Management of high risk T1 gastric adenocarcinoma following endoscopic resection.

Endoscopic submucosal dissection has revolutionized the treatment of early gastric cancer. However, cases that do not meet the curability criteria have a higher risk of lymph node metastasis and salvage surgery is still considered the next treatment approach to increase the chance of cure. Nevertheless, not all high-risk resections entail the same level of risk, emphasizing the utmost importance of individualized stratification for further treatment. In this review, we aim to examine the current evidence concerning the management following a high-risk non-curative resection, highlighting the existing approaches, while also presenting upcoming strategies that attempt to improve patient outcomes, minimize adverse events, and provide a tailored management.

Association of metabolic syndrome components and NAFLD with quality of life: Insights from a cross-sectional study.

AIM: Metabolic syndrome (MetS) is associated with higher cardiovascular and metabolic risks, as well as with psychosocial disorders. Data regarding quality of life (QoL) in patients with MetS, point towards a significative association between MetS and a worse QoL. It remains unclear whether MetS components and non-alcoholic fatty liver disease (NAFLD) are associated with QoL in these individuals. We aimed to evaluate the association between QoL of patients with MetS and prespecified metabolic parameters (anthropometric, lipidic and glucose profiles), the risk of hepatic steatosis and fibrosis, and hepatic elastography parameters. METHODS: Cross-sectional study including patients from microDHNA cohort. This cohort includes patients diagnosed with MetS, 18 to 75 years old, followed in our tertiary center. The evaluation included anamnesis, physical examination, a QoL questionnaire (Short-Form Health Survey, SF-36), blood sampling and hepatic elastography. We used ordered logistic regression models adjusted to sex, age and body mass index to evaluate the associations between the QoL domains evaluated by SF-36 and the prespecified parameters. RESULTS: We included a total of 65 participants with MetS, with 54% being female and the mean age 61.9 ± 9.6 years old. A worse metabolic profile, specifically higher waist circumference, lower HDL, higher triglycerides, and more severe hepatic steatosis, were associated with worse QoL scores in several domains. We found no significant association of hepatic fibrosis with QoL. CONCLUSION: Our data suggests that there is a link between a worse metabolic profile (specifically poorer lipidic profile and presence of hepatic steatosis) and a worse QoL in patients with MetS.

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.

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.

Anastomotic Leakages after Surgery for Gastroesophageal Cancer: A Systematic Review and Meta-Analysis on Endoscopic versus Surgical Management.

Introduction: With the increase of esophageal and gastric cancer, surgery will be more often performed. Anastomotic leakage (AL) is one of the most feared postoperative complications of gastroesophageal surgery. It can be managed by conservative, endoscopic (such as endoscopic vacuum therapy and stenting), or surgical methods, but optimal treatment remains controversial. The aim of our meta-analysis was to compare (a) endoscopic and surgical interventions and (b) different endoscopic treatments for AL following gastroesophageal cancer surgery. Methods: Systematic review and meta-analysis, with search in three online databases for studies evaluating surgical and endoscopic treatments for AL following gastroesophageal cancer surgery. Results: A total of 32 studies comprising 1,080 patients were included. Compared with surgical intervention, endoscopic treatment presented similar clinical success, hospital length of stay, and intensive care unit length of stay, but lower in-hospital mortality (6.4% [95% CI: 3.8-9.6%] vs. 35.8% [95% CI: 23.9-48.5%]. Endoscopic vacuum therapy was associated with a lower rate of complications (OR 0.348 [95% CI: 0.127-0.954]), shorter ICU length of stay (mean difference -14.77 days [95% CI: -26.57 to -2.98]), and time until AL resolution (17.6 days [95% CI: 14.1-21.2] vs. 39.4 days [95% CI: 27.0-51.8]) when compared with stenting, but there were no significant differences in terms of clinical success, mortality, reinterventions, or hospital length of stay. Conclusions: Endoscopic treatment, in particular endoscopic vacuum therapy, seems safer and more effective when compared with surgery. However, more robust comparative studies are needed, especially for clarifying which is the best treatment in specific situations (according to patient and leak characteristics).

