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Background: Primary care (PC) is crucial in the care of substance use disorder (SUD) patients. However, the relationship between PC and addiction settings is complex and collaboration issues stand out. Available evidence suggests that integration of SUD and PC services can improve physical and mental health of SUD patients and reduce health expenses., Objective: To explore the experiences, views and attitudes of PC professionals towards the interaction between PC and SUD services., Methods: Twenty-seven GPs took part in three focus groups. The focus group sessions were audio-taped, transcribed verbatim and analysed using reflexive thematic analysis. Recurrent themes were identified., Results: Four main themes were devised: (1) Differences and specificities of SUD patients, (2) Interaction between providers of PC and addiction services, (3) Patient management (4) Addiction stigma. These main themes reflect the consideration that SUD patients are a specific group with specific care needs that yield specific challenges to GPs themselves. Improved training, availability of a shared medical record system, increased feedback between GP and addiction specialists and the efficiency of the circuit are to be considered the main priority for the majority of the participants., Conclusions: An efficient and effective referral circuit, with increased feedback and shared medical records is considered key to GPs. Its implementation should keep in mind the specific features of both SUD patients and GPs., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Patients with alcohol use disorder (AUD) are likely to suffer disproportionate harms related to the COVID-19 pandemic and related policy measures. While many surveys have been conducted, most are focused on drinking changes in the general population and validation with biological markers is lacking., Method: We performed a retrospective cohort study among patients with AUD attending a urine drug screening program. With mixed-effects logistic regression models, we assessed the probability of screening positive for ethyl glucuronide according to patients' main clinical characteristics and time of analysis (either prior to or after a lockdown was implemented in Spain)., Results: A total of 362 patients provided 2,040 urine samples (1,295 prior to lockdown, 745 during lockdown). The mean age of participants was 52.0 years (SD 12.6), and 69.2% were men. Of the 43% of patients tested for other drugs 22% screened positive. After adjusting for all covariates, the odds of screening positive for ethyl glucuronide during lockdown almost doubled (OR = 1.99, 95% CI 1.20 to 3.33, p = 0.008). Other significant covariates included testing positive for other drugs (OR = 10.79, 95% CI 4.60 to 26.97) and length of treatment (OR = 0.59, 95% CI 0.47 to 0.74)., Conclusions: Our data support an association between the lockdown due to COVID-19 and increased alcohol use in patients with AUD. Thus, addiction healthcare systems could face significant challenges ahead. In light of these findings, it is essential to evaluate prospectively how patients with AUD are affected by the pandemic and how health systems respond to their needs., (© 2021 The Authors. Alcoholism: Clinical & Experimental Research published by Wiley Periodicals LLC on behalf of Research Society on Alcoholism.)

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., (Copyright © 2019 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction and Objective: The sensitivity of colorectal cancer screening programmes determines their effectiveness and is directly related to the interval cancer (IC). This study describes the frequency and characteristics of the IC of the Programme of Barcelona, Spain, and analyses its relationship with the quantitative value of the screening test (FIT)., Material and Methods: ICs after negative FIT of the first two rounds of the Programme (2010-2013) were included, observation period until July 2017. The information source of the ICs was their notification by professionals and patients, hospital databases and CMBD (Spanish Minimum Basic Data Set)., Results: The sensitivity of the Programme is 82%. ICs are diagnosed more in proximal and rectal colon and in advanced stages than screening cancers, and have higher FIT values than overall people with negative FIT., Conclusions: The sensitivity is acceptable and comparable to that of other programmes. The quantitative value of FIT in people with negative test should be included in the personalisation strategies of screening to reduce the risk of IC., (Copyright © 2018 Elsevier España, S.L.U. All rights reserved.)

Introduction: Increased values in the fecal immunochemical test (FIT) are correlated with increasingly severe colorectal neoplasia, but little attention has been given to FIT values below the cut-off point (negative FIT, nFIT). We analysed the relationship between the concentrations of two consecutive nFIT and the risk of following screen-detected advanced neoplasia and interval cancer (IC) in a population-based colorectal cancer screening program., Methods: FIT results were categorised into non-detectable nFIT (0-3.8 μg haemoglobin/g feces), low nFIT (3.9-9.9) and high nFIT (10.0-19.9). Multivariable adjusted logistic regression was used to estimate the odds ratios (OR) of advanced neoplasia and IC with the nFIT results in the first two screens., Results: More than 90% of the 42,524 persons had non-detectable nFIT in the first and second screen; 4.5% and 5.8% had a low nFIT, respectively, and 2.2% and 2.9% had a high nFIT. The probability of testing positive and being diagnosed of advanced neoplasia or IC rose with increasing values of nFIT. Compared with those with two non-detectable nFIT results, the highest OR were found among those who had two high nFIT results (OR 21.75; 95% confidence interval: 12.44, 38.04) and those with one low nFIT and one high nFIT (ORs around 20)., Conclusions: Participants with nFIT results above the detection limit of the test had an increased risk of advanced neoplasia and IC in subsequent participations. This information could be used in the design of personalised screening strategies., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

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., (© 2018 John Wiley & Sons Ltd.)

Objective: To analyse the incidence and outcomes of the different neovascular subtypes in age-related macular degeneration (AMD)., Material and Methods: A retrospective review was carried out on patients with neovascular AMD treated in the University and Polytechnic Hospital la Fe in Valencia by the same retinal physician (RGP) between December 2012 and July 2015. The anatomic classification of the neovascular lesions was recorded, as well as the number of intravitreal treatments administered and the change in visual acuity (VA) obtained throughout the follow-up., Results: A total number of 174 eyes of 156 patients (mean age: 79.9years) with a minimum follow-up of 4 months were included. The anatomic classification of choroidal neovascularisation (CNV) showed the presence of type1 lesions in 40,8%, type2 lesions in 12%, type3 lesions in 31%, and mixed lesions in 14.4%, with 1.7% showing polypoidal choroidal vasculopathy features. Overall, the mean baseline VA was 0,32, improving to 0,38 at 24months, after having received a mean of 9.3 injections. Type2, 3, and mixed forms showed a visual result significantly lower than type1, but there was no significant difference in the polypoidal vasculopathy., Conclusions: Type 1 CNV was the most common finding, and was associated with a better visual prognosis, compared to the other neovascular lesions., (Copyright © 2018 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background and Objective: The Colorectal Cancer Screening Program of Barcelona was implemented in December 2009 and involves pharmacies for the distribution and collection of screening tests. The aim of this article is to describe the main indicators of the first round of the Program (2010-2011), based on the ones suggested by the European Union., Material and Methods: The target population of the Colorectal Cancer Screening Program of Barcelona includes men and women aged 50-69 years who live in the catchment areas of Hospital Clínic and Hospital del Mar. Screening consists of biennial immunochemical fecal occult blood testing, with colonoscopy as confirmatory procedure., Results: Target population comprised 197,795 persons. Participation rate was 43.6%, was higher among women and among those aged 60 and older. 2.1% of the eligible population stated to have been already screened for colorectal cancer. Overall positivity rate was 6.2%, higher among men and with a broad variability among health care areas. The detection rates of low- and high-risk adenoma, and of invasive cancer were 9.1 ‰, 21.7 ‰ and 3.1 ‰, respectively. 48.2% of tumors were stage i., Conclusions: These results are considered satisfactory and consistent with those obtained in other programs and with European standards. Nevertheless, some areas for improvement have been identified. The high participation rate can be attributed, at least in part, to the type of test and to the involvement of community pharmacies., (Copyright © 2014 Elsevier España, S.L.U. All rights reserved.)

