacizumab in monotherapy or combined with chemotherapy in glioblastoma. However, phase 3 trials showed a significant improvement in progression free survival without a benefit in overall survival. To date, there are no predictive biomarker of response for Bevacizumab in glioblastoma. METHODS: We used Immunochemical analysis on tumor samples and pretreatment and post-treatment perfusion-MRI to try to identify possible predictive angiogenesis-related biomarkers of response and survival in patients with glioblastoma treated with bevacizumab in the first recurrence. We analyzed histological parameters: vascular proliferation, mitotic number and Ki-67 index; molecular factors: MGMT promoter methylation, EGFR amplification and EGFR variant III; immunohistochemical: MET, Midkine, HIF1, VEGFA, VEGF-R2, CD44, Olig2, microvascular area and microvascular density; and radiological: rCBV. RESULTS: In the statistical analysis, no significant correlation of any histological, molecular, microvascular or radiological parameters could be demonstrated with the response rate, PFS or OS with bevacizumab treatment. CONCLUSION: Unfortunately, in this histopathological, molecular, immunohistochemical and neuroradiological study we did not find any predictive biomarker of response or survival benefit for Bevacizumab in glioblastoma.

Correction to: SEOM clinical guideline for treatment of kidney cancer (2017).

The conflict of interest declaration was published incorrectly in the original version.

[Modal analysis of failures and effects in intra-hospital transfers]. / Análisis modal de fallos y efectos en las transferencias intrahospitalarias.

OBJECTIVES: To identify gaps in patient safety during intra-hospital transfers. MATERIAL AND METHODS: A working group was set up and patient transfers carried out in the different healthcare areas of a hospital were identified. Using the Modal Failure and Effects Analysis (FMEA), the risks of each failure mode identified were quantified using the Risk Prioritisation Index (RPI) and establishing improvement measures for all RPIs with scores greater than 100. RESULTS: There were 31 critical points that could lead to failures / deficiencies in 20 types of transfers. A total of 35 safety improvement measures were proposed for the transfers in the different areas analysed. CONCLUSIONS: The use of FMEA has made it possible to objectify the risks for patient safety during internal hospital transfers by providing information to prioritise improvement strategies.

SEOM clinical guideline of diagnosis and management of low-grade glioma (2017).

Diffuse infiltrating low-grade gliomas include oligodendrogliomas and astrocytomas, and account for about 5% of all primary brain tumors. Treatment strategies for these low-grade gliomas in adults have recently changed. The 2016 World Health Organization (WHO) classification has updated the definition of these tumors to include their molecular characterization, including the presence of isocitrate dehydrogenase (IDH) mutation and 1p/19p codeletion. In this new classification, the histologic subtype of grade II-mixed oligoastrocytoma has also been eliminated. The precise optimal management of patients with low-grade glioma after resection remains to be determined. The risk-benefit ratio of adjuvant treatment must be weighed for each individual.

Correction to: SEOM clinical guideline of diagnosis and management of low-grade glioma (2017).

The original version of this article unfortunately contained a mistake. Figure 3 was incorrect.

SEOM clinical guideline for treatment of kidney cancer (2017).

The goal of this article is to provide recommendations about the management of kidney cancer. Based on pathologic and molecular features, several kidney cancer variants were described. Nephron-sparing techniques are the gold standard of localized disease. After a randomized trial, sunitinib could be considered in adjuvant treatment in high-risk patients. Patients with advanced disease constitute a heterogeneous population. Prognostic classification should be considered. Both sunitinib and pazopanib are the standard options for first-line systemic therapy in advanced renal cell carcinoma. Based on the results of two randomized trials, both nivolumab and cabozantinib should be considered the standard for second and further lines of therapy. Response evaluation for present therapies is a challenge.

New clinical trials regulation in Spain: analysis of royal decree 1090/2015.

