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Solutions for submucosal injection: What to choose and how to do it

World Journal of Gastroenterology 2019年第7期25卷 777-788页

作者： Rui Castro Diogo Libanio Inês Pita mário dinis-ribeiro Department of Gastroenterology Portuguese Oncology Institute of Porto CIDES/CINTESIS Faculty of Medicine University of Porto

During the past decades, endoscopic resection techniques have gradually improved and gained more importance for the management of premalignant lesions and early cancers. These endoscopic resection techniques can be divided in 3 major groups: snare polipectomy, endoscopic mucosal resection(EmR) and endoscopic submucosal dissection(ESD). The use of submucosal injection is essential for the majority of EmR techniques and is an integral part of ESD,whereas during polipectomy it is not crucial in most cases except to prevent bleeding in large polyps and/or those with large stalks as an alternative to mechanical methods. Injection provides a lifting up effect of the lesion separating it from the muscular layer, thereby reducing thermal injury and the risk of perforation and bleeding while also facilitating en-bloc resection by improving technical feasibility. With this work, we aim to review the most common endoscopic resection techniques and the importance of submucosal injection in each one of them. For that, we present some of the most commonly used submucosal injection solutions, taking into account their advantages and disadvantages. We also discuss, based on current recommendations and our own experience, how and when to preform submucosal injection, depending on lesions features and endoscopic resection technique that′s being used, to assure complete resection and to prevent associated adverse events. Finally, we also present and discuss some new proposed submucosal injection solutions,endoscopic resection techniques and devices that may have a major impact on the future of therapeutic endoscopy.

关键词： Snare polipectomy Endoscopic mucosal resection Endoscopic submucosal dissection Submucosal injection Submucosal injection solution

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Helicobacter pylori and microRNAs:Relation with innate immunity and progression of preneoplastic conditions

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World Journal of Clinical Oncology 2015年第5期6卷 111-132页

作者： Diogo Libanio mário dinis-ribeiro Pedro Pimentel-Nunes Gastroenterology Department Portuguese Oncology Institute Center for Health Technology and Services Resarch Faculty of Medicine University of Porto Department of Health Information and Decision Sciences Faculty of Medicine University of Porto Department of Physiology and Cardio- thoracic Surgery Cardiovascular Research and Development UnitFaculty of Medicine University of Porto

The accepted paradigm for intestinal-type gastric cancer pathogenesis is a multistep progression from chronic gastritis induced by Helicobacter pylori(H. pylori) to gastric atrophy, intestinal metaplasia, dysplasia and ultimately gastric cancer. The genetic and molecular mechanisms underlying disease progression are still not completely understood as only a fraction of colonized individuals ever develop neoplasia suggesting that bacterial, host and environmental factors are involved. micro RNAs are noncoding RNAs that may influence H. pylori-related pathology through the regulation of the transcription and expression of various genes, playing an important role in inflammation, cell proliferation, apoptosis and differentiation. Indeed, H. pylori have been shown to modify micro RNA expression in the gastric mucosa and micro RNAs are involved in the immune host response to the bacteria and in the regulation of the inflammatory response. micro RNAs have a key role in the regulation of inflammatory pathways and H. pylori may influence inflammation-mediated gastric carcinogenesis possibly through DNA methylation and epigenetic silencing of tumor suppressor micro RNAs. Furthermore, micro RNAs influenced by H. pylori also have been found to be involved in cell cycle regulation, apoptosis and epithelial-mesenchymal transition. Altogether, micro RNAs seem to have an important role in the progression from gastritis to preneoplastic conditions and neoplastic lesions and since each micro RNA can control the expression of hundreds to thousands of genes, knowledge of micro RNAs target genes and their functions are of paramount importance. In this article we present a comprehensive review about the role of micro RNAs in H. pylori gastric carcinogenesis, identifying the micro RNAs downregulated and upregulated in the infection and clarifying their biological role in the link between immune host response, inflammation, DNA methylation and gastric carcinogenesis.