Objective: We aimed to perform a serological screening for T. cruzi, Strongyloides stercoralis, HIV, human T cell lymphotropic virus (HTLV) and syphilis in Latin American immigrants admitted to hospital in Spain., Methods: We have carried out a cross-sectional study of Latin American immigrants admitted to the Hospital General Universitario Alicante (Spain) from June 2012 to May 2014, where screening of Chagas disease, strongyloidiasis, HTLV, HIV and syphilis was performed by serology., Results: A total 180 patients were included in the study. Patients' median age was 38 years old, 123 (68.3%; 123/180) were female and 57 (31.7%; 57/180) male. Five of the 180 (2.5%) patients were positive for Chagas disease; associated with knowledge about Chagas disease (p=0.005), previous contact with patients with Chagas disease (p=0.04) and being Bolivian (p<0.001). Forty-two of the 157 (26.8%) patients were positive for Strongyloides serology; associated positively with being male (p<0.001), eosinophilia (p=0.001), hyper-IgE (p<0.001) and being Ecuadorian (p=0.001), and negatively associated with being Colombian (p=0.03). Positive serology of latent syphilis was found in 1.8% (3/171) of patients. Serology of HTLV was negative in all cases. No new cases of HIV infection were diagnosed., Conclusions: We propose that Latin American immigrant patients admitted to hospital in Spain be screened for strongyloidiasis, Chagas disease and syphilis by serology., (© The Author 2015. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background & Aims: The latest generation of fecal immunochemical tests (FIT) allows for quantitation of hemoglobin in feces, allowing for selection of optimal cut-off concentrations. We investigated whether individuals with positive results from quantitative FITs, in combination with other factors, could be identified as being at greatest risk for advanced colorectal neoplasia., Methods: In a retrospective study, we analyzed data from a consecutive series of 3109 participants with positive results from FITs (≥20 μg/g of feces) included in the first round of the Barcelona colorectal cancer screening program, from December 2009 through February 2012. All participants underwent colonoscopy and were assigned to groups with any advanced colorectal neoplasia or with nonadvanced colorectal neoplasia (but with another diagnosis or normal examination findings)., Results: Median fecal hemoglobin concentrations were significantly higher in participants with advanced colorectal neoplasia (105 μg/g; interquartile range, 38-288 μg/g) compared with participants with nonadvanced colorectal neoplasia (47 μg/g; interquartile range, 23-119 μg/g) (P < .001). Positive predictive values for advanced colorectal neoplasia, determined using arbitrary fecal hemoglobin concentrations, differed with sex and age. Multivariate logistic regression analysis identified sex (men: odds ratio [OR], 2.07; 95% confidence interval, 1.78-2.41), age (60-69 y: OR, 1.24; 95% confidence interval, 1.07-1.44), and fecal hemoglobin concentration (>177 μg/g: OR, 3.80; 95% confidence interval, 3.07-4.71) as independent predictive factors for advanced colorectal neoplasia. Combining these factors, we identified 16 risk categories associated with different probabilities of identifying advanced colorectal neoplasia. Risk for advanced colorectal neoplasia increased 11.46-fold among individuals in the highest category compared with the lowest category; positive predictive values ranged from 21.3% to 75.6%., Conclusions: Fecal hemoglobin concentration, in addition to sex and age, in individuals with positive results from FITs can be used to stratify probability for the detection of advanced colorectal neoplasia. These factors should be used to prioritize individuals for colonoscopy examination., (Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Phenotypic traits of familial IBD relative to sporadic cases are controversial, probably related to limited statistical power of published evidence., Aim: To know if there are phenotype differences between familial and sporadic IBD, evaluating the prospective Spanish registry (ENEIDA) with 11,983 cases., Methods: 5783 patients (48.3%) had ulcerative colitis (UC) and 6200 (51.7%) Crohn's disease (CD). Cases with one or more 1st, 2nd or 3rd degree relatives affected by UC/CD were defined as familial case., Results: In UC and CD, familial cases compared with sporadic cases had an earlier disease onset (UC: 33 years [IQR 25-44] vs 37 years [IQR 27-49]; p<0.0001); (CD: 27 years [IQR 21-35] vs 29 years [IQR 22-40]; p<0.0001), higher prevalence of extraintestinal immune-related manifestations (EIMs) (UC: 17.2% vs 14%; p=0.04); (CD: 30.1% vs 23.6%; p<0.0001). Familial CD had higher percentage of ileocolic location (42.7% vs 51.8%; p=0.0001), penetrating behavior (21% vs 17.6%; p=0.01) and perianal disease (32% vs 27.1%; p=0.003). Differences are not influenced by degree of consanguinity., Conclusion: When a sufficiently powered cohort is evaluated, familial aggregation in IBD is associated to an earlier disease onset, more EIMs and more severe phenotype in CD. This feature should be taken into account at establishing predictors of disease course., (© 2013.)

Objective: Genome-wide association studies (GWAS) have identified multiple risk loci for Crohn's disease (CD). However, the cumulative risk exerted by these loci is low, and the likelihood that additional, as-yet undiscovered loci contribute to the risk of CD is very high. We performed a GWAS on a southern European population to identify new CD risk loci., Design: We genotyped 620 901 genome markers on 1341 CD patients and 1518 controls from Spain. The top association signals representing new candidate risk loci were subsequently analysed in an independent replication cohort of 1365 CD patients and 1396 controls., Results: We identified a genome-wide significant association on chromosome 22q13.2 in the intergenic region between the RBX1 and EP300 genes (single nucleotide polymorphism rs4820425, OR 1.27, 95% CI 1.17 to 1.38, p=3.42E-8). We also found suggestive evidence for the association of the IFNGR2 (21q22.11), FOXP2 (7q31), MACROD2 (20p12.1) and AIF1 (6p21.3) loci with CD risk., Conclusions: In this GWAS performed on a southern European cohort, we have identified a new risk locus for CD between RBX1 and EP300. This study demonstrates that using populations of different ancestry is a useful strategy to identify new risk loci for CD.

