Decoding common genetic alterations between Barrett's esophagus and esophageal adenocarcinoma: A bioinformatics analysis.

Background: Esophageal adenocarcinoma (EAC) is a common cancer with a poor prognosis in advanced stages. Therefore, early EAC diagnosis and treatment have gained attention in recent decades. It has been found that various pathological changes, particularly Barrett's Esophagus (BE), can occur in the esophageal tissue before the development of EAC. In this study, we aimed to identify the molecular contributor in BE to EAC progression by detecting the essential regulatory genes that are differentially expressed in both BE and EAC. Materials and methods: We conducted a comprehensive bioinformatics analysis to detect BE and EAC-associated genes. The common differentially expressed genes (DEGs) and common single nucleotide polymorphisms (SNPs) were detected using the GEO and DisGeNET databases, respectively. Then, hub genes and the top modules within the protein-protein interaction network were identified. Moreover, the co-expression network of the top module by the HIPPIE database was constructed. Additionally, the gene regulatory network was constructed based on miRNAs and circRNAs. Lastly, we inspected the DGIdb database for possible interacted drugs. Results: Our microarray dataset analysis identified 92 common DEGs between BE and EAC with significant enrichment in skin and epidermis development genes. The study also identified 22 common SNPs between BE and EAC. The top module of PPI network analysis included SCEL, KRT6A, SPRR1A, SPRR1B, SPRR3, PPL, SPRR2B, EVPL, and CSTA. We constructed a ceRNA network involving three specific mRNAs, 23 miRNAs, and 101 selected circRNAs. According to the results from the DGIdb database, TD101 was found to interact with the KRT6A gene. Conclusion: The present study provides novel potential candidate genes that may be involved in the molecular association between Esophageal adenocarcinoma and Barrett's Esophagus, resulting in developing the diagnostic tools and therapeutic targets to prevent progression of BE to EAC.

Gastroesophageal reflux after sleeve gastrectomy: The dimension of the problem.

Sleeve gastrectomy is a safe and effective bariatric surgery in terms of weight loss and longterm improvement or resolution of comorbidities. However, its achilles heel is the possible association with the development with the novo and/or worsening of pre-existing gastroesophageal reflux disease. The anatomical and mechanical changes that this technique induces in the esophagogastric junction, support or contradict this hypothesis. Questions such as «what is the natural history of gastroesophageal reflux in the patient undergoing gastric sleeve surgery?¼, «how many patients after vertical gastrectomy will develop gastroesophageal reflux?¼ and «how many patients will worsen their previous reflux after this technique?¼ are intended to be addressed in the present article.

The Rare Case of Esophageal Cancer Presenting With Hematemesis in a 29-Year-Old Adult.

Esophageal cancer is a disease with high mortality. This is mainly due to late presentations with nonspecific symptoms. Despite advances in surgery and chemoradiotherapy, it is the eighth most common cancer but the sixth deadliest. It is reportedly common in older patients but rare in young ones. In this case report, we present a 29-year-old male patient with no prior medical condition who presented with hematemesis to the emergency unit and was found to have esophageal cancer with the biopsy. Not only is esophageal cancer rare in young adults, but hematemesis is a rare symptom in esophageal cancer patients.

Potential therapeutic benefit of ursodeoxycholic acid in the management of non hepato-biliary upper gastrointestinal disorders.

OBJECTIVES: To examine the potential therapeutic effects of ursodeoxycholic acid (UDCA) on diseases of the esophagus, stomach, and duodenum. METHODS: A search was conducted using EBSCO, Medline, PubMed, Google Scholar and Web of Science as well as international guidelines using MESH terms for treatment of UDCA for diseases of the upper gastrointestinal disorders in adult humans without regard to publication language or date restrictions. RESULTS: A total of 256 articles and 22 guidelines were initially identified, and 221 were excluded. Final revision of 13 articles and 22 guidelines confirmed that UDCA is found to have a cytoprotective role in Barret's esophagus within esophageal disorders, improves abdominal pain in functional dyspepsia, and does not alter Helicobacter pylori colonization or inflammation. Conflicting results are noted regarding the role of UDCA in the duodenum as chemopreventive treatment for familial adenomatous polyposis, with polyps regressing and their growth characteristics improving with low doses (10-25 mg/kg/day). On the contrary, no positive effect was noted upon the combination with Celecoxib and with doses of 1000-2000 mg or 20-30 mg/kg/d. Gastrointestinal side effects were predominantly reported. No side effects necessitated hospitalization or ICU admission. CONCLUSION: Ursodeoxycholic acid has a limited therapeutic role in functional dyspepsia. There is promising evidence that it may serve as a chemopreventive for Familial adenomatous polyposis and Barret's esophagus, although further research is needed to confirm these findings.PROSPERO No.: CRD 42021267689.

