Publications by authors named "Jaume Boadas"

24 Publications

  • Page 1 of 1

Chronic pancreatitis for the clinician. Part 2: Treatment and follow-up. Interdisciplinary Position Paper of the Societat Catalana de Digestologia and the Societat Catalana de Pàncrees.

Gastroenterol Hepatol 2021 Jun 23. Epub 2021 Jun 23.

CIBERehd, Instituto de Salud Carlos III, Madrid, España; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, España; Servei de Gastroenterologia, ICMDiM, Hospital Clínic, Barcelona, España; Gastrointestinal and Pancreatic Oncology Research Group, Hospital Clínic, Barcelona, España.

Chronic pancreatitis is associated with impaired quality of life, high incidence of comorbidities, serious complications and mortality. Healthcare costs are exorbitant. Some medical societies have developed guidelines for treatment based on scientific evidence, but the gathered level of evidence for any individual topic is usually low and, therefore, recommendations tend to be vague or weak. In the present position papers on chronic pancreatitis from the Societat Catalana de Digestologia and the Societat Catalana de Pàncrees we aimed at providing defined position statements for the clinician based on updated review of published literature and on multidisciplinary expert agreement. The final goal is to propose the use of common terminology and rational diagnostic/therapeutic circuits based on current knowledge. To this end 51 sections related to chronic pancreatitis were reviewed by 21 specialists from 6 different fields to generate 88 statements altogether. Statements were designed to harmonize concepts or delineate recommendations. Part 2 of these paper series discuss topics on treatment and follow-up. The therapeutic approach should include assessment of etiological factors, clinical manifestations and complications. The complexity of these patients advocates for detailed evaluation in multidisciplinary committees where conservative, endoscopic, interventional radiology or surgical options are weighed. Specialized multidisciplinary units of Pancreatology should be constituted. Indications for surgery are refractory pain, local complications, and suspicion of malignancy. Enzyme replacement therapy is indicated if evidence of exocrine insufficiency or after pancreatic surgery. Response should be evaluated by nutritional parameters and assessment of symptoms. A follow-up program should be planned for every patient with chronic pancreatitis.
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http://dx.doi.org/10.1016/j.gastrohep.2021.05.016DOI Listing
June 2021

Pancreatitis crónica para el clínico. Parte 1: Etiología y Diagnóstico. Documento de posicionamiento interdisciplinar de la Societat Catalana de Digestologia y la Societat Catalana de Pàncrees (versión castellana).

Gastroenterol Hepatol 2021 Jun 19. Epub 2021 Jun 19.

CIBERehd, Instituto de Salud Carlos III, Av. Monforte de Lemos, 3-5, Pabellón 11, 28029, Madrid, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer, (IDIBAPS), Carrer del Rosselló, 149, 08036 Barcelona, Spain; Servei de Gastroenterologia, ICMDiM, Hospital Clínic, C. de Villarroel, 170, 08036 Barcelona, Spain; Gastrointestinal and Pancreatic Oncology Research Group, Hospital Clínic, C. de Villarroel 170, 08036 Barcelona, Spain. Electronic address:

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http://dx.doi.org/10.1016/j.gastrohep.2021.05.017DOI Listing
June 2021

Predictive Value of Carcinoembryonic Antigen in Symptomatic Patients without Colorectal Cancer: A Post-Hoc Analysis within the COLONPREDICT Cohort.

Diagnostics (Basel) 2020 Dec 2;10(12). Epub 2020 Dec 2.

Gastroenterology Department, Complexo Hospitalario Universitario de Ourense, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 32005 Ourense, Spain.

We aimed to assess the risk of cancer in patients with abdominal symptoms after a complete colonoscopy without colorectal cancer (CRC), according to the carcinoembryonic antigen (CEA) concentration, as well as its diagnostic accuracy. For this purpose, we performed a post-hoc analysis within a cohort of 1431 patients from the COLONPREDICT study, prospectively designed to assess the fecal immunochemical test accuracy in detecting CRC. Over 36.5 ± 8.4 months, cancer was detected in 115 (8%) patients. Patients with CEA values higher than 3 ng/mL revealed an increased risk of cancer (HR 2.0, 95% CI 1.3-3.1), CRC (HR 4.4, 95% CI 1.1-17.7) and non-gastrointestinal cancer (HR 1.7, 95% CI 1.0-2.8). A new malignancy was detected in 51 (3.6%) patients during the first year and three variables were independently associated: anemia (OR 2.8, 95% CI 1.3-5.8), rectal bleeding (OR 0.3, 95% CI 0.1-0.7) and CEA level >3 ng/mL (OR 3.4, 95% CI 1.7-7.1). However, CEA was increased only in 31.8% (95% CI, 16.4-52.7%) and 50% (95% CI, 25.4-74.6%) of patients with and without anemia, respectively, who would be diagnosed with cancer during the first year of follow-up. On the basis of this information, CEA should not be used to assist in the triage of patients presenting with lower bowel symptoms who have recently been ruled out a CRC.
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http://dx.doi.org/10.3390/diagnostics10121036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7770570PMC
December 2020

Risk of gastrointestinal cancer in a symptomatic cohort after a complete colonoscopy: Role of faecal immunochemical test.

World J Gastroenterol 2020 Jan;26(1):70-85

Gastroenterology Department, Complexo Hospitalario Universitario de Ourense, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Ourense 32005, Spain.

