α,ß-Amyrin prevents steatosis and insulin resistance in a high-fat diet-induced mouse model of NAFLD via the AMPK-mTORC1-SREBP1 signaling mechanism.

Nonalcoholic fatty liver disease (NAFLD), characterized by hepatosteatosis and steatohepatitis, is intrinsically related to obesity. Our previous study reported on the anti-obese activity of α,ß-amyrin (AMY), a pentacyclic triterpene isolated from Protium heptaphyllum. This study investigated its ability to prevent fatty liver and the underlying mechanism using the mouse model of NAFLD. NAFLD was induced in male Swiss mice fed a high fat diet (HFD) for 15 weeks. The controls were fed a normal chow diet (ND). The mice were simultaneously treated with AMY at 10 and 20 mg/kg or fenofibrate at 50 mg/kg. Lipid levels along with metabolic and inflammatory parameters were assessed in liver and serum. The liver sections were histologically examined using H&E staining. RT-qPCR and western blotting assays were performed to analyze signaling mechanisms. Mice fed HFD developed severe hepatic steatosis with elevated triglycerides and lipid droplets compared with ND controls. This was associated with a decrease in AMP-activated protein kinase (AMPK) activity, an increase of mechanistic target of rapamycin complex 1 (mTORC1) signaling, and enhanced sterol regulatory element binding protein 1 (SREBP1) expression, which have roles in lipogenesis, inhibition of lipolysis, and inflammatory response. AMY treatment reversed these signaling activities and decreased the severity of hepatic steatosis and inflammatory response, evidenced by serum and liver parameters as well as histological findings. AMY-induced reduction in hepatic steatosis seemed to involve AMPK-mTORC1-SREBP1 signaling pathways, which supported its beneficial role in the prevention and treatment of NAFLD.

Adolescent Ethanol Exposure Alters Cholinergic Function and Apical Dendritic Branching Within the Orbital Frontal Cortex.

During adolescence, heavy binge-like ethanol consumption can lead to frontocortical structural and functional impairments. These impairments are likely driven by adolescence being a critical time point for maturation of brain regions associated with higher-order cognitive functioning. Rodent models of heavy binge-like ethanol exposure show consistent disruptions to the typical development of the prefrontal cortex (PFC). All deep cortical layers receive cholinergic projections that originate from the Nucleus basalis of Meynert (NbM) complex. These cholinergic projections are highly involved in learning, memory, and attention. Adolescent intermittent ethanol exposure (AIE) induces cholinergic dysfunction as a result of an epigenetic suppression of the genes that drive the cholinergic phenotype. The current study used a model of AIE to assess structural and functional changes to the frontal cortex and NbM following binge-like ethanol exposure in adolescence. Western blot analysis revealed long-term disruptions of the cholinergic circuit following AIE: choline acetyltransferase (ChAT) was suppressed in the NbM and vesicular acetylcholine transporter (VAChT) was suppressed in the orbitofrontal cortex (OFC). In vivo microdialysis for acetylcholine efflux during a spatial memory task determined changes in cholinergic modulation within the PFC following AIE. However, AIE spared performance on the spatial memory task and on an operant reversal task. In a second study, Golgi-Cox staining determined that AIE increased apical dendritic complexity in the OFC, with sex influencing whether the increase in branching occurred near or away from the soma. Spine density or maturity was not affected, likely compensating for a disruption in neurotransmitter function following AIE.

Effects of vitamin D-induced supernatant of placental explants from preeclamptic women on oxidative stress and nitric oxide bioavailability in human umbilical vein endothelial cells.

