Rendimiento diagnóstico de la punción mediante ultrasonografía endoscópica de las lesiones quísticas del páncreas / Diagnostic yield of endoscopic ultrasound with fine-needle aspiration in pancreatic cystic lesions

Introducción: A pesar de los avances en las técnicas de imagen, en muchos casos son insuficientes para establecer el diagnóstico de las lesiones quísticas pancreáticas (LQP). Son escasas las publicaciones en nuestro medio que evalúan la combinación de varios métodos obtenidos mediante la punción aspirativa con aguja fina con ultrasonografía endoscópica (USE-PAAF). El objetivo del estudio fue evaluar la utilidad global de la USE-PAAF en el diagnóstico de las LQP. Material y métodos: Estudio retrospectivo a partir de una base de datos actualizada prospectivamente de una cohorte de pacientes remitidos para USE-PAAF por LQP. Se estudió la sensibilidad, la especificidad, el rendimiento diagnóstico del antígeno carcinoembrionario (CEA), la citología y la viscosidad para detectar lesiones mucinosas. Resultados: Desde noviembre de 2013 a abril del 2018 se realizaron 122 USE por LQP. Se realizó USE-PAAF en 94/122 (77%) y se intervinieron 21/122 (17,2%) pacientes. Se incluyeron 33/122 pacientes que tuvieron confirmación diagnóstica mediante histología, imagen (quiste seroso con patrón típico) o evolución clínica. El estudio de la curva ROC determinó el punto de corte ≥419ng/ml para diferenciar lesión quística mucinosa/no mucinosa. El rendimiento diagnóstico del CEA fue del 87,5% (21/24), de la citología del 81,8% (27/33) y de la viscosidad del 84,4% (27/32). Los 3 parámetros en combinación obtuvieron el mejor resultado (30/33, 90,9%). Conclusión: La combinación del análisis del CEA, la citología y la viscosidad del líquido pancreático obtenido mediante USE-PAAF aumenta el rendimiento en el diagnóstico de las lesiones quísticas pancreáticas mucinosas, siendo superior al 90%

Introduction: Despite advances in imaging techniques, in many cases they are insufficient to establish the diagnosis of pancreatic cystic lesions (PCL). There are few publications in our setting that evaluate the combination of several methods obtained by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). The aim of the study was to evaluate the overall utility of EUS-FNA in the diagnosis of PCL. Material and methods: Retrospective study based on a database updated prospectively of a cohort of patients referred for EUS-FNA due to PCL detected in an imaging test. The sensitivity, specificity and diagnostic yield of carcinoembryonic antigen (CEA), cytology and viscosity were studied to detect mucinous lesions. Results: From November 2013 to April 2018, 122 EUS were performed for PCL. EUS-FNA was performed in 94/122 (77%) and 21/122 (17.2%) patients were operated on. We included 33/122 patients who had diagnostic confirmation by histology, imaging (serous cyst with typical pattern) or clinical evolution. The study of the ROC curve determined the cutoff point ≥419 ng/ml to differentiate mucinous/non-mucinous cystic lesions. The diagnostic yield of CEA was 87.5% (21/24), cytology 81.8% (27/33) and viscosity 84.4% (27/32). The three parameters in combination obtained the best result (30/33, 90.9%). Conclusion: The combination of CEA analysis, cytology and viscosity of pancreatic fluid obtained by EUS-FNA increases the performance in the diagnosis of mucinous pancreatic cystic lesions, with it being greater than 90%

Diagnostic yield of endoscopic ultrasound with fine-needle aspiration in pancreatic cystic lesions. / Rendimiento diagnóstico de la punción mediante ultrasonografía endoscópica de las lesiones quísticas del páncreas.

