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Direct endoscopic visualization of biliary and pancreatic ducts represents one step further in the journey of digestive endoscopy. It allows the identification of lesions that were previously attainable through indirect means. Directed biopsy taking has permitted a better characterization of the lesions. The use of power sources through the cholangiopancreatoscope means that it is now possible to fragment and remove refractory lithiases using traditional endoscopic systems. This document aims to define the advisable workflow when using a single-use, flexible cholangiopancreatoscope with the commercial name of SpyGlass®. Penning a set of guidelines to provide instructions on the technique, as well as tips and tricks related with the operation of these endoscopes will be a useful resource.

Background Colorectal cancers (CRCs) that have microsatellite instability (MSI) and mutL homolog 1 (MLH1) immunoloss are observed in 3 clinical scenarios: Lynch syndrome (LS), sporadic MSI CRC, and Lynch-like syndrome (LLS). v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) mutational analysis is used to differentiate LS from sporadic MSI CRC. The role of MLH1 promoter methylation status for the differential diagnosis of these clinical forms is not well established. The objectives of this study were: 1) to analyze MLH1 promoter methylation in MLH1-deficient CRCs by pyrosequencing, and 2) to assess its role in the differential diagnosis of MLH1-deficient CRCs. Methods In total, 165 CRCs were analyzed, including LS (n = 19), MSI BRAF-mutated CRC (n = 37), MSI BRAF wild-type CRC (n = 60), and a control group of CRCs without MSI (microsatellite stable [MSS] CRC; n = 49). MLH1 promoter methylation status was analyzed by pyrosequencing, and the ability of different strategies to identify LS was assessed. Results The average ± standard deviation methylation in LS (9% ± 7%) was significantly lower than that in MSI BRAF-mutated CRC (42% ± 17%; P < .001) and in MSI BRAF wild-type CRC (25% ± 19%; P = .002). Somatic MLH1 hypermethylation was detected in 3 patients (15.8%) with LS, in 34 patients (91.9%) with MSI BRAF-mutated CRC, and in 37 patients (61.7%) with MSI BRAF wild-type tumors. Patients with MSI BRAF wild-type, unmethylated tumors (ie, LLS) had a stronger family history of CRC than those who had tumors with MLH1 methylation (P < .05). The sensitivity for ruling out LS was 100% for BRAF analysis, 84.2% for MLH1 methylation analysis, and 84.2% for the combination of both analyses. Conclusion Somatic MLH1 promoter methylation occurs in up to 15% of LS CRCs. Somatic BRAF analysis is the most sensitive strategy for ruling out LS. Patients who have CRCs with loss of MLH1 protein expression and neither BRAF mutation nor MLH1 methylation resemble patients with LS.

Background In staged liver resections, associating liver partition and portal ligation for staged hepatectomy (ALPPS) achieves sufficient hypertrophy of the future liver remnant (FLR) in 7 days. This is based on portal vein ligation and transection, and on occlusion of intrahepatic collaterals. This article presents a new surgical technique for achieving rapid hypertrophy of the FLR, which also involves adding intrahepatic collateral occlusion to portal vein transection. Methods Patients scheduled for two-stage liver resection for primary or secondary liver tumours, in whom the FLR was considered too small, were enrolled prospectively. In the first stage, a tourniquet was placed around the parenchymal transection line, and the right portal vein was ligated and cut (associating liver tourniquet and portal ligation for staged hepatectomy, ALTPS). The tourniquet was placed on the umbilical ligament if a staged right trisectionectomy was planned, and on Cantlie's line for staged right hepatectomy. Results From September 2011, 22 ALTPS procedures were carried out (right trisectionectomy in 15, right hepatectomy in 7). Median FLR at 7 days increased from 410 to 700 ml (median increase 61 (range 33–189) per cent). The median duration of the first stage was 125 min and no patient received a blood transfusion. The median duration of the second stage was 150 min and five patients required a blood transfusion. Fourteen patients had complications, most frequently infected collections, and five patients developed postoperative liver failure. Two patients died. Conclusion The ALTPS technique achieved adequate hypertrophy of the FLR after 7 days. It may provide a less aggressive modification of the ALPPS procedure.

