BACKGROUND: Patients with severe aortic stenosis present frequently (∼50%) with concomitant obstructive coronary artery disease. Current guidelines recommend combined surgical aortic valve replacement (SAVR) and coronary artery bypass grafting (CABG) as the preferred treatment. Transcatheter aortic valve implantation (TAVI) and fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) represent a valid treatment alternative. We aimed to test the non-inferiority of FFR-guided PCI plus TAVI versus SAVR plus CABG in patients with severe aortic stenosis and complex coronary artery disease. METHODS: This international, multicentre, prospective, open-label, non-inferiority, randomised controlled trial was conducted at 18 tertiary medical centres across Europe. Patients (aged ≥70 years) with severe aortic stenosis and complex coronary artery disease, deemed feasible for percutaneous or surgical treatment according to the on-site Heart Team, were randomly assigned (1:1) to FFR-guided PCI plus TAVI or SAVR plus CABG according to a computer-generated sequence with random permuted blocks sizes stratified by site. The primary endpoint was a composite of all-cause mortality, myocardial infarction, disabling stroke, clinically driven target-vessel revascularisation, valve reintervention, and life-threatening or disabling bleeding at 1 year post-treatment. The trial was powered for non-inferiority (with a margin of 15%) and if met, for superiority. The primary and safety analyses were done per an intention-to-treat principle. This trial is registered with ClinicalTrials.gov (NCT03424941) and is closed. FINDINGS: Between May 31, 2018, and June 30, 2023, 172 patients were enrolled, of whom 91 were assigned to the FFR-guided PCI plus TAVI group and 81 to the SAVR plus CABG group. The mean age of patients was 76·5 years (SD 3·9). 118 (69%) of 172 patients were male and 54 (31%) patients were female. FFR-guided PCI plus TAVI resulted in favourable outcomes for the primary endpoint (four [4%] of 91 patients) versus SAVR plus CABG (17 [23%] of 77 patients; risk difference -18·5 [90% CI -27·8 to -9·7]), which was below the 15% prespecified non-inferiority margin (pnon-inferiority<0·001). FFR-guided PCI plus TAVI was superior to SAVR plus CABG (hazard ratio 0·17 [95% CI 0·06-0·51]; psuperiority<0·001), which was driven mainly by all-cause mortality (none [0%] of 91 patients vs seven (10%) of 77 patients; p=0·0025) and life-threatening bleeding (two [2%] vs nine [12%]; p=0·010). INTERPRETATION: The TCW trial is the first trial to compare percutaneous treatment versus surgical treatment in patients with severe aortic stenosis and complex coronary artery disease, showing favourable primary endpoint and mortality outcomes with percutaneous treatment. FUNDING: Isala Heart Centre and Medtronic.

• MeSH
• Aortic Valve Stenosis * surgery   complications   MeSH
• Heart Valve Prosthesis Implantation methods   MeSH
• Fractional Flow Reserve, Myocardial * MeSH
• Percutaneous Coronary Intervention * methods   MeSH
• Coronary Artery Bypass * methods   MeSH
• Humans MeSH
• Coronary Artery Disease * surgery   complications   therapy   MeSH
• Prospective Studies MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Transcatheter Aortic Valve Replacement * methods   MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Equivalence Trial MeSH
• Multicenter Study MeSH
• Comparative Study MeSH

