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1.
Am J Gastroenterol ; 115(11): 1786-1796, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33156096

RESUMO

The functional lumen imaging probe (FLIP) measures luminal dimensions using impedance planimetry, performed most often during sedated upper endoscopy. Mechanical properties of the esophageal wall and opening dynamics of the esophagogastric junction (EGJ) can be objectively evaluated in esophageal motor disorders, eosinophilic esophagitis, esophageal strictures, during esophageal surgery and in postsurgical symptomatic states. Distensibility index, the ratio of EGJ cross sectional area to intraballoon pressure, is the most useful FLIP metric. Secondary peristalsis from balloon distension can be displayed topographically as repetitive anterograde or retrograde contractile activity in the esophageal body, similar to high-resolution manometry. Real-time interpretation and postprocessing of FLIP metadata can complement the identification of esophageal outflow obstruction and achalasia, especially when findings are inconclusive from alternate esophageal tests in symptomatic patients. FLIP can complement the diagnosis of achalasia when manometry and barium studies are inconclusive or negative in patients with typical symptoms. FLIP can direct adequacy of disruption of the EGJ in achalasia when used during and immediately after myotomy and pneumatic dilation. Lumen diameter measured using FLIP in eosinophilic esophagitis and in complex strictures can potentially guide management. An abbreviated modification of the Grading of Recommendations Assessment, Development, and Evaluation was used to determine the quality of available evidence and recommendations regarding FLIP utilization. FLIP metrics that are diagnostic or suggestive of an abnormal motor pattern and metrics that define normal esophageal physiology were developed by consensus and are described in this review.


Assuntos
Endoscopia do Sistema Digestório/métodos , Esofagite Eosinofílica/patologia , Acalasia Esofágica/patologia , Estenose Esofágica/patologia , Junção Esofagogástrica/patologia , Refluxo Gastroesofágico/patologia , Dilatação , Impedância Elétrica , Esofagite Eosinofílica/fisiopatologia , Esofagite Eosinofílica/cirurgia , Acalasia Esofágica/fisiopatologia , Acalasia Esofágica/cirurgia , Transtornos da Motilidade Esofágica/patologia , Transtornos da Motilidade Esofágica/fisiopatologia , Transtornos da Motilidade Esofágica/cirurgia , Estenose Esofágica/fisiopatologia , Estenose Esofágica/cirurgia , Fundoplicatura , Refluxo Gastroesofágico/fisiopatologia , Refluxo Gastroesofágico/cirurgia , Miotomia de Heller , Humanos , Manometria , Tamanho do Órgão
2.
PLoS One ; 15(9): e0238852, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32925965

RESUMO

The pathogenesis of esophageal injury in gastroesophageal reflux disease (GERD) is incompletely understood. We modeled exposure of human esophageal myofibroblasts (HEMFs) to gastroesophageal reflux by repeated treatment with pH 4.5 and pH 4.5 bile salts and determined the effects on the epithelium in a 3D organotypic-like air-liquid interface model. Total, basal and supra-basal thickness of the epithelium were measured and immunostaining for p63, for basal (CK 14) and supra-basal (CK 4) squamous differentiation markers, and for cell proliferation (PCNA) were performed. Epithelial cell proliferation in response to HEMF conditioned media was also assessed in 2D culture. In the 3D organotypic model, total epithelial thickness increased similarly with pH 4.5 and pH 4.5 bile salt treated versus untreated and bile salt treated HEMF conditioned media. Epithelial p63 immunostaining was increased and multilayered. There was expansion of the CK14+ basal and CK4+ supra-basal layers in the epithelium established with conditioned media from pH 4.5 and pH 4.5 bile salt treated HEMFs versus untreated HEMF conditioned media. PCNA + cells per µm of tissue were unchanged in the basal layer across all treatment conditions while PCNA + cells per total DAPI + cells were decreased. In 2D culture, basal epithelial proliferation decreased with conditioned media from pH 4.5 and pH 4.5 bile salt treated HEMFs compared to conditioned media from untreated HEMF conditioned media. Secreted factors from HEMFs treated with acidic stimuli encountered in GERD increase epithelial thickness compared to secreted factors from untreated HEMFs and expand both basal and supra-basal layers. Our findings demonstrate for the first time paracrine regulation of the squamous epithelium from acid stimulated HEMFs. The effects of secreted factors from acid treated HEMFs on basal cell proliferation in this model and the mechanism mediating the increase in epithelial thickness merit further investigation.