Introdução: Com o aumento da incidência de cancro esofágico e gástrico, a cirurgia será mais frequentemente realizada. As deiscências anastomóticas (DA) são uma das complicações pós-operatórias mais temidas da cirurgia gastroesofágica. Podem ser tratadas com métodos conservadores, endoscópicos (como terapêutica endoscópica por vácuo e colocação de próteses) ou cirúrgicos, mas a melhor abordagem ainda é controversa. O objetivo da nossa meta-análise foi a comparação a) entre intervenções endoscópicas e cirúrgicas e b) entre diferentes tratamentos endoscópicos para a DA após cirurgia oncológica gastroesofágica. Métodos: Revisão sistemática e meta-análise, com pesquisa em 3 bases de dados online de estudos que avaliassem tratamentos cirúrgicos e endoscópicos da DA após cirurgia oncológica gastroesofágica. Resultados: Um total de 32 estudos englobando 1,080 pacientes foram incluídos. Comparativamente à intervenção cirúrgica, o tratamento endoscópico apresentou sucesso clínico, duração do internamento hospitalar e do internamento na unidade de cuidados intensivos semelhantes, mas menor mortalidade intra-hospitalar (6.4% [95% CI: 3.8­9.6%] vs. 35.8% [95% CI: 23.9­48.5%]). A terapêutica endoscópica por vácuo associou-se a menor taxa de complicações (OR 0.348 [95% CI: 0.127­0.954]), menor duração do internamento na UCI (diferença média −14.77 dias [95% CI: −26.57 to −2.98]) e do tempo até resolução da DA (17.6 dias [95% CI: 14.1­21.2] vs. 39.4 dias [95% CI: 27.0­51.8]) quando comparada com as próteses endoscópicas, mas não houve diferenças significativas em termos de sucesso clínico, mortalidade, reintervenções ou duração do internamento hospitalar. Conclusões: O tratamento endoscópico, em particular a terapêutica endoscópica por vácuo parece ser mais segura e efetiva em comparação com a cirurgia. Porém, estudos comparativos mais robustos são necessários, especialmente para clarificar qual o melhor tratamento em situações específicas (consoante as caraterísticas do paciente e da deiscência).

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.

Pharmacological Treatment of Functional Dyspepsia: An Old Story Revisited or a New Story to Be Told? A Clinical Review.

Dyspepsia incorporates a set of symptoms originating from the gastroduodenal region, frequently encountered in the adult population in the Western world. Most patients with symptoms compatible with dyspepsia eventually end up, in the absence of a potential organic cause, being diagnosed with functional dyspepsia. Many have been the new insights in the pathophysiology behind functional dyspeptic symptoms, namely, hypersensitivity to acid, duodenal eosinophilia, and altered gastric emptying, among others. Since these discoveries, new therapies have been proposed. Even so, an established mechanism for functional dyspepsia is not yet a reality, which makes its treatment a clinical challenge. In this paper, we review some of the possible approaches to treatment, both well established and some new therapeutic targets. Recommendations about dose and time of use are also made.

A dispepsia engloba um conjunto de sintomas provenientes do trato gastroduodenal, frequentes na população adulta ocidental. A maioria dos doentes com sintomas compatíveis com dispepsia, acaba eventualmente, na ausência de causa orgânica, por ser diagnosticado com dispepsia funcional. Novos conhecimentos sobre a fisiopatologia responsável pelos sintomas de dispepsia têm sido adquiridos, nomeadamente a hipersensibilidade ao ácido, eosinofilia duodenal e as alterações do esvaziamento gástrico, entre outros. Estas novas descobertas vieram proporcionar novos possíveis alvos terapêuticos. Ainda assim, um mecanismo exato ainda não é conhecido, o que torna o tratamento da dispepsia funcional tantas vezes um desafio clínico. Neste trabalho, algumas abordagens das possíveis terapêuticas são revisitadas, tanto aquelas que já são uma prática usual, bem como novos alvos terapêuticos. Recomendações sobre dose e duração do tratamento são também elaboradas.