Meta-analyses of observational and clinical studies conducted in recent years have raised serious doubts about the validity of the low-fat dietary recommendations introduced in the late 1970s/early 1980s, due to the absence of any convincing link between saturated fat and the risk of cardiovascular diseases. At the same time, long-term food supply statistics from the FAOSTAT database show that these recommendations were at the root of fundamental dietary changes in Western countries, which resulted in a lower consumption of eggs and red meat, a higher consumption of cereals and poultry, a decline in average protein quality and, overall, in a higher glycemic load of the diet. Because current views on human nutrition are based primarily on highly unreliable questionnaire data from observational studies, the purpose of this commentary is to provide an alternative ecological (country-level) perspective and to trace the consequences of these nutritional changes using the FAOSTAT database in combination with available anthropological and health statistics. This comparison shows a close connection between the decline in protein quality and the sudden reversal of the positive height trend in some Western countries, after ∼150 years of continuous growth, which points to suboptimal levels of child nutrition. The sharp increase in the prevalence of obesity and type 2 diabetes is strongly correlated with the increasing consumption of high-glycemic carbohydrates and sweeteners, and is also interconnected with the decrease in body height, because a high-quality, growth-stimulating diet during adolescence is inversely related to obesity. Given the long-term association between height and phenotypic IQ, the lower quality of nutrients in children's diet may also seriously affect intellectual potential and future civilizational development. In light of these findings, current nutritional strategies should be seriously reconsidered and recommended protein intakes for children must be urgently reevaluated.

• MeSH
• Diabetes Mellitus, Type 2 epidemiology   MeSH
• Diet * trends   MeSH
• Child MeSH
• Humans MeSH
• Adolescent MeSH
• Obesity * epidemiology   MeSH
• Body Height * MeSH
• Food Supply * statistics & numerical data   MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Adolescent MeSH
• Publication type
• Journal Article MeSH

This study presents a combined experimental and numerical investigation of fiber transport and deposition in a realistic model of the female respiratory tract, extending to the seventh generation of branching. Numerical simulations were performed using the Euler-Lagrange Euler-Rotation (ELER) method, an efficient alternative to conventional Finite Volume Methods that benefits from explicit formulation and vast scalability, enabling fast parallelization on high-performance clusters. The ELER method was coupled with the Lattice Boltzmann Method (LBM) to simulate fiber dynamics under a realistic inspiratory flow profile. Experimental validation was conducted using an identical physical airway replica. The results demonstrated good agreement between simulations and experiments in the upper airways and trachea, with some discrepancies in the bifurcations, likely owing to the challenges of modeling complex turbulent flow with ELER. This method is more accurate than corresponding effective diameter simulations. Deposition patterns were analyzed as a function of fiber dimensions, revealing higher accuracy of the ELER method for smaller particles and confirming the tendency of higher aspect ratio fibers to penetrate deeper into the lungs. The orientation-dependent deposition mechanism was deployed, underscoring the importance of solving the actual orientations of the fibers. While advancing our understanding of fiber transport in female airways, the findings also reveal limitations in current numerical techniques, particularly in bifurcations. This study emphasizes the distinct behavior of fibrous versus spherical particles, with fibers exhibiting a greater propensity to reach deeper lung regions, which has significant implications for inhalation toxicology and drug delivery.

• MeSH
• Administration, Inhalation MeSH
• Models, Biological * MeSH
• Respiratory System * MeSH
• Humans MeSH
• Lung MeSH
• Computer Simulation MeSH
• Trachea * physiology   MeSH
• Check Tag
• Humans MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

I po maximální standardní léčbě, která zahrnuje maximální chirurgickou resekci, adjuvantní radioterapii a souběžnou a následně adjuvantní chemoterapii alkylační látkou temozolomidem (TMZ), což je režim ověřený klinickými studiemi fáze III, zůstává celkové přežití u glioblastomu (GB), nejčastějšího a nejmalignějšího podtypu gliomu vysokého stupně, omezené. Pětileté přežití je nižší než 10 %, přičemž obvyklou příčinou úmrtí je lokální recidiva. Nejčastěji navrhovanými alternativami čistě paliativní léčby jsou reoperace, opětovné podání alkylačních látek včetně TMZ nebo léčba relapsu lomustinem a opakované ozařování. Opakované ozařování se jeví být možností pro GB v pečlivě vybraných případech a volba ozařovací metody mezi standardní frakcionací, stereotaktickou hypofrakcionovanou radioterapií a stereotaktickou radiochirurgií musí zohledňovat technické a s pacientem související faktory a průběh relapsu. Použití alkylačních látek TMZ a lomustinu v kombinaci s opakovaným ozařováním se zdá být strategií s přínosem zejména po výběru terapie na základě metylačního stavu promotoru O6-metylguanin-DNA-metyltransferázy. Budoucími směry výzkumu jsou neoadjuvantní imunoterapie a identifikace molekulárních biomarkerů, přesnější vymezení cílového objemu na základě pozitronové emisní tomografie/výpočetní tomografie s aminokyselinami, ale také použití inhibitorů glykolýzy ve spojení s látkami proti cévnímu endoteliálnímu růstovému faktoru. Omezení kumulativních ekvivalentních dávek po 2 Gy (EQD2) na mozkovou tkáň parenchym do výše 100 Gy v případě ultrahypofrakcionovaných režimů a do výše < 120 Gy EQD2 v případě jiných frakcionačních schémat by mohlo omezit riziko mozkové radionekrózy pod 10 %.

