Western outcomes of circumferential endoscopic submucosal dissection for early esophageal squamous cell carcinoma.

BACKGROUND AND AIMS: Circumferential endoscopic submucosal dissection (cESD) in the esophagus has been reported to be feasible in small Eastern case series. We assessed the outcomes of cESD in the treatment of early esophageal squamous cell carcinoma (ESCC) in Western countries. METHODS: We conducted an international study at 25 referral centers in Europe and Australia using prospective databases. We included all patients with ESCC treated with cESD before November 2022. Our main outcomes were curative resection according to European guidelines and adverse events. RESULTS: A total of 171 cESDs were performed on 165 patients. En bloc and R0 resections rates were 98.2% (95% confidence interval [CI], 95.0-99.4) and 69.6% (95% CI, 62.3-76.0), respectively. Curative resection was achieved in 49.1% (95% CI, 41.7-56.6) of the lesions. The most common reason for noncurative resection was deep submucosal invasion (21.6%). The risk of stricture requiring 6 or more dilations or additional techniques (incisional therapy/stent) was high (71%), despite the use of prophylactic measures in 93% of the procedures. The rates of intraprocedural perforation, delayed bleeding, and adverse cardiorespiratory events were 4.1%, 0.6%, and 4.7%, respectively. Two patients died (1.2%) of a cESD-related adverse event. Overall and disease-free survival rates at 2 years were 91% and 79%. CONCLUSIONS: In Western referral centers, cESD for ESCC is curative in approximately half of the lesions. It can be considered a feasible treatment in selected patients. Our results suggest the need to improve patient selection and to develop more effective therapies to prevent esophageal strictures.

Colorectal polypectomy and endoscopic mucosal resection: European Society of Gastrointestinal Endoscopy (ESGE) Guideline - Update 2024.

1: ESGE recommends cold snare polypectomy (CSP), to include a clear margin of normal tissue (1-2 mm) surrounding the polyp, for the removal of diminutive polyps (≤ 5 mm).Strong recommendation, high quality of evidence. 2: ESGE recommends against the use of cold biopsy forceps excision because of its high rate of incomplete resection.Strong recommendation, moderate quality of evidence. 3: ESGE recommends CSP, to include a clear margin of normal tissue (1-2 mm) surrounding the polyp, for the removal of small polyps (6-9 mm).Strong recommendation, high quality of evidence. 4: ESGE recommends hot snare polypectomy for the removal of nonpedunculated adenomatous polyps of 10-19 mm in size.Strong recommendation, high quality of evidence. 5: ESGE recommends conventional (diathermy-based) endoscopic mucosal resection (EMR) for large (≥ 20 mm) nonpedunculated adenomatous polyps (LNPCPs).Strong recommendation, high quality of evidence. 6: ESGE suggests that underwater EMR can be considered an alternative to conventional hot EMR for the treatment of adenomatous LNPCPs.Weak recommendation, moderate quality of evidence. 7: Endoscopic submucosal dissection (ESD) may also be suggested as an alternative for removal of LNPCPs of ≥ 20 mm in selected cases and in high-volume centers.Weak recommendation, low quality evidence. 8: ESGE recommends that, after piecemeal EMR of LNPCPs by hot snare, the resection margins should be treated by thermal ablation using snare-tip soft coagulation to prevent adenoma recurrence.Strong recommendation, high quality of evidence. 9: ESGE recommends (piecemeal) cold snare polypectomy or cold EMR for SSLs of all sizes without suspected dysplasia.Strong recommendation, moderate quality of evidence. 10: ESGE recommends prophylactic endoscopic clip closure of the mucosal defect after EMR of LNPCPs in the right colon to reduce to reduce the risk of delayed bleeding.Strong recommendation, high quality of evidence. 11: ESGE recommends that en bloc resection techniques, such as en bloc EMR, ESD, endoscopic intermuscular dissection, endoscopic full-thickness resection, or surgery should be the techniques of choice in cases with suspected superficial invasive carcinoma, which otherwise cannot be removed en bloc by standard polypectomy or EMR.Strong recommendation, moderate quality of evidence.

Predicting residual neoplasia after a non-curative gastric ESD: validation and modification of the eCura system in the Western setting: the W-eCura score.

