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2.
Rev. cuba. cir ; 59(4): e996, oct.-dic. 2020. tab, graf
Artigo em Espanhol | LILACS, CUMED | ID: biblio-1149844

RESUMO

RESUMEN Introducción: La evaluación del mediastino en los pacientes que reciben tratamiento quirúrgico por cáncer del pulmón tiene sus orígenes en la necesidad de definir la extensión anatómica de cada estación nodal, lo cual es indispensable para la categorización patológica de los nódulos linfáticos. Objetivo: Evaluar la utilidad de la linfadenectomía mediastinal en el tratamiento quirúrgico del cáncer pulmonar. Métodos: Se realizó un estudio analítico de carácter prospectivo en el período comprendido entre enero de 2015 al 31 de agosto de 2018. El universo estuvo conformado por 96 pacientes con algún tipo de linfadenectomía mediastinal en el tratamiento quirúrgico del cáncer pulmonar dentro del período señalado. Se utilizaron métodos estadísticos, teóricos y empíricos. Resultados: La edad promedio fue 58,69 ± 9,343, el sexo masculino fue el más afectado y el adenocarcinoma el tipo histológico que predominó. La etapa clínica y patológica mayoritaria fue la III A y la lobectomía superior derecha la intervención más realizada. Se efectuaron un total de 76 disecciones ganglionares sistemáticas, seguidas por 18 muestreos ganglionares y 2 biopsias. Las linfadenectomías realizadas provocaron cambios de estadios en 46 pacientes. El análisis del valor predictivo positivo y negativo, así como de la sensibilidad y la especificidad fueron altos, así como las complicaciones escasas. Conclusiones: La linfadenectomía mediastinal como parte del tratamiento quirúrgico en el cáncer pulmonar constituye un pilar fundamental en la estadificación patológica del TNM, al mostrar una exactitud diagnóstica alta(AU)


ABSTRACT Introduction: Evaluation of the mediastinum in patients receiving surgical treatment for lung cancer has its origins in the need to define the anatomical extension of each node station, which is essential for the pathological categorization of lymph nodes. Objective: To evaluate the usefulness of mediastinal lymphadenectomy in the surgical treatment of lung cancer. Methods: A prospective and analytical study was carried out in the period from January 2015 to August 31, 2018. The universe consisted of 96 patients with some type of mediastinal lymphadenectomy in the surgical treatment of lung cancer within the indicated period. Statistical, theoretical and empirical methods were used. Results: The average age was 58.69 ± 9.343. The male sex was the most affected. Adenocarcinoma was the histological type that predominated. The most manifested clinical and pathological stage was III A. Right upper lobectomy was the most performed intervention. A total of 76 systematic lymph node dissections were performed, followed by 18 lymph node samples and two biopsies. The lymphadenectomies performed caused stage changes in 46 patients. The analysis of positive and negative predictive value, as well as sensitivity and specificity, were high. There were few complications. Conclusions: Mediastinal lymphadenectomy as part of the surgical treatment in lung cancer constitutes a fundamental procedure for the pathological staging of TNM, as it shows high diagnostic accuracy(AU)


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Adenocarcinoma/etiologia , Valor Preditivo dos Testes , Neoplasias Pulmonares/cirurgia , Excisão de Linfonodo/métodos , Estudos Prospectivos , Sensibilidade e Especificidade
3.
JAMA ; 324(24): 2536-2547, 2020 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-33351048

RESUMO

Importance: Gastroesophageal reflux disease (GERD) is defined by recurrent and troublesome heartburn and regurgitation or GERD-specific complications and affects approximately 20% of the adult population in high-income countries. Observations: GERD can influence patients' health-related quality of life and is associated with an increased risk of esophagitis, esophageal strictures, Barrett esophagus, and esophageal adenocarcinoma. Obesity, tobacco smoking, and genetic predisposition increase the risk of developing GERD. Typical GERD symptoms are often sufficient to determine the diagnosis, but less common symptoms and signs, such as dysphagia and chronic cough, may occur. Patients with typical GERD symptoms can be medicated empirically with a proton pump inhibitor (PPI). Among patients who do not respond to such treatment or if the diagnosis is unclear, endoscopy, esophageal manometry, and esophageal pH monitoring are recommended. Patients with GERD symptoms combined with warning symptoms of malignancy (eg, dysphagia, weight loss, bleeding) and those with other main risk factors for esophageal adenocarcinoma, such as older age, male sex, and obesity, should undergo endoscopy. Lifestyle changes, medication, and surgery are the main treatment options for GERD. Weight loss and smoking cessation are often useful. Medication with a PPI is the most common treatment, and after initial full-dose therapy, which usually is omeprazole 20 mg once daily, the aim is to use the lowest effective dose. Observational studies have suggested several adverse effects after long-term PPI, but these findings need to be confirmed before influencing clinical decision making. Surgery with laparoscopic fundoplication is an invasive treatment alternative in select patients after thorough and objective assessments, particularly if they are young and healthy. Endoscopic and less invasive surgical techniques are emerging, which may reduce the use of long-term PPI and fundoplication, but the long-term safety and efficacy remain to be scientifically established. Conclusions and Relevance: The clinical management of GERD influences the lives of many individuals and is responsible for substantial consumption of health care and societal resources. Treatments include lifestyle modification, PPI medication, and laparoscopic fundoplication. New endoscopic and less invasive surgical procedures are evolving. PPI use remains the dominant treatment, but long-term therapy requires follow-up and reevaluation for potential adverse effects.