关键词： Helicobacter pylori microRNA Gastric cancer Inflammation DNA methylation Preneoplastic conditions Stomach neoplasms Immune response

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-765G > C COX-2 polymorphism may be a susceptibility marker for gastric adenocarcinoma in patients with atrophy or intestinal metaplasia

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World Journal of Gastroenterology 2006年第34期12卷 5473-5478页

作者： Carina Pereira Hugo Sousa Paula Ferreira maria Fragoso Luís moreira-Dias Carlos Lopes Rui medeiros mário dinis-ribeiro molecular Oncology Group Portuguese Institute of Oncology of Porto Portugal and ICBAS Abel Salazar Institute for the Biomedical Sciences Porto Portugal Oncology Department Portuguese Institute of Oncology of Porto Portugal Gastroenterology Department Portuguese Institute of Oncology of Porto Portugal and Cintesis / Faculty of medicine University of Porto Porto Portugal

AIm： To investigate the relationship between the -765G 〉 C COX-2 polymorphism and the development of different gastric lesions： atrophy or intestinal metaplasia and gastric adenocarcinoma. mETHODS： A cross-sectional study was performed involving 320 Portuguese individuals （210 without evidence of neoplastic disease, 73 patients with gastric adenocarcinomas and 37 with atrophy or intestinal metaplasia） using a PCR-RFLP method.RESULTS： -765C allele was overrepresented in the patients with gastric adenocarcinoma （51%） when compared either with the control group （38%） or patients with atrophy or intestinal metaplasia （27%）. Callele was found to be very common in our population （0.22）, and a multivariate logistic regression analysis revealed nearly 3-fold increased risk for the progression to gastric adenocarcinoma in patients with atrophy or intestinal metaplasia carrying the -765C allele （OR = 2.67, 95% CI = 1.03-6.93; P = 0.04）.CONCLUSION： -765C carrier status should be considered as another susceptibility marker for gastric adenocarcinoma development in patients with atrophy or intestinal metaplasia.

关键词： Gastric adenocarcinoma Atrophy Intestinal metaplasia COX-2 Polymorphism PCR-RFLP Pharmacogenomic

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Toll-Like Receptors as Biomarkers of Gastric Carcinogenesis:Implications for Diagnosis,Prognosis and Treatment

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Journal of Cancer Therapy 2013年第5期4卷 1037-1047页

作者： Pedro Pimentel-Nunes Joao Bruno Soares mário dinis-ribeiro Department of Physiology Cardiovascular Research&Development UnitFaculty of MedicineUniversity of PortoPortoPortugal Gastroenterology Department Portuguese Oncology InstitutePortoPortugal Gastroenterology Department Hospital de BragaBragaPortugal CIDES/CINTESIS Faculty of MedicineUniversity of PortoPortoPortugal

Toll-like receptors (TLR) are essential for Helicobacter pylori (Hp) recognition and subsequent innate and adaptive immunity responses. TLR2 appears to be the receptor responsible for most of the immunologic reaction against Hp infection. However, TLR4, TLR9 and eventually TLR5 may also have a synergic effect with TLR2 against Hp. It has been shown that gastric Hp infection increases TLR expression in the gastric mucosa. moreover, recent studies have shown that human gastric carcinogenesis is associated not only with increased expression of TLR but also with decreased expression of their inhibitors such as Toll-Interacting Protein (TOLLIP) and peroxisome proliferator-activated receptor (PPAR)-g. Indeed, gastric dysplasia and adenocarcinoma are associated with high expression levels of TLR and low levels of TOLLIP and PPAR-g, suggesting increased activation of these receptors throughout human gastric carcinogenesis. In this article we discuss how these novels findings could be used not only for the diagnosis and prognosis of gastric lesions associated with Hp infection but also for their treatment. Specifically, we discuss the potential use of TLR agonists in addition to antibiotics to improve eradication rates of Hp and of TLR antagonists to slow the progression of gastric preneoplastic lesions. We also discuss the potential value of TLR signalling blockers and quantification of tumoral TLR expression, respectively, in the treatment and prognosis of gastric cancer. In conclusion, TLRs can be an important link between Hp and the sequence of gastric carcinogenesis and they can be used as biomarkers of gastric carcinogenesis. In this article, future lines of investigation related with these novel scientific findings are proposed and discussed.

