Consensus of experts from the Spanish Pharmacogenetics and Pharmacogenomics Society and the Spanish Society of Medical Oncology for the genotyping of DPYD in cancer patients who are candidates for treatment with fluoropyrimidines.

5-Fluorouracil (5-FU) and oral fluoropyrimidines, such as capecitabine, are widely used in the treatment of cancer, especially gastrointestinal tumors and breast cancer, but their administration can produce serious and even lethal toxicity. This toxicity is often related to the partial or complete deficiency of the dihydropyrimidine dehydrogenase (DPD) enzyme, which causes a reduction in clearance and a longer half-life of 5-FU. It is advisable to determine if a DPD deficiency exists before administering these drugs by genotyping DPYD gene polymorphisms. The objective of this consensus of experts, in which representatives from the Spanish Pharmacogenetics and Pharmacogenomics Society and the Spanish Society of Medical Oncology participated, is to establish clear recommendations for the implementation of genotype and/or phenotype testing for DPD deficiency in patients who are candidates to receive fluoropyrimidines. The genotyping of DPYD previous to treatment classifies individuals as normal, intermediate, or poor metabolizers. Normal metabolizers do not require changes in the initial dose, intermediate metabolizers should start treatment with fluoropyrimidines at doses reduced to 50%, and poor metabolizers are contraindicated for fluoropyrimidines.

Metaplasia sinovial capsular mamaria: a propósito de un caso / Mammary capsular synovial metaplasia: a case report

La metaplasia sinovial capsular mamaria es una patología poco frecuente, de origen desconocido, que se presenta generalmente con aumento de volumen mamario (colección líquida) en un período breve y frecuentemente unilateral el posoperatorio (3 meses o más). Su diagnóstico se realiza por punción con aguja fina guiada por ecografía y estudios histomorfológico y de inmunohistoquímica. Debe diferenciarse del linfoma anaplásico de células grandes asociado a implantes mamarios. El tratamiento consiste en extracción por punción de la colección líquida, reposo del brazo del lado afectado y en caso de recidivas cambio de implante e instilación de corticoides en bolsillo capsular. Presentación a propósito de un caso.

Breast capsular Synovial Metaplasia is a rare pathology of unknown origin, which usually occurs with increased breast volume (liquid collection) in a short and often unilateral postoperatively (3 months or more). Diagnosis is made with fine needle puncture guided by ultrasound and histomorphological and immunohistochemistry studies. It should differ from anaplastic large cell lymphoma associated with breast implants. Treatment consists of puncture extraction of the liquid collection, rest of the arm of the affected side and in case of relapses implant change and installation of Corticoids in capsular pocket. Filing on a case

Introducing FDG PET/CT-guided chemoradiotherapy for stage III NSCLC in low- and middle-income countries: preliminary results from the IAEA PERTAIN trial.

PURPOSE: Patients with stage III non-small-cell lung cancer (NSCLC) treated with chemoradiotherapy (CRT) in low- and middle-income countries (LMIC) continue to have a poor prognosis. It is known that FDG PET/CT improves staging, treatment selection and target volume delineation (TVD), and although its use has grown rapidly, it is still not widely available in LMIC. CRT is often used as sequential treatment, but is known to be more effective when given concurrently. The aim of the PERTAIN study was to assess the impact of introducing FDG PET/CT-guided concurrent CRT, supported by training and quality control (QC), on the overall survival (OS) and progression-free survival (PFS) of patients with stage III NSCLC. METHODS: The study included patients with stage III NSCLC from nine medical centres in seven countries. A retrospective cohort was managed according to local practices between January 2010 and July 2014, which involved only optional diagnostic FDG PET/CT for staging (not for TVD), followed by sequential or concurrent CRT. A prospective cohort between August 2015 and October 2018 was treated according to the study protocol including FDG PET/CT in treatment position for staging and multimodal TVD followed by concurrent CRT by specialists trained in protocol-specific TVD and with TVD QC. Kaplan-Meier analysis was used to assess OS and PFS in the retrospective and prospective cohorts. RESULTS: Guidelines for FDG PET/CT image acquisition and TVD were developed and published. All specialists involved in the PERTAIN study received training between June 2014 and May 2016. The PET/CT scanners used received EARL accreditation. In November 2018 a planned interim analysis was performed including 230 patients in the retrospective cohort with a median follow-up of 14 months and 128 patients in the prospective cohort, of whom 69 had a follow-up of at least 1 year. Using the Kaplan-Meier method, OS was significantly longer in the prospective cohort than in the retrospective cohort (23 vs. 14 months, p = 0.012). In addition, median PFS was significantly longer in the prospective cohort than in the retrospective cohort (17 vs. 11 months, p = 0.012). CONCLUSION: In the PERTAIN study, the preliminary results indicate that introducing FDG PET/CT-guided concurrent CRT for patients with stage III NSCLC in LMIC resulted in a significant improvement in OS and PFS. The final study results based on complete data are expected in 2020.

