Cáncer de recto: Patrones y parámetros ecográficos útiles en la valoración de los ganglios linfáticos pararrectales

El cáncer colorrectal es el segundo tumor más frecuente en USA tras el cáncer de pulmón en hombres y el de mama en mujeres, y el más frecuente gastrointestinal. Aproximadamente 155.000 casos nuevos son diagnosticados cada año y la mayoría de esos pacientes son sometidos a cirugía, bien sea con intención curativa o paliativa El pronóstico de los pacientes con cáncer colorrectal depende fundamentalmente del estadio en que se encuentra en el momento del diagnóstico y del tratamiento inicial. Por otro lado, se trata de un cáncer cuya incidencia no desciende, como ocurre en otras neoplasias malignas, sino que está experimentando, en algunas regiones un apreciable incremento. Aunque la incidencia media anual (IMA: 10,2 x 100.000) sitúa a Aragón como una región de riesgo medio de cáncer colorrectal, se ha observado un incremento significativo de la misma (IMA: 15,6 x 100.000) (1). La supervivencia global a los 5 años del cáncer colorrectal es aproximadamente del 50 %. Para el sistema de Dukes modificado, la supervivencia a los 5 años es en el estadio A del 81 %-85 %, en el estadio B del 64 %-78 %, en el C del 27 %-33% y en el estadio D entre el 5 %-14 %. Aun cuando el grado de invasión de la pared rectal es un factor pronóstico muy importante, hay un consenso general que el factor pronóstico más importante es la presencia o ausencia de metástasis en los ganglios linfáticos. Ello refleja la diferencia de más del 50 % en la supervivencia a 5 años, entre los tumores en estadios B y C. Conclusiones El método de análisis de los ganglios linfáticos mesorrectales en pacientes con cáncer de recto mediante ecografía endorrectal y posterior tratamiento digital de las imágenes obtenidas, constituye un método exacto y reproducible. Gracias a este tratamiento de imágenes, los ganglios linfáticos pararrectales pueden ser estudiados con exactitud mediante parámetros ecográficos métricos, densitométricos y morfológicos. De todos los parámetros ecográficos métricos analizados en el estudio: el área, el perímetro, el contorno del perímetro, el diámetro mayor, el diámetro menor, el diámetro equivalente, y la elipse A y B, diferencian significativamente los ganglios metastásicos de los inflamatorios. Los parámetros densitométricos de ecogenicidad ganglionar, estudiados mediante el coeficiente de reflectancia I y II, establecen diferencias entre ganglio inflamatorio y tumoral. Tras analizar los diferentes parámetros ecográficos métricos y densitométricos mediante el análisis multivariante, los parámetros “diámetro equivalente y coeficiente de reflectancia I”, son los que proporcionan el mayor valor predictivo en la diferenciación linfática ganglionar. El test elaborado con estos dos parámetros para detectar los ganglios positivos o tumorales tiene una sensibilidad del 81,7 % y una especificidad del 84 %, con un VPP de 68,5 %, un VPN de 91,54 % y una precisión global del 83,3 %, estableciendo el punto de corte en 0,3 como alto riesgo de ser maligno. La asociación de “lobulación, ecogenicidad y reflexión hiliar” son los parámetros ecográficos morfológicos que proporcionan el mayor valor predictivo en la determinación de los ganglios linfáticos metastásicos de todos los parámetros morfológicos estudiados en el análisis multivariante. La utilización de estos tres parámetros morfológicos para elaborar el test diagnóstico, establece un punto de corte en 0,5 como alto riesgo de ser maligno. Este test tiene una sensibilidad del 99% y una especificidad del 99,1%, con un VPP de 98%, un VPN de 99,5 %, y una precisión global del 99,1%. La aplicación del sumatorio obtenido con los ocho parámetros morfológicos estudiados, nos ha permitido elaborar un test de fácil aplicación. Este test establece el punto de corte en 25 como riesgo de ser un ganglio metastásico y muestra una elevada sensibilidad (98%) y especificidad (99,1%), con un VPP del 98%, un VPN de 99,1% y una precisión global del 98,7 %.<br /

Vaspin in atherosclerotic disease and cardiovascular risk in axial spondyloarthritis: a genetic and serological study