Background: Screening for colorectal cancer with sigmoidoscopy benefits from the fact that distal findings predict the risk of advanced proximal neoplasms (APNs). This study was aimed at comparing the existing strategies of postsigmoidoscopy referral to colonoscopy in terms of accuracy and resources needed., Methods: Asymptomatic individuals aged 50-69 years were eligible for a randomized controlled trial designed to compare colonoscopy and fecal immunochemical test. Sigmoidoscopy yield was estimated from results obtained in the colonoscopy arm according to three sets of criteria of colonoscopy referral (from those proposed in the UK Flexible Sigmoidoscopy, Screening for COlon REctum [SCORE], and Norwegian Colorectal Cancer Prevention [NORCCAP] trials). Advanced neoplasm detection rate, sensitivity, specificity, and number of individuals needed to refer for colonoscopy to detect one APN were calculated. Logistic regression analysis was performed to identify distal findings associated with APN. All statistical tests were two-sided., Results: APN was found in 255 of 5059 (5.0%) individuals. Fulfillment of UK (6.2%), SCORE (12.0%), and NORCCAP (17.9%) criteria varied statistically significantly (P < .001). The NORCCAP strategy obtained the highest sensitivity for APN detection (36.9%), and the UK approach reached the highest specificity (94.6%). The number of individuals needed to refer for colonoscopy to detect one APN was 6 (95% confidence interval [CI] = 4 to 7), 8 (95% CI = 6 to 9), and 10 (95% CI = 8 to 12) when the UK, SCORE, and NORCCAP criteria were used, respectively. The logistic regression analysis identified distal adenoma ≥10 mm (odds ratio = 3.77; 95% CI = 2.52 to 5.65) as the strongest independent predictor of APN., Conclusions: Whereas the NORCCAP criteria achieved the highest sensitivity for APN detection, the UK recommendations benefited from the lowest number of individuals needed to refer for colonoscopy.

Background: The cause of collagenous colitis (CC) and lymphocytic colitis (LC) is unknown and epidemiological risk factors for CC and LC are not well studied. The aim was to evaluate in a case-control study epidemiological risk factors for CC and LC., Methods: In all, 120 patients with CC, 70 with CL, and 128 controls were included. For all cases and controls information was prospectively recorded. A binary logistic regression analysis was performed separately for CC and LC., Results: Independent associations observed with the diagnosis of CC were: current smoking (odds ratio [OR], 2.4), history of polyarthritis (OR, 20.8), and consumption of lansoprazole (OR, 6.4), low-dose aspirin (OR, 3.8), beta-blockers (OR, 3.6), and angiotensin II receptor antagonists (OR 0.20). In the case of LC they were: current smoking (OR, 3.8), associated autoimmune diseases (OR, 8), and consumption of sertraline (OR, 17.5), omeprazole (OR 2.7), low-dose aspirin (OR, 4.7), and oral antidiabetic drugs (OR, 0.14)., Conclusions: The consumption of drugs, current smoking, and associated autoimmune diseases were independently associated with the risk of microscopic colitis.

Background: Colorectal cancer (CRC) is a disease of complex aetiology, with much of the expected inherited risk being due to several common low risk variants. Genome-Wide Association Studies (GWAS) have identified 20 CRC risk variants. Nevertheless, these have only been able to explain part of the missing heritability. Moreover, these signals have only been inspected in populations of Northern European origin., Results: Thus, we followed the same approach in a Spanish cohort of 881 cases and 667 controls. Sixty-four variants at 24 loci were found to be associated with CRC at p-values <10-5. We therefore evaluated the 24 loci in another Spanish replication cohort (1481 cases and 1850 controls). Two of these SNPs, rs12080929 at 1p33 (Preplication=0.042; Ppooled=5.523x10-03; OR (CI95%)=0.866(0.782-0.959)) and rs11987193 at 8p12 (Preplication=0.039; Ppooled=6.985x10-5; OR (CI95%)=0.786(0.705-0.878)) were replicated in the second Phase, although they did not reach genome-wide statistical significance., Conclusions: We have performed the first CRC GWAS in a Southern European population and by these means we were able to identify two new susceptibility variants at 1p33 and 8p12 loci. These two SNPs are located near the SLC5A9 and DUSP4 loci, respectively, which could be good functional candidates for the association signals. We therefore believe that these two markers constitute good candidates for CRC susceptibility loci and should be further evaluated in other larger datasets. Moreover, we highlight that were these two SNPs true susceptibility variants, they would constitute a decrease in the CRC missing heritability fraction.

Introduction: colorectal cancer is one of the most common malignancies in developed countries. Data on specific and 10-year survival are scarce. This study analyzes overall and disease-specific survival for patients with colorectal cancer and assesses the value of clinical factors on disease-specific survival., Methods: a retrospective cohort study of newly diagnosed invasive colorectal cancer cases diagnosed from 1992 to 2007 were identified through the Hospital del Mar Cancer Registry. Five-and 10-year survival functions were estimated using Kaplan-Meier method. Cox proportional hazard models were used to assess prognostic factors., Results: a total of 2,080 patients with colorectal cancer were identified. The median age at diagnosis was 72 years and 58.5%were men. By the end of the follow-up period (December 2008), 1,225 patients had died and 68.4% of deaths were due to colorectal cancer. The 5- and 10-year cancer-specific survival rates were 55.5% (95%CI 53.9-57.9%) and 48.5% (95%CI 45.6-51.3%), respectively. The 5-year specific survival rate improved in the last period (2003-2007) (60.4%, 95%CI 55.4-65.0) compared with 1992-1997(53.4%; 95%CI 49.2-57.4) and 1998-2002 (52.0%; 95%CI 47.8-56.2). Various factors were independently associated with excess CRC mortality: male sex (HR 1.21), age at diagnosis > 75 years(HR 1.97), rectal location (HR 1.33), more advanced stages (stage IV: HR 18.54), poorly differentiated/undifferentiated tumors (HR 1.80), and admission through the emergency department (HR 1.52)., Conclusions: cancer-specific survival improved from 1992 to 2007. This improvement could be due to more effective treatment, since changes in stage distribution or age at diagnosis were not observed during the study period. Overall survival rates should notably improve with the implementation of a population-based colorectal cancer screening program in Spain.

