Received: 8 January 2021 DOI: 10.1002/ueg2.12101 ORIGINAL ARTICLE - Accepted: 16 March 2021 Implementation of endoscopic submucosal dissection in a country with a low incidence of gastric cancer: Results from a prospective national registry Gloria Fernández‐Esparrach1 | José‐Carlos Marín‐Gabriel2 | Alberto H. de Tejada3 | Eduardo Albéniz4 | Oscar Nogales5 | Andres J. del Pozo‐García2 | Pedro J. Rosón6 | Unai Goicotxea7 | Hugo Uchima8 | Alvaro Terán9 | Alvarez Alberto10 | Rodríguez‐Sánchez Joaquín11 | Rivero‐Sánchez Liseth1 | Santiago José3 | en representación del grupo de DSE de la SEED 1 Endoscopy Unit, Gastroenterology Department, ICMDM, CIBEREHD, IDIBAPS, Abstract Hospital Clínic, University of Barcelona, Introduction: Endoscopic submucosal dissection (ESD) has become the treatment of Barcelona, Spain 2 choice for early gastric malignancies. In recent years, the ESD technique has been Endoscopy Unit, Gastroenterology Department, “i+12 Research Institute”, implemented in Western countries with increasing use. Hospital Universitario 12 de Octubre, Objectives: To describe the results of gastric ESD in a Western country with a low Universidad Complutense, Madrid, Spain 3 Endoscopy Unit, Gastroenterology incidence of gastric cancer. Department, IDIPHISA, Hospital Universitario Patients and Methods: The prospective national registry was conducted over Puerta de Hierro, Autonomous University of Madrid, Madrid, Spain 4 years in 23 hospitals, including 30 endoscopists. Epithelial and subepithelial le- 4 Complejo Hospitalario de Navarra, sions (SEL) qualified to complete removal with ESD were assessed. The technique, Navarrabiomed Biomedical Research Center, instruments, and solution for submucosal injection varied at the endoscopist's UPNA, IdiSNA, Pamplona, Spain 5 discretion. ESD was defined as difficult when: en‐bloc resection was not achieved, Hospital Gregorio Marañón, Marañón, Madrid, Spain had to be converted to a hybrid resection, lasted more than 2 h or an intra- 6 Hospital Quirón, Málaga, Spain procedural perforation occurred. Additionally, independent risk factors for difficult 7 Hospital Universitario de Donostia, San ESD were analyzed. Sebastián, Spain Results: Two hundred and thirty gastric ESD in 225 patients were performed from 8 Centro Médico Teknon, Barcelona, Barcelona, Spain January 2016 to December 2019 (196 epithelial and 34 SEL). Most lesions were 9 Hospital Universitario Marqués de Valdecilla, located in the lower stomach (111; 48.3%). One hundred and twenty‐eight (55.6%) Santander, Spain ESD were considered difficult. The median procedure time was 105 min (inter- 10 Complejo Universitario de Salamanca, quartile range [IQR]: 60–150). The procedure time for SEL was shorter than for Salamanca, Spain 11 epithelial lesions (90 min [45–121] vs. 110 min [62–160]; p = 0.038). En‐bloc, R0, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain and curative resection rates were 91.3%, 75.2%, and 70.9%, respectively. Difficult ESD had lower R0 resection rates than ESD that did not meet the difficulty criteria Correspondence Gloria Fernández‐Esparrach, Endoscopy Unit, (64.8% and 87.6%; p = 0.000, respectively). Fibrosis and poor maneuverability were Gastroenterology Department, ICMDM, - This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. © 2021 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC. on behalf of United European Gastroenterology. 718 United European Gastroenterol J. 2021;9:718–726. wileyonlinelibrary.com/journal/ueg2 FERNÁNDEZ‐ESPARRACH ET AL. - 719 Hospital Clínic, University of Barcelona, CIBEREHD, IDIBAPS, Barcelona, Spain independent factors associated with difficult ESD (OR 3.6, 95%CI 1.1–11.74 and OR Email: MGFERNAN@clinic.cat 5.07, 95%CI 1.6–16.08; respectively). Conclusions: Although the number of cases is limited, the results of this analysis show acceptable en‐bloc and R0 rates in gastric ESD considering the wide variability in experience among the operators. Fibrosis and poor maneuverability were asso- ciated with more difficulty in completing ESD. KEYWORDS early gastric cancer, en‐bloc, endoscopic resection, endoscopic submucosal dissection, gastric premalignant lesions, resection Key summary Summarize the established