Background: Vaspin is a novel anti-inflammatory adipokine associated with cardiovascular (CV) disease and inflammation in chronic inflammatory conditions different from axial spondyloarthritis (axSpA). Given the high incidence of CV disease (mainly due to accelerated atherosclerosis) exhibited by axSpA patients, we wondered if vaspin could also be a key molecule in this process. However, data on the role of vaspin regarding atherosclerotic disease in the context of axSpA is scarce. For this reason, we aimed to evaluate the implication of vaspin, at the genetic and serological level, in subclinical atherosclerosis and CV risk in axSpA. Methods: This study included 510 patients diagnosed with axSpA. Carotid ultrasound (US) was performed to evaluate the presence of subclinical atherosclerosis. Three vaspin gene variants (rs2236242, rs7159023, and rs35262691) were genotyped by TaqMan probes. Serum vaspin levels were assessed by enzyme-linked immunosorbent assay. Statistical analysis was performed using STATA® v.11.1. Results: Serum vaspin levels were significantly higher in female patients than in males and also in obese patients when compared to those with normal weight (p < 0.05). At the genetic level, we disclosed that the minor allele of rs2236242 (A) was associated with lower serum vaspin levels in axSpA, while the rs7159023 minor allele (A) was linked to higher serum levels (p < 0.05). When the three polymorphisms assessed were combined conforming haplotypes, we disclosed that the TGC haplotype related to high serum levels of vaspin (p = 0.01). However, no statistically significant association was observed between vaspin and markers of subclinical atherosclerosis, both at the genetic and serological level. Conclusions: Our results revealed that vaspin is linked to CV risk factors that may influence on the atherosclerotic process in axSpA. Additionally, we disclosed that serum vaspin concentration is genetically modulated in a large cohort of patients with axSpA.This work was partially supported by funds of a NEXT-VAL grant (NVAL17/10) (Instituto de Investigación Sanitaria IDIVAL) awarded to FG. RL-M is a recipient of a Miguel Servet type I programme fellowship (grant CP16/00033) from the “Instituto de Salud Carlos III” (ISCIII) and co-funded by the European Social Fund, ESF). SR-M is supported by funds of the RETICS Program (RD16/0012/0009) from ISCIII and co-funded by the European Regional Development Fund. VP-C is supported by a pre-doctoral grant from IDIVAL (PREVAL18/01). LL-G is supported by funds of a Miguel Servet type I programme fellowship from ISCIII (grant CP16/00033, co-funded by the ESF). OG is beneficiary of a grant funded by Xunta de Galicia, Consellería de Educación, Universidade e Formación Profesional and Consellería de Economía, Emprego e Industria (GAIN), GPC IN607B2019/10

Factors associated with atherosclerosis in radiographic and non-radiographic axial spondyloarthritis. A multicenter study on 838 patients

Objectives: To identify disease-related factors associated with subclinical atherosclerosis and cardiovascular (CV) events in a large series of patients with axial spondyloarthritis (axSpA) and to identify possible differences in the effect of the potential pro-atherogenic factors between ankylosing spondylitis (AS) non-radiographic axSpA (nr-axSpA). Methods: This is a cross-sectional observational study of the AtheSpAin cohort, a Spanish multicenter cohort to study atherosclerosis in axSpA. Subclinical atherosclerosis determined by carotid ultrasound included assessment of carotid intima-media thickness (cIMT) and plaque detection. Results: 639 AS and 167 nr-axSpA patients were recruited. CV risk factors (CRF) and several disease-related factors showed a statistically significant association with subclinical atherosclerosis in the crude analysis. After adjustment for age, sex, and smoking (model 1), associations remained statistically significant for spinal mobility, inflammatory bowel disease, use of prednisone, and Disease-modifying antirheumatic drugs (DMARD) when assessing carotid plaques and for acute phase reactants (APR) at diagnosis, use of prednisone, DMARD, and TNF-inhibitors when measuring cIMT. In model 2, which also included classic CRF as confounding factors to identify axSpA features with a potential independent pro-atherogenic effect, the functional status was the only variable significantly associated with plaques and the use of prednisone and APR at diagnosis with cIMT. No association differences were found between both subtypes of patients. Besides, APR at diagnosis were also associated with subsequent development of CV events that had occurred in 33 patients. Conclusion: Apart from CRF, atherosclerotic disease in AxSpA is associated with disease-related factors such as inflammatory response and disease severity, with no differences between AS and nr-axSpA

Cardiovascular and disease-related features associated with extra-articular manifestations in axial spondyloarthritis. A multicenter study of 888 patients