Gloria Fernandez-Esparrach, Angel Calderon, Joaquin de-la-Pena, Jose B. Diaz-Tasende, Jose Miguel Esteban, Antonio Zebenzuy Gimeno-Garcia, Alberto Herreros-de-Tejada, David Martinez-Ares, David Nicolas-Perez, Oscar Nogales, Akiko Ono, Aitor Orive-Calzada, Adolfo Parra-Blanco, Sarbelio Rodriguez-Munoz, Eloy Sanchez-Hernandez, Andres Sanchez-Yague, Enrique Vazquez-Sequeiros, Juan Vila and Leopoldo Lopez-Roses; on behalf of the Sociedad Espanola de Endoscopia Digestiva (SEED)

Many colorectal cancers (CRCs) develop in genetically susceptible individuals most of whom are not carriers of germ line mismatch repair or APC gene mutations and much of the heritable risk of CRC appears to be attributable to the co-inheritance of multiple low-risk variants. The accumulated experience to date in identifying this class of susceptibility allele has highlighted the need to conduct statistically and methodologically rigorous studies and the need for the multi-centre collaboration. This has been the motivation for establishing the COGENT (COlorectal cancer GENeTics) consortium which now includes over 20 research groups in Europe, Australia, the Americas, China and Japan actively working on CRC genetics. Here, we review the rationale for identifying low-penetrance variants for CRC and the current and future challenges for COGENT.

Resumen Introduccion La mortalidad en la hemorragia digestiva alta no varicosa (HDA-NV) no ha variado. Se necesita conocer mas informacion para mejorar las estrategias de tratamiento. Los objetivos de este estudio fueron: a) describir el perfil de presentacion de los episodios de HDA-NV; b) el manejo clinico segun practica clinica habitual, y c) establecer cuales son los resultados clinicos asociados a los tratamientos endoscopicos y medicos en Espana. Metodos ENERGIB fue un estudio retrospectivo de cohortes que recogio informacion del manejo y forma de presentacion de HDA-NV en Europa. Presentamos los datos relativos a Espana. Los pacientes se trataron segun la practica clinica habitual. Para las variables cuantitativas se calculo la media y la desviacion estandar y para las categoricas se calcularon frecuencias absolutas y relativas. Resultados Los pacientes (n = 403) fueron hombres (71%), con edad media 65 anos, asociaron comorbilidad (62,5%). Los equipos encargados de su manejo fueron gastroenterologos (57,1%) o medicos internistas (25,1%). Los inhibidores de la bomba de protones se usaron de forma empirica preendoscopia en un 80% de los casos. El 6,4% presento persistencia y el 6,7% resangrado despues de la endoscopia. La tasa de mortalidad en los 30 dias posteriores fue del 3,5%. Conclusiones Este estudio permite conocer el perfil de presentacion de los episodios de HDA-NV en Espana y el manejo en practica clinica habitual. Este se ajusta a los estandares propuestos por las recientes guias de practica clinica. Entre otros datos destaca que los pacientes con hemorragia son cada vez de edad mas avanzada y presentan un mayor numero de enfermedades asociadas, lo que podria explicar que la mortalidad se haya mantenido estable a pesar de los evidentes avances en el manejo de esta entidad.

Purpose: The aim of this study was to evaluate the benefits of an oral isosmolar solution of electrolytes (ISE) administered to interrupt a prolonged fasting period in children undergoing an elective surgical procedure under general anesthesia. Methods: Forty unpremedicated children aged 3 to 12 years, ASA I, undergoing a surgical procedure requiring general anesthesia were assigned randomly to 1 of 2 groups. Group 1 consisted of patients with an overnight fasting period for milk and solids of at least 8 hours. In group 2, patients under a similar fasting period received a volume of 4 mL/kg of an oral ISE 3 hours before completing the fasting period. After anesthetic induction, blood glucose level (BGL) was quantified, and patients underwent an endoscopic examination to obtain the gastric content to determine the residual gastric volume (RGV) and pH levels. Results: In group 1, the RGV was 0.78 ± 0.44 mL/kg, pH was 1.75 ± 0.38, and BGL was 86.4 ± 14.5. In group 2, the RGV was 0.40 ± 0.29 mL/kg, pH was 3.18 ± 0.61, and BGL was 85.1 ± 12.6. Only RGV and pH were significantly different between groups. Conclusion: A prolonged fasting period interrupted with oral ISE administration resulted in an RGV of low risk, without counterbalancing a potential fasting-induced hypoglycemia. J Pediatr Surg 36:457-459. Copyright © 2001 by W.B. Saunders Company.

