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Introduccion: la diseccion submucosa endoscopica (DSE) en colon es una tecnica en expansion en paises occidentales. Existen pocos estudios con seguimiento a largo plazo. Objetivo: analizar supervivencia libre de enfermedad a largo plazo tras DSE y comparar las tasas de recidiva en funcion de diferentes factores. Material y metodos: cohorte prospectiva de pacientes con DSE planeada entre septiembre de 2008 y diciembre de 2015. Cuando no fue posible tecnicamente completar DSE se realizo diseccion hibrida en bloque o fragmentada. Se analizo la tasa de recurrencia a cinco anos mediante curvas de Kaplan-Meier y se compararon en funcion de diferentes factores usando test de log-rank. Resultados: se incluyo una cohorte inicial de 89 pacientes en los que se consiguio seguimiento en 69. De los 69 pacientes, en 31 (45%) se realizo DSE; en once (16%), DSE hibrida; y en 27 (39%), DSE hibrida fragmentada. La mediana de seguimiento fue de 27 meses. La supervivencia libre de enfermedad a cinco anos fue del 81%. La media de endoscopias para eliminar la recurrencia fueron dos (rango 1-7) y ninguna requirio cirugia. La tasa de recidiva fue significativamente menor tras DSE “en bloque” respecto a fragmentada (15% vs. 27%, p = 0,036) y en resecciones R0 respecto a R1 (0% vs. 26%, p = 0,034). Las resecciones con margenes laterales negativos en lesiones resecadas en bloque presentaron menor tasa de recidiva respecto a aquellas con margenes afectos/desconocidos, que no alcanzaron la significacion estadistica (0% vs. 28%, p = 0,09). Conclusiones: en nuestro estudio, la supervivencia libre de enfermedad a cinco anos fue del 81% y ningun paciente requirio cirugia durante el seguimiento. Las resecciones fragmentadas y R1 se asociaron de forma significativa con mayor tasa de recurrencia.

Introduccion: la diseccion submucosa endoscopica sobre lesiones gastricas (DSE-G) es una tecnica que permite la reseccion de tumores gastricos precoces en bloque, con una tasa de curacion similar a la cirugia y una morbimortalidad menor. Objetivo: analizar la supervivencia total, la supervivencia libre de enfermedad y la tasa de recidiva en pacientes sometidos a DSE-G en una cohorte espanola a lo largo de su evolucion clinica. Material y metodos: estudio observacional prospectivo. Inclusion de pacientes sometidos a DSE-G de 2008 a 2015, con seguimiento entre seis y 60 meses. Se analizo la recurrencia a cinco anos mediante curvas de Kaplan-Meier y los resultados fueron comparados entre diferentes factores (en bloque vs. reseccion fragmentada, resecciones curativas R0 vs. margen lateral afecto ML+) usando test log-rank. Resultados: se analizaron 35 pacientes sometidos a DSE-G, con una mediana de seguimiento de 33,62 meses. Se identificaron cuatro recidivas en este periodo (11,4%), tres de ellas tratadas mediante nueva DSE-G. La presencia de ML+ en la pieza histologica se relaciono con mayor tasa de recidiva local durante el seguimiento (p = 0,06). Las resecciones fragmentadas presentaron un mayor riesgo de recidiva pero sin detectarse diferencias estadisticamente significativas (p = 0,49). No se registraron fallecimientos por neoplasia gastrica ni gastrectomia por persistencia de enfermedad en este periodo. La tasa de supervivencia global en nuestra serie fue de 94,3%. Conclusiones: la DSE-G realizada en nuestro medio permite una tasa elevada de curacion a largo plazo evitando la cirugia. Estos resultados se asemejan a las series europeas publicadas y aun se encuentran lejos de las tasas de curacion y recidiva de las cohortes asiaticas. Los casos de recidiva local pueden ser controlados mediante endoscopia.

I have read Dr. Luzon's article (1) and have shared his opinions for a long time. As I indicated in my letter 13 years ago (2), all of our patients need to receive adequate sedation in endoscopic explorations, including ERCP. It is also our obligation as the person responsible for the procedure, to ensure that this is so. At present and without renouncing any of my beliefs, I think it is necessary to ask ourselves several questions: .

