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Background and aims: Inflammatory Bowel Disease (IBD) with colonic involvement increases colorectal cancer risk. However, the distinction between IBD related and sporadic dysplasia in IBD patients is difficult. Some data favors the importance of abnormal DNA methylation in IBD-related carcinogenesis. We aimed to define methylation patterns in patients with colonic cancer or dysplasia diagnosis following an IBD diagnosis.Methods: Multicentric cross-sectional study-91 samples from colonic mucosa with/without dysplasia from 9 patients with IBD-related dysplasia/cancer and 26 patients with IBD and sporadic dysplasia/cancer were included. Methylation patterns of CpG islands in the promoter regions of 67 genes were studied by Methylation-specific Multiplex Ligation-dependent Probe Amplification.Results: Mean age at IBD diagnosis: 42 ± 16 years;at dysplasia diagnosis: 56 ± 14 years. Twenty-ninepatients had ulcerative colitis. Twenty-five patients had at least 1 lesion endoscopically described as adenoma-like, 4 at least 1 non-adenoma like, 3 had cancer and 3 had dysplasia in flat mucosa. No patient had both adenoma-like and non-adenoma-like lesions. Patients with an IBD-related lesion were significantly younger at IBD diagnosis (p = .003) and at dysplasia/cancer diagnosis (p = .039). Promoter methylation of IGF2, RARB, ESR1, CHFR, CDH13, WT1, GATA5, WIF1genes was significantly associated to dysplasia/cancer; methylation of MSH6, TIMP3 was significantly associated to IBD-related dysplasia/cancer. Promoter methylation of MSH6, MSH3, RUNX3, CRABP1, TP73, RARB, CDH13, PAX5, WT1, THBS1, TP53, SFRP1, WIF1, APAF1, BCL2 genes was significantly associated to active IBD.Conclusions: Methylation analysis, namely of MSH6, may contribute to the classification of dysplastic lesions in IBD- to be further tested in prospective studies.
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Adenoma/genética , Colite Ulcerativa/genética , Colo/patologia , Neoplasias do Colo/genética , Metilação de DNA/genética , Mucosa Intestinal/patologia , Adenoma/patologia , Adulto , Biomarcadores Tumorais/genética , Carcinogênese/genética , Colite Ulcerativa/patologia , Neoplasias do Colo/patologia , Estudos Transversais , Proteínas de Ligação a DNA/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Portugal , Regiões Promotoras Genéticas/genéticaRESUMO
BACKGROUND: In current guidelines, endoscopic ultrasound with fine-needle aspiration (EUS-FNA) is recommended in pancreatic cystic lesions (PCLs) with worrisome features (size ≥ 3 cm, mural nodule, or Wirsung dilation). OBJECTIVE: To evaluate the diagnostic ability and assess the accuracy of EUS-FNA in PCLs smaller than 3 cm. METHODS: Retrospective study of PCLs < 3 cm (2007-2016) undergoing EUS-FNA. Clinical, EUS and pancreatic cystic fluid (PCF) data were prospectively registered. Performance of EUS-FNA with PCF analysis for the detection of malignancy and accuracy in surgical cohort were analyzed. RESULTS: We evaluated 115 patients with PCLs < 3 cm who underwent EUS-FNA. 19 patients underwent surgery, 7 had malignant, 8 pre-malignant, and the remaining 4 benign lesions. Mass/mural nodule was present in 27% of the cysts, CEA level was higher than 192 ng/mL in 39.4% of patients, and only 35% of cytologic samples were informative. Nevertheless, additional FNA for PCF analysis improved the diagnostic performance of EUS imaging-AUC = 0.80 versus AUC = 60. CONCLUSION: EUS-FNA has good accuracy in PCLs < 3 cm. It confirmed malignancy even in lesions without worrisome features (nodule/mass), with two in every five resections showing high-risk/malignant lesions. EUS-FNA was also useful to diagnose benign cysts, possibly allowing surveillance to be stopped in one in every five patients.