The coming into force of Directive 2001/20/EC represented a step forward in harmonising clinical trial regulation in European countries, guaranteeing a uniform protection of subjects participating in clinical research across Europe. However, it led to a disproportionate increase in the bureaucratization, and thus, it became evident that procedures needed to be simplified without detriment to patient's safety. Thus, Regulation 536/2014, that repealed Directive 2001/20/EC, with the aim of decreasing the growing bureaucratization and stimulating clinical research in Europe, established simplified procedures, such as regulating a common procedure for authorising trials in Europe, the institution of strict assessment timelines, or the definition of new concepts, such as "low-intervention clinical trial". The legal form of a Regulation allowed the norm to be directly applied to Member States without the need for transposition. By means of the new Royal Decree, the national legislation is adapted to make the application of the regulation feasible and it allows the development of the aspects that the Regulation leaves to national legislation. Both documents seek to stimulate clinical research with medicinal products to foster knowledge, facilitate transparency, and reinforce subjects' safety. This will surely be the case, but with this revision, we will look at the novelties and key aspects that are most relevant to investigators and we will analyse the consequences for all parties involved in clinical research.

Classification of oligodendroglial tumors based on histopathology criteria is a significant predictor of survival--clinical, radiological and pathologic long-term follow-up analysis.

BACKGROUND: The clinical course of oligodendroglial tumors is variable and there is a lack of consensus with regard to precisely diagnose which minimal criteria are required to make a diagnosis of a high-grade oligodendrial tumor. The aims of the present study are to assess pathologic factors with prognostic significance, in addiction to clinical and neuroradiologic variables, in an attempt to identify reproducible histological parameters that are useful for classification of oligodendroglial tumors. METHODS: 80 oligodendroglial tumors diagnosed between 1977 and 2004 were analyzed. To make a diagnosis of anaplastic tumor we used reproducible parameters: endothelial proliferation, high cellularity, increased mitotic activity and necrosis. Oligoastrocytomas (mixed gliomas) were diagnosed when the astrocytic component was clearly identified as part of the neoplastic cell population. Survival univariate analysis was made constructing survival curves using Kaplan-Meier method and comparing subgroups by log-rank probability test. A Cox regression model was made for multivariable analysis. RESULTS: The histologic diagnosis was low-grade oligodendroglioma in 35 patients (43.75%), anaplastic oligodendroglioma in 23 patients (28.75%), low-grade oligoastrocytoma in 11 patients (13.75%) and anaplastic oligoastrocytoma in 11 patients (13.75%). Median overall survival of the whole series was 80 months. The median overall survival of oligodendroglioma, anaplastic oligodendroglioma, oligoastrocytoma and anaplastic oligoastrocytoma was 148, 105, 47 and 7 months, respectively (p < 0.0001). Multivariate analysis revealed that age, Karnofsky performance status, histological grade and histological diagnosis (oligodendroglioma vs. oligoastrocytoma) were independently associated with survival. CONCLUSIONS: Clear cut histopathological criteria (endothelial proliferation, high cellularity, mitotic activity and necrosis) allow to establish different oligodendroglial tumor entities with distinct survival outcome.

[Temporal lobe epilepsy. Aetiological classification in 61 paediatric patients]. / Epilepsia del lóbulo temporal. Clasificación etiológica en 61 pacientes en edad pediátrica.

INTRODUCTION: There are very few studies on the aetiology of temporal lobe epilepsy (TLE) in childhood. The purpose of the present study is to analyse the data of 61 children diagnosed with TLE, in order to describe the aetiology of TLE in children seen in a neuropaedriatic clinic. We also discuss the currently proposed classification. PATIENTS AND METHODS: A retrospective analysis was carried out on patients diagnosed with TLE. Patients consisted of 61 children less than 15 years old. RESULTS: Patients were classified into three groups: Group 1 (symptomatic temporal lobe epilepsy) consisted of 25 patients (40.98 %) with any temporal lesion on neuroimaging (tumours, malformations or infections) or significant history; Group 2 (Mesial temporal sclerosis) consisted of 17 patients (27.86 %), a history of simple and complex febrile seizure were common in this group; and Group 3 (Cryptogenic epilepsy) consisted of 19 patients (31.15 %) with no abnormalities on neuroimaging or significant history. CONCLUSION: To our knowledge, this is the largest paediatric series of childhood new-onset TLE assessed only by MRI in the literature. We have modified the previous aetiological classification in order to make the groups more realistic.