Background: Several models have recently been developed to predict mismatch repair (MMR) gene mutations. Their comparative performance with clinical criteria or universal molecular screening in a population based colorectal cancer (CRC) cohort has not been assessed. Methods: All 1222 CRC from the EPICOLON cohort underwent tumour MMR testing with immunohistochemistry and microsatellite instability, and those with MMR deficiency (n= 91) underwent MLH1/ MSH2 germline testing. Sensitivity, specificity and positive predictive value (PPV) of the PREMM1,2 and the Barnetson models for identification of MLH1/ MSH2 mutation carriers were evaluated and compared with the revised Bethesda guidelines (RBG), Amsterdam II criteria, and tumour analysis for MMR deficiency. Overall discriminative ability was quantified by the area under the ROC curve (AUC), and calibration was assessed by comparing the average predictions versus the observed prevalence. Results: Both models had similar AUC (0.93 and 0.92, respectively). Sensitivity of the RBG and a PREMM1,2 score > 5% was 100% (95% CI 71% to 100%); a Barnetson score.0.5% missed one mutation carrier (sensitivity 87%, 95% CI 51% to 99%). PPVs of all three strategies were 2 - 3%. Presence of MMR deficiency increased specificity and PPV of predictive scores ( 97% and 21% for PREMM1,2 score > 5%, and 98% and 21% for Barnetson > 0.5%, respectively). Conclusions: The PREMM1,2 and the Barnetson models offer a quantitative systematic approach to select CRC patients for identification of MLH1/MSH2 mutation carriers with a similar performance to the RBG.

Endoscopic Submucosal Dissection With Hydrodissection Technique: Results and Learning Curve in an Animal Model Joaquin De La Pena*, Jose Miguel Esteban, Oscar Nogales Rincon, Sarbelio RodriGuez-MunOz, Angel Calderon, Aitor Orive-Calzada, Leopoldo Lopez-Roses, David Martinez-Ares, Eloy Sanchez-Hernandez, Juan J. Vila, Gloria Fernandez-Esparrach Experimental surgery, HVirtual Valdecilla, Santander, Spain; Endoscopia, H clinico San Carlos, Madrid, Spain; Endoscopia, h 12 Octubre, Madrid, Spain; Digestivo, h Basurto, Bilbao, Spain; Digestivo, h Galdakao-usansolo, Galdakao, Spain; Digestivo, CHU Lugo, Lugo, Spain; Digestivo, CHU Vigo, Vigo, Spain; Digestivo, CHU Ourense, Ourense, Spain; Digestivo, CH Navarra, Pamplona, Spain; Endoscopy unit Institut de Malalties Digestives i Metaboliques, H Clinic, Barcelona, Spain; Digestivo, H Gregorio Maranon, Madrid, Spain Background: ESD in an effective but time-consuming treatment for early neoplasia that requires a high level of expertise. The combination of high-pressure water jet with electrocautery needle in the same device could facilitate the procedure, especially among beginners. Aim: To assess the efficacy and learning curve of gastric ESD with ERBE hybrid knife in a set of endoscopists with preliminary experience with ESD in experimental models. Methods: Hybrid and classic gastric ESD were alternatively performed in live pigs. For Hybrid technique we used a water-jet hybrid knife (ERBE). For classic ESD we used needle Knife (DND2718A,PENTAX) and Mucosectome isolated (DP-D2518, PENTAX). Dissection with electrocautery was alternate with submucosal fluid injection as many times as needed. All the endoscopists had previously completed their training in animal models. Variables analyzed were: number of ESD completed, number of ESD with all marks included (R0), size of specimens, time and speed of dissection and complications. Results: 10 endoscopists performed a total of 50 gastric ESD (30 hybrid and 20 classic). 46 (92%) ESD were completed and 25 (50%) were R0 (hybrid: n 12, 40%; classic: n 13, 65%; p 0.004). The size of the specimens was not different in both groups (hybrid: 40.3 13.2 mm; classic: 35.5 10.9 mm; p 0.826). Hybrid ESD was faster than classic (time: 44.6 21.4 minutes vs 68.7 33.5 minutes; p 0.009 and velocity: 20.8 9.2 mm2/seg vs 14.3 9.3 mm2/seg; p 0.033). Complications were no different with an incidence of perforation of 4 (13%) and 2 (10%), respectively (p 0.722). It was a trend to improve the velocity with both techniques (hybrid: from 20.33 to 28.18 mm2/seg; p 0.615 and classic: from 6.4 to 19.48 mm2/seg; p 0.607). the learning curve showed an improvement in R0 rate in the hybrid group (from 30% to 100%). Conclusions: ESD with hydrodissection technique is faster than classic ESD but is associated with a decrease in R0. The learning curve with the hydrodissection technique is short and shows a rapid improvement. ESD is a very effective technique when performed properly and the introduction of new tools to facilitate the implementation of ESD should be done with caution to avoid a negative impact on the results.

