Publications by authors named "Luisa de Castro"

26 Publications

  • Page 1 of 1

Effectiveness and safety of ustekinumab in ulcerative colitis: Real-world evidence from the ENEIDA registry.

J Crohns Colitis 2021 Apr 16. Epub 2021 Apr 16.

Hospital General San Jorge, Huesca, Spain.

Background: The development program (UNIFI) has shown promising results of ustekinumab in ulcerative colitis (UC) treatment that should be confirmed in clinical practice.

Aims: To evaluate the durability, effectiveness and safety of ustekinumab in UC in real-life.

Methods: Patients included in the prospectively maintained ENEIDA registry who received at least one intravenous dose of ustekinumab due to active UC [Partial Mayo Score (PMS) >2] were included. Clinical activity and effectiveness were defined based on PMS. Short-term response was assessed at week 16.

Results: A total of 95 patients were included. At week 16, 53% of patients had response (including 35% of patients in remission). In the multivariate analysis, elevated serum C-reactive protein was the only variable significantly associated with lower likelihood of achieving remission. Remission was achieved in 39% and 33% of patients at weeks 24 and 52, respectively. Thirty-six percent of patients discontinued the treatment with ustekinumab during a median follow-up of 31 weeks. The probability of maintaining ustekinumab treatment was 87% at week 16, 63% at week 56, and 59% at week 72; primary failure was the main reason for ustekinumab discontinuation. No variable was associated with risk of discontinuation. Three patients reported adverse events; one of them had a fatal severe SARS-CoV-2 infection.

Conclusions: Ustekinumab is effective both in the short and the long-term in real-life, even in a highly refractory cohort. Higher inflammatory burden at baseline correlated with lower probability of achieving remission. Safety was consistent with the known profile of ustekinumab.
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http://dx.doi.org/10.1093/ecco-jcc/jjab070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8083263PMC
April 2021

The use of 5-aminosalicylate for patients with Crohn's disease in a prospective European inception cohort with 5 years follow-up - an Epi-IBD study.

United European Gastroenterol J 2020 10 26;8(8):949-960. Epub 2020 Jul 26.

Hull University Teaching Hospitals NHS Trust, Hull, UK.

Background: The lack of scientific evidence regarding the effectiveness of 5-aminosalicylate in patients with Crohn's disease is in sharp contrast to its widespread use in clinical practice.

Aims: The aim of the study was to investigate the use of 5-aminosalicylate in patients with Crohn's disease as well as the disease course of a subgroup of patients who were treated with 5-aminosalicylate as maintenance monotherapy during the first year of disease.

Methods: In a European community-based inception cohort, 488 patients with Crohn's disease were followed from the time of their diagnosis. Information on clinical data, demographics, disease activity, medical therapy and rates of surgery, cancers and deaths was collected prospectively. Patient management was left to the discretion of the treating gastroenterologists.

Results: Overall, 292 (60%) patients with Crohn's disease received 5-aminosalicylate period during follow-up for a median duration of 28 months (interquartile range 6-60). Of these, 78 (16%) patients received 5-aminosalicylate monotherapy during the first year following diagnosis. Patients who received monotherapy with 5-aminosalicylate experienced a mild disease course with only nine (12%) who required hospitalization, surgery, or developed stricturing or penetrating disease, and most never needed more intensive therapy. The remaining 214 patients were treated with 5-aminosalicylate as the first maintenance drug although most eventually needed to step up to other treatments including immunomodulators (75 (35%)), biological therapy (49 (23%)) or surgery (38 (18%)).

Conclusion: In this European community-based inception cohort of unselected Crohn's disease patients, 5-aminosalicylate was commonly used. A substantial group of these patients experienced a quiescent disease course without need of additional treatment during follow-up. Therefore, despite the controversy regarding the efficacy of 5-aminosalicylate in Crohn's disease, its use seems to result in a satisfying disease course for both patients and physicians.
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http://dx.doi.org/10.1177/2050640620945949DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7707880PMC
October 2020

Increased Th17-Related Cytokine Serum Levels in Patients With Multiple Polyps of Unexplained Origin.

Clin Transl Gastroenterol 2020 03;11(3):e00143

Laboratorio de Investigación, Hospital General Universitario de Alicante, Instituto de Investigación sanitaria y Biomédica de Alicante (ISABIAL), Alicante, Spain.

Objectives: Most patients with multiple colonic polyps do not have a known genetic or hereditary origin. Our aim was to analyze the presence of inflammatory cytokines and levels of glucose, insulin, and C-reactive protein (CRP) in patients with multiple colonic polyps.

Methods: Eighty-three patients with 10 or more adenomatous or serrated polyps and 53 control people with normal colonoscopy were included. Smoking habits were registered, and glucose, CRP, and basal insulin in the serum/blood were measured. Quantification of IL-2, IL-4, IL-6, IL-10, IL-11, IL-17A, and IL-23 cytokine levels in the serum was performed by a high-sensitivity enzyme-linked immunosorbent assay.

Results: Smoking and diabetes were more prevalent in those with colonic polyps than in the control people (67% vs 16%, P = 0.001; 11% vs 2%, P = 0.048). In addition, the cytokine serum levels were higher, i.e., IL-2 (P = 0.001), IL-4 (P = 0.001), IL-6 (P = 0.001), IL-17A (P = 0.001), IL-23 (P = 0.014), and CRP (P = 0.003). Adjusting for sex, smoking, and diabetes in a multivariate analysis, IL-2, IL-4, IL-6, IL-17A, and IL-23 remained independently elevated in cases with multiple polyps.

Discussion: These results indicate that immune responses mediated by Th17 cells may be involved in the pathogenesis of multiple colonic polyps.
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http://dx.doi.org/10.14309/ctg.0000000000000143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7145049PMC
March 2020

Changes in the requirement for early surgery in inflammatory bowel disease in the era of biological agents.

J Gastroenterol Hepatol 2020 Dec 10;35(12):2080-2087. Epub 2020 May 10.

Hospital Universitari Germans Trias i Pujol (Badalona, Catalonia), Barcelona, Spain.

Background And Aim: Biological therapies may be changing the natural history of inflammatory bowel diseases (IBDs), reducing the need for surgical intervention. We aimed to assess whether the availability of anti-TNF agents impacts the need for early surgery in Crohn's disease (CD) and ulcerative colitis (UC).

Methods: Retrospective, cohort study of patients diagnosed within a 6-year period before and after the licensing of anti-TNFs (1990-1995 and 2007-2012 for CD; 1995-2000 and 2007-2012 for UC) were identified in the ENEIDA Registry. Surgery-free survival curves were compared between cohorts.