Assuntos
Fundoplicatura , Refluxo Gastroesofágico/diagnóstico , Refluxo Gastroesofágico/terapia , Inibidores da Bomba de Prótons/uso terapêutico , Adenocarcinoma/etiologia , Esôfago de Barrett/etiologia , Diagnóstico Diferencial , Neoplasias Esofágicas/etiologia , Refluxo Gastroesofágico/complicações , Humanos , Omeprazol/administração & dosagem , Inibidores da Bomba de Prótons/administração & dosagem , Inibidores da Bomba de Prótons/efeitos adversos , Comportamento de Redução do Risco
4.
Acta Cir Bras ; 35(9): e202000904, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33027361

RESUMO

PURPOSE: To investigate the role of omeprazole and nitrites on the gastric mucosa of rats submitted to specific techniques to induce duodenogastric reflux. METHODS: One hundred and twenty Wistar rats were divided into three groups: Group I (n=40) -gastrotomy; Group II (n=40) - duodenogastric reflux after gastrojejunoanastomosis latero-lateral (DGR); Group III (n=40) - retrograde duodenogastric reflux through the pylorus (DGR-P). The groups were divided into 4 subgroups of 10 animals, respectively treated for 16 weeks with water, omeprazole 1.6 mg / rat / day, nitrite 600 mg / kg / day and omeprazole plus nitrite simultaneously. RESULTS: The proliferative lesions found were: squamous hyperplasia - 69.1%, adenomatous hyperplasia in the anastomosis - 29.1% and prepyloric adenomatous hyperplasia - 42.5%. Adenocarcinomas were registered in 7 animals (5.8%): one in Group I (omeprazole plus nitrite), two in Group II (omeprazole and nitrite plus omeprazole) and four in Group III (water, nitrite, omeprazole and omeprazole plus nitrite). CONCLUSIONS: The occurrence of squamous hyperplasia, adenomatous hyperplasia and adenocarcinoma increased after gastrojejunal anastomoses, which cause duodenogastric reflux. The association of omeprazole did not protect the development of proliferative lesions and cancer induced by duodenogastric reflux in rats.


Assuntos
Adenocarcinoma , Refluxo Duodenogástrico , Omeprazol , Inibidores da Bomba de Prótons , Adenocarcinoma/etiologia , Adenocarcinoma/prevenção & controle , Animais , Refluxo Duodenogástrico/complicações , Mucosa Gástrica , Humanos , Omeprazol/farmacologia , Inibidores da Bomba de Prótons/farmacologia , Ratos , Ratos Wistar
5.
PLoS One ; 15(7): e0235906, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32697782

RESUMO

BACKGROUND: Esophageal cancer is a deadly cancer with 5-year survival <20%. Although multiple risk factors for esophageal adenocarcinoma (EAC) including obesity, GERD and smoking have been identified, these risk factors do not fully explain the rising incidence of EAC. In this study, we evaluated the association between prior history of tonsillectomy and EAC. Our goal was to determine whether tonsillectomies were more frequent in patients with EAC (cases) than in our thoracic surgery controls. METHODS: Cases included 452 esophagectomy cases, including 396 with EAC and 56 who underwent esophagectomy for Barrett's esophagus (BE) with high grade dysplasia (HGD). 1,102 thoracic surgery patients with surgical indications other than dysplastic BE or esophageal cancer represented the controls for our analysis. The association of tonsillectomy and HGD/EAC were primarily evaluated by using univariate tests and then verified by logistic regression analysis. Baseline demographics, medical history, and thoracic surgery controls were compared by using χ2 tests or 95% CIs. Significant risk factors were considered as covariates in the multivariate models while evaluating the association between tonsillectomy and HGD/EAC. P-values or odds ratios were estimated with 95% confidence limits to identify significances which was more appropriate. RESULTS: Tonsillectomy was more common in cases than controls and was found to have a significant association with esophageal cancer (19.9% vs. 12.7%; p-value = 0.0003). This significant association persisted after controlling for other known risk factors/covariates. CONCLUSION: A prior history of tonsillectomy was significantly associated with HGD/EAC and may represent an independent risk factor for the development of EAC. However, the underlying biology driving this association remains unclear.


