Fecal Hemoglobin Concentration, a Good Predictor of Risk of Advanced Colorectal Neoplasia in Symptomatic and Asymptomatic Patients

Background: Periodical fecal immunochemical testing (FIT) is a cost-effective strategy in colon cancer screening programmes. FIT is also used as a diagnostic test in symptomatic patients, but data, are scarce.Aim: To determine the association between FIT-Hb concentration and the risk of advanced neoplasia (AN) detected in colonoscopy in two different populations.Methods: The outcomes of colonoscopies performed after a positive FIT (>117 ng/ml) (Sentinel Gold test) result were analyzed in patients included within a population-based CRC screening programme (screening group) and, as diagnostic evaluation in symptomatic patients (symptomatic group). The study was performed between January 1st, 2014 and October 31, 2016. Data are reported as medians with interquartile ranges or frequencies and percentages. Positive predictive value (PPV) at arbitrary fecal hemoglobin concentrations were also reported calculated for AN.Results: We recruited 2742 patients who underwent a colonoscopy procedure, 1515 (53.5%) of them within the CRC screening programme. Patients in the screening group were younger (65.0 ± 3.3 vs. 66.2 ± 13.4 years, p < 0.001) and more frequently male (p < 0.001) vs. the symptomatic group. Colonoscopy found more frequently neoplastic lesions in the screening compared to the symptomatic group (61.9 vs. 44.8% p < 0.001). Hb concentration in FIT was significantly higher in patients with AN compared with patients without AN in both groups (p < 0.001). The age-adjusted risk of AN increased significantly in both groups according to FIT Hb concentration in the Quartile 3 [OR (95% CI): 2.94 (2.33–3.71)] and Quartile 4 [OR: 5.52 (4.36–6.99)]. Males, in both groups showed a higher probability of presenting AN. FIT values were higher for left- than for right-sided AN in the screening, but not in the symptomatic group. Positive predictive values for AN were higher in the screening group in positive FIT tests (range 43.9–70.5%; 117 to >1,000 ng/ml) compared to those in the symptomatic group (36.3–52.5%). Similar trends were observed for cancer diagnosis alone.Conclusions: Male gender, age, and FIT Hb concentration are predictors of risk of advanced adenoma and colorectal cancer and can be used to prioritize colonoscopy in patients with suspected advanced neoplasia, both in screening and in symptomatic patients

Two-component regulatory systems in Helicobacter pylori and Campylobacter jejuni: attractive targets for novel antibacterial drugs

Two-component regulatory systems (TCRS) are ubiquitous signal transduction mechanisms evolved by bacteria for sensing and adapting to the constant changes that occur in their environment. Typically consisting of two types of proteins, a membrane sensor kinase and an effector cytosolic response regulator, the TCRS modulate via transcriptional regulation a plethora of key physiological processes, thereby becoming essential for bacterial viability and/or pathogenicity and making them attractive targets for novel antibacterial drugs. Some members of the phylum Campylobacterota (formerly Epsilonproteobacteria), including Helicobacter pylori and Campylobacter jejuni, have been classified by WHO as “high priority pathogens” for research and development of new antimicrobials due to the rapid emergence and dissemination of resistance mechanisms against first-line antibiotics and the alarming increase of multidrug-resistant strains worldwide. Notably, these clinically relevant pathogens express a variety of TCRS and orphan response regulators, sometimes unique among its phylum, that control transcription, translation, energy metabolism and redox homeostasis, as well as the expression of relevant enzymes and virulence factors. In the present mini-review, we describe the signalling mechanisms and functional diversity of TCRS in H. pylori and C. jejuni, and provide an overview of the most recent findings in the use of these microbial molecules as potential novel therapeutic targets for the development of new antibiotics

The impact of COVID-19 pandemic in the diagnosis and management of colorectal cancer patients