Results: A total of 7370 CD patients (2022 in Cohort 1 and 5348 in Cohort 2) and 8069 UC patients (2938 in Cohort 1 and 5131 in Cohort 2) were included. Immunosuppressants were used significantly earlier and more frequently in both CD and UC post-biological cohorts. The cumulative probability of surgery was lower in CD following anti-TNF approval (16% and 11%, 22% and 16%, and 29% and 19%, at 1, 3, and 5 years, respectively P < 0.0001), although not in UC (3% and 2%, 4% and 4%, and 6% and 5% at 1, 3, and 5 years, respectively; P = 0.2). Ileal involvement, older age at diagnosis and active smoking in CD, and extensive disease in UC, were independent risk factors for surgery, whereas high-volume IBD centers (in both CD and UC) and immunosuppressant use (in CD) were protective factors.

Conclusions: Anti-TNF availability was associated with a reduction in early surgery for CD (driven mainly by earlier and more widespread immunosuppressant use) but not in UC.
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http://dx.doi.org/10.1111/jgh.15084DOI Listing
December 2020

Patterns of antimicrobial consumption in neonatal and pediatric intensive care units in Germany and Brazil.

Eur J Clin Microbiol Infect Dis 2020 Feb 31;39(2):249-255. Epub 2019 Oct 31.

Infectiology Service, Dr. von Hauner Children's Hospital, LMU Munich, 80337, Munich, Germany.

Antibiotic consumption (AC) is a key component of antimicrobial stewardship programs to recognize local patterns of antibiotic use. Our aim was to measure AC in neonatal units, including neonatal (NICU)/paediatric (PICU) intensive care units in different countries. We conducted a multicenter, retrospective, cohort study in three NICUs, one neonatal ward, and three PICUs with a total of 84 beds. Global and individual AC in days of therapy (DOT) and DOT per 1000 patient-days were assessed. During the study period, 2567 patients were admitted, corresponding to 4961 patient-days in neonatal units and 9243 patient-days in PICUs. Multidrug-resistant Gram-negative bacteria and methicillin-resistant Staphylococcus aureus were more frequent in Brazil than in Germany. Average AC was 386.5 and 1335.5 DOT/1000PD in German and Brazilian neonatal units, respectively. Aminopenicillins plus 3rd generation cephalosporins were the most commonly prescribed antibiotics in German neonatal units, while aminopenicillins plus aminoglycosides were the class most commonly used in Brazilian NICU. Average AC was 888.1 and 1440.7 DOT/1000PD in German and Brazilian PICUs, respectively. Antipseudomonal penicillins were most commonly used in the German PICU, and glycopeptides were the most frequently prescribed in Brazilian PICUs. Carbapenems represented 2.3-14% of total DOTs in German neonatal units and 4% in the Brazilian NICU and 13.0% in the German PICU and 6-12.2% in Brazilian PICUs. We concluded that different patterns of most commonly prescribed antibiotics were observed in neonatal units and PICUs in these two countries, probably related to different local patterns of antibiotic resistance, with a higher antibiotic consumption in Brazilian study units.
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http://dx.doi.org/10.1007/s10096-019-03714-9DOI Listing
February 2020

Effectiveness and Safety of the Sequential Use of a Second and Third Anti-TNF Agent in Patients With Inflammatory Bowel Disease: Results From the Eneida Registry.

Inflamm Bowel Dis 2020 03;26(4):606-616

Gastroenterology Department at Hospital Clínico Universitario de Salamanca, Salamanca.

Background: The effectiveness of the switch to another anti-tumor necrosis factor (anti-TNF) agent is not known. The aim of this study was to analyze the effectiveness and safety of treatment with a second and third anti-TNF drug after intolerance to or failure of a previous anti-TNF agent in inflammatory bowel disease (IBD) patients.

Methods: We included patients diagnosed with IBD from the ENEIDA registry who received another anti-TNF after intolerance to or failure of a prior anti-TNF agent.

Results: A total of 1122 patients were included. In the short term, remission was achieved in 55% of the patients with the second anti-TNF. The incidence of loss of response was 19% per patient-year with the second anti-TNF. Combination therapy (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.8-3; P < 0.0001) and ulcerative colitis vs Crohn's disease (HR, 1.6; 95% CI, 1.1-2.1; P = 0.005) were associated with a higher probability of loss of response. Fifteen percent of the patients had adverse events, and 10% had to discontinue the second anti-TNF. Of the 71 patients who received a third anti-TNF, 55% achieved remission. The incidence of loss of response was 22% per patient-year with a third anti-TNF. Adverse events occurred in 7 patients (11%), but only 1 stopped the drug.

Conclusions: Approximately half of the patients who received a second anti-TNF achieved remission; nevertheless, a significant proportion of them subsequently lost response. Combination therapy and type of IBD were associated with loss of response. Remission was achieved in almost 50% of patients who received a third anti-TNF; nevertheless, a significant proportion of them subsequently lost response.
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http://dx.doi.org/10.1093/ibd/izz192DOI Listing
March 2020

Clinical Characteristics, Associated Malignancies and Management of Primary Sclerosing Cholangitis in Inflammatory Bowel Disease Patients: A Multicentre Retrospective Cohort Study.

J Crohns Colitis 2019 Dec;13(12):1492-1500

Consorci Sanitari Terrassa, Terrassa, Spain.

Background And Aims: Primary sclerosing cholangitis [PSC] is usually associated with inflammatory bowel disease [IBD]. An increased risk of malignancies, mainly colorectal cancer [CRC] and cholangiocarcinoma [CCA], has been reported in PSC-IBD patients. Our aim was to determine the clinical characteristics and management of PSC in IBD patients, and the factors associated with malignancies.

Methods: PSC-IBD patients were identified from the Spanish ENEIDA registry of GETECCU. Additional data were collected using the AEG-REDCap electronic data capture tool.

Results: In total, 277 PSC-IBD patients were included, with an incidence rate of 61 PSC cases per 100 000 IBD patient-years, 69.7% men, 67.5% ulcerative colitis and mean age at PSC diagnosis of 40 ± 16 years. Most patients [85.2%] were treated with ursodeoxycholic acid. Liver transplantation was required in 35 patients [12.6%] after 79 months (interquartile range [IQR] 50-139). It was more common in intra- and extrahepatic PSC compared with small-duct PSC (16.3% vs 3.3%; odds ratio [OR] 5.7: 95% confidence interval [CI] = 1.7-19.3). The incidence rate of CRC since PSC diagnosis was 3.3 cases per 1000 patient-years [95% CI = 1.9-5.6]. Having symptoms of PSC at PSC diagnosis was the only factor related to an increased risk of CRC after IBD diagnosis [hazard ratio= 3.3: 95% CI = 1.1-9.9]. CCA was detected in seven patients [2.5%] with intra- and extrahepatic PSC, with median age of 42 years [IQR 39-53], and presented a lower life expectancy compared with patients without CCA and patients with or without CRC.