knowledge on this subject � Endoscopic submucosal dissection (ESD) is the standard of care for treatment of early gastric cancers (GC). Due to a lower incidence of GC in European countries, the introduction of gastric ESD has been more gradual than in the East. � ESD complications, technical and clinical success depend on the endoscopist's experience, the presence of submucosal fibrosis or invasive cancer, and poor access location. What are the significant and/or new findings of this study? � This study shows the results from a prospective nationwide registry of gastric ESD in a low GC incidence country. Despite a relative low number of cases, quite acceptable outcomes (en‐bloc, R0 and curative resection of 91.3%, 75.2% and 70.9%, respectively) were observed considering the wide variability in experience among the operators. � Difficult ESD were mainly associated with the presence of submucosal fibrosis and poor maneuverability; however, independent pre‐procedural factors were not identified. There was a trend of association between ESD difficulty and the location of the lesion in the upper/middle stomach INTRODUCTION widespread than in Asian countries such as Japan and South Korea.6 A survey among European endoscopists clearly indicated that ESD Endoscopic submucosal dissection (ESD) has become the standard of was not common practice in Europe in 2010.7 In this survey, only 20 1 care for the treatment of early gastric cancer (EGC). The main centers provided data on gastric ESD, which was mainly performed advantage of ESD relies in its ability to achieve en‐bloc instead of by a single endoscopist. While in 2010 surgery was still considered piecemeal resection regardless of the size of the lesion or presence of the treatment of choice for EGC in the West, nowadays ESD is fibrosis. This minimally invasive treatment approach not only offers considered the standard of care1,5,8–13 as confirmed by a new survey an excellent prognosis but also substantially improves the quality of published in 2020 in which the results of gastric ESD are very similar life of patients with EGC.2,3 to the reported in Eastern countries.14,15 Despite the above, ESD is a highly demanding technique with a Endoscopists without expertise or trainees, often cannot suc- 4 higher risk of perforation than standard EMR methods. It requires a cessfully complete the procedure or adequately manage adverse fully skilled endoscopist to ensure success and reduce adverse events, such as bleeding or perforation. In addition, difficult ESD is events; this entails specific training and an appropriate learning associated to a longer procedure time with the consequent impact on curve. Moreover, longer time slots, specific equipment, and infra- the organization of the Endoscopy Units. Kim et al. found that diffi- structure for adequate management of adverse events (i.e., possi- cult ESD procedures are associated with the size of the lesion, its bility of admitting patients to award, access to appropriate surgical location, submucosal fibrosis, and submucosal invasive cancer.16 teams, and/or interventional radiology) are required before starting In this study, we present the results of gastric ESD in a an ESD.1,5 Western country with low incidence of gastric cancer. As sec- Due to the low incidence of gastric cancer in Western countries, ondary objective, we assessed the risk factors associated with the introduction and availability of ESD has been gradual and less difficult gastric ESD. 720 - UNITED EUROPEAN GASTROENTEROLOGY JOURNAL METHODS those R0 resections with no features of poor prognosis (≤500 μm of submucosal invasion, G1‐2, and no lymphovascular invasion), it Spanish ESD Patient Registry means, with low risk for local or distant recurrence that did not require further therapies. ESD was considered hybrid when the The Spanish ESD Patient Registry is a multicenter collaborative specimen was resected en‐bloc with the help of a snare. A piece- registry that collects data of procedures and outcomes of patients meal resection was defined as a specimen removed in several treated with ESD for early gastrointestinal neoplasia, preneoplastic fragments. lesions, and subepithelial lesions (SEL) in 23 