The novel coronavirus disease 2019 (COVID-19) pandemic has posed an unprecedented challenge to healthcare systems worldwide, causing downscaling of almost all other activities, especially in its early stages. Currently, the availability of vaccines along with the spread of new viral variants has modified the epidemiology of the disease, and the previous activity is being gradually resumed in most healthcare facilities. In this review, we have summarized the influence of the COVID-19 pandemic in the diagnosis and management of colorectal cancer (CRC) patients. Population-based screening with either colonoscopy or fecal occult blood tests has proven to reduce CRC incidence and mortality, so screening programs have been implemented in most western countries. However, during the first COVID-19 wave, most of these programs had to be disrupted temporarily. In this review, we have thoroughly analyzed the consequences of these disruptions of screening programs as well as of the forced delays in diagnostic and therapeutic services on CRC prognosis, although its exact impact cannot be exactly measured yet. In any way, strategies to minimize its effect, such as catch-up strategies expanding the colonoscopy capacity or using fecal occult blood concentration and other risk factors to prioritize patients, are urgently needed. The COVID-19 pandemic has also led to a change in CRC patient presentation, with an overall temporary decreased incidence due to postponed diagnoses, but with more patients presenting in need of an emergency admission or with symptoms. Finally, changes in treatment approaches in CRC patients have been reported during the pandemic, namely a drop in the proportion of laparoscopic surgeries or a rise in short-term radiotherapy courses. We have therefore aimed to summarize the available evidence to guide the healthcare professionals treating CRC patients to choose the best treatment options in the current pandemic situation

Adding genetic scores to risk models in colorectal cancer

Colorectal cancer (CRC) represents the second most common cancer worldwide and the third leading cause of cancer death. Most CRCs arise from premalignant colorectal lesions (mainly adenomas) that require years to develop an invasive disease..

Riesgo de hemorragia gastrointestinal alta y baja asociada al tratamiento con AINEs, antiagregantes plaquetarios y anticoagulantes orales. Estudio de casos y controles

Introducción y objetivos: El tratamiento con antiinflamatorios no esteroideos (AINEs) o ácido acetilsalicílico (AAS) a bajas dosis se asocia con un incremento en el riesgo de hemorragia digestiva alta. Existe menos evidencia sobre el riesgo asociado a antiagregantes plaquetarios (AP) y anticoagulantes orales (ACO), tanto nuevos como clásicos. Sin embargo, la toxicidad de estos fármacos no ha sido bien estudiada en relación al tracto digestivo bajo. El objetivo principal de este estudio es cuantificar el riesgo de hospitalización por HDA y por HDB no varicosas, asociadas al uso de AINEs, AAS u otros AP, y ACO; y su relación potencial con factores que pueden modificar dicho riesgo. Material y métodos: Se diseñó un estudio de casos y controles, en el que se incluyeron los pacientes que fueron ingresados por hemorragia digestiva, confirmada mediante endoscopia u otros procedimientos. Pacientes no hospitalizados fueron utilizados como controles y emparejados por sexo y edad (± 5 años), cumpliendo los mismos criterios de elegibilidad que el caso. El consumo de fármacos en los 7 días previos al ingreso por hemorragia digestiva fue considerado como reciente. El análisis de los datos se llevó a cabo mediante el test de Chi-Cuadrado y el test U Mann-Whitney. Para analizar normalidad de las variables se usó el test de Kolmogorov-Smirnov. Para estimar los Odds Ratio (OR) ajustados y los intervalos de confianza (IC 95%) se realizó regresión logística binaria. Resultados: El consumo reciente de AAS a bajas dosis, AP o ACO se asoció con un aumento del riesgo de hemorragia digestiva; siendo el riesgo dos veces mayor para los ACO (OR 3,351; IC 95% 1,928 – 5,826) que para el AAS (OR 1,724; IC 95% 1,072-2,775). El tratamiento con AINEs también se asoció con un incremento del riesgo de hemorragia digestiva. El riesgo aumentó para HDA (OR 3,798; IC 95% 1,645 – 8,768), pero no se evidenció con HDB (OR 1,000; IC 95% 0,509 – 1,964).El uso de IBP se asoció a un mayor riesgo de HDB (OR 2,586; IC 95% 1,550 – 4,316). Conclusiones: El consumo de AINEs, AAS a bajas dosis, ACO y AP se asocia con un aumento del riesgo de hemorragia digestiva. El tratamiento con ACO parece ser el factor que más aumentó el riesgo de hemorragia digestiva. El tratamiento con IBP se asoció con un riesgo incrementado de HDB

Melatonina asociada a inhibición ácida como estrategia de quimioprevención en Esófago de Barrett.