Background: Faecal immunochemical test (FIT) has been recommended to assess symptomatic patients for colorectal cancer (CRC) detection. Nevertheless, some conditions could theoretically favour blood originating in proximal areas of the gastrointestinal tract passing through the colon unmetabolized. A positive FIT result could be related to other gastrointestinal cancers (GIC).

Aim: To assess the risk of GIC detection and related death in FIT-positive symptomatic patients (threshold 10 μg Hb/g faeces) without CRC.

Methods: Post hoc cohort analysis performed within two prospective diagnostic test studies evaluating the diagnostic accuracy of different FIT analytical systems for CRC and significant colonic lesion detection. Ambulatory patients with gastrointestinal symptoms referred consecutively for colonoscopy from primary and secondary healthcare, underwent a quantitative FIT before undergoing a complete colonoscopy. Patients without CRC were divided into two groups (positive and negative FIT) using the threshold of 10 μg Hb/g of faeces and data from follow-up were retrieved from electronic medical records of the public hospitals involved in the research. We determined the cumulative risk of GIC, CRC and upper GIC. Hazard rate (HR) was calculated adjusted by age, sex and presence of significant colonic lesion.

Results: We included 2709 patients without CRC and a complete baseline colonoscopy, 730 (26.9%) with FIT ≥ 10 µgr Hb/gr. During a mean time of 45.5 ± 20.0 mo, a GIC was detected in 57 (2.1%) patients: An upper GIC in 35 (1.3%) and a CRC in 14 (0.5%). Thirty-six patients (1.3%) died due to GIC: 22 (0.8%) due to an upper GIC and 9 (0.3%) due to CRC. FIT-positive subjects showed a higher CRC risk (HR 3.8, 95%CI: 1.2-11.9) with no differences in GIC (HR 1.5, 95%CI: 0.8-2.7) or upper GIC risk (HR 1.0, 95%CI: 0.5-2.2). Patients with a positive FIT had only an increased risk of CRC-related death (HR 10.8, 95%CI: 2.1-57.1) and GIC-related death (HR 2.2, 95%CI: 1.1-4.3), with no differences in upper GIC-related death (HR 1.4, 95%CI: 0.6-3.3). An upper GIC was detected in 22 (0.8%) patients during the first year. Two variables were independently associated: anaemia (OR 5.6, 95%CI: 2.2-13.9) and age ≥ 70 years (OR 2.7, 95%CI: 1.1-7.0).

Conclusion: Symptomatic patients without CRC have a moderate risk increase in upper GIC, regardless of the FIT result. Patients with a positive FIT have an increased risk of post-colonoscopy CRC.
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http://dx.doi.org/10.3748/wjg.v26.i1.70DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6952298PMC
January 2020

Prediction of advanced colonic neoplasm in symptomatic patients: a scoring system to prioritize colonoscopy (COLONOFIT study).

BMC Cancer 2019 Jul 25;19(1):734. Epub 2019 Jul 25.

Department of Gastroenterology, Hospital Parc Taulí, Sabadell, Barcelona, Spain.

Background: Fast-track colonoscopy to detect patients with colorectal cancer based on high-risk symptoms is associated with low sensitivity and specificity. The aim was to derive a predictive score of advanced colonic neoplasia in symptomatic patients in fast-track programs.

Methods: All patients referred for fast-track colonoscopy were evaluated. Faecal immunological haemoglobin test (3 samples; positive> 4 μg Hb/g), and a survey to register clinical variables of interest were performed. Colorectal cancer and advanced adenoma were considered as advanced colonic neoplasia. A sample size of 600 and 500 individuals were calculated for each phase 1 and phase 2 of the study, respectively (Phase 1, derivation and Phase 2, validation cohort). A Bayesian logistic regression analysis was used to derive a predictive score.

Results: 1495 patients were included. Age (OR, 21), maximum faecal-Hb value (OR, 2.3), and number of positive samples (OR, 28) presented the highest ORs predictive of advanced colonic neoplasia. The additional significant predictive variables adjusted for age and faecal-Hb variables in Phase 1 were previous colonoscopy (last 5 years) and smoking (no, ex/active). With these variables a predictive score of advanced colonic neoplasia was derived. Applied to Phase 2, patients with a Score > 20 had an advanced colonic neoplasia probability of 66% (colorectal cancer, 32%), while those with a Score ≤ 10, a probability of 10% (colorectal cancer, 1%). Prioritizing patients with Score > 10, 49.4% of patients would be referred for fast-track colonoscopy, diagnosing 98.3% of colorectal cancers and 77% of advanced adenomas.

Conclusions: A scoring system was derived and validated to prioritize fast-track colonoscopies according to risk, which was efficient, simple, and robust.
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http://dx.doi.org/10.1186/s12885-019-5926-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6659265PMC
July 2019

Influence of age, body mass index and comorbidity on major outcomes in acute pancreatitis, a prospective nation-wide multicentre study.

United European Gastroenterol J 2018 Dec 3;6(10):1508-1518. Epub 2018 Sep 3.

Department of Gastroenterology, Hospital General Universitario de Alicante, Alicante, Spain.

Background: There are few large prospective cohort studies evaluating predictors of outcomes in acute pancreatitis.

Objectives: The purpose of this study was to determine the role of age and co-morbid disease in predicting major outcomes in acute pancreatitis.

Methods: Data points were collected according to a predefined electronic data collection form. Acute pancreatitis and its complications were defined according to the revised Atlanta classification. Univariable and multivariable analyses were conducted using Cox proportional hazard regression and multiple logistic regression.

