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1.
Am J Gastroenterol ; 119(3): 438-449, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38857483

RESUMO

Gastrointestinal (GI) bleeding is the most common GI diagnosis leading to hospitalization within the United States. Prompt diagnosis and treatment of GI bleeding is critical to improving patient outcomes and reducing high healthcare utilization and costs. Radiologic techniques including computed tomography angiography, catheter angiography, computed tomography enterography, magnetic resonance enterography, nuclear medicine red blood cell scan, and technetium-99m pertechnetate scintigraphy (Meckel scan) are frequently used to evaluate patients with GI bleeding and are complementary to GI endoscopy. However, multiple management guidelines exist which differ in the recommended utilization of these radiologic examinations. This variability can lead to confusion as to how these tests should be used in the evaluation of GI bleeding. In this document, a panel of experts from the American College of Gastroenterology and Society of Abdominal Radiology provide a review of the radiologic examinations used to evaluate for GI bleeding including nomenclature, technique, performance, advantages, and limitations. A comparison of advantages and limitations relative to endoscopic examinations is also included. Finally, consensus statements and recommendations on technical parameters and utilization of radiologic techniques for GI bleeding are provided.


Assuntos
Hemorragia Gastrointestinal , Humanos , Hemorragia Gastrointestinal/diagnóstico por imagem , Hemorragia Gastrointestinal/diagnóstico , Consenso , Estados Unidos , Gastroenterologia/normas , Sociedades Médicas , Diagnóstico por Imagem/métodos , Diagnóstico por Imagem/normas , Endoscopia Gastrointestinal
2.
J Clin Gastroenterol ; 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38630852

RESUMO

GOALS: We aimed to evaluate whether direct access colonoscopy (DAC) is noninferior to office-scheduled colonoscopy (OSC) for achieving successful colonoscopy. BACKGROUND: DAC may improve access to colonoscopy. We developed an algorithm assessing eligibility, risk for inadequate preparation, and need for nursing/navigator assistance. STUDY: This was a retrospective, single-center study of DAC and OSC patients from June 5, 2018, to July 31, 2019. Patients were 45 to 75 years old with an indication of screening or surveillance. A successful colonoscopy met 3 criteria: complete colonoscopy (cecum, anastomosis, or ileum), adequate preparation (Boston Score ≥2/segment), and performed <90 days from initial patient contact. Unsuccessful colonoscopy did not meet ≥1 criteria. Secondary end points included days to successful colonoscopy, preparation quality, polyp detection, and 10-year recall rate. Noninferiority against risk ratio value of 0.85 was tested using 1-sided alpha of 0.05. RESULTS: A total of 1823 DAC and 828 OSC patients were eligible. DAC patients were younger, with a greater proportion of black patients and screening indications. For the outcome of successful colonoscopy, DAC was noninferior to OSC (DAC vs. OSC: 62.7% vs. 57.1%, RR 1.16, 95% LCL 1.09, P=0.001). For DAC, days to colonoscopy were fewer, and likelihood of 10-year recall after negative screening greater. Boston Score and polyp detection were similar for groups. Black patients were less likely to achieve successful colonoscopy; otherwise, groups were similar. For unsuccessful colonoscopies, proportionally more DAC patients canceled or no-showed while more OSC patients scheduled >90 days. DAC remained noninferior to OSC at 180 days. CONCLUSIONS: DAC was noninferior to OSC for achieving successful colonoscopy, comparing similarly in quality and efficiency outcomes.