Objetivo: establecer si la melatonina, un potente antioxidante, previene la progresión neoplásica del Esófago de Barrett (EB). Determinar si el tratamiento con melatonina interfiere con fenómenos biológicos celulares asociados a la progresión neoplásica en el esófago de Barrett. Específicamente: a) Determinar si la melatonina reduce el estrés oxidativo de la mucosa esofágica de Barrett tras 6 meses de tratamiento continuado. 2) Evaluar si la melatonina afecta a otros mecanismos asociados a progresión neoplásica en pacientes con EB: índices de proliferación y apoptosis así como marcadores moleculares de progresión: 17pLOH, 9pLOH, metilación de p16, alteraciones en el contenido de ADN (tetraploidía y/o aneuploidía). Metodología: ensayo clínico piloto en fase IV, abierto, aleatorizado para evaluar efecto de melatonina en EB. Se incluirán pacientes de ambos sexos (>18 años) diagnosticados de Esófago de Barrett > 2 cm en endoscopia rutinaria o revisión (no dirigida específicamente a la inclusión de pacientes para este estudio), sin esofagitis, que firmen el consentimiento informado y se distribuirán en dos grupos: 1) tratamiento con Inhibidor bomba protones (IBP); 2) IBP+ Melatonina (6 mg/12 horas). Endoscopia+biopsias: inicio y tras 6 meses de tratamiento. Determinaciones: a) estudio histológico; grado de displasia, b) Marcadores de estrés oxidativo: niveles de peroxinitritos en mucosa esofágica (inmunohistoquímica nitrotirosina) y de 8-hidroxi-2deoxiguanosina como marcador de daño oxidativo de ADN. c) Marcadores subclínicos de progresión: índices de apoptosis (caspasa 3 activa) y proliferación (ki67), alteraciones ploidía ADN (tetra y/o aneuploidía) mediante citometría de imagen, metilación de p16 (pirosecuenciacion), 9pLOH y 17p LOH (PCR, electroforesis capilar). Los datos se evaluarán desde una perspectiva temporal y en función de la intensidad o grado de respuesta. En pacientes se realizarán análisis por "Intencion de tratar modificada" y "por protocolo". Se utilizaran los paquetes estadísticos de SPSS y BMDP

CD24 Expression Is Increased in 5-Fluorouracil-Treated Esophageal Adenocarcinoma Cells

The cancer stem cell (CSC) model suggests that there are subsets of cells within a tumor with increased proliferation and self-renewal capacity, which play a key role in therapeutic resistance. The importance of cyclooxygenase-2 (COX-2) in carcinogenesis has been previously established and the use of COX-2 inhibitors as celecoxib has been shown to exert antitumor effects. The present study investigated whether treatment of esophageal adenocarcinoma (EAC) cells with 5-fluorouracil (5-FU) or the growth of tumor spheres increased the proportion of CSCs and also if treatment with celecoxib was able to reduce the putative CSC markers in this tumor. OE19 and OE33 EAC cells surviving 5-FU exposure exhibited an increase in CSC markers CD24 and ABCG2 and also an increased resistance to apoptosis. EAC cell lines had the capacity to form multiple spheres displaying typical CSC functionalities such as self-renewal and increased CD24 levels. In addition, after the induction of differentiation, cancer cells reached levels of CD24 similar to those observed in the parental cells. Treatment with celecoxib alone or in combination with 5-FU also resulted in a reduction of CD24 expression. Moreover, celecoxib inhibited the growth of tumor spheres. These findings showing a reduction in CSC markers induced by celecoxib suggest that the COX-2 inhibitor might be a candidate for combined chemotherapy in the treatment of EAC. However, additional clinical and experimental studies are needed

Fighting the antibiotic crisis: flavonoids as promising antibacterial drugs against Helicobacter pylori infection

