Implementation of esophageal endoscopic submucosal dissection in Spain: Results from the nationwide registry. / Implementación de la disección endoscópica submucosa esofágica en España: resultados del registro nacional.

INTRODUCTION AND AIMS: The outcomes of endoscopic submucosal dissection (ESD) in the esophagus have not been assessed in our country. Our primary aim was to analyze the effectiveness and safety of the technique. MATERIAL AND METHODS: Analysis of the prospectively maintained national registry of ESD. We included all superficial esophageal lesions removed by ESD in 17 hospitals (20 endoscopists) between January 2016 and December 2021. Subepithelial lesions were excluded. The primary outcome was curative resection. We conducted a survival analysis and used logistic regression analysis to assess predictors of non-curative resection. RESULTS: A total of 102 ESD were performed on 96 patients. The technical success rate was 100% and the percentage of en-bloc resection was 98%. The percentage of R0 and curative resection was 77.5% (n=79; 95%CI: 68%-84%) and 63.7% (n=65; 95%CI: 54%-72%), respectively. The most frequent histology was Barrett-related neoplasia (n=55 [53.9%]). The main reason for non-curative resection was deep submucosal invasion (n=25). The centers with a lower volume of ESD obtained worse results in terms of curative resection. The rate of perforation, delayed bleeding and post-procedural stenosis were 5%, 5% and 15.7%, respectively. No patient died or required surgery due to an adverse effect. After a median follow-up of 14months, 20patients (20.8%) underwent surgery and/or chemoradiotherapy, and 9 patients died (mortality 9.4%). CONCLUSIONS: In Spain, esophageal ESD is curative in approximately two out of three patients, with an acceptable risk of adverse events.

Underwater versus conventional EMR of large nonpedunculated colorectal lesions: a multicenter randomized controlled trial.

BACKGROUND AND AIMS: Underwater EMR (UEMR) is an alternative procedure to conventional EMR (CEMR) to treat large, nonpedunculated colorectal lesions (LNPCLs). In this multicenter, randomized controlled clinical trial, we aimed to compare the efficacy and safety of UEMR versus CEMR on LNPCLs. METHODS: We conducted a multicenter, randomized controlled clinical trial from February 2018 to February 2020 in 11 hospitals in Spain. A total of 298 patients (311 lesions) were randomized to the UEMR (n = 149) and CEMR (n = 162) groups. The main outcome was the lesion recurrence rate in at least 1 follow-up colonoscopy. Secondary outcomes included technical aspects, en bloc resection rate, R0 resection rates, and adverse events, among others. RESULTS: There were no differences in the overall recurrence rate (9.5% UEMR vs 11.7% CEMR; absolute risk difference, -2.2%; 95% CI, -9.4 to 4.9). However, considering polyp sizes between 20 and 30 mm, the recurrence rate was lower for UEMR (3.4% UEMR vs 13.1% CEMR; absolute risk difference, -9.7%; 95% CI, -19.4 to 0). The R0 resection showed the same tendency, with significant differences favoring UEMR only for polyps between 20 and 30 mm. Overall, UEMR was faster and easier to perform than CEMR. Importantly, the techniques were equally safe. CONCLUSIONS: UEMR is a valid alternative to CEMR for treating LNPCLs and could be considered the first option of treatment for lesions between 20 and 30 mm due to its higher en bloc and R0 resection rates. (Clinical trial registration number: NCT03567746.).

Hepatic subcapsular hematoma post-endoscopic retrograde cholangiopancreatography requiring embolization.

Endoscopic retrograde cholangiopancreatography (ERCP) placement of biliary stents is the procedure of choice for bile duct strictures. Complications of endoscopic retrograde cholangiopancreatography have a low incidence. Hepatic subcapsular hematoma is uncommon but potentially serious. It is caused by laceration of the bile duct with guidewire or biliary traction during the procedure. Initial management is conservative with supportive measures. In case of hemodynamic instability or superinfection, embolization of the affected branch or even surgery could be performed.

Ileal metastasis from Phyllodes breast tumor.