Assuntos
Adenocarcinoma/etiologia , Neoplasias Esofágicas/etiologia , Tonsilectomia/efeitos adversos , Adenocarcinoma/diagnóstico , Idoso , Esôfago de Barrett/patologia , Esôfago de Barrett/cirurgia , Estudos de Casos e Controles , Neoplasias Esofágicas/diagnóstico , Esofagectomia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Lesões Pré-Cancerosas/patologia , Estudos Retrospectivos , Fatores de Risco
6.
Oncogene ; 39(22): 4465-4474, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32350444

RESUMO

Helicobacter pylori infection is the main risk factor for the development of gastric cancer, the third leading cause of cancer death worldwide. H. pylori colonizes the human gastric mucosa and persists for decades. The inflammatory response is ineffective in clearing the infection, leading to disease progression that may result in gastric adenocarcinoma. We have shown that polyamines are regulators of the host response to H. pylori, and that spermine oxidase (SMOX), which metabolizes the polyamine spermine into spermidine plus H2O2, is associated with increased human gastric cancer risk. We now used a molecular approach to directly address the role of SMOX, and demonstrate that Smox-deficient mice exhibit significant reductions of gastric spermidine levels and H. pylori-induced inflammation. Proteomic analysis revealed that cancer was the most significantly altered functional pathway in Smox-/- gastric organoids. Moreover, there was also less DNA damage and ß-catenin activation in H. pylori-infected Smox-/- mice or gastric organoids, compared to infected wild-type animals or gastroids. The link between SMOX and ß-catenin activation was confirmed in human gastric organoids that were treated with a novel SMOX inhibitor. These findings indicate that SMOX promotes H. pylori-induced carcinogenesis by causing inflammation, DNA damage, and activation of ß-catenin signaling.


Assuntos
Adenocarcinoma/etiologia , Dano ao DNA , Gastrite/enzimologia , Infecções por Helicobacter/enzimologia , Helicobacter pylori/patogenicidade , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/fisiologia , Espermina/metabolismo , Neoplasias Gástricas/etiologia , Adenocarcinoma/microbiologia , Animais , Transformação Celular Neoplásica , Gastrite/genética , Gastrite/microbiologia , Gastrite/patologia , Infecções por Helicobacter/genética , Infecções por Helicobacter/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Organoides , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/deficiência , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/genética , Proteoma , RNA Mensageiro/biossíntese , Transdução de Sinais , Espermidina/biossíntese , Neoplasias Gástricas/microbiologia , beta Catenina/fisiologia
7.
BMJ Case Rep ; 13(4)2020 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-32303529

RESUMO

Adenocarcinoma of the bowel is a dreadful sequelae of inflammatory bowel disease that can be difficult to diagnose and has been shown to have poor prognosis. The diagnosis is often made on histopathological examination of the resected specimen for what is suspected to be an exacerbation of the underlying intestinal Crohn's. A 39-year-old woman who was being treated for small bowel Crohn's disease for 4 years presented with features of intermittent intestinal obstruction that was refractory to medical therapy. A contrast CT of the abdomen was suggestive of ileocaecal Crohn's disease, and colonoscopy revealed a stricture at proximal transverse colon with multiple superficial ulcers. She underwent a mesentery sparing right hemicolectomy and had an uneventful recovery. The biopsy, however, was reported to be moderately differentiated adenocarcinoma stage T3N0 with a harvest of four pericolic nodes. Adjuvant chemotherapy was advised, which she deferred. Ten months later, she presented to the emergency room with features of intestinal obstruction. Contrast CT of the abdomen showed thickening at the anastomotic site with intestinal obstruction. On exploratory laparotomy, tumour recurrence was noted at the site of the anastomosis and diffuse peritoneal metastasis. A palliative diversion ileostomy was done due to inoperable obstructing disease. She was then given palliative therapy and subsequently succumbed to the illness. The inclusion of mesentery with the resected specimen in Crohn's disease has been a debate over many years. Since the preoperative diagnosis of carcinoma of the bowel in Crohn's disease is challenging, all ileocolic resections should be radical as done in oncological resections. This would yield better oncological safety and may improve survival rates.


Assuntos
Adenocarcinoma/cirurgia , Neoplasias do Ceco/cirurgia , Doença de Crohn/complicações , Neoplasias do Íleo/cirurgia , Adenocarcinoma/etiologia , Adulto , Neoplasias do Ceco/etiologia , Feminino , Humanos , Neoplasias do Íleo/etiologia
8.
Curr Diab Rep ; 20(6): 19, 2020 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-32277298

RESUMO

PURPOSE OF REVIEW: Fibrocalculous pancreatic diabetes (FCPD) is an uncommon form of diabetes occurring in underprivileged developing countries of the world. We attempt to review the latest evidence on epidemiology, secular trends, etiopathogenic mechanisms, and treatment modalities of FCPD with particular reference to studies from the past decade. RECENT FINDINGS: There has been little new data on FCPD over the past decade even from countries where it was considered to be prevalent. There appears to be a decline in prevalence of the condition of late. There is also some evidence to show that the condition develops due to as yet unknown environmental influences acting on a background of genetic susceptibility. FCPD is a severe form of diabetes and may be a premalignant condition. FCPD deserves more attention than it currently receives, because of its unique clinical features and management strategies, and its propensity to develop pancreatic adenocarcinoma.