Results: From June 2013-February 2015, 1655 adult patients were recruited from 23 centres across Spain. Co-morbid disease, obesity, open surgical necrosectomy within 30 days, and pancreatic necrosis were independently associated with both 30-day mortality and persistent organ failure ( < 0.05 for all). Age was not associated with persistent organ failure, however the extreme of age (>85 years) was associated with mortality ( < 0.05). Co-morbid disease and obesity were not independently associated with a prolonged length of stay or other markers of morbidity on adjusted analysis ( > 0.05).

Conclusion: Comorbidity and obesity are important determinates of mortality and persistent organ failure in acute pancreatitis, but in the absence of organ failure they do not appear to independently contribute to morbidity. This has important implications for severity classification and predictive models of severity in acute pancreatitis.
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http://dx.doi.org/10.1177/2050640618798155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6297924PMC
December 2018

New Methylation Biomarker Panel for Early Diagnosis of Dysplasia or Cancer in High-Risk Inflammatory Bowel Disease Patients.

Inflamm Bowel Dis 2018 11;24(12):2555-2564

Department of General and Digestive Surgery, Colorectal Unit, University Hospital Bellvitge (HUB-IDIBELL)-CIBERONC, L'Hospitalet de Llobregat, Barcelona, Spain.

Background: The risk of developing colorectal cancer (CRC) is increased in patients with inflammatory bowel disease (IBD) of the colon. The aim of the study was to evaluate the effectiveness of selected methylation gene panel for the early detection of CRC in high-risk IBD patients.

Methods: In a discovery phase, 73 biopsies of 48 IBD patients (associated or not to CRC) were analyzed from genome-wide DNA methylation analysis using the Illumina Human Methylation 450K BeadChip. The panel of 5 genes selected (EYA4, SLIT2, FLI1, USP44, and SND1) was validated prospectively using methylation-specific melting curve analysis in biopsies of diseased and adjacent healthy tissue of 203 patients: 38 with IBD and associated neoplasia, 81 patients with IBD (25 of them with high risk), 48 with sporadic CRC, and 36 healthy controls.

Results: The prevalence of methylation was higher in patients with IBD and associated neoplasia (both in diseased and adjacent healthy tissue, 71% and 52%, respectively) than in healthy controls (2/36, 6%; P = 6.72E-05). Methylation in IBD patients at high risk of dysplasia or cancer was more frequently detected than in patients at low risk (92% vs 57%; odds ratio, 8.63; P = 0.001). EYA4 and SLIT2 were the markers most frequently methylated. Differences in methylation levels were more evident in healthy mucosa (82% vs 15% high vs low risk, respectively; P = 1.25E-05).

Conclusions: Analysis of this panel of methylation markers may help in the early identification of colorectal dysplasia or cancer in high-risk IBD patients.
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http://dx.doi.org/10.1093/ibd/izy255DOI Listing
November 2018

Effect of aspirin on the diagnostic accuracy of the faecal immunochemical test for colorectal advanced neoplasia.

United European Gastroenterol J 2018 Feb 21;6(1):123-130. Epub 2017 Apr 21.

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

Background: Aspirin (ASA) is a drug that can cause gastrointestinal lesions and symptoms. Colorectal cancer (CRC) is the most prevalent type of cancer in Western countries. We assessed the effect of aspirin on the diagnostic accuracy of the faecal immunochemical test (FIT) for CRC and/or advanced neoplasia (AN) in patients undergoing colonoscopy for gastrointestinal symptoms.

Methods: We conducted a prospective multicentre observational study of diagnostic tests that included patients with gastrointestinal symptoms undergoing colonoscopy between March 2012 and 2014 (the COLONPREDICT study). Symptoms were assessed and a FIT and blood tests assessing haemoglobin and carcinoembryonic antigen (CEA) levels were performed.

Results: The study included 3052 patients: A total of 2567 did not take aspirin (non-user group) and 485 (16%) took aspirin (user group). Continuous treatment with ASA did not change the AUC (0.88, 0.82;  = 0.06), sensitivity (92%, 88%;  = 0.5) or specificity (71%, 67%;  = 0.2) of the FIT for CRC detection. Similarly, we found no differences in the AUC (0.81, 0.79;  = 0.6), sensitivity (74%, 75.5%;  = 0.3) or specificity (76%, 73.6%;  = 0.3) for AN detection. Patients with an aspirin use of ≥ 300 mg/day had a lower prevalence of AN and the sensitivity, specificity and AUC for AN for these patients were 54%, 68% and 0.66, significantly lower than for the non-user group ( = 0.03).

Conclusions: Aspirin does not modify the diagnostic accuracy of FIT for CRC and/or AN in patients with gastrointestinal symptoms. Aspirin use of ≥ 300 mg/day decreases the accuracy of the test.
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http://dx.doi.org/10.1177/2050640617707094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5802670PMC
February 2018

The fecal hemoglobin concentration, age and sex test score: Development and external validation of a simple prediction tool for colorectal cancer detection in symptomatic patients.

Int J Cancer 2017 May 6;140(10):2201-2211. Epub 2017 Mar 6.

Centre for Research into Cancer Prevention and Screening, University of Dundee, Ninewells Hospital & Medical School, Dundee, Scotland, United Kingdom.

