Colonoscopy quality assessment in a mass population screening programme based on faecal occult blood test

Background and aim: the success of colorectal cancer (CRC) screening programmes largely depends on the quality of the events, processes and outcomes and therefore, quality assurance of endoscopy is an essential component. The quality indicators for colonoscopy in a screening programme setting are different from those performed in symptomatic people. The objective of this study was to report the main quality indicators of colonoscopies performed after a positive faecal occult blood test (FOBT) in a CRC screening programme in Catalonia. Methods: the period of study includes three rounds of the CRC screening programme from June 2006 to July 2013. Two types of FOBT were used: a qualitative biochemical guaiac-based test (gFOBT) and a quantitative immunochemical test (FIT). Quality indicators analysed in this study were compared to recommended colonoscopy standards from the published guidelines. Results: during the study period, 1,806 colonoscopies were performed in 1,691 individuals with a positive FOBT. All indicators were within the standard except waiting time to colonoscopy. Caecal intubation rate was 95.6 % and adequate bowel cleansing 93.6 %. Adenoma detection rate was better using FIT than gFOBT, 30.7 and 3.8 per 1,000 screenees, respectively. Cancer detection rate was also greater using FIT. Nearly 62 % of cancers were diagnosed at an early stage. The overall complication rate was 10.7 . Conclusion: although the majority of results reached the recommended standards, some areas have been identified for quality enhancement. Continuous monitoring of quality indicators is essential for improving the current effectiveness of CRC screening programmes

Tratamiento de la enfermedad inflamatoria intestinal refractaria a tratamiento convencional

Malaltia inflamatòria intestinal; Colitis ulcerosa; Malaltia de Crohn; Tractament biològicEnfermedad inflamatoria intestinal; Colitis ulcerosa; Enfermedad de Crohn; Tratamiento biológicoInflammatory bowel disease; Ulcerative colitis; Crohn's disease; Biological treatmentLa malaltia inflamatòria intestinal engloba la colitis ulcerosa i la malaltia de Crohn. Totes dues condicionen un alt impacte en la qualitat de vida i el seu maneig implica elevats costs directes i indirectes. Les opcions terapèutiques per als pacients amb malaltia inflamatòria intestinal han augmentat considerablement en els darrers vint anys. Actualment, disposem de cinc medicaments biotecnològics que actuen en diferents dianes terapèutiques: tres inhibidors del factor de necrosi tumoral (infliximab, adalimumab i golimumab), una antiintegrina a4β7 (vedolizumab) i un anticòs anti-IL-12/23 (ustekinumab). A més, disposem del primer fàrmac sintètic dirigit enfront de la cinasa Janus (tofacitinib) per a la colitis ulcerosa. La incorporació de medicaments biosimilars (actualment, infliximab i adalimumab) ha permès reduir-ne considerablement el cost. En aquest article es revisaran les principals indicacions d’aquests medicaments i els estudis més importants que han permès la seva incorporació en pràctica clínica, així com els principals efectes secundaris.La enfermedad inflamatoria intestinal engloba la colitis ulcerosa y la enfermedad de Crohn. Todas ellas condicionan un alto impacto en la calidad de vida, y su manejo implica elevados costes directos e indirectos. Las opciones terapéuticas, para los pacientes con enfermedad inflamatoria intestinal, han aumentado considerablemente en los últimos veinte años. Actualmente, disponemos de cinco medicamentos biotecnológicos que actúan en diferentes dianas terapéuticas: 3 inhibidores del factor de necrosis tumoral (infliximab, adalimumab y golimumab), una anti-integrina a4β7 (vedolizumab) y un anticuerpo anti-IL12 / 23 (ustekinumab). Además, disponemos del primer fármaco sintético dirigido frente la Janus quinasa (tofacitinib) para la colitis ulcerosa. La incorporación de medicamentos biosimilares (actualmente, de infliximab y adalimumab) ha permitido reducir considerablemente su coste. En este artículo se revisarán las principales indicaciones de estos medicamentos, los estudios más importantes que han permitido su incorporación en práctica clínica, así como los principales efectos secundarios

Proton pump inhibitors reduce the accuracy of faecal immunochemical test for detecting advanced colorectal neoplasia in symptomatic patients