Endoscopic Resection of Gastrointestinal Neuroendocrine Tumors: Long-Term Outcomes and Comparison of Endoscopic Techniques.

Introduction: Gastrointestinal neuroendocrine tumors (GI-NETs) are being more frequently diagnosed and treated by endoscopic resection (ER) techniques. However, comparison studies of the different ER techniques or long-term outcomes are rarely reported. Methods: This was a single-center retrospective study analyzing short and long-term outcomes after ER of gastric, duodenum, and rectal GI-NETs. Comparison between standard EMR (sEMR), EMR with a cap (EMRc), and endoscopic submucosal dissection (ESD) was made. Results: Fifty-three patients with GI-NET (25 gastric, 15 duodenal, and 13 rectal; sEMR = 21; EMRc = 19; ESD = 13) were included in the analysis. Median tumor size was 11 mm (range 4-20), significantly larger in the ESD and EMRc groups compared to the sEMR group (p < 0.05). Complete ER was possible in all cases with 68% histological complete resection (no difference between the groups). Complication rate was significantly higher in the EMRc group (EMRc 32%, ESD 8%, and EMRs 0%, p = 0.01). Local recurrence occurred in only one patient, and systemic recurrence in 6%, with size ≥ 12 mm being a risk factor for systemic recurrence (p = 0.05). Specific disease-free survival after ER was 98%. Conclusion: ER is a safe and highly effective treatment particularly for less than 12 mm luminal GI-NETs. EMRc is associated with a high complication rate and should be avoided. sEMR is an easy and safe technique that is associated with long-term curability, and it is probably the best therapeutic option for most luminal GI-NETs. ESD appears to be the best option for lesions that cannot be resected en bloc with sEMR. Multicenter, prospective randomized trials should confirm these results.

Introdução: Os tumores neuroendócrinos gastrointestinais (GI-NET) são frequentemente diagnosticados e tratados por técnicas de resseção endoscópica (ER). Contudo, estudos comparativos das diferentes técnicas de ER ou resultados a longo prazo são raramente descritos. Métodos: Estudo unicêntrico retrospectivo que analisa resultados a curto e longo prazo após ER de NETs gástricos, duodenais e retais. Realizou-se uma análise comparativa entre as técnicas de mucosectomia convencional (sEMR), mucosectomia com cap (EMRc) e disseção endoscópica da submucosa (ESD). Resultados: Foram incluídos 53 doentes com GI-NET (25 gástricos, 15 duodenais e 13 rectais; sEMR=21; EMRc=19; ESD=13). A mediana do tamanho da lesão foi 11 mm (âmbito 4-20), sendo significativamente maiores nos grupos ESD e EMRc quando comparado com sEMR (p < 0.05). A ER completa foi possível em todos os casos com taxa de resseção histológica completa de 68% (sem diferença entre os grupos). A taxa de complicações foi significativamente superior no grupo EMRc (EMRc 32%, ESD 8% e EMRs 0%, p = 0.01). Recorrência local apenas ocorreu em 1 doente e recorrência sistémica em 6%, com o tamanho da lesão ≥ 12mm a ser um factor de risco para recorrência sistémica (p = 0.05). Sobrevida específica de doença após ER de 98%. Conclusão: ER é segura e altamente eficaz para o tratamento de GI-NETs principalmente com tamanho inferior a 12 mm. EMRc está associada a uma taxa de complicações elevada e deve ser evitada. sEMR é uma técnica segura e eficaz que se associa a curabilidade a longo prazo, sendo provavelmente a melhor opção terapêutica para a maioria dos GI-NETs luminais. ESD parece ser a melhor opção para as lesões que não podem ser removidas em bloco pela técnica de sEMR. Estudos randomizados, prospectivos e multicêntricos devem confirmar estes resultados.