The study evaluated the effect of the supernatant of placental explants from preeclamptic (PE) and normotensive (NT) pregnant women after tissue treatment with or without vitamin D (VD) on oxidative stress and nitric oxide (NO) bioavailability in human umbilical vein endothelial cells (HUVEC). Placental explants were prepared from eight NT and eight PE women, and supernatants were obtained after incubation with or without hydrogen peroxide (H2O2) and/or VD. HUVEC were cultured for 24 h with supernatants, and the following parameters were analyzed in HUVEC cultures: NO, nitrate (NO3-), and nitrite (NO2-) levels, lipid peroxidation, and intracellular reactive oxygen species (ROS). Results showed that the production of NO3-, NO2-, malondialdehyde (MDA), and ROS were significantly higher in HUVEC treated with explant supernatant from PE compared to NT pregnant women, while the supernatant of PE explants treated with VD led to a decrease in these parameters. A significantly high production of NO was detected in HUVEC cultured with control supernatant of NT group, and in cultures treated with supernatant of PE explants treated with VD. Taken together, these results demonstrated that cultures of placental explants from PE women with VD treatment generated a supernatant that decreased oxidative stress and increased the bioavailability of NO in endothelial cells.

Effects of vitamin D-induced supernatant of placental explants from preeclamptic women on oxidative stress and nitric oxide bioavailability in human umbilical vein endothelial cells

The study evaluated the effect of the supernatant of placental explants from preeclamptic (PE) and normotensive (NT) pregnant women after tissue treatment with or without vitamin D (VD) on oxidative stress and nitric oxide (NO) bioavailability in human umbilical vein endothelial cells (HUVEC). Placental explants were prepared from eight NT and eight PE women, and supernatants were obtained after incubation with or without hydrogen peroxide (H2O2) and/or VD. HUVEC were cultured for 24 h with supernatants, and the following parameters were analyzed in HUVEC cultures: NO, nitrate (NO3-), and nitrite (NO2-) levels, lipid peroxidation, and intracellular reactive oxygen species (ROS). Results showed that the production of NO3-, NO2-, malondialdehyde (MDA), and ROS were significantly higher in HUVEC treated with explant supernatant from PE compared to NT pregnant women, while the supernatant of PE explants treated with VD led to a decrease in these parameters. A significantly high production of NO was detected in HUVEC cultured with control supernatant of NT group, and in cultures treated with supernatant of PE explants treated with VD. Taken together, these results demonstrated that cultures of placental explants from PE women with VD treatment generated a supernatant that decreased oxidative stress and increased the bioavailability of NO in endothelial cells.

α, ß-Amyrin prevents steatosis and insulin resistance in a high-fat diet-induced mouse model of NAFLD via the AMPK-mTORC1-SREBP1 signaling mechanism

Nonalcoholic fatty liver disease (NAFLD), characterized by hepatosteatosis and steatohepatitis, is intrinsically related to obesity. Our previous study reported on the anti-obese activity of α,β-amyrin (AMY), a pentacyclic triterpene isolated from Protium heptaphyllum. This study investigated its ability to prevent fatty liver and the underlying mechanism using the mouse model of NAFLD. NAFLD was induced in male Swiss mice fed a high fat diet (HFD) for 15 weeks. The controls were fed a normal chow diet (ND). The mice were simultaneously treated with AMY at 10 and 20 mg/kg or fenofibrate at 50 mg/kg. Lipid levels along with metabolic and inflammatory parameters were assessed in liver and serum. The liver sections were histologically examined using H&E staining. RT-qPCR and western blotting assays were performed to analyze signaling mechanisms. Mice fed HFD developed severe hepatic steatosis with elevated triglycerides and lipid droplets compared with ND controls. This was associated with a decrease in AMP-activated protein kinase (AMPK) activity, an increase of mechanistic target of rapamycin complex 1 (mTORC1) signaling, and enhanced sterol regulatory element binding protein 1 (SREBP1) expression, which have roles in lipogenesis, inhibition of lipolysis, and inflammatory response. AMY treatment reversed these signaling activities and decreased the severity of hepatic steatosis and inflammatory response, evidenced by serum and liver parameters as well as histological findings. AMY-induced reduction in hepatic steatosis seemed to involve AMPK-mTORC1-SREBP1 signaling pathways, which supported its beneficial role in the prevention and treatment of NAFLD.