Conclusions: PSC-IBD patients with symptoms of PSC at PSC diagnosis have an increased risk of CRC. CCA was only diagnosed in patients with intra- and extrahepatic PSC and was associated with poor survival.
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http://dx.doi.org/10.1093/ecco-jcc/jjz094DOI Listing
December 2019

Adalimumab or Infliximab for the Prevention of Early Postoperative Recurrence of Crohn Disease: Results From the ENEIDA Registry.

Inflamm Bowel Dis 2019 10;25(11):1862-1870

Complejo Hospitalario Universitario de Vigo, Vigo, Spain.

Background: Anti-tumor necrosis factor agents (anti-TNFs) are efficacious at preventing the postoperative recurrence (POR) of Crohn disease, as demonstrated in 2 randomized controlled trials. However, real-life data for infliximab or adalimumab in this setting are scarce. Our aim was to assess both the efficiency of anti-TNFs at preventing early POR of Crohn disease in clinical practice and the associated risk factors for POR.

Methods: Patients in whom anti-TNFs were prescribed for the prevention of POR within 3 months after ileocolonic resection and who had an endoscopic assessment within 18 months were identified from the ENEIDA registry. Clinical and endoscopic features were collected within 18 months after surgery.

Results: In total, 152 patients were included (55 treated with infliximab, 97 with adalimumab, and 39% with concomitant immunosuppressants). Anti-TNF treatment was started after a median time of 29 days (IQR 13-44) after surgery. Eighty-two percent of patients had at least one risk factor for POR, and 82% had been exposed to anti-TNFs before the index surgery. Overall, 34% had endoscopic POR (as defined using a Rutgeerts endoscopic score > i1); 14% had advanced endoscopic POR (>i2); and 20% had clinical POR, with no differences between infliximab and adalimumab. In the multivariate analysis, only perianal disease (odds ratio 2.73, 95% confidence interval [CI] 1.26-5.91) and rectal involvement (odds ratio 2.79, 95% CI 1.09-7.14) were independent predictors of endoscopic POR.

Conclusions: In clinical practice, anti-TNFs for the prevention of POR of Crohn disease are frequently used in patients experienced with anti-TNFs and with concomitant immunosuppressants. The efficacy of infliximab and adalimumab for POR prevention is similar and in accordance with the results obtained in randomized controlled trials.
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http://dx.doi.org/10.1093/ibd/izz084DOI Listing
October 2019

Accuracy of the Narrow-Band Imaging International Colorectal Endoscopic Classification System in Identification of Deep Invasion in Colorectal Polyps.

Gastroenterology 2019 01 6;156(1):75-87. Epub 2018 Oct 6.

Gastroenterology Department, Institut de Malalties Digestives i Metabòliques, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Biomedical Research Networking Center in Hepatic and Digestive Diseases, Madrid, Spain.

Background & Aims: T1 colorectal polyps with at least 1 risk factor for metastasis to lymph node should be treated surgically and are considered endoscopically unresectable. Optical analysis, based on the Narrow-Band Imaging International Colorectal Endoscopic (NICE) classification system, is used to identify neoplasias with invasion of the submucosa that require endoscopic treatment. We assessed the accuracy of the NICE classification, along with other morphologic characteristics, in identifying invasive polyps that are endoscopically unresectable (have at least 1 risk factor for metastasis to lymph node).

Methods: We performed a multicenter, prospective study of data collected by 58 endoscopists, from 1634 consecutive patients (examining 2123 lesions) at 17 university and community hospitals in Spain from July 2014 through June 2016. All consecutive lesions >10 mm assessed with narrow-band imaging were included. The primary end point was the accuracy of the NICE classification for identifying lesions with deep invasion, using findings from histology analysis as the reference standard. Conditional inference trees were fitted for the analysis of diagnostic accuracy.

Results: Of the 2123 lesions analyzed, 89 (4.2%) had features of deep invasion and 91 (4.3%) were endoscopically unresectable. The NICE classification system identified lesions with deep invasion with 58.4% sensitivity (95% CI, 47.5-68.8), 96.4% specificity (95% CI, 95.5-97.2), a positive-predictive value of 41.6% (95% CI, 32.9-50.8), and a negative-predictive value of 98.1% (95% CI, 97.5-98.7). A conditional inference tree that included all variables found the NICE classification to most accurately identify lesions with deep invasion (P < .001). However, pedunculated morphology (P < .007), ulceration (P = .026), depressed areas (P < .001), or nodular mixed type (P < .001) affected accuracy of identification. Results were comparable for identifying lesions that were endoscopically unresectable.

Conclusions: In an analysis of 2123 colon lesions >10 mm, we found the NICE classification and morphologic features identify those with deep lesions with >96% specificity-even in non-expert hands and without magnification. ClinicalTrials.gov number NCT02328066.
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http://dx.doi.org/10.1053/j.gastro.2018.10.004DOI Listing
January 2019

Natural Disease Course of Ulcerative Colitis During the First Five Years of Follow-up in a European Population-based Inception Cohort-An Epi-IBD Study.

J Crohns Colitis 2019 Feb;13(2):198-208

IBD Clinical and Research Centre, ISCARE, Prague, Czech Republic.

Background And Aims: Few population-based cohort studies have assessed the disease course of ulcerative colitis [UC] in the era of biological therapy and widespread use of immunomodulators. The aim of this study was to assess the 5-year outcome and disease course of patients with UC in the Epi-IBD cohort.

Methods: In a prospective, population-based inception cohort of unselected patients with UC, patients were followed up from the time of their diagnosis, which included the collection of their clinical data, demographics, disease activity, medical therapy, and rates of surgery, cancers, and deaths. Associations between outcomes and multiple covariates were analysed by Cox regression analysis.

Results: A total of 717 patients were included in the study. During follow-up, 43 [6%] patients underwent a colectomy and 163 [23%] patients were hospitalised. Of patients with limited colitis [distal to the left flexure], 90 [21%] progressed to extensive colitis. In addition, 92 [27%] patients with extensive colitis experienced a regression in disease extent, which was associated with a reduced risk of hospitalisation (hazard ratio [HR]: 0.5 95% CI: 0.3-0.8]. Overall, patients were treated similarly in both geographical regions; 80 [11%] patients needed biological therapy and 210 [29%] patients received immunomodulators. Treatment with immunomodulators was found to reduce the risk of hospitalisation [HR: 0.5 95% CI: 0.3-0.8].

Conclusions: Although patients in this population-based cohort were treated more aggressively with immunomodulators and biological therapy than in cohorts from the previous two decades, their disease outcomes, including colectomy rates, were no different. However, treatment with immunomodulators was found to reduce the risk of hospitalisation.
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http://dx.doi.org/10.1093/ecco-jcc/jjy154DOI Listing
February 2019

Short and long-term effectiveness and safety of vedolizumab in inflammatory bowel disease: results from the ENEIDA registry.

Aliment Pharmacol Ther 2018 10;48(8):839-851

Barcelona, Spain.

Background: Effectiveness of vedolizumab in real world clinical practice is unknown.