Even after administration of a maximal standard treatment, including gross surgical resection, adjuvant radiotherapy plus concurrent and subsequently adjuvant chemotherapy with an alkylating agent, temozolomide (TMZ), a regimen validated by phase III clinical trials, the overall survival in glioblastoma (GB), which is the most frequent and malignant subtype of high-grade glioma, remains limited. With a 5-year survival rate below 10%, local recurrence is the usual cause of death. Re-operation, re-challenge with alkylating agents including TMZ or treatment of relapse with lomustine, and re-irradiation are the most frequently proposed alternatives to purely palliative treatment. Re-irradiation seems to be an option for GB in carefully selected cases, and the choice of irradiation method between standard fractionation, stereotactic hypo-fractionated radiotherapy, and stereotactic radiosurgery must take into account technical and patient-related factors and relapse pattern. The use of alkylating agents TMZ and lomustine, in combination with re-irradiation, seems to be a strategy with benefits especially after a selection of therapy based on the methylation status of the O6-methylguanine-DNA-methyltransferase promoter. Neo-adjuvant immunotherapy and identification of molecular biomarkers, more precise delineation of the target volume, based on amino-acid positron emission tomography/CT (PET-CT), but also the use of glycolytic inhibitors in association with anti-vascular endothelial growth factor agents are future research directions. Limiting the cumulative equivalent dose in 2 Gy (EQD2) received by the brain tissue to 100 Gy in the case of ultra-hypo-fractionated regimens and to < 120 Gy EQD2 in the case of other fractionation schemes could limit the risk of cerebral radio-necrosis below 10%.

• Keywords
• radionekróza,
• MeSH
• Glioblastoma * radiotherapy   MeSH
• Humans MeSH
• Retreatment MeSH
• Radiosurgery methods   MeSH
• Radiotherapy methods   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

Invazivní karcinom močového měchýře (MIBC) je tradičně léčen neoadjuvantní chemoterapií (NAC) a radikální cystektomií (RACE). Přestože trimodální terapie (TMT), zahrnující maximální transuretrální resekci (TUR) a chemoradioterapii (CHRT), přináší srovnatelné výsledky, není dosud považována za standardní léčbu. Tato práce analyzuje výsledky recentních studií a doporučení týkajících se TMT v léčbě MIBC. Retrospektivní analýzy naznačují, že TMT dosahuje podobného přežití bez metastáz (MFS) a přežití bez nemoci (DFS) jako NAC s RACE. Neexistence přímého srovnání TMT a NAC s RACE však omezuje implementaci TMT jako standardní metody léčby. I přesto nová doporučení uznávají TMT jako rovnocennou alternativu pro pacienty s omezenou způsobilostí k NAC nebo RACE nebo preferující zachování močového měchýře. Nové strategie zahrnující imunoterapii ukazují potenciál ke zlepšení výsledků. Závěrem lze říci, že TMT představuje účinný orgán záchovný postup u vybraných pacientů s MIBC, avšak volba léčebné strategie vyžaduje individuální přístup a multi­disciplinární spolupráci.