Assuntos
Ácidos e Sais Biliares/farmacologia , Meios de Cultivo Condicionados/farmacologia , Células Epiteliais/patologia , Esôfago/patologia , Refluxo Gastroesofágico/patologia , Miofibroblastos/citologia , Comunicação Parácrina , Técnicas de Cultura de Células , Células Cultivadas , Células Epiteliais/efeitos dos fármacos , Esôfago/efeitos dos fármacos , Humanos , Técnicas In Vitro
3.
Ann N Y Acad Sci ; 1481(1): 59-71, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32770542

RESUMO

Since its discovery, Helicobacter pylori (H. pylori) has attracted attention in the biomedical world with its numerous pathophysiologic implications, both gastrointestinal and systemic. Beyond its well-established carcinogenic properties, emerging evidence also supports "harmful" proinflammatory and neurodegenerative roles of H. pylori. On the other hand, H. pylori infection has been proposed to be "protective" against several diseases, such as asthma and gastroesophageal reflux disease. Eosinophilic esophagitis (EoE) is a relatively new, allergen/immune-mediated disease, which has also been linked to these considerations. Main arguments are a postulated shift of immune responses by H. pylori from T helper 2 (TH 2) to TH 1 polarization, as well as a potential decline of the H. pylori burden with the dramatic parallel rise of ΕοΕ: a series of observational studies reported an inverse association. In this review, we counter these arguments by providing further epidemiological data, which point out that this generalization might be rather incomplete. We also discuss the limitations of the existing studies evaluating a possible association. Furthermore, we provide current evidence on common pathogenetic components, which share both entities. In summary, the claim that H. pylori is protective against EoE is rather incomplete, and further mechanistic studies are necessary to elucidate a possible association.


Assuntos
Esofagite Eosinofílica/imunologia , Refluxo Gastroesofágico/imunologia , Infecções por Helicobacter/imunologia , Helicobacter pylori/imunologia , Células Th1/imunologia , Células Th2/imunologia , Esofagite Eosinofílica/microbiologia , Esofagite Eosinofílica/patologia , Refluxo Gastroesofágico/microbiologia , Refluxo Gastroesofágico/patologia , Infecções por Helicobacter/patologia , Humanos , Células Th1/patologia , Células Th2/patologia
4.
Medicine (Baltimore) ; 99(29): e20471, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32702810

RESUMO

Traditional Chinese medicine tongue diagnosis can mirror the status of the internal organ, but evidence is lacking regarding the accuracy of tongue diagnosis to gastroesophageal reflux disease (GERD). This study was to investigate the association between GERD and tongue manifestation, and whether tongue imaging could be initial diagnosis of GERD noninvasively.We conducted a cross-sectional, case-controlled observational study at Kaohsiung Chang Gung Memorial Hospital in Taiwan from January 2016 to September 2017. Participants aged over 20 years old with GERD were enrolled and control group without GERD were matched by sex. Tongue imaging were acquired with automatic tongue diagnosis system, then followed by endoscope examination. Nine tongue features were extracted, and a receiver operating characteristic (ROC) curve, analysis of variance, and logistic regression were used.Each group enrolled 67 participants. We found that the saliva amount (P = .009) and thickness of the tongue's fur (P = .036), especially that in the spleen-stomach area (%) (P = .029), were significantly greater in patients with GERD than in those without. The areas under the ROC curve of the amount of saliva and tongue fur in the spleen-stomach area (%) were 0.606 ±â€Š0.049 and 0.615 ±â€Š0.050, respectively. Additionally, as the value of the amount of saliva and tongue fur in the spleen-stomach area (%) increased, the risk of GERD rose by 3.621 and 1.019 times, respectively. The tongue fur in the spleen-stomach area (%) related to severity of GERD from grade 0 to greater than grade B were 51.67 ±â€Š18.72, 58.10 ±â€Š24.60, and 67.29 ±â€Š24.84, respectively.The amount of saliva and tongue fur in the spleen-stomach area (%) might predict the risk and severity of GERD and might be noninvasive indicators of GERD. Further large-scale, multi-center, randomized investigations are needed to confirm the results.Trial registration: NCT03258216, registered August 23, 2017.


