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1.
Gastrointest Endosc ; 97(2): 226-231.e2, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36228698

RESUMO

BACKGROUNDS AND AIMS: Flexible endoscopic Zenker's diverticulotomy (EZD) is well established as a safe and effective technique. Because of rare but concerning adverse events, most centers admit patients for observation and barium swallow study. Our center routinely performs EZD as a day procedure, discharging appropriate patients on the same day after clinical review. This study evaluates outcomes of this cohort compared with previously published studies where patients are admitted for observation. METHODS: A retrospective analysis was performed of EZD procedures done at our center using a flexible endoscope and, in most cases, a diverticulotomy overtube with patients under moderate sedation or general anesthesia. Patients were observed for 2 hours and discharged if no clinical concerns were found. Patient comorbidities, American Society of Anesthesiologists physical status, and endoscopic adverse events were recorded against the American Society for Gastrointestinal Endoscopy severity grading system. RESULTS: Two hundred forty EZD procedures were performed between January 2015 and February 2021. Eleven (4.6%) intraprocedural adverse events occurred: 4 perforations, 4 bleeds, and 1 each postprocedural pain, delirium, and vomiting, respectively. All were recognized within the 2-hour observation period and were managed conservatively, except 1 patient who required surgery. Six patients (2.5%) presented with delayed adverse events: 2 bleeds, 2 perforations, and 2 postprocedural pain. All patients recovered uneventfully with supportive care. CONCLUSIONS: All significant adverse events requiring endoscopic or surgical intervention were identified before discharge. Delayed adverse events occurred in 2.5% of cases, all of which were managed supportively. Our data are comparable with published cohorts of admitted patients, demonstrating that appropriately selected patients may be managed as outpatients while maintaining similar safety outcomes.


Assuntos
Esofagoscopia , Divertículo de Zenker , Humanos , Esofagoscopia/métodos , Pacientes Ambulatoriais , Divertículo de Zenker/cirurgia , Estudos Retrospectivos , Endoscópios , Dor/etiologia , Resultado do Tratamento
2.
Surg Endosc ; 36(7): 5041-5048, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-34750708

RESUMO

BACKGROUND AND AIMS: Endoscopic mucosal resection (EMR) and radiofrequency ablation (RFA) for Barrett's esophagus (BE)-related high-grade dysplasia (HGD) and early esophageal adenocarcinoma (EAC) are considered effective treatments for eradication of BE. Little is known about the impact of achieving complete eradication of intestinal metaplasia (CE-IM) following the complete eradication of neoplasia (CE-N), specifically if CE-IM reduces the risk of recurrent dysplasia. METHODS: Retrospective cohort study of consecutive patients with BE and HGD or intramucosal cancer (IMC)-treated endoscopically at a tertiary referral center between 2001 and 2019. Association between CE-IM and recurrent dysplasia after CE-N was evaluated. RESULTS: A total of 433 patients treated with EMR and/or RFA were included. Of these, 381 (88%) achieved CE-N, of which 345 (80%) had adequate follow-up for inclusion in the analysis. A total of 266 (77%) patients achieved CE-IM; with a median follow-up since initial treatment for HGD/IMC of 45.9 months (IQR 25.9, 93.1); 20 patients (5.8%) had recurrent dysplasia after achieving CE-N. Kaplan Meier survival curves revealed that time free of recurrence in those who achieved CE-IM was significantly higher (p = 0.002). In the multivariable analysis, CE-IM was associated with a significant lower hazard of recurrence (HR 0.2, 95% CI 0.1, 0.6), whereas the number of endoscopic treatments to achieve CE-N was associated with a significant higher hazard of recurrence (HR 1.1, 95% CI 1.0, 1.2). CONCLUSION: Achieving CE-IM following CE-N reduces the risk of recurrent dysplasia and should be considered a treatment target among patients with BE undergoing endoscopic therapies for HGD or EAC.