Aim: To evaluate the effectiveness of infliximab as a second-line therapy in Crohn's disease patients after adalimumab failure., Methods: A historical cohort study in a community-based gastroenterology practice evaluated Crohn's disease patients treated with infliximab (induction plus maintenance) after adalimumab failure. Patients were identified using a large Spanish database (ENEIDA)., Results: We included 15 Crohn's disease patients who received infliximab after adalimumab failure. Five patients discontinued adalimumab due to loss of response, 3 due to adverse events and 7 due to partial response. After infliximab therapy was started, all patients who had interrupted adalimumab due to loss of efficacy regained response. All patients who discontinued adalimumab due to adverse events responded to infliximab and maintained this response; one of these patients had an uneventful course on infliximab, but 2 developed adverse events. None of the 7 patients who interrupted adalimumab due to partial response reached remission with infliximab., Conclusion: Switching from adalimumab to infliximab may be useful in patients who develop adverse effects or loss of response, however, the benefit of infliximab in primary nonresponders was not established.

Purpose: Bethesda guidelines are used to recognize patients at risk for Lynch syndrome. However, obtaining personal and familial tumor data can sometimes be difficult. The Microsatellite Path Score (MsPath), a pathological score, based on age, tumor location, and pathologic features, has been developed to effectively predict colorectal cancer with DNA mismatch repair (MMR) deficiencies. However, the MsPath model's performance in an unselected, population-based colorectal cancer (CRC) population is unknown., Patients and Methods: We analyzed all patients with CRC regardless of age, personal or family history, and tumor characteristics from the EPICOLON study, an independent, prospective, multicenter, population-based cohort (N = 1,222). All patients underwent tumor microsatellite instability (MSI) analysis and immunostaining for MLH1/MSH2, and those with MMR underwent tumor BRAF mutation analysis and MLH1/MSH2 germline testing. All the pathologic features were centralized and evaluated blinded to the MMR status., Results: MsPath score for prediction of having MSI high, with the recommended MsPath cutoff score ≥1.0, had a sensitivity, specificity, and positive predictive value (PPV) of 92.8% (95% CI, 86.9 to 98.3), 64.1% (95% CI, 61.1 to 66.8), and 15.8% (95% CI, 12.2 to 18.6), respectively. MsPath score had a sensitivity, specificity, and PPV of 81.8% (95% CI, 59.0 to 99.8), 60.6% (95% CI, 57.8 to 63.4), and 1.9% (95% CI, 0.7 to 3.1), respectively, for the identification of MLH1/MSH2 gene carriers. Application of the MsPath score, resulted in two (18%) of 11 mutation carriers being missed, both pathogenic germline MSH2 mutations., Conclusion: In the general nonselected population, the MsPath score accurately predicted the probability of bearing a MSI high CRC, but it was insufficiently accurate to use for the selection of patients warranting MLH1/MSH2 mutation testing in the setting of Lynch syndrome.

Background: Colorectal cancer (CRC) is the second leading cause of cancer death in developed countries. Familial aggregation in CRC is also important outside syndromic forms and, in this case, a polygenic model with several common low-penetrance alleles contributing to CRC genetic predisposition could be hypothesized. Mucins and GALNTs (N-acetylgalactosaminyltransferase) are interesting candidates for CRC genetic susceptibility and have not been previously evaluated. We present results for ten genetic variants linked to CRC risk in previous studies (previously identified category) and 18 selected variants from the mucin gene family in a case-control association study from the Spanish EPICOLON consortium., Methods: CRC cases and matched controls were from EPICOLON, a prospective, multicenter, nationwide Spanish initiative, comprised of two independent stages. Stage 1 corresponded to 515 CRC cases and 515 controls, whereas stage 2 consisted of 901 CRC cases and 909 controls. Also, an independent cohort of 549 CRC cases and 599 controls outside EPICOLON was available for additional replication. Genotyping was performed for ten previously identified SNPs in ADH1C, APC, CCDN1, IL6, IL8, IRS1, MTHFR, PPARG, VDR and ARL11, and 18 selected variants in the mucin gene family., Results: None of the 28 SNPs analyzed in our study was found to be associated with CRC risk. Although four SNPs were significant with a P-value < 0.05 in EPICOLON stage 1 [rs698 in ADH1C (OR = 1.63, 95% CI = 1.06-2.50, P-value = 0.02, recessive), rs1800795 in IL6 (OR = 1.62, 95% CI = 1.10-2.37, P-value = 0.01, recessive), rs3803185 in ARL11 (OR = 1.58, 95% CI = 1.17-2.15, P-value = 0.007, codominant), and rs2102302 in GALNTL2 (OR = 1.20, 95% CI = 1.00-1.44, P-value = 0.04, log-additive 0, 1, 2 alleles], only rs3803185 achieved statistical significance in EPICOLON stage 2 (OR = 1.34, 95% CI = 1.06-1.69, P-value = 0.01, recessive). In the joint analysis for both stages, results were only significant for rs3803185 (OR = 1.12, 95% CI = 1.00-1.25, P-value = 0.04, log-additive 0, 1, 2 alleles) and borderline significant for rs698 and rs2102302. The rs3803185 variant was not significantly associated with CRC risk in an external cohort (MCC-Spain), but it still showed some borderline significance in the pooled analysis of both cohorts (OR = 1.08, 95% CI = 0.98-1.18, P-value = 0.09, log-additive 0, 1, 2 alleles)., Conclusions: ARL11, ADH1C, GALNTL2 and IL6 genetic variants may have an effect on CRC risk. Further validation and meta-analyses should be undertaken in larger CRC studies.

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.

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., (Copyright © 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Familial adenomatous polyposis is an inherited disorder characterized by the presence of multiple colorectal adenomas (more than 100 in the classic form and between 10 and 100 in the attenuated one), with a high risk of colorectal cancer development. To improve the diagnostic and therapeutic management of these patients, the Spanish Registry of Familial Adenomatous Polyposis was created in 2007.We aimed to evaluate the clinicopathological characteristics of patients with familial adenomatous polyposis in Spain., Patients and Methods: All patients included in the Registry during one year were evaluated with respect to their demographic, clinical, pathological, and genetic characteristics., Results: 243 patients of 156 unrelated families from 15 Spanish centers were included. One hundred thirty patients were male, and the mean age at diagnosis was 40 years. According to the clinical presentation, 127 corresponded to the classic form and 116 to the attenuated one. Colorectal adenoma with high-grade dysplasia was identified in 67 (28%) patients, and colorectal cancer in 42 (17%). Extracolonic manifestations were: duodenal involvement (n=46), gastric involvement (n=44), desmoid tumors (n=24), thyroid cancer (n=8), osteomas (n=6) and brain tumor (n=1). APC and/or MYH gene testing was performed in 140 (90%) families, detecting the causative mutation in 75 (54%) of them (70 in the APC gene and 5 in the MYH gene)., Conclusions: During its first year of operability, a large number of patients and families were included in the Registry. The reduced prevalence of colorectal cancer as well as the large proportion of families submitted to gene testing demonstrated a high-quality clinical practice in Spain., (Copyright (c) 2009 Elsevier España, S.L. All rights reserved.)

