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1.
Dig Dis ; 41(1): 34-48, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35816999

RESUMO

BACKGROUND: Despite the important advances in research on neuroendocrine neoplasms of the gastro-entero-pancreatic tract, their precursor lesions are much less well known. SUMMARY: This review analyzes the preneoplastic neuroendocrine lesions of the gastro-entero-pancreatic tract, by adopting a coherent anatomical benchmark. In particular, the settings in which neuroendocrine precursor lesions represent well-recognized pathophysiological and morphological entities (with eventual molecular correlates) have been distinguished from the ones in which the nature of preneoplastic changes is still obscure. KEY MESSAGES: The aim of the paper was to summarize what is known about precursor lesions of gastro-entero-pancreatic neuroendocrine tumors, with the goal of providing a useful tool for future research aimed at obtaining a fuller understanding of the underlying biology and early development of these diseases.


Assuntos
Neoplasias Intestinais , Tumores Neuroendócrinos , Neoplasias Pancreáticas , Neoplasias Gástricas , Humanos , Neoplasias Pancreáticas/patologia , Tumores Neuroendócrinos/patologia , Pâncreas/patologia , Neoplasias Gástricas/patologia , Neoplasias Intestinais/patologia
2.
Int J Mol Sci ; 24(4)2023 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-36834698

RESUMO

In this study, we aimed to assess the accuracy of the proposed novel, noninvasive serum DSC test in predicting the risk of gastric cancer before the use of upper endoscopy. To validate the DSC test, we enrolled two series of individuals living in Veneto and Friuli-Venezia Giulia, Italy (n = 53 and n = 113, respectively), who were referred for an endoscopy. The classification used for the DSC test to predict gastric cancer risk combines the coefficient of the patient's age and sex and serum pepsinogen I and II, gastrin 17, and anti-Helicobacter pylori immunoglobulin G concentrations in two equations: Y1 and Y2. The coefficient of variables and the Y1 and Y2 cutoff points (>0.385 and >0.294, respectively) were extrapolated using regression analysis and an ROC curve analysis of two retrospective datasets (300 cases for the Y1 equation and 200 cases for the Y2 equation). The first dataset included individuals with autoimmune atrophic gastritis and first-degree relatives with gastric cancer; the second dataset included blood donors. Demographic data were collected; serum pepsinogen, gastrin G17, and anti-Helicobacter pylori IgG concentrations were assayed using an automatic Maglumi system. Gastroscopies were performed by gastroenterologists using an Olympus video endoscope with detailed photographic documentation during examinations. Biopsies were taken at five standardized mucosa sites and were assessed by a pathologist for diagnosis. The accuracy of the DSC test in predicting neoplastic gastric lesions was estimated to be 74.657% (65%CI; 67.333% to 81.079%). The DSC test was found to be a useful, noninvasive, and simple approach to predicting gastric cancer risk in a population with a medium risk of developing gastric cancer.


Assuntos
Gastrite Atrófica , Gastrite , Infecções por Helicobacter , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico , Estudos Retrospectivos , Detecção Precoce de Câncer , Pepsinogênio A , Infecções por Helicobacter/diagnóstico , Biomarcadores
3.
Int J Mol Sci ; 24(19)2023 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-37834330