Assuntos
Esôfago de Barrett , Ablação por Cateter , Neoplasias Esofágicas , Adenocarcinoma , Esôfago de Barrett/complicações , Esôfago de Barrett/patologia , Esôfago de Barrett/cirurgia , Neoplasias Esofágicas/etiologia , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Esofagoscopia , Humanos , Metaplasia , Estudos Retrospectivos , Resultado do Tratamento
3.
Surg Endosc ; 35(10): 5468-5479, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-32989547

RESUMO

BACKGROUND AND AIMS: Multimodal endoscopic treatment for Barrett's esophagus (BE) related high-grade dysplasia (HGD) and early esophageal adenocarcinoma (EAC) is safe and effective. However, there is a paucity of data to predict the response to endoscopic treatment. This study aimed to identify predictors of failure to achieve complete eradication of neoplasia (CE-N) and complete eradication of intestinal metaplasia (CE-IM). METHODS: We performed a retrospective analysis of prospectively collected data of all HGD/EAC cases treated endoscopically at a tertiary referral center. Only patients with confirmed HGD/EAC from initial endoscopic mucosal resection (EMR) were included. Potential predictive variables including clinical characteristics, endoscopic features, and index histologic parameters of the EMR specimens were evaluated using multivariate Cox regression. RESULTS: A total of 457 patients were diagnosed with HGD/EAC by initial EMR from January 2008 to January 2019. Of these, 366 patients who underwent subsequent endoscopic treatment with or without RFA were included. Cumulative incidence rates at 3 years for CE-N and CE-IM were 91.4% (95% CI 87.8-94.2%) and 66.8% (95% CI 61.2-72.3%), respectively during a median follow-up period of 35 months. BE segment of 3-10 cm (HR 0.45; 95% CI 0.36-0.57) and > 10 cm (HR 0.25; 95% CI 0.15-0.40) were independent clinical predictors associated with failure to achieve CE-N. With respect to CE-IM, increasing age (HR 0.88; 95% CI 0.78-1.00) was another predictor along with BE segment of 3-10 cm (HR 0.37; 95% CI 0.28-0.49) and > 10 cm (HR 0.15; 95% CI 0.07-0.30). Lymphovascular invasion increased the risk of CE-N and CE-IM failure in EAC cases. CONCLUSION: Failure to achieve CE-N and CE-IM is associated with long-segment BE and other clinical variables. Patients with these predictors should be considered for a more intensive endoscopic treatment approach at expert centers.


Assuntos
Adenocarcinoma , Esôfago de Barrett , Neoplasias Esofágicas , Lesões Pré-Cancerosas , Adenocarcinoma/cirurgia , Esôfago de Barrett/cirurgia , Neoplasias Esofágicas/cirurgia , Esofagoscopia , Humanos , Lesões Pré-Cancerosas/cirurgia , Estudos Retrospectivos
4.
Gastroenterology ; 156(8): 2198-2207.e1, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30742834