Linking dysbiosis to precancerous stomach through inflammation: Deeper than and beyond imaging.

Upper gastrointestinal endoscopy is considered the gold standard for gastric lesions detection and surveillance, but it is still associated with a non-negligible rate of missing conditions. In the Era of Personalized Medicine, biomarkers could be the key to overcome missed lesions or to better predict recurrence, pushing the frontier of endoscopy to functional endoscopy. In the last decade, microbiota in gastric cancer has been extensively explored, with gastric carcinogenesis being associated with progressive dysbiosis. Helicobacter pylori infection has been considered the main causative agent of gastritis due to its interference in disrupting the acidic environment of the stomach through inflammatory mediators. Thus, does inflammation bridge the gap between gastric dysbiosis and the gastric carcinogenesis cascade and could the microbiota-inflammation axis-derived biomarkers be the answer to the unmet challenge of functional upper endoscopy? To address this question, in this review, the available evidence on the role of gastric dysbiosis and chronic inflammation in precancerous conditions of the stomach is summarized, particularly targeting the nuclear factor-κB (NF-κB), toll-like receptors (TLRs) and cyclooxygenase-2 (COX-2) pathways. Additionally, the potential of liquid biopsies as a non-invasive source and the clinical utility of studied biomarkers is also explored. Overall, and although most studies offer a mechanistic perspective linking a strong proinflammatory Th1 cell response associated with, but not limited to, chronic infection with Helicobacter pylori, promising data recently published highlights not only the diagnostic value of microbial biomarkers but also the potential of gastric juice as a liquid biopsy pushing forward the concept of functional endoscopy and personalized care in gastric cancer early diagnosis and surveillance.

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.

Anastomotic Leaks following Esophagectomy for Esophageal and Gastroesophageal Junction Cancer: The Key Is the Multidisciplinary Management.

Introduction: Anastomotic leakage after esophagectomy is associated with high mortality and impaired quality of life. Aim: The objective of this work was to determine the effectiveness of management of esophageal anastomotic leakage (EAL) after esophagectomy for esophageal and gastroesophageal junction (GEJ) cancer. Methods: Patients submitted to esophagectomy for esophageal and GEJ cancer at a tertiary oncology hospital between 2014 and 2019 (n = 119) were retrospectively reviewed and EAL risk factors and its management outcomes determined. Results: Older age and nodal disease were identified as independent risk factors for anastomotic leak (adjusted OR 1.06, 95% CI 1.00-1.13, and adjusted OR 4.89, 95% CI 1.09-21.8). Patients with EAL spent more days in the intensive care unit (ICU; median 14 vs. 4 days) and had higher 30-day mortality (15 vs. 2%) and higher in-hospital mortality (35 vs. 4%). The first treatment option was surgical in 13 patients, endoscopic in 10, and conservative in 3. No significant differences were noticeable between these patients, but sepsis and large leakages were tendentially managed by surgery. At follow-up, 3 patients in the surgery group (23%) and 9 in the endoscopic group (90%) were discharged under an oral diet (p = 0.001). The in-hospital mortality rate was 38% in the surgical group, 33% in the conservative group, and 10% in endoscopic group (p = 0.132). In patients with EAL, the presence of septic shock at leak diagnosis was the only predictor of mortality (p = 0.004). ICU length-of-stay was non-significantly lower in the endoscopic therapy group (median 4 days, vs. 16 days in the surgical group, p = 0.212). Conclusion: Risk factors for EAL may help change pre-procedural optimization. The results of this study suggest including an endoscopic approach for EAL.