RESUMO

Cytokines contribute to the pathogenesis of lupus nephritis (LN), yet their value as prognostic biomarkers is still debated. We aimed to describe the serum cytokines' profiles and prospectively assess correlations with disease features and renal response in a multicentric cohort of consecutive adult patients with biopsy-proven active LN. Cytokine associations with clinical and serological data were performed at LN diagnosis (T0), and at 3 (T3) and 6 months (T6) of follow up. Renal response according to EULAR definition was assessed at T3, T6 and T12. BAFF and interleukin (IL)-37 were measured by ELISA; IL-2, IL-10, IL-17A and IL-18 by a bead-based multiplex cytokine assay (Luminex). Thirty-nine patients with active LN (age 40.5 ± 15.6 years; F 71.8%; 84.6% proliferative LN) were enrolled, of whom twenty-nine displayed complete longitudinal records. At T0, we observed higher levels of IL-37 and IL-17 in proliferative vs. non-proliferative LN (IL-37: 0.0510 (0.0110-0.2300) vs. 0.0000 (0.0000-0.0397) ng/mL, p = 0.0441; IL-17: 2.0920 (0.5125-17.9400) vs. 0.0000 (0.0000-0.6025) pg/mL, p = 0.0026, respectively), and positive correlations between IL-10 and 24 h proteinuria (r = 0.416, p = 0.0249) and anti-dsDNA levels (r = 0.639, p = 0.0003). BAFF was higher in patients with low complement (p < 0.0001). We observed a sustained correlation between BAFF and IL-10 throughout T6 (r = 0.654, p = 0.0210). Higher baseline IL-37 and BAFF levels were associated with renal response at T3 and T6, respectively, while baseline IL-18 levels were higher in patients achieving response at T12. Our study highlights the complexity of the cytokine network and its potential value as a marker of active LN and renal response.


Assuntos
Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Adulto , Humanos , Adulto Jovem , Pessoa de Meia-Idade , Interleucina-18 , Interleucina-10 , Interleucina-17 , Citocinas , Biomarcadores
4.
Mar Drugs ; 20(9)2022 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-36135761

RESUMO

Recently, some preclinical and clinical studies have demonstrated the ability of brown seaweeds in reducing the risk factors for metabolic syndrome. Here, we analyzed the beneficial effect of a nutraceutical formulation containing a phytocomplex extracted from seaweeds and chromium picolinate in animal models of liver steatosis of differing severities (rats with non-alcoholic fatty liver disease (NAFLD) and its complication, non-alcoholic steatohepatitis (NASH)). This treatment led to a significant drop in hepatic fat deposition in both models (p < 0.01 vs. untreated animals), accompanied by a reduction in plasma inflammatory cytokines, such as interleukin 6, tumor necrosis factor α, and C reactive protein, and myeloperoxidase expression in liver tissue. Furthermore, a modulation of the molecular pathways involved in lipid metabolism and storage was demonstrated, since we observed the significant reduction of the mRNA levels of fatty acid synthase, diacylglycerol acyltransferases, the sterol-binding protein SREBP-1, and the lipid transporter perilipin-2, in both treated NAFLD and NASH rats in comparison to untreated ones. In conclusion, this nutraceutical product was effective in reducing liver steatosis and showed further beneficial effects on hepatic inflammation and glycemic control, which were particularly evident in rats characterized by a more severe condition, thus representing a therapeutic option for the treatment of NAFLD and NASH patients.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Phaeophyceae , Alga Marinha , Animais , Proteína C-Reativa/metabolismo , Suplementos Nutricionais , Diglicerídeos/metabolismo , Ácido Graxo Sintases , Inflamação/metabolismo , Interleucina-6/metabolismo , Metabolismo dos Lipídeos , Fígado , Camundongos , Camundongos Endogâmicos C57BL , Modelos Teóricos , Hepatopatia Gordurosa não Alcoólica/metabolismo , Perilipina-2/metabolismo , Peroxidase/metabolismo , Phaeophyceae/metabolismo , RNA Mensageiro/metabolismo , Ratos , Alga Marinha/química , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Esteróis/farmacologia , Fator de Necrose Tumoral alfa/metabolismo
5.
Dig Dis ; 39(3): 179-189, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33002891