Assuntos
Refluxo Gastroesofágico/diagnóstico , Refluxo Gastroesofágico/patologia , Doenças da Língua/diagnóstico por imagem , Doenças da Língua/patologia , Adulto , Idoso , Estudos de Casos e Controles , Estudos Transversais , Endoscopia/métodos , Feminino , Refluxo Gastroesofágico/complicações , Humanos , Masculino , Medicina Tradicional Chinesa/métodos , Pessoa de Meia-Idade , Saliva/fisiologia , Índice de Gravidade de Doença , Taiwan/epidemiologia , Língua , Doenças da Língua/etiologia
5.
Am Surg ; 86(11): 1525-1527, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32683926

RESUMO

Non-ablative radiofrequency treatment to the lower esophageal sphincter (Stretta) has been shown to be beneficial after failed Nissen fundoplication. To our knowledge, this is the first report of Stretta after transoral incisionless fundoplication (TIF). This patient is a 17-year-old female who had gastroesophageal reflux disease (GERD) symptoms for 9 years. She presented with heartburn, regurgitation, and epigastric discomfort. She used omeprazole for 9 years. Esophagogastroduodenoscopy (EGD) showed a 2 cm sliding hiatal hernia and DeMeester score of 25. The GERD Health-Related Quality of Life (GERD-HRQL) score on omeprazole was 14. Patient underwent a TIF procedure, which was uneventful. Her symptoms resolved, and she discontinued omeprazole. Six months later, she had episodes of repeated violent vomiting followed by recurrence of regurgitation, nausea, bloating, and dysphagia. She resumed omeprazole. Diagnostic workup included gastric emptying scan, which was normal. EGD showed no hiatal hernia and partial disruption of the TIF valve. DeMeester score was 36.3. Esophageal manometry with impedance showed intact peristalsis and normal relaxation of the lower esophageal sphincter. The patient underwent Stretta, which was uneventful. The previous TIF did not increase the complexity of the procedure. There were no immediate or postoperative complications. The patient reported gradual improvement of her symptoms with complete resolution 2 months postoperatively. She discontinued omeprazole. The GERD-HRQL score 17 months post-Stretta was 0. This case highlights the feasibility, safety, and efficacy of performing Stretta following TIF. It provides an endoluminal alternative to complex revisional antireflux surgery. Prospective studies with longer follow-up are required to validate this concept.


Assuntos
Esfíncter Esofágico Inferior/cirurgia , Fundoplicatura , Terapia por Radiofrequência/métodos , Adolescente , Esfíncter Esofágico Inferior/patologia , Esofagoscopia , Feminino , Fundoplicatura/métodos , Refluxo Gastroesofágico/patologia , Refluxo Gastroesofágico/cirurgia , Humanos , Falha de Tratamento , Resultado do Tratamento
6.
Aliment Pharmacol Ther ; 52(4): 637-645, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32656869

RESUMO

BACKGROUND: Oesophageal radiofrequency reduces use of proton pump inhibitors (PPIs) in patients with gastro-oesophageal reflux disease responding to PPIs. AIM: To determine the efficacy of oesophageal radiofrequency in patients with PPI-refractory heartburn. METHODS: A randomised, double-blind, sham-controlled multicentre study was designed to assess the efficacy of oesophageal radiofrequency in PPI non-responding patients with heartburn. Patients had moderate-to-severe heartburn defined by at least 3 occurrences a week, and not improved by continuous PPI treatment. The primary endpoint was clinical success at week 24, defined by intake of less than 7 PPI doses over the 2 preceding weeks and adequate symptom control determined by the patient. RESULTS: Sixty two patients were randomised, 29 to the oesophageal radiofrequency group and 33 to the sham group. Intention-to-treat analysis showed that 1/29 (3.4%) and 5/33 (15.1%) achieved the primary endpoint in the oesophageal radiofrequency and sham groups, respectively (NS). There was no significant difference between oesophageal radiofrequency and sham regarding the number of days without heartburn, days with PPI consumption in the last 2 weeks, and patients not taking PPIs. No pH-impedance parameter was associated with clinical response. The occurrence of adverse events was similar in both groups. CONCLUSION: This sham-controlled, randomised study did not demonstrate any efficacy of oesophageal radiofrequency for the treatment of PPI-refractory heartburn regarding symptom relief or consumption of PPIs. ClinicalTrials.gov NCT01682265.