Prediction models for colorectal cancer (CRC) detection in symptomatic patients, based on easily obtainable variables such as fecal haemoglobin concentration (f-Hb), age and sex, may simplify CRC diagnosis. We developed, and then externally validated, a multivariable prediction model, the FAST Score, with data from five diagnostic test accuracy studies that evaluated quantitative fecal immunochemical tests in symptomatic patients referred for colonoscopy. The diagnostic accuracy of the Score in derivation and validation cohorts was compared statistically with the area under the curve (AUC) and the Chi-square test. 1,572 and 3,976 patients were examined in these cohorts, respectively. For CRC, the odds ratio (OR) of the variables included in the Score were: age (years): 1.03 (95% confidence intervals (CI): 1.02-1.05), male sex: 1.6 (95% CI: 1.1-2.3) and f-Hb (0-<20 µg Hb/g feces): 2.0 (95% CI: 0.7-5.5), (20-<200 µg Hb/g): 16.8 (95% CI: 6.6-42.0), ≥200 µg Hb/g: 65.7 (95% CI: 26.3-164.1). The AUC for CRC detection was 0.88 (95% CI: 0.85-0.90) in the derivation and 0.91 (95% CI: 0.90-093; p = 0.005) in the validation cohort. At the two Score thresholds with 90% (4.50) and 99% (2.12) sensitivity for CRC, the Score had equivalent sensitivity, although the specificity was higher in the validation cohort (p < 0.001). Accordingly, the validation cohort was divided into three groups: high (21.4% of the cohort, positive predictive value-PPV: 21.7%), intermediate (59.8%, PPV: 0.9%) and low (18.8%, PPV: 0.0%) risk for CRC. The FAST Score is an easy to calculate prediction tool, highly accurate for CRC detection in symptomatic patients.
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http://dx.doi.org/10.1002/ijc.30639DOI Listing
May 2017

Development and external validation of a faecal immunochemical test-based prediction model for colorectal cancer detection in symptomatic patients.

BMC Med 2016 08 31;14(1):128. Epub 2016 Aug 31.

Gastroenterology Department, Complexo Hospitalario Universitario de Ourense, Rua Ramón Puga 52-54, 32005, Ourense, Spain.

Background: Risk prediction models for colorectal cancer (CRC) detection in symptomatic patients based on available biomarkers may improve CRC diagnosis. Our aim was to develop, compare with the NICE referral criteria and externally validate a CRC prediction model, COLONPREDICT, based on clinical and laboratory variables.

Methods: This prospective cross-sectional study included consecutive patients with gastrointestinal symptoms referred for colonoscopy between March 2012 and September 2013 in a derivation cohort and between March 2014 and March 2015 in a validation cohort. In the derivation cohort, we assessed symptoms and the NICE referral criteria, and determined levels of faecal haemoglobin and calprotectin, blood haemoglobin, and serum carcinoembryonic antigen before performing an anorectal examination and a colonoscopy. A multivariate logistic regression analysis was used to develop the model with diagnostic accuracy with CRC detection as the main outcome.

Results: We included 1572 patients in the derivation cohort and 1481 in the validation cohorts, with a 13.6 % and 9.1 % CRC prevalence respectively. The final prediction model included 11 variables: age (years) (odds ratio [OR] 1.04, 95 % confidence interval [CI] 1.02-1.06), male gender (OR 2.2, 95 % CI 1.5-3.4), faecal haemoglobin ≥20 μg/g (OR 17.0, 95 % CI 10.0-28.6), blood haemoglobin <10 g/dL (OR 4.8, 95 % CI 2.2-10.3), blood haemoglobin 10-12 g/dL (OR 1.8, 95 % CI 1.1-3.0), carcinoembryonic antigen ≥3 ng/mL (OR 4.5, 95 % CI 3.0-6.8), acetylsalicylic acid treatment (OR 0.4, 95 % CI 0.2-0.7), previous colonoscopy (OR 0.1, 95 % CI 0.06-0.2), rectal mass (OR 14.8, 95 % CI 5.3-41.0), benign anorectal lesion (OR 0.3, 95 % CI 0.2-0.4), rectal bleeding (OR 2.2, 95 % CI 1.4-3.4) and change in bowel habit (OR 1.7, 95 % CI 1.1-2.5). The area under the curve (AUC) was 0.92 (95 % CI 0.91-0.94), higher than the NICE referral criteria (AUC 0.59, 95 % CI 0.55-0.63; p < 0.001). On the basis of the thresholds with 90 % (5.6) and 99 % (3.5) sensitivity, we divided the derivation cohort into three risk groups for CRC detection: high (30.9 % of the cohort, positive predictive value [PPV] 40.7 %, 95 % CI 36.7-45.9 %), intermediate (29.5 %, PPV 4.4 %, 95 % CI 2.8-6.8 %) and low (39.5 %, PPV 0.2 %, 95 % CI 0.0-1.1 %). The discriminatory ability was equivalent in the validation cohort (AUC 0.92, 95 % CI 0.90-0.94; p = 0.7).

Conclusions: COLONPREDICT is a highly accurate prediction model for CRC detection.
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http://dx.doi.org/10.1186/s12916-016-0668-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5007726PMC
August 2016

Impact of endoscopic ultrasonography (EUS) and EUS-guided fine-needle aspiration on the management of pancreatic cystic lesions.

Eur J Gastroenterol Hepatol 2016 Sep;28(9):1094-9

aEndoscopy Unit, Hospital Clínic, IDIBAPS, CIBERehd Departments of bDigestive Surgery cGastroenterology, Hospital Clínic dDepartment of Gastroenterology, Hospital Vall d'Hebron, Barcelona eDepartment of Gastroenterology, Hospital de Terrassa, Terrassa fDepartment of Digestive Surgery, Hospital de Bellvitge, Hospitalet de Llobregat, Spain.