RESUMO

BACKGROUND: Guidelines give robust recommendations on which biopsies should be taken when there is endoscopic suggestion of gastric inflammation. Adherence to these guidelines often seems arbitrary. This study aimed to give an overview on current practice in tertiary referral centres across Europe. METHODS: Data were collected at 10 tertiary referral centres. Demographic data, the indication for each procedure, endoscopic findings, and the number and sampling site of biopsies were recorded. Findings were compared between centres, and factors influencing the decision to take biopsies were explored. RESULTS: Biopsies were taken in 56.6% of 9,425 procedures, with significant variation between centres (p < 0.001). Gastric biopsies were taken in 43.8% of all procedures. Sampling location varied with the procedure indication (p < 0.001) without consistent pattern across the centres. Fewer biopsies were taken in centres which routinely applied the updated Sydney classification for gastritis assessment (46.0%), compared to centres where this was done only upon request (75.3%, p < 0.001). This was the same for centres stratifying patients according to the OLGA system (51.8 vs. 73.0%, p < 0.001). More biopsies were taken in centres following the MAPS guidelines on stomach surveillance (68.1 vs. 37.1%, p < 0.001). Biopsy sampling was more likely in younger patients in 8 centres (p < 0.05), but this was not true for the whole cohort (p = 0.537). The percentage of procedures with biopsies correlated directly with additional costs charged in case of biopsies (r = 0.709, p = 0.022). CONCLUSION: Adherence to guideline recommendations for biopsy sampling at gastroscopy was inconsistent across the participating centres. Our data suggest that centre-specific policies are applied instead.


Assuntos
Endoscopia Gastrointestinal , Encaminhamento e Consulta , Centros de Atenção Terciária , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
6.
Int J Mol Sci ; 22(18)2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34576114

RESUMO

Gastric carcinoma (GC) represents one of the most common and most lethal malignancies worldwide. The histopathological characterization of GC precursor lesions has provided great knowledge about gastric carcinogenesis, with the consequent introduction of effective strategies of primary and secondary prevention. In recent years, a large amount of data about the molecular events in GC development is emerging, flanking the histomorphological descriptions. In this review, we describe the landscape of molecular alterations in gastric pre-invasive lesions with a glance at their potential use in the diagnostic and therapeutic decision-making process.


Assuntos
Lesões Pré-Cancerosas/patologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Humanos , Terapia de Alvo Molecular , Invasividade Neoplásica , Fatores de Risco , Neoplasias Gástricas/classificação , Neoplasias Gástricas/epidemiologia
7.
Int J Mol Sci ; 21(4)2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-32102481

RESUMO

DNA methylation plays an important role in cancer development. Cancer cells exhibit two types of DNA methylation alteration: site-specific hypermethylation at promoter of oncosuppressor genes and global DNA hypomethylation. This study evaluated the methylation patterns of long interspersed nuclear element (LINE-1) sequences which, due to their relative abundance in the genome, are considered a good surrogate indicator of global DNA methylation. LINE-1 methylation status was investigated in the cell-free DNA (cfDNA) of 21 patients, 19 with esophageal adenocarcinoma (EADC) and 2 with Barrett's esophagus (BE). The two BE patients and one EADC patient were also analyzed longitudinally. Methylation status was analyzed using restriction enzymes and DNA amplification. This methodology was chosen to avoid bisulfite conversion, which we considered inadequate for cfDNA analysis. Indeed, cfDNA is characterized by poor quality and low concentration, and bisulfite conversion might worsen these conditions. Results showed that hypomethylated LINE-1 sequences are present in EADC cfDNA. Furthermore, longitudinal studies in BE suggested a correlation between methylation status of LINE-1 sequences in cfDNA and progression to EADC. In conclusion, our study indicated the feasibility of our methodological approach to detect hypomethylation events in cfDNA from EADC patients, and suggests LINE-1 methylation analysis as a new possible molecular assay to integrate into patient monitoring.


Assuntos
Adenocarcinoma/genética , Esôfago de Barrett/genética , Ácidos Nucleicos Livres/genética , Metilação de DNA , Neoplasias Esofágicas/genética , Elementos Nucleotídeos Longos e Dispersos/genética , Adenocarcinoma/patologia , Adulto , Idoso , Esôfago de Barrett/patologia , Progressão da Doença , Neoplasias Esofágicas/patologia , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica/métodos
8.
Br J Cancer ; 121(3): 257-263, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31235864