Assuntos
Refluxo Gastroesofágico/terapia , Azia/terapia , Inibidores da Bomba de Prótons/uso terapêutico , Terapia por Radiofrequência/métodos , Adolescente , Adulto , Idoso , Terapia Combinada , Método Duplo-Cego , Resistência a Medicamentos/efeitos da radiação , Feminino , França , Refluxo Gastroesofágico/complicações , Refluxo Gastroesofágico/tratamento farmacológico , Refluxo Gastroesofágico/patologia , Azia/tratamento farmacológico , Azia/etiologia , Azia/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Placebos , Índice de Gravidade de Doença , Falha de Tratamento , Adulto Jovem
7.
Anticancer Res ; 40(7): 3991-3994, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32620642

RESUMO

BACKGROUND: Russell body gastroesophagitis is a rare entity characterized by the accumulation of immunoglobulins within the cytoplasm of plasma cells. CASE REPORT: Here, we present the case of a 41-year-old male with history of gastroesophageal reflux disease who presented with nausea, vomiting, and altered mental status. Candida esophagitis was noted on upper endoscopy. After treatment, a surveillance endoscopy revealed salmon colored mucosa in the distal esophagus and mild gastric erythema. The biopsy confirmed Barrett's esophagus that was negative for dysplasia and mild chronic inactive gastritis. Interestingly, diffusely infiltrating Russell body-containing plasma cells (Mott cells) were present in the distal esophagus and extending into the gastric cardia. The Mott cells were highlighted on CD138 immunostaining and Periodic acid-Schiff stain. Immunostaining for cytokeratin AE1/AE3 was negative. There was no evidence of Helicobacter pylori organisms on the gastric mucosa. CONCLUSION: This is the first report on Russell body-containing plasma cells diffusely involving both esophagus and gastric cardia with concurrent Barrett's esophagus.


Assuntos
Esôfago de Barrett/complicações , Esofagite/complicações , Gastrite/complicações , Refluxo Gastroesofágico/complicações , Adulto , Esôfago de Barrett/patologia , Candidíase/complicações , Candidíase/patologia , Esofagite/patologia , Gastrite/patologia , Refluxo Gastroesofágico/patologia , Humanos , Masculino
8.
Otolaryngol Head Neck Surg ; 163(3): 560-562, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32340545

RESUMO

Gastroesophageal reflux disease (GERD) has been hypothesized as a risk factor for development of laryngeal cancer. A case-control study was performed to assess the association of laryngeal neoplasia with GERD. Cases consisted of patients with a history of laryngeal cancer or carcinoma in situ. Controls were patients without neoplasia who matched cases 2:1 on age, sex, race, and smoking history. Univariate and multivariate analyses were performed to assess risk of laryngeal neoplasia and GERD. In total, 2094 patients were included. Cases had higher rates of GERD. Univariate analysis demonstrated a positive association between GERD and laryngeal neoplasia (odds ratio, 1.33; 95% CI, 1.07-1.64). Multivariate analysis controlling for alcohol use history also demonstrated a positive association between GERD and laryngeal neoplasia (adjusted odds ratio, 1.29; 95% CI, 1.04-1.59). These results suggest increased odds of laryngeal carcinoma and carcinoma in situ in patients with GERD when controlling for smoking and drinking history.


Assuntos
Consumo de Bebidas Alcoólicas , Carcinoma in Situ/psicologia , Refluxo Gastroesofágico/complicações , Neoplasias Laríngeas/epidemiologia , Neoplasias Laríngeas/psicologia , Fumar , Idoso , Idoso de 80 Anos ou mais , Carcinoma in Situ/epidemiologia , Carcinoma in Situ/patologia , Estudos de Casos e Controles , Feminino , Refluxo Gastroesofágico/patologia , Refluxo Gastroesofágico/psicologia , Humanos , Neoplasias Laríngeas/patologia , Masculino , Pessoa de Meia-Idade , Razão de Chances
9.
J Laparoendosc Adv Surg Tech A ; 30(8): 869-874, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32208948