3.
Radiology ; 310(3): e232298, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38441091

RESUMO

Gastrointestinal (GI) bleeding is the most common GI diagnosis leading to hospitalization within the United States. Prompt diagnosis and treatment of GI bleeding is critical to improving patient outcomes and reducing high health care utilization and costs. Radiologic techniques including CT angiography, catheter angiography, CT enterography, MR enterography, nuclear medicine red blood cell scan, and technetium-99m pertechnetate scintigraphy (Meckel scan) are frequently used to evaluate patients with GI bleeding and are complementary to GI endoscopy. However, multiple management guidelines exist, which differ in the recommended utilization of these radiologic examinations. This variability can lead to confusion as to how these tests should be used in the evaluation of GI bleeding. In this document, a panel of experts from the American College of Gastroenterology and Society of Abdominal Radiology provide a review of the radiologic examinations used to evaluate for GI bleeding including nomenclature, technique, performance, advantages, and limitations. A comparison of advantages and limitations relative to endoscopic examinations is also included. Finally, consensus statements and recommendations on technical parameters and utilization of radiologic techniques for GI bleeding are provided. © Radiological Society of North America and the American College of Gastroenterology, 2024. Supplemental material is available for this article. This article is being published concurrently in American Journal of Gastroenterology and Radiology. The articles are identical except for minor stylistic and spelling differences in keeping with each journal's style. Citations from either journal can be used when citing this article. See also the editorial by Lockhart in this issue.


Assuntos
Hemorragia Gastrointestinal , Radiologia , Humanos , Hemorragia Gastrointestinal/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Angiografia , Catéteres
4.
J Clin Gastroenterol ; 2023 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-38059772

RESUMO

GOALS: This study aims to address gaps in medical knowledge by determining whether adenoma detection rate (ADR) in average-risk screening patients aged 45 to 49 is equivalent to screening patients aged 50 to 54. BACKGROUND: Current guidelines recommend initiating colon cancer screening at age 45, yet our understanding of the effects of ADR in average-risk individuals among 45- to 49-year-olds is still limited. STUDY: A retrospective analysis was conducted on records of average-risk screening colonoscopies performed on patients aged 45 to 54 from January 2018 to August 2022. Exclusions were prior diagnoses of colorectal cancer or adenomatous polyps, inflammatory bowel disease, personal or family history of genetic cancer syndromes, incomplete colonoscopy, and inadequate bowel preparation. The primary outcome was ADR in the age 45 to 49 group compared with the age 50 to 54 group. RESULTS: Of the 3199 average-risk screening colonoscopies performed, 879 and 2116 patients were included in the age 45 to 49 and 50 to 54 groups, respectively. Both groups were predominantly female, White ethnicity, never smokers, and obese. ADR was found to be 27% in the age 45 to 49 group compared with 34% in the age 50 to 54 group (odds ratio 0.70, 90% CI: 0.60-0.83, P-value for equivalence=0.81 w/ margin 0.77 to 1.30). CONCLUSIONS: The study did not demonstrate equivalent ADR between the 2 age groups, with ADR being substantially lower in the age 45 to 49 group (27% vs. 34%). Despite this, the ADR in the 45 to 49 age range surpasses the established benchmark of 25%, supporting the decision to lower the screening age to 45 years. Ongoing national monitoring is essential to comprehensively evaluate the impact of these updated guidelines.

5.
Radiographics ; 43(6): e220192, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37167088

RESUMO

Gastrointestinal (GI) bleeding is a potentially life-threatening condition accounting for more than 300 000 annual hospitalizations. Multidetector abdominopelvic CT angiography is commonly used in the evaluation of patients with GI bleeding. Given that many patients with severe overt GI bleeding are unlikely to tolerate bowel preparation, and inpatient colonoscopy is frequently limited by suboptimal preparation obscuring mucosal visibility, CT angiography is recommended as a first-line diagnostic test in patients with severe hematochezia to localize a source of bleeding. Assessment of these patients with conventional single-energy CT systems typically requires the performance of a noncontrast series followed by imaging during multiple postcontrast phases. Dual-energy CT (DECT) offers several potential advantages for performing these examinations. DECT may eliminate the need for a noncontrast acquisition by allowing the creation of virtual noncontrast (VNC) images from contrast-enhanced data, affording significant radiation dose reduction while maintaining diagnostic accuracy. VNC images can help radiologists to differentiate active bleeding, hyperattenuating enteric contents, hematomas, and enhancing masses. Additional postprocessing techniques such as low-kiloelectron voltage virtual monoenergetic images, iodine maps, and iodine overlay images can increase the conspicuity of contrast material extravasation and improve the visibility of subtle causes of GI bleeding, thereby increasing diagnostic confidence and assisting with problem solving. GI bleeding can also be diagnosed with routine single-phase DECT scans by constructing VNC images and iodine maps. Radiologists should also be aware of the potential pitfalls and limitations of DECT. ©RSNA, 2023 Quiz questions for this article are available through the Online Learning Center.