INTRODUCTION: Despite advances in imaging techniques, in many cases they are insufficient to establish the diagnosis of pancreatic cystic lesions (PCL). There are few publications in our setting that evaluate the combination of several methods obtained by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). The aim of the study was to evaluate the overall utility of EUS-FNA in the diagnosis of PCL. MATERIAL AND METHODS: Retrospective study based on a database updated prospectively of a cohort of patients referred for EUS-FNA due to PCL detected in an imaging test. The sensitivity, specificity and diagnostic yield of carcinoembryonic antigen (CEA), cytology and viscosity were studied to detect mucinous lesions. RESULTS: From November 2013 to April 2018, 122 EUS were performed for PCL. EUS-FNA was performed in 94/122 (77%) and 21/122 (17.2%) patients were operated on. We included 33/122 patients who had diagnostic confirmation by histology, imaging (serous cyst with typical pattern) or clinical evolution. The study of the ROC curve determined the cutoff point ≥419 ng/ml to differentiate mucinous/non-mucinous cystic lesions. The diagnostic yield of CEA was 87.5% (21/24), cytology 81.8% (27/33) and viscosity 84.4% (27/32). The three parameters in combination obtained the best result (30/33, 90.9%). CONCLUSION: The combination of CEA analysis, cytology and viscosity of pancreatic fluid obtained by EUS-FNA increases the performance in the diagnosis of mucinous pancreatic cystic lesions, with it being greater than 90%.

Periendoscopic management of antiplatelet therapy: Prospective evaluation of adherence to guidelines / Manejo perioendoscópico del tratamiento antiagregante plaquetario: evaluación prospectiva del cumplimiento de las guías clínicas

Introducción: Adherence to guidelines on the periendoscopic management of antiplatelet therapy (APT) has not been analyzed in detail. Our aim was to assess adherence to guidelines in patients referred to our Endoscopy Unit on a case-by-case basis, describing in detail the detected deviations and identifying areas of improvement. Patients and methods: Cross-sectional study of outpatients consecutively scheduled for an unsedated upper or lower gastrointestinal endoscopy between January and June 2015. Patients on anticoagulant therapy were excluded. Results: 675 patients were evaluated, including 91 (13.5%) patients on APT [upper GI endoscopy 25 (27.5%), lower GI endoscopy 66 (72.5%)]. Contrary to the clinical guidelines, aspirin was discontinued in 25 of the 77 patients previously prescribed the drug (32.5%) but this modification was patient's own decision in 11 cases. Most of the apparent deviations in the management of clopidogrel and dual antiplatelet therapy (DAPT) were not true non-adherence cases. The Primary Care physician modified an APT prescribed by another physician in 8 of 9 cases (88.9%), always in cases with aspirin. No relationship was found between the endoscopic procedure's predicted risk of bleeding or the patient's thrombotic risk and modification of therapy. Discussion: In many patients, the peri-procedural management of APT goes against current guidelines, but some of these inconsistencies cannot be considered true deviations from practice. Identified areas for improvement are increasing patient awareness about APT, disseminating the guidelines in Primary Care, and underscoring the significance of thrombotic risk related to APT withdrawal

Introducción: El cumplimiento de las guías clínicas sobre el manejo periendoscópico del tratamiento antiagregante plaquetario (TAP) no se ha analizado con detalle. Nuestro objetivo fue analizar caso por caso el cumplimiento de las guías en los pacientes que acuden a nuestra Unidad de Endoscopia, describiendo con detalle las desviaciones detectadas e identificando áreas de mejora. Pacientes y métodos: Estudio transversal sobre pacientes consecutivos programados para gastroscopia o colonoscopia realizadas sin sedación entre enero y junio de 2015. Se excluyeron los pacientes en tratamiento anticoagulante. Resultados: Se evaluaron 675 pacientes de los que se incluyeron 91 (13,5%) por estar en tratamiento con antiagregante plaquetario (gastroscopias 25 [27,5%], colonoscopias 66 [72,5%]). La aspirina se interrumpió contrariamente a las guías clínicas en 25 de los 77 pacientes que la llevaban (32,5%), pero esta modificación fue una decisión del propio paciente en 11 casos. Muchas de las aparentes desviaciones en el manejo del clopidogrel y del tratamiento antiagregante plaquetario doble (TAPD) no eran verdaderos casos de no cumplimiento. El médico de Atención Primaria modificó el TAP prescrito por otro especialista en 8 de 9 casos (88,9%), siempre en casos de aspirina. No se encontró relación entre el riesgo de sangrado del procedimiento endoscópico o el riesgo de trombosis del paciente y la modificación del tratamiento. Discusión: En una proporción significativa de pacientes el manejo periprocedimiento del TAP va en contra de las guías clínicas, pero algunas de estas desviaciones no pueden considerarse verdaderos incumplimientos. Áreas de mejora son aumentar la información al paciente sobre el TAP, extender la diseminación de las guías a atención primaria y resaltar la importancia del riesgo trombótico relacionado con la suspensión del TAP

Periendoscopic management of antiplatelet therapy: Prospective evaluation of adherence to guidelines.