RESUMO

Introduction: Adenocarcinoma of the esophagus and cardia is a rare cancer, associated with chronic reflux disease. Its associated mortality is still very high, reflecting both aggressive biology and lack of adequate treatments. The aim of this article was to describe up to date management of these complex tumors. Materials and Methods: A systematic review of the literature was performed, using PubMed Central database. Articles published after the year 2000 were included, with no language exclusion. Results: Reflux disease and Barrett esophagus are strongly associated with esophageal adenocarcinoma. A strict surveillance should be initiated at diagnosis. Both proton pump inhibitors and antireflux surgery failed to influence the incidence of cancer. Surgery and multimodal therapies are keystones for curative treatment, but no clear consensus exists for the best option. A clear trend in standardization of the surgical approach is observed since last ten years. However, the optimal approach for the tumors of the cardia is still not completely set. Complication rate is still high, but real progresses are made, through the implementation of less invasive techniques. Conclusion: Progress has been made in the management of esophageal cancer. However, the multiplicity of choices failed to lead to standardization. The development of international consensus regarding multimodal treatment and surgical approaches is needed.


Assuntos
Adenocarcinoma/etiologia , Adenocarcinoma/terapia , Cárdia/patologia , Neoplasias Esofágicas/etiologia , Neoplasias Esofágicas/terapia , Refluxo Gastroesofágico/complicações , Neoplasias Gástricas/etiologia , Neoplasias Gástricas/terapia , Adenocarcinoma/diagnóstico , Adenocarcinoma/patologia , Esôfago de Barrett/patologia , Esôfago de Barrett/terapia , Terapia Combinada , Detecção Precoce de Câncer/métodos , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/patologia , Esofagectomia , Refluxo Gastroesofágico/patologia , Refluxo Gastroesofágico/terapia , Humanos , Lesões Pré-Cancerosas/patologia , Lesões Pré-Cancerosas/terapia , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patologia
10.
Georgian Med News ; (298): 88-93, 2020 Jan.
Artigo em Russo | MEDLINE | ID: mdl-32141857

RESUMO

The article is devoted to the study of the diagnostic effectiveness of using magnifying chromoendoscopy when examining the oral cavity in patients with a gastroenterological profile with extra-esophageal manifestations of reflux disease. Pathologies of the oral cavity are often one of the additional symptoms, according to the Montreal Consensus and classification of gastroesophageal reflux disease (GERD). Barrett's esophagus is a serious complication of GERD, in which a cylindrical epithelium with intestinal metaplasia is found in the epithelial lining of the mucous membrane of the esophagus, which is a marker of this disease often in combination with dysplasia instead of squamous stratified non-keratinized epithelium. The relevance is due to the fact that this disease is considered as a precancerous condition and is associated with an increased risk of developing adenocarcinoma of the lower third of the esophagus. In this regard, timely diagnosis of Barrett's esophagus and monitoring of these patients will improve the prognosis of the disease and reduce the frequency of deaths.


Assuntos
Esôfago de Barrett/diagnóstico , Esofagite Péptica/diagnóstico , Esofagoscopia/métodos , Refluxo Gastroesofágico/diagnóstico , Boca/diagnóstico por imagem , Esôfago de Barrett/patologia , Esofagite Péptica/patologia , Refluxo Gastroesofágico/patologia , Humanos , Valor Preditivo dos Testes , Ampliação Radiográfica
11.
Int J Biochem Cell Biol ; 122: 105736, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32135301

RESUMO

Esophageal adenocarcinoma essentially develops from esophageal inflammation caused by chronic GERD. During GERD episodes, the lower esophageal epithelium is repeatedly exposed to stomach acid, which often contains duodenal bile salts that prompt malignant transformation. TRAIL is one of the cytokines produced in response to such insults and targets the transformed cells exclusively. In this study, we simulated GERD episodes in vitro by exposing the cancer cells to acid or acid/bile combination and found that the cancer cells lived through acid attacks by expression of the decoy receptors and c-FLIPR but died of TRAIL-mediated apoptosis when bile salts were present. Further investigation revealed that acid/bile exposure downregulated the decoy receptors and thereby facilitated TRAIL signaling; meantime, it inhibited protein kinase C activity and thus expedited c-FLIPR degradation, allowing apoptosis to take place.