BACKGROUND: The faecal immunochemical test (FIT) is used in colorectal cancer (CRC) screening and for the detection of advanced colorectal neoplasia (AN) in symptomatic patients, but its accuracy could be improved. Our objective was to assess the impact of proton pump inhibitors (PPI) on the accuracy of the FIT in the detection of AN, namely advanced colorectal adenoma and CRC. METHODS AND FINDINGS: We performed a prospective study of 1002 individuals referred for a diagnostic colonoscopy at Bellvitge University Hospital from September 2011 through to October 2012. An exhaustive interview was performed by a gastroenterologist, prescription drug dispensing database was reviewed and the patient was given a FIT prior to colonoscopy. The positivity threshold of FIT used was ≥ 20 μg Hb/g feces and the main outcome was AN. AN was detected in 13.2% (133) of patients. The accuracy of FIT for detecting AN in the PPI users and non-PPI users were: sensitivity 43.0% vs 65.6%, P = 0.009; specificity 86.9% vs 92.3%, P = 0.010; and, predictive positive value 34.4% vs 55.5%, P = 0.007, respectively. In multivariate analysis, adjusting for potential confounders, PPIs were associated with false positives in AN detection by FIT (OR 1.63 CI 95% 1.02-2.59, P < 0.037). The ROC curve for the FIT in the detection of AN in the PPI users and non-PPI users was 0.68 (CI 95% 0.61-0.76) and 0.85 (CI 95% 0.79-0.90). CONCLUSIONS: PPI therapy reduces the accuracy of FIT for detecting AN in symptomatic patients

The use of faecal immunochemical testing in the decision-making process for the endoscopic investigation of iron deficiency anaemia

Background: Blood loss from the gastrointestinal (GI) tract is the most common cause of iron deficiency anaemia (IDA) in adult men and postmenopausal women. Gastroduodenal endoscopy (GDE) and colonoscopy are frequently recommended, despite uncertainty regarding the coexistence of lesions in the upper and lower GI tract. The faecal immunochemical test (FIT) measures the concentration of faecal haemoglobin (f-Hb) originating only from the colon or rectum. We aimed to assess whether the FIT was able to select the best endoscopic procedure for detecting the cause of IDA. Methods: A prospective study of 120 men and postmenopausal women referred for a diagnostic study of IDA were evaluated with an FIT, GDE and colonoscopy. The endoscopic finding of a significant upper lesion (SUL) or a significant bowel lesion (SBL) was considered to be the cause of the IDA. Results: The diagnoses were 35.0% SUL and 20.0% SBL, including 13.3% GI cancer. In the multivariate analysis, the concentration of blood haemoglobin (b-Hb) <9 g/dL (OR: 2.60; 95% CI 1.13-6.00; p = 0.025) and non-steroidal anti-inflammatory drugs NSAIDs (2.56; 1.13-5.88; p = 0.024) were associated with an SUL. Age (0.93; 0.88-0.99; p = 0.042) and f-Hb ≥ 15 μg Hb/g faeces (38.53; 8.60-172.50; p < 0.001) were associated with an SBL. A 'FIT plus gastroscopy' strategy, in which colonoscopy is performed only when f-Hb ≥15 μg Hb/g faeces, would be able to detect 92.4% of lesions and be 100% accurate in the detection of cancer while avoiding 71.6% of colonoscopies. Conclusions The FIT is an accurate method for selecting the best endoscopy study for the evaluation of IDA. An FIT-based strategy is more cost-effective than the current bidirectional endoscopy-based strategy and could improve endoscopic resource allocatio

Colorectal cancer screening programme in Spain: results of key performance indicators after five rounds (2000-2012)

A l'article en PDF consta com a vol. 5Effective quality assurance is essential in any screening programme. This article provides a unique insight into key quality indicators of five rounds of the first population-based colorectal cancer screening programme implemented in Spain (2000-2012), providing the results according to the type of screening (prevalent or first screen and incident or subsequent screen) and test (guaiac or immunochemical). The total crude participation rate increased from 17.2% (11,011) in the first round to 35.9% (22,988) in the last one. Rescreening rate was very high (88.6% in the fifth round). Positivity rate was superior with the faecal immunochemical test (6.2%) than with the guaiac-based test (0.7%) (p< 0.0001) and detection rates were also better with the immunochemical test. The most significant rise in detection rate was observed for high risk adenoma in men (45.5 per 1,000 screened). Most cancers were diagnosed at an early stage (61.4%) and there was a statistically significant difference between those detected in first or subsequent screening (52.6% and 70.0% respectively; p= 0.024). The availability of these results substantially improves data comparisons and the exchange of experience between screening programmes

Gut microbiome diversity detected by high-coverage 16S and shotgun sequencing of paired stool and colon sample