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Cisto Pancreático , Neoplasias Pancreáticas , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Endossonografia , Humanos , Cisto Pancreático/diagnóstico por imagem , Neoplasias Pancreáticas/diagnóstico por imagem , Estudos RetrospectivosRESUMO
Primary esophageal cancer (EC) frequently presents as a locally advanced disease with airway involvement. Placement of combined esophageal and airway stents has been reported in small series to be an effective palliation strategy. Our aims are to present the largest cohort of EC patients who underwent double stent palliation and to evaluate the safety and efficacy of this approach. Longitudinal cohort study of patients with primary EC undergoing two-stage esophageal and airway stent placement at an oncology referral institute (January 2000-January 2019). Assessments: baseline demographics and clinical variables; baseline and week 2 dysphagia, dyspnea and performance status (PS) scores; baseline and week 8 body mass index (BMI); overall survival. Statistics: paired t-test; Kaplan-Meier method. Seventy patients (89% men, mean age 60.20 ± 8.41) underwent double stenting. Esophageal stent was placed for esophageal stenosis and dysphagia (n = 41; placement of a second stent due to recurrence in nine cases) or esophagorespiratory fistulas (ERFs) (n = 29); airway stent was required for ERF sealing (n = 29 + 7 new ERFs after esophageal stent) and to ensure airway patency due to malignant stenosis (n = 29; placement of a second stent due to recurrence in 13 cases) or compression (n = 5). There were 13, endoscopically managed, major complications after esophageal stent [hemorrage (n = 1), migration (n = 5) and new fistulas (n = 7)]. As for airway stents, four major complications were recorded [hemorrage (n = 1) and three deaths due to respiratory infection and ultimately respiratory failure 3-7 days after the procedure]. Overall, patients showed significant improvement in dysphagia and dyspnea symptoms (3.21 vs. 1.31 e 15.56 vs. 10.87; P < 0.001). There was a PS improvement for 89.2% (n = 58) of the patients. BMI at week 8 was comparable to baseline records. Mean survival was 137.83 ± 24.14 days (95% CI: 90.51-185.15). Survival was longer for better PS (PS1, 249.95 days; PS2, 83.74 days; PS3, 22.43 days; PS4, 30.00 days). This is the largest comprehensive assessment of double stent palliation in advanced incurable EC. For both esophageal or airway stenosis and fistula, placement of combined esophageal and airway stents was a feasible, effective, fast-acting and safe modality for symptom palliation and body mass maintenance. Patient autonomy followed symptom improvement. Since it is impossible to provide treatment for cure in most of these cases, this endoscopic strategy, performed in differentiated units with the required technical capacity, may guarantee treatment for the relief of palliative EC.
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Transtornos de Deglutição , Neoplasias Esofágicas , Estenose Esofágica , Cuidados Paliativos , Idoso , Transtornos de Deglutição/etiologia , Neoplasias Esofágicas/complicações , Neoplasias Esofágicas/cirurgia , Estenose Esofágica/etiologia , Estenose Esofágica/cirurgia , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , StentsRESUMO
The diagnosis of periodontal disease is commonly based on objective evaluations of the patient's medical/dental history as well as clinical and radiographic examinations. However, periodontal disease should also be evaluated subjectively through measures that quantify its impact on oral health-related quality of life. The aim of this study was to evaluate the impact of periodontal disease on quality of life among adolescents, adults and older adults. A systematic search of the literature was performed for scientific articles published up to July 2015 using electronic databases and a manual search. Two independent reviewers performed the selection of the studies, extracted the data and assessed the methodological quality. Thirty-four cross-sectional studies involving any age group, except children, and the use of questionnaires for the assessment of the impact of periodontal disease on quality of life were included. Twenty-five studies demonstrated that periodontal disease was associated with a negative impact on quality of life, with severe periodontitis exerting the most significant impact by compromising aspects related to function and esthetics. Unlike periodontitis, gingivitis was associated with pain as well as difficulties performing oral hygiene and wearing dentures. Gingivitis was also negatively correlated with comfort. The results indicate that periodontal disease may exert an impact on quality of life of individuals, with greater severity of the disease related to greater impact. Longitudinal studies with representative samples are needed to ensure validity of the findings.
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Doenças Periodontais/psicologia , Qualidade de Vida , Adolescente , Adulto , Idoso , Humanos , Pessoa de Meia-Idade , Perfil de Impacto da DoençaRESUMO
Cardiac mucosa (CM) of the adult, regardless its location, shares phenotypic characteristics with Barrett's epithelium, namely villin expression and a Barrett's pattern of cytokeratins 7 and 20 expression. As far as we know, the phenotypic profile of CM in children has not been studied. The objective was to evaluate the phenotypic profile of cardiac mucosa from the esophagogastric junction of children with reflux symptoms. Biopsies routinely performed at the esophagogastric junction of children submitted to upper-gastrointestinal endoscopy for complaints suggestive of reflux were retrieved from the archive and used for the purposes of this study. Biopsies were assessed for the presence of squamous epithelium, cardiac and oxyntic mucosa and intestinal metaplasia. Samples displaying both squamous and columnar epithelia were immunohistochemically evaluated for the presence of villin and sucrase-isomaltae and for the expression of cytokeratins 7 and 20. From the 42 biopsies samples retrieved, 30 had simultaneously squamous and columnar epithelia. Cardiac mucosa was present in 86.7% of the cases, and intestinal metaplasia was observed only in one (3.3%). Villin expression in cardiac mucosa was observed in 96% of the cases and a cytokeratins 7 and 20 Barrett's pattern in 73%. Sucrase-isomaltase and MUC2 were only expressed in the case with intestinal metaplasia. Cardiac mucosa was high prevalent in biopsies from the esophagogastric junction of children with reflux. As in adults, cardiac mucosa in children has an immunoprofile similar to Barrett's esophagus. For the first time, it was shown that pediatric cardiac mucosa frequently expresses villin.