Aim: To evaluate the short and long-term effectiveness of vedolizumab in patients with inflammatory bowel disease (IBD).

Methods: Patients who received at least 1 induction dose of vedolizumab were included. Effectiveness was defined based on Harvey-Bradshaw index (HBI) in Crohn's disease (CD) and Partial Mayo Score (PMS) in ulcerative colitis (UC). Short-term response was assessed at week 14. Variables associated with short-term remission were identified by logistic regression analysis. The Kaplan-Meier method was used to evaluate the long-term durability of vedolizumab treatment. Cox model was used to identify factors associated with discontinuation of treatment and loss of response.

Results: 521 patients were included (median follow-up 10 months [interquartile range 5-18 months]). At week 14, 46.8% had remission and 15.7% clinical response. CD (vs UC), previous surgery, higher CRP concentration and disease severity at baseline were significantly associated with impaired response. The rate of vedolizumab discontinuation was 37% per patient-year of follow-up (27.6% in UC and 45.3% in CD, P < 0.01). CD (vs UC), anaemia at baseline, steroids during induction and CRP concentration were associated with lower durability of treatment. Seven per cent of patients developed adverse events, infections being the most frequent.

Conclusions: Over 60% of IBD patients respond to vedolizumab. Many patients discontinue treatment over time. CD and disease burden impair both short- and long-term response. Vedolizumab seems to be safe in clinical practice.
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http://dx.doi.org/10.1111/apt.14930DOI Listing
October 2018

Increased Risk of Colorectal Cancer in Patients With Multiple Serrated Polyps and Their First-Degree Relatives.

Gastroenterology 2017 07 9;153(1):106-112.e2. Epub 2017 Apr 9.

Research Laboratory, Alicante University General Hospital, Alicante Institute for Health and Biomedical Research Instituto de Investigación Sanitaria y Biomédica de Alicante, Alicante, Spain; Service of Digestive Medicine, Alicante University General Hospital, Alicante Institute for Health and Biomedical Research Instituto de Investigación Sanitaria y Biomédica de Alicante, Alicante, Spain. Electronic address:

Background & Aims: We investigated whether patients with multiple serrated polyps, but not meeting the World Health Organization criteria for serrated polyposis syndrome, and their relatives have similar risks for colorectal cancer (CRC) as those diagnosed with serrated polyposis.

Methods: We collected data from patients with more than 10 colonic polyps, recruited in 2008-2009 from 24 hospitals in Spain for a study of causes of multiple colonic polyps. We analyzed data from 53 patients who met the criteria for serrated polyposis and 145 patients who did not meet these criteria, but who had more than 10 polyps throughout the colon, of which more than 50% were serrated. We calculated age- and sex-adjusted standardized incidence ratios (SIRs) for CRC in both groups, as well as in their first-degree relatives.

Results: The prevalence of CRC was similar between patients with confirmed serrated polyposis and multiple serrated polyps (odds ratio, 1.35; 95% confidence interval [CI], 0.64-2.82; P = .40). The SIR for CRC in patients with serrated polyposis (0.51; 95% CI, 0.01-2.82) did not differ significantly from the SIR for CRC in patients with multiple serrated polyps (0.74; 95% CI, 0.20-1.90; P = .70). The SIR for CRC also did not differ significantly between first-degree relatives of these groups (serrated polyposis: 3.28, 95% CI, 2.16-4.77; multiple serrated polyps: 2.79, 95% CI, 2.10-3.63; P = .50). Kaplan-Meier analysis showed no differences in the incidence of CRC between groups during the follow-up period (log-rank, 0.6).

Conclusions: The risk of CRC in patients with multiple serrated polyps who do not meet the criteria for serrated polyposis, and in their first-degree relatives, is similar to that of patients diagnosed with serrated polyposis.
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http://dx.doi.org/10.1053/j.gastro.2017.04.003DOI Listing
July 2017

Real-life chromoendoscopy for neoplasia detection and characterisation in long-standing IBD.

Gut 2018 01 9;67(1):70-78. Epub 2016 Sep 9.

Gastroenterology Department, Hospital Clínic de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain.

Objective: Outside clinical trials, the effectiveness of chromoendoscopy (CE) for long-standing IBD surveillance is controversial. We aimed to assess the effectiveness of CE for neoplasia detection and characterisation, in real-life.

Design: From June 2012 to 2014, patients with IBD were prospectively included in a multicentre cohort study. Each colonic segment was evaluated with white light followed by 0.4% indigo carmine CE. Specific lesions' features were recorded. Optical diagnosis was assessed. Dysplasia detection rate between expert and non-expert endoscopists and learning curve were ascertained.

Results: Ninety-four (15.7%) dysplastic (1 cancer, 5 high-grade dysplasia, 88 low-grade dysplasia) and 503 (84.3%) non-dysplastic lesions were detected in 350 patients (47% female; mean disease duration: 17 years). Colonoscopies were performed with standard definition (41.5%) or high definition (58.5%). Dysplasia miss rate with white light was 40/94 (57.4% incremental yield for CE). CE-incremental detection yield for dysplasia was comparable between standard definition and high definition (51.5% vs 52.3%, p=0.30). Dysplasia detection rate was comparable between expert and non-expert (18.5% vs 13.1%, p=0.20). No significant learning curve was observed (8.2% vs 14.2%, p=0.46). Sensitivity, specificity, and positive and negative predictive values for dysplasia optical diagnosis were 70%, 90%, 58% and 94%, respectively. Endoscopic characteristics predictive of dysplasia were: proximal location, loss of innominate lines, polypoid morphology and Kudo pit pattern III-V.

Conclusions: CE presents a high diagnostic yield for neoplasia detection, irrespectively of the technology and experience available in any centre. In vivo, CE optical diagnosis is highly accurate for ruling out dysplasia, especially in expert hands. Lesion characteristics can aid the endoscopist for in situ therapeutic decisions.

Trial Registration Number: NCT02543762.
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http://dx.doi.org/10.1136/gutjnl-2016-312332DOI Listing
January 2018

Endoscopic surveillance in patients with multiple (10-100) colorectal polyps.

Endoscopy 2016 Jan 10;48(1):56-61. Epub 2015 Jul 10.

Department of Gastroenterology, Complexo Hospitalario Universitario de Ourense, Ourense, Spain.

Background And Study Aims: Endoscopic surveillance in patients with multiple colorectal polyps aims to reduce colorectal cancer (CRC) incidence and mortality, as well as the need for colorectal surgery. The aim of this study was to determine the risk of developing CRC or the need for surgery during endoscopic surveillance in a cohort of patients with multiple (10 - 100) colorectal polyps.

Patients And Methods: This was a multicentrer, longitudinal, observational study in 15 CRC high risk clinics in Spain, carried out between January 2009 and December 2010. Patients who were included in the EPIPOLIP trial and had at least 1 year of follow-up were included in the study. The primary outcome of interest was the incidence of CRC at least 1 year following the initial colonoscopy. The secondary outcome was the need for colorectal surgery.