Assuntos
Adenocarcinoma/etiologia , Diabetes Mellitus/diagnóstico , Neoplasias Pancreáticas/etiologia , Pancreatite Crônica/diagnóstico , Lesões Pré-Cancerosas/etiologia , Adenocarcinoma/diagnóstico , Calcinose/etiologia , Países em Desenvolvimento , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/etiologia , Diabetes Mellitus/terapia , Fibrose/etiologia , Interação Gene-Ambiente , Predisposição Genética para Doença , Humanos , Neoplasias Pancreáticas/diagnóstico , Pancreatite Crônica/epidemiologia , Pancreatite Crônica/etiologia , Pancreatite Crônica/terapia , Lesões Pré-Cancerosas/diagnóstico , Prevalência , Clima Tropical
10.
Sci Rep ; 10(1): 4899, 2020 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-32184470

RESUMO

Barrett's esophagus (BE) is the only known precursor to esophageal adenocarcinoma (EAC). Methods of identifying BE patients at high risk for progression to high-grade dysplasia (HGD) or EAC are needed to improve outcomes and identify who will benefit most from intensive surveillance or ablative therapy. Clinical predictors of BE progression to HGD or EAC are poorly understood, with multiple contradictory studies. We performed a retrospective study which included 460 patients at Johns Hopkins Hospital who underwent at least 2 upper endoscopies 6 months apart showing biopsy-documented BE between 1992 and 2013. Patients with EAC or HGD at the initial endoscopy were excluded. Demographic, clinicopathological, and endoscopic data were collected. Univariate and multivariate Cox proportional hazards analyses with time to progression to HGD and EAC were performed. Among 460 patients included in the study, 132 BE patients developed HGD and 62 developed EAC. Significant EAC risk factors included age, abdominal obesity, caffeine intake, and the presence of HGD. Risk factors for HGD or EAC included age, caffeine intake, and low-grade dysplasia while colonic adenomas trended towards significance. Notably, a history of statin or SSRI usage reduced the risk of EAC or HGD by 49% or 61%, respectively. Our study validated several known and identified several novel risk factors, including a history of colonic adenomas or caffeine usage. Low-grade dysplasia was a risk factor for progression but various endoscopic characteristics were not, suggesting that screening strategies should focus on histology instead. We identified SSRIs as a new potentially chemoprotective medication.


Assuntos
Adenocarcinoma/etiologia , Esôfago de Barrett/complicações , Neoplasias Esofágicas/etiologia , Lesões Pré-Cancerosas/etiologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
11.
PLoS One ; 15(3): e0230220, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32163505

RESUMO

Helicobacter pylori is a Gram-negative bacterium that causes chronic atrophic gastritis and peptic ulcers and it has been associated with the development of gastric adenocarcinoma and mucosa-associated lymphoid tissue (MALT). One of the more remarkable characteristics of H. pylori is its ability to survive in the hostile environment of the stomach. H. pylori regulates the expression of specific sets of genes allowing it to survive high acidity levels and nutrient scarcity. In the present study, we determined the expression of virulence associated protein D (VapD) of H. pylori inside adenocarcinoma gastric (AGS) cells and in gastric biopsies. Using qRT-PCR, VapD expression was quantified in intracellular H. pylori-AGS cell cultures at different time points and in gastric mucosa biopsies from patients suffering from chronic atrophic gastritis, follicular gastritis, peptic ulcers, gastritis precancerous intestinal metaplasia and adenocarcinoma. Our results show that vapD of H. pylori presented high transcription levels inside AGS cells, which increased up to two-fold above basal values across all assays over time. Inside AGS cells, H. pylori acquired a coccoid form that is metabolically active in expressing VapD as a protection mechanism, thereby maintaining its permanence in a viable non-cultivable state. VapD of H. pylori was expressed in all gastric biopsies, however, higher expression levels (p = 0.029) were observed in gastric antrum biopsies from patients with follicular gastritis. The highest VapD expression levels were found in both antrum and corpus gastric biopsies from older patients (>57 years old). We observed that VapD in H. pylori is a protein that is only produced in response to interactions with eukaryotic cells. Our results suggest that VapD contributes to the persistence of H. pylori inside the gastric epithelial cells, protecting the microorganism from the intracellular environment, reducing its growth rate, enabling long-term infection and treatment resistance.


Assuntos
Proteínas de Bactérias/genética , Gastrite Atrófica/etiologia , Helicobacter pylori/genética , Glicoproteínas de Membrana/genética , Estômago/microbiologia , Estômago/patologia , Adenocarcinoma/etiologia , Adenocarcinoma/microbiologia , Adenocarcinoma/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Técnicas de Cocultura/métodos , Feminino , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Gastrite Atrófica/microbiologia , Gastrite Atrófica/patologia , Gastroscopia/métodos , Infecções por Helicobacter/complicações , Infecções por Helicobacter/patologia , Humanos , Intestinos/microbiologia , Intestinos/patologia , Masculino , Metaplasia/microbiologia , Metaplasia/patologia , Pessoa de Meia-Idade , Úlcera Péptica/metabolismo , Úlcera Péptica/patologia , Lesões Pré-Cancerosas/etiologia , Lesões Pré-Cancerosas/microbiologia , Lesões Pré-Cancerosas/patologia , Antro Pilórico/microbiologia , Antro Pilórico/patologia , Neoplasias Gástricas/etiologia , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/patologia , Virulência/genética , Adulto Jovem
12.
Helicobacter ; 25(3): e12688, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32175626