Atypical Motor Neuron Disease variants: Still a diagnostic challenge in Neurology.

Motor neuron disease (MND) represents a wide and heterogeneous expanding group of disorders involving the upper or lower motor neurons, mainly represented by amyotrophic lateral sclerosis (ALS), primary lateral sclerosis, progressive muscular atrophy and progressive bulbar palsy. Primary motor neuronopathies are characterized by progressive degenerative loss of anterior horn cell motoneurons (lower motor neurons) or loss of giant pyramidal Betz cells (upper motor neurons). Despite its well-known natural history, pathophysiological and clinical characteristics for the most common MND, atypical clinical presentation and neurodegenerative mechanisms are commonly observed in rare clinical entities, so-called atypical variants of MND-ALS, including flail-leg syndrome, flail-arm syndrome, facial-onset sensory and motor neuronopathy (FOSMN), finger extension weakness and downbeat nystagmus (FEWDON-MND) and long-lasting and juvenile MND-ALS. Herein, we provide a review article presenting clinical, genetic, pathophysiological and neuroimaging findings of atypical variants of MND-ALS in clinical practice.

O'Sullivan-McLeod syndrome: Unmasking a rare atypical motor neuron disease.

Atypical motor neuron disease represents a rare heterogeneous group of neurodegenerative disorders with clinical, genetic and neuroimaging features distinct from those of the classic spinal or bulbar-onset amyotrophic lateral sclerosis (ALS). O'Sullivan-McLeod syndrome represents an extremely rare lower motor neuronopathy with early adult-onset distal amyotrophy and weakness in the upper limbs with asymmetrical involvement. To add to the few case series and epidemiological and genetic studies describing this variant syndrome, our team here presents a series of seven unrelated Brazilian patients with O'Sullivan-McLeod syndrome in a detailed review of their clinical, neuroimaging, laboratory and neurophysiological findings. A male-to-female ratio of 2.5 to 1 and a mean age at onset of 34.3years was observed, with a mean time delay of 6.6years between symptom-onset and a definitive diagnosis. A positive family history was observed in one case, yet whole-exome sequencing results were negative. Neuroimaging studies were unremarkable. All cases presented with chronic denervation restricted to cervical myotomes and normal sensory nerve conduction studies. This case series, one of the largest groups of patients with O'Sullivan-McLeod syndrome reported in the literature, confirms the sporadic nature of the condition and the difficulties faced in arriving at a definite diagnosis, and also expands the age limit in late adult-onset cases.

Pediatric Renal Transplantation: Evaluation of Long-Term Outcomes and Comparison to Adult Population.

BACKGROUND: In Europe, pediatric transplantation accounts for only about 4% of all kidney transplantations performed. The aim of our work is to evaluate the evolution of pediatric renal transplantation in our department over time, but also to compare this special population with the adult one. METHODS: We evaluated all pediatric renal transplantations performed in our department between January 1981 and December 2016. We performed the analysis of clinical, analytical, and surgical factors to look for predictive factors of graft loss or decrease of survival. In addition, we performed a comparative study of pediatric and adult populations and an evaluation of the evolution of pediatric renal transplantation in our department over time. RESULTS: We evaluated 101 renal transplantations performed in patients younger than 18 years. Pediatric transplantations corresponded to 3.4% of all renal transplantations performed in our department. The rate of living donors was 12%. Donors of grafts for the pediatric population were significantly younger than in the adult population. The increase in donor age was associated with lower renal graft survival rates. Acute rejections were more frequent in the pediatric population. Eleven pediatric recipients (10.9%) died in the follow-up period. Renal graft survival in the pediatric population was 94.8%, 77.4%, and 66.5% at 1, 5, and 10 years, respectively. There was no significant difference in graft survival in the pediatric and adult population. The pediatric overall survival rate at 1, 5 and 10 years was 97.9%, 96.8%, and 91.9%, respectively. CONCLUSION: Pediatric renal transplantation presents results identical to those identified in adults.