Background And Study Aims: Endoscopic ultrasonography (EUS) and EUS-guided fine-needle aspiration (EUS-FNA) are well-recognized techniques for the study of pancreatic cystic lesions (PCLs). However, little evidence exists on their impact on clinical care. The aim of this study is to determine how often EUS and EUS-FNA alter the diagnosis and management of patients with PCLs.

Patients And Methods: Eight physicians expert in pancreatic diseases were asked to report their diagnoses and management recommendations for 49 different PCLs. Clinical information was sequentially disclosed in a stepwise manner - progressively from clinical data plus computed tomography or MRI (level 1), to EUS (level 2) and EUS-FNA results including cytology, carcinoembryonic antigen, and amylase levels (level 3).

Results: EUS led to a change in the diagnosis and management in 30% [95% confidence interval (CI): 26-35%] and 19% (95% CI: 16-23%) of cases, respectively, usually to a more intensive approach (14%; 95% CI: 11-18%). EUS-FNA altered the diagnosis and management in an additional 39% (95% CI: 34-44%) and 21% (95% CI: 17-25%) of the evaluations, respectively. EUS-FNA also increased the consensus in the diagnosis among the specialists that ranged from fair with computed tomography/MRI (κ-index=0.32) to substantial with EUS-FNA (κ-index=0.43).

Conclusion: EUS and EUS-FNA impact the diagnosis and management of patients with PCLs; therefore, both are necessary in the workup of these patients. EUS-FNA markedly improves the agreement between physicians in terms of diagnosis, but not management. This study highlights the need for more research and standardization in the field.
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http://dx.doi.org/10.1097/MEG.0000000000000678DOI Listing
September 2016

Evidence-based Guidelines for the Management of Exocrine Pancreatic Insufficiency After Pancreatic Surgery.

Ann Surg 2016 Dec;264(6):949-958

*Department of Surgery, Hospital Clinico, University of Valencia, Valencia, Spain †Department of Surgery, Complejo Hospitalario Universitario de Vigo, Vigo, Spain ‡Department of Surgery, University Medical Center Utrecht, Utrecht, The Netherlands §Department of Gastroenterology, Consorci Sanitari de Terrassa, Terrassa, Spain ¶Department of Gastroenterology, Complejo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela, Spain ||Department of Surgery, Università Vita e Salute, Ospedale San Raffaele IRCCS, Milano, Italy **Department of Surgery, Institut de Malalties Digestives I Metabòliques, Hospital Clínic, IDIBAPS, Barcelona, Spain ††Department of Medicine, Pancreas Center, University of Verona, Verona, Italy ‡‡Department of Endocrinology and Nutrition, Hospital General Universitario de Alicante, Instituto de Investigación Sanitaria y Biomédica de Alicante, Alicante, Spain. §§Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden ¶¶Department of Surgery, Hospital General Universitario de Alicante, Instituto de Investigación Sanitaria y Biomédica de Alicante, Alicante, Spain. ||||Department of Surgery, Hospital Universitario de La Princesa, Madrid, Spain ***Department of Gastroenterology, Complejo Hospitalario de Navarra, Pamplona, Spain †††Unidad de Cirugía Hepato-bilio-pancreática y Trasplante, Hospital Universitari i Politecnic. La Fe, Valencia, Spain ‡‡‡NIHR Pancreas Biomedical Research Unit, Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK §§§Department of Gastroenterology, Hospital Clinico, University of Valencia, Valencia, Spain ¶¶¶Unit of Digestive Disease, Agencia Sanitaria Costa del Sol, Marbella, Málaga ||||||Department Digestive System, Sant'Orsola-Malpighi Hospital, Bologna, Italy ****Department of Surgery, Hospital Universitario de Guadalajara, Guadalajara, Spain ††††Department of HPB Surgery and Liver Transplantation, Hospital Carlos Haya, Malaga, Spain ‡‡‡‡Exocrine Pancreas Research Unit, Hospital Universitari Vall d'Hebron, Institut de Recerca, Universitat Autònoma de Barcelona, CIBEREHD, Barcelona, Spain §§§§Department of Digestive Surgery- Division of HBP Surgery, Hospital Universitario Donostia, San Sebastián, Spain ¶¶¶¶Department of Gastroenterology, Institut de Malalties Digestives i Metabòliques, Hospital Clínic, IDIBAPS, CiberEHD, Barcelona, Spain ||||||||Department of Gastroenterology, Hospital General Universitario de Alicante, Instituto de Investigación Sanitaria y Biomédica de Alicante, Alicante, Spain.

Objective: To provide evidence-based recommendations for the management of exocrine pancreatic insufficiency (EPI) after pancreatic surgery.

Background: EPI is a common complication after pancreatic surgery but there is certain confusion about its frequency, optimal methods of diagnosis, and when and how to treat these patients.

Methods: Eighteen multidisciplinary reviewers performed a systematic review on 10 predefined questions following the GRADE methodology. Six external expert referees reviewed the retrieved information. Members from Spanish Association of Pancreatology were invited to suggest modifications and voted for the quantification of agreement.

Results: These guidelines analyze the definition of EPI after pancreatic surgery, (one question), its frequency after specific techniques and underlying disease (four questions), its clinical consequences (one question), diagnosis (one question), when and how to treat postsurgical EPI (two questions) and its impact on the quality of life (one question). Eleven statements answering those 10 questions were provided: one (9.1%) was rated as a strong recommendation according to GRADE, three (27.3%) as moderate and seven (63.6%) as weak. All statements had strong agreement.