Muscle-invasive bladder cancer (MIBC) has traditionally been treated with neoadjuvant chemotherapy (NAC) and radical cystectomy (RACE). Although trimodal therapy (TMT), involving maximal transurethral resection (TUR) and chemoradiotherapy (CRT), yields comparable results, it is not yet considered standard treatment. This paper analyses the results of recent studies and recommendations concerning TMT in the treatment of MIBC. Retrospective analyses suggest that TMT achieves metastasis-free survival (MFS) and disease-free survival (DFS) rates similar to those obtained by NAC with RACE. However, the lack of direct comparison of TMT and NAC plus RACE limits the implementation of TMT as a standard treatment method. Nevertheless, new recommendations recognise TMT as an equally valid alternative for patients with restricted eligibility for NAC or RACE, or for those who prefer bladder preservation. Novel strategies including immunotherapy show potential for improved outcomes. In conclusion, TMT is an effective organ-preserving procedure in selected patients with MIBC; however, the choice of treatment strategy requires a tailored approach and multidisciplinary collaboration.

• MeSH
• Chemoradiotherapy methods   MeSH
• Neoplasm Invasiveness MeSH
• Organ Sparing Treatments methods   MeSH
• Humans MeSH
• Urinary Bladder Neoplasms * drug therapy   radiotherapy   MeSH
• Radiotherapy methods   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

AIMS: Theranostics utilizes the nuclear properties of radioactive isotopes, especially for molecular imaging and targeted therapy. Radiopharmaceuticals (RPs), which combine a pharmaceutical ligand with a radionuclide, enable accurate diagnosis and treatment of various diseases through modalities such as PET and SPECT imaging. The aim of this papare is to review adverse reactions associated with diagnostic and therapeutic radiopharmaceuticals, with an emphasis on their severity and clinical management. MATERIALS AND METHODS: This review evaluates documented adverse effects (AEs) related to RPs used in nuclear medicine imaging (PET and SPECT) and radionuclide therapy, focusing on their severity and clinical management strategies. It also considers the mechanisms of RPs toxicity, distinguishes between general and specific AEs, and highlights the limitations in current adverse drug reaction (ADR) assessment tools. The methodology used was the research and synthesis of most relevant published literature data; most relevant papers were synthesized regarding the reporting system of ARs and categorized by the specific and systemic adverse effects of RPs. RESULTS: Side effects from diagnostic RPs are relatively rare and typically minimal. Therapeutic RPs, selected for their high-energy radiation properties, can cause DNA damage to malignant cells while minimizing harm to healthy tissues. Although adverse effects do occur, they are generally fewer and less severe compared to conventional therapies. Severe toxicity is rare and often preventable. Both patient- and provider-reported ADRs offer important safety insights, though validated assessment instruments remain limited. CONCLUSION: Radionuclide therapy offers a targeted approach that is a less invasive alternative to conventional treatments with a favorable safety profile. Continued evaluation of adverse reactions and the development of standardized ADR assessment tools are essential for improving patient outcomes and RP safety monitoring.

• MeSH
• Humans MeSH
• Neoplasms * radiotherapy   diagnostic imaging   MeSH
• Drug-Related Side Effects and Adverse Reactions * etiology   MeSH
• Radiopharmaceuticals * adverse effects   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

The selection of proper reference genes and materials is critical in the design of PCR experiments, especially for differential expression studies. In this study, we propose a method to identify robust endogenous control miRNAs in the visceral adipose tissue of C57BL/6J mice with non-alcoholic fatty liver disease induced by alternating Western and control diets. This study outlines a comprehensive methodology for the analysis of microRNA endogenous controls using microfluidic cards in conjunction with miRNA profiling through small RNA sequencing and subsequent validation by quantitative PCR and the RefFinder algorithm. Criteria included were fold change, p-value, reads per million, and gene stability assessment. A set of six putative endogenous microRNAs was identified (miR-331-3p, let-7a-5p, miR-1839-5p, miR-151a-5p, let-7d-5p, and let-7c-5p). Subsequent validation and analysis using the RefFinder algorithm assessed the stability of the selected genes, and a combination of the three most stable endogenous miRNA controls (miR-331-3p, let-7a- 5p, and miR-1839-5p) exhibiting consistent expression patterns with minimal variability was set. Given the absence of universal endogenous controls, individual evaluation of normalizers for each experiment is imperative for accurate miRNA expression measurements. This approach, which combines multiple techniques and assessments, provides a reliable strategy for identifying and validating endogenous controls in miRNA studies.