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Junção Esofagogástrica/patologia , Mucosa Gástrica/patologia , Refluxo Gastroesofágico/patologia , Adolescente , Esôfago de Barrett/patologia , Cárdia/patologia , Criança , Pré-Escolar , Junção Esofagogástrica/química , Esôfago/patologia , Feminino , Mucosa Gástrica/química , Humanos , Imuno-Histoquímica , Queratina-20/análise , Queratina-7/análise , Masculino , Proteínas dos Microfilamentos/análise , Mucina-2/análise , Fenótipo , Estudos Retrospectivos , Complexo Sacarase-Isomaltase/análiseRESUMO
Patient safety and quality of healthcare delivery systems are an objective of WHO. This study aims to present and analyse Portuguese clinical data on risk and malpractice in dental practice. Data from the Forensic Dentistry Laboratory (Faculty of Medicine, University of Coimbra) was analysed, between the years of 2013 to 2018. One hundred and seven technical reports were selected, and seventy nine files were included in the iatrogenic sequelae group. Data included the analysis of the performance of dental professionals. Sequelae were divided in descending order of occurrence:1) mandibular dysfunction (53,2%)[(42)79]; 2) neurological deficit (39,2%)[(31)79]; 3) tooth loss (6,3%)[(5)79]; and 4) opening deficit (1,3%)[(1)79].Three major areas with significant expression in the field of expert evaluations were analysed: 1) orthodontic treatment (51,9%), implant rehabilitation (29,1%), and oral surgery. Given the prevalence of malpractice, the need to assess its causes and recognise standards for its prevention is necessary.
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Responsabilidade Legal , Imperícia , Assistência Odontológica , Odontologia Legal , Humanos , PortugalRESUMO
Pyogenic granuloma is a benign vascular lesion, uncommon in the gastrointestinal tract, and extremely rare in the small bowel. The diagnosis can be challenging prior to surgery, because of its unusual endoscopic appearance.We present a case of pyogenic granuloma of the jejunum diagnosed by capsule endoscopy and double-balloon enteroscopy and successfully managed by surgical resection.
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Anemia/etiologia , Granuloma Piogênico/complicações , Granuloma Piogênico/diagnóstico por imagem , Doenças do Jejuno/complicações , Doenças do Jejuno/diagnóstico por imagem , Idoso , Endoscopia por Cápsula , Enteroscopia de Duplo Balão , Feminino , HumanosRESUMO
INTRODUCTION AND AIMS: Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is closely associated with Helicobacter pylori (HP) infection. Our aim was to evaluate demographic, clinical and endoscopic characteristics of gastric MALT lymphoma patients, as well as to analyse response to treatment and factors that affect complete remission (CR) and relapse. We also assessed the long-term prognosis. METHODS: The study involved a retrospective evaluation of consecutive patients admitted with gastric MALT lymphoma (1993-2013). RESULTS: A total of 144 patients (76 men; mean age 56) were included. At stage EI, 94/103 patients (92%) received HP eradication and 78 (83%) achieved CR after a mean period of 7 months (2-63 months) and 67 (86%) remained in CR after a mean follow-up time of 105 months. HP infection status (p = 0.004) and lymphoma localisation to the antrum plus body (p = 0.016) were associated with higher and lower CR rates, respectively. Relapse occurred in 11/78 (14%) patients after a mean period of 21 months. The absence of HP re-infection (p = 0.038), the need of only one eradication regimen (p = 0.009) and antrum lymphomas (p = 0.031) correlated with lower relapse rates. At stage EII, HP eradication was performed in 17/24 patients but only five experienced CR (30%). Among 16 patients diagnosed at stage EIV, nine achieved CR after chemotherapy ± surgery and 3/7 without remission died due to disease progression. The 5- and 10-year overall disease free survival rates were 90.5% and 79.1%, respectively. CONCLUSIONS: Most patients were diagnosed at an early stage. Eradication therapy was highly effective in inducing complete remission. Long-term evaluation showed that the long-term prognosis was very favourable.