Falls in older people: comparing older and younger fallers in a developing country.

PURPOSE: While falls are common in older people, causing significant mortality and morbidity, this phenomenon has not been extensively studied in the Caribbean. This study aimed to compare falls in older and younger people in this setting. METHODS: We conducted a prospective observational study of older trauma patients in Trinidad, comparing older and younger patients sustaining falls. RESULTS: 1432 adult trauma patients were included (1141 aged 18-64 years and 291 aged 65 years and older). Older fallers were more likely to be female (66.7 vs 47.2%; p < 0.001), suffer from multiple pre-existing diseases (24.7 vs 2.4%; p < 0.001) and take multiple medications (16.1 vs 0.8%; p < 0.001). They also sustained more severe injuries and presented with higher acuity than younger fallers. Admission rates were higher among older fallers (29.9 vs 13.1%; p < 0.001). CONCLUSIONS: In our study, older patients who fell were a distinct group from younger falls victims, with unique demographic, clinical and injury related characteristics. Their increased risk of injury within the home, coupled with their propensity for more severe injuries made them a high risk patient group. More research is needed to better understand this patient group and plan specific preventive interventions.

Long-Term Outcomes of Gastric Endoscopic Submucosal Dissection: Focus on Metachronous and Non-Curative Resection Management.

INTRODUCTION: Endoscopic submucosal dissection (ESD) is an effective treatment for gastric superficial neoplasms and curative in 80-85% of the patients. The aims of this study were to identify risk factors for non-curative resection and metachronous development, and to evaluate patient management and outcome after non-curative resection. METHODS: In this single-centre study, the outcome of consecutive patients submitted to gastric ESD was assessed during a minimum follow-up of 18 months. Univariate analysis and multivariate logistic regression were performed to identify risk factors. RESULTS: ESD was performed in 194 lesions (164 patients) between 2005 and 2014. The median follow-up was 40 months. En bloc and complete resection rates were 95.3 and 93.8%, respectively. Male sex, larger tumor size, longer procedural time, and more advanced histology were associated with a non-curative resection (p < 0.05), but only carcinoma detected in biopsies before resection was identified as a significant risk factor on multivariate analysis. Metachronous lesions occurred in 18.4%, and the incidence rate was 4.7 lesions/100 person-years. Older age at diagnosis was identified as the only predictor of metachronous development in logistic regression. In the non-curative resection group, survival did not differ between patients allocated to surveillance and those submitted to gastrectomy; 75% of gastrectomy specimens showed no residual lesion. CONCLUSIONS: The risk factors identified for non-curative resection help to improve patient selection and patient information. Older patients had an increased risk for the development of metachronous lesions. In patients with non-curative resections, individualized patient management and surveillance seems to be an adequate option in selected cases.

INTRODUÇÃO: A disseção endoscópica da submucosa (ESD) é um tratamento eficaz nas neoplasias gástricas precoces, sendo curativa em 80-85%. Os objetivos deste estudo foram identificar fatores de risco para resseção não curativa e para o desenvolvimento de lesões metácronas, bem como avaliar a abordagem e os resultados após resseção não curativa. MÉTODOS: Estudo de coorte, unicêntrico, incluindo doentes consecutivos submetidos a ESD gástrica com tempo mínimo de follow-up de 18 meses. Análise univariada e multivariada utilizadas na identificação de fatores de risco. RESULTADOS: Entre 2005 e 2014, 194 lesões (164 doentes) foram submetidas a ESD (tempo mediano de follow-up 40 meses). Resseções em bloco e completa: 95.3 e 93.8%. Sexo masculino, lesão maior, procedimento demorado e histologia mais avançada associaram-se a resseção não curativa (p < 0.05); na análise multivariada, adenocarcinoma nas biopsias foi identificado como fator preditor. Ocorreram lesões metácronas em 18.4% (taxa de incidência 4.7/100 pessoas-ano), sendo a idade mais avançada fator de risco independente para lesões metácronas. Nos casos de resseção não curativa, a sobrevivência foi semelhante nos doentes alocados para vigilância e nos submetidos a gastrectomia; em 75% não havia doença residual na peça cirúrgica. CONCLUSÕES: Os fatores de risco identificados são úteis na seleção apropriada dos doentes e na transmissão da informação. A incidência de lesões metácronas é significativa, estando os doentes mais velhos em maior risco. Após resseção não curativa a decisão deve ser individualizada, sendo a vigilância apropriada em casos selecionados.