RESUMO

BACKGROUND & AIMS: Topically applied methylene blue dye chromoendoscopy is effective in improving detection of colorectal neoplasia. When combined with a pH- and time-dependent multimatrix structure, a per-oral methylene blue formulation (MB-MMX) can be delivered directly to the colorectal mucosa. METHODS: We performed a phase 3 study of 1205 patients scheduled for colorectal cancer screening or surveillance colonoscopies (50-75 years old) at 20 sites in Europe and the United States, from December 2013 through October 2016. Patients were randomly assigned to groups given 200 mg MB-MMX, placebo, or 100 mg MB-MMX (ratio of 2:2:1). The 100-mg MB-MMX group was included for masking purposes. MB-MMX and placebo tablets were administered with a 4-L polyethylene glycol-based bowel preparation. The patients then underwent colonoscopy by an experienced endoscopist with centralized double-reading. The primary endpoint was the proportion of patients with 1 adenoma or carcinoma (adenoma detection rate [ADR]). We calculated odds ratios (ORs) and 95% confidence intervals (CIs) for differences in detection between the 200-mg MB-MMX and placebo groups. False-positive (resection rate for non-neoplastic polyps) and adverse events were assessed as secondary endpoints. RESULTS: The ADR was higher for the MB-MMX group (273 of 485 patients, 56.29%) than the placebo group (229 of 479 patients, 47.81%) (OR 1.46; 95% CI 1.09-1.96). The proportion of patients with nonpolypoid lesions was higher in the MB-MMX group (213 of 485 patients, 43.92%) than the placebo group (168 of 479 patients, 35.07%) (OR 1.66; 95% CI 1.21-2.26). The proportion of patients with adenomas ≤5 mm was higher in the MB-MMX group (180 of 485 patients, 37.11%) than the placebo group (148 of 479 patients, 30.90%) (OR 1.36; 95% CI 1.01-1.83), but there was no difference between groups in detection of polypoid or larger lesions. The false-positive rate did not differ significantly between groups (83 [23.31%] of 356 patients with non-neoplastic lesions in the MB-MMX vs 97 [29.75%] of 326 patients with non-neoplastic lesions in the placebo group). Overall, 0.7% of patients had severe adverse events but there was no significant difference between groups. CONCLUSIONS: In a phase 3 trial of patients undergoing screening or surveillance colonoscopies, we found MB-MMX led to an absolute 8.5% increase in ADR, compared with placebo, without increasing the removal of non-neoplastic lesions. Clinicaltrials.gov no: NCT01694966.


Assuntos
Colonoscopia/métodos , Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer/métodos , Aumento da Imagem/métodos , Azul de Metileno/administração & dosagem , Administração Oral , Idoso , Método Duplo-Cego , Europa (Continente) , Feminino , Humanos , Internacionalidade , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Estados Unidos
5.
Gastrointest Endosc ; 92(2): 259-268.e2, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32240684

RESUMO

BACKGROUND AND AIMS: Multiband mucosectomy (MBM) is a widely used technique for the treatment of Barrett's esophagus (BE). However, large multicenter studies enabling a generalizable estimation of the risk of serious adverse events, such as perforation and postprocedural bleeding, are lacking. The aim of this study was to estimate the rate of, and risk factors for, serious adverse events associated with MBM. METHODS: In this retrospective analysis, consecutive patients who underwent MBM for treatment of BE in 14 tertiary referral centers in Europe, the United States, Canada, and Australia were included. Primary outcomes were perforation and postprocedural bleeding rate. Potential risk factors were identified by logistic regression. RESULTS: Between 2001 and 2016, a total of 3827 MBM procedures were performed in 2447 patients (84% male, mean age 66 years, median BE length C2M4). Perforation occurred in 17 procedures (0.4%; 95% confidence interval [CI], 0.3-0.7), of which 15 could be treated endoscopically or conservatively. Female gender was an independent risk factor for perforation (odds ratio [OR], 2.77; 95% CI, 1.02-7.57; P = .05). Postprocedural bleeding occurred after 35 procedures (0.9%; 95% CI, 0.6-1.3). The number of resections (OR, 1.15; 95% CI, 1.06-1.25; P < .001) was significantly associated with postprocedural bleeding. CONCLUSION: The results of this study show that MBM for BE is safe with a low risk of serious adverse events. In addition, most of the adverse events could be managed endoscopically or conservatively. The number of resections was an independent risk factor for postprocedural bleeding.