OBJECTIVE: To evaluate the risk factors for lymph node metastasis (LNM) after a non-curative (NC) gastric endoscopic submucosal dissection (ESD) and to validate and eventually refine the eCura scoring system in the Western setting. Also, to assess the rate and risk factors for parietal residual disease. DESIGN: Retrospective multicentre multinational study of prospectively collected registries from 19 Western centres. Patients who had been submitted to surgery or had at least one follow-up endoscopy were included. The eCura system was applied to assess its accuracy in the Western setting, and a modified version was created according to the results (W-eCura score). The discriminative capacities of the eCura and W-eCura scores to predict LNM were assessed and compared. RESULTS: A total of 314 NC gastric ESDs were analysed (72% high-risk resection (HRR); 28% local-risk resection). Among HRR patients submitted to surgery, 25% had parietal disease and 15% had LNM in the surgical specimen. The risk of LNM was significantly different across the eCura groups (areas under the receiver operating characteristic curve (AUC-ROC) of 0.900 (95% CI 0.852 to 0.949)). The AUC-ROC of the W-eCura for LNM (0.916, 95% CI 0.870 to 0.961; p=0.012) was significantly higher compared with the original eCura. Positive vertical margin, lymphatic invasion and younger age were associated with a higher risk of parietal residual lesion in the surgical specimen. CONCLUSION: The eCura scoring system may be applied in Western countries to stratify the risk of LNM after a gastric HRR. A new score is proposed that may further decrease the number of unnecessary surgeries.

Metachronous lesions after gastric endoscopic submucosal dissection: first assessment of the FAMISH prediction score.

BACKGROUND: Surveillance after gastric endoscopic submucosal dissection (ESD) is recommended for all patients owing to the persistent risk of metachronous gastric lesions (MGLs). We developed and validated a prediction score to estimate MGL risk after ESD for early neoplastic gastric lesions, to define an individualized and cost-saving approach. METHODS: Clinical predictors and a risk score were derived from meta-analysis data. A retrospective, single-center, cohort study including patients with ≥ 3 years of standardized surveillance after ESD was conducted for score validation. Predictive accuracy of the score by the area under the receiver operating characteristic curve (AUC) was assessed and cumulative probabilities of MGL were estimated. RESULTS: The risk score (0-9 points) included six clinical predictors (scored 0-3): positive family history of gastric cancer, older age, male sex, corpus intestinal metaplasia, synchronous gastric lesions, and persistent Helicobacter pylori infection (FAMISH). The study population included 263 patients. The MGL rate was 16 %. The score diagnostic accuracy for predicting MGL at 3 years' follow-up, measured by the AUC, was 0.704 (95 %CI 0.603-0.806). At 3 years and a cutoff < 2, the score achieved maximal sensitivity and negative predictive value; 15 % of patients could be assigned to a low-risk group, in which the progression to MGL was significantly lower than for the high-risk group (P = 0.04). CONCLUSION: The FAMISH score might be a useful tool to accurately identify patients with low-to-intermediate risk for MGL at 3 years of follow-up who could have surveillance intervals extended to reduce the burden of care.

Endoscopic submucosal dissection techniques and technology: European Society of Gastrointestinal Endoscopy (ESGE) Technical Review.

ESGE suggests conventional endoscopic submucosal dissection (ESD; marking and mucosal incision followed by circumferential incision and stepwise submucosal dissection) for most esophageal and gastric lesions. ESGE suggests tunneling ESD for esophageal lesions involving more than two-thirds of the esophageal circumference. ESGE recommends the pocket-creation method for colorectal ESD, at least if traction devices are not used. The use of dedicated ESD knives with size adequate to the location/thickness of the gastrointestinal wall is recommended. It is suggested that isotonic saline or viscous solutions can be used for submucosal injection. ESGE recommends traction methods in esophageal and colorectal ESD and in selected gastric lesions. After gastric ESD, coagulation of visible vessels is recommended, and post-procedural high dose proton pump inhibitor (PPI) (or vonoprazan). ESGE recommends against routine closure of the ESD defect, except in duodenal ESD. ESGE recommends corticosteroids after resection of  > 50 % of the esophageal circumference. The use of carbon dioxide when performing ESD is recommended. ESGE recommends against the performance of second-look endoscopy after ESD. ESGE recommends endoscopy/colonoscopy in the case of significant bleeding (hemodynamic instability, drop in hemoglobin > 2 g/dL, severe ongoing bleeding) to perform endoscopic hemostasis with thermal methods or clipping; hemostatic powders represent rescue therapies. ESGE recommends closure of immediate perforations with clips (through-the-scope or cap-mounted, depending on the size and shape of the perforation), as soon as possible but ideally after securing a good plane for further dissection.