We present the case of a 72-year-old woman with a history of right radical mastectomy due to the Phyllodes Tumor. Two months later, she went to the emergency room for intestinal occlusion. Analytically, she had anemia and thrombocytopenia. The abdominal tomography noticed signs of occlusion of the small bowell and injury of 5cm at the pericaecal level. Urgent exploratory laparotomy was performed and objectified distal ileum attached to the cecum with signs of irreversible ischemia, so an ileocaecal resection was performed with ileo-colonic anastomosis. In the postoperative period she presented paralytic ileus and paraneoplastic syndrome with bicytopenia refractory to corticosteroid treatment. To rule out abdominal complications, abdominal tomography was performed on the 5th day post-op that confirmed the integrity of the anastomosis and absence of signs of mechanical occlusion. The patient's evolution was unfavorable, went on to exitus on the 14th day. The anatomopathological study diagnosed metastasis of malignant Phyllodes Tumor at the ileal level.

Image-enhanced endoscopy in the diagnosis of gastric premalignant conditions and gastric cancer. / Técnicas de imagen avanzada en la detección y caracterización de las lesiones precursoras del cáncer gástrico y del cáncer gástrico precoz.

Diagnosis of early gastric cancer and its precancerous lesions remains a challenge for great part of western endoscopists. Changes seen in the mucosal pattern are generally subtle and hence difficult to identify. In this article, we will review the usefulness of conventional and virtual chromoendoscopy and magnification endoscopy in the recognition and classification of these lesions.

Deep Brain Stimulation for Severe and Intractable Aggressive Behavior.

Aggressive behavior in patients with intellectual disability can be resistant to pharmacological treatment and have detrimental consequences to themselves, family members, and caregivers. Hypothalamic deep brain stimulation (DBS) has been used to improve this type of behavior in severe and refractory cases. Here, we present the description and analysis of DBS of the posteromedial hypothalamus (PMH) and its long-term impact as treatment to improve severe and refractory aggressive behaviors, even with previous bilateral hypothalamotomy without improvement in patients with intellectual disability. Eleven patients underwent bilateral DBS of the PMH. Their medical records were reviewed, and the impact on behavior was measured using preoperative and postoperative Modified Overt Aggression Scale (MOAS) during the last follow-up medical visit. Nine of 11 patients presented a significant decrease in the severity of aggressive behavior, with a preoperative and postoperative MOAS average value of 50.5 and 18.7, respectively. An overall improvement of 63% was seen with a mean follow-up time of 4 years. A patient who previously underwent a bilateral hypothalamotomy via radiofrequency was included in this group. During follow-up, 3 patients presented deterioration of symptoms subsequent to pulse generator depletion but made a full clinical recovery after battery replacement. We posit that DBS of the PMH may be a safe and effective in improving severe and refractory aggressive behavior in patients with long-term intellectual disability.

Endoscopic view of the intrahepatic biliary ducts by direct per-oral cholangioscopy in a patient with a choledochal cyst.

Sixty year old female with hypertension and crampy abdominal pain episodes. Admitted to hospital (September-2020) by obstructive jaundice. MRCP: biliary dilation due to Todani Ic (fusiform) choledocal cyst (CC), distal sludge. ERCP: normal mucosa prominent papilla; biliary dilation compatible with CC; choledocholithiasis; 8-mm CHD filling defect. Sphincterotomy, removal of stones/sludge, brush-cytology of the filling defect (pathology: atypias). US: dilation resolution (CBD: 6.5 mm).

An Animal Able To Tolerate D2 O.

It is possible to gain a deeper insight into the role of water in biology by using physicochemical variant molecules, such as deuterium oxide (D2 O); however, D2 O is toxic to multicellular organisms in high concentrations. By using a unique desiccation-rehydration process, we demonstrate that the anhydrobiotic nematode Panagrolaimus superbus is able to tolerate and proliferate in 99 % D2 O. Moreover, we analysed P. superbus' water-channel protein (aquaporin; AQP), which is associated with dehydration/rehydration, by comparing its primary structure and modelling its tertiary structure in silico. Our data evidence that P. superbus' AQP is an aquaglyceroporin, a class of water channel known to display a wider pore; this helps to explain the rapid and successful organismal influx of D2 O into this species. This is the first demonstration of an animal able to withstand high D2 O levels, thus paving a way for the investigation of the effects D2 O on higher levels of biological organization.

Implementation of a peroral endoscopic myotomy program.