Introduction: Colon capsule endoscopy (CCE) is an alternative approach for the examination of the colon in patients who refuse colonoscopy or after incomplete colonoscopy (IC). We conducted a study to determine the frequency of complete colonoscopy after IC, the diagnostic yield of CCE, the therapeutic impact of lesions found in CCE, the level of colon cleanliness and the safety of the procedure. Methods: We performed a prospective, multicenter study involving ten Spanish hospitals. Consecutive outpatients aged ≥ 18 years with previous IC were invited to participate. The latest version of the CCE device, PillCam™ COLON 2 (CCE-2), was administered to all patients according to the protocol. Results: The study population comprised 96 patients. The most frequent cause of IC was the inability to move past a loop using standard maneuvers (75/96 patients, 78%). Complete visualization of the colon was obtained with CCE-2 in 69 patients (71.9%). Of the 27 patients in whom the CCE-2 did not reach the hemorrhoidal plexus, it passed the colonic segment explored with the previous colonoscopy in 20 cases; therefore, it could be inferred that a combined approach (CCE-2 plus colonoscopy) enabled complete visualization of the colonic mucosa in 92.7% of patients. CCE-2 revealed new lesions in 58 patients (60.4%). Polyps were the most frequent finding (41 patients; 42.7% of the total number of patients). In 43 of the 58 patients (44.8% of the total number of patients), the new lesions observed led to modification of therapy, which included a new colonoscopy for polyp resection or surgery in patients with colonic neoplasm. Conclusions: CCE-2 is a suitable diagnostic procedure that can lead to more frequent diagnosis of significant colonic lesions after IC.

Background Adenoma and polyp detection rates (ADR and PDR, respectively) are important indicators of endoscopy quality, particularly in colorectal carcinoma screening. Objective To assess the influence of the endoscopist's experience on the ADR and PDR. Patients and Methods In this study, 9635 colonoscopies were screened during a 5-year period. Only 5738 were finally analyzed due to exclusion criteria. The endoscopists were separated in three groups of experience according to the number of colonoscopies performed in the past (yearly and total). The number of polyps and adenomas, as well as the size and histology of these polyps were recorded. Results The ADR and PDR were similar regardless of the experience of the endoscopist, but those with more experience clearly found more polyps of less than 10 mm (P = 0.01) and of less than 3 mm (P

We examined intraepithelial lymphocytes (IELs) in 213 ileal biopsies from 16 bowel grafts and compared them with 32 biopsies from native intestines. During the first year posttransplantation, grafts exhibited low levels of IELs (percentage of CD103(+) cells) principally due to reduced CD3(+) CD8(+) cells, while CD103(+) CD3(-) cell numbers became significantly higher. Changes in IEL subsets did not correlate with histology results, isolated intestine, or multivisceral transplants, but CD3(-) IELs were significantly higher in patients receiving corticosteroids. Compared with controls, more CD3(-) IELs of the grafts expressed CD56, NKp44, interleukin (IL)-23 receptor, retinoid-related orphan receptor gamma t (RORγt), and CCR6. No difference was observed in granzyme B, and CD3(-) CD127(+) cells were more abundant in native intestines. Ex vivo, and after in vitro activation, CD3(-) IELs in grafts produced significantly more interferon (IFN)-γ and IL-22, and a double IFNγ(+) IL-22(+) population was observed. Epithelial cell-depleted grafts IELs were cytotoxic, whereas this was not observed in controls. In conclusion, different from native intestines, a CD3(-) IEL subset predominates in grafts, showing features of natural killer cells and intraepithelial ILC1 (CD56(+) , NKp44(+) , CCR6(+) , CD127(-) , cytotoxicity, and IFNγ secretion), ILC3 (CD56(+) , NKp44(+) , IL-23R(+) , CCR6(+) , RORγt(+) , and IL-22 secretion), and intermediate ILC1-ILC3 phenotypes (IFNγ(+) IL-22(+) ). Viability of intestinal grafts may depend on the balance among proinflammatory and homeostatic roles of ILC subsets.

Adenoma and polyp detection rates (ADR and PDR, respectively) are important indicators of endoscopy quality, particularly in colorectal carcinoma screening.To assess the influence of the endoscopist's experience on the ADR and PDR.In this study, 9635 colonoscopies were screened during a 5-year period. Only 5738 were finally analyzed due to exclusion criteria. The endoscopists were separated in three groups of experience according to the number of colonoscopies performed in the past (yearly and total). The number of polyps and adenomas, as well as the size and histology of these polyps were recorded.The ADR and PDR were similar regardless of the experience of the endoscopist, but those with more experience clearly found more polyps of less than 10 mm (P = 0.01) and of less than 3 mm (P0.0001). Most of the differences were due to a higher number of flat polyps detected by the experienced group. This study also shows that more experienced endoscopists detect adenomas with more advanced histology (P0.0001).Even though the ADR and PDR are similar in all groups of endoscopists, the less experienced endoscopists could be missing some of the smaller polyps, sometimes with more advanced histology.