Evaluation and management of gastric epithelial polyps.

Gastric polyps include a wide spectrum of lesions with different histology and neoplastic potential. They are found in up to 6% of upper gastrointestinal endoscopy and are usually asymptomatic and incidentally diagnosed, being in the vast majority epithelial gastric polyps. Hyperplastic, fundic gland and adenomas are the most common types of gastric polyps and, although each type may have typical endoscopic appearances, they all must be sampled at the initial endoscopy for histological assessment. Also, the normal appearing gastric mucosa should be sampled to stage atrophic changes, rule out endoscopically non-visible dysplasia and to diagnose Helicobacter pylori. Polyposis syndromes that affect the stomach are rare but should be taken into account. Hamartomatous polyps can be found in Juvenile polyposis, Cowden syndrome and Peutz-Jeghers syndrome. On the other hand, multiple fundic gland polyps are present in the majority of patients with familial adenomatous polyposis. In this study we provide a comprehensive review on the evaluation and management of gastric epithelial polyps, in this way helping physicians to properly handle this type of lesions.

Duplicated or Hybridized Peptide Functional Domains Promote Oral Homeostasis.

Proteins that have existed for millions of years frequently contain repeats of functional domains within their primary structure, thereby improving their functional capacity. In the evolutionary young statherin protein contained within the in vivo-acquired enamel pellicle (AEP), we identified a single functional domain (DR9) located within the protein N-terminal portion that exhibits a higher affinity for hydroxyapatite and more efficient protection against enamel demineralization compared to other native statherin peptides. Thus, we tested the hypothesis that multiplication of functional domains of naturally occurring pellicle peptides amplifies protection against enamel demineralization. In addition, a specific amino acid sequence from histatin 3 (RR-14) was introduced to the hybrid peptides for further testing. Enamel specimens were sectioned to 150-µm thickness and randomly grouped as follows: DR9, DR9-DR9, DR9-RR14, statherin, histatin 1, or distilled water (control). After submersion for 2 h at 37°C, the specimens were placed in 2 mL demineralization solution for 12 d at 37°C. Upon sample removal, the remaining solution was subjected to colorimetric assays to determine the amount of calcium and phosphate released from each specimen. DR9-DR9 amplified protection against enamel demineralization when compared to single DR9 or statherin. Notably, the hybrid peptide DR9-RR14 demonstrated relatively strong protection when the antimicrobial property of these peptides was tested against Candida albicans and Streptococcus mutans. DR9-RR14 was able to maintain 50% of the antifungal activity compared with RR14 for C. albicans and similar values of S. mutans killing activity. This study has pioneered the functional exploration of the natural peptide constituents of the AEP and their evolution-inspired engineered peptides. The knowledge obtained here may provide a basis for the development of stable (proteinase-resistant) synthetic peptides for therapeutic use against dental caries, dental erosion, and/or oral candidiasis.

Prostate Cancer in Renal Transplant Recipients: Diagnosis and Treatment.