Assuntos
Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Ácidos e Sais Biliares/farmacologia , Proteína Reguladora de Apoptosis Semelhante a CASP8 e FADD/antagonistas & inibidores , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Receptores Chamariz do Fator de Necrose Tumoral/antagonistas & inibidores , Apoptose/efeitos dos fármacos , Proteína Reguladora de Apoptosis Semelhante a CASP8 e FADD/metabolismo , Linhagem Celular Tumoral , Refluxo Gastroesofágico/induzido quimicamente , Refluxo Gastroesofágico/metabolismo , Refluxo Gastroesofágico/patologia , Humanos , Ácido Clorídrico/farmacologia , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Transfecção , Receptores Chamariz do Fator de Necrose Tumoral/metabolismo
12.
Int J Biol Macromol ; 150: 354-361, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32057860

RESUMO

This study aimed to evaluate the in vitro protective effect of topical treatment with a native sulfated polysaccharide of G. caudata (SP-Gc), hydrolyzed (H-SP-Gc), or desulfated (D-SP-Gc) polysaccharide of Gracilaria caudata in esophageal biopsies obtained from GERD patients. Biopsies were obtained from nonerosive reflux disease (NERD) patients and from erosive esophagitis patients. Then, the biopsies were mounted in an Ussing chamber to measure the basal transepithelial electrical resistance (TEER). The effect of mucosal exposure to an acid solution on TEER was analyzed with or without different concentrations (1, 0.3 or 1%) of SP-Gc, H-SP-Gc, or D-SP-Gc, precoated on the mucosa. Basal esophageal mucosal electrical resistance was significantly lower in erosive esophagitis than from NERD. Mucosal samples precoated with native SP-Gc (1%) significantly prevented TEER drop induced by an acidic solution in NERD, but this effect was not observed in erosive esophagitis. Topical application of D-SP-Gc showed no difference compared to native SP-Gc. However, when treated with chemically-modified SP-Gc, the protective effect observed with native SP-Gc was lost. The present study indicated that SP-Gc protects the human esophageal mucosal barrier in NERD patients. This effect is dependent on the structure but is independent of the presence of sulfate.


Assuntos
Produtos Biológicos/química , Produtos Biológicos/farmacologia , Gracilaria/química , Membrana Mucosa/efeitos dos fármacos , Polissacarídeos/química , Polissacarídeos/farmacologia , Substâncias Protetoras/química , Substâncias Protetoras/farmacologia , Adulto , Idoso , Biópsia , Esôfago , Feminino , Refluxo Gastroesofágico/tratamento farmacológico , Refluxo Gastroesofágico/etiologia , Refluxo Gastroesofágico/metabolismo , Refluxo Gastroesofágico/patologia , Humanos , Hidrólise , Masculino , Pessoa de Meia-Idade , Análise Espectral , Adulto Jovem
13.
Clin Transl Gastroenterol ; 11(1): e00125, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31934893

RESUMO

OBJECTIVES: Barrett's esophagus (BE) is the precursor lesion and a major risk factor for esophageal adenocarcinoma (EAC). Although patients with BE undergo routine endoscopic surveillance, current screening methodologies have proven ineffective at identifying individuals at risk of EAC. Since microRNAs (miRNAs) have potential diagnostic and prognostic value as disease biomarkers, we sought to identify an miRNA signature of BE and EAC. METHODS: High-throughput sequencing of miRNAs was performed on serum and tissue biopsies from 31 patients identified either as normal, gastroesophageal reflux disease (GERD), BE, BE with low-grade dysplasia (LGD), or EAC. Logistic regression modeling of miRNA profiles with Lasso regularization was used to identify discriminating miRNA. Quantitative reverse transcription polymerase chain reaction was used to validate changes in miRNA expression using 46 formalin-fixed, paraffin-embedded specimens obtained from normal, GERD, BE, BE with LGD or HGD, and EAC subjects. RESULTS: A 3-class predictive model was able to classify tissue samples into normal, GERD/BE, or LGD/EAC classes with an accuracy of 80%. Sixteen miRNAs were identified that predicted 1 of the 3 classes. Our analysis confirmed previous reports indicating that miR-29c-3p and miR-193b-5p expressions are altered in BE and EAC and identified miR-4485-5p as a novel biomarker of esophageal dysplasia. Quantitative reverse transcription polymerase chain reaction validated 11 of 16 discriminating miRNAs. DISCUSSION: Our data provide an miRNA signature of normal, precancerous, and cancerous tissue that may stratify patients at risk of progressing to EAC. We found that serum miRNAs have a limited ability to distinguish between disease states, thus limiting their potential utility in early disease detection.