Results: A total of 265 patients were followed for a median of 3.8 years. Patients underwent a median of 5 colonoscopies, and 17 patients (6.4 %) were diagnosed with CRC. A total of 32 patients (12.1 %) underwent surgery, including 15 (5.7 %) for prophylaxis without a diagnosis of CRC. The corresponding incidence density rates for CRC and colorectal surgery were 1.4 (95 % confidence interval [CI] 0.7 to 2.1) and 2.7 (95 %CI 1.7 to 3.6) per 100 patient-years, respectively. Only the presence of symptoms at first colonoscopy was independently associated with CRC diagnosis (hazard ratio [HR] 7.7, 95 %CI 1.1 to 59.3) and colorectal surgery (HR 4.6, 95 %CI 1.02 to 20.6).

Conclusions: Patients with more than 10 neoplastic polyps required frequent colonoscopies within a short follow-up period. More than 10 % of patients required colorectal surgery within 4 years, more than half for incident CRC.
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http://dx.doi.org/10.1055/s-0034-1392515DOI Listing
January 2016

Diagnostic accuracy of fecal immunochemical test in average- and familial-risk colorectal cancer screening.

United European Gastroenterol J 2014 Dec;2(6):522-9

Department of Gastroenterology, Complexo Hospitalario Universitario de Ourense, Ourense, Spain.

Background: There is little information about the fecal immunochemical test (FIT) in familial-risk colorectal cancer (CRC) screening.

Objectives: The objective of this article is to investigate whether FIT diagnostic accuracy for advanced neoplasia (AN) differs between average and familial-risk (first-degree relative) patients.

Methods: A total of 1317 consecutive participants (595 familial) who collected one stool sample before performing a colonoscopy as a CRC screening test were included. FIT diagnostic accuracy for AN was evaluated with Chi-square test at a 20 µg hemoglobin/g of feces cut-off value. Finally, we determined which variables were independently related to AN.

Results: An AN was found in 151 (11.5%) patients. The overall accuracy was not statistically different between both cohorts for AN (88.4%, 91.7%; p = 0.051). At the cut-off stablished, differences in FIT sensitivity (31.1%, 40.6%; p = 0.2) or specificity (96.5%, 97.3%; p = 0.1) were not statistically significant. Finally, independent variables such as sex (male) (odds ratio (OR) 2.1, 95% confidence interval (CI) 1.4-3.1), age (50-65, >65 years) (OR 2.1, 95% CI 1.1-4.3; OR 2.7, 95% CI 1.2-6.1), previous colonoscopy (OR 0.4, 95% CI 0.2-0.9) and FIT ≥20 µg/g feces (OR 17.7, 95% CI 10.8-29.1) were associated with AN diagnosis.

Conclusions: FIT accuracy for AN detection is equivalent in average and familial-risk CRC screening cohorts.
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http://dx.doi.org/10.1177/2050640614553285DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4245302PMC
December 2014

Diagnostic performance of fecal immunochemical test and sigmoidoscopy for advanced right-sided colorectal neoplasms.

Dig Dis Sci 2015 May 19;60(5):1424-32. Epub 2014 Nov 19.

Department of Gastroenterology, Complexo Hospitalario Universitario de Ourense, Rua Ramón Puga 52-54, 32003, Ourense, Spain.

Background: Colorectal cancer screening effect on right-sided colorectal neoplasia is limited. We compared fecal immunochemical test and simulated sigmoidoscopy diagnostic accuracy for advanced right-sided neoplasia detection.

Methods: We analyzed 1,292 individuals with complete screening colonoscopy with a fecal immunochemical test determination before colonoscopy. Sigmoidoscopy and "hybrid strategy" (sigmoidoscopy or fecal hemoglobin concentration ≥ 20 µg hemoglobin/g) diagnostic yield were simulated according to UK Flexible Sigmoidoscopy, Screening for COlon REctum (SCORE), and Norwegian Colorectal Cancer Prevention (NORCCAP) trials criteria to complete colonic examination. We compared sensitivity and specificity of both strategies and of "hybrid strategy" for advanced right-sided neoplasia with McNemar test.

Results: An advanced right-sided neoplasia was detected in 47 (3.6 %) subjects. A fecal hemoglobin concentration ≥ 20 µg hemoglobin/g was determined in 6.6 % of the subjects and 10.1, 12.7, and 23.5 % met UK, SCORE, and NORCCAP criteria, respectively. Fecal immunochemical test was statistically more specific than sigmoidoscopy strategies (93.8 %, UK 90.3 %, SCORE 87.7 %, NORCCAP 77.8 %; p < 0.001). In contrast, fecal immunochemical test sensitivity for advanced right-sided neoplasia (17 %) was not statistically different than UK (21.3 %; p = 0.7) or SCORE (23.4 %; p = 0.5), although it was inferior than NORCCAP strategy (42.5 %; p < 0.001). Adding fecal immunochemical test to sigmoidoscopy increased number of positives (8.5-25.7 %), sensitivity (10-30 %), and significantly reduced advanced right-sided neoplasia specificity (p < 0.001).

Conclusions: Fecal immunochemical test and sigmoidoscopy diagnostic yield for advanced right-sided neoplasia are low. Fecal immunochemical test is more specific than sigmoidoscopy but less sensitive than sigmoidoscopy according to NORCCAP criteria.
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http://dx.doi.org/10.1007/s10620-014-3434-6DOI Listing
May 2015

Characteristics of adenomas detected by fecal immunochemical test in colorectal cancer screening.

Cancer Epidemiol Biomarkers Prev 2014 Sep 24;23(9):1884-92. Epub 2014 Jun 24.

Department of Gastroenterology, Complexo Hospitalario Universitario de Ourense, Ourense, Spain.

Background: Fecal immunochemical test (FIT) diagnostic accuracy for colorectal adenoma detection in colorectal cancer screening is limited.

Methods: We analyzed 474 asymptomatic subjects with adenomas detected on colonoscopy in two blinded diagnostic tests studies designed to assess FIT diagnostic accuracy. We determined the characteristics of adenomas (number, size, histology, morphology, and location) and the risk of metachronous lesions (according to European guidelines). Finally, we performed a logistic regression to identify those variables independently associated with a positive result.

