SEOM-GEMCAD-TTD clinical guidelines for the systemic treatment of metastatic colorectal cancer (2022)

Colorectal cancer; Metastatic disease; Systemic treatmentCàncer colorectal; Malaltia metastàtica; Tractament sistèmicCáncer colorrectal; Enfermedad metastásica; Tratamiento sistémicoColorectal cancer (CRC) is the second leading cause of cancer deaths in Spain. Metastatic disease is present in 15–30% of patients at diagnosis and up to 20–50% of those with initially localized disease eventually develop metastases. Recent scientific knowledge acknowledges that this is a clinically and biologically heterogeneous disease. As treatment options increase, prognosis for individuals with metastatic disease has steadily improved over recent decades. Disease management should be discussed among experienced, multidisciplinary teams to select the most appropriate systemic treatment (chemotherapy and targeted agents) and to integrate surgical or ablative procedures, when indicated. Clinical presentation, tumor sidedness, molecular profile, disease extension, comorbidities, and patient preferences are key factors when designing a customized treatment plan. These guidelines seek to provide succinct recommendations for managing metastatic CRC

Modelo de gestión en base al cuadro de mando integral, como herramienta para auditoria interna de las Asociaciones cooperativas de ahorro y crédito del municipio de San Salvador.

En El Salvador el reciente crecimiento y fortalecimiento del sector cooperativo y su alta incidencia en el mercado financiero, ha obligado que este sea más vigilado y regulado, debido a la actividad en que este se desempeña. En consecuencia, surge la necesidad de que los profesionales en contaduría pública dedicados a la labor de auditoría interna en el sector cooperativo tengan conocimiento en herramientas de evaluación empresarial, que permitan evaluar y conocer de una forma más acertada la situación actual de las cooperativas. Es por esta razón que se realizó una investigación que permitió desarrollar una herramienta de apoyo al auditor para evaluar la gestión de los riesgos y verificar el cumplimiento de objetivos estratégicos basada en el cuadro de mando integral. Por las deficiencias encontradas en la investigación respecto a la correcta evaluación de gestión de los riesgos y el alcance de los objetivos estratégicos, resulta favorable para el auditor interno contar con una herramienta que permita dar seguimiento y cumplimiento a estas actividades de una forma más eficiente. Los objetivos que se trazaron en la investigación están encaminados a que los auditores internos de las asociaciones cooperativas posean una herramienta que permita evaluar la gestión de los riesgos y el cumplimiento de objetivos mediante indicadores clave de desempeño. Para la realización del estudio se tomó de base 29 asociaciones cooperativas del municipio de San Salvador, las cuales permitieron inferir en la comprensión de la situación problemática de la población por medio del cuestionario, el cual sirvió de fuente principal de información y obtención de resultados. Se analizó cada pregunta con sus respectivas respuestas; así como también se realizó un cruce de preguntas esto con el propósito de relacionar la información y determinar el grado de concordancia que mantienen entre sí. Como resultado se obtuvo que las unidades de auditoría interna no están implementando los estándares y lineamientos del Cuadro de Mando Integral, no obstante, manifestaron su interés en la aplicación de la herramienta por considerar que estas prácticas fortalecerían la evaluación de la gestión de riesgo y del cumplimiento de objetivos estratégicos, por lo anterior se recomienda el uso del modelo expuesto por los beneficios que este conllevada para la realización de sus actividades y el aporte a los procesos de mejora continua

Caregiver Burden Domains and Their Relationship with Anxiety and Depression in the First Six Months of Cancer Diagnosis

Cancer caregiving is associated with burden and a poor psychological state. However, there is no previous information about the predictive utility of specific burden domains on anxiety and depression in the first six months after a partner’s cancer diagnosis. In a longitudinal study, 67 caregivers completed the Zarit Burden Interview (ZBI) and Hospital Anxiety and Depression Scale (HADS) at T1 (45–60 days after diagnosis) and T2 (180–200 days after diagnosis). Most of the caregivers were female (65.7%, mean age = 51.63, SD = 13.25), while patients were mostly male (56.7%). The TRIPOD checklist was applied. ZBI scores were moderate and HADS anxiety reached significant values. There were no differences in ZBI and HADS between T1 and T2. The relationship between burden, anxiety, and depression were more consistent at T2, while emotional burden at T1 were related and predicted anxiety and depression at T2. Some burden domains were related and predicted anxiety in caregivers in the first six months after partner cancer diagnosis. This information could be useful to prevent the onset of these symptoms in the first six months after diagnosis

Basal VEGF-A and ACE Plasma Levels of Metastatic Colorectal-Cancer Patients Have Prognostic Value for First-Line Treatment with Chemotherapy Plus Bevacizumab