Background Endoscopic submucosal dissection (ESD) is an effective but time-consuming treatment for early neoplasia that requires a high level of expertise. Objective The objective of this study was to assess the efficacy and learning curve of gastric ESD with a hybrid knife with high pressure water jet and to compare with standard ESD. Material and methods We performed a prospective non survival animal study comparing hybrid-knife and standard gastric ESD. Variables recorded were: Number of en-bloc ESD, number of ESD with all marks included (R0), size of specimens, time and speed of dissection and adverse events. Ten endoscopists performed a total of 50 gastric ESD (30 hybrid-knife and 20 standard). Results Forty-six (92 %) ESD were en-bloc and 25 (50 %) R0 (hybrid-knife: n = 13, 44 %; standard: n = 16, 80 %; p = 0.04). Hybrid-knife ESD was faster than standard (time: 44.6 +/- 21.4 minutes vs. 68.7 +/- 33.5 minutes; p = 0.009 and velocity: 20.8 +/- 9.2 mm(2)/min vs. 14.3 +/- 9.3 mm(2)/min (p = 0.079). Adverse events were not different. There was no change in speed with any of two techniques (hybrid-knife: From 20.33 +/- 15.68 to 28.18 +/- 20.07 mm(2)/min; p = 0.615 and standard: From 6.4 +/- 0.3 to 19.48 +/- 19.21 mm(2)/min; p = 0.607). The learning curve showed a significant improvement in R0 rate in the hybrid-knife group (from 30 % to 100 %). Conclusion despite the initial performance of hybrid-knife ESD is worse than standard ESD, the learning curve with hybrid knife ESD is short and is associated with a rapid improvement. The introduction of new tools to facilitate ESD should be implemented with caution in order to avoid a negative impact on the results.