RESUMO

BACKGROUND: Claudin-18 (CLDN18) is a highly specific tight junction protein of the gastric mucosa. An isoform of CLDN18, the Claudin 18.2, has recently emerged as an innovative drug target for metastatic gastric cancer. METHODS: We investigated the immunohistochemical profile of CLDN18, p53, p16, E-cadherin, MSH2, MSH6, MLH1, PSM2, HER2, and PDL-1 in a large series of 523 primary gastric carcinomas (GCs; n = 408) and gastro-oesophageal carcinomas (GECs; n = 115) and 135 matched and synchronous nodal metastases. The status of HER2 and EBER by means of chromogenic in situ hybridisation (CISH) was also evaluated. RESULTS: High membranous CLDN18 expression was present in 150/510 (29.4%) primary cases and in 45/132 (34.1%) metastases. An abnormal expression (i.e. nuclear and/or cytoplasmic) was observed in 115 (22.5%) primary cases and in 33 (25.0%) metastases. A 38.8% of the cases showed significant CLDN18 intratumoural variability among the different tissue microarray cores obtained from the same tumour. Positive membrane CLDN18 expression was statistically associated with non-antral GCs (p = 0.016), Lauren diffuse type (p = 0.009), and with EBV-associated cancers (p < 0.001). CONCLUSIONS: CLDN18 is frequently expressed in gastric and gastro-oesophageal cancers; further studies should investigate the prognostic significance of CLDN18 heterogeneity in order to implement its test into clinical practice.


Assuntos
Adenocarcinoma/química , Claudinas/análise , Neoplasias Gástricas/química , Análise Serial de Tecidos/métodos , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RNA Viral/análise , Neoplasias Gástricas/patologia
10.
Int J Food Sci Nutr ; 69(8): 904-915, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29516760

RESUMO

Colorectal cancer is the third most common cancer worldwide. Growing evidence shows that about 47% of cases of colorectal cancer can be prevented by a healthy lifestyle. We performed a systematic review and meta-analysis aimed to evaluate the association between dietary fibre intake and the risk of colon cancer. We performed a structured computer search on PubMed, including epidemiological studies reporting results of dietary fibre intake and risk of colon cancer in women or men. We compared subjects exposed to the highest versus the lowest consumption. The search strategy identified 376 papers. After screening, 25 datasets were included in our meta-analysis. Results suggest a protective role of dietary fibre intake on colon cancer risk ES = 0.74 (95% CI = 0.67-0.82), p value = .000, but, moderate statistical heterogeneity (χ2 = 42.73, p value = .011) was found. Due to the high mortality of colorectal cancer, it is important to identify effective preventive measures, especially those of a healthy lifestyle, such as a healthy diet.


Assuntos
Neoplasias do Colo/prevenção & controle , Fibras na Dieta/administração & dosagem , Feminino , Humanos , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco
11.
Int J Mol Sci ; 19(4)2018 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-29662006

RESUMO

Hyperinsulinemia could have a role in the growing incidence of esophageal adenocarcinoma (EAC) and its pre-cancerous lesion, Barrett's Esophagus, a possible consequence of Gastro-Esophageal Reflux Disease. Obesity is known to mediate esophageal carcinogenesis through different mechanisms including insulin-resistance leading to hyperinsulinemia, which may mediate cancer progression via the insulin/insulin-like growth factor axis. We used the hyperinsulinemic non-obese FVB/N (Friend leukemia virus B strain) MKR (muscle (M)-IGF1R-lysine (K)-arginine (R) mouse model to evaluate the exclusive role of hyperinsulinemia in the pathogenesis of EAC related to duodeno-esophageal reflux. FVB/N wild-type (WT) and MKR mice underwent jejunum-esophageal anastomosis side-to end with the exclusion of the stomach. Thirty weeks after surgery, the esophagus was processed for histological, immunological and insulin/Insulin-like growth factor 1 (IGF1) signal transduction analyses. Most of the WT mice (63.1%) developed dysplasia, whereas most of the MKR mice (74.3%) developed squamous cell and adenosquamous carcinomas, both expressing Human Epidermal growth factor receptor 2 (HER2). Hyperinsulinemia significantly increased esophageal cancer incidence in the presence of duodenal-reflux. Insulin receptor (IR) and IGF1 receptor (IGF1R) were overexpressed in the hyperinsulinemic condition. IGF1R, through ERK1/2 mitogenic pattern activation, seems to be involved in cancer onset. Hyperinsulinemia-induced IGF1R and HER2 up-regulation could also increase the possibility of forming of IGF1R/HER2 heterodimers to support cell growth/proliferation/progression in esophageal carcinogenesis.