hospitals (17 tertiary Intraprocedural bleeding was defined as oozing or jet bleeding academic centers, 4 private, and 2 community centers) in Spain. requiring the use coagulation forceps (and/or clips, topic gel agents, Endoscopists were properly trained in ESD, most of them having etc.) or other nonendoscopic treatments such as interventional radi- visited Japanese expert centers as observer trainees. The registry did ology or surgery. Delayed bleeding was defined as any of the following not mandate specific protocols for performing the procedure. Insti- criteria: episode of hematemesis and/or melena, drop of 2 g/dl of the tutional review board approval was obtained from the Ethics Com- hemoglobin level, and suspicion of bleeding that required a new mittee of each hospital and all patients provided written informed endoscopy after the completion of ESD and within 30 days. consent for inclusion in the registry. Consecutive patients were Perforation was defined as deep mural injury with or without enrolled from January 2016 to December 2019 and only lesions an obvious hole in the muscularis propia. Intraprocedural perfora- planned to be completely removed by ESD were included. tions were defined as those detected by the endoscopist during the procedure and which were managed either endoscopically (closure with through‐the‐scope or over‐the‐scope clips) or surgically. Lesion assessment Delayed perforations were those not suspected during the pro- cedure, diagnosed after the completion of ESD, and confirmed by Epithelial lesions were characterized according to the Paris classifi- imaging tests. cation.17 Lesion margins were assessed with chromoendoscopy (and Submucosal fibrosis was generally described when a dense near focus or magnification when available). Additionally, lesions whitish or scar tissue was present at the submucosal space (Figure 1). were classified according to the Vienna classification at histology. SEL Maneuverability was considered good (good access to the lesion originated from submucosa were previously assessed with endo- with a stable position and one‐to‐one movements with straight scopic ultrasound. The stomach was divided into upper (cardia, scope) or poor. fundus, and body), middle (incisura), and lower (antrum) part. ESD procedures Data collection ESD procedures were performed by 30 endoscopists, the majority The registry included pre‐procedural data such as demographics, under general anesthesia with endotracheal intubation. The tools comorbidities, chronic use of antiplatelet agents/anticoagulants, and selection (electrosurgical knives and solutions for the injection) any previous intervention for the lesion. depended on the endoscopist's discretion. ESD were performed Procedural data were prospectively collected. This included: type following the different steps described elsewhere, with coagulation of sedation (deep sedation or general anesthesia with endotracheal of exposed, nonbleeding vessels before completing the procedure. intubation), characteristics of the lesion (location, macroscopic Pathologic specimens were pinned and submitted for histopatho- morphology according to Paris classification17), technical aspects (i.e., logical analysis in formalin. type of knife and submucosal solution, use of traction systems), All patients were hospitalized for a variable period (1–5 days) procedural time of each ESD step, the presence of fibrosis or fat in and the proton pump inhibitors were administered for 8 weeks. Peri the submucosa, completeness of the resection (complete/incomplete, procedural antibiotics were not routinely used. en‐bloc or piecemeal resection), and intraprocedural adverse events. The estimation of the size of the lesion was not registered; instead, the diameter of the full specimen assessed by the pathologist after Outcomes and definitions the resection was recorded. Post‐procedural data included delayed adverse events and histology. ESD was considered difficult when en‐bloc resection was not ach- Personal and clinical data were codified, anonymously registered, ieved, turned to hybrid resection, it lasted more than 2 h or an and managed recorded on standardized case report forms and intraprocedural perforation