Insights into the Paradox of the Weak Association Between Sleeve Gastrectomy and Barrett's Esophagus.

Sleeve gastrectomy (SG) is deemed a refluxogenic operation but with a low incidence of postoperative Barrett´s esophagus (BE). We aimed to shed some light on the potential paradox of the weak association between SG, BE and esophageal adenocarcinoma (EAC). The high incidence of GERD after SG is not followed by an increased rate of BE and EAC, as these rates are similar to the general population. We hypothesized that this paradox may occur due to a difference in the gastro-esophageal reflux composition secondary to a lower content of bile, to a decrease in inflammation due to weight loss and hormonal changes, and to acquisition of healthier habits such as exercise, smoking cessation, and better eating behavior.

Resultados del cálculo de la lente intraocular con fórmula Holladay 2 y Barret Universal 2 / Results of Intraocular Lens Calculation with Holladay 2 and Barret Universal 2 formula

Objetivo: Determinar los resultados refractivos con las fórmulas Holladay 2 y Barret Universal 2 a partir del cálculo de la lente intraocular en pacientes operados de catarata. Métodos: Se realizó un estudio descriptivo prospectivo y longitudinal con 60 ojos de 50 pacientes operados de catarata mediante la técnica de facoemulsificación. Se empleó para el cálculo de la lente el IOL Master 700 y el Pentacam AXL con la fórmula Holladay 2 y Barret Universal 2, respectivamente. Resultados: Predominó el sexo femenino y el grupo etario mayor de 60 años. Los ojos mayores de 26 mm mostraron la mayor diferencia entre el poder dióptrico de la lente intraocular que se implantó según Holladay y en menores de 22 mm según Barret Universal. Ambos grupos presentaron una disminución del equivalente esférico, siendo superior a 7 y 5 dioptrías en ojos mayores de 26 mm en el posoperatorio de ambas fórmulas. Posterior a la cirugía se observó una mejoría en la agudeza visual sin corrección y corregida de más de 4 líneas en la cartilla de Snellen, independiente de la longitud axial, para ambos grupos en estudio. Sin cambios significativos en el cilindro queratométrico. En el 70,0 por ciento de los casos, el resultado refractivo final estuvo en rango de la emetropía para el grupo Holladay 2 y el 66,7 por ciento para el grupo Barret Universal 2. Conclusiones: Ambas fórmulas resultan útiles para el cálculo de la lente intraocular en todos los rangos de longitud axial(AU)

Objective: To determine refractive outcomes with the Holladay 2 and Barret Universal 2 formulas from intraocular lens calculation in cataract surgery patients. Methods: A prospective and longitudinal descriptive study was performed with 60 eyes of 50 patients who underwent cataract surgery by phacoemulsification. The IOL Master 700 and Pentacam AXL with the Holladay 2 and Barret Universal 2 formula, respectively, were used to calculate the lens. Results: Female gender and age group older than 60 years predominated. Eyes larger than 26 mm showed the greatest difference between the dioptric power of the intraocular lens implanted according to Holladay and those smaller than 22 mm according to Barret Universal. Both groups presented a decrease of the spherical equivalent, being higher than 7 and 5 diopters in eyes larger than 26 mm postoperatively in both formulas. Postoperatively, there was an improvement in uncorrected and corrected visual acuity of more than 4 lines in the Snellen chart, independent of axial length, for both groups under study. No significant changes in keratometric cylinder. In 70.0 percent of the cases, the final refractive result was in the emmetropia range for the Holladay 2 group and 66.7 percent for the Barret Universal 2 group. Conclusions: Both formulas are useful for the calculation of the intraocular lens in all axial length ranges(AU)

Nanofiber capsules for minimally invasive sampling of biological specimens from gastrointestinal tract.