Conclusions: EPI is a frequent but under-recognized complication of pancreatic surgery. These guidelines provide evidence-based recommendations for the definition, diagnosis, and management of EPI after pancreatic surgery.
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http://dx.doi.org/10.1097/SLA.0000000000001732DOI Listing
December 2016

[Assessment and treatment of acute pancreatitis. Position document of the Catalan Society of Gastroenterology, Catalan Society of Surgery and Catalan Society of the Pancreas].

Gastroenterol Hepatol 2015 Feb 6;38(2):82-96. Epub 2014 Nov 6.

Servicio de Digestivo, Hospital Universitari Vall d'Hebron, Barcelona, España.

The incidence of acute pancreatitis (AP) is increasing. AP is one of the gastrointestinal diseases that most frequently requires hospital admission in affected individuals. In the last few years, considerable scientific evidence has led to substantial changes in the medical and surgical treatment of this disease. New knowledge of the physiopathology of AP indicates that its severity is influenced by its systemic effects (organ failure), especially if the disease is persistent, and also by local complications (fluid collections or necrosis), especially if these become infected. Treatment should be personalized and depends on the patient's clinical status, the location of the necrosis, and disease stage.
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http://dx.doi.org/10.1016/j.gastrohep.2014.09.006DOI Listing
February 2015

[Recommendations of the Spanish Pancreatic Club on the diagnosis and treatment of chronic pancreatitis: part 2 (treatment)].

Gastroenterol Hepatol 2013 Jun-Jul;36(6):422-36. Epub 2013 Apr 30.

Unidad Pancreática, Hospital General Universitario de Alicante, Alicante, España.

Chronic pancreatitis (CP) is a complex disease with a wide spectrum of clinical manifestations ranging from asymptomatic disease to disabling forms or serious complications. The management of CP frequently differs among geographical areas and even among centers. These differences are due to the scarcity of high-quality studies and clinical practice guidelines that focus on the diagnosis and treatment of this disease. The aim of the Spanish Pancreatic Club was to create evidence-based recommendations for the management of CP. Two coordinators chose a multidisciplinary panel of 24 experts in this disease. These experts were selected on the basis of their clinical and research experience in CP. A list of questions was drawn up and each question was then reviewed by two panelists. These questions were then used to produce a draft, which was discussed in a face-to-face meeting with all the participants. Levels of evidence were based on the classification of the Oxford Centre for Evidence-Based Medicine. In the second part of the consensus process, recommendations were established for the management of pain, pseudocysts, biliary and duodenal stenosis, pancreatic fistula and ascites, left portal hypertension, diabetes mellitus, exocrine pancreatic insufficiency, and nutritional support in CP.
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http://dx.doi.org/10.1016/j.gastrohep.2012.12.003DOI Listing
April 2014

[Recommendations of the Spanish Pancreatic Club on the diagnosis and treatment of chronic pancreatitis: part 1 (diagnosis)].

Gastroenterol Hepatol 2013 May 6;36(5):326-39. Epub 2013 Apr 6.

Unidad Pancreática, Hospital General Universitario de Alicante, Alicante, España.

Chronic pancreatitis (CP) is a relatively uncommon, complex and highly heterogeneous disease. There is no clear pattern applicable to the initial stages of CP, which hampers its early diagnosis. Some of the complications of CP, especially chronic pain, can be difficult to manage. There is wide variation in the diagnosis and treatment of CP and its complications among centers and health professionals. The Spanish Pancreatic Club has developed a consensus document on the management of CP. Two coordinators chose a multidisciplinary panel of 24 experts in this disease. A list of questions was drawn up. Each question was reviewed by two experts. These questions were then used to produce a draft, which was discussed in a face-to-face meeting with all the participants. The first part of the consensus document focusses on the diagnosis of CP and its complications.
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http://dx.doi.org/10.1016/j.gastrohep.2012.12.004DOI Listing
May 2013

Safety and efficacy of treatment with pegylated interferon alpha-2a with ribavirin in chronic hepatitis C genotype 4.

Ann Hepatol 2013 Jan-Feb;12(1):30-5

Consorcio Hospital General Universitario de Valencia, Spain.

The hepatitis C virus (HCV) genotype is an important predictive outcome parameter for pegylated interferon plus ribavirin therapy. Most published therapeutic trials to date have enrolled mainly patients with HCV genotypes 1, 2 and 3. Limited studies have focused on genotype 4 patients, who have had a poor representation in pivotal trials. Our aim was to evaluate the efficacy and safety of treatment with standard dose pegylated interferon alfa-2a in combination with weight-based ribavirin in patients with chronic hepatitis C genotype 4. In this prospective observational study, 198 patients with HCV-4 were included in this study from February 2004 to August 2005,188 patients who received at least 1 dose of drugs were included in the ITT analysis and they were treated with pegylated interferon alfa-2a and ribavirin for 48 weeks. Baseline and demographic characteristics, response to treatment at weeks 12, 48 and 72, and the nature and frequency of adverse effects were analyzed. Virological response at week 12 was achieved in 144 patients (76.6%). Virological response at the end of treatment was present in 110 patients (58.5%). At week 72, 99 patients presented SVR (52.7%). The reported adverse events were similar to those found in the literature for treatments of similar dose and duration. In conclusion, combined treatment with pegylated interferon alfa-2a and ribavirin was well tolerated and effective in chronic hepatitis C genotype 4, yielding response rates between those reported for genotype 1 and those of genotypes 2-3.
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June 2013

Nanofluidic digital PCR for KRAS mutation detection and quantification in gastrointestinal cancer.

Clin Chem 2012 Sep 27;58(9):1332-41. Epub 2012 Jun 27.