Results: Advanced adenomas were found in 145 patients (75.6% distal and 24.3% only proximal to splenic flexure). Patients were classified as low (59.5%), intermediate (30.2%), and high risk (10.3%) according to European guidelines. At a 100-ng/mL threshold, FIT was positive in 61 patients (12.8%). Patients with advanced adenomas [odds ratio (OR), 8.8; 95% confidence interval (CI), 4.76-16.25], distal advanced adenomas (OR, 6.7; 95% CI, 1.9-8.8), high risk (OR, 20.1; 95% CI, 8.8-45.8), or intermediate risk lesions (OR, 6; 95% CI, 2.9-12.4) had more probabilities to have a positive test. The characteristics of adenomas independently associated were number of adenomas (OR, 1.22; 95% CI, 1.04-1.42), distal flat adenomas (OR, 0.44; 95% CI, 0.21-0.96), pedunculated adenomas (OR, 2.28; 95% CI, 1.48-3.5), and maximum size of distal adenomas (mm; OR, 1.24; 95% CI, 1.16-1.32).

Conclusions: European guidelines classification and adenoma location correlates with the likelihood of a positive FIT result.

Impact: This information allows us to understand the FIT impact in colorectal cancer prevention. Likewise, it should be taken into account in the development of new colorectal adenomas biomarkers.
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http://dx.doi.org/10.1158/1055-9965.EPI-13-1346DOI Listing
September 2014

Fecal immunochemical test accuracy in average-risk colorectal cancer screening.

World J Gastroenterol 2014 Jan;20(4):1038-47

Vicent Hernandez, Felipe Iglesias, Lucía Cid, Luisa de Castro, Jose Antonio Hermo, Alfonso Martínez-Turnes, David Martínez-Ares, Pamela Estevez, M Carmen Vidal, Jose Ignacio Rodriguez-Prada; the COLONPREV study investigators, Department of Gastroenterology, Complexo Hospitalario Universitario de Vigo, 36200 Vigo, Spain.

Aim: To assess the fecal immunochemical test (FIT) accuracy for colorectal cancer (CRC) and advanced neoplasia (AN) detection in CRC screening.

Methods: We performed a multicentric, prospective, double blind study of diagnostic tests on asymptomatic average-risk individuals submitted to screening colonoscopy. Two stool samples were collected and the fecal hemoglobin concentration was determined in the first sample (FIT1) and the highest level of both samples (FITmax) using the OC-sensor™. Areas under the curve (AUC) for CRC and AN were calculated. The best FIT1 and FITmax cut-off values for CRC were determined. At this threshold, number needed to scope (NNS) to detect a CRC and an AN and the cost per lesion detected were calculated.

Results: About 779 individuals were included. An AN was found in 97 (12.5%) individuals: a CRC in 5 (0.6%) and an advanced adenoma (≥ 10 mm, villous histology or high grade dysplasia) in 92 (11.9%) subjects. For CRC diagnosis, FIT1 AUC was 0.96 (95%CI: 0.95-0.98) and FITmax AUC was 0.95 (95%CI: 0.93-0.97). For AN, FIT1 and FITmax AUC were similar (0.72, 95%CI: 0.66-0.78 vs 0.73, 95%CI: 0.68-0.79, respectively, P = 0.34). Depending on the number of determinations and the positivity threshold cut-off used sensitivity for AN detection ranged between 28% and 42% and specificity between 91% and 97%. At the best cut-off point for CRC detection (115 ng/mL), the NNS to detect a CRC were 10.2 and 15.8; and the cost per CRC was 1814€ and 2985€ on FIT1 and FITmax strategies respectively. At this threshold the sensitivity, NNS and cost per AN detected were 30%, 1.76, and 306€, in FIT1 strategy, and 36%, 2.26€ and 426€, in FITmax strategy, respectively.

Conclusion: Performing two tests does not improve diagnostic accuracy, but increases cost and NNS to detect a lesion.
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http://dx.doi.org/10.3748/wjg.v20.i4.1038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3921527PMC
January 2014

Prevalence and characteristics of MUTYH-associated polyposis in patients with multiple adenomatous and serrated polyps.

Clin Cancer Res 2014 Mar 27;20(5):1158-68. Epub 2014 Jan 27.

Authors' Affiliations: Unidad de Investigación, Departments of Pathology, and Gastroenterology, Hospital General Universitario, Alicante; Department of Gastroenterology, Complexo Hospitalario Universitario de Ourense, Ourense; Department of Gastroenterology, Bellvitge University Hospital; Institut de Malaties Digestives i Metabòliques, CIBERehd, Hospital Clínic; Department of Oncology, Hospital Vall d'Hebrón, Barcelona; Gastroenterology Department, Complexo Hospitalario de Vigo, Vigo; Department of Gastroenterology, Hospital Donostia, CIBERehd, Universidad del País Vasco, San Sebastián; Department of Gastroenterology, Hospital Universitario de Canarias, La Laguna, Tenerife; Department of Gastroenterology, Clínica Universitaria de Navarra, Pamplona; Department of Gastroenterology, Hospital Mútua de Terrassa, Terrassa; Department of Gastroenterology, Hospital Puerta de Hierro, Madrid; Department of Oncology, Hospital Arnau de Vilanova, Lleida; Department of Gastroenterology, Hospital Bidasoa, Irún; Department of Gastroenterology, Hospital Universitario Virgen del Rocío, Sevilla; Department of Gastroenterology, Hospital Basurto, Bilbao; Department of Molecular Genetics, Hospital General Universitario, Elche, Spain; and Gastrointestinal Cancer Research Laboratory, Baylor Research Institute, Baylor University Medical Center, Dallas, Texas.

Purpose: The present study aimed to determine the prevalence of MUTYH mutations in patients with multiple colonic polyps and to explore the best strategy for diagnosing MUTYH-associated polyposis (MAP) in these patients.

Experimental Design: This study included 405 patients with at least 10 colonic polyps each. All cases were genetically tested for the three most frequent MUTYH mutations. Whole-gene analysis was performed in heterozygous patients and in 216 patients lacking the three most frequent mutations. Polyps from 56 patients were analyzed for the KRAS-Gly12Cys and BRAF V600E somatic mutations.

Results: Twenty-seven (6.7%) patients were diagnosed with MAP, of which 40.8% showed serrated polyps. The sensitivity of studying only the three common variants was 74.1%. Of 216 patients without any monoallelic mutation in common variants, whole-gene analysis revealed biallelic pathogenic mutation in only one. G396D mutation was associated with serrated lesions and older age at diagnosis. There was a strong association between germinal MUTYH mutation and KRAS Gly12Cys somatic mutation in polyps. BRAF V600E mutation was found in 74% of serrated polyps in MUTYH-negative patients and in none of the polyps of MAP patients.

Conclusions: We observed a low frequency of MUTYH mutations among patients with multiple adenomatous and serrated polyps. The MAP phenotype frequently included patients with serrated polyps, especially when G396D mutation was involved. Our results show that somatic molecular markers of polyps can be useful in identifying MAP cases and support the need for the complete MUTYH gene analysis only in patients heterozygous for recurrent variants.
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http://dx.doi.org/10.1158/1078-0432.CCR-13-1490DOI Listing
March 2014

Clinical subtypes and molecular characteristics of serrated polyposis syndrome.