Assuntos
Refluxo Duodenogástrico/complicações , Neoplasias Esofágicas/etiologia , Esôfago/patologia , Hiperinsulinismo/complicações , Animais , Modelos Animais de Doenças , Refluxo Duodenogástrico/metabolismo , Refluxo Duodenogástrico/patologia , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Esôfago/metabolismo , Feminino , Hiperinsulinismo/metabolismo , Hiperinsulinismo/patologia , Insulina/análise , Insulina/metabolismo , Masculino , Camundongos , Receptor ErbB-2/análise , Receptor ErbB-2/metabolismo , Transdução de Sinais
12.
Eur J Nutr ; 55(4): 1563-71, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26155779

RESUMO

PURPOSE: While adherence to the World Cancer Research Fund (WCRF) guidelines on lifestyle and cancer was recently proven to be associated with an increased risk of esophageal cancer, no investigation has yet been carried out on its role on Barrett's esophagus (BE) development and its progression to esophageal adenocarcinoma (EAC). The primary aim of this study was to evaluate the role of adherence to WCRF lifestyle recommendations in BE onset and progression. The secondary aim was to investigate the association between disease progression and specific aspects of diet and lifestyle. METHODS: Established risk factors for BE and EAC development and adherence to WCRF guidelines were assessed in 107 consecutive patients undergoing an upper gastrointestinal endoscopy for symptoms suggesting gastroesophageal reflux (GERD) and a suspected diagnosis of BE/dysplasia on BE. Patients were divided according to histology: those with GERD without metaplasia, with non-dysplastic BE, with low-grade dysplasia, with high-grade dysplasia or with early EAC. The four groups were expressed as an ordered categorical variable of disease progression. An ordered logit model was estimated to identify the independent predictors of disease progression. RESULTS: Adherence to WCRF guidelines was identified as independent protective factor (OR 0.51, 95 % CI 0.37-0.67) of disease progression. Disease progression was associated with reduced adherence to guidelines on physical activity (from 48.2 to 5.3 %, p = 0.001), sedentary habits (from 33.3 to 0 %, p = 0.03), fruit consumption (from 37.0 to 5.6 %, p = 0.02) and processed meat consumption (from 51.9 to 10.5 %, p = 0.002). CONCLUSION: Adherence to WCRF guidelines has a protective factor in BE onset and its evolution to EAC.


Assuntos
Adenocarcinoma/prevenção & controle , Esôfago de Barrett/prevenção & controle , Neoplasias Esofágicas/prevenção & controle , Estilo de Vida , Cooperação do Paciente , Idoso , Índice de Massa Corporal , Dieta Saudável , Progressão da Doença , Exercício Físico , Feminino , Frutas , Refluxo Gastroesofágico/prevenção & controle , Humanos , Modelos Logísticos , Masculino , Produtos da Carne , Pessoa de Meia-Idade , Projetos Piloto , Fatores de Risco , Inquéritos e Questionários , Verduras , Circunferência da Cintura
13.
Surg Endosc ; 30(1): 159-67, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25829063