RESUMO

BACKGROUND: Helicobacter pylori (H. pylori) is associated with lower risks of Barrett's esophagus and esophageal adenocarcinoma, but whether H. pylori eradication increases the risk of these conditions is unknown. This study aimed to test the hypothesis that H. pylori eradication leads to gradually increased risks of Barrett's esophagus and esophageal adenocarcinoma over time, while esophageal squamous cell carcinoma was assessed for comparison reasons. MATERIAL AND METHODS: This Swedish nationwide, population-based cohort study in 2005-2012 used data from the Swedish Prescribed Drug Registry to assess eradication treatment for H. pylori. Barrett's esophagus was identified from the Swedish Patient Registry, and esophageal adenocarcinoma and squamous cell carcinoma from the Swedish Cancer Registry. Standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) were calculated by dividing the observed risk in the H. pylori eradication treatment cohort by the expected risk derived from the Swedish population of the same age, sex, and calendar period. RESULTS: The cohort included 81 919 patients having had eradication treatment. For Barrett's esophagus (n = 178), the overall SIR was increased (SIR 3.67, 95% CI 3.15-4.25), but the SIRs slightly decreased over time after eradication treatment. For esophageal adenocarcinoma (n = 11), the overall SIR was 1.26 (95% CI 0.62-2.26), and the SIRs did not increase over time. The SIRs of esophageal squamous cell carcinoma (n = 10) were not influenced by eradication treatment. CONCLUSIONS: This study did not provide any evidence of an increasing risk of Barrett's esophagus or esophageal adenocarcinoma (or esophageal squamous cell carcinoma) over time after eradication treatment for H. pylori.


Assuntos
Adenocarcinoma/etiologia , Esôfago de Barrett/etiologia , Erradicação de Doenças , Neoplasias Esofágicas/etiologia , Infecções por Helicobacter , Antibacterianos/uso terapêutico , Estudos de Coortes , Carcinoma de Células Escamosas do Esôfago , Feminino , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/epidemiologia , Helicobacter pylori/efeitos dos fármacos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Inibidores da Bomba de Prótons/uso terapêutico , Fatores de Risco
13.
Sci Rep ; 10(1): 2754, 2020 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-32066788

RESUMO

The number of colon cancer cases is increasing worldwide, and type II diabetes patients have an increased risk of developing colon cancer. Diet-borne advanced glycation end-products (AGEs) may promote neoplastic transformation; however, the mechanisms involved remain elusive. The present study helped to define the relationship between dietary AGEs and cancer progression. C2BBe1 adenocarcinoma enterocytes were exposed to 200 µg/mL glycated casein (AGEs-Csn) for up to 24 h. AGEs-Csn exposure resulted in increased cell proliferation, maladaptative changes in SOD and CAT activity and moderate levels of hydrogen peroxide (H2O2) intracellular accumulation. AGEs-Csn activated pro-survival and proliferation signalling, such as the phosphorylation of mTOR (Ser2448) and Akt (Ser473). GSK-3ß phosphorylation also increased, potentially inducing extracellular matrix remodelling and thus enabling metastasis. Moreover, AGEs-Csn induced MMP-1, -3, -7, -9 and -10 expression and activated MMP-2 and MMP-9, which are regulators of the extracellular matrix and cytokine functions. AGEs-Csn induced inflammatory responses that included extracellular IL-1ß at 6 h; time-dependent increases in IL-8; RAGE and NF-κB p65 upregulation; and IκB inhibition. Co-treatment with anti-RAGE or anti-TNF-α blocking antibodies and AGEs-Csn partially counteracted these changes; however, IL-8, MMP-1 and -10 expression and MMP-9 activation were difficult to prevent. AGEs-Csn perpetuated signalling that led to cell proliferation and matrix remodelling, strengthening the link between AGEs and colorectal cancer aggressiveness.


Assuntos
Caseínas/farmacologia , Enterócitos/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica , Produtos Finais de Glicação Avançada/farmacologia , Adenocarcinoma/etiologia , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/metabolismo , Caseínas/química , Catalase/genética , Catalase/metabolismo , Linhagem Celular Tumoral , Neoplasias do Colo/etiologia , Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Enterócitos/metabolismo , Enterócitos/patologia , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/metabolismo , Glicogênio Sintase Quinase 3 beta/genética , Glicogênio Sintase Quinase 3 beta/metabolismo , Glicosilação , Humanos , Proteínas I-kappa B/genética , Proteínas I-kappa B/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-8/genética , Interleucina-8/metabolismo , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Modelos Biológicos , NF-kappa B/genética , NF-kappa B/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo
14.
World J Surg Oncol ; 18(1): 43, 2020 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-32106866