• MeSH
• Algorithms MeSH
• MicroRNAs * genetics   metabolism   MeSH
• Disease Models, Animal * MeSH
• Mice, Inbred C57BL MeSH
• Mice MeSH
• Non-alcoholic Fatty Liver Disease * genetics   metabolism   pathology   MeSH
• Intra-Abdominal Fat * metabolism   MeSH
• Gene Expression Regulation MeSH
• Gene Expression Profiling methods   MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

BACKGROUND: The canonical Wnt signaling pathway controls the continuous renewal of the intestinal epithelium and the specification of epithelial cell lineages. Tcf4, a nuclear mediator of Wnt signaling, is essential for the differentiation and maintenance of Paneth cells in the small intestine. Its deficiency is associated with reduced expression of key α-defensins, highlighting its role in host-microbe interactions. However, the exact function of Tcf4 in specifying the secretory lineage and its contribution to antimicrobial peptide production remain incompletely understood. Remarkably, α-defensin expression has also been detected in human colon adenomas, where aberrant Wnt signaling is a hallmark. This raises important questions: What is the role of these Paneth-like cells in tumor biology, and how does Tcf4 influence their identity and function? METHODS: We investigated cell specification in small intestinal crypts and colon tumors using conditional Tcf7l2 deletion, cell type-specific Cre recombinases, and reporter alleles in mice. Transcriptomic (single-cell and bulk RNA sequencing) and histological analyses were performed and complemented by microbiome profiling, antibiotic treatment, and intestinal organoids to functionally validate the main findings. RESULTS: The inactivation of Tcf4 depletes Paneth cells and antimicrobial peptides, disrupting the gut microbiota balance. In secretory progenitors, loss of Tcf4 shifts differentiation toward goblet cells. In the small intestine, alternative secretory progenitors produce Wnt ligands to support stem cells and epithelial renewal in the absence of Paneth cells. In colon tumors, Paneth-like cells form a tumor cell population, express Wnt ligands, and require Tcf4 for their identity. Loss of Tcf4 redirects their differentiation toward goblet cells. CONCLUSIONS: Tcf4 controls the balance between Paneth and goblet cells and is essential for antimicrobial peptide production in the small intestine. In colon adenomas, Paneth-like tumor cells drive antimicrobial gene expression and provide Wnt3 ligands, which may have implications for cancer therapy.

• MeSH
• alpha-Defensins metabolism   MeSH
• Cell Differentiation MeSH
• Humans MeSH
• Mice MeSH
• Colonic Neoplasms * pathology   genetics   microbiology   metabolism   MeSH
• Organoids metabolism   MeSH
• Paneth Cells metabolism   MeSH
• Goblet Cells metabolism   MeSH
• Wnt Signaling Pathway MeSH
• Gastrointestinal Microbiome * MeSH
• Intestine, Small * metabolism   pathology   microbiology   MeSH
• Transcription Factor 4 * metabolism   genetics   MeSH
• Transcriptome * MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Epilepsy, affecting over 50 million people globally, presents a significant neurological challenge. Effective prevention of epileptic seizures relies on proper administration and monitoring of Anti-Seizure Medication (ASMs). Therapeutic Drug Monitoring (TDM) ensures optimal dosage adjustment, minimizing adverse effects and potential drug interactions. While traditional venous blood collection for TDM may be stressful, emerging alternative sampling methods, particularly Dried Blood Spot (DBS) or oral fluid offer less invasive way of sampling. This study aimed to develop and validate an analytical method for the determination of lamotrigine in such alternative samples. The sample, either DBS or oral fluid, was subjected to extraction, evaporation, and reconstitution in 15 % acetonitrile containing 0.1 % formic acid. A Kinetex C18 Polar column was used for liquid chromatographic separation and MS in ESI+ mode was used for detection and quantitation of lamotrigine using an isotopically labelled internal standard according to EMA guidelines. The calibration range of the developed method enables the determination of lamotrigine in the concentration range of 1-30 μg/mL in DBS and 0.5-20 μg/mL in oral fluid. Oral fluid and DBS samples from patients treated with lamotrigine analysed by the developed method were compared to plasma concentrations measured by the hospital's accredited laboratory. Preliminary results indicate a promising potential for these alternative matrices in clinical TDM applications. By offering a less invasive sampling approach, this method improves the accessibility and safety of pharmacotherapy for epilepsy patients. The results of this study lay the foundation for further clinical applications by implementing alternative matrix TDM, which may significantly advance personalized care in epilepsy management.