A rare case of an esophageal neuroendocrine carcinoma arising on an endoscopic resection scar.

Here we report a case of a 61-year-old woman who underwent en-bloc endoscopic submucosal dissection (ESD) of a 10mm depressed lesion (Paris 0-IIc, Figure A) in the mid-esophagus. Histopathology showed a lesion with high-grade squamous dysplasia (R0). On follow-up endoscopy at 6 and 12 months the scar was regular, without signs of recurrence. Seven months after the last endoscopy, the patient presented with chest pain and dysphagia. Endoscopy showed an ulcero-vegetating tumor with 3cm at the same location of previous ESD (Figure B), and biopsies showed a poorly differentiated small cell neuroendocrine carcinoma (NEC). Subsequent computed tomography identified peri-tumor and hilar lymph nodes, and an extensive periceliac nodal conglomerate adherent to the liver (stage IV). This is, to our knowledge, the first case described of esophageal NEC arising on the endoscopic resection scar.

Spontaneous regression of a rectal cancer.

A 42-year-old woman underwent a total colonoscopy due to haematochezia and weight loss. A rectal lateral spreading lesion with 2 5mm in diameter was identified and biopsies revealed villous adenoma with high-grade dysplasia. After referral to our centre, sigmoidoscopy confirmed the presence of a 25 mm lesion (NICE 3) with non-lifting sign and EUS showed a hypoechoic lesion with at least submucosal invasion and suspicious images of muscularis propria invasion - uT1/2N0. New biopsies shown the presence of adenocarcinoma. The patient was submitted to surgical anterior resection of the rectum. Intraoperative extemporaneous examination of the specimen did not identify the lesion and an intraoperative colonoscopy was performed not showing any lesion in the rectal stump. Pathological examination, after total inclusion of the specimen, showed a 7mm scar with fibrosis of the submucosa, chronic inflammatory infiltrate, vascular ectasia and congestion and mucosal erosion, without identification of residual neoplasia.To date (20 months of follow-up) there is no evidence of disease persistence or recurrence with a sigmoidoscopy performed 3 months after surgery.

Risk factors for gastric metachronous lesions after endoscopic or surgical resection: a systematic review and meta-analysis.

INTRODUCTION : Metachronous gastric lesions (MGL) are a significant concern after both endoscopic and surgical resection for early gastric cancer. Identification of risk factors for MGL could help to individualize surveillance schedules and potentially reduce the burden of care, but data are inconclusive. We aimed to identify risk factors for MGL and compare the incidence after endoscopic resection (ER) and subtotal gastrectomy. METHODS : We conducted a systematic review by searching PubMed, ISI, and Scopus, and performed meta-analysis. RESULTS : 52 studies were included. Pooled cumulative MGL incidence after ER was 9.3 % (95 % confidence interval [CI] 7.7 % to 11.0 %), significantly higher than after subtotal gastrectomy (1.2 %, 95 %CI 0.5 % to 2.2 %). After adjusting for mean follow-up, predicted MGL at 5 years was 9.5 % after ER and 0.7 % after subtotal gastrectomy. Older age (mean difference 1.08 years, 95 %CI 0.21 to 1.96), male sex (odds ratio [OR] 1.43, 95 %CI 1.22 to 1.66), family history of gastric cancer (OR 1.88, 95 %CI 1.03 to 3.41), synchronous lesions (OR 1.72, 95 %CI 1.30 to 2.28), severe gastric mucosal atrophy (OR 2.77, 95 %CI 1.22 to 6.29), intestinal metaplasia in corpus (OR 3.15, 95 %CI 1.67 to 5.96), persistent Helicobacter pylori infection (OR 2.08, 95 %CI 1.60 to 2.72), and lower pepsinogen I/II ratio (mean difference -0.54, 95 %CI -0.86 to -0.22) were significantly associated with MGL after ER. Index lesion characteristics were not significantly associated with MGL. ER treatment was possible in 83.2 % of 914 MGLs (95 %CI 72.2 to 91.9 %). CONCLUSION : Follow-up schedules should be different after ER and subtotal gastrectomy, and individualized further based on diverse risk factors.