Assuntos
Hemorragia Gastrointestinal , Imagem Radiográfica a Partir de Emissão de Duplo Fóton , Tomografia Computadorizada por Raios X , Humanos , Hemorragia Gastrointestinal/diagnóstico por imagem , Intestino Delgado , Iodo , Imagem Radiográfica a Partir de Emissão de Duplo Fóton/métodos , Tomografia Computadorizada por Raios X/métodos
6.
Clin Cancer Res ; 29(9): 1678-1688, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-36892581

RESUMO

PURPOSE: To assess whether MUC1 peptide vaccine produces an immune response and prevents subsequent colon adenoma formation. PATIENTS AND METHODS: Multicenter, double-blind, placebo-controlled randomized trial in individuals age 40 to 70 with diagnosis of an advanced adenoma ≤1 year from randomization. Vaccine was administered at 0, 2, and 10 weeks with a booster injection at week 53. Adenoma recurrence was assessed ≥1 year from randomization. The primary endpoint was vaccine immunogenicity at 12 weeks defined by anti-MUC1 ratio ≥2.0. RESULTS: Fifty-three participants received the MUC1 vaccine and 50 placebo. Thirteen of 52 (25%) MUC1 vaccine recipients had a ≥2-fold increase in MUC1 IgG (range, 2.9-17.3) at week 12 versus 0/50 placebo recipients (one-sided Fisher exact P < 0.0001). Of 13 responders at week 12, 11 (84.6%) responded to a booster injection at week 52 with a ≥2-fold increase in MUC1 IgG measured at week 55. Recurrent adenoma was observed in 31 of 47 (66.0%) in the placebo group versus 27 of 48 (56.3%) in the MUC1 group [adjusted relative risk (aRR), 0.83; 95% confidence interval (CI), 0.60-1.14; P = 0.25]. Adenoma recurrence occurred in 3/11 (27.3%) immune responders at week 12 and week 55 (aRR, 0.41; 95% CI, 0.15-1.11; P = 0.08 compared with placebo). There was no difference in serious adverse events. CONCLUSIONS: An immune response was observed only in vaccine recipients. Adenoma recurrence was not different than placebo, but a 38% absolute reduction in adenoma recurrence compared with placebo was observed in participants who had an immune response at week 12 and with the booster injection.


Assuntos
Adenoma , Neoplasias do Colo , Neoplasias Colorretais , Adulto , Idoso , Humanos , Pessoa de Meia-Idade , Adenoma/prevenção & controle , Neoplasias Colorretais/prevenção & controle , Imunoglobulina G , Vacinas de Subunidades Antigênicas
7.
Cancer Biol Ther ; 22(10-12): 544-553, 2021 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-34632925