The identification of factors that respond to anti-angiogenic therapy would represent a significant advance in the therapeutic management of metastatic-colorectal-cancer (mCRC) patients. We previously reported the relevance of VEGF-A and some components of the renin–angiotensin-aldosterone system (RAAS) in the response to anti-angiogenic therapy in cancer patients. Therefore, this prospective study aims to evaluate the prognostic value of basal plasma levels of VEGF-A and angiotensin-converting enzyme (ACE) in 73 mCRC patients who were to receive bevacizumab-based therapies as a first-line treatment. We found that high basal VEGF-A plasma levels were significantly associated with worse overall survival (OS) and progression-free survival (FPS). On the other hand, low ACE levels were significantly associated with poor OS. Importantly, a simple scoring system combining the basal plasma levels of VEGF-A and ACE efficiently stratified mCRC patients, according to OS, into high-risk or low-risk groups, prior to their treatment with bevacizumab. In conclusion, our study supports that VEGF-A and ACE may be potential biomarkers for selecting those mCRC patients who will most benefit from receiving chemotherapy plus bevacizumab treatment in first-line therapy. Additionally, our data reinforce the notion of a close association between the RAAS and the anti-angiogenic response in cancer

Clinical Utility of microRNAs in Exhaled Breath Condensate as Biomarkers for Lung Cancer.

This study represents a novel proof of concept of the clinical utility of miRNAs from exhaled breath condensate (EBC) as biomarkers of lung cancer (LC). Genome-wide miRNA profiling and machine learning analysis were performed on EBC from 21 healthy volunteers and 21 LC patients. The levels of 12 miRNAs were significantly altered in EBC from LC patients where a specific signature of miR-4507, miR-6777-5p and miR-451a distinguished these patients with high accuracy. Besides, a distinctive miRNA profile between LC adenocarcinoma and squamous cell carcinoma was observed, where a combined panel of miR-4529-3p, miR-8075 and miR-7704 enabling discrimination between them. EBC levels of miR-6777-5p, 6780a-5p and miR-877-5p predicted clinical outcome at 500 days. Two additional miRNA signatures were also associated with other clinical features such as stage and invasion status. Dysregulated EBC miRNAs showed potential target genes related to LC pathogenesis, including CDKN2B, PTEN, TP53, BCL2, KRAS and EGFR. We conclude that EBC miRNAs might allow the identification, stratification and monitorization of LC, which could lead to the development of precision medicine in this and other respiratory diseases

Value Of [f-18]fdg-pet/ct and Ca125, serum levels and kinetic parameters, in early detection of ovarian cancer recurrence. Influence of histological subtypes and tumor stages

To assess the diagnostic accuracy of CA125, its kinetic values and positron emission tomography/computed tomography with 2-deoxy-2-[F-18]fluoro-d-glucose ([F-18]FDG-PET/CT), in relation with tumor characteristics for suspected recurrence of ovarian cancer. To evaluate the performance of CA125-related parameters as a selection criteria to perform a [F-18]FDG-PET/CT.A retrospective analysis of 69 [F-18]FDG-PET/CT for suspected recurrence of ovarian cancer was performed. All patients had 2 measurements of CA125, before PET/CT, to calculate kinetic values, as CA125vel (CA125vel = [CA125a - CA125b]/time) and CA125dt (CA125dt = [log(2) x time]/[logCA125a - CA125b]). Maximum standard uptake value (SUVmax) was calculated. The diagnostic accuracy was calculated for all the variables and the optimal cut-off value of each of them by the receiver-operating characteristics (ROC) analysis. All the tests were compared with tumor characteristics and clinical-radiological evolution during follow-up of at least 6 months.Fifty-five cases were diagnosed of recurrence (11 with CA125<35 U/mL), while 14 showed no disease (11 with CA125< 35 U/mL). All of them were correctly cataloged by PET/CT. CA125, CA125vel, and SUVmax showed higher levels in recurrent patients (mean 129.54U/mL, 24.58U/mL per mo, and 8.69g/mL, respectively) than in nonrecurrent (mean 20.35U/mL, 0.60U/mL per mo, and 0.64g/mL, respectively). No statistical differences in CA125dt were found. Patients with recurrence of high-grade serous carcinoma (HGSC) showed higher CA125 and CA125vel, without differences in the rest of subtypes and International Federation of Gynecology and Obstetrics stages. The ROC analyses for CA125, CA125vel, and CA125dt showed an area under the curve (AUC) of 0.873 (95% confidence interval [CI] 0.77-0.969), 0.903 (95% CI 0.813-0.994), and 0.727 (95% CI 0.542-0.913), respectively, with an optimal cut-off point of 23.95U/mL, 4.49U/mL per mo, and 3.36 months, respectively, while for the SUVmax the AUC was of 0.982 (95% CI 0.948-1.000), and the cut-off point of 2. Multivariate regression analysis identified CA125 and CA125vel as predictors of recurrence.[F-18]FDG-PET/CT is more accurate than the parameters obtained from the CA125 to detect early recurrence. CA125vel is the most suitable parameter, mainly in HGSC. Levels of CA125vel 4.49U/mL per mo facilitate earlier detection by the execution of a [F-18]FDG-PET/CT. The calculation of these parameters is independent of tumor stage at diagnosis