Over half of the world’s population is estimated to be infected with Helicobacter pylori. Chronic infection with this microbial class I carcinogen is considered the most important risk factor for developing gastric cancer. The increasing antimicrobial resistance to first-line antibiotics mainly causes the failure of current eradication therapies, inducing refractory infections. The alarming increase in multidrug resistance in H. pylori isolates worldwide is already beginning to limit the efficacy of existing treatments. Consequently, the World Health Organization (WHO) has included H. pylori in its list of “priority pathogens” for which new antibiotics are urgently needed. Novel strategies must be followed to fight this antibiotic crisis, including properly exploiting the proven therapeutic potential of medicinal plants and plant-derived phytochemicals. In this mini-review, we overview the impressive properties of naturally occurring flavonoids as effective antimicrobial agents against H. pylori, which support the use of these plant-derived bioactive compounds as promising drug candidates for inclusion in novel and personalized combinatory therapies against H. pylori infection

Estudio del riesgo de hemorragia gastrointestinal asociada al tratamiento de agentes anticoagulantes y antiplaquetarios en prevención cardiovascular.

Introducción y objetivos: El tratamiento con antiinflamatorios no esteroideos (AINEs) o ácido acetilsalicílico (AAS) a dosis bajas se asocia al aumento de riesgo de hemorragia digestiva alta. Existe menos evidencia sobre el riesgo asociado a anticoagulantes orales (ACOs), nuevos y clásicos. Además, la toxicidad de estos fármacos en tracto digestivo bajo ha sido menos estudiada. El objetivo principal del estudio es cuantificar el riesgo de hemorragia digestiva asociada a la toma de AINEs, AAS a bajas dosis o ACOS. Material y métodos: Se realizó un estudio de casos y controles, en el que se incluyeron pacientes que ingresaron consecutivamente por hemorragia digestiva durante un año, con diagnóstico confirmado mediante pruebas endoscópicas u otros procedimientos. Los controles fueron sujetos no hospitalizados y se emparejaron con los casos según sexo y edad. El consumo de un fármaco en los 7 días previos al ingreso por hemorragia se consideró exposición reciente. Se realizaron análisis de regresión logística binaria para estimar los valores Odds Ratio (OR) y los intervalos de confianza (ICs) 95% obtenidos. Resultados: El tratamiento reciente con AINEs o ACOs se asoció a un aumento de riesgo de hemorragia digestiva; siendo este riesgo mayor para ACOs (OR 5,2; IC 95%, 2,1 – 12,6) que para AINEs (OR 3,4; IC 95%, 1,5 – 7,4). No se encontraron diferencias para el consumo de AAS a dosis bajas. Se identificó asociación entre el consumo de AINEs y el aumento de riesgo de HDA (OR 3,8; IC 95%, 1,2 – 11,8) y entre el consumo de ACOs y aumento de riesgo de HDB (OR 3,9; IC 95%, 1,6 – 9,4). Conclusiones: El consumo de ACOs o AINEs se asocia con un aumento de riesgo de hemorragia digestiva. El consumo de ACOs parece ser el factor de riesgo que más se asocia a hemorragia digestiva

Riesgo de hemorragia digestiva alta y baja asociada al tratamiento con AINEs, antiagregantes plaquetarios y anticoagulantes orales: Estudio de casos y controles.

Se trata de un estudio de casos y controles en el que se recogieron datos mediante una encuesta de pacientes hospitalizados por hemorragia digestiva (n= 532) en 2 hospitales de Zaragoza (España). Los controles se emparejaron por sexo, edad y hospital con los casos. El objetivo era conocer la asociación de riesgo del consumo de los diferentes fármacos y las comorbilidades de los pacientes que ingresan por hemorragia digestiva en nuestro medio. Se recogieron numerosas variables clínicas, antecedentes y consumo de fármacos en el momento de la hemorragia de forma prospectiva. El tratamiento con AINES, agentes antiplaquetarios y anticoagulantes se asocia a hemorragia digestiva. La toma ACOs parece ser el factor de riesgo que más aumenta el riesgo de hemorragia gastrointestinal. Tanto los ACOs como el AAS y otros AP presentan mayor riesgo de sangrado a nivel gastrointestinal bajo, mientras que los AINEs presentan mayor riesgo de HDA