Epilepsia del lóbulo temporal. Clasificación etiológica en 61 pacientes en edad pediátrica / Temporal lobe epilepsy. Aetiological classification in 61 paediatric patients

Introducción. La etiología de la epilepsia del lóbulo temporal (ELT) en la edad pediátrica se ha descrito en escasas ocasiones. El propósito de este estudio es analizar el diagnóstico etiológico de 61 pacientes con ELT atendidos en una consulta de neurología infantil. Analizamos y comentamos la clasificación actual. Pacientes y métodos. Se trata de un estudio de carácter retrospectivo, en el que se incluyó a 61 pacientes con ELT. Resultados. Los pacientes fueron clasificados en tres grupos en función del diagnóstico etiológico: grupo 1 (ELT sintomática), incluye a 25 pacientes (40,98 %) con lesiones en el lóbulo temporal (malformación, tumor o infección) o antecedentes significativos para presentar epilepsia; grupo 2 (esclerosis mesial temporal [EMT]), incluye a 17 pacientes (27,86 %), el antecedente de crisis febriles (tanto simples como complejas) se encontraba presente en un porcentaje elevado de pacientes con EMT; grupo 3 (ELT criptogénica), incluye a 19 pacientes (31,15 %), sin hallazgos patológicos en la resonancia magnética (RM) craneal o antecedentes significativos. Conclusión. Hasta la fecha, es la mayor serie que analiza, mediante RM, la etiología de la ELT de comienzo en la edad pediátrica. Hemos pretendido matizar la clasificación etiológica más aceptada, con el propósito de hacer grupos más flexibles y realistas

Introduction. There are very few studies on the aetiology of temporal lobe epilepsy (TLE) in childhood. The purpose of the present study is to analyse the data of 61 children diagnosed with TLE, in order to describe the aetiology of TLE in children seen in a neuropaedriatic clinic. We also discuss the currently proposed classification. Patients and methods. A retrospective analysis was carried out on patients diagnosed with TLE. Patients consisted of 61 children less than 15 years old. Results. Patients were classified into three groups: Group 1 (symptomatic temporal lobe epilepsy) consisted of 25 patients (40.98 %) with any temporal lesion on neuroimaging (tumours, malformations or infections) or significant history; Group 2 (Mesial temporal sclerosis) consisted of 17 patients (27.86 %), a history of simple and complex febrile seizure were common in this group; and Group 3 (Cryptogenic epilepsy) consisted of 19 patients (31.15 %) with no abnormalities on neuroimaging or significant history. Conclusion. To our knowledge, this is the largest paediatric series of childhood new-onset TLE assessed only by MRI in the literature. We have modified the previous aetiological classification in order to make the groups more realistic

[The pathophysiology of migraine. Reflections on the glutamatergic hypothesis]. / Fisiopatologia de la migrana. Reflexiones sobre la hipotesis glutamatergica.

INTRODUCTION AND DEVELOPMENT: Migraine is an episodic primary headache defined by its clinical characteristics. Several pathophysiological hypotheses have been put forward in an attempt to explain the mechanism by which headaches develop in patients suffering from migraine. We believe that there are enough data available to consider that in the cerebral cortex, and in certain situations, there may be either an alteration in the balance of glutamate in the extracellular space or generation of excitatory post-synaptic potentials at rest based on the activation of slightly increased AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) and kainate receptors, which would account for the cortical hyperexcitability and the interictal changes observed in patients with migraine. CONCLUSIONS: Further knowledge about the mechanisms that start and trigger migraines is essential for the development of new therapeutic approaches.