Assuntos
Esôfago de Barrett , Neoplasias Esofágicas , Idoso , Austrália , Esôfago de Barrett/cirurgia , Canadá , Esofagoscopia , Europa (Continente) , Feminino , Humanos , Masculino , Estudos Retrospectivos , Fatores de Risco
6.
Gastrointest Endosc ; 88(4): 647-654, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30220300

RESUMO

BACKGROUND AND AIMS: Early neoplasia in Barrett's esophagus (BE) can be effectively and safely removed by endoscopic resection (ER) using multiband mucosectomy (MBM). This study aimed to document performance of a novel MBM device designed for improved visualization, easier passage of accessories, and better suction power compared with other marketed MBM devices. METHODS: This international, single-arm, prospective registry in 14 referral centers (Europe, 10; United States, 3; Canada, 1) included patients with early BE neoplasia scheduled for ER. The primary endpoint was successful ER defined as complete resection of the delineated area in 1 procedure. Secondary outcomes were adverse events and procedure time. RESULTS: A total of 332 lesions was included in 291 patients (248 men; mean age, 67 years [standard deviation, 9.6]). ER indication was high-grade dysplasia in 64%, early adenocarcinoma in 19%, lesion with low-grade dysplasia in 11%, and a lesion without definite histology in 6%. Successful ER was reached in 322 of 332 lesions (97%; 95% confidence interval [CI], 94.6%-98.4%). A perforation occurred in 3 of 332 procedures (.9%; 95% CI, .31%-2.62%), all were managed endoscopically, and patients were admitted with intravenous antibiotics during days 2, 3, and 9. Postprocedural bleeding requiring an intervention occurred in 5 of 332 resections (1.5%; 95% CI, .65%-3.48%). Dysphagia requiring dilatation occurred in 11 patients (3.8%; 95% CI, 2.1%-6.6%). Median procedure time was 16 minutes (interquartile range, 12.0-26.0). CONCLUSIONS: In expert hands, the novel MBM device proved to be effective for resection of early neoplastic lesions in BE, with successful ER in 97% of procedures. Severe adverse events were rare and were effectively managed endoscopically or conservatively. (Clinical trial registration number: NCT02482701.).


Assuntos
Adenocarcinoma/cirurgia , Esôfago de Barrett/cirurgia , Ressecção Endoscópica de Mucosa/efeitos adversos , Ressecção Endoscópica de Mucosa/instrumentação , Neoplasias Esofágicas/cirurgia , Hemorragia Pós-Operatória/etiologia , Adenocarcinoma/diagnóstico por imagem , Idoso , Esôfago de Barrett/diagnóstico por imagem , Esôfago de Barrett/patologia , Transtornos de Deglutição/etiologia , Neoplasias Esofágicas/diagnóstico por imagem , Perfuração Esofágica/etiologia , Perfuração Esofágica/cirurgia , Esofagoscopia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Hemorragia Pós-Operatória/cirurgia , Estudos Prospectivos , Sucção
7.
Endoscopy ; 50(1): 8-13, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29065436

RESUMO

BACKGROUND AND STUDY AIM: Both endoscopic mucosal resection (EMR) and radiofrequency ablation (RFA) are used to treat Barrett's esophagus (BE) complicated by dysplasia and intramucosal cancer. However, focal areas of BE can remain after otherwise successful application of these techniques. We report the results of hot avulsion using a hot biopsy forceps to resect these residual focal areas. PATIENTS AND METHODS: This was a retrospective study from a prospective database in a tertiary reference center from August 2013 to May 2015. All included patients had undergone hot avulsion for eradication of residual focal areas of BE that were ≤ 1 cm and not suspicious for dysplasia, following at least one previous endoscopic treatment for dysplasia or intramucosal cancer. RESULTS: 35 patients harboring 124 residual areas of 1 - 7 mm were treated with hot avulsion. After a mean follow-up of 17.4 months, all patients achieved complete eradication of residual focal BE. One of the patients required a second hot avulsion treatment. Hot avulsion provided samples in all cases but limited the assessment of dysplasia (cautery artifact) in 20.2 % of them. The only complication was bleeding in two patients, which was easily stopped by soft coagulation. CONCLUSIONS: Hot avulsion appears to be effective and safe in removing focal BE ≤ 1 cm at its greatest length remaining after endoscopic treatment for dysplasia or early cancer. Further studies are required before this technique can be considered the standard of care.