Gastric cancer incidence and mortality trends 2007-2016 in three European countries.

BACKGROUND : Increased awareness of gastric cancer risk, easy access to upper endoscopy, and high definition endoscopes with virtual chromoendoscopy may have led to the increase in early diagnosis of gastric cancer observed in recent years in Europe, which may be associated with improved survival. Currently, no data exist on the impact of early diagnosis on survival at a populational level in Europe. Our aim was to assess gastric cancer incidence, early diagnosis, and survival in northwestern and southern European countries with a low-to-moderate incidence of gastric cancer. METHODS : Data on 41 138 gastric cancers diagnosed in 2007-2016 were retrieved from national cancer registries of Belgium, the Netherlands, and northern Portugal. Age-standardized incidence and mortality rates were assessed and expressed per 100 000 person-years. Early diagnosis was defined as T1 tumors. Net survival estimates for 2007-2011 vs. 2012-2016 were compared. RESULTS : Age-standardized incidence and mortality decreased over time in Belgium, northern Portugal, and the Netherlands (relative incidence decrease 8.6 %, 4.5 %, and 46.8 %, respectively; relative mortality decrease 22.0 %, 30.9 %, and 50.0 %, respectively). Early gastric cancer diagnosis increased over time for all countries. Net 1-year survival improved significantly between the two time periods in all countries, and at 5 years in Belgium and Portugal. CONCLUSIONS : This is the first study comparing trends (2007-2016) in gastric cancer incidence and mortality in some European countries. We found an increasing proportion of T1 gastric cancers and a decrease in age-standardized mortality over time, supporting the use of secondary prevention strategies.

Endoscopic submucosal dissection for superficial gastrointestinal lesions: European Society of Gastrointestinal Endoscopy (ESGE) Guideline - Update 2022.

ESGE recommends that the evaluation of superficial gastrointestinal (GI) lesions should be made by an experienced endoscopist, using high definition white-light and chromoendoscopy (virtual or dye-based).ESGE does not recommend routine performance of endoscopic ultrasonography (EUS), computed tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET)-CT prior to endoscopic resection.ESGE recommends endoscopic submucosal dissection (ESD) as the treatment of choice for most superficial esophageal squamous cell and superficial gastric lesions.For Barrett's esophagus (BE)-associated lesions, ESGE suggests the use of ESD for lesions suspicious of submucosal invasion (Paris type 0-Is, 0-IIc), for malignant lesions > 20 mm, and for lesions in scarred/fibrotic areas.ESGE does not recommend routine use of ESD for duodenal or small-bowel lesions.ESGE suggests that ESD should be considered for en bloc resection of colorectal (but particularly rectal) lesions with suspicion of limited submucosal invasion (demarcated depressed area with irregular surface pattern or a large protruding or bulky component, particularly if the lesions are larger than 20 mm) or for lesions that otherwise cannot be completely removed by snare-based techniques.ESGE recommends that an en bloc R0 resection of a superficial GI lesion with histology no more advanced than intramucosal cancer (no more than m2 in esophageal squamous cell carcinoma), well to moderately differentiated, with no lymphovascular invasion or ulceration, should be considered a very low risk (curative) resection, and no further staging procedure or treatment is generally recommended.ESGE recommends that the following should be considered to be a low risk (curative) resection and no further treatment is generally recommended: an en bloc R0 resection of a superficial GI lesion with superficial submucosal invasion (sm1), that is well to moderately differentiated, with no lymphovascular invasion, of size ≤ 20 mm for an esophageal squamous cell carcinoma or ≤ 30 mm for a stomach lesion or of any size for a BE-related or colorectal lesion, and with no lymphovascular invasion, and no budding grade 2 or 3 for colorectal lesions.ESGE recommends that, after an endoscopically complete resection, if there is a positive horizontal margin or if resection is piecemeal, but there is no submucosal invasion and no other high risk criteria are met, this should be considered a local-risk resection and endoscopic surveillance or re-treatment is recommended rather than surgery or other additional treatment.ESGE recommends that when there is a diagnosis of lymphovascular invasion, or deeper infiltration than sm1, or positive vertical margins, or undifferentiated tumor, or, for colorectal lesions, budding grade 2 or 3, this should be considered a high risk (noncurative) resection, and complete staging and strong consideration for additional treatments should be considered on an individual basis in a multidisciplinary discussion.ESGE recommends scheduled endoscopic surveillance with high definition white-light and chromoendoscopy (virtual or dye-based) with biopsies of only the suspicious areas after a curative ESD.