Aim: To evaluate changes in colorectal cancer (CRC) survival over the last 20 years., Methods: We compared two groups of consecutive CRC patients that were prospectively recruited: Group I included 1990 patients diagnosed between 1980 and 1994. Group II included 871 patients diagnosed in 2001., Results: The average follow up time was 21 mo (1-229) for Group I and 50 mo (1-73.4) for Group II. Overall median survival was significantly longer in Group II than in Group I (73 mo vs 25 mo, P < 0.001) and the difference was significant for all tumor stages. Post surgical mortality was 8% for Group Iand 2% for Group II (P < 0.001). Only 17% of GroupI patients received chemotherapy compared with 50% of Group II patients (P < 0.001)., Conclusion: Survival in colorectal cancer patients has doubled over the past 20 years. This increase seems to be partly due to the generalization in the administration of chemotherapy and to the decrease of post surgical mortality.

Objectives: Limited information suggests the existence of a high prevalence of hepatitis B (HBV) and C virus (HCV) infection in inflammatory bowel disease (IBD). This knowledge is relevant because the viruses may reactivate under immunosuppressive therapy. The objectives of this study are to assess the prevalence of HBV and HCV infection in IBD, in a nationwide study, and to evaluate associated risk factors., Methods: This cross-sectional multicenter study included 2,076 IBD patients, consecutively recruited in 17 Spanish hospitals. Factors related to IBD (severity, invasive procedures, etc.) and to infection (transfusions, drug abuse, etc.) were registered. Independent risk factors for viral infection were evaluated using logistic regression analysis., Results: Present and/or past HBV and HCV infection was found in 9.7% of patients of both ulcerative colitis (UC) and Crohn's disease (CD) (UC: HBsAg 0.8%, anti-HBc 8%, anti-HCV 1.3%; CD: HBsAg 0.6%, anti-HBc 7.1%, anti-HCV 2.3 %). Effective vaccination (anti-HBs, without anti-HBc) was present in 12% of patients. In multivariate analysis, age (odds ratio (OR) 1.04; 95% confidence interval (CI) 1.02-1.06; P=0.000), family history of hepatitis (OR 2.48; 95% CI 1.3-4.74; P=0.006) and moderate-to-severe IBD disease (OR 2.5; 95% CI 1.02-6.15; P=0.046) were significantly related to HBV, whereas transfusions (OR 2.66; 95% CI 1.2-5.87; P=0.015) and antibiotic use (OR 2.66; 95% CI 1.1-6.3; P=0.03) were significantly related to HCV. The significance for transfusions was lost if they were administered after 1991, when HCV markers became mandatory in blood banks., Conclusions: Prevalence of HBV and HCV infection in IBD is similar to that of the general population of reference and lower than that in previously published series. This fact, in addition to the lack of association with invasive procedures, suggests the existence of adequate preventive measures in centers attending to these patients. The low percentage of effective vaccination makes it mandatory to intensify B virus vaccination in IBD.

Background & Aims: Early recognition of patients at risk for Lynch syndrome is critical but often difficult. Recently, a predictive algorithm-the PREMM(1,2) model-has been developed to quantify the risk of carrying a germline mutation in the mismatch repair (MMR) genes MLH1 and MSH2. However, the model's performance in an unselected, population-based colorectal cancer population as well as its performance in combination with tumor MMR testing are unknown., Methods: We included all colorectal cancer cases from the EPICOLON study, a prospective, multicenter, population-based cohort (n = 1222). All patients underwent tumor microsatellite instability analysis and immunostaining for MLH1 and MSH2, and those with MMR deficiency (n = 91) underwent tumor BRAF V600E mutation analysis and MLH1/MSH2 germline testing., Results: The PREMM(1,2) model with a >/=5% cut-off had a sensitivity, specificity, and positive predictive value (PPV) of 100%, 68%, and 2%, respectively. The use of a higher PREMM(1,2) cut-off provided a higher specificity and PPV, at expense of a lower sensitivity. The combination of a >/=5% cut-off with tumor MMR testing maintained 100% sensitivity with an increased specificity (97%) and PPV (21%). The PPV of a PREMM(1,2) score >/=20% alone (16%) approached the PPV obtained with PREMM(1,2) score >/=5% combined with tumor MMR testing. In addition, a PREMM(1,2) score of <5% was associated with a high likelihood of a BRAF V600E mutation., Conclusions: The PREMM(1,2) model is useful to identify MLH1/MSH2 mutation carriers among unselected colorectal cancer patients. Quantitative assessment of the genetic risk might be useful to decide on subsequent tumor MMR and germline testing.

ARLTS1 was recently identified in chromosome 13q14 as a tumor suppressor gene of the ADP-ribosylation factor family with pro-apoptotic characteristics. Additionally, one of its genetic variants (W149X) was hypothesized to be a polymorphism associated with familial cancer. We performed a large case-control association study within the EPICOLON project aimed at evaluating the sporadic and familial colorectal cancer (CRC) risk associated with ARLTS1 genetic variants. Whereas P131L and W149X did not seem to affect CRC risk, C148R did show, for the first time in CRC, statistically significant differences between cases and controls [odds ratio (OR) = 1.45, 95% confidence interval (95% CI) = 1.13-1.86, P = 0.003], sporadic cases and controls (OR = 1.59, 95% CI = 1.13-2.23, P = 0.007) and familial cases and controls (OR = 1.55, 95% CI = 1.10-2.19, P = 0.01) in agreement with a hypothetical moderate increase of the cancer risk linked to the C148R ARLTS1 variant, both in sporadic and familial CRC cases.