occurred. entered online in REDCapTM electronic data capture tools hosted at En‐bloc resection was defined as the entire lesion resected in “i+12 Research Institute” of Hospital Universitario 12 de Octubre.18 one piece and R0 (complete) when deep and lateral margins of the All authors had access to the study data and had reviewed and specimen were free of neoplasia. Curative resection was defined as approved the final manuscript FERNÁNDEZ‐ESPARRACH ET AL. - 721 F I G U R E 1 (a) A case of difficult endoscopic submucosal dissection. Submucosal fibrosis can be seeing as dense whitish tissue in the submucosal space. (b) Normal submucosal space after injection of fluid. A thin penetrating vessel can be observed emerging from the muscular layer (down) whereas the mucosal flap is in the top of the image Statistical analysis coagulopathy and 75 (33.3%) were taking antiplatelet agents and/or anticoagulants. One hundred and ninety‐six lesions were epithelial Efficacy outcomes and technical difficulty of ESD were analyzed in a suspicious of EGC or gastric preneoplastic lesions and the rest per lesion basis whereas delayed adverse events were analyzed in a (n = 34, 14.8%) were SELs. Most lesions were located in the lower per patient basis. Continuous variables were presented as median stomach (111; 48.3%) and the most common morphology of epithelial plus interquartile range (25th and 75th percentiles; IQR) and were lesions was nonpolypoid Paris 0‐IIa (111/196, 56.6%; Table 1). Pro- compared using the Mann–Whitney test. Dichotomous variables cedures were performed under general anesthesia and endotracheal were expressed as frequencies (%) and were compared using Chi‐ intubation in 85% of cases. Hybrid knifes with injection capability square test. were used in 63.9% of procedures and the most common substance All statistical tests were two‐sided, and p values <0.05 were for submucosal injection was gelatin succinylated (30.4%) followed by considered statistically significant. Multiple logistic regression glycerol (26.5%), saline (21.3%), and hydroxyethyl starch (17%), analysis was used in order to evaluate the strength of association whereas hyaluronic acid was only used in a 2.6% of cases. Intra- between difficult ESD and significant variables using backward procedural bleeding occurred in 86 (37.4%) lesions and was endo- stepwise variable selection. The stepwise modeling procedure scopically managed in all cases (coagulation forceps in 62, clips in 17, started with the full model and consisted in eliminating, for each and injection in 7). step, the least statistically significant variable, thus re‐computing The median number of ESD performed per endoscopist was 5 the revised model. Candidate variables for inclusion in the model (IQR: 2–11.5). The median procedure duration was 105 min (IQR: were those achieving a p value ≤0.1 in the univariable analysis. 60–150 min) and the median size of the resected specimens in the Odds ratios (ORs) and associated 95% confidence intervals (CIs) pathology report was 35 mm (IQR: 25–48 mm). ESD for SELs was were used to quantify the level of association. Statistical analysis shorter than for epithelial lesions (90, IQR 45–121 min vs. 110, IQR was performed using SPSS version 23 (IBM). Significance was 62–160 min; p = 0.038). Table 2 shows different procedure times regarded at p value < 0.05. required for completing ESD based on the location and size of the lesions. RESULTS ESD outcomes General A complete removal of the lesions was achieved in 226 (98.3%) cases. Over the course of 4 years, 230 gastric lesions in 225 patients were Reasons for incomplete resection were intraprocedural bleeding in treated by ESD. One hundred and thirty (57.8%) patients were males one patient and extensive fibrosis in three patients. These four le- with a median age of 71 (range 28–93) years. One hundred and nine sions were located in the proximal stomach. In 25 cases (10.9%), the (48.4%) had comorbidities and were ASA III or IV, 8 (3.6%) had a procedure was turned into a hybrid ESD and 16 were piecemeal 722 - UNITED EUROPEAN GASTROENTEROLOGY JOURNAL TABLE 1 Characteristics of the gastric lesions removed with endoscopic submucosal dissection All lesions Epithelial