A colorectal cancer susceptibility new variant at 4q26 in the Spanish population identified by genome-wide association analysis

BACKGROUND: Non-hereditary colorectal cancer (CRC) is a complex disorder resulting from the combination of genetic and non-genetic factors. Genome-wide association studies (GWAS) are useful for identifying such genetic susceptibility factors. However, the single loci so far associated with CRC only represent a fraction of the genetic risk for CRC development in the general population. Therefore, many other genetic risk variants alone and in combination must still remain to be discovered. The aim of this work was to search for genetic risk factors for CRC, by performing single-locus and two-locus GWAS in the Spanish population. RESULTS: A total of 801 controls and 500 CRC cases were included in the discovery GWAS dataset. 77 single nucleotide polymorphisms (SNP)s from single-locus and 243 SNPs from two-locus association analyses were selected for replication in 423 additional CRC cases and 1382 controls. In the meta-analysis, one SNP, rs3987 at 4q26, reached GWAS significant p-value (p = 4.02×10(-8)), and one SNP pair, rs1100508 CG and rs8111948 AA, showed a trend for two-locus association (p = 4.35×10(-11)). Additionally, our GWAS confirmed the previously reported association with CRC of five SNPs located at 3q36.2 (rs10936599), 8q24 (rs10505477), 8q24.21(rs6983267), 11q13.4 (rs3824999) and 14q22.2 (rs4444235). CONCLUSIONS: Our GWAS for CRC patients from Spain confirmed some previously reported associations for CRC and yielded a novel candidate risk SNP, located at 4q26. Epistasis analyses also yielded several novel candidate susceptibility pairs that need to be validated in independent analyses

Predictive Power of the "Trigger Tool" for the detection of adverse events in general surgery: a multicenter observational validation study

Background In spite of the global implementation of standardized surgical safety checklists and evidence-based practices, general surgery remains associated with a high residual risk of preventable perioperative complications and adverse events. This study was designed to validate the hypothesis that a new “Trigger Tool” represents a sensitive predictor of adverse events in general surgery. Methods An observational multicenter validation study was performed among 31 hospitals in Spain. The previously described “Trigger Tool” based on 40 specific triggers was applied to validate the predictive power of predicting adverse events in the perioperative care of surgical patients. A prediction model was used by means of a binary logistic regression analysis. Results The prevalence of adverse events among a total of 1,132 surgical cases included in this study was 31.53%. The “Trigger Tool” had a sensitivity and specificity of 86.27% and 79.55% respectively for predicting these adverse events. A total of 12 selected triggers of overall 40 triggers were identified for optimizing the predictive power of the “Trigger Tool”. Conclusions The “Trigger Tool” has a high predictive capacity for predicting adverse events in surgical procedures. We recommend a revision of the original 40 triggers to 12 selected triggers to optimize the predictive power of this tool, which will have to be validated in future studies

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Autotrasplante de tejido cortical hiperplásico suprarrenal: modelo experimental en el perro

Tesis doctoral inédita leída el 23-7-1987 en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Cirugí

Evaluation of circulating mtDNA as biomarker of metabolic alterations in thyroid cancer

Trabajo presentado al ASCB|EMBO Meeting celebrado en San Diego (USA) del 8 al 12 de diciembre de 2018.Peer Reviewe

Can physiological stimulation prior to ileostomy closure reduce postoperative ileus: a prospective multicenter pilot study

Background The aim of this study was to assess the impact of ileostomy closure following preoperative physiological stimulation (PPS) on postoperative ileus (POI) in patients with loop ileostomy after low anterior resection for rectal cancer. Methods Patients who underwent ileostomy closure between January 2017 and February 2020 in two tertiary referral centers were prospectively included. PPS stimulation was compared to standard treatment. Stimulation was carried out daily during the 15 days prior to ileostomy closure by the patient's self-instillation of 200 ml of fecal contents from the ileostomy bag via the efferent loop, using a rectal catheter. Standard treatment (ST) consisted of observation. Outcomes measures were POI, morbidity, stimulation feasibility, and predictors to ileus. Results A total of 58 patients were included [42 males and 16 females, median age 67 (43–85) years]. PPS was used in 24 patients, who completed the entire stimulation process, and ST in 34 patients. No differences in preoperative factors were found between the two groups. POI was significantly lower in the PPS group (4.2%) vs the ST group (32.4%); p < 0.01, OR: 0.05 (CI 95% 0.01–0.65). The PPS group had a shorter time to restoration of bowel function (1 day vs 3 days) p = 0.02 and a shorter time to tolerance of liquids (1 day vs 2 days), p = 0.04. Age (p = 0.01), open approach at index surgery, p = 0.03, adjuvant capecitabine (p = 0.01). and previous abdominal surgeries (p = 0.02) were associated with POI in the multivariate analysis. C-reactive-protein values on the 3rd (p = 0.02) and 5th (p < 0.01) postoperative day were also associated with POI. Conclusions PPS for patients who underwent ileostomy closure after low anterior resection for rectal cancer is feasible and might reduce POI.Depto. de CirugíaFac. de MedicinaTRUEpu