Endoscopists' diagnostic accuracy in detecting upper gastrointestinal neoplasia in the framework of artificial intelligence studies.

BACKGROUND: Estimates on miss rates for upper gastrointestinal neoplasia (UGIN) rely on registry data or old studies. Quality assurance programs for upper GI endoscopy are not fully established owing to the lack of infrastructure to measure endoscopists' competence. We aimed to assess endoscopists' accuracy for the recognition of UGIN exploiting the framework of artificial intelligence (AI) validation studies. METHODS: Literature searches of databases (PubMed/MEDLINE, EMBASE, Scopus) up to August 2020 were performed to identify articles evaluating the accuracy of individual endoscopists for the recognition of UGIN within studies validating AI against a histologically verified expert-annotated ground-truth. The main outcomes were endoscopists' pooled sensitivity, specificity, positive and negative predictive value (PPV/NPV), and area under the curve (AUC) for all UGIN, for esophageal squamous cell neoplasia (ESCN), Barrett esophagus-related neoplasia (BERN), and gastric adenocarcinoma (GAC). RESULTS: Seven studies (2 ESCN, 3 BERN, 1 GAC, 1 UGIN overall) with 122 endoscopists were included. The pooled endoscopists' sensitivity and specificity for UGIN were 82 % (95 % confidence interval [CI] 80 %-84 %) and 79 % (95 %CI 76 %-81 %), respectively. Endoscopists' accuracy was higher for GAC detection (AUC 0.95 [95 %CI 0.93-0.98]) than for ESCN (AUC 0.90 [95 %CI 0.88-0.92]) and BERN detection (AUC 0.86 [95 %CI 0.84-0.88]). Sensitivity was higher for Eastern vs. Western endoscopists (87 % [95 %CI 84 %-89 %] vs. 75 % [95 %CI 72 %-78 %]), and for expert vs. non-expert endoscopists (85 % [95 %CI 83 %-87 %] vs. 71 % [95 %CI 67 %-75 %]). CONCLUSION: We show suboptimal accuracy of endoscopists for the recognition of UGIN even within a framework that included a higher prevalence and disease awareness. Future AI validation studies represent a framework to assess endoscopist competence.

Expected value of artificial intelligence in gastrointestinal endoscopy: European Society of Gastrointestinal Endoscopy (ESGE) Position Statement.

This ESGE Position Statement defines the expected value of artificial intelligence (AI) for the diagnosis and management of gastrointestinal neoplasia within the framework of the performance measures already defined by ESGE. This is based on the clinical relevance of the expected task and the preliminary evidence regarding artificial intelligence in artificial or clinical settings. MAIN RECOMMENDATIONS:: (1) For acceptance of AI in assessment of completeness of upper GI endoscopy, the adequate level of mucosal inspection with AI should be comparable to that assessed by experienced endoscopists. (2) For acceptance of AI in assessment of completeness of upper GI endoscopy, automated recognition and photodocumentation of relevant anatomical landmarks should be obtained in ≥90% of the procedures. (3) For acceptance of AI in the detection of Barrett's high grade intraepithelial neoplasia or cancer, the AI-assisted detection rate for suspicious lesions for targeted biopsies should be comparable to that of experienced endoscopists with or without advanced imaging techniques. (4) For acceptance of AI in the management of Barrett's neoplasia, AI-assisted selection of lesions amenable to endoscopic resection should be comparable to that of experienced endoscopists. (5) For acceptance of AI in the diagnosis of gastric precancerous conditions, AI-assisted diagnosis of atrophy and intestinal metaplasia should be comparable to that provided by the established biopsy protocol, including the estimation of extent, and consequent allocation to the correct endoscopic surveillance interval. (6) For acceptance of artificial intelligence for automated lesion detection in small-bowel capsule endoscopy (SBCE), the performance of AI-assisted reading should be comparable to that of experienced endoscopists for lesion detection, without increasing but possibly reducing the reading time of the operator. (7) For acceptance of AI in the detection of colorectal polyps, the AI-assisted adenoma detection rate should be comparable to that of experienced endoscopists. (8) For acceptance of AI optical diagnosis (computer-aided diagnosis [CADx]) of diminutive polyps (≤5 mm), AI-assisted characterization should match performance standards for implementing resect-and-discard and diagnose-and-leave strategies. (9) For acceptance of AI in the management of polyps ≥ 6 mm, AI-assisted characterization should be comparable to that of experienced endoscopists in selecting lesions amenable to endoscopic resection.