INTRODUCTION: the aim of our study was to develop a peroral endoscopic myotomy (POEM) program in our Unit following a two-step sequence: training on animal models and supervision by an experienced endoscopist during the first human cases. METHODS: a single endoscopist experienced in advanced endoscopy was trained in POEM. After observing POEM in referral centers, training was implemented on swine models (preclinical phase). Technical aspects and adverse events were prospectively recorded. A first subset of cases (group A) was compared to a second one (group B) to assess our progression. Finally, POEM was implemented in humans under the supervision of an experienced endoscopist (clinical phase). The outcomes and adverse events were prospectively recorded. RESULTS: during the preclinical phase, 15 POEM procedures were performed on live pigs. Severe adverse events (AE) were less frequent in group B than in group A (12 % vs 57 %, p = 0.07). After nine cases, a plateau of adverse events was reached. During the clinical phase, eleven POEM procedures were performed in patients under expert supervision. Technical and clinical (Eckardt score ≤ 3) success were 100 % and 91 %, respectively (follow-up 3-21 months). In two cases, intervention of an experienced endoscopist was required (cases 2 and 3) because of a difficult orientation at the esophagogastric junction. One mild pneumoperitoneum occurred, with no severe adverse events reported. CONCLUSIONS: training in animal models and supervision by an experienced endoscopist during the first cases could provide the necessary skills to perform POEM safely and effectively.

Quality in diagnostic upper gastrointestinal endoscopy for the detection and surveillance of gastric cancer precursor lesions: Position paper of AEG, SEED and SEAP. / Documento de posicionamiento de la AEG, la SEED y la SEAP sobre calidad de la endoscopia digestiva alta para la detección y vigilancia de las lesiones precursoras de cáncer gástrico.

This position paper, sponsored by the Asociación Española de Gastroenterología [Spanish Association of Gastroenterology], the Sociedad Española de Endoscopia Digestiva [Spanish Gastrointestinal Endoscopy Society] and the Sociedad Española de Anatomía Patológica [Spanish Anatomical Pathology Society], aims to establish recommendations for performing an high quality upper gastrointestinal endoscopy for the screening of gastric cancer precursor lesions (GCPL) in low-incidence populations, such as the Spanish population. To establish the quality of the evidence and the levels of recommendation, we used the methodology based on the GRADE system (Grading of Recommendations Assessment, Development and Evaluation). We obtained a consensus among experts using a Delphi method. The document evaluates different measures to improve the quality of upper gastrointestinal endoscopy in this setting and makes recommendations on how to evaluate and treat the identified lesions. We recommend that upper gastrointestinal endoscopy for surveillance of GCPL should be performed by endoscopists with adequate training, administering oral premedication and use of sedation. To improve the identification of GCPL, we recommend the use of high definition endoscopes and conventional or digital chromoendoscopy and, for biopsies, NBI should be used to target the most suspicious areas of intestinal metaplasia. Regarding the evaluation of visible lesions, the risk of submucosal invasion should be evaluated with magnifying endoscopes and endoscopic ultrasound should be reserved for those with suspected deep invasion. In lesions amenable to endoscopic resection, submucosal endoscopic dissection is considered the technique of choice.

Gastric cancer screening in low incidence populations: Position statement of AEG, SEED and SEAP. / Documento de posicionamiento de la AEG, la SEED y la SEAP sobre cribado de cáncer gástrico en poblaciones con baja incidencia.

This positioning document, sponsored by the Asociación Española de Gastroenterología, the Sociedad Española de Endoscopia Digestiva and the Sociedad Española de Anatomía Patológica, aims to establish recommendations for the screening of gastric cancer (GC) in low incidence populations, such as the Spanish. To establish the quality of the evidence and the levels of recommendation, we used the methodology based on the GRADE system (Grading of Recommendations Assessment, Development and Evaluation). We obtained a consensus among experts using a Delphi method. The document evaluates screening in the general population, individuals with relatives with GC and subjects with GC precursor lesions (GCPL). The goal of the interventions should be to reduce GC related mortality. We recommend the use of the OLGIM classification and determine the intestinal metaplasia (IM) subtype in the evaluation of GCPL. We do not recommend to establish endoscopic mass screening for GC or Helicobacter pylori. However, the document strongly recommends to treat H.pylori if the infection is detected, and the investigation and treatment in individuals with a family history of GC or with GCPL. Instead, we recommend against the use of serological tests to detect GCPL. Endoscopic screening is suggested only in individuals that meet familial GC criteria. As for individuals with GCPL, endoscopic surveillance is only suggested in extensive IM associated with additional risk factors (incomplete IM and/or a family history of GC), after resection of dysplastic lesions or in patients with dysplasia without visible lesion after a high quality gastroscopy with chromoendoscopy.