• MeSH
• Anticonvulsants * analysis   blood   MeSH
• Chromatography, Liquid methods   MeSH
• Epilepsy drug therapy   MeSH
• Calibration MeSH
• Liquid Chromatography-Mass Spectrometry MeSH
• Lamotrigine * analysis   blood   MeSH
• Humans MeSH
• Limit of Detection MeSH
• Drug Monitoring * methods   MeSH
• Reproducibility of Results MeSH
• Saliva * chemistry   MeSH
• Tandem Mass Spectrometry methods   MeSH
• Dried Blood Spot Testing * methods   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Validation Study MeSH

At a population level, the European Society of Gastrointestinal Endoscopy (ESGE), the European Helicobacter and Microbiota Study Group (EHMSG), and the European Society of Pathology (ESP) suggest endoscopic screening for gastric cancer (and precancerous conditions) in high-risk regions (age-standardized rate [ASR] > 20 per 100 000 person-years) every 2 to 3 years or, if cost-effectiveness has been proven, in intermediate risk regions (ASR 10-20 per 100 000 person-years) every 5 years, but not in low-risk regions (ASR < 10).ESGE/EHMSG/ESP recommend that irrespective of country of origin, individual gastric risk assessment and stratification of precancerous conditions is recommended for first-time gastroscopy. ESGE/EHMSG/ESP suggest that gastric cancer screening or surveillance in asymptomatic individuals over 80 should be discontinued or not started, and that patients' comorbidities should be considered when treatment of superficial lesions is planned.ESGE/EHMSG/ESP recommend that a high quality endoscopy including the use of virtual chromoendoscopy (VCE), after proper training, is performed for screening, diagnosis, and staging of precancerous conditions (atrophy and intestinal metaplasia) and lesions (dysplasia or cancer), as well as after endoscopic therapy. VCE should be used to guide the sampling site for biopsies in the case of suspected neoplastic lesions as well as to guide biopsies for diagnosis and staging of gastric precancerous conditions, with random biopsies to be taken in the absence of endoscopically suspected changes. When there is a suspected early gastric neoplastic lesion, it should be properly described (location, size, Paris classification, vascular and mucosal pattern), photodocumented, and two targeted biopsies taken.ESGE/EHMSG/ESP do 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 unless there are signs of deep submucosal invasion or if the lesion is not considered suitable for endoscopic resection.ESGE/EHMSG/ESP recommend endoscopic submucosal dissection (ESD) for differentiated gastric lesions clinically staged as dysplastic (low grade and high grade) or as intramucosal carcinoma (of any size if not ulcerated or ≤ 30 mm if ulcerated), with EMR being an alternative for Paris 0-IIa lesions of size ≤ 10 mm with low likelihood of malignancy.ESGE/EHMSG/ESP suggest that a decision about ESD can be considered for malignant lesions clinically staged as having minimal submucosal invasion if differentiated and ≤ 30 mm; or for malignant lesions clinically staged as intramucosal, undifferentiated and ≤ 20 mm; and in both cases with no ulcerative findings.ESGE/EHMSG/ESP recommends patient management based on the following histological risk after endoscopic resection: Curative/very low-risk resection (lymph node metastasis [LNM] risk < 0.5 %-1 %): en bloc R0 resection; dysplastic/pT1a, differentiated lesion, no lymphovascular invasion, independent of size if no ulceration and ≤ 30 mm if ulcerated. No further staging procedure or treatment is recommended.Curative/low-risk resection (LNM risk < 3 %): en bloc R0 resection; lesion with