Fisiopatología de la migraña. Reflexiones sobre la hipótesis glutamatérgica / The pathophysiology of migraine. Reflections on the glutamatergic hypothesis

Introducción y desarrollo. La migraña es una cefaleaprimaria episódica definida por sus características clínicas. Variashan sido las hipótesis fisiopatológicas que han intentado explicarel mecanismo por el cual se desarrolla la cefalea en los pacientesmigrañosos. Creemos que existen datos suficientes como para considerarque en la corteza cerebral, y ante determinadas situaciones,puede existir o bien una alteración en el balance de glutamatoen el espacio extracelular, o bien una generación de potencialespostsinápticos excitatorios en reposo, a partir de la activación dereceptores AMPA (ácido alfa-amino-3-hidroxi-5-metil-4-isoxazolpropiónico)y kainato, ligeramente aumentados, que explicarían lahiperexcitabilidad cortical y los cambios interictales observadosen los pacientes migrañosos. Conclusión. El conocimiento de losmecanismos por los que se inicia y desencadena la migraña resultafundamental para desarrollar nuevos abordajes terapéuticos

Introduction and development. Migraine is an episodic primary headache defined by its clinical characteristics.Several pathophysiological hypotheses have been put forward in an attempt to explain the mechanism by which headachesdevelop in patients suffering from migraine. We believe that there are enough data available to consider that in the cerebralcortex, and in certain situations, there may be either an alteration in the balance of glutamate in the extracellular space orgeneration of excitatory post-synaptic potentials at rest based on the activation of slightly increased AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) and kainate receptors, which would account for the cortical hyperexcitabilityand the interictal changes observed in patients with migraine. Conclusions. Further knowledge about the mechanisms thatstart and trigger migraines is essential for the development of new therapeutic approaches

[Topiramate in comorbid disorders: epilepsy and migraine]. / Topiramato en enfermedades comórbidas: epilepsia y migraña.

INTRODUCTION: With relative frequency epilepsy and migraine are associated in a same patient. Some times it is difficult to distinguish an attack of others. Reason why it would be of utility to have a treatment effective in both pathologies. It is tried to study in patients with this comorbidity, how of effective it is a drug indicated in the two pathologies, as it is topiramate. PATIENTS AND METHODS: An observational, longitudinal and prospective study is made, where 15 patients are recruited with this association, and which they were treated with topiramate. They are revaluated at three and six months of treatment. RESULTS: Significant differences are obtained (p < 0.05) in all the studied variables (severity and duration of the migraine attacks and frequency of the migraine and epileptic attacks), with a medium dose of 100 mg/day of topiramate, at the end of the study. Not serious adverse effects were observed. CONCLUSIONS: Topiramate in monotherapy seems to be a suitable treatment in patients who undergo epileptic and migrainous attacks jointly.

Topiramato en enfermedades comórbidas: epilepsia y migraña / Topiramate in comorbid disorders: epilepsy and migraine

Introducción. Con relativa frecuencia la epilepsia y lamigraña se ven asociadas en un mismo paciente. Algunas veces esdifícil distinguir unas crisis de otras. Por tanto, sería de utilidadposeer un tratamiento que fuera eficaz en ambas patologías. Sepretende estudiar la eficacia del topiramato en el tratamiento delos pacientes que padecen epilepsia y migraña. Pacientes y métodos.Se realiza un estudio observacional, longitudinal y prospectivo,donde se recoge la frecuencia de las crisis, tanto de migrañacomo epilépticas, en una serie de 15 pacientes con dicha comorbilidad,tratados con topiramato. Se reevalúan a los tres y seis mesesde tratamiento. Resultados. Se obtienen diferencias significativas(p < 0,05) en todas las variables estudiadas (intensidad y duraciónde las crisis migrañosas y frecuencia de crisis migrañosas y epilépticas),con una dosis mediana de topiramato de 100 mg/día al finalizarel estudio. No se observaron efectos adversos graves. Conclusiones.El topiramato en monoterapia parece ser un tratamientoefectivo en pacientes que sufren conjuntamente crisis epilépticas ymigrañosas