Assuntos
Esôfago de Barrett/cirurgia , Neoplasias Esofágicas/cirurgia , Terapia de Salvação/métodos , Idoso , Idoso de 80 Anos ou mais , Esôfago de Barrett/complicações , Neoplasias Esofágicas/complicações , Esofagoscopia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
8.
Dig Dis Sci ; 62(5): 1216-1222, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28265829

RESUMO

BACKGROUND AND AIMS: Preliminary single-institution data suggest that fluorescence in situ hybridization (FISH) may be useful for detecting high-grade dysplasia (HGD) and esophageal adenocarcinoma (EA) in patients with Barrett's esophagus (BE). This multicenter study aims to validate the measurement of polysomy (gain of at least two loci) by FISH as a way to discriminate degrees of dysplasia in BE specimens. METHODS: Tissue specimens were collected from four different hospitals and read by both the local pathology department ("Site diagnosis") and a single central pathologist ("Review diagnosis") at a separate institution. The specimens then underwent FISH analysis using probes 8q24 (MYC), 9p21 (CDKN2A), 17q12 (ERBB2), and 20q13 (ZNF217) for comparison. A total of 46 non-BE, 42 non-dysplastic specialized intestinal metaplasia (SIM), 23 indefinite-grade dysplasia (IGD), 10 low-grade dysplasia (LGD), 29 HGD, and 42 EA specimens were analyzed. RESULTS: We found that polysomy, as detected by FISH, was the predominant chromosomal abnormality present as dysplasia increased. Polysomy was also the best predictor for the presence of dysplasia or EA when comparing its area under the curve to that of other FISH abnormalities. We observed that if at least 10% of cells had polysomy within a specimen, the FISH probe was able to differentiate between EA/HGD and the remaining pathologies with a sensitivity of 80% and a specificity of 88%. CONCLUSIONS: This study demonstrates that using FISH to determine the percentage of cells with polysomy can accurately and objectively aid in the diagnosis of HGD/EA in BE specimens.


Assuntos
Adenocarcinoma/diagnóstico , Esôfago de Barrett/complicações , Esôfago de Barrett/patologia , Neoplasias Esofágicas/diagnóstico , Adenocarcinoma/patologia , Neoplasias Esofágicas/patologia , Humanos , Hibridização in Situ Fluorescente , Curva ROC , Sensibilidade e Especificidade
9.
Clin Gastroenterol Hepatol ; 13(4): 665-72.e1-4, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25218668

RESUMO

BACKGROUND & AIMS: Obesity is associated with neoplasia, possibly via insulin-mediated cell pathways that affect cell proliferation. Metformin has been proposed to protect against obesity-associated cancers by decreasing serum insulin. We conducted a randomized, double-blind, placebo-controlled, phase 2 study of patients with Barrett's esophagus (BE) to assess the effect of metformin on phosphorylated S6 kinase (pS6K1), a biomarker of insulin pathway activation. METHODS: Seventy-four subjects with BE (mean age, 58.7 years; 58 men [78%; 52 with BE >2 cm [70%]) were recruited through 8 participating organizations of the Cancer Prevention Network. Participants were randomly assigned to groups given metformin daily (increasing to 2000 mg/day by week 4, n = 38) or placebo (n = 36) for 12 weeks. Biopsy specimens were collected at baseline and at week 12 via esophagogastroduodenoscopy. We calculated and compared percent changes in median levels of pS6K1 between subjects given metformin vs placebo as the primary end point. RESULTS: The percent change in median level of pS6K1 did not differ significantly between groups (1.4% among subjects given metformin vs -14.7% among subjects given placebo; 1-sided P = .80). Metformin was associated with an almost significant reduction in serum levels of insulin (median -4.7% among subjects given metformin vs 23.6% increase among those given placebo, P = .08) as well as in homeostatic model assessments of insulin resistance (median -7.2% among subjects given metformin vs 38% increase among those given placebo, P = .06). Metformin had no effects on cell proliferation (on the basis of assays for KI67) or apoptosis (on the basis of levels of caspase 3). CONCLUSIONS: In a chemoprevention trial of patients with BE, daily administration of metformin for 12 weeks, compared with placebo, did not cause major reductions in esophageal levels of pS6K1. Although metformin reduced serum levels of insulin and insulin resistance, it did not discernibly alter epithelial proliferation or apoptosis in esophageal tissues. These findings do not support metformin as a chemopreventive agent for BE-associated carcinogenesis. ClinicalTrials.gov number, NCT01447927.