关键词： Toll-Like Receptors Gastric Cancer TOLLIP Carcinogenesis Helicobacter pylori

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Gastric cancer in a Caucasian population: Role of pepsinogen C genetic variants

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World Journal of Gastroenterology 2006年第31期12卷 5033-5036页

作者： Ana L Pinto-Correia Hugo Sousa maria Fragoso Luís moreira-Dias Carlos Lopes Rui medeiros mário dinis-ribeiro molecular Oncology GroupPortuguese Institute of Oncology of Porto Portugal Oncology DepartmentPortuguese Institute of Oncology of Porto Portugal Gastroenterology DepartmentPortuguese Institute of Oncology of Porto Portugal and ICBAS Abel Salazar Institute for the Biomedical SciencesPortoPortugal and CINTESIS/Faculty of medicine University of Porto PortoPortugal

AIm： To study the role of an insertion/deletion polymorphism in the pepsinogen C （PGC） gene, an effective marker for terminal differentiation of the stomach mucosa, in the susceptibility to the development of gastric lesions. mETHODS： The study was performed with 99 samples of known gastric lesions and 127 samples without evidence of neoplastic disease. PCR was employed and the 6 polymorphic alleles were amplified： Allele 1 （510 bp）, Allele 2 （480 bp）, Allele 3/4 （450/460 bp）, Allele 5 （400 bp） and Allele 6 （310 bp）. RESULTS： Our results revealed that Allele 6 carriers seemed to have protection against the development of any gastric lesion （OR = 0.34; P 〈 0.001）, non-dysplastic lesions associated with gastric adenocarcinoma such as atrophy or intestinal metaplasia （OR = 0.28; P 〈 0.001） or invasive GC （OR = 0.39; P = 0.004）. CONCLUSION： Our study reveals that the Allele 6 carrier status has a protective role in the development of gastric lesions, probably due to its association with higher expression of PGC. moreover, the frequency of Allele 6 carriers in the control group is far higher than that obtained in Asian populations, which might represent a genetic gap between Caucasian and Asian populations.

关键词： Gastric adenocarcinoma Pepsinogen C Polymorphism

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Association between EGF +61A/G polymorphism and gastric cancer in Caucasians

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World Journal of Gastroenterology 2011年第4期17卷 488-492页

作者： Ana Paula Araújo Bruno m Costa Ana L Pinto-Correia maria Fragoso Paula Ferreira mário dinis-ribeiro Sandra Costa Rui m Reis Rui medeiros molecular Oncology Group Portuguese Institute of Oncology of Porto Life and Health Sciences Research Institute (ICVS) School of Health Sciences Oncology Department Portuguese Institute of Oncology of Porto Gastroenterology Department Portuguese Institute of Oncology of Porto Portugal Cintesis/Faculty of medicine University of Porto Centro de Estudos em Biomedicina Health Sciences Faculty-Fernando Pessoa University Instituto de Ciencias Biomédicas de Abel Salazar Abel Salazar Institute for the Biomedical Sciences

AIm: To investigate the association between epidermal growth factor (EGF) +61A/G polymorphism and susceptibility to gastric cancer, through a cross-sectional study. mETHODS: Polymerase chain reaction resctriction fragment lenght polymorphism analyses were used to genotype EGF +61 in 207 patients with gastric lesions (162 patients with gastric adenocarcinomas, 45 with atrophy or intestinal metaplasia) and 984 controls. All subjects were Caucasian. RESULTS: Genotype distribution was 23.5% for GG and 76.5% for GA/AA in the control group, 18.4% for GG and 68.6% for GA/AA in the entire group with gastric lesions and 17.9% for GG and 82.1% for GA/AA in the group with gastric adenocarcinoma. No statistically significant associations were found between EGF +61 variants and risk for developing gastric cancer [odds ratios (OR) = 1.41, 95% confidence intervals (CI): 0.90-2.21, P = 0.116]. However, the stratification of individuals by gender revealed that males carrying A alleles (EGF +61A/G or AA) had an increased risk for developing gastric cancer as compared to GG homozygous males (OR = 1.55, 95% CI: 1.05-2.28, P = 0.021). CONCLUSION: In summary, we found that males who were A carriers for EGF +61 had an increased risk for developing gastric cancer. This result may be explained by the suggestion that women secrete less gastric acid than men.