Background & Aims: Whereas it has conclusively been demonstrated that biallelic MutY human homolog (MYH) mutations confer a significant risk for colorectal cancer (CRC), the influence of monoallelic mutations remains controversial. Characterization of MYH-associated CRC is critical to identify individuals who might benefit from preventive strategies. This prospective, multicenter, case-control, population-based study was aimed at (1) establishing the CRC risk associated with specific germline MYH mutations and (2) devising a set of clinical criteria to identify MYH carriers among newly diagnosed CRC., Methods: Genotyping for Y165C and G382D was performed by TaqMan technology. Single-stranded conformation polymorphism analysis was performed in heterozygotes to screen for mutations in the entire gene. All individuals were re-screened for any additional pathogenic variant., Results: Biallelic and monoallelic MYH mutations were found in 8 (0.7%) and 19 (1.7%) of 1116 CRC patients, respectively. None of the 934 control subjects carried biallelic mutations, whereas 22 (2.3%) of them were monoallelic carriers. In a meta-analysis including all previous case-control studies, monoallelic MYH carriers were not at increased risk for CRC (odds ratio, 1.11; 95% confidence interval, 0.90-1.37), although a significant association was found with the Y165C mutation in either homozygotes or heterozygotes (odds ratio, 1.67; 95% confidence interval, 1.17-2.40). Furthermore, presence of more than 15 synchronous colorectal adenomas or CRC diagnosed before the age of 50 years was the most effective set of criteria for the identification of biallelic MYH mutation carriers., Conclusions: This study proposes the first set of clinical criteria designed to identify CRC patients with biallelic MYH mutations, and it argues against an increased risk for monoallelic carriers.

We report the first case of human cryptococcosis due to Cryptococcus neoformans var. gattii described in our country, which was presented as brain cryptococcoma in an immunocompetent patient. An extensive sampling of the patient's environment was carried out to find the source of infection.

Purpose: Patients with colorectal cancer have an increased risk for developing synchronous and metachronous neoplasms. However, besides those cases with inherited disorders predisposing to tumor multicentricity, it is unknown which patients are prone to this condition. This study was designed to identify individual and familial characteristics associated with the development of synchronous colorectal neoplasms in patients with colorectal cancer., Methods: During a one-year period, all patients with colorectal cancer attended in 25 Spanish hospitals were included. Exclusion criteria were colorectal cancer developed in the context of familial adenomatous polyposis or inflammatory bowel disease, refusal to participate in the study, incomplete family history, and inadequate examination of the colon and rectum. In addition to demographic, clinical, pathology, molecular (microsatellite instability status), and familial characteristics, presence of synchronous colorectal neoplasms (adenoma or carcinoma) were analyzed., Results: A total of 1,522 patients were included in the study. Synchronous colorectal neoplasms were documented in 505 patients (33.2 percent): adenoma (n = 411), carcinoma (n = 27), or both (n = 67). Development of these lesions was associated with male gender (odds ratio, 1.94; 95 percent confidence interval, 1.43-2.65), personal history of colorectal adenoma (odds ratio, 3.39; 95 percent confidence interval, 1.58-7.31), proximal location of primary tumor (odds ratio, 1.40; 95 percent confidence interval, 1.02-1.94), tumor TNM Stage II (odds ratio, 1.31; 95 percent confidence interval, 1.15-4.66), mucinous carcinoma (odds ratio, 1.89; 95 percent confidence interval, 1.19-2.99), and family history of gastric cancer (odds ratio, 2.03; 95 percent confidence interval, 1.17-3.52)., Conclusions: Based on individual and familial characteristics associated with synchronous colorectal neoplasms, it has been possible to identify a subgroup of patients with colorectal cancer prone to tumor multicentricity with potential implications on the delineation of preventive strategies.

Background: Colorectal cancer is the third leading cause of cancer mortality in Western countries. Hereditary nonpolyposis colorectal cancer is the most common type of hereditary colorectal cancer, but its incidence remains controversial, ranging from 1 to 5%., Objective: This present prospective, multicentre, nationwide study was aimed at compiling prominent epidemiological and clinical data with respect to hereditary non-polyposis colorectal cancer and other familial colorectal cancer forms in Spain, where information is lacking., Methods: All patients with a de-novo diagnosis of colorectal cancer and who attended between November 2000 and October 2001 in 25 hospitals all over Spain were registered. Demographic, clinical and tumour-related characteristics of probands, and detailed family history, were obtained., Results: A total of 1872 colorectal cancer patients were included. Clinical diagnosis of hereditary non-polyposis colorectal cancer was established in 46 (2.5%) patients according to the Amsterdam II criteria. Comparison between patients fulfilling either the Amsterdam I or the Amsterdam II criteria revealed no differences with respect to demographic, clinical and tumour-related characteristics. A total of 504 (27.0%) patients had a family history of hereditary non-polyposis colorectal cancer-related neoplasm not fulfilling the Amsterdam criteria (familial colorectal cancer), while 360 (19.2%) patients fulfilled at least one of the Bethesda's criteria., Conclusion: These clinicoepidemiological data provide a more accurate characterization of hereditary non-polyposis colorectal cancer and other familial colorectal cancer forms in Spain, with potential implications in preventive strategies.

Background and Objective: Despite the number of plans leading to lose weight among individuals in the developed countries, the prevalence of obesity has increased since 1980. The knowledge of ponderal evolution in a given population is very important because the adverse effects of obesity vary greatly among individuals and populations. The objective of the present paper was to determine the modifications in the different degrees of body adiposity in a population in Catalunya., Patients and Methods: A measurement was made of weight and height of 24554 users aged over 14 years (10595 males and 13959 females) attended at four basic health areas (BHA): Girona 1, Girona 4, Salt and Camprodon, and a Primary Health Center (PHC) in the Girona province, for a five-year period, 1995-1999. The prevalence of the different degrees of obesity was compared with that obtained in a previous study with 6373 individuals during the 1986-1989 period (4,579 males and 1794 females)., Results: The prevalence of women with overweight (defined as a body mass index [BMI] > 25 kg/m2) increased from 7.3% (1986-1989, study 0) to 17.6% (1995-1999, study 1) for women aged 15 to 24 years ( p < 0.001), from 17.9 % to 28.1% for women aged 25 to 34 years (p < 0.001), and from 37.5% to 44.7 % for women aged 35 to 44 years (p < 0.001). In the latter age group, the proportion of women with obesity (BMI > 30 kg/m2) increased from 6.9% to 12.9%. Similar trends were observed among men, and the change in the 35-44 year age group (from 10.5 % of obese men to 16% [p < 0.001]), and 55 to 65 years (from 16.6% of obese men to 22.7% [p < 0.001] was particularly significant. And lastly, it is also noteworthy the proportion of individuals with low weight (BMI < 18.5 kg/m2) which increased from 7.3% to 11.6% for women aged 15 to 24 years, and from 0.3% to 2.2% for women aged 35 to 44 years. This trend was also observed for men aged 15 to 24 years (11% to 17.2%)., Conclusions: The relative increase in the prevalence of overweight and obesity runs in parallel to that found in other surrounding countries. Also, it is worth mentioning that among women aged 15 to 24 years the increase in the prevalence of low weight and obesity is almost identical, which invalidates the mean and median values as a means to assess the ponderal evolution in this population. The current compartmentalization between the extreme BMIs, particularly among the youngest portion of population should be addressed from a multidisciplinary perspective.