Translational Research Laboratory, Catalan Institute of Oncology-ICO-IDIBELL, Hospitalet de Llobregat, Barcelona, Spain.

Background: Concomitant quantification of multiple mutant KRAS (v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) alleles may provide information in addition to that provided by standard mutation-detection procedures. We assessed the feasibility of a nanofluidic digital PCR array platform to detect and quantify KRAS mutations simultaneously in clinically relevant samples.

Methods: We assessed 2 groups of patients (colorectal and pancreatic disease): Group 1 consisted of 27 patients with colorectal carcinomas, 14 patients with adenomas, and 5 control individuals; group 2 consisted of 42 patients with pancreatic carcinoma, 4 with adenocarcinomas of the ampulla, and 6 with chronic pancreatitis). Digital PCR was performed with the Digital Array Chip (Fluidigm).

Results: Nanofluidic digital PCR detected mutant alleles at 0.05% to 0.1%, depending on the variant analyzed. For the colorectal disease group, conventional PCR detected 9 (64%) of 14 adenomas that were positive for KRAS mutants, whereas digital PCR increased this number to 11 (79%) of 14. Sixteen (59%) of 27 carcinomas showed KRAS mutation with conventional PCR. Two additional cases were detected with digital PCR. In 5 cases (3 adenomas, 2 carcinomas), the total number of mutant alleles changed. For the pancreatic disease group, digital PCR increased the number of positive cases from 26 to 34 (81%) and identified ≥ 2 mutant alleles in 25 cases, compared with conventional PCR, which identified multiple KRAS mutant alleles in only 12 cases. A good correlation was observed between results obtained with tumor biopsies and those obtained with pancreatic juice.

Conclusions: Digital PCR provides a robust, quantitative measure of the proportion of KRAS mutant alleles in routinely obtained samples. It also allows a better classification of tumors, with potential clinical relevance.
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http://dx.doi.org/10.1373/clinchem.2012.186577DOI Listing
September 2012

Novel methylation panel for the early detection of neoplasia in high-risk ulcerative colitis and Crohn's colitis patients.

Inflamm Bowel Dis 2013 Jan;19(1):165-73

Translational Research Laboratory, Catalan Institute of Oncology, IDIBELL, Hospitalet de Llobregat, Barcelona, Spain.

Background: Patients with ulcerative colitis and Crohn's colonic disease are at increased risk of developing colorectal cancer (CRC). The aim of the study was to analyze the methylation status of selected genes as a risk marker for CRC in inflammatory bowel disease (IBD) patients.

Methods: We evaluated the methylation status of four genes (TGFB2, SLIT2, HS3ST2, and TMEFF2) in biopsies of four groups of patients: 60 patients with sporadic CRC, 32 patients with IBD-associated neoplasia, 85 patients with IBD without associated neoplasia (20 at high risk and 65 at low risk), and 28 healthy controls. Methylation-specific melting curve analysis (MS-MCA) was used. Methylation status of these genes was also assessed in stool DNA from 60 IBD patients without neoplasia.

Results: Methylation of the panel of genes analyzed was a very common phenomenon (78%) in IBD-associated neoplasia. The prevalence of methylation in adjacent nonneoplastic mucosa was also high (12/30). This prevalence was higher than in mucosa from healthy controls (2/28;7.1%; P < 0.05). Methylation of SLIT2 and TMEFF2 was more frequently detected in the mucosa of IBD patients at high risk of dysplasia or cancer (15/20) than patients at low risk (32/63) (P = 0.05 and P = 0.03, respectively). When stool samples were assessed, only SLIT2 gene methylation was more frequently methylated in the group of patients at high risk of dysplasia or cancer (4/16) compared to low risk (0/37) (P = 0.006).

Conclusions: Analysis of a panel of methylation markers may help in the early identification of colorectal dysplasia or cancer in high-risk IBD patients.
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http://dx.doi.org/10.1002/ibd.22994DOI Listing
January 2013

[Emergency care of patients with upper gastrointestinal bleeding in regional hospitals in Catalonia].

Gastroenterol Hepatol 2011 Nov 14;34(9):605-10. Epub 2011 Oct 14.

Hospital Universitari Sant Joan, Reus, España.

Objective: To evaluate the resources available in Catalan regional hospitals for the emergency care of upper gastrointestinal hemorrhage.

Methods: We analyzed a survey sent to 32 hospitals on the availability, composition and resources of a duty endoscopy service for the year 2009.

Results: Responses were obtained from 24 centers, covering 3,954,000 inhabitants. Duty endoscopists were available in 12 hospitals. A total of 1,483,000 inhabitants were unable to access a duty endoscopist in the referral center. Centers with duty endoscopists had more beds and had a larger catchment area. Duty services were composed of 4.5 endoscopists (range 2-11), covering 82.1 (33.2-182.5) duty shifts/year. Seventeen centers reported 1,571 episodes (51%, range: 3-280, 39.68/100,000 inhabitants). Centers with a duty service reported a greater number of cases (76 vs. 43, p=0.047). Centers without this service referred a greater number of patients (147 vs. 17, p=0.001). Patients in the emergency department were under the care of the internal medicine department in four centers, the surgery department in 14 centers and under the care of both departments in six. Admitted patients were under the care of the gastroenterology department in only six hospitals. The most widely used procedures were ligation of varicose bleeding and injection therapies in non-varicose bleeding. Twenty-one percent of centers did not perform combined treatment.