Assuntos
Esôfago de Barrett/complicações , Esôfago de Barrett/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Neoplasias Esofágicas/prevenção & controle , Metformina/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Esôfago de Barrett/patologia , Método Duplo-Cego , Endoscopia do Sistema Digestório , Feminino , Humanos , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Placebos/administração & dosagem , Estudos Prospectivos , Proteínas Quinases S6 Ribossômicas/análise , Adulto Jovem
10.
Ann Surg ; 259(1): 102-8, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23478525

RESUMO

OBJECTIVE: Defining processes of care, which are appropriate and necessary for management of gastric cancer (GC), is an important step toward improving outcomes. METHODS: Using a RAND/UCLA Appropriateness Method, an international multidisciplinary expert panel created 22 statements reflecting optimal management. All statements were scored for appropriateness and necessity. RESULTS: The following tenets were scored appropriate and necessary: (1) preoperative staging by computed tomography of abdomen/pelvis; (2) positron-emission tomographic scans not routinely indicated; (3) consideration for adjuvant therapy; (4) further clinical trials; (5) multidisciplinary decision making; (6) sufficient support at hospitals; (7) assessment of 16 or more lymph nodes (LNs); (8) in metastatic disease, surgery only for palliation of major symptoms; (9) surgeons experienced in GC management; (10) and surgeons experienced in both GC management and advanced laparoscopic surgery for laparoscopic resection. The following were scored appropriate, but of indeterminate necessity: (1) diagnostic laparoscopy before treatment; (2) a multidisciplinary approach to linitis plastica; (3) genetic assessment for diffuse GC and family history, or age less than 45 years; (4) endoscopic removal of select T1aN0 lesions; (5) D2 LN dissection in curative intent cases; (6) D1 LN dissection for early GC or patients with comorbidities; (7) frozen section analysis of margins; (8) nonemergent cases performed in a hospital with a volume of more than 15 resections per year; and (9) by a surgeon with more than 6 resection per year. CONCLUSIONS: The expert panel has created 22 statements for the perioperative management of GC patients, to provide guidance to clinicians and improve the care received by patients.


Assuntos
Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/terapia , Humanos , Internacionalidade , Metástase Linfática , Tomografia por Emissão de Pósitrons , Guias de Prática Clínica como Assunto , Neoplasias Gástricas/cirurgia , Tomografia Computadorizada por Raios X
12.
Am J Clin Nutr ; 119(3): 809-820, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38157986