RESUMO

BACKGROUND: 50% of esophageal cancers are inoperable at the time of diagnosis, and around 15% involve the cervical esophagus. The hypopharynx is often involved by these malignancies as well. Palliation of cervical esophageal malignancies through stent insertion is considered limited due to technical challenges, poor patient tolerance and high complication rate. The aim of this study is to review our experience with stent insertion in the cervical segment of the esophagus and to evaluate outcome differences between stent insertions involving or sparing the hypopharynx. METHODS: We retrospectively reviewed data on 69 consecutive patients that underwent stent insertion for malignant strictures in the cervical esophagus at our Department. Patients were divided according to involvement or sparing of the lower hypopharynx. Dysphagia severity was measured with the Mellow-Pinkas scale before the procedure and on monthly follow-ups. Any complication and its management were recorded. The main outcome parameters were as follows: dysphagia improvement, rate of successful dysphagia palliation (i.e., a reduction of the score to 0 or 1 after stent insertion) and complication rate. Multivariable analysis was carried out to assess the influence of patient- and procedure-related factors on the outcome of the procedure. RESULTS: Stent insertion was achieved in 100% patients. At 4 weeks, dysphagia score improved from a median of 3-0 (p < 0.001), and a successful palliation was achieved in 76.8% patients. The 30-day mortality rate was 14.5%. Successful palliation throughout the follow-up was achieved in 72.9% of the surviving patients. Complications occurred in 31.9% patients. Dilation before stent insertion was associated with a less efficient short-term dysphagia palliation (OR 6.77, 95% CI 1.46-31.29, p = 0.02). CONCLUSIONS: Stent insertion is a safe and effective palliative treatment for malignant cervical esophageal strictures. Results are consistent even in patients with hypopharyngeal lesions. Dilation should be avoided before stent insertion.


Assuntos
Transtornos de Deglutição/terapia , Neoplasias Esofágicas/complicações , Estenose Esofágica/terapia , Hipofaringe/patologia , Cuidados Paliativos , Stents , Idoso , Idoso de 80 Anos ou mais , Transtornos de Deglutição/etiologia , Estenose Esofágica/etiologia , Esofagoscopia , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
14.
Dig Endosc ; 27(7): 728-33, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25975384

RESUMO

BACKGROUND AND AIM: Flexible endoscopic septum division is becoming a prominent treatment option for Zenker's diverticulum (ZD). Over the years, various techniques have been developed and many cutting tools have been tested with varying results. We report our experience with a recently designed, monopolar, rotating, scissor-shaped device (SB Knife). METHODS: Data on 31 consecutive patients that underwent flexible endoscopic treatment for ZD with the use of the SB Knife were retrieved. Dysphagia, regurgitation, and respiratory symptom severity before the procedure were graded. Procedure duration, rate of complications, symptom changes after the procedure and rate of relapsing patients during follow up were recorded. RESULTS: The procedure was carried out successfully in all patients. Median procedure time was 14 min. One case of late-onset bleeding developed 1 week after the procedure, and was managed endoscopically. A significant symptom improvement was achieved (dysphagia: median score <3, median score >0, P < 0.001; regurgitation: median score <2, median score >0, P < 0.001; respiratory symptoms: median score <2, median score >0, P = 0.009). Two patients had mild relapsing symptoms, respectively, after 4 and 9 months from the procedure but refused further treatment. CONCLUSIONS: Endoscopic treatment of ZD using this new device is safe and efficient at short term follow up. No perforations were observed and there was a substantial reduction of symptoms after the treatment. Larger studies are needed to fully assess advantages of this new device for endoscopic treatment of ZD.


Assuntos
Esofagoscópios , Esofagoscopia/instrumentação , Divertículo de Zenker/cirurgia , Idoso , Idoso de 80 Anos ou mais , Desenho de Equipamento , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
15.
Sci Rep ; 14(1): 2032, 2024 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-38263232

RESUMO

Polyps are well-known cancer precursors identified by colonoscopy. However, variability in their size, appearance, and location makes the detection of polyps challenging. Moreover, colonoscopy surveillance and removal of polyps are highly operator-dependent procedures and occur in a highly complex organ topology. There exists a high missed detection rate and incomplete removal of colonic polyps. To assist in clinical procedures and reduce missed rates, automated methods for detecting and segmenting polyps using machine learning have been achieved in past years. However, the major drawback in most of these methods is their ability to generalise to out-of-sample unseen datasets from different centres, populations, modalities, and acquisition systems. To test this hypothesis rigorously, we, together with expert gastroenterologists, curated a multi-centre and multi-population dataset acquired from six different colonoscopy systems and challenged the computational expert teams to develop robust automated detection and segmentation methods in a crowd-sourcing Endoscopic computer vision challenge. This work put forward rigorous generalisability tests and assesses the usability of devised deep learning methods in dynamic and actual clinical colonoscopy procedures. We analyse the results of four top performing teams for the detection task and five top performing teams for the segmentation task. Our analyses demonstrate that the top-ranking teams concentrated mainly on accuracy over the real-time performance required for clinical applicability. We further dissect the devised methods and provide an experiment-based hypothesis that reveals the need for improved generalisability to tackle diversity present in multi-centre datasets and routine clinical procedures.