关键词： Epidermal growth factor polymorphism Epidermal growth factor receptor Gastric cancer

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Web-based system for training and dissemination of a magnification chromoendoscopy classification

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World Journal of Gastroenterology 2008年第46期14卷 7086-7092页

作者： mário Jorge dinis-ribeiro Ricardo Cruz Correia Cristina Santos Sónia Fernandes Ernesto Palhares Rui Almeida Silva Pedro Amaro miguel Areia Altamiro Costa-Pereira Luis moreira-Dias Gastroenterology Department Portuguese Oncology Institute Center for Research in Information Systems and Health Technologies (CINTESIS)/Department of Biostatistics and medical Informatics Porto Faculty of Medicine Gastroenterology Department Coimbra University Hospital

AIm： To evaluate the use of web-based technologies to assess the learning curve and reassess reproducibility of a simplified version of a classification for gastric magnification chromoendoscopy （mC）. mETHODS： As part of a multicenter trial, a hybrid approach was taken using a CD-ROm, with 20 films of mC lasting 5 s each and an ＂autorun＂ file triggering a local HTmL frameset referenced to a remote questionnaire through an Internet connection. Three endoscopists were asked to prospectively and independently classify 10 of these films randomly selected with at least 3 d apart. The answers were centrally stored and returned to participants together with adequate feedback with the right answer. RESULTS： For classification in 3 groups, both intra- [Cohen＇s kappa （K） = 0.79-1.00 to 0.89-1.00] and inter-observer agreement increased from 1st （moderate） to 6th observation （k = 0.94）. Also, agreement with reference increased in the last observations （0.90, 1.00 and 1.00, for observers A, B and C, respectively）. Validity of 100% was obtained by all observers at their 4th observation. When a 4th （sub）group was considered, inter-observer agreement was almost perfect （K = 0.92） at 6th observation. The relation with reference clearly improved into K （0.93-1.00） and sensitivity （75%-100%） at their 6th observations. CONCLUSION： This mC classification seems to be easily explainable and learnable as shown by excellent intra- and inter-observer agreement, and improved agreement with reference. A web system such as the one used in this study may be useful for endoscopic or other image based diagnostic procedures with respect to definition, education and dissemination.

关键词： magnification Chromoendoscopy Reproducibility Learning curve

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Biomarkers of hypoxic-ischemic encephalopathy:a systematic review

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World Journal of Pediatrics 2023年第6期19卷 505-548页

作者： Ines Caramelo margarida Coelho miguel Rosado Carla m.P.Cardoso Alexandra dinis Carlos B.Duarte mario Graos Bruno manadas CNC-Center for Neuroscience and Cell Biology University of Coimbra3004‑504 CoimbraPortugal PhD Programme in Experimental Biology and Biomedicine Institute for Interdisciplinary Research(IIIUC)University of CoimbraCasa Costa Alemão3030‑789 CoimbraPortugal Chemistry Department Faculty of Sciences and TechnologyUniversity of Coimbra3004‑535 CoimbraPortugal Stemlab SA 3060‑197 CantanhedePortugal Pediatric Intensive Care Unit Hospital PediátricoCentro Hospitalar E Universitário de Coimbra3000‑075 CoimbraPortugal Department of Life Sciences University of Coimbra3001‑401 CoimbraPortugal Biocant Technology Transfer Association3060‑197 CantanhedePortugal Institute for Interdisciplinary Research University of Coimbra(IIIUC)3030‑789 CoimbraPortugal

