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.

Curriculum for training in endoscopic mucosal resection in the colon: European Society of Gastrointestinal Endoscopy (ESGE) Position Statement.

Endoscopic mucosal resection (EMR) is the standard of care for the complete removal of large (≥ 10 mm) nonpedunculated colorectal polyps (LNPCPs). Increased detection of LNPCPs owing to screening colonoscopy, plus high observed rates of incomplete resection and need for surgery call for a standardized approach to training in EMR. 1 : Trainees in EMR should have achieved basic competence in diagnostic colonoscopy, < 10-mm polypectomy, pedunculated polypectomy, and common methods of gastrointestinal endoscopic hemostasis. The role of formal training courses is emphasized. Training may then commence in vivo under the direct supervision of a trainer. 2 : Endoscopy units training endoscopists in EMR should have specific processes in place to support and facilitate training. 3: A trained EMR practitioner should have mastered theoretical knowledge including how to assess an LNPCP for risk of submucosal invasion, how to interpret the potential difficulty of a particular EMR procedure, how to decide whether to remove a particular LNPCP en bloc or piecemeal, whether the risks of electrosurgical energy can be avoided for a particular LNPCP, the different devices required for EMR, management of adverse events, and interpretation of reports provided by histopathologists. 4: Trained EMR practitioners should be familiar with the patient consent process for EMR. 5: The development of endoscopic non-technical skills (ENTS) and team interaction are important for trainees in EMR. 6: Differences in recommended technique exist between EMR performed with and without electrosurgical energy. Common to both is a standardized technique based upon dynamic injection, controlled and precise snare placement, safety checks prior to the application of tissue transection (cold snare) or electrosurgical energy (hot snare), and interpretation of the post-EMR resection defect. 7: A trained EMR practitioner must be able to manage adverse events associated with EMR including intraprocedural bleeding and perforation, and post-procedural bleeding. Delayed perforation should be avoided by correct interpretation of the post-EMR defect and treatment of deep mural injury. 8: A trained EMR practitioner must be able to communicate EMR procedural findings to patients and provide them with a plan in case of adverse events after discharge and a follow-up plan. 9: A trained EMR practitioner must be able to detect and interrogate a post-endoscopic resection scar for residual or recurrent adenoma and apply treatment if necessary. 10: Prior to independent practice, a minimum of 30 EMR procedures should be performed, culminating in a trainer-guided assessment of competency using a validated assessment tool, taking account of procedural difficulty (e. g. using the SMSA polyp score). 11: Trained practitioners should log their key performance indicators (KPIs) of polypectomy during independent practice. A guide for target KPIs is provided in this document.

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.

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.

Endoscopic management of subepithelial lesions including neuroendocrine neoplasms: European Society of Gastrointestinal Endoscopy (ESGE) Guideline.

1: ESGE recommends endoscopic ultrasonography (EUS) as the best tool to characterize subepithelial lesion (SEL) features (size, location, originating layer, echogenicity, shape), but EUS alone is not able to distinguish among all types of SEL.Strong recommendation, moderate quality evidence. 2: ESGE suggests providing tissue diagnosis for all SELs with features suggestive of gastrointestinal stromal tumor (GIST) if they are of size > 20 mm, or have high risk stigmata, or require surgical resection or oncological treatment.Weak recommendation, very low quality evidence. 3: ESGE recommends EUS-guided fine-needle biopsy (EUS-FNB) or mucosal incision-assisted biopsy (MIAB) equally for tissue diagnosis of SELs ≥ 20 mm in size.Strong recommendation, moderate quality evidence. 4: ESGE recommends against surveillance of asymptomatic gastrointestinal (GI) tract leiomyomas, lipomas, heterotopic pancreas, granular cell tumors, schwannomas, and glomus tumors, if the diagnosis is clear.Strong recommendation, moderate quality evidence. 5: ESGE suggests surveillance of asymptomatic esophageal and gastric SELs without definite diagnosis, with esophagogastroduodenoscopy (EGD) at 3-6 months, and then at 2-3-year intervals for lesions < 10 mm in size, and at 1-2-year intervals for lesions 10-20 mm in size. For asymptomatic SELs > 20 mm in size that are not resected, ESGE suggests surveillance with EGD plus EUS at 6 months and then at 6-12-month intervals.Weak recommendation, very low quality evidence. 6: ESGE recommends endoscopic resection for type 1 gastric neuroendocrine neoplasms (g-NENs) if they grow larger than 10 mm. The choice of resection technique should depend on size, depth of invasion, and location in the stomach.Strong recommendation, low quality evidence. 7: ESGE suggests considering removal of histologically proven gastric GISTs smaller than 20 mm as an alternative to surveillance. The decision to resect should be discussed in a multidisciplinary meeting. The choice of technique should depend on size, location, and local expertise.Weak recommendation, very low quality evidence. 8: ESGE suggests that, to avoid unnecessary follow-up, endoscopic resection is an option for gastric SELs smaller than 20 mm and of unknown histology after failure of attempts to obtain diagnosis.Weak recommendation, very low quality evidence. 9: ESGE recommends basing the surveillance strategy on the type and completeness of resection. After curative resection of benign SELs no follow-up is advised, except for type 1 gastric NEN for which surveillance at 1-2 years is advised.Strong recommendation, low quality evidence. 10: For lower or upper GI NEN with a positive or indeterminate margin at resection, ESGE recommends repeating endoscopy at 3-6 months and another attempt at endoscopic resection in the case of residual disease.Strong recommendation, low quality evidence.