BACKGROUND: We currently know that prostate cancer (Pca) risk is reduced in patients undergoing kidney transplantation. However, its impact and treatment are not widely studied. METHODS: This was a retrospective study of male patients submitted to kidney transplantation in our center from 1980 to 2016 evaluating incidence, treatment, and follow-up of Pca in our population. RESULTS: In 1805 patients undergoing kidney transplantation, 20 men were diagnosed with Pca, leading to an incidence of 1.1%. Median age at renal transplantation was 53.4 years with a median age at diagnosis of Pca of 61.2 years. Initial median prostate-specific antigen (PSA) was 6 ng/mL and Gleason score was 7 (3 + 4) in about 50% of cases. Bone metastasis developed in 10% and no visceral metastases were diagnosed. The majority of patients were submitted to radical prostatectomy and bilateral pelvic lymph node dissection. Some other cancers occurred in these patients such as skin and pulmonary cancers. In 35% of the cases, the graft was lost. The main cause of patient death was cardiovascular. The mean graft survival was about 14 years. The majority of patients are alive with functioning grafts (65%). CONCLUSION: In our center the clinical incidence of Pca in patients undergoing kidney transplantation is 1.1% and surgical treatment seems to be a good initial option.

National Alcohol Survey of households in Trinidad and Tobago (NASHTT): Alcohol use in households.

BACKGROUND: To determine the patterns of alcohol use among households in Trinidad and Tobago (T&T) and to estimate the association between alcohol use and negative psychological, social, or physical events experienced by the household. METHODS: A convenience sample of 1837 households across T&T. We identified bivariate correlates of alcohol use, and heavy episodic drinking using chi-square and t-test analyses and used multivariable logistic regression to estimate adjusted associations between household alcohol use and experiences within the past 12 months adjusted for sociodemographic covariates. RESULTS: One thousand five hundred two households had complete data for all variables (82% response rate). Nearly two thirds (64%) of households included alcohol users; 57% of household that consumed alcohol also reported heavy episodic drinking. Households that reported alcohol consumption were significantly more likely to report illnesses within the households, relationship problems, and behavioral and antisocial problems with children. Among households where a member was employed, those who consumed alcohol were nearly twice as likely (OR = 1.98; 95% confidence interval (CI) 1.03, 3.82) to have a household member call in sick to work and 2.9 times as likely (OR = 2.9; CI 1.19, 7.04) to have a household member suffer work related problems compared with households who reported not consuming alcohol. CONCLUSIONS: Approximately two thirds of households in T&T reported using alcohol. These households were more likely to report psychological, physical, and social problems. These findings would support efforts to enforce current policies, laws, and regulations as well as new strategies to reduce the impact of harmful alcohol consumption on households in T&T.

Pilot scale nanofiltration treatment of olive mill wastewater: a technical and economical evaluation.

The treatment of large volumes of olive mill wastewater is presently a challenge. This study reports the technical and economical feasibility of a sequential treatment of olive mill wastewater comprising a dissolved air flotation pre-treatment and nanofiltration. Different pilot nanofiltration assays were conducted in a concentration mode up to different volume reduction factors (29, 45, 58, and 81). Data attained demonstrated that nanofiltration can be operated at considerably high volume reduction factors and still be effective towards the removal of several components. A flux decline of approximately 50% was observed at the highest volume reduction factor, mainly due to increase of the osmotic pressure. Considerably high rejections were obtained across all experiments for total suspended solids (83 to >99%), total organic carbon (64 to 99%), chemical oxygen demand (53 to 77%), and oil and grease (67 to >82%). Treated water was in compliance with European legal limits for discharge regarding total suspended solids and oil and grease. The potential recovery of phenolic compounds was evaluated and found not relevant. It was demonstrated that nanofiltration is economically feasible, involving operation costs of approximately 2.56-3.08 €/m3, depending on the working plan schedule and volume reduction factor, and requiring a footprint of approximately 52 m2 to treat 1000 m3 of olive mill wastewater.

Complications of endoscopic resection techniques for upper GI tract lesions.

Adverse events can occur during and after the endoscopic resection of upper gastrointestinal lesions. Their incidence can be minimized through the adoption of preventive measures and their final outcomes can be optimized through prompt identification and adequate treatment. In this evidence-based review we describe the risk factors for adverse events, preventive measures to avoid them and their management when they occur. Algorithms of action are also provided. Oesophageal strictures can be prevented with corticosteroids (either locally injected or systemically administered) and treated with endoscopic dilatation. Bleeding can be minimized through the adoption of prophylactic coagulation and novel preventive measures are emerging and being evaluated. Bleeding management includes coagulation therapy, clips and haemostatic powders. Perforations can nowadays be successfully treated endoscopically in the majority of the cases and conservative treatment is associated with favourable outcomes although optimal management is unclear.