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BACKGROUND: The definition of Barrett's oesophagus lacks consensus, particularly the requirement of intestinal metaplasia for diagnosis. Scarce information exists on the prevalence and natural history of columnar-lined oesophagus without intestinal metaplasia. AIM: To evaluate the demographics and natural history of columnar-lined oesophagus without intestinal metaplasia ≥ 2 cm in length. METHODS: Patients with columnar-lined oesophagus ≥ 2 cm in length and no intestinal metaplasia in biopsy specimens from two consecutive endoscopies with at least a 1-year interval were prospectively followed. A cohort of Barrett's oesophagus patients was used as a control. RESULTS: Columnar-lined oesophagus without intestinal metaplasia (n = 15) had a similar gender distribution, reflux symptoms prevalence and length as those of Barrett's oesophagus (n = 205). Patients were significantly younger (28.6 vs. 60 years, P < 0.0001) and accounted for 48% of patients aged <40 years in the two cohorts, but only 1% of those aged >40 years (P < 0.001). Patient distribution in both cohorts in 5 age brackets (0-19, 20-29, 30-39, 40-49, and >50 years) was significantly different, except for patients aged 40-49 years. Intestinal metaplasia was documented in 60% of the cohort after a mean follow-up of 7.1 years. CONCLUSIONS: Columnar-lined oesophagus without intestinal metaplasia ≥ 2 cm is infrequent in the setting of a systematic biopsy protocol, is associated with a younger age in comparison with Barrett's oesophagus, and appears to be an intermediate step between squamous and intestinal lining of the oesophagus.
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Esôfago de Barrett/patologia , Índice de Gravidade de Doença , Adolescente , Adulto , Esôfago de Barrett/complicações , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Metaplasia/complicações , Metaplasia/patologia , Pessoa de Meia-Idade , Adulto JovemRESUMO
Intestinal metaplasia is a prerequisite criterion for the diagnosis of Barrett's metaplasia and the sole columnar esophageal lining associated with malignancy. It is recognized by the presence of goblet cells, but columnar non-goblet elements, producing gastric or intestinal proteins, are the prevalent cell population. The cellular heterogeneity of Barrett's metaplasia is well documented but the relationship between the distinct cell subtypes and neoplasia is unclear. Our aim was to clarify the relationship between the different metaplastic populations and malignancy in order to investigate putative markers for risk stratification of Barrett's patients. We studied 46 columnar-lined esophageal segments, 15 with associated adenocarcinoma. The presence of the gastric, MUC5AC and MUC6, and the intestinal, MUC2, proteins was evaluated in metaplastic (columnar and goblet) and neoplastic cells. In neoplasia MUC5AC and MUC6 were detected in 100% and 86.6% of the cases, respectively. In metaplasia there were no differences in MUC5AC and MUC6 immunoreactivity, between cases with and without associated neoplasia, except for goblet elements producing MUC6 that were exclusive of metaplasia adjacent to adenocarcinoma (P < 0.05). MUC2 was present in 86.6% of the neoplasia. In metaplasia it was restricted to Barrett's cases and was more frequent in areas with intestinal metaplasia. Columnar-lined esophagus without intestinal metaplasia did not express MUC2. Our study suggests a relationship between the metaplastic population with gastric phenotype and malignancy, and points to the involvement of columnar as well as goblet elements in tumorigenesis. The association between goblet cells aberrantly producing MUC6 and the presence of neoplasia suggests they may be useful for risk stratification.
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Adenocarcinoma/patologia , Esôfago de Barrett/patologia , Neoplasias Esofágicas/patologia , Mucosa Gástrica/patologia , Biomarcadores Tumorais/biossíntese , Transformação Celular Neoplásica/patologia , Diagnóstico Diferencial , Mucinas Gástricas/biossíntese , Células Caliciformes/patologia , Humanos , Imuno-Histoquímica , Intestinos/patologia , Metaplasia , Mucina-6 , Mucinas/biossínteseRESUMO
OBJECTIVE: Microsatellite instability (MSI) detected in non-neoplastic mucosa of patients with ulcerative colitis has been ascribed to an excess of DNA damage associated with chronic inflammation. Folate deficiency, commonly found in patients with long-standing disease, could further contribute to this defect because folate is essential for DNA replication and repair. We evaluated MSI in the colonic mucosa of 26 patients with ulcerative colitis for >10 yr and 10 patients with Crohn's colitis and correlated MSI with folate status. METHODS: DNA was amplified using primers directed at nine different loci. Folate concentrations in serum, whole blood, and colonic mucosa were determined using the Lactobacillus casei assay. RESULTS: MSI was found in 3/23 patients (13%) with ulcerative colitis and in none of the patients with Crohn's colitis. All three patients with MSI had inactive histological disease, whereas all patients with active disease were negative for MSI (p = 0.08). Serum, whole blood, and colonic concentrations of folate were 30-50% lower in patients with MSI (p > 0.05), and folate supplements had been administered less frequently during the past 5-yr (p = 0.06). One of the patients with MSI was randomized to receive folate 5 mg/d for 6 months, and a clear change in MSI pattern was observed in three of six markers. CONCLUSIONS: A defect in DNA repair associated with a low folate status may be one additional cause for patients with ulcerative colitis exhibiting MSI in non-neoplastic mucosa.