Risk of neoplastic change in large gastric hyperplastic polyps and recurrence after endoscopic resection.

BACKGROUND: Gastric hyperplastic polyps (GHPs) have a risk of neoplastic transformation reaching 5 %. Current endoscopic resection techniques appear suboptimal with a high risk of local recurrence. This study assessed the outcomes of endoscopic resection for GHPs and identified risk factors for recurrence and neoplastic transformation. METHODS: This retrospective, multicenter, European study included adult patients with at least one GHP ≥ 10 mm who underwent endoscopic resection and at least one follow-up endoscopy. Patients with recurrent GHPs or hereditary gastric polyposis were excluded. All data were retrieved from the endoscopy, pathology, and hospitalization reports. RESULTS: From June 2007 to August 2018, 145 GHPs in 108 patients were included. Recurrence after endoscopic resection was 51.0 % (74 /145) in 55 patients. R0 resection or en bloc resection did not impact the risk of polyp recurrence. In multivariate analysis, cirrhosis was the only risk factor for recurrence (odds ratio [OR] 4.82, 95 % confidence interval [CI] 1.33 - 17.46; P = 0.02). Overall, 15 GHPs (10.4 %) showed neoplastic transformation, with size > 25 mm (OR 10.24, 95 %CI 2.71 - 38.69; P < 0.001) and presence of intestinal metaplasia (OR 5.93, 95 %CI 1.56 - 22.47; P = 0.01) being associated with an increased risk of neoplastic transformation in multivariate analysis. CONCLUSIONS: Results confirmed the risk of recurrence and neoplastic transformation of large GHPs. The risk of neoplastic change was significantly increased for lesions > 25 mm, with a risk of high grade dysplasia appearing in polyps ≥ 50 mm. The risk of recurrence was high, particularly in cirrhosis patients, and long-term follow-up is recommended in such patients.

SSD - a free software for designing multimeric mono-, bi- and trivalent shRNAs.

RNA interference (RNAi) is a powerful gene silencing technology, widely used in analyses of reverse genetics, development of therapeutic strategies and generation of biotechnological products. Here we present a free software tool for the rational design of RNAi effectors, named siRNA and shRNA designer (SSD). SSD incorporates our previously developed software Strand Analysis to construct template DNAs amenable for the large scale production of mono-, bi- and trivalent multimeric shRNAs, via in vitro rolling circle transcription. We tested SSD by creating a trivalent multimeric shRNA against the vitellogenin gene of Apis mellifera. RT-qPCR analysis revealed that our molecule promoted a decrease in more than 50% of the target mRNA, in a dose-dependent manner, when compared to the control group. Thus, SSD software allows the easy design of multimeric shRNAs, for single or multiple simultaneous knockdowns, which is especially interesting for studies involving large amounts of double-stranded molecules.

Endoscopic submucosal dissection for gastric epithelial lesions: long-term results in a Spanish cohort.

INTRODUCTION: endoscopic submucosal dissection for gastric lesions (ESD-G) is a technique that allows en-bloc resection of early gastric tumors, with a cure rate similar to that of surgery but lower morbidity and mortality rates. OBJECTIVE: to assess total survival, disease-free survival and relapse rate during the course of disease in a Spanish cohort of patients undergoing ESD-G. MATERIAL AND METHODS: this was a prospective observational study of patients undergoing ESD-G from 2008 to 2015, with a follow-up ranging from six to 60 months. Recurrence at five years was analyzed using Kaplan-Meier curves and the results were compared according to several factors using the log-rank test. These included en-bloc versus piecemeal resection and R0 curative resection versus resection with affected lateral margins (LM+). RESULTS: a total of 35 patients undergoing ESD-G were assessed, with a median follow-up of 33.62 months. Four relapses were identified (11.4%) during this period, of which three were managed with repeat ESD-G. A histological specimen with LM+ was associated with a higher local relapse rate during follow-up (p = 0.06). Piecemeal resections had a higher relapse risk, although no statistically significant differences were identified (p = 0.49). No deaths from gastric cancer occurred and no gastrectomies due to persistent disease were performed during this period. The overall survival rate in our series was 94.3%. CONCLUSIONS: ESD-G in our setting provides high long-term cure rates, while avoiding surgery. These results are similar to those reported by the European series and remain far removed from the cure and relapse rates obtained in Asian cohorts. Local relapse cases may be monitored with endoscopy.