Background: Parvovirus B19 (PVB19) has been identified as the cause of erythema infectiosum. The epidemiology of PVB19 has not been extensively studied in Spain or in the autonomic community of Valencia. The aim of this work is to describe an outbreak of PVB19 infection occurring in the area of Monforte del Cid, Alicante., Methods: A probable case was defined as: all subjects living in Monforte who presented a rash (mainly facial) and/or arthralgia starting from November 1999. A confirmed case was defined as: a probable case confirmed by laboratory analysis or a case having an epidemiological link. Laboratory confirmation included specific IgG or IgM antibodies to PVB19. Cases were mainly detected through the Monforte del Cid Primary Health Care Center., Results: The outbreak occurred from November 1999 to August 2000. A total of 118 cases were detected, giving an overall attack rate (AR) of 23.2 cases per 1,000 inhabitants. The highest rates were in the age groups of 0-4 years old (AR 5 114.5 per 1,000) and 5-9 years old (AR 5 180.3 per 1,000). By gender, the AR per 1,000 inhabitants was 26.9 in men and 16.7 in women. Two of the cases were pregnant women and one of them had a miscarriage., Conclusions: The outbreak of erythema infectiosum lasted 10 months and mainly affected children under 14 years old. Active surveillance was focussed on women in the first three months of pregnancy.

Background: The effectiveness of the different laboratory test methods to diagnose Legionella spp. in clinical specimens varies according to the epidemiological context. In this study, the usefulness of the laboratory methods used for an outbreak that occurred in the municipality of Alcoy (Alicante, Spain) are evaluated., Materials and Methods: 222 community-acquired cases of infection caused by Legionella pneumophila serogroup 1, subtype Pontiac-Knoxville, genotypes I and II were studied, that had been diagnosed by the Microbiology laboratory from January 1999 to December 2000, corresponding to patients residing in the municipality of Alcoy (Alicante). The methods used were direct antigen detection in respiratory specimens by immunoflurescence, direct antigen detection in urine, cultures and serology., Results: The detection of the antigen in urine diagnosed 201 cases (90,5%). Direct immunofluorescence provided a high number of false positives (n=24). A culture was essential to confirm the etiology of the outbreak (25 sputum) strains from 22 patients). Serology complemented the other methods and helped to retrospectively diagnose 21 patients (9%) when the other tests were not carried out or when they provided negative results., Conclusions: A rapid diagnosis is essential to evaluate the patients and to control epidemical outbreaks, and the detection of the urinary antigen is very useful, but should be complemented with other methods. The culture of the respiratory specimens and the subsequent typing of the strains means that the etiology can be established with certainty and this helps to determine the source(s) of the infection. Serology complemented the diagnosis in 9% of the cases.

Objectives: To estimate the prevalence of obesity and overweight in the population of Girona (Spain) between 1995 and 1999 and to divide the prevalences in geographical areas according to age and sex., Methods: Height and weight were directly measures in 24,554 health care consumers older than 14 years (10,595 men and 13,959 women) treated in four primary health care areas: Girona 1, Girona 4, Salt and Camprodon and in one primary health care center in the province of Girona. Body mas index (BMI) was calcuted by dividing weight in kilograms bye height in meters squared. Obesity was defined as grades II and III of Garrow's index (BMI >= 30 kg/m2) and overweight as degree I (25 kg/m2 >= BMI < 30 kg/m2). Because the sample was not randomized, the prevalences were adequately weighted. The comparison between prevalences in two different primary health care areas for each sex (in the same Garrow's index and age group) was carried out using a parametric test of differences in proportions (Student's t-test). A hierarchical logistic regression was used to compare prevalences in the same grade Garrow's index, controlling for age and sex., Results: The prevalence of obesity was estimated as 15.6% in men aged from 20-74 years (from 14.0% in Girona 1 to 22.4% in Camprodon) and 17.5% for women (15.6% in Girona 1, 22.7% in Camprodon). The weighted mean was 16.7%. The prevalence of overweight was 44% in men and 33% in women and the weighted mean was 37.8%. The prevalence of obesity was graduated with statistically significant differences between Girona 1, Salt, Girona 4, Camprodon and Sils., Conclusions: The estimates of the prevalences of obesity and overweight obtained in this study were closer to those of other studies in similar populations than previously believed. Indeed, the prevalences may be similar to those of the European Union and, in some age groups, to those of the United States.

Background: The aim was to analyse the magnitude, direction and predictors of change in the main hospital discharge diagnosis (HDD) after a clinical expert review, among patients included in a multicentre molecular epidemiologic study of biliopancreatic diseases., Methods: A total of 602 patients with a suspicion diagnosis of pancreas cancer (PC), cancer of the extrahepatic biliary system (CEBS) or benign biliopancreatic pathologies (BPP) were prospectively recruited at five general hospitals. A structured form was used to collect information from medical records. A panel of experts revised all diagnostic information and established the main clinicopathological diagnosis (CPD) by consensus., Results: Of the 204 cases with a HDD of PC, 176 (86%) were deemed to have a CPD of PC, eight of CEBS, twelve a neoplasm of different origin, four BPP and four syndromic diagnoses. Thus, 28 cases (14%) were false positives. Of the 129 patients with a HDD of CEBS, 15 (12%) were false positives. Nine of the 396 cases with a HDD of non-PC (2%) had a CPD of PC (false negatives), whilst 14 of 471 patients with a HDD of non-CEBS (3%) were deemed to have CEBS. Overall, sensitivity and specificity of HDD for PC were, respectively, 95 and 93%, and for CEBS, 89 and 97%. Cytohistological confirmation and laparotomy were independent predictors of diagnostic change., Conclusions: Validity of the HDD was high, but its association with some clinical variables suggests that sole reliance on HDD can significantly bias results, and highlights the need to review all HDDs. Alternatively, only patients at high risk of misdiagnosis could be reviewed: primarily, those lacking a cytohistological diagnosis or a laparotomy. No exclusions appear warranted solely on the basis of age, gender or tumour spread.