Introdução: A deiscência anastomótica após esofagectomia está associada a uma elevada taxa de mortalidade e qualidade de vida comprometida. Objetivo: Avaliar a eficácia da abordagem da deiscência de anastomose esofágica após esofagectomia por neoplasia do esófago e da junção esofagogastrica (JEG). Métodos: Foram revistos retrospetivamente todos os doentes submetidos a esofagectomia por neoplasia do esófago e da JEG num hospital terciário entre 2014 e 2019 (n = 119) e analisados os fatores de risco e as diferentes abordagens na deiscência anastomótica. Resultados: A idade avançada e a presença de metastização ganglionar foram identificados como fatores de risco independentes para deiscência anastomótica (OR 1.06, 95% IC 1.00­1.13 e 4.89, IC 1.09­21.8). Os doentes com deiscência anastomótica estiveram mais dias internados na unidade de cuidados intensivos (UCI) (mediana 14 vs. 4 dias) e tiveram uma mortalidade aos 30 dias e intra-hospitalar mais elevada (15% vs. 2% e 35% vs. 4%, respectivamente). A primeira abordagem terapêutica foi cirúrgica em 13 doentes, endoscópica em 10 e conservadora em 3. Não foram encontradas diferenças estatisticamente significativas entre estes doentes, com uma tendência para a presença de sépsis e de deiscências de maior dimensão nos doentes abordados cirurgicamente. Durante o seguimento, 3 doentes do grupo cirúrgico (23%) e 9 do grupo endoscópico (90%) tiveram alta hospitalar sob dieta oral (p = 0.001). A taxa de mortalidade intra-hospitalar foi de 38% no grupo cirúrgico, 33% no grupo conservador e 10% no grupo endoscópico (p = 0.132). Nos doentes com deiscência anastomótica, a presença de choque sético ao diagnóstico foi o único preditor de mortalidade (p = 0.004). O tempo de internamento na UCI não foi significativamente menor no grupo submetido a tratamento endoscópico (mediana de 4 dias vs. 16 dias no grupo cirúrgico, p = 0.212). Conclusão: A identificação de fatores de risco para deiscência anastomótica após esofagectomia pode ajudar a alterar a optimização pré-procedimento. Os resultados deste estudo sugerem incluir uma abordagem endoscópica nos doentes com deiscência anastomótica.

Microbiota Modulation in Patients with Metabolic Syndrome.

Metabolic syndrome (MS) comprises a vast range of metabolic dysfunctions, which can be associated to cardiovascular disease risk factors. MS is reaching pandemic levels worldwide and it currently affects around 25% in the adult population of developed countries. The definition states for the diagnosis of MS may be clear, but it is also relevant to interpret the patient data and realize whether similar criteria were used by different clinicians. The different criteria explain, at least in part, the controversies on the theme. Several studies are presently focusing on the microbiota changes according to the components of MS. It is widely accepted that the gut microbiota is a regulator of metabolic homeostasis, being the gut microbiome in MS described as dysbiotic and certain taxonomic groups associated to metabolic changes. Probiotics, and more recently synbiotics, arise as promising therapeutic alternatives that can mitigate some metabolic disturbances, namely by correcting the microbiome and bringing homeostasis to the gut. The most recent studies were revised and the promising results and perspectives revealed in this review.

Improving the Diagnosis and Treatment of Early Gastric Cancer in the West.

Gastric cancer is the third leading cause of cancer-related death. In Western countries, its lower prevalence and the absence of mass screening programmes contribute to late diagnosis and a slower implementation of minimally invasive treatments. A secondary prevention strategy through endoscopic surveillance of patients at high risk of intestinal-type gastric adenocarcinoma or by screening gastric cancer within colorectal screening programmes is cost-effective in intermediate-risk countries, though the identification of these patients remains challenging. Virtual chromoendoscopy with narrow-band imaging improves the accuracy of endoscopic diagnosis, significantly increasing the sensitivity for intestinal metaplasia while preserving specificity. Endoscopic grading of gastric intestinal metaplasia is feasible, correlates well with histological staging systems and also with gastric neoplasia risk and can be used to stratify risk. Endoscopic submucosal dissection (ESD) in the West achieves efficacy and safety outcomes similar to those reported for Eastern countries, and the long-term disease-specific survival is higher than 95%. A prospective comparative study with gastrectomy confirms its higher safety and its benefits concerning health-related quality of life. However, ESD is associated with a 5% risk of postprocedural bleeding and a 20% risk of non-curative resection. The knowledge of risk factors for adverse events and non-curative resection can improve patient selection. The risk of metachronous lesions after ESD is high (3-5% per year), and endoscopic surveillance is needed. The management of patients with non-curative resection can be optimized using risk scoring systems for lymph node metastasis.