The members of the Gastrointestinal Oncology Group of the Spanish Gastroenterological Association are: Hospital 12 de Octubre, Madrid: Juan Diego Morillas (local coordinator), Raquel Muñoz, Marisa Manzano, Francisco Colina, Jose Díaz, Carolina Ibarrola, Guadalupe López, Alberto Ibáñez; Hospital Clínic, Barcelona: Antoni Castells (local coordinator), Virgínia Piñol, Sergi Castellví-Bel, Francesc Balaguer, Victoria Gonzalo, Teresa Ocaña, María Dolores Giráldez, Maria Pellisé, Anna Serradesanferm, Leticia Moreira, Miriam Cuatrecasas, Josep M. Piqué; Hospital Clínico Universitario, Zaragoza: Ángel Lanas (local coordinator), Javier Alcedo, Javier Ortego; Hospital Cristal-Piñor, Complexo Hospitalario de Ourense: Joaquin Cubiella (local coordinator), Ma Soledad Díez, Mercedes Salgado, Eloy Sánchez, Mariano Vega; Hospital del Mar, Barcelona: Montserrat Andreu (local coordinator), Anna Abuli, Xavier Bessa, Mar Iglesias, Agustín Seoane, Felipe Bory, Gemma Navarro, Beatriz Bellosillo, Josep Ma Dedeu, Cristina Álvarez, Begoña Gonzalez; Hospital San Eloy, Baracaldo and Hospital Donostia, CIBERehd, University of Country Basque, San Sebastián: Luis Bujanda (local coordinator) Ángel Cosme, Inés Gil, Mikel Larzabal, Carlos Placer, María del Mar Ramírez, Elisabeth Hijona, Jose M. Enríquez-Navascués, Jose L. Elosegui; Hospital General Universitario de Alicante: Artemio Payá (EPICOLON I local coordinator), Rodrigo Jover (EPICOLON II local coordinator), Cristina Alenda, Laura Sempere, Nuria Acame, Estefanía Rojas, Lucía Pérez-Carbonell; Hospital General de Granollers: Joaquim Rigau (local coordinator), Ángel Serrano, Anna Giménez; Hospital General de Vic: Joan Saló (local coordinator), Eduard Batiste-Alentorn, Josefina Autonell, Ramon Barniol; Hospital General Universitario de Guadalajara and Fundación para la Formación e Investigación Sanitarias Murcia: Ana María García (local coordinator), Fernando Carballo, Antonio Bienvenido, Eduardo Sanz, Fernando González, Jaime Sánchez, Akiko Ono; Hospital General Universitario de Valencia: Mercedes Latorre (local coordinator), Enrique Medina, Jaime Cuquerella, Pilar Canelles, Miguel Martorell, José Ángel García, Francisco Quiles, Elisa Orti; CHUVI-Hospital Meixoeiro, Vigo: EPICOLON I: Juan Clofent (local coordinator), Jaime Seoane, Antoni Tardío, Eugenia Sanchez; EPICOLON II: Ma Luisa de Castro (local coordinator), Antoni Tardío, Juan Clofent, Vicent Hernández; Hospital Universitari Germans Trias i Pujol, Badalona and Section of Digestive Diseases and Nutrition, University of Illinois at Chicago, Chicago, IL: Xavier Llor (local coordinator), Rosa M. Xicola, Marta Piñol, Mercè Rosinach, Anna Roca, Elisenda Pons, José M. Hernández, Miquel A. Gassull; Hospital Universitari Mútua de Terrassa: Fernando Fernández-Bañares (local coordinator), Josep M. Viver, Antonio Salas, Jorge Espinós, Montserrat Forné, Maria Esteve; Hospital Universitari Arnau de Vilanova, Lleida: Josep M. Reñé (local coordinator), Carmen Piñol, Juan Buenestado, Joan Viñas; Hospital Universitario de Canarias: Enrique Quintero (local coordinator), David Nicolás, Adolfo Parra, Antonio Martín; Hospital Universitario La Fe, Valencia: Lidia Argüello (local coordinator), Vicente Pons, Virginia Pertejo, Teresa Sala; Hospital Sant Pau, Barcelona: Dolors Gonzalez (local coordinator), Eva Roman, Teresa Ramon, Maria Poca, Ma Mar Concepción, Marta Martin, Lourdes Pétriz; Hospital Xeral Cies, Vigo: Daniel Martinez (local coordinator); Fundacion Publica Galega de Medicina Xenomica (FPGMX), CIBERER, Genomic Medicine Group-University of Santiago de Compostela, Santiago de Compostela, Galicia, Spain: Ángel Carracedo (local coordinator), Clara Ruiz-Ponte, Ceres Fernández-Rozadilla, Ma Magdalena Castro; Hospital Universitario Central de Asturias: Sabino Riestra (local coordinator), Luis Rodrigo; Hospital de Galdácano, Vizcaya: Javier Fernández (local coordinator), Jose Luis Cabriada; Fundación Hospital de Calahorra (La Rioja) La Rioja: Luis Carreño (local coordinator), Susana Oquiñena, Federico Bolado; Hospital Royo Villanova, Zaragoza: Elena Peña (local coordinator), José Manuel Blas, Gloria Ceña, Juan José Sebastián; Hospital Universitario Reina Sofía, Córdoba: Antonio Naranjo (local coordinator). Epigenetics are thought to play a major role in the carcinogenesis of multiple sporadic colorectal cancers (CRC). Previous studies have suggested concordant DNA hypermethylation between tumor pairs. However, only a few methylation markers have been analyzed. This study was aimed at describing the epigenetic signature of multiple CRC using a genome-scale DNA methylation profiling. We analyzed 12 patients with synchronous CRC and 29 age-, sex-, and tumor location-paired patients with solitary tumors from the EPICOLON II cohort. DNA methylation profiling was performed using the Illumina Infinium HM27 DNA methylation assay. The most significant results were validated by Methylight. Tumors samples were also analyzed for the CpG Island Methylator Phenotype (CIMP); KRAS and BRAF mutations and mismatch repair deficiency status. Functional annotation clustering was performed. We identified 102 CpG sites that showed significant DNA hypermethylation in multiple tumors with respect to the solitary counterparts (difference in β value ≥0.1). Methylight assays validated the results for 4 selected genes (p = 0.0002). Eight out of 12(66.6%) multiple tumors were classified as CIMP-high, as compared to 5 out of 29(17.2%) solitary tumors (p = 0.004). Interestingly, 76 out of the 102 (74.5%) hypermethylated CpG sites found in multiple tumors were also seen in CIMP-high tumors. Functional analysis of hypermethylated genes found in multiple tumors showed enrichment of genes involved in different tumorigenic functions. In conclusion, multiple CRC are associated with a distinct methylation phenotype, with a close association between tumor multiplicity and CIMP-high. Our results may be important to unravel the underlying mechanism of tumor multiplicity. This work was supported by grants from the Hospital Clínic of Barcelona (Josep Font grant), Ministerio de Economí­a y Competitividad (SAF 2007-64873 and SAF2010-19273), Fundación Científica de la Asociación Española contra el Cáncer, and Instituto de Salud Carlos III (PI10/00384). “Cofinanciado por el Fondo Europeo de Desarrollo Regional (FEDER). Unión Europea. Una manera de hacer Europa”. CIBEREHD is funded by the Instituto de Salud Carlos III.