The gut microbiome has a fundamental role in human health and disease. However, studying the complex structure and function of the gut microbiome using next generation sequencing is challenging and prone to reproducibility problems. Here, we obtained cross-sectional colon biopsies and faecal samples from nine participants in our COLSCREEN study and sequenced them in high coverage using Illumina pair-end shotgun (for faecal samples) and IonTorrent 16S (for paired feces and colon biopsies) technologies. The metagenomes consisted of between 47 and 92 million reads per sample and the targeted sequencing covered more than 300 k reads per sample across seven hypervariable regions of the 16S gene. Our data is freely available and coupled with code for the presented metagenomic analysis using up-to-date bioinformatics algorithms. These results will add up to the informed insights into designing comprehensive microbiome analysis and also provide data for further testing for unambiguous gut microbiome analysis

Evaluación de dos estrategias de cribado de cáncer colorrectal: Test inmunológico versus test bioquímico. Cataluña, 2008-2010

Fundamento: El objetivo del estudio fue evaluar el cambio de estrategia de cribado (test inmunológico cuantitativo) en un programa poblacional de detección precoz de cáncer colorrectal (CCR) en Cataluña. Métodos: La cuarta ronda del programa de cribado de CCR en Hospitalet de Llobregat se implementó en 2008-2010. Se ofreció un test bioquímico a 50.227 individuos y uno inmunológico cuantitativo a 12.707 individuos. Se analizaron diferencias en las dos estrategias de cribado respecto a variables de aceptabilidad (entre participación, abandonos y adherencia a la colonoscopia), de precisión diagnóstica (valor predictivo positivo y tasas de detección), de resultados (tamaño y localización de lesiones, estadio de los cánceres detectados) y de recursos (número necesario de colonoscopias e intervalo de tiempo entre el resultado positivo del test y la colonoscopia). Resultados: La participación en el cribado fue superior entre los individuos que utilizaron el test inmunológico (OR: 1,35; IC95%:1,27-1,42). Las tasas de detección fueron superiores para el test inmunológico destacando la de adenomas de alto riesgo (26,7 vs 3,0 ). El valor predictivo positivo para adenomas de alto riesgo fue del 45,0% y del 46,9% en el inmunológico y el guayaco, respectivamente. El número de colonoscopias necesarias para detectar un cáncer fue de casi el doble que en el guayaco (13,6 vs 7,4). Conclusiones: El test inmunológico es una buena estrategia de cribado especialmente sensible para la detección de adenomas de alto riesgo. Sin embargo, requiere realizar un gran número de colonoscopias y por ello se debe disponer de los recursos y medios necesarios

Relationship between methylation and colonic inflammation in inflammatory bowel disease

AIM: To investigate the relationship between the methylation status in the SLIT2 and TGFB2 promoters and colonic inflammation in inflammatory bowel disease patients. METHODS: We evaluated the methylation status of 2 genes (SLIT2 and TGFB2) in 226 biopsies taken from 62 colonoscopies of 38 patients (29 ulcerative colitis and 9 Crohn's colitis) using methylation-specific melting curve analysis. The relationships between methylation status and clinical, biological, endoscopic and histological activities were evaluated. Twenty-three of the 38 patients had a second colonoscopy and were included in a longitudinal analysis. Numerical results were given as the means ± SD of the sample and range, except when specified. Student t analysis, U Mann Whitney and ANOVA factor were used to compare the means. Qualitative results were based on the χ2 test. RESULTS: SLIT2 methylation was more frequent in samples with endoscopic activity than with endoscopic remission (55% vs 18%, P < 0.001). SLIT2 methylation was also higher in samples with acute inflammation (56.5%) than in samples with chronic (24%) or absent inflammation (15%) (P < 0.001). For TGFB2 methylation, the correlation was only significant with endoscopic activity. Methylation was higher in the distal colon for both genes (P < 0.001 for SLIT2 and P = 0.022 for TGFB2). In the multivariate analysis, only inflammation status (and not disease duration or extension) was independently associated with SLIT2 methylation [OR = 6.6 (95%CI: 1.65-27.36), P = 0.009]. In the longitudinal analysis, the maintenance of endoscopic remission was protective for methylation

Telomere length alterations in microsatellite stable colorectal cancer and association with the immune response