INTRODUCCIóN: Adherence to guidelines on the periendoscopic management of antiplatelet therapy (APT) has not been analyzed in detail. Our aim was to assess adherence to guidelines in patients referred to our Endoscopy Unit on a case-by-case basis, describing in detail the detected deviations and identifying areas of improvement. PATIENTS AND METHODS: Cross-sectional study of outpatients consecutively scheduled for an unsedated upper or lower gastrointestinal endoscopy between January and June 2015. Patients on anticoagulant therapy were excluded. RESULTS: 675 patients were evaluated, including 91 (13.5%) patients on APT [upper GI endoscopy 25 (27.5%), lower GI endoscopy 66 (72.5%)]. Contrary to the clinical guidelines, aspirin was discontinued in 25 of the 77 patients previously prescribed the drug (32.5%) but this modification was patient's own decision in 11 cases. Most of the apparent deviations in the management of clopidogrel and dual antiplatelet therapy (DAPT) were not true non-adherence cases. The Primary Care physician modified an APT prescribed by another physician in 8 of 9 cases (88.9%), always in cases with aspirin. No relationship was found between the endoscopic procedure's predicted risk of bleeding or the patient's thrombotic risk and modification of therapy. DISCUSSION: In many patients, the peri-procedural management of APT goes against current guidelines, but some of these inconsistencies cannot be considered true deviations from practice. Identified areas for improvement are increasing patient awareness about APT, disseminating the guidelines in Primary Care, and underscoring the significance of thrombotic risk related to APT withdrawal.

A long-term prospective study of the efficacy and safety of endoscopic septotomy using the LigaSure(R) system for the treatment of Zenker's diverticulum

Background and objectives: endoscopic septotomy of the cricopharyngeal muscle (ESCM) is a technique used for the treatment of Zenker's diverticulum (ZD). The experience with computerized vascular sealing systems (LigaSure(R) type) is limited. The objective of this study was to evaluate the efficacy and safety of ESCM using LigaSure(R). Methods: this was a long-term prospective study of 18 patients with ZD, who were referred to our hospital due to ESCM between 2010 and 2016. The severity of the symptoms was determined using the Dakkak-Bennett validated scale for dysphagia and the rest with numerical scales. The rates of relapse and retreatment were evaluated. Results: ESCM with LigaSure(R) was performed in 17 cases, one case was excluded due to technical difficulties. The median age was 72 years and regurgitation, dysphagia and respiratory symptoms were found in 100%, 89% and 56% of cases, respectively. The median size of the diverticulum was 28 mm (20-60 mm). The median time of the procedure was 35 minutes (25-45 minutes). There were four complications, two hemorrhages and two perforations. The median follow-up was 13 months (range: 12-82 months). Clinical improvements were observed for all symptoms and were maintained 12 months after treatment (p < 0.05). There was no relapse during follow-up in 13 patients. A complete section was not achieved and clinical relapse occurred after a median time of seven months that required retreatment in the remaining patients. Conclusions: ESCM with LigaSure(R) may be a safe and effective technique in long-term follow-up situations, with low rates of relapse

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Non-guided self-learning program for high-proficiency optical diagnosis of diminutive and small colorectal lesions: A single-endoscopist pilot study.