lesions Subepithelial lesion N = 230 N = 196 N = 34 Size (maximum diameter, mm) median (IQR) 35 (25–48) 35 (25–50) 27 (20–40) Location, n (%) Cardia (upper) 14 (6.1%) 13 (6.6%) 1 (2.9%) Fundus (upper) 5 (2.2%) 3 (1.5%) 2 (5.9%) Body (upper) 71 (30.9%) 55 (28.1%) 16 (47.1%) Incisura (middle) 29 (12.6%) 28 (14.3%) 1 (2.9%) Antrum (lower) 111 (48.3%) 97 (49.5%) 14 (41.2%) Paris classification, n (%) 0‐IIa ‐ 111 (56.6%) ‐ 0‐IIb ‐ 14 (7.1%) ‐ 0‐IIc ‐ 27 (13.8%) ‐ 0‐IIa + 0‐II c ‐ 44 (22.5%) ‐ Most advanced histology, n (%) Mucosal lesions Negative for neoplasia ‐ 14 (7.1%) ‐ LGD ‐ 61 (31.1%) ‐ HGD ‐ 42 (21.4%) ‐ Noninvasive carcinoma ‐ 18 (9.2%) ‐ Intramucosal carcinoma ‐ 34 (17.3%) ‐ Submucosal invasive carcinoma ‐ 21 (10.7%) ‐ Missing ‐ 6 (3%) ‐ Subepithelial lesions Carcinoid ‐ ‐ 14 (41.2%) Inflammatory fibroid polyp ‐ ‐ 8 (23.5%) GIST ‐ ‐ 4 (11.8%) Leyomioma ‐ ‐ 2 (5.9%) Other ‐ ‐ 6 (17.6%) resections (8 of them with the help of a snare). In two cases of en‐ bloc resection not achieved in 20 (8.7%), and perforation in 6 (2.6%). bloc resection of epithelial lesions, the specimen could not be Difficulty was translated into lower rates of en‐bloc, R0 and curative retrieved and in 35 of them the margins were positive (21 with resection (Table 3). vertical and 14 with affected horizontal margins). Histopathology of In the univariate analysis, the nonlifting sign, location in the the lesions is shown in Table 1. Rates of en‐bloc, R0, and curative upper/middle stomach, poor maneuverability, fibrosis, submucosal resection were 91.3%, 75.2%, and 70.9%, respectively (Figure 2). fat, and intraprocedural bleeding were associated with a more diffi- Twenty‐eight out of 225 patients (12.4%) presented a delayed cult ESD (Table 4). Difficulty was not related with experience of the bleeding. No delayed perforations were registered. endoscopist (53.2% and 65.2% difficult ESD in endoscopists with <10 or ≥10 procedures; p = 0.093). The presence of fibrosis and poor maneuverability were independent factor associated with difficult Risk factors for difficult ESD ESD (OR 3.60, 95%CI 1.10–11.74, p = 0.034 and OR 5.07, 95%CI 1.60–16.08, p = 0.006; respectively [Table 4]). We did not identify One hundred and twenty‐eight (55.6%) ESD were considered diffi- any independent predictive variable that could be assessed before cult: procedure time >2 h in 77 (33.4%), hybrid ESD in 25 (10.9%), en‐ starting the procedure. FERNÁNDEZ‐ESPARRACH ET AL. - 723 T A B L E 2 Time (minutes) required for completing ESD based on type, location, and size of the resected lesion Location Lower Middle Upper Size stomach stomach stomach ≤35 mma N 65 13 49 Median 85 89.5 97.5 IQR 50–120 56.2–117.5 41.2–128.2 >35 mm N 46 16 41 Median 97 170 145 IQR 64–150 112.5–238.7 98.2–240 Note: Cells display three different colors corresponding to different median times: less than 90 min, 90–100 min, and more than 120 min. Time tends to increase from the upper left to the lower right. a Median of size of lesions included in the registry. DISCUSSION In this study, we present the experience with gastric ESD in Spain, with rates of complete endoscopic resection, en‐bloc, histological R0, and curative resection of 98.3%, 91.3%, 75.2%, and 70.9%, respec- tively. Despite the relatively low number of cases compared to other series in the East, our outcomes are very similar to those published in other Western reports.1,5,8–13 Spain is considered a low‐incidence area for gastric cancer,6 which could explain that only 230 proced- ures were performed in 4 years. The first report on the experience of a European country in gastric ESD was published in 2009. It was a retrospective single center study performed in Portugal with 19 patients that showed FIGURE 2 Flow chart histological R0 and en‐bloc rates of 79% and 89%, respectively.11 Since then, more series have been published (most of them retro- spective and with a maximum of three endoscopists) showing a clear improvement between the oldest and most recent studies. Whereas lesions were evaluated with chromoendoscopy, in this analysis the studies performed before 2011 included less than 100 patients with lesion was not properly delineated, resulting in positive horizontal an R0 and