Assuntos
Crowdsourcing , Aprendizado Profundo , Pólipos , Humanos , Colonoscopia , Computadores
16.
Nutrients ; 15(13)2023 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-37447211

RESUMO

Esophageal adenocarcinoma (EAC) is the consequence of longstanding gastroesophageal reflux, which leads to inflammation and could cause Barrett's esophagus (BE), the main risk factor for EAC development. The 5 year survival rate of EAC is poor since the diagnosis occurs at the late stage of the disease. To improve patient management, a better comprehension of the mechanism undergoing the evolution through to adenocarcinoma is needed. Within this scenario, the resident microbiome investigation was studied. This study aimed to explore the esophageal microbial profile in patients affected by non-dysplastic BE, low- and high-grade dysplastic BE, and EAC to identify parameters characterizing cancer progression and to develop a score suitable for clinical practice to stratify cancer risk. The microbiota was investigated through the 16S rRNA gene sequencing of esophageal biopsies. The microbial composition was evaluated at each different taxonomic level along the disease progression. To further investigate bacteria potentially associated with cancer development, non-dysplastic and dysplastic/cancer patients were compared. The presence of the six significant microbial features with multivariate analysis was used to develop a multiparametric score (Resident Esophageal Microbial Dysbiosis Test) to predict the risk of progression toward EAC. Finally, the diagnostic ability of the test and its discrimination threshold for its ability to identify dysplastic/cancer patients were demonstrated. Since EAC has been related to obesity, the relationship between these microbial parameters and patients' diet/lifestyle habits was also investigated. Developing microbiome-based risk prediction models for esophageal adenocarcinoma onset could open new research avenues, demonstrating that the resident microbiome may be a valid cancer risk biomarker.


Assuntos
Adenocarcinoma , Esôfago de Barrett , Neoplasias Esofágicas , Microbiota , Humanos , Disbiose/complicações , Disbiose/microbiologia , RNA Ribossômico 16S/genética , Neoplasias Esofágicas/patologia , Adenocarcinoma/patologia , Hiperplasia , Estilo de Vida , Progressão da Doença
17.
Sci Data ; 10(1): 75, 2023 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-36746950

RESUMO

Polyps in the colon are widely known cancer precursors identified by colonoscopy. Whilst most polyps are benign, the polyp's number, size and surface structure are linked to the risk of colon cancer. Several methods have been developed to automate polyp detection and segmentation. However, the main issue is that they are not tested rigorously on a large multicentre purpose-built dataset, one reason being the lack of a comprehensive public dataset. As a result, the developed methods may not generalise to different population datasets. To this extent, we have curated a dataset from six unique centres incorporating more than 300 patients. The dataset includes both single frame and sequence data with 3762 annotated polyp labels with precise delineation of polyp boundaries verified by six senior gastroenterologists. To our knowledge, this is the most comprehensive detection and pixel-level segmentation dataset (referred to as PolypGen) curated by a team of computational scientists and expert gastroenterologists. The paper provides insight into data construction and annotation strategies, quality assurance, and technical validation.


Assuntos
Neoplasias do Colo , Pólipos do Colo , Humanos , Pólipos do Colo/diagnóstico , Colonoscopia/métodos
18.
JCI Insight ; 8(15)2023 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-37551712