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)

Reversible protein phosphorylation is one of the most important forms of cellular regulation. Thus, phosphoproteomic analysis of protein phosphorylation in cells is a powerful tool to evaluate cell functional status. The importance of protein kinase-regulated signal transduction pathways in human cancer has led to the development of drugs that inhibit protein kinases at the apex or intermediary levels of these pathways. Phosphoproteomic analysis of these signalling pathways will provide important insights for operation and connectivity of these pathways to facilitate identification of the best targets for cancer therapies. Enrichment of phosphorylated proteins or peptides from tissue or bodily fluid samples is required. The application of technologies such as phosphoenrichments, mass spectrometry (MS) coupled to bioinformatics tools is crucial for the identification and quantification of protein phosphorylation sites for advancing in such relevant clinical research. A combination of different phosphopeptide enrichments, quantitative techniques and bioinformatic tools is necessary to achieve good phospho-regulation data and good structural analysis of protein studies. The current and most useful proteomics and bioinformatics techniques will be explained with research examples. Our aim in this article is to be helpful for cancer research via detailing proteomics and bioinformatic tools., This study was supported by: the Spanish Ministerio de Ciencia e Innovación through grants SAF2007-61926 (to PGP) and the European Commission through grant FP7 HEALTH-F3-2009-223431 (to PGP). Biomol-Informatics was financed by the European Social Fund. Support from the "Fundación Ramón Areces" is acknowledged. We also thank the Centro de Computación Científica-UAM for computational support. Special thanks Prof. Ernest Feytmans (Honorary Director at Swiss Institute of Bioinformatics -Location Geneva Area, Switzerland) and Prof. Shabaz Mohammed (Theme Leader at the Netherlands Proteomics Centre, Lecturer Utrecht University) who contributed to the publication of this article.

Endoscopic biliary stenting is a well-established palliative treatment in patients with unresectable malignant biliary strictures. Obstruction of uncovered self-expanding metal stent (SEMS) due to tumor ingrowth is the most frequent complication. Partially covered SEMS might increase stent patency but could favor complications related to stent covering, such as pancreatitis, cholecystitis, and migration. The aim of this study was to evaluate the efficacy and safety of partially covered SEMS in patients with an unresectable malignant biliary stricture. Patients with malignant extrahepatic biliary obstruction treated endoscopically with partially covered SEMS were included in this multicenter, prospective, nonrandomized study. One hundred ninety-nine patients were endoscopically treated with partially covered SEMS in 32 Spanish hospitals. Clinical success after deep cannulation was 96%. Early complications occurred in 4% (3 pancreatitis, 2 cholangitis, 1 hemorrhage, 1 perforation, and 1 cholecystitis). Late complications occurred in 19.5% (18 obstructions, 10 migrations, 6 cholangitis without obstruction, 3 acute cholecystitis, and 2 pancreatitis), with no tumor ingrowth in any case. Median stent patency was 138.9 ± 112.6 days. One-year actuarial probability of stent patency was 70% and that of nonmigration was 86%. Multivariate analysis showed adjuvant radio- or chemotherapy as the only independent predictive factor of stent patency and previous insertion of a biliary stent was the only predictive factor of migration. The partially covered SEMS was easily inserted, had a high clinical success rate, and prevented tumor ingrowth. The incidence of possible complications related to stent coverage, namely, migration, pancreatitis, and cholecystitis, was lower than in previously published series.

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.

Continuous infusions of levodopa directly into the duodenum-yeyunum is an effective therapy to reduce daily off time in an advanced stage of Parkinson's disease, but it is not without complications, particularly device related problems. We present our experience in three Spanish hospitals with these complications, including a severe case with migration, several decubitus ulcers, and one case of perforation of the bowel and finally death.

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.

Background “It's not what we do, it's the way that we do it”. Never has this maxim been truer in proteomics than now. Mass Spectrometry‐based proteomics/phosphoproteomics tools are critical to understand the structure and dynamics (spatial and temporal) of signalling that engages and migrates through the entire proteome. Approaches such as affinity purification followed by Mass Spectrometry (MS) have been used to elucidate relevant biological questions disease vs. health. Thousands of proteins interact via physical and chemical association. Moreover, certain proteins can covalently modify other proteins post‐translationally. These post‐translational modifications (PTMs) ultimately give rise to the emergent functions of cells in sequence, space and time. Findings Understanding the functions of phosphorylated proteins thus requires one to study proteomes as linked‐systems rather than collections of individual protein molecules. Indeed, the interacting proteome or protein‐network knowledge has recently received much attention, as network‐systems (signalling pathways) are effective snapshots in time, of the proteome as a whole. MS approaches are clearly essential, in spite of the difficulties of some low abundance proteins for future clinical advances. Conclusion Clinical proteomics‐MS has come a long way in the past decade in terms of technology/platform development, protein chemistry, and together with bioinformatics and other OMICS tools to identify molecular signatures of diseases based on protein pathways and signalling cascades. Hence, there is great promise for disease diagnosis, prognosis, and prediction of therapeutic outcome on an individualized basis. However, and as a general rule, without correct study design, strategy and implementation of robust analytical methodologies, the efforts, efficiency and expectations to make biomarkers (especially phosphorylated kinases) a useful reality in the near future, can easily be hampered.