Clin Gastroenterol Hepatol 2013 Jun 30;11(6):705-11; quiz e46. Epub 2013 Jan 30.

Unidad de Investigación, Hospital General Universitario de Alicante, Alicante, Spain.

Background & Aims: We investigated clinical and molecular differences between the different phenotypes of serrated polyposis syndrome (SPS) and the frequency of mutations in BRAF or KRAS in polyps from patients with SPS.

Methods: We collected data on clinical and demographic characteristics of 50 patients who fulfilled the criteria for SPS. Polymerase chain reaction and sequence analysis were used to identify BRAF and KRAS mutations in 432 polyps collected from 37 patients; we analyzed CpG island methylator phenotypes in 272 of these polyps.

Results: Fifteen patients (30%) had type 1 SPS and 35 had type 2 SPS. There were no significant differences in age at diagnosis, sex, smoking frequency, body mass index, or colorectal cancer predisposition between groups of patients, or in the pathologic or molecular characteristics of their polyps. A familial history of colorectal cancer or colonic polyps was reported more frequently by patients with type 2 SPS. BRAF mutations were found in 63% of polyps and KRAS mutations were found in 9.9%; 43.4% of polyps had the CpG island methylator phenotype-high phenotype. A per-patient analysis revealed that all patients had a BRAF or KRAS mutation in more than 25% of their polyps; 84.8% of patients had a mutation in BRAF or KRAS in more than 50% of their polyps.

Conclusions: Except for a greater likelihood of familial history of colorectal cancer or colonic polyps in patients with type 2 SPS, we found no significant demographic, pathologic, or molecular differences between types 1 and 2 SPS. All patients had a BRAF or KRAS mutation in at least 25% of their polyps.
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http://dx.doi.org/10.1016/j.cgh.2012.12.045DOI Listing
June 2013

Risk of cancer in cases of suspected lynch syndrome without germline mutation.

Gastroenterology 2013 May 24;144(5):926-932.e1; quiz e13-4. Epub 2013 Jan 24.

Unidad de Gastroenterología, Hospital General Universitario de Alicante, Alicante, Spain.

Background & Aims: Colorectal cancers (CRCs) with microsatellite instability (MSI) and a mismatch repair (MMR) immunohistochemical deficit without hypermethylation of the MLH1 promoter are likely to be caused by Lynch syndrome. Some patients with these cancers have not been found to have pathogenic germline mutations and are considered to have Lynch-like syndrome (LLS). The aim of this study was to determine the risk of cancer in families of patients with LLS.

Methods: We studied a population-based cohort of 1705 consecutive patients, performing MSI tests and immunohistochemical analyses of MMR proteins. Patients were diagnosed with Lynch syndrome when they were found to have pathogenic germline mutations. Patients with MSI and loss of MSH2 and/or MSH6 expression, isolated loss of PMS2 or loss of MLH1 without MLH1 promoter hypermethylation, and no pathogenic mutation were considered to have LLS. The clinical characteristics of patients and the age- and sex-adjusted standardized incidence ratios (SIRs) of cancer in families were compared between groups.

Results: The incidence of CRC was significantly lower in families of patients with LLS than in families with confirmed cases of Lynch syndrome (SIR for Lynch syndrome, 6.04; 95% confidence interval [CI], 3.58-9.54; SIR for LLS, 2.12; 95% CI, 1.16-3.56; P < .001). However, the incidence of CRC was higher in families of patients with LLS than in families with sporadic CRC (SIR for sporadic CRC, 0.48; 95% CI, 0.27-0.79; P < .001).

Conclusions: The risk of cancer in families with LLS is lower that of families with Lynch syndrome but higher than that of families with sporadic CRC. These results confirm the need for special screening and surveillance strategies for these patients and their relatives.
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http://dx.doi.org/10.1053/j.gastro.2013.01.044DOI Listing
May 2013

Modifiable endoscopic factors that influence the adenoma detection rate in colorectal cancer screening colonoscopies.

Gastrointest Endosc 2013 Mar 4;77(3):381-389.e1. Epub 2012 Dec 4.

Unidad de Gastroenterología, Hospital General Universitario de Alicante, Alicante, Spain.

Background: Adenoma detection rate (ADR) has become the most important quality indicator for colonoscopy.

Objective: The aim of this study was to investigate which modifiable factors, directly related to the endoscopic procedure, influenced the ADR in screening colonoscopies.

Design: Observational, nested study.

Setting: Multicenter, randomized, controlled trials.

Patients: Asymptomatic people aged 50 to 69 years were eligible for a multicenter, randomized, controlled trial designed to compare colonoscopy and fecal immunochemical testing in colorectal cancer screening. A total of 4539 individuals undergoing a direct screening colonoscopy were included in this study.

Intervention: Colonoscopy.

Main Outcome Measurements: Bowel cleansing, sedation, withdrawal time in normal colonoscopies, and cecal intubation were analyzed as possible predictors of adenoma detection by using logistic regression analysis, adjusted for age and sex.

Results: In multivariate analysis, after adjustment for age and sex, factors independently related to the ADR were a mean withdrawal time longer than 8 minutes (odds ratio [OR] 1.51; 95% CI, 1.17-1.96) in normal colonoscopies and split preparation (OR 1.26; 95% CI, 1.01-1.57). For advanced adenomas, only withdrawal time maintained statistical significance in the multivariate analysis. For proximal adenomas, withdrawal time and cecal intubation maintained independent statistical significance, whereas only withdrawal time longer than 8 minutes and a <10-hour period between the end of preparation and colonoscopy showed independent associations for distal adenomas.

Limitations: Only endoscopic variables have been analyzed.

Conclusion: Withdrawal time was the only modifiable factor related to the ADR in colorectal cancer screening colonoscopies associated with an increased detection rate of overall, advanced, proximal, and distal adenomas.
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http://dx.doi.org/10.1016/j.gie.2012.09.027DOI Listing
March 2013

Single nucleotide polymorphisms in the Wnt and BMP pathways and colorectal cancer risk in a Spanish cohort.

PLoS One 2010 Sep 9;5(9). Epub 2010 Sep 9.

Galician Public Foundation of Genomic Medicine (FPGMX), Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Genomics Medicine Group, Hospital Clínico, Santiago de Compostela, University of Santiago de Compostela, Galicia, Spain.

Background: Colorectal cancer (CRC) is considered a complex disease, and thus the majority of the genetic susceptibility is thought to lie in the form of low-penetrance variants following a polygenic model of inheritance. Candidate-gene studies have so far been one of the basic approaches taken to identify these susceptibility variants. The consistent involvement of some signaling routes in carcinogenesis provided support for pathway-based studies as a natural strategy to select genes that could potentially harbour new susceptibility loci.