Accurate and rapid point-of-care tissue and microbiome sampling is critical for early detection of cancers and infectious diseases and often result in effective early intervention and prevention of disease spread. In particular, the low prevalence of Barrett's and gastric premalignancy in the Western world makes population-based endoscopic screening unfeasible and cost-ineffective. Herein, we report a method that may be useful for prescreening the general population in a minimally invasive way using a swallowable, re-expandable, ultra-absorbable, and retrievable nanofiber cuboid and sphere produced by electrospinning, gas-foaming, coating, and crosslinking. The water absorption capacity of the cuboid- and sphere-shaped nanofiber objects is shown ∼6000% and ∼2000% of their dry mass. In contrast, unexpanded semicircular and square nanofiber membranes showed <500% of their dry mass. Moreover, the swallowable sphere and cuboid were able to collect and release more bacteria, viruses, and cells/tissues from solutions as compared with unexpanded scaffolds. In addition to that, an expanded sphere shows higher cell collection capacity from the esophagus inner wall as compared with the unexpanded nanofiber membrane. Taken together, the nanofiber capsules developed in this study could provide a minimally invasive method of collecting biological samples from the duodenal, gastric, esophagus, and oropharyngeal sites, potentially leading to timely and accurate diagnosis of many diseases. STATEMENT OF SIGNIFICANCE: Recently, minimally invasive technologies have gained much attention in tissue engineering and disease diagnosis. In this study, we engineered a swallowable and retrievable electrospun nanofiber capsule serving as collection device to collect specimens from internal organs in a minimally invasive manner. The sample collection device could be an alternative endoscopy to collect the samples from internal organs like jejunum, stomach, esophagus, and oropharynx without any sedation. The newly engineered nanofiber capsule could be used to collect, bacteria, virus, fluids, and cells from the abovementioned internal organs. In addition, the biocompatible and biodegradable nanofiber capsule on a string could exhibit a great sample collection capacity for the primary screening of Barret Esophagus, acid reflux, SARS-COVID-19, Helicobacter pylori, and gastric cancer.

Impact of the Tumor Microenvironment for Esophageal Tumor Development-An Opportunity for Prevention?

Despite therapeutical advancements, and in contrast to other malignancies, esophageal adenocarcinoma (EAC) prognosis remains dismal while the incidence has markedly increased worldwide over the past decades. EAC is a malignancy of the distal esophageal squamous epithelium at the squamocolumnar junction with gastric cells expanding into the esophagus. Most EAC patients have a history of Barret's esophagus (BE), a metaplastic adaption to chronic reflux, initially causing an inflammatory microenvironment. Thus, the immune system is highly involved early on in disease development and progression. Normally, anti-tumor immunity could prevent carcinogenesis but in rare cases BE still progresses over a dysplastic intermediate state to EAC. The inflammatory milieu during the initial esophagitis phase changes to a tolerogenic immune environment in BE, and back to pro-inflammatory conditions in dysplasia and finally to an immune-suppressive tumor microenvironment in EAC. Consequently, there is a huge interest in understanding the underpinnings that lead to the inflammation driven stepwise progression of the disease. Since knowledge about the constellations of the various involved cells and signaling molecules is currently fragmentary, a comprehensive description of these changes is needed, allowing better preventative measures, diagnosis, and novel therapeutic targets.

Factores de riesgo asociados a esófago de Barrett en pacientes hospitalizados / Risk Factors Associated With Barrett's Esophagus In Hospitalized Patients

Objetivo: El objetivo de este artículo es realizar una revisión sistemática de artículos científicos que revelen los factores de riesgo asociados a Esófago de Barrett en pacientes hospitalizados. Métodos: La revisión fue efectuada mediante búsqueda electrónica de artículos relacionados a factores de riesgo asociadas a Esófago de Barrett en pacientes hospitalizados. La pregunta PEO fue ¿Cuáles son los factores de riesgo asociados a Esófago de Barret en pacientes hospitalizados? Las fuentes de búsqueda fueron en PUBMED. Los términos de búsqueda fueron: Factores de Riesgo; Esófago de Barrett; pacientes hospitalizados. Para esta revisión se seleccionaron los artículos publicados a partir el año 2010 que tuvieron experiencias investigativas y aspectos teórico-conceptuales. Resultados: De los 389 resultados encontrados con fuentes de indexación, se seleccionaron un total de 25 artículos donde 22 artículos contenían resultados de investigación y 3 fueron considerados para aspectos teórico ­ conceptuales que se relacionan con el propósito del estudio. La búsqueda dio como resultado factores de riesgo asociados a Esófago de Barrett según las características demográficas y rasgos del paciente, presentación y datos clínicos y estilos de vida. Conclusión: Se evidencia una asociación de diversos factores de riesgo con Esófago de Barret en pacientes hospitalizados. Los factores de riesgo asociados a Esófago de Barrett en la revisión que fueron más concordantes son sexo masculino, edad incrementada, síndrome metabólico, hernia hiatal, uso de inhibidores de bomba de protones, reflujo gastroesofágico(RGE), apnea obstructiva del sueño y esofagitis erosiva.