RESUMO

Guanylyl cyclase C (GUCY2C) is a tumor-suppressing receptor silenced by loss of expression of the luminocrine hormones guanylin and uroguanylin early in colorectal carcinogenesis. This observation suggests oral replacement with a GUCY2C agonist may be an effective targeted chemoprevention agent. Previous studies revealed that linaclotide, an oral GUCY2C agonist formulated for gastric release, did not persist to activate guanylyl cyclase signaling in the distal rectum. Dolcanatide is an investigational oral uroguanylin analog, substituted with select D amino acids, for enhanced stability and extended persistence to activate GUCY2C in small and large intestine. However, the ability of oral dolcanatide to induce a pharmacodynamic (PD) response by activating GUCY2C in epithelial cells of the colorectum in humans remains undefined. Here, we demonstrate that administration of oral dolcanatide 27 mg daily for 7 d to healthy volunteers did not activate GUCY2C, quantified as accumulation of its product cyclic GMP, in epithelial cells of the distal rectum. These data reveal that the enhanced stability of dolcanatide, with persistence along the rostral-caudal axis of the small and large intestine, is inadequate to regulate GUCY2C across the colorectum to prevent tumorigenesis. These results highlight the importance of developing a GUCY2C agonist for cancer prevention formulated for release and activity targeted to the colorectum.


Assuntos
Neoplasias Colorretais , GMP Cíclico , Método Duplo-Cego , Voluntários Saudáveis , Humanos , Peptídeos , Receptores de Enterotoxina , Receptores Acoplados a Guanilato Ciclase
8.
Gut ; 70(11): 2115-2122, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-33443017

RESUMO

OBJECTIVE: Colon capsule endoscopy (CCE) has shown promise for colorectal neoplasia detection compared with optical colonoscopy (OC), but has not been compared with other screening tests in average risk screening patients. DESIGN: Patients 50 to 75 years of age (African Americans, 45-75 years) were randomised to CCE or CT colonography (CTC) and subsequent blinded OC. The primary endpoint was diagnostic yield of polyps ≥6 mm with CCE or CTC. Secondary endpoints included accuracy for size and histology, examination completeness, number/proportion of subjects with polyps and adenomas ≥6 mm and ≥10 mm, subject satisfaction and safety. RESULTS: From 320 enrolled subjects, data from 286 (89.4%) were evaluable. The proportion of subjects with any polyp ≥6 mm confirmed by OC was 31.6% for CCE versus 8.6% for CTC (pPr non-inferiority and superiority=0.999). The diagnostic yield of polyps ≥10 mm was 13.5% with CCE versus 6.3% with CTC (pPr non-inferiority=0.9954). The sensitivity and specificity of CCE for polyps ≥6 mm was 79.2% and 96.3% while that of CTC was 26.8% and 98.9%. The sensitivity and specificity of CCE for polyps ≥10 mm was 85.7% and 98.2% compared with 50% and 99.1% for CTC. Both tests were well tolerated/safe. CONCLUSION: CCE was superior to CTC for detection of polyps ≥6 mm and non-inferior for identification of polyps ≥10 mm. CCE should be considered comparable or superior to CTC as a colorectal neoplasia screening test, although neither test is as effective as OC. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov no: NCT02754661.


Assuntos
Endoscopia por Cápsula , Colonografia Tomográfica Computadorizada , Neoplasias Colorretais/diagnóstico , Idoso , Pólipos do Colo/diagnóstico , Feminino , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Estudos Prospectivos
9.
Anesthesiol Res Pract ; 2020: 7246570, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32636880

RESUMO

BACKGROUND: Although anesthesia providers may plan for moderate sedation, the depth of sedation is rarely quantified. Using processed electroencephalography (EEG) to assess the depth of sedation, this study investigates the incidence of general anesthesia with variable burst suppression in patients receiving propofol for outpatient colonoscopy. The lessons learned from neuromonitoring can then be used to guide institutional best sedation practice. METHODS: This was a prospective observational study of 119 outpatients undergoing colonoscopy at Thomas Jefferson University Hospital (TJUH). Propofol was administered by CRNAs under anesthesiologists' supervision. The Patient State Index (PSi™) generated by the Masimo SedLine® Brain Root Function monitor (Masimo Corp., Irvine, CA) was used to assess the depth of sedation. PSi data correlating to general anesthesia with variable burst suppression were confirmed by neuroelectrophysiologists' interpretation of unprocessed EEG. RESULTS: PSi values of <50 consistent with general anesthesia were attained in 118/119 (99.1%) patients. Of these patients, 33 (27.7%) attained PSi values <25 consistent with variable burst suppression. The 118 patients that reached PSi <50 spent a significantly greater percentage (53.1% vs. 42%) of their case at PSi levels <50 compared to PSi levels >50 (p=0.001). Mean total propofol dose was significantly correlated to patient PSi during periods of PSi <25 (R=0.406, p=0.021). CONCLUSION: Although providers planned for moderate to deep sedation, processed EEG showed patients were under general anesthesia, often with burst suppression. Anesthesiologists and endoscopists may utilize processed EEG to recognize their institutional practice patterns of procedural sedation with propofol and improve upon it.