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.

Multichannel photodissociation dynamics in CS2 studied by ultrafast electron diffraction.

The structural dynamics of photoexcited gas-phase carbon disulfide (CS2) molecules are investigated using ultrafast electron diffraction. The dynamics were triggered by excitation of the optically bright 1B2(1Σu+) state by an ultraviolet femtosecond laser pulse centred at 200 nm. In accordance with previous studies, rapid vibrational motion facilitates a combination of internal conversion and intersystem crossing to lower-lying electronic states. Photodissociation via these electronic manifolds results in the production of CS fragments in the electronic ground state and dissociated singlet and triplet sulphur atoms. The structural dynamics are extracted from the experiment using a trajectory-fitting filtering approach, revealing the main characteristics of the singlet and triplet dissociation pathways. Finally, the effect of the time-resolution on the experimental signal is considered and an outlook to future experiments provided.

Incorporating mitogenome sequencing into integrative taxonomy: The multidisciplinary redescription of the ciliate Thuricola similis (Peritrichia, Vaginicolidae) provides new insights into the evolutionary relationships among Oligohymenophorea subclasses.

The evolutionary relationships among Oligohymenophorea subclasses are under debate as the phylogenomic analysis using a large dataset of nuclear coding genes is significantly different to the 18S rDNA phylogeny, and it is unfortunately not stable within and across different published studies. In addition to nuclear genes, the faster-evolving mitochondrial genes have also shown the ability to solve phylogenetic problems in many ciliated taxa. However, due to the paucity of mitochondrial data, the corresponding work is scarce, let alone the phylogenomic analysis based on mitochondrial gene dataset. In this work, we presented the characterization on Thuricola similis Bock, 1963, a loricate peritrich (Oligohymenophorea), incorporating mitogenome sequencing into integrative taxonomy. As the first mitogenome for the subclass Peritrichia, it is linear, 38,802 bp long, and contains two rRNAs, 12 tRNAs, and 43 open reading frames (ORFs). As a peculiarity, it includes a central repeated region composed of tandemly repeated A-T rich units working as a bi-transcriptional start. Moreover, taking this opportunity, the phylogenomic analyses based on a set of mitochondrial genes were also performed, revealing that T. similis, as a representative of Peritrichia subclass, branches basally to other three Oligohymenophorea subclasses, namely Hymenostomatia, Peniculia, and Scuticociliatia. Evolutionary relationships among those Oligohymenophorea subclasses were discussed, also in the light of recent phylogenomic reconstructions based on a set of nuclear genes. Besides, as a little-known species, T. similis was also redescribed and neotypified based on data from two populations collected from wastewater treatment plants (WWTPs) in Brazil and Italy, by means of integrative methods (i.e., living observation, silver staining methods, scanning and transmission electron microscopy, and 18S rDNA phylogeny). After emended diagnosis, it is characterized by: (1) the sewage habitat; (2) the lorica with a single valve and small undulations; (3) the 7-22 µm-long inner stalk; and (4) the presence of only a single postciliary microtubule on the left side of the aciliferous row in the haplokinety. Among Vaginicolidae family, our 18S rRNA gene-based phylogenetic analysis revealed that Thuricola and Cothurnia are monophyletic genera, and Vaginicola could be a polyphyletic genus.

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.

Ciliate Diversity From Aquatic Environments in the Brazilian Atlantic Forest as Revealed by High-Throughput DNA Sequencing.

Rainforest aquatic ecosystems include complex habitats with scarce information on their unicellular eukaryote diversity and community structure. We have investigated the diversity of ciliates in freshwater and brackish environments along the Brazilian Atlantic Forest, based on the hypervariable V4 region of the 18S-rDNA obtained by high-throughput DNA sequencing. Our analyses detected 409 ciliate taxonomic units (OTUs), mostly attributed to the classes Oligohymenophorea and Spirotrichea. A total of 11 classes, 12 subclasses, 112 genera, and 144 species were reported. We found the following: (a) the ciliate communities are more diverse in freshwater- than in Atlantic Forest-associated brackish environments; (b) the ciliate communities are composed by a small amount of highly abundant OTUs, but a high number of low-abundant or rare OTUs; (c) nearly one-third of the ciliate OTUs share less than 97% sequence identity to reference sequences and (d) phylogenetic inference supports the hypothesis that the V4 region of the Ciliophora 18S-rDNA is a suitable marker for accurate evolutionary inferences at class level. Our results showed that a considerable fraction of the HTS-detected diversity of ciliates from Brazilian Atlantic Forest is not represented in the currently available molecular databases.

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.

IDN2 Interacts with RPA and Facilitates DNA Double-Strand Break Repair by Homologous Recombination in Arabidopsis.