Assuntos
Adenocarcinoma/genética , Esôfago de Barrett/genética , Neoplasias Esofágicas/genética , Esôfago/metabolismo , Refluxo Gastroesofágico/genética , MicroRNAs/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Esôfago de Barrett/metabolismo , Esôfago de Barrett/patologia , Estudos de Casos e Controles , Análise Discriminante , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Esôfago/patologia , Refluxo Gastroesofágico/metabolismo , Refluxo Gastroesofágico/patologia , Humanos , Modelos Logísticos , MicroRNAs/sangue , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Gradação de Tumores , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transcriptoma
14.
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
15.
Dis Esophagus ; 33(1)2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-31778151

RESUMO

The radial distribution of esophago-gastric junction (EGJ) pressures with regard to troublesome dysphagia (TDysph) after antireflux surgery is poorly understood. Before and after antireflux surgery, end-expiratory and peak-inspiratory EGJ pressures were measured at eight angles of 45° radial separation in patients with reflux disease. All 34 patients underwent posterior crural repair, then either 90° anterior (N = 13) or 360° fundoplication (N = 21). Dysphagia was assessed prospectively using a validated questionnaire (score range 0-45) and TDysph defined as a dysphagia score that was ≥5 above pre-op baseline. Compared with before surgery, for 90° fundoplication, end-expiratory EGJ pressures were highest in the left-anterolateral sectors, the position of the partial fundoplication. In other sectors, pressures were uniformly elevated. Compared with 90° fundoplication, radial pressures after 360° fundoplication were higher circumferentially (P = 0.004), with a posterior peak. Nine patients developed TDysph after surgery with a greater increase in end-expiratory and peak-inspiratory EGJ pressures (P = 0.03 and 0.03, respectively) and significantly higher inspiratory pressure at the point of maximal radial pressure asymmetry (P = 0.048), compared with 25 patients without TDysph. Circumferential elevation of end-expiratory EGJ pressure after 90° and 360° fundoplication suggests hiatal repair elevates EGJ pressure by extrinsic compression. The highly localized focal point of elevated EGJ pressure upon inspiration in patients with TDysph after surgery is indicative of a restrictive diaphragmatic hiatus in the presence of a fundoplication.


Assuntos
Transtornos de Deglutição/etiologia , Fundoplicatura/efeitos adversos , Refluxo Gastroesofágico/cirurgia , Herniorrafia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Adulto , Idoso , Transtornos de Deglutição/patologia , Junção Esofagogástrica/patologia , Feminino , Refluxo Gastroesofágico/etiologia , Refluxo Gastroesofágico/patologia , Hérnia Hiatal/complicações , Hérnia Hiatal/patologia , Hérnia Hiatal/cirurgia , Humanos , Masculino , Manometria , Pessoa de Meia-Idade , Complicações Pós-Operatórias/patologia , Pressão , Estudos Prospectivos , Adulto Jovem
16.
Hum Exp Toxicol ; 39(4): 492-499, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31868530

RESUMO

The current study was undertaken to evaluate the effect of combined therapy of gabapentin and pantoprazole against forestomach and pylorus ligation-induced gastric esophageal reflux disease (GERD) in albino Wistar rats. Rats were randomly divided into five groups, each group consisting of six rats, fasted for 24 h, underwent forestomach and pylorus ligation, received normal saline (3 ml/kg, p.o.), normal control, toxic control, pantoprazole (30 mg/kg, p.o.), gabapentin (50 mg/kg, p.o.), or their combination. After 10 h, animals were killed by cervical dislocation and evaluated for pH of gastric content, volume of gastric juice, total acidity, and esophagitis index. Esophageal tissues were further analyzed for biochemical parameters such as superoxide dismutase, glutathione, catalase, thiobarbituric acid reactive substances, and protein carbonyl, and scanning electron microscopy (SEM) and histopathology were used for morphological evaluation. The results show the combination therapy of gabapentin and pantoprazole significantly inhibited the volume of gastric juice and total acidity esophagitis index and significantly increased the pH of gastric juice. Treatment with gabapentin and pantoprazole exhibited maximum antioxidant effect in comparison with monotherapy. Marked protection and restoration of normal morphology was observed through SEM and histopathology in the combination therapy as compared to monotherapy. Finally, it was concluded that combination therapy of pantoprazole and gabapentin has beneficial effect against GERD.