BACKGROUND: The implementation of optical diagnosis (OD) of diminutive colorectal lesions in clinical practice has been hampered by differences in performance between community and academic settings. One possible cause is the lack of a standardized learning tool. Since the factors related to better learning are not well described, strong evidence upon which a consistent learning tool could be designed is lacking. We hypothesized that a self-designed learning program may be enough to achieve competency in OD of diminutive lesions of the colon. AIM: To assess the accuracy of OD of diminutive lesions in real colonoscopies after application of a self-administered learning program. METHODS: This was a single-endoscopist prospective pilot study, in which an experienced endoscopist followed a self-designed, self-administered learning program in OD of colorectal lesions. An assessment phase divided in two halves with a 6-mo period in between without performance of OD was developed in a population-based colorectal cancer screening program. The accomplishment of the Preservation and Incorporation of Valuable Endoscopic Innovations criteria and performance measures were calculated overall and in the two halves of the assessment phase, assessing their response to the 6-mo stopping period. The evolution of performance through blocks of 50 lesions was also assessed. RESULTS: Overall, 152 patients and 522 lesions (≤ 5 mm: 399, and 6-9 mm: 123) were included. The negative predictive value for the OD of adenoma in rectosigmoid lesions diagnosed with high confidence was 91.7% [95% confidence interval (CI): 87.3-96.6]. The proportion of agreement on surveillance interval between OD and pathological diagnosis was higher than 95%. Overall accuracy for diminutive lesions diagnosed with high confidence was 89.5% (95%CI: 86.3-92.7). The overall accuracy of OD was similar in the two halves of the assessment phase [90.1 (95%CI: 85.6-94.7) vs 88.2 (95%CI: 87.9-95.9)]. All the other performance parameters were also equivalent, except for specificity. Specificity, negative predictive value and accuracy were the parameters most affected by the stopping period between the two halves. Upon analyzing trends on blocks of 50 lesions, an improvement on sensitivity (P = 0.02) was detected only in the first half and an improvement on accuracy (P = 0.01) was detected only in the second half. CONCLUSION: A self-administered learning program is sufficient to achieve expert-level OD. To maintain performance, continuous practice is needed, with a refresher course following any long non-practice period.

A long-term prospective study of the efficacy and safety of endoscopic septotomy using the LigaSure® system for the treatment of Zenker's diverticulum.

BACKGROUND AND OBJECTIVES: endoscopic septotomy of the cricopharyngeal muscle (ESCM) is a technique used for the treatment of Zenker's diverticulum (ZD). The experience with computerized vascular sealing systems (LigaSure® type) is limited. The objective of this study was to evaluate the efficacy and safety of ESCM using LigaSure®. METHODS: this was a long-term prospective study of 18 patients with ZD, who were referred to our hospital due to ESCM between 2010 and 2016. The severity of the symptoms was determined using the Dakkak-Bennett validated scale for dysphagia and the rest with numerical scales. The rates of relapse and retreatment were evaluated. RESULTS: ESCM with LigaSure® was performed in 17 cases, one case was excluded due to technical difficulties. The median age was 72 years and regurgitation, dysphagia and respiratory symptoms were found in 100%, 89% and 56% of cases, respectively. The median size of the diverticulum was 28 mm (20-60 mm). The median time of the procedure was 35 minutes (25-45 minutes). There were four complications, two hemorrhages and two perforations. The median follow-up was 13 months (range: 12-82 months). Clinical improvements were observed for all symptoms and were maintained 12 months after treatment (p < 0.05). There was no relapse during follow-up in 13 patients. A complete section was not achieved and clinical relapse occurred after a median time of seven months that required retreatment in the remaining patients. CONCLUSIONS: ESCM with LigaSure® may be a safe and effective technique in long-term follow-up situations, with low rates of relapse.

Rate of adverse events of gastroduodenal snare polypectomy for non-flat polyp is low: A prospective and multicenter study.

AIM: To evaluate the rate of adverse events (AEs) during consecutive gastric and duodenal polypectomies in several Spanish centers. METHODS: Polypectomies of protruded gastric or duodenal polyps ≥ 5 mm using hot snare were prospectively included. Prophylactic measures of hemorrhage were allowed in predefined cases. AEs were defined and graded according to the lexicon recommended by the American Society for Gastrointestinal Endoscopy. Patients were followed for 48 h, one week and 1 mo after the procedure. RESULTS: 308 patients were included and a single polypectomy was performed in 205. Only 36 (11.7%) were on prior anticoagulant therapy. Mean polyp size was 15 ± 8.9 mm (5-60) and in 294 cases (95.4%) were located in the stomach. Hemorrhage prophylaxis was performed in 219 (71.1%) patients. Nine patients presented AEs (2.9%), and 6 of them were bleeding (n = 6, 1.9%) (in 5 out of 6 AE, different types of endoscopic treatment were performed). Other 24 hemorrhagic episodes could be managed without any change in the outcome of the endoscopy and, consequently, were considered incidents. We did not find any independent risk factor of bleeding. CONCLUSION: Gastroduodenal polypectomy using prophylactic measures has a rate of AEs small enough to consider this procedure a safe and effective method for polyp resection independently of the polyp size and location.