en‐bloc rates of 64%–89% and 79%–90%, recent studies margins in 14 cases, thus stressing the importance of an accurate include more than 100 patients with rates between 87%–92% and evaluation and delineation of the lesions (in our series, the R0 83%–95%, respectively.10–13,19–22 These studies confirm that the would have increased up to 81.3%). prevalence of EGC remains low in most non‐Eastern countries since Another important aspect for achieving proficiency in ESD is the the rate of inclusion of cases is still low, requiring between 3 and continuous training. In this regard, the Spanish Society of Digestive 12 years for treating less than 200 patients. Endoscopy promotes educational activities among its members.26 An adequate training is the main prerequisite for a safe and Only seven of the 30 endoscopists met the requirement to perform a effective ESD.5 In early reports from Europe, gastric ESD was minimum of 25 ESD per year as recommended by the ESGE.5 performed by endoscopists without a standard learning program, Moreover, most of those with less than five cases have either usually in a self‐taught manner followed by a short visit to Japan stopped doing ESD or are starting after having been trained by a as observer trainee.12 Spanish endoscopists have performed a senior endoscopist in the same center. variable and non‐systematic training that includes hands‐on cour- Besides the experience, for successful ESD it is mandatory to 23 ses and visits as observer trainee to Japan and other European predict the degree of technical difficulty before starting the pro- and Spanish hospitals with a high volume of cases. Moreover, all cedure. As shown in our study, difficult ESD is associated with an endoscopists performing ESD in Spain have expertise in advanced incomplete or noncurative resection. Difficult ESD procedures entail diagnostic endoscopy, proficiency in EMR techniques and man- more device exchanges for tissue elevation, more bleeding, and more 5,24,25 agement of adverse events as recommended by the ESGE. time. This certainly has significant implications in most health care However, despite the experience in colonic EMR and that all environments because of the associated cost. Therefore, when a 724 - UNITED EUROPEAN GASTROENTEROLOGY JOURNAL TABLE 3 Therapeutic outcomes according to the ESD difficulty All ESD Difficult ESD Not difficult ESD N = 230 N = 128 N = 97 p value Complete endoscopic resection rate, n (%) 226 (98.3%) 124 (96.9%) 97 (100%) 0.079 En‐bloc resection rate, n (%) 210 (91.3%) 108 (84.4%) 97 (100%) 0.000 R0 resection rate, n (%) 173 (75.2%) 83 (64.8%) 85 (87.6%) 0.000 Curative resection rate, n (%) 163 (70.9%) 76 (58.4%) 82 (84.5%) 0.000 Abbreviation: ESD, endoscopic submucosal dissection. TABLE 4 Independent predictive factors for difficult ESD Difficult ESD Not difficult ESD N = 128 (%) N = 97 (%) OR (95%CI) p valuea Adjusted OR (95%CI) p valueb Anesthesiologist, n (%) No 13 (10.2%) 1 (1.0%) 0.09 (0.01–0.72) 0.005 0.25 (0.26–1.46) 0.238 Yes 115 (89.8%) 95 (97.9%) Endoscopist experience, n (%) <10 ESD 45 (35.2%) 24 (24.7%) 0.60 (0.33–1.09) 0.093 0.80 (0.33–1.92) 0.623 10 or more 83 (64.8%) 73 (75.2%) Nonlifting sign, n (%) No 44 (84.6%) 41 (100%) 0.55 (0.49–0.62) 0.008 NV NV Yes 8 (15.4%) 00 (0%) Location, n (%) Lower 50 (39.1%) 58 (59.8%) 2.32 (1.35–3.97) 0.002 1.61 (0.78–3.32) 0.189 Middle/Upper 78 (60.9%) 39 (40.2%) Maneuverability, n (%) Good 73 (58.4%) 70 (82.3%) 3.32 (1.71–6.44) <0.001 5.07 0.006 Poor 52 (40.6%) 15 (17.7%) (1.60–16.08) Fibrosis, n (%) No 41 (32%) 75 (78.1%) 7.57 (4.11–13.94) <0.001 3.60 0.034 Yes 87 (68%) 21 (21.9%) (1.10–11.74) Submucosal fat, n (%) No 62 (73%) 65 (98.5%) 24.11 (3.16–183.98) <0.001 NV NV Yes 23 (27%) 1 (1.5%) Use of any type of traction, n (%) No 94 (81.7%) 85 (91.4%) 2.37 (0.99–5.64) 0.046 0.34 (0.57–2.13) 0.254 Yes 21 (18.3%) 8 (8.6%) Intraprocedural bleeding, n (%) No 57 (44.5%) 82 (84.5%) 6.80 (3.54–13.06) <0.001 1.36 (0.30–6.60) 0.681 Yes 71 (55.5%) 15 (15.5%) Abbreviations: ESD, endoscopic submucosal dissection; NV, not valuable. a Univariable analysis. b Multivariable analysis. FERNÁNDEZ‐ESPARRACH ET AL. - 725 difficult ESD is expected, appropriate preparation must be consid- A C KN O W L E D GM E NT S ered, including consultation with more experienced endoscopists. The authors thank Dr. Fernando Mújica (currently retired) and Ter- Fibrosis in the submucosal space has been reported as a factor esa García Morales (REDCapTM manager). Glòria Fernández‐Espar- for difficulty in other series.16 To overcome difficult ESD procedures, rach had a personal grant from Instituto de Salud Carlos III (PI17/ several endoscopic knives and accessories have been developed 00894). 