Objective: The objective of this article is to carry out a systematic review of scientific articles that reveal the risk factors associated with Barrett's esophagus in hospitalized patients. Methods: The review was performed by electronic search for articles related to risk factors associated with Barrett's esophagus in hospitalized patients. The PEO question was: What are the risk factors associated with Barrett's esophagus in hospitalized patients? The search sources were in PUBMED. The search terms were: Risk Factors; Barrett's esophagus; hospitalized patients. For this review, articles published from 2010 that had research experiences and theoretical-conceptual aspects were selected. Results: Of the 389 results found with indexing sources, a total of 25 articles were selected where 22 articles contained research results and 3 were considered for theoretical-conceptual aspects that are related to the purpose of the study. The search resulted in risk factors associated with Barrett's esophagus according to demographic characteristics and patient traits, presentation, and clinical data and lifestyles. Conclusion: An association of various risk factors with Barrett's esophagus is evidenced in hospitalized patients. The most concordant risk factors associated with Barrett's esophagus in the review were male sex, increased age, metabolic syndrome, hiatal hernia, use of proton pump inhibitors, gastroesophageal reflux (GER), obstructive sleep apnea, and erosive esophagitis.

Caracterización clínica, epidemiológica y anatómica del cáncer de esófago / Clinical, Epidemiological and Anatomical Characterization of Esophagus Cancer

Introducción: El cáncer de esófago es una enfermedad muy frecuente con tasas de supervivencia desalentadoras, debido a su naturaleza extremadamente agresiva. Objetivo: Caracterizar clínica, epidemiológica y anatómicamente a los pacientes con cáncer de esófago. Método: Se realizó un estudio descriptivo de casos clínicos que acudieron al servicio de Gastroenterología del Hospital Dr. Juan Bruno Zayas Alfonso, en el período comprendido entre junio -noviembre del año 2018. El universo de estudio estuvo conformado por el total de los pacientes de ambos sexos cuya cifra ascendió a 35. Resultados: El grupo de edad que predominó en ambos sexos fue el de 70 años y más, con 37,1 por ciento entre los hombres y 17,1 por ciento en las mujeres. Los hombres fueron los más afectados (68,6 por ciento). La localización anatómica que prevaleció fue a nivel del tercio inferior en un 37,1 por ciento entre los hombres y un 17,1 por ciento entre las féminas. El 57,1 por ciento resultó encontrarse bajo peso, en su mayoría presentaron el esófago de Barret como antecedente patológico personal, acompañado de odinofagia en el 88,6 por ciento de los pacientes. Conclusiones: El estudio permitió caracterizar a los pacientes con cáncer de esófago según variables clínicas, epidemiológicas y anatómicas. Aparece con mayor frecuencia en las últimas décadas de la vida y en etapas avanzadas de la enfermedad, se localiza con mayor frecuencia en el tercio inferior y asociados a antecedentes patológicos personales(AU)

Introduction: Esophageal cancer is a very frequent disease. Due to its extremely aggressive nature, it presents poor survival rates. Objective: To characterize clinically, epidemiologically and anatomically patients with esophageal cancer. Method: A descriptive study was carried out with clinical cases that attended the gastroenterology service at Dr. Juan Bruno Zayas Alfonso Hospital, in the period between June and November 2018. The study population was made up of the total number of patients of both sexes, whose number amounted to 35. Results: The age group that predominated in both sexes was 70 years and over, accounting for 37.1 percent among men and for 17.1 percent among women. Men were the most affected (68.6 percent). The anatomical location that prevailed was the level of the lower third, accounting for 37.1 percent among men and for 17.1 percent among women. 57.1 percent turned out to be underweight; most of them presented Barrett esophagus as a personal pathological history, accompanied by odynophagia in 88.6 percent of the patients. Conclusions: The study allowed characterizing patients with esophageal cancer according to clinical, epidemiological and anatomical variables. It appears more frequently in the last decades of life and in advanced stages of the disease. It is most frequently located in the lower third and associated with a personal pathological history(AU)