The future of endoscopic resection for early gastric cancer.

Endoscopic resection for early gastric cancer is recommended when the risk of lymph node metastasis is negligible and should be performed through submucosal dissection due to well-established short- and long-term results. To overcome technical difficulties and decrease adverse events some techniques have been studied. This review outlines current strategies for improving patient selection and highlights innovative techniques that help minimize adverse events. Moreover, we discuss how to improve management after curative and noncurative resections.

Gastric cancer screening: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Gastric cancer (GC) screening is recommended in high-risk populations, although screening methods and intervals vary. In intermediate-risk populations, screening through esophagogastroduodenoscopy (EGD) may be considered depending on local resources. The aim of this study was to compare GC screening methods regarding effect on mortality, diagnostic yield and adherence. METHODS: Systematic review and meta-analysis including studies evaluating population-based GC screening. Search was conducted in three online databases (MEDLINE, Scopus and clinicaltrials.gov), along with manual search. RESULTS: Forty-four studies were included. Studies in upper gastrointestinal series (UGIS) demonstrated that GC screening was associated with significantly lower GC mortality rates (OR 0.63, 95% CI 0.55 - 0.73). Benefits on mortality were also found in EGD and serum pepsinogen (PG) studies. EGD was associated with significantly higher GC (0.55%, 95% CI 0.39 - 0.75%) and early-GC (EGC) detection rates (0.48%, 95% CI 0.34 - 0.65%) when compared to UGIS (GC 0.19%, 95% CI 0.10 - 0.31%; EGC 0.08%, 95% CI 0.04 - 0.13%) and PG (GC 0.10%, 95% CI 0.05 - 0.16%; EGC 0.10%, 95% CI 0.04 - 0.19%). Non-invasive methods tended to higher adherence rates when compared to EGD. Regardless of the screening method, individualized recruitment performed better. DISCUSSION: Screening positively impacted GC mortality rates. EGD was associated with higher diagnostic yield, while UGIS and PG tended to higher adherence rates. Screening uptake was predominantly impacted by recruitment strategies independently of the adopted method.

Best additional management after non-curative endoscopic resection of esophageal squamous cell carcinoma: a systematic review and meta-analysis.

INTRODUCTION: Endoscopic resection (ER) is an accepted first-line treatment for superficial esophageal squamous cell carcinoma (ESCC), but when curative resection is not achieved, further treatment is not standardised. We aimed at evaluating outcomes of management strategies (esophagectomy, chemoradiotherapy/radiotherapy (CRT/RT) or follow-up (FUP)) after a non-curative ESCC ER. METHODS: A systematic review was performed evaluating outcomes of different management strategies after ESCC submitted to primary ER (T1a/T1b), without curative criteria (R1/Rx, T1a-m3/T1b, lymphovascular invasion (LVI) or poor differentiation). Primary outcomes included recurrence, overall survival (OS) and cancer-specific survival (CSS). Secondary outcomes consisted of treatment-related adverse events. RESULTS: Seventeen studies were included for qualitative analysis (16 observational and 1 randomized controlled trial) including 788 patients with ESCC submitted to ER, managed by additional CRT/RT (n = 530), surgery (n = 98) or FUP (n = 160). Eight studies suited quantitative analysis. Patients only followed up after ER experienced recurrence rates of 0-36.4% (OR 3.6 (95%CI 1.06-12.20) vs further treatments). When submitted to CRT/RT following non-curative ER, recurrence was observed in 0-27.2% (OR 8.00 (95%CI 1.74-36.80) whereas after surgery no recurrence was noticeable. Reported 5 y-OS after CRT/RT for non-curative ER ranged among 75-100% whereas, for those offered surgeries, 5 y-OS was 89.5%. OS ranged between 54.5% and 100% after FUP. CRT/RT and surgery-related adverse events ranged from 0% to 32% and 14% to 28.5%. CONCLUSIONS: Additional treatment should be provided in ESCC after non-curative ER. Adjuvant esophagectomy might be the preferred treatment to medically fit patients with high-risk features (namely LVI). Properly designed trials assessing the role of CRT/RT are needed to manage these patients.