Morphological alterations in salivary glands of Rhipicephalus sanguineus ticks (Acari: Ixodidae) exposed to neem seed oil with known azadirachtin concentration.

Neem (Azadirachta indica) has attracted the attention of researchers worldwide due to its repellent properties and recognized effects on the morphology and physiology of arthropods, including ticks. Therefore, this study aimed to demonstrate the effects of neem seed oil enriched with azadirachtin on salivary glands of Rhipicephalus sanguineus ticks, targets of great veterinary interest because of their ability to transmit pathogens to dogs. For this, R. sanguineus semi-engorged females were subjected to treatment with neem seed oil, with known azadirachtin concentrations (200, 400 and 600ppm). After dissection, salivary glands were collected and evaluated through morphological techniques in light microscopy, confocal scanning laser microscopy and transmission electron microscopy, so that the possible relation between neem action and further impairment in these ectoparasites feed performance could be established. Neem oil demonstrated a clear dose-dependent effect in the analyzed samples. The agranular (type I) and granular acini (types II and III) showed, particularly in individuals treated with the highest concentrations of the product, cells with irregular shape, intense cytoplasmic disorganization and vacuolation, dilation of rough endoplasmic reticulum lumen, besides alterations in mitochondrial intermembrane space. These morphological damages may indicate modifications in salivary glands physiology, demonstrating the harmful effects of compounds present in neem oil on ticks. These results reinforce the potential of neem as an alternative method for controlling R. sanguineus ticks, instead of synthetic acaricides.

Endoscopic submucosal dissection: European Society of Gastrointestinal Endoscopy (ESGE) Guideline

This Guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE). The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system 1 2 was adopted to define the strength of recommendations and the quality of evidence. Main Recommendations: 1 ESGE recommends endoscopic en bloc resection for superficial esophageal squamous cell cancers (SCCs), excluding those with obvious submucosal involvement (strong recommendation, moderate quality evidence). Endoscopic mucosal resection (EMR) may be considered in such lesions when they are smaller than 10 mm if en bloc resection can be assured. However, ESGE recommends endoscopic submucosal dissection (ESD) as the first option, mainly to provide an en bloc resection with accurate pathology staging and to avoid missing important histological features (strong recommendation, moderate quality evidence). 2 ESGE recommends endoscopic resection with a curative intent for visible lesions in Barrett's esophagus (strong recommendation, moderate quality evidence). ESD has not been shown to be superior to EMR for excision of mucosal cancer, and for that reason EMR should be preferred. ESD may be considered in selected cases, such as lesions larger than 15 mm, poorly lifting tumors, and lesions at risk for submucosal invasion (strong recommendation, moderate quality evidence). 3 ESGE recommends endoscopic resection for the treatment of gastric superficial neoplastic lesions that possess a very low risk of lymph node metastasis (strong recommendation, high quality evidence). EMR is an acceptable option for lesions smaller than 10 - 15 mm with a very low probability of advanced histology (Paris 0-IIa). However, ESGE recommends ESD as treatment of choice for most gastric superficial neoplastic lesions (strong recommendation, moderate quality evidence). 4 ESGE states that the majority of colonic and rectal superficial lesions can be effectively removed in a curative way by standard polypectomy and/or by EMR (strong recommendation, moderate quality evidence). ESD can be considered for removal of colonic and rectal lesions with high suspicion of limited submucosal invasion that is based on two main criteria of depressed morphology and irregular or nongranular surface pattern, particularly if the lesions are larger than 20 mm; or ESD can be considered for colorectal lesions that otherwise cannot be optimally and radically removed by snare-based techniques (strong recommendation, moderate quality evidence).(AU)