Esôfago de Barrett: o estado da arte / Barrett's Esophagus: the state of the art

Objetivo: Demonstrar fatores envolvidos nos distúrbios do sono em profissionais que fazem plantões. Métodos: Trata-se de estudo transversal, cuja amostra foi composta de 244 voluntários, plantonistas da área da saúde, sendo 191 do sexo feminino, que responderam a um questionário socioeconômico, associado à aplicação da Escala de Sonolência de Epworth e ao Índice de Qualidade do Sono de Pittsburgh. Os dados foram analisados pelos coeficientes de Spearman e de Kendall Tau, com distribuição de probabilidade gama. Resultados: Houve significância (p<0,05) com o Índice de Qualidade do Sono de Pittsburgh e a atividade física (+0,216), ergonomia (+0,148), filhos (-0,146), valor da remuneração (+0,112) e disfunção durante o dia (+0,352). Também houve significância com a Escala de Sonolência de Epworth e atividade física (+0,138), renda familiar (-0,118), trabalho semanal (-0,151), latência do sono (-0,106), duração do sono (-0,107), eficiência do sono (-0,139) e disfunção durante o dia (+0,170). Por fim, a eficiência do sono teve significiância com profissão (-0,209), tabagismo (+0,402), Escala de Sonolência de Epworth (-0,139) e dissonias com a obesidade (índice de massa corporal >30; razão de chance de 1,40; intervalo de confiança de 95% de 1,02-1,94). Conclusão: As medidas autorrelatadas são prontamente obtidas com questionários validados, como a Escala de Sonolência de Epworth e o Índice de Qualidade do Sono de Pittsburgh, encontrando-se correlações com renda familiar, ter ou não filhos, índice de massa corporal, atividade física, ergonomia, condições de trabalho, tabagismo e componentes biopsicossociais. Em virtude do caráter transversal deste estudo é indispensável mais estudos com maior follow-up

Objective: To demonstrate factors involved in sleep disorders in professionals who take shifts. Methods: This is a cross-sectional study whose sample consists of 244 volunteers, on-duty health workers, 191 females, who answered a socioeconomic questionnaire, associated with application of the Epworth Sleepiness Scale and the Pittsburgh Sleep Quality Index. Data were analyzed with Spearman's and Kendall Tau coefficients, and gamma probability distribution. Results: There was significance (p<0,05) with the Pittsburgh Sleep Quality Index and physical activity (+0,216), ergonomics (+0,148), children (-0,146), the wage (+0,112), dysfunction during the day (+0,352). Also there was significance with the Epworth Sleepiness Scale and physical activity (+0,138), family income (-0,118), weekly workload (-0,151), sleep latency (-0,106), sleep duration (-0,107), sleep efficiency (-0,139), and dysfunction during the day (+0,170). Finally, sleep efficiency was significant with occupation (-0,209), smoking habits (+0,402), Epworth Sleepiness Scale (-0,139), dyssomnia with obesity (body index mass >30; OR of 1,40; CI 95% 1,02-1,94). Conclusion: Self-reported measures are readily obtained with validated questionnaires such as Epworth Sleepiness Scale and Pittsburgh Sleep Quality Index, with correlations with family income, having children or not, body mass index, physical activity, ergonomics, working conditions, smoking habits, and biopsychosocial components. Due to the cross-sectional nature of this study, further research with longer follow-up is indispensable

Effect of Aromatic Amines on the Properties of Formaldehyde-Based Xerogels.

This study investigates the synthesis of formaldehyde-based xerogels using alternative aromatic precursors, with comparison to traditional resorcinol-formaldehyde analogues, in order to alter the chemical composition of the resulting gels. By replacing resorcinol with aromatic amine molecules, i.e., ammeline, melamine and melem, each expected to undergo similar reactions with formaldehyde as the substituted species, we found that for all substituted gels, at low additive contents, the gel structure was compromised and non-porous materials were formed, as opposed to the most abundant monomers, and therefore, these additives seem to act as impurities at low levels. Working towards higher additive contents, melem monomers exhibited low solubility (~5%), even at elevated temperatures, thereby limiting the range to which melem could act as a substitute, while melamine could be incorporated up to ~40% under acidic conditions, with enhanced microporosity over this range. Pure gels were successfully synthesised from ammeline, but their performance was inferior to resorcinol-formaldehyde gels, while melamine-formaldehyde analogues required acidic reaction conditions but shrank considerably on sub-critical drying, adversely affecting the gel properties and demonstrating their lack of potential as sorbents. This demonstrates the potential for the inclusion of aminated aromatics within resorcinol-based gel systems, however, only as partial substitutes and not complete replacements.