The appropriateness of colonoscopies at a teaching hospital: magnitude, associated factors, and comparison of EPAGE and EPAGE-II criteria.

BACKGROUND: The growing demand for colonoscopies and inappropriate colonoscopies have become a significant problem for health care. OBJECTIVES: To assess the appropriateness of colonoscopies and to analyze the association with some clinical and organizational factors. To compare the results of the European Panel of Appropriateness of Gastrointestinal Endoscopy (EPAGE) and the EPAGE-II criteria. DESIGN: Cross-sectional study. SETTING: Endoscopy unit of a teaching hospital in Spain. PATIENTS: Patients referred for colonoscopy, excluding urgent, therapeutic indications, and poor cleansing. MAIN OUTCOME MEASUREMENTS: Appropriateness of colonoscopies according to the EPAGE criteria. RESULTS: From 749 colonoscopies, 619 were included. Most patients were referred by gastroenterologists (66.1%) in an outpatient setting (80.6%). Hematochezia was the most frequent indication (31.5%) followed by colorectal cancer-related indications (27.3%); a clinically relevant diagnosis was established in 41%. Inappropriate use was higher with EPAGE (27.0%) than EPAGE-II (17.4%) criteria. Surveillance after colonic polypectomy and uncomplicated lower abdominal pain were the indications exhibiting higher inadequacy. Inappropriate use was less with older age, in hospitalized patients, with referrals from internal medicine, and in colonoscopies with clinically relevant diagnoses. Agreement between EPAGE and EPAGE-II was fair (weighted κ = 0.31) but improved to moderate (simple κ = 0.60) after grouping appropriate and uncertain levels. LIMITATIONS: The appropriateness criteria are based on panel opinions. Some patients (12%) could not be evaluated with the EPAGE criteria. CONCLUSIONS: Our study identifies substantial colonoscopy overuse, especially in tumor disease surveillance. The EPAGE-II criteria decrease the inappropriate rate and the possibility of overlooking potentially severe lesions.

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

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.

¿Debe indicarse una colangiopancreatografía retrógrada endoscópica con esfinterotomía precoz en todas las pancreatitis agudas graves? / Should early ERCP with sphincterotomy be indicated in all cases of severe

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Recomendaciones del Club Español Biliopancreático para el Tratamiento de la Pancreatitis Aguda. Conferencia de Consenso / Recommendations of the Spanish Biliopancreatic Club for the Treatment of Acute Pancreatitis. Consensus development conference

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Evaluation of postsurgical recurrence in Crohn's disease: a new indication for capsule endoscopy?

BACKGROUND: Recurrence after surgery to treat Crohn's disease is frequent and unpredictable. The efficacy of postsurgery capsule endoscopy in detecting recurrence in patients with Crohn's disease is yet to be confirmed. OBJECTIVE: To assess the safety, accuracy, and therapeutic impact of capsule endoscopy in these patients. DESIGN: Crohn's disease recurrence at the neoileum (Rutgeers score) was assessed in the patients by colonoscopy and capsule endoscopy. The M2A Patency Capsule (Given Imaging, Yoqneam, Israel) was administered 1 week before capsule endoscopy. Capsule endoscopy was performed within 2 weeks of colonoscopy. Investigators were blinded to the results of each technique. Patient comfort during the procedures was recorded. PATIENTS: Twenty-four patients with Crohn's disease with ileocolonic anastomosis were prospectively included. All patients were asymptomatic and did not receive any prophylactic treatment. MAIN OUTCOME MEASUREMENTS: Neoileum recurrence. RESULTS: A colonoscopy was performed in all patients, although the neoileum could not be reached in 3 of them. M2A Patency Capsule excretion was delayed in 2 patients; thus capsule endoscopy was given only to 22 patients. Recurrence was visualized with colonoscopy in 6 patients and with capsule endoscopy in 5. Ten additional recurrences were visualized only with capsule endoscopy. Moreover, proximal involvement was detected in 13 patients. Therapeutic management was modified in 16 patients. All patients preferred capsule endoscopy. CONCLUSIONS: Capsule endoscopy is more effective in the evaluation of recurrence after surgery for Crohn's disease and is better tolerated than colonoscopy. This is of significant therapeutic relevance.