Impact of International Atomic Energy Agency support to the development of nuclear cardiology in low-and-middle-income countries: Case of Latin America and the Caribbean.

Cardiovascular diseases (CVDs) are the leading cause of death in Latin America and the Caribbean (LAC) region as well as worldwide. Lifestyle, nutritional habits and the upsurge of obesity have contributed to the increase in the prevalence of CVDs in the region. The role of nuclear cardiology in the management of patients with CVDs is well established. Particularly, myocardial perfusion imaging is widely used in LAC countries and has been increasingly integrated into the healthcare systems in the region for the diagnosis of coronary artery disease, risk stratification and to guide patient management. In its role to support countries around the world to address their health needs through the peaceful applications of nuclear techniques, the International Atomic Energy Agency (IAEA) has provided assistance to the LAC region for the establishment and strengthening of the nuclear cardiology practice. To that extent, the IAEA provides support in building capacities of multidisciplinary teams of professionals, the provision of medical equipment and the promotion of communication and exchange of knowledge among the different stakeholders. In addition, the IAEA encourages the participation of nuclear medicine centers in international multi-center research studies. In this paper, we present some of the projects through which the IAEA has supported the LAC region, including regional technical cooperation projects and coordinated research projects related to cardiology within the current multimodality approach to cardiac imaging.

SEOM clinical guidelines for diagnosis and treatment of metastatic colorectal cancer (2018).

Colorectal cancer (CRC) is the second cause of cancer death in Spain, the objective of this guide published by the Spanish Society of Medical Oncology is to develop a consensus for the diagnosis and management of metastatic disease. The optimal treatment strategy for patients with metastatic CRC should be discussed in a multidisciplinary expert team to select the most appropriate treatment, and integrate systemic treatment and other options such as surgery and ablative techniques depending on the characteristics of the tumour, the patient and the location of the disease and metastases.

Appropriate use of noninvasive ischemia testing to guide revascularization decision making following acute ST elevation myocardial infarction in Latin American countries: Results from an expert panel meeting of the International Atomic Energy Agency. / Uso adecuado de las pruebas no invasivas de isquemia para guiar la toma de decisión sobre revascularización tras un infarto agudo de miocardio con elevación del segmento ST en países iberoamericanos: Resultados de la reunión de un panel de expertos de la International Atomic Energy Agency.

Across Latin American and Caribbean countries, cardiovascular disease and especially ischemic heart disease is currently the main cause of death both in men and in women. For most Latin American and Caribbean countries, public and community health efforts aim to define care strategies which are both clinically and cost effective and promote primary and secondary prevention, resulting in improved patient outcomes. The optimal approach to deal with acute events such as ST-elevation myocardial infarction (STEMI) is a matter of controversy; however, there is an expanding role for assessing residual ischemic burden in STEMI patients following primary percutaneous coronary intervention. Although randomized clinical trials have established the value of staged fractional flow reserve-guided revascularization, the use of noninvasive functional imaging modalities may play a similar role at a much lower cost. For LAC, available stress imaging techniques could be applied to define residual ischemia in the non-infarct related artery and to target revascularization in a staged procedure after primary percutaneous coronary intervention The use of nuclear cardiac imaging, supported by its relatively wide availability, moderate cost, and robust quantitative capabilities, may serve to guide effective care and to reduce subsequent cardiac events in patients with coronary artery disease. This noninvasive approach may avert potential safety issues with repeat and lengthy invasive procedures, and serve as a baseline for subsequent follow-up stress testing following the index STEMI event. This consensus document was devised from an expert panel meeting of the International Atomic Energy Agency, highlighting available evidence with a focus on the utility of stress myocardial perfusion imaging in post-STEMI patients. The document could serve as guidance to the prudent and appropriate use of nuclear imaging for targeting therapeutic management and avoiding unnecessary invasive procedures within Latin American and Caribbean countries, where resources could be scarce.