Impact of Gastric Bypass on Erosive Esophagitis and Barret's Esophagus.

BACKGROUND: The association between gastroesophageal reflux disease (GERD) and obesity is clearly defined. The incidence of erosive esophagitis (EE) and Barrett's esophagus (BE) are as high as 26 and 6%, respectively. Gastric bypass (GBP) is considered the gold standard for obese patients with GERD. Evidence about the impact of GBP on EE and BE is not yet clear but more inspiring every day. METHODS: Obese patients operated by GBP with EE or BE were included for this study. Demographics, BMI, %EWL, and the evolution of EE and BE with pre and postoperative upper endoscopy were analyzed. RESULTS: In this study, 64 patients were included, 55 with EE and 9 with BE. The preoperative BMI was 44.29 km/m2 ± 3.5 and the %EWL was 78.5 ± 5.8 in the first year postoperative. Preoperatively, EE was distributed as follows: A: 54.5% (30), B: 34.5% (19), C: 9% (5), D: 2% (1). BE findings were the following: short segment (SSBE): 45% (4) and long segment (LSBE): 55% (5). Postoperatively, 80% of the patients with EE resolved their condition, 11% improved, 7% had no changes, and 2% worsened. From the patients with SSBE, 75% resolved their condition and 40% with LSBE resolved their condition after 24 months and no patient progressed to dysplasia. CONCLUSION: Patients with EE had a statistically significant resolution after GBP. BE was improved or even resolved in many patients without acquiring significance but also without progression. Long-term surveillance data is necessary to define the certain evolution of EE and BE after GBP.

Screening and Prevention of Barrett's Esophagus.

Barrett's esophagus (BO) is a risk factor for esophageal adenocarcinoma. However, screening for BO is difficult since it is not yet clear who should be screened and which screening method is cost-effective. Screening methods could be upper endoscopy at the time of the first screening colonoscopy, transnasal endoscopy, esophageal capsule endoscopy, or cytosponge. In order to prevent the development of BO or its neoplastic progression, there are modifiable risk factors like obesity or smoking that can be influenced. In addition, several drugs like proton pump inhibitors, aspirin, nonsteroidal anti-inflammatory drugs and statins have shown promising effects in mostly observational studies. However, data from prospective randomized trials are scarce in order to draw final conclusions.

Barretts's carcinogenesis.

Barrett's esophagus is considered a precancerous lesion of esophageal adenocarcinoma (EAC). Long-segment Barrett's esophagus, which is generally associated with intestinal metaplasia, has a higher rate of carcinogenesis than short-segment Barrett's esophagus, which is mainly composed of cardiac-type mucosa. However, a large number of cases reportedly develop EAC from the cardiac-type mucosa which has the potential to involve intestinal phenotypes. There is no consensus regarding whether the definition of Barrett's epithelium should include intestinal metaplasia. Basic researches using rodent models have provided information regarding the origins of Barrett's epithelium. Nevertheless, it remains unclear whether differentiated gastric columnar epithelium or stratified esophageal squamous epithelium undergo transdifferentiation into the intestinal-type columnar epithelium, transcommittment into the columnar epithelium, or whether the other pathways exist. Reflux of duodenal fluid including bile acids into the stomach may occur when an individual lies down after eating, which could cause the digestive juices to collect in the fornix of the stomach. N-nitroso-bile acids are produced with nitrites that are secreted from the salivary glands, and bile acids can drive expression of pro-inflammatory cytokines via EGFR or the NF-κB pathway. These steps may contribute significantly to carcinogenesis.

Expression of metalloproteinase-9 in patients with mild and severe forms of gastroesophageal reflux disease.