Background: Organochlorine compounds such as 1,1,1-trichloro-2,2-bis(p-chlorophenyl)-ethane (p,p'-DDT), 1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene (p,p'-DDE), and some polychlorinated biphenyls (PCBs) are carcinogenic to animals and possibly also to human beings. Occupational exposure to DDT may increase the risk of pancreas cancer. The high frequency of K-ras mutations in pancreatic cancer remains unexplained. We analysed the relation between serum concentrations of selected organochlorine compounds and mutations in codon 12 of the K-ras gene in patients with exocrine pancreatic cancer., Methods: Cases were prospectively identified in five hospitals. Mutations in K-ras were analysed by PCR and artificial restriction fragment length polymorphism. Cases of pancreatic cancer with wild-type K-ras (n=17) were frequency matched for age and sex to cases of pancreatic cancer with a K-ras mutation (n=34, case-case study). These 51 cases were further compared with 26 hospital controls (case-control comparison). Serum organochlorine concentrations were measured by high-resolution gas chromatography with electron-capture detection and negative ion chemical ionisation mass spectrometry., Findings: Serum concentrations of p,p'-DDT were significantly higher in pancreatic cancer cases with a K-ras mutation than in cases without a mutation (odds ratio for upper tertile 8.7 [95% CI 1.6-48.5], p for trend=0.005). For p,p'-DDE the corresponding figures were 5.3 (1.1-25.2, p for trend=0.031). These estimates held after adjusting for total lipids, other covariates, and total PCBs. A specific association was observed between a glycine to valine substitution at codon 12 and both p,p'-DDT and p,p'-DDE concentrations (odds ratio 15.9, p=0.044 and odds ratio 24.1, p=0.028; respectively). A similar pattern was shown for the major di-ortho-chlorinated PCBs (congeners 138, 153, and 180), even after adjustment for p,p'-DDE, but without a specific association with spectrum. Concentrations of p,p'-DDT and p,p'-DDE were similar among wild-type cases and controls, but significantly higher for K-ras mutated cases than for controls (p<0.01)., Interpretation: Organochlorine compounds such as p,p'-DDT, p,p'-DDE, and some PCBs could play a part in the pathogenesis of exocrine pancreatic cancer through modulation of K-ras activation. The results require replication, but they suggest new roles for organochlorines in the development of several cancers in human beings.

Study Objective: To analyse the relation between coffee consumption and mutations in the K-ras gene in exocrine pancreatic cancer., Design: Case-case study. Consumption of coffee among cases with the activating mutation in the K-ras gene was compared with that of cases without the mutation., Setting and Patients: All cases of pancreatic cancer newly diagnosed at five hospitals in Spain during three years were included in the PANKRAS II Study (n = 185, of whom 121 whose tissue was available for molecular analysis are the object of the present report). Over 88% were personally interviewed in hospital. DNA was amplified from paraffin wax embedded tissues, and mutations in codon 12 of K-ras were detected by the artificial RFLP technique., Main Results: Mutations were found in tumours from 94 of 121 patients (77.7%). Mutations were more common among regular coffee drinkers than among non-regular coffee drinkers (82.0% v 55.6%, p = 0.018, n = 107). The odds ratio adjusted by age, sex, smoking and alcohol drinking was 5.41 (95% CI 1.64, 17.78). The weekly intake of coffee was significantly higher among patients with a mutated tumour (mean of 14.5 cups/week v 8.8 among patients with a wild type tumour, p < 0.05). With respect to non-regular coffee drinkers, the odds ratio of a mutated tumour adjusted by age, sex, smoking and alcohol drinking was 3.26 for drinkers of 2-7 cups/week, 5.77 for drinkers of 8-14 cups/week and 9.99 for drinkers of > or = 15 cups/week (p < 0.01, test for trend)., Conclusions: Pancreatic cancer cases without activating mutations in the K-ras gene had drank significantly less coffee than cases with a mutation, with a significant dose response relation: the less they drank, the less likely their tumours were to harbour a mutation. In exocrine pancreatic cancer the K-ras gene may be activated less often among non-regular coffee drinkers than among regular drinkers. Caffeine, other coffee compounds or other factors with which coffee drinking is associated may modulate K-ras activation.

Epidemiologic studies on exocrine pancreatic cancer show a large heterogeneity in diagnostic criteria applied to define "caseness." Reanalyses conducted after review of diagnostic information have yielded substantially different results than those based on more crude classifications of disease. During a multicenter prospective study on mutations in the K-ras gene in pancreatic and biliary diseases, hospital diagnoses from 602 patients were reviewed by a panel of experts. There were two main motivations to do so: a generic interest for the quality of the diagnostic data, and the anticipation that a firm diagnosis could be needed to assess whether patients whose tumors did not harbor the mutation were true negatives or false negatives. In addition, the review of diagnoses was helpful to minimize tissue misclassification, and it had a high educational value for clinicians and epidemiologists. This article illustrates why and how this was so through a brief presentation of the 10 most significant cases. With respect to selection and classification of subjects, the main issues that studies on pancreatic cancer need to address are the differential diagnosis of exocrine pancreatic cancer and pancreatitis, the differential diagnosis of exocrine pancreatic cancer and other abdominal tumors, and the use of survival as a hallmark of pancreatic cancer. In epidemiologic studies of pancreatic cancer, it is warranted that a panel of experts centrally reviews all the existing diagnostic evidence (cytohistological and other) of all patients, regardless of whether they have cytohistological confirmation and of their hospital discharge diagnosis.

The authors reviewed 54 cases of bacteremia in 48 patients with chronic liver disease over a period of two years. Thirty-three were outpatients and 21 were hospitalized. Fifty-eight microorganisms were detected, which represented 10.3% of the total number of germs isolated in all the cases of bacteremia in the hospital during that same period of time. Gram-negative bacilli were predominant, especially Escherichia coli (19 cases); among the gram-positive ones, the most frequent was Staphylococcus aureus (8 cases). There was ascites in 62.9% of the patients, but the predominant symptom was fever. The most frequent sources of infection were: unknown (29.6%), urinary (22.2%), catheter (16.6%) and lung (14.8%). All the in-hospital cases were preceded by an aggressive diagnostic or therapeutic technique. The rate of mortality was 29.6%, and it was highest among patients with gram-negative bacteremia, ascites, Child C (p less than 0.05), complications (hepatic encephalopathy, hemorrhage and/or septic shock) (p less than 0.03), unknown origin or originating from catheter and in-hospital episodes.