RESUMO

BACKGROUND: Total gastrectomy (TG) is a widely accepted procedure for treating gastric stump cancer (GSC). However, subtotal gastrectomy (SG) would benefit elective patients with GSC. The aim of this study was to clarify the safety and long-term prognosis of SG in treating GSC after distal gastrectomy for benign lesions. METHODS: A total of 53 patients with GSC located at the anastomotic site or gastric body between May 1999 and December 2018 at our hospital were included. In total, 21 patients underwent SG, and the remaining 24 patients underwent TG. Clinicopathological data, operative data, and overall survival (OS) were compared. RESULTS: The operative duration, estimated blood loss volume, and length of hospital stay were similar between the SG and TG groups. The postoperative complications were similar between the two groups, but no cases of anastomotic leakage were noted in the SG group. TG was associated with significantly more retrieved lymph nodes than SG (18.5 ± 11.5 vs. 10.7 ± 9.2; p = 0.017), while the number of metastatic lymph nodes did not differ between the groups (2.9 ± 3.5 vs. 1.9 ± 3.6; p = 0.329). The median survival time in the SG group was 81.0 months (95% confidence interval (CI), 68.906 to 93.094 months), which was similar to the 45.0 months (95% CI, 15.920 to 74.080 months) observed in the TG group (p = 0.236). Both univariate and multivariate analyses showed that tumor location and histological type were prognostic factors, while surgery type was not a prognostic factor. Further stratified analyses according to tumor location revealed that OS was not significantly different between the two groups among patients with tumors located at the anastomotic site, while OS in the TG group was significantly better than that in the SG group among patients with tumors located in the gastric body (p = 0.046). CONCLUSIONS: The results of the current study indicate that SG is a suitable alternative surgical procedure for GSC located at the anastomotic site after distal gastrectomy for benign lesions. The short-term outcomes and long-term prognoses of SG are comparable with those of TG.


Assuntos
Adenocarcinoma/cirurgia , Gastrectomia/métodos , Coto Gástrico/patologia , Complicações Pós-Operatórias/cirurgia , Reoperação/métodos , Neoplasias Gástricas/cirurgia , Adenocarcinoma/etiologia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Idoso , Anastomose Cirúrgica/efeitos adversos , Feminino , Gastrectomia/efeitos adversos , Coto Gástrico/cirurgia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/patologia , Prognóstico , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Taxa de Sobrevida , Resultado do Tratamento
15.
Sci Rep ; 10(1): 1355, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31992826

RESUMO

Due to its poor clinical outcome, there is an urgent need to identify novel prognostic markers for stomach adenocarcinoma (STAD). Here, we aimed to explore the relationship between VGLL3 expression and clinico-pathological features, dendritic cells, macrophages, and prognosis of STAD. VGLL3 expression levels were significantly associated with histological grade, T stage, and TNM stage. VGLL3 levels and patient's age were also independent prognostic factors of the clinical outcome of STAD. In addition, VGLL3 was associated with the abundance of macrophages and dendritic cells in tumor infiltrates, of which only VGLL3 and macrophage counts were the independent prognostic factors of immune cell infiltration in the TIMER Database. Extracellular matrix receptor interaction, focal adhesion, pathways in cancer, MAPK, JAK STAT, and WNT signaling pathways were enriched in VGLL3 high-expressing datasets as determined by Gene Set Enrichment Analysis (GSEA), while DNA replication, glyoxylate, and dicarboxylate metabolism, glutathione metabolism, homologous recombination, and glycosylphosphatidylinositol gpi banchor biosynthesis were enriched in VGLL3 low-expressing datasets. Thus, VGLL3 is a novel prognostic biomarker of both the clinical outcome and immune infiltration in STAD, and may therefore be a promising therapeutic target.


Assuntos
Adenocarcinoma/etiologia , Adenocarcinoma/patologia , Neoplasias Gástricas/etiologia , Neoplasias Gástricas/patologia , Fatores de Transcrição/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Células Dendríticas/patologia , Feminino , Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Macrófagos/imunologia , Macrófagos/metabolismo , Macrófagos/patologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidade , Fatores de Transcrição/metabolismo , Microambiente Tumoral
16.
Syst Rev ; 9(1): 20, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31996261