Telomeres are repetitive sequences (TTAGGG) located at the end of chromosomes. Telomeres progressively shorten with each cell replication cycle, ultimately leading to chromosomal instability and loss of cell viability. Telomere length anomaly appears to be one of the earliest and most prevalent genetic alterations in malignant transformation. Here we aim to estimate telomere length from whole-exome sequencing data in colon tumors and normal colonic mucosa, and to analyze the potential association of telomere length with clinical factors and gene expression in colon cancer. Reads containing at least five repetitions of the telomere sequence (TTAGGG) were extracted from the raw sequences of 42 adjacent normal-tumor paired samples. The number of reads from the tumor sample was normalized to build the Tumor Telomere Length Ratio (TTLR), considered an estimation of telomere length change in the tumor compared to the paired normal tissue. We evaluated the associations between TTLR and clinical factors, gene expression and copy number (CN) aberrations measured in the same tumor samples. Colon tumors showed significantly shorter telomeres than their paired normal samples. No significant association was observed between TTLR and gender, age, tumor location, prognosis, stromal infiltration or molecular subtypes. The functional gene set enrichment analysis showed pathways related to immune response significantly associated with TLLR. By extracting a relative measure of telomere length from whole-exome sequencing data, we have assessed that colon tumor cells predominantly shorten telomeres, and this alteration is associated with expression changes in genes related to immune response and inflammation in tumor cells

C4BP(β-)-mediated immunomodulation attenuates inflammation in DSS-induced murine colitis and in myeloid cells from IBD patients

16 p.-9 fig.-1 tab.The most recent and promising therapeutic strategies for inflammatory bowel disease (IBD) have engaged biologics targeting single effector components involved in major steps of the immune-inflammatory processes, such as tumor necrosis factor, interleukins or integrins. Nevertheless, these molecules have not yet met expectations regarding efficacy and safety, resulting in a significant percentage of refractory or relapsing patients. Thus, novel treatment options are urgently needed. The minor isoform of the complement inhibitor C4b-binding protein, C4BP(β-), has been shown to confer a robust anti-inflammatory and immunomodulatory phenotype over inflammatory myeloid cells. Here we show that C4BP(β-)-mediated immunomodulation can significantly attenuate the histopathological traits and preserve the intestinal epithelial integrity in dextran sulfate sodium (DSS)-induced murine colitis. C4BP(β-) downregulated inflammatory transcripts, notably those related to neutrophil activity, mitigated circulating inflammatory effector cytokines and chemokines such as CXCL13, key in generating ectopic lymphoid structures, and, overall, prevented inflammatory immune cell infiltration in the colon of colitic mice. PRP6-HO7, a recombinant curtailed analogue with only immunomodulatory activity, achieved a similar outcome as C4BP(β-), indicating that the therapeutic effect is not due to the complement inhibitory activity. Furthermore, both C4BP(β-) and PRP6-HO7 significantly reduced, with comparable efficacy, the intrinsic and TLR-induced inflammatory markers in myeloid cells from both ulcerative colitis and Crohn’s disease patients, regardless of their medication. Thus, the pleiotropic anti-inflammatory and immunomodulatory activity of PRP6-HO7, able to “reprogram” myeloid cells from the complex inflammatory bowel environment and to restore immune homeostasis, might constitute a promising therapeutic option for IBD.We thank CERCA Programme/Generalitat de Catalunya for institutional support. This work was supported by the Ministerio de Ciencia, Innovación y Universidades (Madrid, Spain) (grants FIS-ISCIII PI20/00464, PI16/00377 and DTS20/00016), and the “Departament de Recerca i Universitats de la Generalitat de Catalunya” (grants 2019PROD00081, 2021INNOV00020, and 2021SGR00521), all co-funded by FEDER funds/European Regional Development Fund (ERDF)-a way to build Europe-. Additionally, the project that gave rise to these results has received funding from the “La Caixa” Foundation and the European Institute of Innovation and Technology, EIT (body of the European Union that receives support from the European Union’s Horizon 2020 research and innovation programme), under the grant agreement CI22–00230. Likewise, this study was financially promoted by the “hna Foundation”. Dr. Vega is supported by the Spanish “Ministerio de Ciencia, Innovación y Universidades/FEDER” [RTI2018–102242-B-I00]. Dr. Rodriguez de Córdoba is supported by the Spanish “Ministerio de Economia y Competitividad/FEDER [SAF2015–66287-R]. Dr. Vega and Dr. Rodriguez de Córdoba are also funded by the Autonomous Region of Madrid [S2022/BMD-7278] and the European Commission – NextGenerationEU through CSIC’s Global Health Platform (”PTI Salud Global”) [SGL2103020].Peer reviewe