Long-term follow-up after endoscopic submucosal dissection of colorectal lesions in a Spanish cohort.

INTRODUCTION: ESD in the colon is an increasingly important technique in Western countries. There are few studies that include long term follow-up. AIM: to analyze the long term recurrence free survival rate after ESD and to compare recurrence rates according to different variables. METHODS: this was a prospective observational study of patients with a planned ESD from September 2008 to December 2015. When it was not possible to achieve an ESD, hybrid ESD was performed, either en bloc or piecemeal. Kaplan-Meier survival curves were used to assess the five year local recurrence free survival rate and the recurrence rate. The results were compared according to different factors. RESULTS: of the 89 patients scheduled for ESD who were initially enrolled in the study, 69 were finally included for follow-up. ESD was performed in 31 (45%) patients, KAR in eleven (16%) and pKAR in 27 (39%). The median follow-up was 27 months (range 6-60). The five year disease free survival rate was 81%. The average number of endoscopies needed to eliminate recurrence was two (range 2-7) and no patient required surgery for this reason. The recurrence rate was significantly higher in piecemeal resections vs en bloc resections (27% vs 15%, p = 0.036) and R1 resections vs R0 resections (26% vs 0%, p = 0.034). The presence of affected or unknown lateral margins in en bloc resections without other poor prognosis factors had higher recurrence rates but the difference was not statistically significant (28% vs 0%, p = 0.09). CONCLUSIONS: in our study, the five year disease free survival rate was 81% and no patient required surgery during follow-up. Piecemeal and R1 resections had significantly higher recurrence rates, as well as LM involvement, although this was not statistically significant.

AEG-SEED position paper for the resumption of endoscopic activity after the peak phase of the COVID-19 pandemic. / Documento de posicionamiento AEG-SEED para el reinicio de la actividad endoscópica tras la fase pico de la pandemia de COVID-19.

INTRODUCTION: The COVID-19 pandemic has led to the suspension of programmed activity in most of the Endoscopy Units in our environment. The aim of this document is to facilitate the resumption of elective endoscopic activity in an efficient and safe manner. MATERIAL AND METHODS: A series of questions considered to be of clinical and logistical relevance were formulated. In order to elaborate the answers, a structured bibliographic search was carried out in the main databases and the recommendations of the main Public Health and Digestive Endoscopy institutions were reviewed. The final recommendations were agreed upon through telematic means. RESULTS: A total of 33 recommendations were made. The main aspects discussed are: 1) Reassessment and prioritization of the indication, 2) Restructuring of spaces, schedules and health personnel, 3) Screening for infection, 4) Hygiene measures and personal protective equipment. CONCLUSION: The AEG and SEED recommend restarting endoscopic activity in a phased, safe manner, adapted to local resources and the epidemiological situation of SARS-CoV-2 infection.

Predicting N Status in Maize with Clip Sensors: Choosing Sensor, Leaf Sampling Point, and Timing.

Nitrogen (N) losses from agricultural systems increase air and water pollution, and these losses are highly correlated with the excessive fertilization. An adjusted N fertilization is then a key factor in increasing the N fertilizer efficiency, and leaf clip sensors can help to improve it. This study (combining five different field experiments in Central Spain) tried to identify the ability of the clip sensors in maize N status identification and yield prediction, comparing two different devices (SPAD-502® and Dualex®) and identifying the best protocol for maize leaf sampling. As a result, the study demonstrated that different leaf clip chlorophyll sensors presented similar results, although some differences appeared at larger N concentrations. Complementary polyphenol information (as flavonol) can improve the maize N deficiency prediction. Moreover, valuable information for a proper sampling protocol was obtained with this study. It proved that the sampling position (in the leaf and in the plant) and sampling time were crucial for a better estimation of the maize N status. Proper fertilization recommendations could be achieved based on clip chlorophyll sensor measurements.

Use of electrosurgical units in the endoscopic resection of gastrointestinal tumors.

Electrosurgical units (ESUs) are indispensable devices in our endoscopy units. However, many endoscopists are not well-trained on their use and their physical bases are usually not properly studied or understood. In addition, comparative data concerning the settings that may be applied in different circumstances are scarce in the medical literature. Given that it is important to be aware of their strengths and risks, we conducted a review of the available information and research on this topic.