RESUMO

BACKGROUND: Two reviews and an overview were produced for the Canadian Task Force on Preventive Health Care guideline on screening for esophageal adenocarcinoma in patients with chronic gastroesophageal reflux disease (GERD) without alarm symptoms. The goal was to systematically review three key questions (KQs): (1) The effectiveness of screening for these conditions; (2) How adults with chronic GERD weigh the benefits and harms of screening, and what factors contribute to their preferences and decision to undergo screening; and (3) Treatment options for Barrett's esophagus (BE), dysplasia or stage 1 EAC (overview of reviews). METHODS: Bibliographic databases (e.g. Ovid MEDLINE®) were searched for each review in October 2018. We also searched for unpublished literature (e.g. relevant websites). The liberal accelerated approach was used for title and abstract screening. Two reviewers independently screened full-text articles. Data extraction and risk of bias assessments were completed by one reviewer and verified by another reviewer (KQ1 and 2). Quality assessments were completed by two reviewers independently in duplicate (KQ3). Disagreements were resolved through discussion. We used various risk of bias tools suitable for study design. The GRADE framework was used for rating the certainty of the evidence. RESULTS: Ten studies evaluated the effectiveness of screening. One retrospective study reported no difference in long-term survival (approximately 6 to 12 years) between those who had a prior esophagogastroduodenoscopy and those who had not (adjusted HR 0.93, 95% confidence interval (CI) 0.58-1.50). Though there may be higher odds of a stage 1 diagnosis than a more advanced diagnosis (stage 2-4) if an EGD had been performed in the previous 5 years (OR 2.27, 95% CI 1.00-7.67). Seven studies compared different screening modalities, and showed little difference between modalities. Three studies reported on patients' unwillingness to be screened (e.g. due to anxiety, fear of gagging). Eleven systematic reviews evaluated treatment modalities, providing some evidence of early treatment effect for some outcomes. CONCLUSIONS: Little evidence exists on the effectiveness of screening and values and preferences to screening. Many treatment modalities have been evaluated, but studies are small. Overall, there is uncertainty in understanding the effectiveness of screening and early treatments. SYSTEMATIC REVIEW REGISTRATIONS: PROSPERO (CRD42017049993 [KQ1], CRD42017050014 [KQ2], CRD42018084825 [KQ3]).


Assuntos
Adenocarcinoma/etiologia , Esôfago de Barrett/patologia , Neoplasias Esofágicas/etiologia , Refluxo Gastroesofágico/complicações , Lesões Pré-Cancerosas/patologia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Diagnóstico Precoce , Endoscopia do Sistema Digestório , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Refluxo Gastroesofágico/diagnóstico , Refluxo Gastroesofágico/patologia , Humanos , Guias de Prática Clínica como Assunto , Fatores de Risco , Taxa de Sobrevida , Revisões Sistemáticas como Assunto
18.
Intern Med ; 59(6): 779-782, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31787691

RESUMO

Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is widely used as a first-line procedure for the definitive diagnosis of pancreatic solid tumor. Adverse events associated with the EUS-FNA procedure include acute pancreatitis, bleeding, infection, and duodenal perforation. Rarely, pancreatic tumors disseminate in the peritoneal cavity or seed in the gastric wall via the biopsy needle tract after EUS-FNA. Such seeding has been noted primarily in cases of adenocarcinomas and has not been associated with solid pseudopapillary neoplasm (SPN), a rare and potentially malignant tumor of the pancreas. This is the first report of a case of tumor seeding in the gastric wall after EUS-FNA of pancreatic SPN.


Assuntos
Adenocarcinoma/patologia , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/efeitos adversos , Inoculação de Neoplasia , Neoplasias Pancreáticas/patologia , Doença Aguda , Adenocarcinoma/diagnóstico , Adenocarcinoma/etiologia , Idoso , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Humanos , Masculino , Pâncreas/patologia , Neoplasias Pancreáticas/diagnóstico , Estômago/patologia
19.
Gastroenterology ; 158(3): 760-769, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31730766