27,28 including hybrid knives with injection capability or lifting devices. The use of any type of traction (clips, fishing line, rubber band, etc.) D A T A A V A I L A B I L I T Y S T A T E M E NT may also be helpful.27 These alternatives can be used depending on The data that support the findings of this study are available from the the operator's preference and the individual circumstances of each corresponding author upon reasonable request. case. Intraprocedural bleeding is difficult to avoid and occurs in almost O RC I D all ESD.29 In our definition, we did not include the bleeding that stops Gloria Fernández‐Esparrach https://orcid.org/0000-0002-3378- spontaneously or is easily managed with the endoscopic knife. 3940 Although a bleeding that requires other endoscopic treatments such as coagulation forceps or clip placement can be tough to control, R E F E R E N CE S 1. Pimentel‐Nunes P, Dinis‐Ribeiro M, Ponchon T, Repici A, Vieth M, prolongs the duration of the procedure and makes the dissection De Ceglie A, et al. Endoscopic submucosal dissection: European more difficult, it is not considered an adverse event. On the other Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy. hand, a difficult ESD due to severe fibrosis or poor maneuverability 2015;47(09):829–854. https://doi.org/10.1055/s‐0034‐1392882. can also lead to more bleeding episodes due to an impaired visibility 2. Lee SS, Chung HY, Kwon OK, Yu W. Quality of life in cancer survivors 5 years or more after total gastrectomy: a case‐control study. Int J or uncontrolled movements. Surg. 2014;12(7):700–5. https://doi.org/10.1016/j.ijsu.2014.05.067. Most of variables associated with difficult gastric ESD (such as 3. Libânio D, Braga V, Ferraz S, Castro R, Lage J, Pita I, et al. Pro- fibrosis, poor maneuverability, or submucosal invasive cancer) cannot spective comparative study of endoscopic submucosal dissection be determined before starting the procedure.16,30,31 We did not and gastrectomy for early neoplastic lesions including patients’ identify any independent pre‐procedural factor that predicted a perspectives. Endoscopy. 2019;51(01):30–9. https://doi.org/10. 1055/a‐0628‐6601. difficult gastric ESD. However, there was an association between 4. Cao Y, Liao C, Tan A, Gao Y, Mo Z, Gao F. Meta‐analysis of endo- difficulty and location in the upper/middle stomach in the univariate scopic submucosal dissection versus endoscopic mucosal resec- analysis. As expected, ESD of lesions located in the upper and middle tion for tumors of the gastrointestinal tract. Endoscopy. stomach was also associated with longer procedural time, especially 2009;41(9):751–7. https://doi.org/10.1055/s‐0029‐1215053. 5. Pimentel‐Nunes P, Pioche M, Albéniz E, Berr F, Deprez P, Ebigbo A. in the case of epithelial lesions. et al. Curriculum for endoscopic submucosal dissection training in The main strength of our study is the representation of the real Europe: European Society of Gastrointestinal Endoscopy (ESGE) practice of ESD in Spain with a registry that included consecutive Position Statement. Endoscopy. 2019;51(10):980–992. https://doi. cases performed by multiple operators with variable level of training. org/10.1055/a‐0996‐0912. 6. World Health Organization. Cancer Today. International Agency for To our knowledge, this is the only registry published in Europe in Research on Cancer. 2020. https://gco.iarc.fr/today/home which all endoscopists performing ESD in the country have 7. Ribeiro‐Mourão F, Pimentel‐Nunes P, Dinis‐Ribeiro M. Endoscopic participated. submucosal dissection for gastric lesions: results of an European The present study has some limitations. First, the relatively inquiry. 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