RESUMO

Age-associated sarcopenia, characterized by a progressive loss in muscle mass and strength, is the largest cause of frailty and disability in the elderly worldwide. Current treatments involve nonpharmacological guidelines that few subjects can abide by, highlighting the need for effective drugs. Preclinical models were employed to test the benefits of RJx-01, a combination drug composed of metformin and galantamine, on sarcopenia. In worms, RJx-01 treatment improved lifespan, locomotion, pharyngeal pumping, and muscle fiber organization. The synergistic effects of RJx-01 were recapitulated in a transgenic mouse model that displays an exacerbated aging phenotype (Opa1-/-). In these mice, RJx-01 ameliorated physical performance, muscle mass and force, neuromuscular junction stability, and systemic inflammation. RJx-01 also improved physical performance and muscle strength in 22-month-old WT mice and also improved skeletal muscle ultrastructure, mitochondrial morphology, autophagy, lysosomal function, and satellite cell content. Denervation and myofiber damage were decreased in RJx-01-treated animals compared with controls. RJx-01 improved muscle quality rather than quantity, indicating that the improvement in quality underlies the beneficial effects of the combination drug. The studies herein indicate synergistic beneficial effects of RJx-01 in the treatment of sarcopenia and support the pursuit of RJx-01 in a human clinical trial as a therapeutic intervention for sarcopenia.


Assuntos
Metformina , Sarcopenia , Humanos , Camundongos , Animais , Idoso , Lactente , Sarcopenia/tratamento farmacológico , Galantamina/farmacologia , Metformina/farmacologia , Envelhecimento/fisiologia , Músculo Esquelético/patologia , Camundongos Transgênicos
19.
J Clin Med ; 12(8)2023 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-37109171

RESUMO

Many tumors may secondarily involve the pancreas; however, only retrospective autopic and surgical series are available. We retrospectively collected data from all consecutive patients with histologically confirmed secondary tumors of the pancreas referred to five Italian centers between 2010 and 2021. We described clinical and pathological features, therapeutic approach and treatment outcomes. EUS characteristics of the lesions and the tissue acquisition procedures (needle, passages, histology) were recorded. A total of 116 patients (males/females 69/47; mean age 66.7) with 236 histologically confirmed pancreatic metastases were included; kidney was the most common primary site. EUS was performed to confirm the diagnosis in 205 lesions which presented as predominantly solitary (59), hypoechoic (95) and hypervascular (60), with a heterogeneous (n = 54) pattern and well-defined borders (n = 52). EUS-guided tissue acquisition was performed in 94 patients with an overall accuracy of 97.9%. Histological evaluation was possible in 88.3% of patients, obtaining final diagnosis in all cases. When cytology alone was performed, the final diagnosis was obtained in 83.3% of cases. A total of 67 patients underwent chemo/radiation therapy, and surgery was attempted in 45 (38.8%) patients. Pancreatic metastases are a possible event in the natural history of solid tumors, even long after the diagnosis of the primary site. EUS-guided fine needle biopsy may be suggested to implement the differential diagnosis.

20.
J Gastrointestin Liver Dis ; 32(4): 433-437, 2023 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-38147598

RESUMO

BACKGROUND AND AIMS: International guidelines advise improving esophagogastroduodenoscopy (EGD) quality in Western countries, where gastric cancer is still diagnosed in advanced stages. This nationwide study investigated some indicators for the quality of EGD performed in endoscopic centers in Italy. METHODS: Clinical, endoscopic, and procedural data of consecutive EGDs performed in one month in the participating centers were reviewed and collected in a specific database. Some quality indicators before and during endoscopic procedures were evaluated. RESULTS: A total of 3,219 EGDs performed by 172 endoscopists in 28 centers were reviewed. Data found that some relevant information (family history for GI cancer, smoking habit, use of proton pump inhibitors) were not collected before endoscopy in 58.5-80.7% of patients. Pre-endoscopic preparation for gastric cleaning was routinely performed in only 2 (7.1%) centers. Regarding the procedure, sedation was not performed in 17.6% of patients, and virtual chromoendoscopy was frequently (>75%) used in only one (3.6%) center. An adequate sampling of the gastric mucosa (i.e., antral and gastric body specimens) was heterogeneously performed, and it was routinely performed only by 23% of endoscopists, and in 14.3% centers. CONCLUSIONS: Our analysis showed that the quality of EGD performed in clinical practice in Italy deserves to be urgently improved in different aspects.


Assuntos
Neoplasias Gastrointestinais , Neoplasias Gástricas , Humanos , Endoscopia do Sistema Digestório/métodos , Endoscopia Gastrointestinal , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/epidemiologia , Itália
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