Gastrointestinal endoscopy can lead to infectious complications, and endoscopes must be disinfected to prevent them.to evaluate three methods of disinfection: 1) usual cleaning technique and immersion in glutaraldehyde phenolate (GP); 2) meticulous cleaning and immersion in GP, and 3) meticulous cleaning and immersion in hydrogen peroxide.thirty endoscopes (15 gastroscopes and 15 colonoscopes) were disinfected with each method. Samples were taken following endoscopic exploration, after cleaning and after disinfection, and were cultured. The number of positive culture (cfu/ml1) was counted.the rate of contamination of endoscopes did not decrease significantly after cleaning with method 1 (66 vs 60%), but did decrease with method 2 (38 vs 16%) and method 3 (53 vs 17%). The contamination rate after cleaning was significantly lower with methods 2 and 3 (p0.005). This rate was also lower after disinfection (p0.025). Method 3 achieved 0% contamination following disinfection.the greatest decrease in contamination rate was achieved with conscientious cleaning followed by disinfection. Both disinfectants yielded similar results, although hydrogen peroxide produced a higher level of disinfection.

To evaluate the results of an endoscopic follow-up assistance protocol for colorectal cancer (CRC) after curative surgery.Between 1994 and 1996, 205 patients with CRC were submitted to curative surgery in our hospital. An endoscopic follow-up was proposed to the patients based on an endoscopy six months following surgery, in the case they did not have a complete endoscopy prior to surgery, or one year after surgery if they did, another one two years later, and a third endoscopy between the third and fifth year. We retrospectively analyzed the follow-up outcome and endoscopic findings.155 patients were submitted to follow-up, of which 74,2% completed the protocol. 3 synchronous tumours, 4 anastomosis relapses and 2 metachronous tumours were detected. Curative surgery was performed on 100% of the synchronous tumours, 50% of the relapses and 50% of the metachronous tumours. 48.3% and 20.6% of the patients had synchronous and metachronous polyps, respectively. 14.7% of the polyps were larger than 1 cm, 21.7% and 4.8% were tubulovillous and villous, respectively, and 3.7% had severe dysplasia. Finally, patients with synchronous polyps had higher risk of developing metachronous polyps (RR 7.1, CI 95% 2.3; 22.2, p0.0001).The rate of adenomatous polyps with high risk of malignant degeneration, metachronous tumours or relapses detected by colonoscopy is low in our series. On the other hand, the detection of polyps during follow-up was related to the presence of synchronous polyps.