Estadificación dinámica del riesgo en cáncer diferenciado de tiroides: ¿es posible implementar nuevos modelos con biomarcadores metabólicos?. Estudio de prx3 en leucocitos

Resumen del póster presentado a la VI Reunión Ibérica de Cirugía Endocrina: "Cáncer Medular de Tiroides y Endocrinopatías Familiares", celebrada en Sevilla (España) del 26 al 28 de abril de 2017.El cáncer de tiroides es la neoplasia más común del sistema endocrino y representa actualmente 1-3% de todos los procesos tumorales. Su incidencia se ha duplicado en las últimas tres décadas. Este incremento puede asociarse en parte a la mejora en las técnicas de diagnostico, pero puede también deberse al incremento en la prevalencia de factores de riesgo como es el caso de las enfermedades metabólicas. El objetivo del proyecto fue evaluar el impacto de las disfunciones metabólicas en la agresividad tumoral e identificar marcadores de riesgo tumoral con valor pronóstico detectables en sangre periférica. Se seleccionó una corte de 32 pacientes sometidos a tiroidectomía por sospecha de proceso neoplásico. Se aislaron leucocitos de muestras de sangre periférica (PBMCs) en los que se evaluaron los niveles de las proteínas PGC-1a, como marcador de actividad mitocondrial, PFKB3, como marcador de flujo glicolítico, y Prx3 como marcador de estrés oxidativo, observándose que los niveles de estos tres marcadores estaban significativamente mas elevados en pacientes con adenocarcinoma que en pacientes con hiperplasia benigna, y esta elevación se correspondía con mayores niveles de proliferación tumoral medidos con el marcador Ki67. Para realizar una primera evaluación del valor predictivo de Prx3 en PBMCs como marcador de agresividad se subdividieron los pacientes en dos grupos según los niveles de Prx3 (alto/bajo) y se evaluó en cada uno de los grupos la agresividad tumoral mediante: la evaluación histológica del nivel de desestructuración tisular (tinción H&E), determinación de los niveles de proliferación (núcleos positivos para Ki67), y grado de alteración vascular (presencia de hemorragias, niveles de VEGFR2, alteración en la morfología vascular en muestras marcadas con SMA). Se observó que los pacientes con Prx3 alto mostraban mayores niveles de todos los marcadores de agresividad tumoral estudiados. Seguidamente se analizó si la elevación de Prx3 en PBMC correlacionaba con una mayor alteración metabólica en los tejidos tumorales, para ellos se determinó el grado de actividad de la quinasa AKT, midiendo en el tejido tumoral los niveles y localización de su forma activa (fosforilada) y la estructura de la red mitocondrial, mediante tinción con anticuerpos dirigidos contra la proteína mitocondrial TOM22. Observamos que los pacientes con niveles elevados de Prx3 mostraban también una mayor alteración en los marcadores metabólicos coherente con una mayor activación del metabolismo glicolítico y una supresión del metabolismo oxidativo. Concluimos por tanto, que la determinación de los niveles de Prx3 en PBMC puede tener valor pronóstico para la estadificación de los pacientes con cáncer de tiroides.Peer Reviewe

IMPACT OF THE APPENDICEAL POSITION ON THE DIAGNOSIS AND TREATMENT OF PEDIATRIC APPENDICITIS

ABSTRACT Objective: To investigate how symptoms vary according to the appendiceal position in pediatric patients and to demonstrate that the laparoscopic approach is safe and effective in any appendiceal location by comparing each location to another. Methods: The medical records of 1,736 children aged 14 or younger who underwent laparoscopic appendectomy over a period of 14 years were analyzed retrospectively. Patients were divided according to the position of the appendiceal tip into four groups: anterior, pelvic, retrocecal and subhepatic. The Kruskal-Wallis and chi-square tests were used with the Bonferroni correction, with a significant p<0.05. Results: The appendiceal location was anterior in 1,366 cases, retrocecal in 248 cases, pelvic in 66 cases and subhepatic in 56 cases. There were no significant differences between the groups in terms of patient age and gender. Abdominal pain was the only symptom with statistically significant differences between the groups. The rate of perforated appendicitis was higher in the subhepatic and pelvic positions. Intraoperative complications and conversions were not statistically significant. Technical difficulties and operative time were higher in subhepatic position. The rate of postoperative complications was similar between the different locations, except for bowel obstruction, which was higher in pelvic appendicitis. Conclusions: The clinical symptoms of appendicitis hardly ever change with the position of the appendix. The laparoscopic approach is safe and effective, regardless the appendiceal location

Laparoscopic sigmoid resection for a giant colonic diverticulum -a video vignette

A giant colonic diverticulum (GCD) is a rare manifestiation of colonic diverticular disease. It is more often located in the sig moid colon. It is defined by a colonic diverticulum greater than 4 cm in diameter (medium size 4–9 cm) and is usually located at the anti-mesenteric border of the sigmoid colon [2]. It was first described in 1946, although <200 cases are reported in the lit erature, mostly as case reports. While GCD pathophysiology remains unclear, the ‘ball-valve’ theory is the most accepted. GCD should be managed with surgical excision.Depto. de CirugíaFac. de MedicinaTRUEpu