Objectives: To determine the potential impact of extra-articular manifestations (EAMs) on disease characteristics and cardiovascular (CV) risk in patients with axial spondylarthritis (axSpA). Methods: This is a cross-sectional study from the AtheSpAin cohort, a Spanish multicenter cohort to study atherosclerosis in axSpA. Data on the history of CV events, subclinical carotid atherosclerosis, and disease-related features, including EAMs, were collected. Results: 888 axSpA patients were recruited. Concomitant acute anterior uveitis (AAU), psoriasis (PSO), and inflammatory bowel disease (IBD) were present in 177 (19.9%), 96 (10.8%), and 57 (6.4%) patients, respectively. When compared with axSpA patients without EAMs, a significant increase in past CV events was observed in patients with PSO (9% versus 4%, p = 0.048) and in those with at least one EAM (7% versus 4%, p = 0.032) or with more than one EAM (11% versus 4%, p = 0.022). The frequency of carotid plaques and the values of cIMT were higher in patients with EAMs than in those without EAMs, although only the univariable analysis for carotid plaques in patients with PSO (39% versus 30%, p = 0.038) and for cIMT in patients with AAU (665 ± 156 µm versus 637 ± 139 µm, p = 0.042) and those with at least one EAM (661 ± 155 µm versus 637 ± 139 µm, p = 0.024) showed significant results. In addition, patients with PSO or IBD were found to have specific disease-related features, such as higher ESR at diagnosis, and more frequent use of glucocorticoids and TNF inhibitors than those without EAMs. Also, PSO patients had more commonly peripheral involvement and those with AAU more severe radiographic damage than those without EAMs. The frequency of HLA B27 was higher in patients with AAU and lower in those with PSO or IBD compared to those without EAMs. Conclusion: Patients with axSpA and EAMs, in addition to displaying their own disease-related features, are likely to have an increased CV risk that appears proportional to the number of EAMs and could be related to proatherogenic factors other than traditional CV risk factors, such as the inflammatory load and the use of glucocorticoids.Ankylosing spondylitisNon-radiographic spondyloarthritisAtherosclerosisCardiovascularExtraarticular manifestationsPsoriasisInflammatory bowel diseaseUveíti

Irisin as a Novel Biomarker of Subclinical Atherosclerosis, Cardiovascular Risk and Severe Disease in Axial Spondyloarthritis

Introduction: Patients with axial spondyloarthritis (axSpA) have a high disease burden mainly due to the rheumatic disease itself, and also exhibit accelerated atherosclerosis, that leads to a higher incidence of cardiovascular (CV) disease. Accordingly, the identification of biomarkers of CV risk and inflammation in axSpA patients is clinically relevant. In this sense, given the beneficial functions exerted by the adipomyokine irisin in processes related to CV disease and inflammation, our aim was to assess, for the first time, the role of irisin as a genetic and serological biomarker of subclinical atherosclerosis, CV risk and disease severity in axSpA patients. Methods: A large cohort of 725 Spanish patients with axSpA was included. Subclinical atherosclerosis (presence of plaques and abnormal carotid intima-media thickness values) was evaluated by carotid ultrasound. Four irisin polymorphisms (rs16835198 G/T, rs3480 A/G, rs726344 G/A, and rs1570569 G/T) were genotyped by TaqMan probes. Additionally, serum irisin levels were determined by ELISA. Results: Low irisin levels were linked to the presence of plaques (p=0.002) and atherogenic index values ?4 (p=0.01). Serum irisin were positively correlated with C-peptide levels (p2.1 (Odds Ratio (OR): 0.48 [0.28-0.83] and OR: 0.73 [0.57-0.92], respectively, p=0.01 in both cases). Additionally, the frequency of rs1570569 T allele was higher in these patients (OR: 1.46 [1.08-1.97], p=0.01). Furthermore, the GGGT haplotype was more frequent in patients with ASDAS values >2.1 (OR: 1.73 [1.13-2.66], p=0.01). Conclusions: Our results indicate that low serum irisin levels could be indicators of the presence of subclinical atherosclerosis, high CV risk and more severe disease in axSpA patients. In addition, irisin may also constitute a genetic biomarker of disease activity in axSpA.FUNDING: This work was partially supported by grants from Instituto de Investigación Sanitaria IDIVAL (NVAL17/10) and from the ‘Asociación Cántabra de Reumatologıá ’ awarded to FG. FG and JR-G are beneficiaries of a grant funded by ‘Instituto de Salud Carlos III’ (ISCIII) (PI20/00059). FG is supported by funds of the RICORS Program (RD21/0002/0025) from ISCIII, co-funded by the European Union. SR-M and VP-C are supported by funds of the RETICS Program (RD16/0012/0009) from ISCIII, co-funded by the European Regional Development Fund. RL-M is a recipient of a Miguel Servet type II Program fellowship from ISCIII, co-funded by the European Social Fund, `Investing in your future´ (CPII21/00004). ACKNOWLEDGMENTS: We are indebted to the patients for their essential collaboration to this study.Axial spondyloarthritisBiomarkerCardiovascular riskDisease severityIrisinSubclinical atherosclerosi