Revising the European Society of Gastrointestinal Endoscopy (ESGE) research priorities: a research progress update.

BACKGROUND: One of the aims of the European Society of Gastrointestinal Endoscopy (ESGE) is to encourage high quality endoscopic research at a European level. In 2016, the ESGE research committee published a set of research priorities. As endoscopic research is flourishing, we aimed to review the literature and determine whether endoscopic research over the last 4 years had managed to address any of our previously published priorities. METHODS: As the previously published priorities were grouped under seven different domains, a working party with at least two European experts was created for each domain to review all the priorities under that domain. A structured review form was developed to standardize the review process. The group conducted an extensive literature search relevant to each of the priorities and then graded the priorities into three categories: (1) no longer a priority (well-designed trial, incorporated in national/international guidelines or adopted in routine clinical practice); (2) remains a priority (i. e. the above criterion was not met); (3) redefine the existing priority (i. e. the priority was too vague with the research question not clearly defined). RESULTS: The previous ESGE research priorities document published in 2016 had 26 research priorities under seven domains. Our review of these priorities has resulted in seven priorities being removed from the list, one priority being partially removed, another seven being redefined to make them more precise, with eleven priorities remaining unchanged. This is a reflection of a rapid surge in endoscopic research, resulting in 27 % of research questions having already been answered and another 27 % requiring redefinition. CONCLUSIONS: Our extensive review process has led to the removal of seven research priorities from the previous (2016) list, leaving 19 research priorities that have been redefined to make them more precise and relevant for researchers and funding bodies to target.

Gastric microbiome profile throughout gastric carcinogenesis: beyond helicobacter.

BACKGROUND: Gastric dysbiosis has been hinted as a potential cause of gastric cancer. However, changes in microbiome throughout the major stages of gastric carcinogenesis remain mostly unknown. OBJECTIVE: To describe gastric microbiome at different stages, analysing for the first time dysbiosis specifically in patients with early gastric cancer (EGC). METHODS: Cross-sectional study including patients (n = 77) with endoscopically and histologically confirmed normal stomachs (controls; n = 25), advanced atrophic gastritis with intestinal metaplasia (IM; n = 18) and EGC (n = 34). Endoscopic biopsies from antrum and corpus (n = 154) were analyzed. Next-generation sequencing was performed characterizing microbial communities down to the species level based on full-length 16SrRNA gene profiling. RESULTS: Significant differences were found in the microbiome profile between the groups. Firmicutes were more frequent (p = .012) and Proteobacteria were less frequent (p = .04) both in the IM and EGC when comparing to controls. Relative frequency of Helicobacter pylori, when present, was much higher in the controls (83%) when comparing to the other groups (IM 1%, EGC 27%; p = .006), being the dominant bacteria only in the controls. Dysbiosis was present already and more significantly at the IM stage, with two bacteria progressively increasing from controls to IM then to cancer: Gemella from 1.48 to 3.9% (p = .014); and Streptococcus from 19.3 to 33.7% (p = .04), being the EGC dominant bacteria. CONCLUSIONS: Our results confirm Helicobacter pylori dominancy in non-atrophic stomachs and progressive dysbiosis throughout gastric carcinogenesis. Gemella but particularly Streptococcus is significantly increased in patients with EGC. Specific modulation of these bacteria may change gastric cancer risk.

Endoscopic submucosal dissection (ESD): how do Western endoscopists value animal models?

INTRODUCTION: Endoscopic Submucosal Dissection (ESD)was introduced in the West later than in the East. Our aim was to assess how Western endoscopists performing ESD have been trained and how they value animal models for training. MATERIAL AND METHODS: An online survey regarding training in ESD was sent to Western endoscopists who published articles on advanced resection techniques. RESULTS: From 279 endoscopists, 58 (21%) completed the questionnaire, of which 50 confirmed performance of clinical ESD. Endoscopists had a median of 15 years of endoscopic experience (IQR 9.75-20.25) and all of them were performing conventional EMR, before starting ESD. Prior to clinical ESD, 74% (n = 37) underwent training with ex vivo models, 84% (n = 42) with live animal models and 92% (n = 46) with at least, one of the two models. After starting clinical ESD, as trainers, 52% (n = 26) were involved with ex vivo and 60% (n = 30) with live animal models. Personal usefulness of ex vivo and live animal models was rated with a median of 9 (IQR 8-10) and 10 (IQR 8-10), out of 10, respectively. Courses with ex vivo and live animal models were considered a prerequisite before clinical practice by 84% (n = 42) and 78% (n = 39), respectively. CONCLUSIONS: Western endoscopists have extensive endoscopic experience before starting ESD. The majority had pre-clinical training with ex vivo and live animal models and more than half are acting as trainers of other endoscopists with these models. Animal models are considered very useful and deemed a prerequisite before clinical practice by the majority of the endoscopists.