KRAS genetic variant as a prognostic factor for recurrence in resectable non-small cell lung cancer.

PURPOSE: Several angiogenic prognostic markers are under investigation because of their potential clinical utility, aiming to improve patient outcomes. We hypothesized that genetic variant in the VEGF pathway could be used as prognostic markers of survival in non-small cell lung cancer (NSCLC) patients undergoing pulmonary resection. METHODS: We evaluated the relationship between genetic variants in the VEGF pathway and relapse-free survival (RFS, main endpoint) and overall survival (OS, secondary endpoint) among 131 patients with stage I-III NSCLC treated with surgical resection from 2009 to 2013. Clinical, pathological and surgical data were prospectively collected. Twenty-five variants in sixteen relevant genes were selected and genotyped in tumor samples by real time PCR. The Kaplan-Meier method with the log-rank test and Cox's regression models were used for RFS and OS analyses. RESULTS: With a median follow-up of 36 (min = 2.8; max = 67.4) months, there were 31 (24%) relapses and 31 (24%) deaths. Overall, median RFS was not reached and median OS was 65 [95% confidence interval (CI) 56-75] months. The KRAS rs1137282 and PIK3C2A rs4356203 variants were significantly associated with RFS. For KRAS rs1137282, the 3-year RFS was 76% [95% CI 64-84%] in patients harboring an A/A genotype compared to 53% [95% CI 37-69%] in patients harboring an A/G or G/G genotype (p = 0.02). For PIK3C2A rs4356203, patients with an A/A or an A/G genotype had a 3-year RFS of 72% [95% CI 58-76%], whereas in patients with a G/G genotype was 49% [95% CI 28-70%] (p = 0.02). These associations remained statistically significant after adjusting for all the relevant clinical parameters in the multivariable analysis. CONCLUSION: Genetic variants in VEGF pathway may be associated with recurrence in stage I-III NSCLC. Specifically, the KRAS rs1137282 could be considered as a prognostic factor for recurrence in resectable NSCLC patients. Although PIK3C2A rs4356203 was associated with RFS, further analyses are necessary to confirm these data.

Prazosin vs Hidroclorotiazida en el tratamiento de la hipertensión arterial esencial leve y moderada y sus efectos sobre el metabolismo del potasio, magnesio y calcio / Prazosin vs Hidroclorotiazida in the treatment of the essential mild hypertension and its effects on potassium, magnesium and calcium metabolism

Catorce pacientes adultos (33-58 años) con HAE leve a moderada, y función renal normal, recibieron monoterapia con Prazosin (PR) o Hidroclorotiazida (HCTZ) después de respectivas Fases de Placebo I y II, (PI), (PII) en forma controlada y cruzada. La PAs/d (mmHg), en posición supina, después de PI fue: 162.7 (6.4)/103.2 (3.4) y con PR descendió 142.0 (6.9)/88.9 (4.2) a las 8 semanas (p<0.001) a la dosis media de 4.8 mg/dia. En PII la PA supina fue de 161.9 (5.4)/104.1 (3.6) y con HCTZ descendió a 140.1 (6.1)/90.2 (2.8) a las 8 semanas (p<0.001> a la dosis media de 51.1 mg/dia. No se observaron cambios significativos en la frecuencia cardiaca y peso corporal con PR. Con HCTZ el peso disminuyó de 78.1 (11.0) Kg a 76.6 (11.0) Kg, (p<0.05). Se evidenció una disminución de K+ y Mg+ sérico con HCTZ de 4.52 (0.35) mEq/l y 1.79 (0.2) mg/dl a 3.39 (0.27) mEq/l y 1.26 (0.13) mg/dl respectivamente (p<0.01) y un incremento del Ca sérico de 9.38 (0.65) mg/dl a 10.9 (0.24) mg/dl (p<0.05); no observándose cambios con PR. Con la HCTZ se produjo un aumento en ácido úrico y triglicéridos plasmáticos de 4.6 (1.1) mg/dl y 154.8 (38.8) mg/dl a 7.56 (1.64) mg/dl y 187.1 (44.0) mg/dl respectivamente (p<0.001 y p<0.05), con PR se observó una disminución no significativa en los triglicéridos. La Dcr (ml/min) disminuyó de 83.1 (7.3) (PII) a 77.4 (6.1) a las 8 semanas con HCTZ (p<0.025), y no se modificó con PR..