Background Current diagnostic criteria for hypoxic–ischemic encephalopathy in the early hours lack objective measurement ***,this systematic review aims to identify putative molecules that can be used in diagnosis in daily clinical practice(PROSPERO ID:CRD42021272610).Data sources Searches were performed in Pubmed,Web of Science,and Science Direct databases until November *** original papers analyzing samples from newborns>36 weeks that met at least two American College of Obstetricians and Gynecologists diagnostic criteria and/or imaging evidence of cerebral damage were *** was assessed by the Newcastle–Ottawa *** search and data extraction were verified by two authors *** From 373 papers,30 met the inclusion *** from samples collected in the first 72 hours were extracted,and increased serum levels of neuron-specific enolase and S100-calcium-binding protein-B were associated with a worse prognosis in newborns that suffered an episode of perinatal *** addition,the levels of glial fibrillary acidic protein,ubiquitin carboxyl terminal hydrolase isozyme-L1,glutamic pyruvic transaminase-2,lactate,and glucose were elevated in newborns diagnosed with hypoxic–ischemic ***,pathway analysis revealed insulin-like growth factor signaling and alanine,aspartate and glutamate metabolism to be involved in the early molecular response to *** Neuron-specific enolase and S100-calcium-binding protein-B are potential biomarkers,since they are correlated with an unfavorable outcome of hypoxic-ischemic encephalopathy ***,more studies are required to determine the sensitivity and specificity of this approach to be validated for clinical practice.

关键词： Biomarker Hypoxic-ischemic encephalopathy Neonatal brain injury Newborn Neuron-specific enolase S100-calcium-binding protein-B

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microglial exosomes in retinal neuroinflammation: focus in glaucoma

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Neural Regeneration Research 2021年第9期16卷 1801-1802页

作者： Ines dinis Aires Ana Raquel Santiago University of Coimbra Coimbra Institute for Clinical and Biomedical Research(iCBR)Faculty of MedicineCoimbraPortugal University of Coimbra Center for Innovative Biomedicine and Biotechnology(CIBB)CoimbraPortugal Clinical Academic Center of Coimbra(CACC) CoimbraPortugal Association for Innovation and Biomedical Research on Light and Image(AIBILI) CoimbraPortugal

Glaucoma is a leading cause of irreversible blindness, expected to affect 140 million people worldwide by the year 2040. The pathophysiology of glaucoma involves retinal ganglion cell loss, optic nerve atrophy and cupping of the optic disk, culminating in visual field loss(Boia et al., 2020). Glaucoma is a multifactorial disease in which increased intraocular pressure is the main risk factor.

关键词： glaucoma inflammation al.

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Analysis of the testimonial evidence of Portugal's first major forensic case:part Ⅱ

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Forensic Sciences Research 2020年第4期5卷 266-285页

作者： Ricardo Jorge dinis-Oliveira Department of Public Health and Forensic Sciences and Medical EducationFaculty of MedicineUniversity of PortoPortoPortugal IINFACTS-Institute of Research and Advanced Training in Health Sciences and Technologies Department of SciencesUniversity Institute of Health Sciences(IUCS)Advanced Polytechnic and University Cooperative(CESPU)CRLGandraPortugal UCIBIO-REQUImTE Laboratory of Toxicology

The crime possibly perpetrated by a doctor named Vicente Urbino de Freitas in 1890 is one of the most famous cases of poisoning,and it had echoes in the Portuguese and foreign press for several *** prestigious doctor was convicted of the fatal poisoning of his *** also attempted the homicide of two nieces and their mother-in-law,who only escaped because they obstinately refused to comply with the"therapeutics"prescribed by the family *** motive of the crime should have been Vicente Urbino de Freitas'ambition to receive the family inheritance of his wife,the daughter of the well-known mer-chant Jose Antonio Sampaio of Flores Street in *** Urbino de Freitas was con-victed but doubt about his guilt persists for more than a *** second work aimed to collect and analyse all the relevant and contradictory testimonial evidence of the prosecu-tion and defence *** case represents an odd historical record obtained through more than 12years of research on the first major significant Portuguese forensic *** and unprecedented testimonial evidence and photographs were obtained from different countries and then repaired,since these also provide an important historical record of the medical photography.

关键词： History of legal medicine forensic sciences forensic toxicology Vicente Urbino de Freitas mário Guilherme Augusto de Sampaio testimonial evidence Flores Street

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