BACKGROUND: Gastroesophageal reflux disease develops when the stomach contents causes troublesome symptoms and complications. Mild forms are non-erosive and erosive esophagitis, and severe forms are Barrett's esophagus and Esophageal adenocarcinoma. Matrix metalloproteinases are endopeptidases that can degrade components of the extracellular matrix, they play an important role in tumor invasion as well as in metastasis. OBJECTIVE: To correlate the expression of metalloproteinase 9 (MMP-9) in esophageal biopsies from patients with mild and severe forms of Gastroesophageal reflux disease. METHOD: Cross-sectional study. The expression of MMP-9 was determined in biopsies of esophageal tissue of patients with mild and severe GRD. The included variables were age, sex, diagnosis, smoking and alcoholic habits, body mass index (BMI) and expression of MMP-9. Descriptive statistics was performed, Kappa for concordance in diagnosis as well as X2. RESULTS: There were 50 patients, 32 (64%) men and 18 (36%) women, mean age 52.13 ± 14.75 years of age. 12 (24%) with smoking and 7 (14%) with alcoholism. Average BMI was 26.71 ± 4.07 kg/m2 (15 to 33); 40 (80%) with obesity. The inter observer concordance for histopathological diagnosis was 1.0 and 0.84 for esophagitis degrees. 27 (54%) patients had esophagitis, 16 (32%) Barrett's esophagus and 7 (14%) esophageal cancer. There was expression of MMP-9 in four patients with esophagitis, five with Barrett's esophagus and five with esophageal cancer. Statistical significance was found between the expression of MMP-9 and smoking (p = 0.011) and histopathological diagnosis (p = 0.052). CONCLUSIONS: The expression of MMP-9 is most common in severe forms compared to the mild forms of GRD.

ANTECEDENTES: La enfermedad por reflujo gastroesofágico (ERGE) se desarrolla cuando el contenido estomacal ocasiona síntomas molestos o complicaciones. Las formas leves son esofagitis no erosiva y erosiva; las graves, esófago de Barrett y adenocarcinoma esofágico. Las metaloproteinasas de la matriz degradan componentes de la matriz extracelular, y tienen un papel importante en la invasión tumoral y la metástasis. OBJETIVO: Relacionar la expresión de la metaloproteinasa-9 (MMP-9) en biopsias esofágicas de pacientes con formas leves y graves de ERGE. MÉTODO: Estudio transversal. Se determinó la expresión de MMP-9 en biopsias esofágicas de pacientes con ERGE grave y leve. Las variables fueron edad, sexo, diagnóstico, tabaquismo, alcoholismo, índice de masa corporal (IMC) y expresión de MMP-9. Se realizó estadística descriptiva, concordancia para el diagnóstico y prueba de ji al cuadrado. RESULTADOS: 50 pacientes, 32 (64%) hombres y 18 (36%) mujeres, con edad media de 52.13 ± 14.75 años. Doce (24%) fumadores y 7 (14%) con alcoholismo. El IMC promedio fue de 26.71 ± 4.07 kg/m2 (rango: 15-33); 40 (80%) eran obesos. La concordancia entre observadores para el diagnóstico histopatológico fue de 1.0, y de 0.84 para esofagitis. Veintisiete (54%) tuvieron esofagitis, 16 (32%) esófago de Barrett y 7 (14%) cáncer de esófago. Hubo expresión de MMP-9 en cuatro pacientes con esofagitis, cinco con esófago de Barrett y cinco con cáncer esofágico. Encontramos diferencia estadísticamente significativa entre la expresión de MMP-9 y el tabaquismo (p = 0.011) y el diagnóstico histopatológico (p = 0.052). CONCLUSIONES: La expresión de MMP-9 es más frecuente en las formas graves que en las leves de ERGE.

Management of Early Stage Gastric and Gastroesophageal Junction Malignancies.

Esophageal and gastric carcinomas are prevalent malignancies worldwide. In contrast to the poor prognosis associated with advanced stages of disease, early stage disease has a favorable prognosis. Early stage gastric cancer (ESGC) is defined as cancer in which the depth of invasion is limited to the submucosal layer of the stomach on histologic examination, regardless of lymph node status. ESGC that meets standard or expanded criteria can be treated via endoscopic mucosal resection and endoscopic submucosal dissection. Similar indications for endoscopic interventions exist for gastroesophageal junction and esophageal malignancies."

Increase of CD45-positive Immune Cells in Liver Parenchyma Indicates a More Favorable Prognosis for Patients With Barrett's Cancer.