Repair of DNA double-strand breaks (DSBs) is critical for the maintenance of genome integrity. We previously showed that DSB-induced small RNAs (diRNAs) facilitate homologous recombination-mediated DSB repair in Arabidopsis thaliana Here, we show that INVOLVED IN DE NOVO2 (IDN2), a double-stranded RNA binding protein involved in small RNA-directed DNA methylation, is required for DSB repair in Arabidopsis. We find that IDN2 interacts with the heterotrimeric replication protein A (RPA) complex. Depletion of IDN2 or the diRNA binding ARGONAUTE2 leads to increased accumulation of RPA at DSB sites and mislocalization of the recombination factor RAD51. These findings support a model in which IDN2 interacts with RPA and facilitates the release of RPA from single-stranded DNA tails and subsequent recruitment of RAD51 at DSB sites to promote DSB repair.

Image-enhanced endoscopy for gastric preneoplastic conditions and neoplastic lesions: a systematic review and meta-analysis.

BACKGROUND : Image-enhanced endoscopy (IEE) improves the accuracy of endoscopic diagnosis. We aimed to assess the value of IEE for gastric preneoplastic conditions and neoplastic lesions. METHODS : Medline and Embase were searched until December 2018. Studies allowing calculation of diagnostic measures were included. Risk of bias and applicability were assessed using QUADAS-2. Subgroup analysis was performed to explore heterogeneity. RESULTS : 44 studies met the inclusion criteria. For gastric intestinal metaplasia (GIM), narrow-band imaging (NBI) obtained a pooled sensitivity and specificity of 0.79 (95 %CI 0.72-0.85) and 0.91 (95 %CI 0.88-0.94) on per-patient basis; on per-biopsy basis, it was 0.84 (95 %CI 0.81-0.86) and 0.95 (95 %CI 0.94-0.96), respectively. Tubulovillous pattern was the most accurate marker to detect GIM and it was effectively assessed without high magnification. For dysplasia, NBI showed a pooled sensitivity and specificity of 0.87 (95 %CI 0.84-0.89) and 0.97 (95 %CI 0.97-0.98) on per-biopsy basis. The use of magnification improved the performance of NBI to characterize early gastric cancer (EGC), especially when the vessel plus surface (VS) classification was applied. Regarding other technologies, trimodal imaging also obtained a high accuracy for dysplasia (sensitivity 0.93 [95 %CI 0.85-0.98], specificity 0.98 [95 %CI 0.92-1.00]). For atrophic gastritis, no specific pattern was noted and none of the technologies reached good diagnostic yield. CONCLUSION : NBI is highly accurate for GIM and dysplasia. The presence of tubulovillous pattern and the VS classification seem to be useful to detect GIM and characterize EGC, respectively. These features should be used in current practice and to standardize endoscopic criteria for other technologies.

Curriculum for small-bowel capsule endoscopy and device-assisted enteroscopy training in Europe: European Society of Gastrointestinal Endoscopy (ESGE) Position Statement.

The European Society of Gastrointestinal Endoscopy (ESGE) has recognized the need to formalize training in small-bowel endoscopy across European centers. The following criteria and framework for training in small-bowel capsule endoscopy (SBCE) and device-assisted enteroscopy (DAE), which aim to provide uniform and high quality training to ensure that small-bowel endoscopists are competent to operate independently, are based on the current literature and experience of experts in the field. Three main areas are covered: skills required prior to commencing training in small-bowel endoscopy; structured training for trainees to become independent endoscopists; and ways of ensuring competence is achieved. 1 : Centers providing training in SBCE should perform a minimum of 75 - 100 SBCEs/year. 2 : Experience in bidirectional endoscopies is desirable for structured training in SBCE. 3 : SBCE courses should consist of at least 50 % hands-on training and cover information on technology, indications and contraindications for SBCE, pathologies that can be encountered on SBCE, and standard terminology that should be used during reporting of SBCE. An SBCE course should be completed prior to achieving competence in SBCE reporting. 4 : Competence in SBCE can be assessed by considering a minimum of 30 SBCEs. Direct Observation of Procedural Skills, short SBCE videos, and multiple-choice questions can be useful to assess improvement in the skills of trainees. 5 : Centers offering training in DAE should aim to carry out at least 75 DAEs/year, should have direct links with an SBCE service, and should allow regular discussion of cases at a radiology small-bowel MDT. Training centers with lower numbers are encouraged to offer training by "buddying-up" with other centers, or using mentoring systems. 6 : DAE trainees must be independent in bidirectional endoscopies and have experience in level 1 polypectomy prior to commencement of training. They should also be competent in reviewing SBCEs. 7 : Training in DAE should be structured with a minimum of 75 procedures, including 35 retrograde DAEs, with therapeutic procedures undertaken in at least 50 % of the DAEs performed. Training should cover the indications, contraindications, complications including prevention, and technicalities of the DAE procedure; formal evaluation should follow. DAE trainees must acquire skills to independently manage and advise on small-bowel pathology following DAE procedures. 8 : It is highly recommended that international societies develop online modules and courses on DAE, which are currently lacking across Europe.