El Pirulejo: resultados preliminares de la campaña de 1991

Se presenta un resumen de los resultados obtenidos en la excavación d l verano de 1991 en "El Pirulejo", que ha proporcionado nuevos niveles prehistóricos con sepulturas de la Edad del Bronce y nuevos materiales del Paleolítico Superior (Solutrense)

The Combination of Neutrophil–Lymphocyte Ratio and Platelet–Lymphocyte Ratio with Liquid Biopsy Biomarkers Improves Prognosis Prediction in Metastatic Pancreatic Cancer

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with a highly inflammatory microenvironment and liquid biopsy has emerged as a promising tool for the noninvasive analysis of this tumor. In this study, plasma was obtained from 58 metastatic PDAC patients, and neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), circulating cell-free DNA (cfDNA) concentration, and circulating RAS mutation were determined. We found that NLR was significantly associated with both overall survival (OS) and progression-free survival. Remarkably, NLR was an independent risk factor for poor OS. Moreover, NLR and PLR positively correlated, and combination of both inflammatory markers significantly improved the prognostic stratification of metastatic PDAC patients. NLR also showed a positive correlation with cfDNA levels and RAS mutant allelic fraction (MAF). Besides, we found that neutrophil activation contributed to cfDNA content in the plasma of metastatic PDAC patients. Finally, a multi-parameter prognosis model was designed by combining NLR, PLR, cfDNA levels, RAS mutation, RAS MAF, and CA19-9, which performs as a promising tool to predict the prognosis of metastatic PDAC patients. In conclusion, our study supports the idea that the use of systemic inflammatory markers along with circulating tumor-specific markers may constitute a valuable tool for the clinical management of metastatic PDAC patients

Circulating Cell-Free DNA-Based Liquid Biopsy Markers for the Non-Invasive Prognosis and Monitoring of Metastatic Pancreatic Cancer

Liquid biopsy may assist in the management of cancer patients, which can be particularly applicable in pancreatic ductal adenocarcinoma (PDAC). In this study, we investigated the utility of circulating cell-free DNA (cfDNA)-based markers as prognostic tools in metastatic PDAC. Plasma was obtained from 61 metastatic PDAC patients, and cfDNA levels and fragmentation were determined. BEAMing technique was used for quantitative determination of RAS mutation allele fraction (MAF) in cfDNA. We found that the prognosis was more accurately predicted by RAS mutation detection in plasma than in tissue. RAS mutation status in plasma was a strong independent prognostic factor for both overall survival (OS) and progression-free survival (PFS). Moreover, RAS MAF in cfDNA was also an independent risk factor for poor OS, and was strongly associated with primary tumours in the body/tail of the pancreas and liver metastases. Higher cfDNA levels and fragmentation were also associated with poorer OS and shorter PFS, body/tail tumors, and hepatic metastases, whereas cfDNA fragmentation positively correlated with RAS MAF. Remarkably, the combination of CA19-9 with MAF, cfDNA levels and fragmentation improved the prognostic stratification of patients. Furthermore, dynamics of RAS MAF better correlated with patients’ outcome than standard CA19-9 marker. In conclusion, our study supports the use of cfDNA-based liquid biopsy markers as clinical tools for the non-invasive prognosis and monitoring of metastatic PDAC patients

Respiratory viruses detected in Mexican children younger than 5 years old with community-acquired pneumonia: a national multicenter study

Background: Acute respiratory infections are the leading cause of mortality in children worldwide, especially in developing countries. Pneumonia accounts for 16% of all deaths of children under 5 years of age and was the cause of death of 935 000 children in 2015. Despite its frequency and severity, information regarding its etiology is limited. The aim of this study was to identify respiratory viruses associated with community-acquired pneumonia (CAP) in children younger than 5 years old. Methods: One thousand four hundred and four children younger than 5 years of age with a clinical and/or radiological diagnosis of CAP in 11 hospitals in Mexico were included. Nasal washes were collected, placed in viral medium, and frozen at �70 C until processing. The first 832 samples were processed using the multiplex Bio-Plex/Luminex system and the remaining 572 samples using the Anyplex multiplex RT-PCR. Clinical data regarding diagnosis, clinical signs and symptoms, radiographic pattern, and risk factors were obtained and recorded. Results: Of the samples tested, 81.6% were positive for viruses. Respiratory syncytial virus (types A and B) was found in 23.7%, human enterovirus/rhinovirus in 16.6%, metapneumovirus in 5.7%, parainfluenza virus (types 1–4) in 5.5%, influenza virus (types A and B) in 3.6%, adenovirus in 2.2%, coronavirus (NL63, OC43, 229E, and HKU1) in 2.2%, and bocavirus in 0.4%. Co-infection with two or more viruses was present in 22.1%; 18.4% of the samples were negative. Using biomass for cooking, daycare attendance, absence of breastfeeding, and co-infections were found to be statistically significant risk factors for the presence of severe pneumonia. Conclusions: Respiratory syncytial virus (types A and B), human enterovirus/rhinovirus, and metapneumovirus were the respiratory viruses identified most frequently in children younger than 5 years old with CAP. Co-infection was present in an important proportion of the children