no lymphovascular invasion and: a) pT1b, invasion ≤ 500 μm, differentiated, size ≤ 30 mm; or b) pT1a, undifferentiated, size ≤ 20 mm and no ulceration. Staging should be completed, and further treatment is generally not necessary, but a multidisciplinary discussion is required. Local-risk resection (very low risk of LNM but increased risk of local persistence/recurrence): Piecemeal resection or tumor-positive horizontal margin of a lesion otherwise meeting curative/very low-risk criteria (or meeting low-risk criteria provided that there is no submucosal invasive tumor at the resection margin in the case of piecemeal resection or tumor-positive horizontal margin for pT1b lesions [invasion ≤ 500 μm; well-differentiated; size ≤ 30 mm, and VM0]). Endoscopic surveillance/re-treatment is recommended rather than other additional treatment. High-risk resection (noncurative): Any lesion with any of the following: (a) a positive vertical margin (if carcinoma) or lymphovascular invasion or deep submucosal invasion (> 500 μm from the muscularis mucosae); (b) poorly differentiated lesions if ulceration or size > 20 mm; (c) pT1b differentiated lesions with submucosal invasion ≤ 500 μm with size > 30 mm; or (d) intramucosal ulcerative lesion with size > 30 mm. Complete staging and strong consideration for additional treatments (surgery) in multidisciplinary discussion.ESGE/EHMSG/ESP suggest the use of validated endoscopic classifications of atrophy (e. g. Kimura-Takemoto) or intestinal metaplasia (e. g. endoscopic grading of gastric intestinal metaplasia [EGGIM]) to endoscopically stage precancerous conditions and stratify the risk for gastric cancer.ESGE/EHMSG/ESP recommend that biopsies should be taken from at least two topographic sites (2 biopsies from the antrum/incisura and 2 from the corpus, guided by VCE) in two separate, clearly labeled vials. Additional biopsy from the incisura is optional.ESGE/EHMSG/ESP recommend that patients with extensive endoscopic changes (Kimura C3 + or EGGIM 5 +) or advanced histological stages of atrophic gastritis (severe atrophic changes or intestinal metaplasia, or changes in both antrum and corpus, operative link on gastritis assessment/operative link on gastric intestinal metaplasia [OLGA/OLGIM] III/IV) should be followed up with high quality endoscopy every 3 years, irrespective of the individual's country of origin.ESGE/EHMSG/ESP recommend that no surveillance is proposed for patients with mild to moderate atrophy or intestinal metaplasia restricted to the antrum, in the absence of endoscopic signs of extensive lesions or other risk factors (family history, incomplete intestinal metaplasia, persistent H. pylori infection). This group constitutes most individuals found in clinical practice.ESGE/EHMSG/ESP recommend H. pylori eradication for patients with precancerous conditions and after endoscopic or surgical therapy.ESGE/EHMSG/ESP recommend that patients should be advised to stop smoking and low-dose daily aspirin use may be considered for the prevention of gastric cancer in selected individuals with high risk for cardiovascular events.

• MeSH
• Biopsy MeSH
• Early Detection of Cancer * methods   standards   MeSH
• Gastroscopy * standards   MeSH
• Risk Assessment MeSH
• Helicobacter Infections complications   MeSH
• Humans MeSH
• Stomach Neoplasms * pathology   diagnosis   therapy   MeSH
• Precancerous Conditions * pathology   diagnosis   therapy   MeSH
• Societies, Medical MeSH
• Gastric Mucosa pathology   diagnostic imaging   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Practice Guideline MeSH
• Geographicals
• Europe MeSH