Original Article: MicroRNA Dysregulation in the Gastric Carcinogenesis Cascade: Can We Anticipate Its Role in Individualized Care?

BACKGROUND: Gastric carcinogenesis progresses from normal mucosa, atrophic/metaplastic gastritis, and dysplasia to adenocarcinoma. MicroRNAs (miRNAs) regulate DNA expression and have been implicated; however, their role is not fully established. AIMS: The aim of this study was to characterize plasma and tissue expression of several miRNAs in gastric carcinogenesis stages. METHODS: Single-center cross-sectional study in 64 patients: 19 controls (normal mucosa); 15 with extensive atrophic/metaplastic gastritis; and 30 with early gastric neoplasia (EGN). Seven miRNAs (miR-21, miR-146a, miR-181b, miR-370, miR-375, miR 181b, and miR-490) were quantified by real time-qPCR in peripheral blood and endoscopic biopsy samples. RESULTS: We found a significant upregulation of miR-181b, miR-490, and miR-21 in the EGN mucosa (overexpression 2-14-times higher than controls). We observed a significant underexpression of miR-146a and miR-370 in atrophic/metaplastic gastritis (86 and 66% decrease, p = 0.008 and p = 0.001) and in EGN (89 and 62% reduction, p = 0.034 and p = 0.032) compared with controls. There were no differences between lesions and nonneoplastic mucosa and no dysregulation of plasma miRNAs. CONCLUSION: We found significant dysregulation of 5 miRNAs in gastric carcinogenesis, suggesting a tumor suppressor role for miR-146a and miR-370 and oncogenic potential for miR-21, miR-181, and miR-490. These changes happen diffusely in the gastric mucosa, suggesting a high-risk field defect, which may influence these patients' surveillance.

Endoscopic grading of gastric intestinal metaplasia on risk assessment for early gastric neoplasia: can we replace histology assessment also in the West?

OBJECTIVES: To assess the value of endoscopic grading of gastric intestinal metaplasia (EGGIM), operative link on gastritis assessment (OLGA) and operative link on gastric intestinal metaplasia (OLGIM) on risk stratification for early gastric neoplasia (EGN) and to investigate other factors possibly associated with its development. DESIGN: Single centre, case-control study including 187 patients with EGN treated endoscopically and 187 age-matched and sex-matched control subjects. Individuals were classified according to EGGIM, OLGA and OLGIM systems. EGN risk according to gastritis stages and other clinical parameters was further evaluated. RESULTS: More patients with EGN had EGGIM of ≥5 than control subjects (68.6% vs 13.3%, p<0.001). OLGA and OLGIM stages III/IV were more prevalent in patients with EGN than in control subjects (68% vs 11%, p<0.001, and 61% vs 3%, p<0.001, respectively). The three systems were the only parameters significantly related to the risk of EGN in multivariate analysis: for EGGIM 1-4 (adjusted OR (AOR) 12.9, 95% CI 1.4 to 118.6) and EGGIM 5-10 (AOR 21.2, 95% CI 5.0 to 90.2); for OLGA I/II (AOR 5.0, 95% CI 0.56 to 44.5) and OLGA III/IV (AOR 11.1, 95% CI 3.7 to 33.1); for OLGIM I/II (AOR 11.5, 95% CI 4.1 to 32.3) and OLGIM III/IV (AOR 16.0, 95% CI 7.6 to 33.4). CONCLUSION: This study confirms the role of histological assessment as an independent risk factor for gastric cancer (GC), but it is the first study to show that an endoscopic classification of gastric intestinal metaplasia is highly associated with that outcome. After further prospective validation, this classification may be appropriate for GC risk stratification and may simplify every day practice by reducing the need for biopsies.