RESUMO

DESCRIPTION: The purpose of this best practice advice article is to describe the role of Barrett's endoscopic therapy (BET) in patients with Barrett's esophagus (BE) with dysplasia and/or early cancer and appropriate follow-up of these patients. METHODS: The best practice advice provided in this document is based on evidence and relevant publications reviewed by the committee. BEST PRACTICE ADVICE 1: In BE patients with confirmed low-grade dysplasia, a repeat examination with high-definition white-light endoscopy should be performed within 3-6 months to rule out the presence of a visible lesion, which should prompt endoscopic resection. BEST PRACTICE ADVICE 2: Both BET and continued surveillance are reasonable options for the management of BE patients with confirmed and persistent low-grade dysplasia. BEST PRACTICE ADVICE 3: BET is the preferred treatment for BE patients with high-grade dysplasia (HGD). BEST PRACTICE ADVICE 4: BET should be preferred over esophagectomy for BE patients with intramucosal esophageal adenocarcinoma (T1a). BEST PRACTICE ADVICE 5: BET is a reasonable alternative to esophagectomy in patients with submucosal esophageal adenocarcinoma (T1b) with low-risk features (<500-µm invasion in the submucosa [sm1], good to moderate differentiation, and no lymphatic invasion) especially in those who are poor surgical candidates. BEST PRACTICE ADVICE 6: In all patients undergoing BET, mucosal ablation should be applied to 1) all visible esophageal columnar mucosa; 2) 5-10 mm proximal to the squamocolumnar junction and 3) 5-10 mm distal to the gastroesophageal junction, as demarcated by the top of the gastric folds (ie, gastric cardia) using focal ablation in a circumferential fashion. BEST PRACTICE ADVICE 7: Mucosal ablation therapy should only be performed in the presence of flat BE without signs of inflammation and in the absence of visible abnormalities. BEST PRACTICE ADVICE 8: BET should be performed by experts in high-volume centers that perform a minimum of 10 new cases annually. BEST PRACTICE ADVICE 9: BET should be continued until there is an absence of columnar epithelium in the tubular esophagus on high-definition white-light endoscopy and preferably optical chromoendoscopy. In case of complete endoscopic eradication, the neosquamous mucosa and the gastric cardia are sampled by 4-quadrant biopsies. BEST PRACTICE ADVICE 10: If random biopsies obtained from the neosquamous epithelium demonstrate intestinal metaplasia/dysplasia or subsquamous intestinal metaplasia, a repeat endoscopy should be performed and visible islands or tongues should undergo targeted focal ablation. BEST PRACTICE ADVICE 11: Intestinal metaplasia of the gastric cardia (without residual columnar epithelium in the tubular esophagus) should not warrant additional ablation therapy. BEST PRACTICE ADVICE 12: When consenting patients for BET, the most common complication of therapy to be quoted is post-procedural stricture formation, occurring in about 6% of cases. Bleeding and perforation occur at rates <1%. BEST PRACTICE ADVICE 13: After complete eradication (endoscopic and histologic) of intestinal metaplasia has been achieved with BET, surveillance endoscopy with biopsies should be performed at the following intervals: for baseline diagnosis of HGD/esophageal adenocarcinoma: at 3, 6, and 12 months and annually thereafter; and baseline diagnosis of low-grade dysplasia: at 1 and 3 years. BEST PRACTICE ADVICE 14: Endoscopic surveillance post therapy should be performed with high-definition white-light endoscopy, including careful inspection of the neosquamous mucosal and retroflexed inspection of the gastric cardia. BEST PRACTICE ADVICE 15: The approach to recurrent disease is similar to that of the initial therapy; visible recurrent nodular lesions require endoscopic resection, whereas flat areas of columnar mucosa in the tubular esophagus can be treated with mucosal ablation. BEST PRACTICE ADVICE 16: Patients should be counseled on cancer risk in the absence of BET, as well as after BET, to allow for informed decision-making between the patient and the physician.


Assuntos
Técnicas de Ablação , Adenocarcinoma/cirurgia , Esôfago de Barrett/cirurgia , Ressecção Endoscópica de Mucosa , Neoplasias Esofágicas/cirurgia , Vigilância da População/métodos , Técnicas de Ablação/efeitos adversos , Adenocarcinoma/etiologia , Adenocarcinoma/patologia , Esôfago de Barrett/complicações , Esôfago de Barrett/patologia , Biópsia , Ressecção Endoscópica de Mucosa/efeitos adversos , Mucosa Esofágica/patologia , Neoplasias Esofágicas/etiologia , Neoplasias Esofágicas/patologia , Esofagoscopia , Humanos , Metaplasia/diagnóstico por imagem , Metaplasia/patologia , Metaplasia/cirurgia , Recidiva
20.
J Gastroenterol Hepatol ; 35(5): 730-743, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31733067

RESUMO

BACKGROUND AND AIM: A large number of papers reporting the relationships between body mass index (BMI) and esophageal cancer (EC) risk have been published in the past few decades; however, these results are inconsistent. Therefore, we carried out meta-analyses to explore the relationships between BMI and the risk of EC (including esophageal squamous cell carcinoma [ESCC] and esophageal adenocarcinoma [EADC]). METHODS: We used the Web of Science, PubMed, and Embase to identify all published/online articles before December 30, 2018, which yielded 25 articles eligible for data extraction (including 16,561 cases and 11,954,161 controls), and then pooled the relative risks (RRs) and corresponding 95% confidence intervals (CIs) using random-effects model. RESULTS: Our study presented that underweight had statistically significant association with the risk of EC (RR = 1.78, 95% CI = 1.48, 2.14, P < 0.001) and ESCC (RR = 1.57, 95% CI = 1.20, 2.06, P = 0.001) when compared with normal weight. Interestingly, both overweight and obesity could increase the risk of EADC (RR = 1.56, 95% CI = 1.42, 1.71, P < 0.001; RR = 2.34, 95% CI = 2.02, 2.70, P < 0.001) while decrease the risk of ESCC (RR = 0.71, 95% CI = 0.60, 0.84, P < 0.001; RR = 0.63, 95% CI = 0.60, 0.84, P = 0.002). Additionally, obesity could increase the risk of EC (RR = 1.51, 95% CI = 1.21, 1.89, P < 0.001). CONCLUSION: These meta-analyses provide a comprehensive and updated epidemiological evidence to confirm the associations between BMI and EC risk. These findings have public health implications with respect to better control bodyweight and then reduce the occurrence of EC (including ESCC and EADC).


Assuntos
Adenocarcinoma/etiologia , Índice de Massa Corporal , Carcinoma de Células Escamosas/etiologia , Neoplasias Esofágicas/etiologia , Estudos Observacionais como Assunto , Adenocarcinoma/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Neoplasias Esofágicas/epidemiologia , Humanos , Obesidade/complicações , Risco
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