O cancro gástrico é a terceira causa de morte por cancro. Nos países Ocidentais, a sua menor prevalência e a ausência de programas de rastreio contribuem para o diagnóstico tardio e para uma implementação mais lenta de tratamentos minimamente invasivos. Estratégias de prevenção secundária através da vigilância de indivíduos em maior risco de adenocarcinoma gástrico tipo intestinal ou de rastreio de cancro gástrico (enquadradas em programas de rastreio do cancro colo-retal) é custo-efetiva em países de incidência intermédia, apesar de a identificação destes indivíduos permanecer desafiante. A cromoendoscopia virtual com narrow-band imaging melhora a validade do diagnóstico endoscópico, aumentando significativamente a sensibilidade para metaplasia intestinal preservando a especificidade. O estadiamento endoscópico da metaplasia intestinal é exequível, correlaciona-se com os sistemas de estadiamento histológicos e também com o risco de neoplasia gástrica, podendo ser utilizada para estratificar o risco. A disseção endoscópica da submucosa (DES) no Ocidente tem eficácia e segurança semelhante à reportada nos países Orientais, e a sobrevida específica de doença é superior a 95%. Estudos comparativos com a gastrectomia confirmam a sua maior segurança e benefícios na qualidade de vida. Contudo, a DES associa-se a risco de hemorragia pós-procedimento (5%) e de resseção não curativa (20%). A identificação de fatores de risco para eventos adversos e resseção não curativa podem melhorar a seleção dos doentes para esta técnica. O risco de lesões metácronas após DES é elevado (3­5% ano) e a vigilância endoscópica é necessária. A abordagem dos doentes com resseções não curativas pode ser otimizada através da utilização de classificações de risco para metástases ganglionares.

Endoscopic submucosal dissection: a country dissemination experience and outcomes.

OBJECTIVE: An increasing use of endoscopic submucosal dissection (ESD) has been reported in Western countries, although some differences in training schemes and outcomes have been described. We aimed to report the training model, implementation, and outcomes of ESD in Portugal. METHODS: All endoscopists trained at our center from our country (n = 9) were invited to a survey regarding: (a) training period; (b) ESD outcomes and (c) implementation of ESD in each respective center. RESULTS: All endoscopists completed the survey. Learning ESD was centered on human ESD assistance in a high-volume center during a median time of 6 months and complemented mainly by hands-on courses (89%). During the surveyed period, a total of 1229 ESD were performed, mostly in gastric locations (74%). Median complete R0 and curative resection rate were 92% (IQR, 81-96.8) and 87% (IQR, 74-93.3), respectively, and median perforation rate was 0.89% (IQR, 0.25-6.22). The main limitations encountered during the implementation of ESD were related to the lack of initial mentoring or insufficient expertise to progress to more difficult lesions. CONCLUSION: Learning ESD through participation in hands-on courses and visiting high-volume centers seems to be adequate to achieve a good competence at the initial stage of ESD, which in fact is in consonance with the European Society of Gastrointestinal Endoscopy recommendations. However, mentoring is essential for technical progression, and this represents the fundamental barrier during the adoption of ESD, which may be overcome by increasing hands-on training in animal or artificial simulators, but preferably with the implementation of a structured training program.

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.

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.

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.

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.