Methodology/principal Findings: We selected two main carcinogenesis-related pathways: Wnt and BMP, in order to screen the implicated genes for new risk variants. We then conducted a case-control association study in 933 CRC cases and 969 controls based on coding and regulatory SNPs. We also included rs4444235 and rs9929218, which did not fulfill our selection criteria but belonged to two genes in the BMP pathway and had consistently been linked to CRC in previous studies. Neither allelic, nor genotypic or haplotypic analyses showed any signs of association between the 37 screened variants and CRC risk. Adjustments for sex and age, and stratified analysis between sporadic and control groups did not yield any positive results either.

Conclusions/significance: Despite the relevance of both pathways in the pathogenesis of the disease, and the fact that this is indeed the first study that considers these pathways as a candidate-gene selection approach, our study does not present any evidence of the presence of low-penetrance variants for the selected markers in any of the considered genes in our cohort.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0012673PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2936577PMC
September 2010

Susceptibility genetic variants associated with colorectal cancer risk correlate with cancer phenotype.

Gastroenterology 2010 Sep 2;139(3):788-96, 796.e1-6. Epub 2010 Jun 2.

Department of Gastroenterology, Hospital del Mar, Institut Municipal d'Investigació Mèdica, Pompeu Fabra University, Barcelona, Catalonia, Spain.

Background & Aims: Ten common low-penetrant genetic variants have been consistently associated with colorectal cancer (CRC) risk; little is known about the correlation between these variants and CRC phenotype. Characterization of such a correlation would improve CRC management and prevention programs. We assessed the association between these genetic variants and CRC phenotype in patients and modeled pairwise combinations to detect epistasis.

Methods: The validation population corresponded to a prospective, multicenter, population-based cohort (EPICOLON I) of 1096 patients with newly diagnosed CRC. The replication set was an independent, prospective, multicenter Spanish cohort (EPICOLON II) of 895 patients with newly diagnosed CRC. For individual single nucleotide polymorphism (SNP) association analyses, a multivariate method using logistic regression was applied in EPICOLON I and subsequently prospectively validated in EPICOLON II. Interactions between SNPs were assessed using the likelihood ratio test.

Results: Validated results confirmed that the C allele on 8q23.3 (rs16892766) was significantly associated with advanced-stage tumors (odds ratio [OR], 1.48; 95% confidence interval [CI], 1.15-1.90; P value = 4.9 x 10(-3)). The G allele on 8q24.21 (rs6983267) was more common in patients with a familial history of CRC (OR, 2.02; 95% CI, 1.35-3.03; P value = 3.9 x 10(-4)). The combination of rs6983267 on 8q24.21 and rs9929218 on 16q22.2 was associated with a history of colorectal adenoma (carriers of GG and AA, respectively; OR, 2.28; 95% CI, 1.32-3.93; P = 5.0 x 10(-4)).

Conclusions: CRC susceptibility variants at 8q23.3, 8q24.21, and 16q22.2 appear to be associated with cancer phenotype. These findings might be used to develop screening and surveillance strategies.
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http://dx.doi.org/10.1053/j.gastro.2010.05.072DOI Listing
September 2010

Colorectal cancer susceptibility quantitative trait loci in mice as a novel approach to detect low-penetrance variants in humans: a two-stage case-control study.

Cancer Epidemiol Biomarkers Prev 2010 Feb;19(2):619-23

Galician Public Foundation of Genomic Medicine (FPGMX), CIBERER, Genomics Medicine Group, Hospital Clínico, Santiago de Compostela, University of Santiago de Compostela, Galicia, Spain.

Thirty-five percent of colorectal cancer (CRC) susceptibility is thought to be attributable to genetics, but only a small proportion of the cases (<6%) can be explained by highly penetrant mutations. The rest of the susceptibility could be explained by a number of low-penetrance variants following a polygenic model of inheritance. Genetic modeling in rodents has been a successful tool for the unraveling of the genetic basis of diseases. The investigation of mouse quantitative trait loci led to the discovery of 15 "susceptibility to colorectal cancer" (Scc) loci. Thus, we aimed to analyze the human-mouse syntenic regions defined by these Scc loci and select human candidate genes within. Twenty-one genes were chosen and their single-nucleotide polymorphisms were tested as possible low-penetrance variants predisposing to CRC risk. Our most strongly associated single-nucleotide polymorphism, rs954353, seems to be in the 5' region of the CYR61 gene, which could implicate it in terms of the cis-regulation of the gene. CYR61 has been proposed as a connection point among signaling pathways and a probable marker for early CRC detection. However, we could not replicate the association. Despite our negative results, we believe that our candidate gene selection strategy could be quite useful in the future determination of variants predisposing to disease.
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http://dx.doi.org/10.1158/1055-9965.EPI-09-1175DOI Listing
February 2010

Detection of metachronous neoplasms in colorectal cancer patients: identification of risk factors.

Dis Colon Rectum 2007 Jul;50(7):971-80

Gastroenterology Department, Hospital del Mar, and University of Barcelona, Spain.

Purpose: Patients with colorectal cancer have a high risk of developing metachronous neoplasms. Identification of predictive factors associated with such conditions would allow individualized follow-up strategies in these patients. This study was designed to identify individual and familial factors associated with the development of metachronous colorectal neoplasms in patients with colorectal cancer.

Methods: In the context of a prospective, multicenter, general population-based study-the EPICOLON project-all patients with colorectal cancer attended in ten Spanish hospitals during a one-year period were included. Patients with familial adenomatous polyposis or inflammatory bowel disease were excluded. All patients were monitored by colonoscopy within two years of the diagnoses. Demographic, clinical, pathologic, molecular (microsatellite instability status and immunohistochemistry for MSH2 and MLH1), and familial characteristics (fulfillment of Amsterdam I or II criteria, and revised Bethesda guidelines) were analyzed.

Results: A total of 353 patients were included in the study. At two years of follow-up, colonoscopy revealed the presence of adenomas in 89 (25 percent) patients and colorectal cancer in 14 (3.9 percent) patients, in 7 cases restricted to anastomosis. Univariate analysis demonstrated that development of metachronous neoplasm (adenoma or colorectal cancer) was associated with personal history of previous colorectal cancer (odds ratio, 5.58; 95 percent confidence interval, 1.01-31.01), and presence of previous or synchronous adenomas (odds ratio, 1.77; 95 percent confidence interval, 1.21-3.17). Although nonstatistical significance was achieved, metachronisms were associated with gender (P<0.09) and differentiation degree (P<0.08). Multivariate analysis identified previous or synchronous adenomas (odds ratio, 1.98; 95 percent confidence interval, 1.16-3.38) as independent predictive factor. Neither presence of tumor DNA microsatellite instability nor family history correlated with the presence of metachronous neoplasms.

Conclusions: Patients with previous or synchronous colorectal adenoma have an increased risk of developing metachronous colorectal neoplasms. Accordingly, this subgroup of patients may benefit from specific surveillance strategies.
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http://dx.doi.org/10.1007/s10350-007-0237-2DOI Listing
July 2007