RESUMO

BACKGROUND: Folic acid supplementation during the periconceptional period reduces the risk of neural tube defects in infants, but concern over chronic folic acid exposure remains. An improved understanding of folate absorption may clarify potential risks. Folate transporters have been characterized in the small intestine, but less so in the colon of healthy, free-living humans. The impact of folic acid fortification or supplementation on regulation of these transporters along the intestinal tract is unknown. OBJECTIVE: The objective was to characterize expression of folate transporters/receptor (FT/R) and folate hydrolase, glutamate carboxypeptidase II (GCPII), from the terminal ileum and throughout the colon of adults and assess the impact of supplemental folic acid. METHODS: In this 16-wk open-labeled randomized clinical trial, adults consumed a low folic acid-containing diet, a folate-free multivitamin, and either a 400 µg folic acid supplement or no folic acid supplement. Dietary intakes and blood were assessed at baseline, 8 wk, and 16 wk (time of colonoscopy). Messenger RNA (mRNA) expression and protein expression of FT/R and GCPII were assessed in the terminal ileum, cecum, and ascending and descending colon. RESULTS: Among 24 randomly assigned subjects, no differences in dietary folate intake or blood folate were observed at baseline. Mean ± SD red blood cell folate at 16 wk was 1765 ± 426 and 911 ± 242 nmol/L in the 400 and 0 µg folic acid group, respectively (P < 0.0001). Reduced folate carrier, proton-coupled folate transporter, and folate-receptor alpha expression were detected in the terminal ileum and colon, as were efflux transporters of breast cancer resistance protein and multidrug resistance protein-3. Other than a higher mRNA expression of FR-alpha and GCPII in the 400 µg supplement group in the ascending colon, no treatment differences were observed (P < 0.02). CONCLUSIONS: Folate transporters are present throughout the terminal ileum and colon; there is little evidence that a low dose of folic acid supplementation affects colonic absorption. This trial was registered at clinicaltrials.gov as NCT03421483.


Assuntos
Ácido Fólico , Proteínas de Neoplasias , Adulto , Humanos , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Suplementos Nutricionais , Transportadores de Ácido Fólico , Íleo , RNA Mensageiro , Colo
13.
Gastroenterology ; 143(4): 917-26.e1, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22796132

RESUMO

UNLABELLED: BACKGROUND& AIMS: Proton pump inhibitors and nonsteroidal anti-inflammatory drugs might prevent esophageal adenocarcinoma in patients with Barrett's esophagus (BE), but there are limited data from clinical trials to support this concept. We conducted a randomized, double-blind, placebo-controlled, phase 2 trial to assess the effects of the combination of aspirin (3 different doses) and esomeprazole on tissue concentrations of prostaglandin (PG) E(2) in patients with BE with no dysplasia or low-grade dysplasia. METHODS: Participants were recruited through the multicenter Cancer Prevention Network and randomly assigned to groups that were given 40 mg esomeprazole twice daily in combination with an aspirin placebo once daily (arm A; n = 30), with 81 mg aspirin once daily (arm B; n = 47), or with 325 mg aspirin once daily (arm C; n = 45) for 28 days. We collected esophageal biopsy specimens before and after the intervention period to determine the absolute change in mean concentration of PGE(2) (the primary end point). RESULTS: Based on data from 114 patients, baseline characteristics were similar among groups. The absolute mean tissue concentration of PGE(2) was reduced by 67.6 ± 229.68 pg/mL in arm A, 123.9 ± 284.0 pg/mL in arm B (P = .10 vs arm A), and 174.9 ± 263.62 pg/mL in arm C (P = .02 vs arm A). CONCLUSIONS: In combination with esomeprazole, short-term administration of higher doses of aspirin, but not lower doses or no aspirin, significantly reduced tissue concentrations of PGE(2) in patients with BE with either no dysplasia or low-grade dysplasia. These data support further evaluation of higher doses of aspirin and esomeprazole to prevent esophageal adenocarcinoma in these patients. Clinical trial registration number NCT00474903.


Assuntos
Aspirina/administração & dosagem , Esôfago de Barrett/tratamento farmacológico , Esôfago de Barrett/metabolismo , Inibidores de Ciclo-Oxigenase/administração & dosagem , Dinoprostona/metabolismo , Esomeprazol/uso terapêutico , Inibidores da Bomba de Prótons/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Aspirina/uso terapêutico , Esôfago de Barrett/patologia , Biomarcadores/metabolismo , Biópsia , Inibidores de Ciclo-Oxigenase/uso terapêutico , Método Duplo-Cego , Regulação para Baixo , Quimioterapia Combinada , Esofagoscopia , Esôfago/metabolismo , Esôfago/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
15.
Ann Surg Oncol ; 20(2): 533-41, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22941158