BACKGROUND: Despite advances in perioperative management, the 5-year survival rate of patients with esophageal adenocarcinoma (Barrett's cancer) is poor. Adjuvant immunotherapies are currently the subject of clinical trials. The prognostic role of tumor-infiltrating T-lymphocytes (TILs) expressing CD45 has only been investigated in primary tumors. The significance of TILs in the target organs of distant metastases, in particular the liver, is unclear. This study examined the influence of CD45-positive cells in liver parenchyma and primary tumors on cumulative survival. MATERIALS AND METHODS: The density of CD45-positive cells was analyzed immunohistochemically using tissue microarrays. Sixty-five patients for whom a liver biopsy was available in addition to the primary tumor were included in the study. Liver metastases were found in 21 patients. The results of the immunohistochemical analysis were correlated with patient's outcomes. The Cox proportional hazard model was used to compute mortality hazard ratio in consideration of clinical variables. RESULTS: Elevated density of CD45-positive cells in the liver biopsy corresponded with a better cumulative survival rate (p<0.001), while no significant differences were found for primary tumors. Multivariate Cox regression analysis showed that a high density of CD45-positive cells in the liver parenchyma was an independent prognostic parameter of longer overall survival (hazard ratio(HR)=0.432, p=0.048). CONCLUSION: The density of CD45-positive cells in the liver parenchyma is an easily measured prognostic biomarker that can identify patient subgroups with a better prognosis. In addition, the density of CD45-positive cells in the liver may assist as a criterion for selecting patients with a high potential for response to adjuvant immunotherapy.

In-vivo Barrett's esophagus digital pathology stage classification through feature enhancement of confocal laser endomicroscopy.

Barrett's esophagus (BE) is a premalignant condition that has an increased risk to turn into esophageal adenocarcinoma. Classification and staging of the different changes (BE in particular) in the esophageal mucosa are challenging since they have a very similar appearance. Confocal laser endomicroscopy (CLE) is one of the newest endoscopy tools that is commonly used to identify the pathology type of the suspected area of the esophageal mucosa. However, it requires a well-trained physician to classify the image obtained from CLE. An automatic stage classification of esophageal mucosa is presented. The proposed model enhances the internal features of CLE images using an image filter that combines fractional integration with differentiation. Various features are then extracted on a multiscale level, to classify the mucosal tissue into one of its four types: normal squamous (NS), gastric metaplasia (GM), intestinal metaplasia (IM or BE), and neoplasia. These sets of features are used to train two conventional classifiers: support vector machine (SVM) and random forest. The proposed method was evaluated on a dataset of 96 patients with 557 images of different histopathology types. The SVM classifier achieved the best performance with 96.05% accuracy based on a leave-one-patient-out cross-validation. Additionally, the dataset was divided into 60% training and 40% testing; the model achieved an accuracy of 93.72% for the testing data using the SVM. The presented model showed superior performance when compared with four state-of-the-art methods. Accurate classification is essential for the intestinal metaplasia grade, which most likely develops into esophageal cancer. Not only does our method come to the aid of physicians for more accurate diagnosis by acting as a second opinion, but it also acts as a training method for junior physicians who need practice in using CLE. Consequently, this work contributes to an automatic classification that facilitates early intervention and decreases samples of required biopsy.

Optimization of Decellularization Procedure in Rat Esophagus for Possible Development of a Tissue Engineered Construct.

Background: Current esophageal treatment is associated with significant morbidity. The gold standard therapeutic strategies are stomach interposition or autografts derived from the jejunum and colon. However, severe adverse reactions, such as esophageal leakage, stenosis and infection, accompany the above treatments, which, most times, are life threating. The aim of this study was the optimization of a decellularization protocol in order to develop a proper esophageal tissue engineered construct. Methods: Rat esophagi were obtained from animals and were decellularized. The decellularization process involved the use of 3-[(3-cholamidopropyl) dimethylammonio]-1-propanesulfonate (CHAPS) and sodium dodecyl sulfate (SDS) buffers for 6 h each, followed by incubation in a serum medium. The whole process involved two decellularization cycles. Then, a histological analysis was performed. In addition, the amounts of collagen, sulphated glycosaminoglycans and DNA content were quantified. Results: The histological analysis revealed that only the first decellularization cycle was enough to produce a cellular and nuclei free esophageal scaffold with a proper extracellular matrix orientation. These results were further confirmed by biochemical quantification. Conclusions: Based on the above results, the current decellularization protocol can be applied successfully in order to produce an esophageal tissue engineered construct.