Conclusions: A significant proportion of the population does not have access to a duty endoscopist in referral centers. Duty shifts represent significant workload in regional hospitals. Coordination among health professionals and centers would allow the efficient application of therapeutic resources and a duty endoscopy service to be established in centers lacking this resource.
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http://dx.doi.org/10.1016/j.gastrohep.2011.07.003DOI Listing
November 2011

Postoperative surveillance in patients with colorectal cancer who have undergone curative resection: a prospective, multicenter, randomized, controlled trial.

J Clin Oncol 2006 Jan 19;24(3):386-93. Epub 2005 Dec 19.

Gastroenterology Department, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona (IDIBAPS), Barcelona, Catalonia, Spain.

Purpose: Although systematic postoperative surveillance of patients with colorectal cancer has been demonstrated to improve survival, it remains unknown whether a more intensive strategy provides any significant advantage. This prospective, multicenter, randomized, controlled trial was aimed at comparing the efficacy of two different surveillance strategies in terms of both survival and recurrence resectability.

Patients And Methods: Patients with stage II or III colorectal cancer were allocated randomly to either a simple surveillance strategy including clinical evaluation and serum carcinoembryonic antigen monitoring, or an intensive strategy in which abdominal computed tomography or ultrasonography, chest radiograph, and colonoscopy were added.

Results: A total of 259 patients were included: 132 were observed according to the simple strategy and 127 were observed according to the intensive strategy. Both groups were similar with respect to baseline characteristics and rate and type of tumor recurrence. After a median follow-up of 48 months, there was no difference in the probability of overall survival in the whole series (hazard ratio [HR] = 0.87; 95% CI, 0.49 to 1.54; P = .62). However, the intensive strategy was associated with higher overall survival in patients with stage II tumors (HR = 0.34; 95% CI, 0.12 to 0.98; P = .045) and in those with rectal lesions (HR = 0.09; 95% CI, 0.01 to 0.81; P = .03), mainly due to higher rate of resectability for recurrent tumors. Colonoscopy was responsible for the detection of the highest proportion (44%) of resectable tumor recurrence in the intensive arm.

Conclusion: A more intensive surveillance strategy improves the prognosis of patients with stage II colorectal cancer or those with rectal tumors. Inclusion of regular performance of colonoscopy seems justified up to the fifth year of follow-up, at least.
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http://dx.doi.org/10.1200/JCO.2005.02.0826DOI Listing
January 2006

Different CFTR mutational spectrum in alcoholic and idiopathic chronic pancreatitis?

Pancreas 2004 May;28(4):374-9

Medical and Molecular Genetics Center-IRO, Hospital DIR, Barcelona, Spain.

Objective: Cystic fibrosis transmembrane conductance regulator (CFTR) mutations are responsible for cystic fibrosis (CF) and have been postulated as a predisposing risk factor to chronic pancreatitis (CP), but controversial results demand additional support. We have therefore investigated the role of the CFTR gene in a cohort of 68 CP patients.

Methods: We have performed the CFTR gene analysis using 2 screening techniques. Fragments showing abnormal migration patterns were characterized by sequencing. Patients were classified in alcoholic (ACP) (n = 37) and idiopathic (ICP) (n = 31) chronic pancreatitis. Clinical features of CP and CF were evaluated.

Results: Sixteen mutations/variants were identified in 27 patients (40%), most of them (35%) presenting a single CFTR mutant gene. The 1716G/A variant showed the highest frequency accounting for 22% in ICP and 5% in ACP, in contrast with other more common mutations such as F508del found in 8% of ACP and the 5T variant identified in 7% of patients. Acute pancreatitis, abdominal pain, tobacco, pancreatic calcifications, and pancreatic pseudocysts showed significant higher values in ACP than ICP patients. No significant differences were found between patients with and without CFTR mutations.

Conclusions: Apart from reinforcing previous findings our data highlight the increased susceptibility of CFTR heterozygous to developing CP. Heterozygosity, combined with other factors, places these individuals at greater risk.
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http://dx.doi.org/10.1097/00006676-200405000-00004DOI Listing
May 2004

[Induction therapy with interferon alfa-2a in compensated hepatitis C virus-related cirrhosis. Randomized, multicenter study].

Med Clin (Barc) 2002 May;118(17):641-4

Hospital Universitari Germans Trias i Pujol. Badalona. BArcelona. Spain.

Background: Although standard dose interferon (IFN) is successful in only 5% of patients with compensated hepatitis C virus (HCV)-related cirrhosis, it has been suggested that this therapy might decrease the risk of complications or the incidence of hepatocellular carcinoma. Based on HCV kinetics, daily IFN may improve response rates.

Patients And Method: Forty cirrhotic patients were randomised to receive (Group I: 19) or not (Group II: 21) treatment with IFN (4.5 MU/daily for 24 weeks, followed by 4.5 MU/48 hours for a further 24 weeks period, only if ALT was within normal values).

Results: Dose reduction and discontinuation for adverse events was required in 11 (58%) and 6 (31.5%) cases, respectively. End-of-treatment response was not observed in any of the 21 controls but in 4 of the 19 (21%) treated patients (p = 0.04); a sustained response was achieved in only 2 treated patients (10.5%). The 3-year probability of developing any of the following: ascites, hepatocellular carcinoma, transplantation or death was lower in Group I than in Group II (6% vs 27%; p = 0.05).

Conclusion: Although induction IFN therapy is associated with common side effects and poor sustained response in compensated HCV-related cirrhosis, it might improve the outcome of patients at the medium-term.
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http://dx.doi.org/10.1016/s0025-7753(02)72483-4DOI Listing
May 2002
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