Utilidad de la ultrasonografía endoscópica para el diagnóstico de localización de tumores neuroendocrinos pancreáticos: presentación de 2 insulinomas benignos / Usefulness of endoscopic ultrasonography in the localization of pancreatic neuroendocrine tumours: report of 2 benign insulinomas

Los insulinomas son tumores neuroendocrinos que se manifiestan por episodios de hipoglucemia de ayuno. El diagnóstico se basa en la sospecha clínica, que debe ir seguida de la demostración de hiperinsulinismo y la localización tumoral. Sin embargo, la localización no siempre es posible con las técnicas de imagen habituales, por lo que se debe recurrir a otras más complejas. Presentamos 2 casos de insulinomas cuya localización tumoral no fue posible con técnicas de imagen convencionales, pero sí con ultrasonografía endoscópica (AU)

Insulinomas are neuroendocrine tumors that usually present as fasting hypoglycemia. Diagnosis is based on clinical suspicion followed by confirmation of endogenous hyperinsulinism and tumoral localization. Nevertheless, localization cannot always be achieved with routine imaging techniques, in which case invasive imaging techniques are required. We present 2 cases of insulinomas that were not identified by conventional imaging techniques but were successfully identified by endoscopic ultrasonography (AU)

Clinical performance of original and revised Bethesda guidelines for the identification of MSH2/MLH1 gene carriers in patients with newly diagnosed colorectal cancer: proposal of a new and simpler set of recommendations.

UNLABELLED: Identification of individuals who should undergo hereditary nonpolyposis colorectal cancer (HNPCC) genetic testing is a critical and difficult issue. For this purpose, the National Cancer Institute outlined a set of recommendations, the Bethesda guidelines, which have recently been revised. OBJECTIVE: To compare the clinical performance of original and revised Bethesda guidelines for the detection of MSH2/MLH1 gene carriers in patients with colorectal cancer. METHODS: A total of 1,222 patients with newly diagnosed colorectal cancer were included in the EPICOLON study, a prospective, multicenter, nationwide epidemiology survey aimed at establishing the incidence of HNPCC in Spain (JAMA 2005; 293:1986-1994). Performance characteristics of the original and revised Bethesda guidelines were assessed with respect to the presence of MSH2/MLH1 germline mutations. Logistic regression analysis was performed to establish the most effective strategy. RESULTS: Original or revised Bethesda guidelines were equivalent strategies in terms of sensitivity (100%vs 100%; ns), specificity (98.1%vs 97.9%; ns), and overall accuracy (98.1%vs 97.9%; ns), as well as positive (25.8%vs 24.2%) and negative predictive values (100%vs 100%). The most discriminating individual variables were criteria number 1 (i.e., fulfillment of the Amsterdam criteria; RR = 34.14; 95% CI = 6.85-170.16; p < 0.001) and number 2 (i.e., individuals with two HNPCC-related neoplasms; RR = 35.63; 95% CI = 4.83-262.6; p < 0.001) of the original guidelines, and criterion number 1 of the revised guidelines (i.e., colorectal cancer diagnosed under 50 yr of age; RR = 29.34; 95% CI = 3.81-225.96; p= 0.001). The aggregation of these three criteria was equivalent to both Bethesda guidelines in terms of sensitivity (100%) and negative predictive value (100%), but superior to the revised criteria regarding specificity (98.5%; p < 0.05), overall accuracy (98.5%; p < 0.05), and positive predictive value (30.8%). CONCLUSIONS: Original and revised Bethesda guidelines are equivalent, highly effective criteria for the identification of MSH2/MLH1 gene mutation carriers in patients with newly diagnosed colorectal cancer. A new set of recommendations, based on a combination of some of their individual criteria, may provide additional advantages in terms of effectiveness.