Introduction. With relative frequency epilepsy and migraine are associated in a same patient. Some times it isdifficult to distinguish an attack of others. Reason why it would be of utility to have a treatment effective in both pathologies.It is tried to study in patients with this comorbidity, how of effective it is a drug indicated in the two pathologies, as it istopiramate. Patients and methods. An observational, longitudinal and prospective study is made, where 15 patients arerecruited with this association, and which they were treated with topiramate. They are revaluated at three and six months oftreatment. Results. Significant differences are obtained (p < 0.05) in all the studied variables (severity and duration of themigraine attacks and frequency of the migraine and epileptic attacks), with a medium dose of 100 mg/day of topiramate, at theend of the study. Not serious adverse effects were observed. Conclusions. Topiramate in monotherapy seems to be a suitabletreatment in patients who undergo epileptic and migrainous attacks jointly

Miopatía sarcoidea. Presentación de dos casos y revisión de la bibliografía / Sarcoid myopathy. Report of two cases and review of the bibliography

Introducción. El 5% de los pacientes con sarcoidosis presentan complicaciones neurológicas, de las cuales la miopatía es una de las alteraciones menos comunes. Presentamos el curso clínico y la respuesta terapéutica de dos pacientes con miopatía sarcoidea. Casos clínicos. Se trata de dos mujeres de 63 y 55 años de edad, diagnosticadas con anterioridad de sarcoidosis, en un caso cutánea y oftálmica, y en la otra pulmonar, asintomáticas desde el punto de vista sistémico cuando consultan en Neurología. Ambas pacientes desarrollan una miopatía crónica (nueve meses y seis años de evolución), de predominio proximal, dolorosa y con una concentración de creatinfosfocinasa normal o ligeramente elevada. El EMG fue claramente miopático en ambas. La biopsia muscular mostró un infiltrado mononuclear con formación de granulomas no caseificantes. Las dos pacientes se trataron con prednisona; sin embargo, la respuesta terapéutica fue diferente en cada caso. Una de las pacientes presentó una importante mejoría a los pocos días, mientras que en el otro caso la enfermedad continuó estable, a pesar de añadir primero azatioprina y después metotrexato al tratamiento. Conclusiones. La sarcoidosis puede causar una miopatía crónica, de predominio proximal, que afecta principalmente a mujeres de más de 50 años. La respuesta terapéutica a esteroides e inmunosupresores varía (AU)

Introduction. 5% of patients with sarcoidosis are affected by neurological complications, of which myopathy is one of the least frequent. We report the clinical course and therapeutic response of two patients with sarcoid myopathy. Case reports. We observed two females aged 63 and 55 who were previously diagnosed with sarcoidosis, which in one case was cutaneous and ophthalmic and in the other pulmonary. Both were asymptomatic from a systemic point of view when they visited the Neurology department. Both patients developed chronic myopathy (with a history of 9 months and 6 years), which was predominantly proximal, painful and both of them had normal or slightly high levels of creatine phosphokinase. The EMG was clearly myopathic in the two patients. A muscle biopsy showed a mononuclear-cell infiltrate with the formation of noncaseating granulomas. Both patients were treated with prednisone, although the therapeutic response was different in each case. One of the patients showed an important improvement in just a few days, while in the other case the disease remained stable, despite adding, first, azathioprine and later methotrexate to the treatment. Conclusions. Sarcoidosis can cause chronic, predominantly proximal, myopathy, and chiefly affects females over 50 years of age. The therapeutic response to steroids and immunosuppressants varies from case to case (AU)