Assuntos
Gabapentina/uso terapêutico , Refluxo Gastroesofágico/prevenção & controle , Pantoprazol/uso terapêutico , Inibidores da Bomba de Prótons/uso terapêutico , Estômago/efeitos dos fármacos , Vias Aferentes/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Quimioterapia Combinada , Gabapentina/administração & dosagem , Esvaziamento Gástrico/efeitos dos fármacos , Refluxo Gastroesofágico/patologia , Pantoprazol/administração & dosagem , Inibidores da Bomba de Prótons/administração & dosagem , Ratos Wistar , Estômago/inervação , Estômago/patologia
18.
Scand J Gastroenterol ; 54(9): 1118-1123, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31524029

RESUMO

Gastric cancer, a disease with a reduced frequency for decades, now appears to be on the rise again in young Americans. The epidemiology of gastric cancer differs between tumors in the cardia and those of the more distal parts of the stomach. The tumors are divided into the intestinal type showing glandular growth pattern and the diffuse type with a different pattern. The latter often expresses neuroendocrine and more specifically ECL-cell markers suggesting that they originate from the ECL cell, the target cell for the antral hormone, gastrin. Helicobacter pylori gastritis is accepted as the major cause of gastric cancer, but only after having induced oxyntic atrophy which reduces gastric acid secretion and thus induces hypoacidity leading to hypergastrinemia. Long-term hypergastrinemia is known to induce malignant neoplasia in the stomach of animals as well as man. Recently treatment with proton pump inhibitor after Helicobacter pylori eradication in patients with gastroesophageal reflux disease, has been reported to predispose to gastric cancer. Since profound acid inhibition is a well-known cause of gastric neoplasia, it is to be expected that Helicobacter pylori infection and profound acid inhibition has an additive or possibly potentiating effect on the development of gastric cancer.


Assuntos
Gastrinas/sangue , Gastrite/microbiologia , Refluxo Gastroesofágico/patologia , Infecções por Helicobacter/patologia , Neoplasias Gástricas/patologia , Animais , Celulas Tipo Enterocromafim/metabolismo , Celulas Tipo Enterocromafim/patologia , Refluxo Gastroesofágico/tratamento farmacológico , Helicobacter pylori/patogenicidade , Humanos , Inibidores da Bomba de Prótons/farmacologia , Neoplasias Gástricas/classificação
20.
Cytokine ; 123: 154782, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31369967

RESUMO

Reflux esophagitis is a result of esophageal exposure to acid and bile during episodes of gastroesophageal reflux. Aside from chemical injury to the esophageal epithelium, it has been shown that acid and bile induce cytokine-mediated injury by stimulating the release of pro-inflammatory cytokines. During the repair and healing process following reflux injury, the squamous esophageal cells are replaced with a columnar epithelium causing Barrett's metaplasia, which predisposes patients to esophageal adenocarcinoma. We identified a novel player in gastroesophageal reflux injury, the TGFß family member Activin A (ActA), which is a known regulator of inflammation and tissue repair. In this study, we show that in response to bile salt and acidified media (pH 4) exposure, emulating the milieu to which the distal esophagus is exposed during gastroesophageal reflux, long-term treated, tolerant esophageal keratinocytes exhibit increased ActA secretion and a pro-inflammatory cytokine signature. Furthermore, we noted increased motility and expression of the stem cell markers SOX9, LGR5 and DCLK1 supporting the notion that repair mechanisms were activated in the bile salt/acid-tolerant keratinocytes. Additionally, these experiments demonstrated that de-differentiation as characterized by the induction of YAP1, FOXO3 and KRT17 was altered by ActA/TGFß signaling. Collectively, our results suggest a pivotal role for ActA in the inflammatory GERD environment by modulating esophageal tissue repair and de-differentiation.


Assuntos
Ativinas/metabolismo , Desdiferenciação Celular , Células Epiteliais/metabolismo , Esôfago/metabolismo , Refluxo Gastroesofágico/metabolismo , Modelos Biológicos , Células Epiteliais/patologia , Esôfago/patologia , Refluxo Gastroesofágico/patologia , Humanos
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