RESUMO

BACKGROUND: Hereditary diffuse gastric cancer (HDGC) represents a minority of gastric cancer (GC) cases. The goal of this study is to use a RAND/University of California Los Angeles (UCLA) appropriateness methodology to examine indications for genetic referral, CDH1 testing, and consideration of prophylactic total gastrectomy (PTG). METHODS: A multidisciplinary expert panel of 16 physicians from six countries scored 47 scenarios. Appropriateness of scenarios was scored from 1 (highly inappropriate) to 9 (highly appropriate). Median appropriateness scores (AS) of 1-3 were considered inappropriate, 4-6 uncertain, and 7-9 appropriate. Agreement was reached when 12 of 16 panelists scored the statement similarly. Appropriate scenarios agreed upon were subsequently scored for necessity. RESULTS: The panel felt that patients with family history of diffuse gastric cancer (DGC), lobular breast cancer, or multiple family members with GC should be referred for genetic assessment and multidisciplinary decision-making. The panel felt that it is appropriate for patients with DGC to have CDH1 mutation testing in a family with (1) ≥2 cases of GC, with at least one case of DGC diagnosed before age of 50 years; (2) ≥3 cases of GC diagnosed at any age, one or more of which is DGC; (3) a patient diagnosed with DGC and lobular breast carcinoma; or (4) patients diagnosed with DGC under age of 35 years. The panel felt that PTG should be offered to CDH1 mutation carriers 20 years or older. CONCLUSIONS: Identification of genetic mutations in patients at risk for hereditary GC is important, and criteria for testing are suggested.


Assuntos
Neoplasias da Mama/genética , Caderinas/genética , Carcinoma Lobular/genética , Predisposição Genética para Doença , Testes Genéticos , Mutação/genética , Neoplasias Gástricas/genética , Adulto , Antígenos CD , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Carcinoma Lobular/patologia , Carcinoma Lobular/cirurgia , Gerenciamento Clínico , Família , Feminino , Gastrectomia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia
17.
J Can Assoc Gastroenterol ; 6(4): 137-144, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37538188

RESUMO

Background: Barrett's esophagus (BE) is a premalignant condition to esophageal adenocarcinoma (EAC). Low socioeconomic (SES) status adversely impacts care and outcomes in patients with EAC, but this has not been evaluated in BE. As the treatment of BE is similarly intensive, we aimed to evaluate the effect of SES on achieving complete eradication of intestinal metaplasia (CE-IM), dysplasia (CE-D) and development of invasive EAC. Methods: Our study was a retrospective cohort study. Consecutive patients between January 1, 2010, to December 31, 2018, referred for BE-associated high-grade dysplasia or intramucosal adenocarcinoma were included. Pre, intra and post-procedural data were collected. Household income data was collected from the 2016 census based on postal code region. Patients were divided into income groups relative to the 2016 median household income in Ontario. Multivariate regression was performed for outcomes of interest. Results: Four hundred and fifty-nine patients were included. Rate of CE-IM was similar between income groups. Fifty-five per cent (n = 144/264) versus 65% (n = 48/264) in the below and above-income groups achieved CE-D, respectively, P = 0.02. Eighteen per cent (n = 48/264) versus 11% (n = 22/195) were found to have invasive EAC during their treatment course in below and above-income groups, respectively, P = 0.04. Residing in a below-median-income district was associated with developing invasive EAC (Odds Ratio, [OR] 1.84, 95% confidence interval [CI] 1.01 to 3.35) and failure to achieve CE-D (OR 0.64, 95% CI 0.42 to 0.97). Conclusions: Residing in low-income districts is associated with worse outcomes in patients with advanced BE. Further research is needed to guide future initiatives to address the potential impact of SES barriers in the optimal care of BE.

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