10.
United European Gastroenterol J ; 7(2): 225-229, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-31080607

RESUMO

Background: The significance of a family history of esophageal adenocarcinoma in the progression to esophageal adenocarcinoma in patients with Barrett's esophagus has not been thoroughly evaluated. The purpose of this study is to evaluate the presence of esophageal adenocarcinoma in a first-degree relative in patients with Barrett's esophagus. Methods: A retrospective cohort study was conducted of patients with Barrett's esophagus at a tertiary care center undergoing radiofrequency ablation. Family history, demographics, and pathology and endoscopy reports were assessed in all patients. Findings: Three hundred and one patients with Barrett's esophagus were assessed. Nineteen patients who had a diagnosis of esophageal adenocarcinoma on index endoscopy were excluded. Nineteen (6.7%) patients had a first-degree relative with esophageal adenocarcinoma. Four (21.1%) of these patients progressed to esophageal adenocarcinoma. Of patients without first-degree relative with esophageal adenocarcinoma 22/263 (8.7%) progressed to esophageal adenocarcinoma. In a logistic regression model adjusted for sex and the number of radiofrequency ablation treatments, we found that family history of esophageal adenocarcinoma was a significant independent predictor of progression to esophageal adenocarcinoma (odds ratio = 5.55, 95% confidence interval: 1.47-20.0). Conclusion: Our study indicates that Barrett's esophagus patients with a first-degree family member with esophageal adenocarcinoma are at 5.5-fold higher risk for disease progression to esophageal adenocarcinoma. Family history of esophageal adenocarcinoma in Barrett's esophagus patients should be considered in patient surveillance and radiofrequency ablation treatment, beyond recommended guidelines.


Assuntos
Adenocarcinoma/etiologia , Esôfago de Barrett/complicações , Suscetibilidade a Doenças , Neoplasias Esofágicas/etiologia , Núcleo Familiar , Adenocarcinoma/diagnóstico , Adenocarcinoma/epidemiologia , Adenocarcinoma/terapia , Adulto , Esôfago de Barrett/diagnóstico , Esôfago de Barrett/epidemiologia , Esôfago de Barrett/terapia , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/terapia , Esofagoscopia , Esofagostomia , Feminino , Seguimentos , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Ablação por Radiofrequência , Estudos Retrospectivos , Medição de Risco , Fatores de Risco
11.
J Gastrointest Oncol ; 9(4): 769-777, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30151274

RESUMO

Colorectal cancer (CRC) is the third most common newly diagnosed cancer in both men and women in the Unites States. Colonoscopy has become increasingly popular in CRC screening and represents the gold standard for detecting and removing pre-cancerous lesions. Although colonoscopy is considered a relatively safe procedure, it is invasive and bowel preparation can be challenging for patients. As interest in the gut microbiome has expanded, there have been new links established between bacteria and the development of CRC. These developing associations could prove to be a useful adjunct to colonoscopy for CRC screening in the future. This review examines current research evaluating multiple proposed pathogenic microorganisms including sulfidogenic bacteria such as Bilophila wadsworthia, as well as Streptococcus bovis, Helicobacter pylori, Bacteroides fragilis, and Clostridium septicum. This discussion primarily focuses on bacterial pathogenesis, evidence of association with CRC, and the proposed mechanisms of carcinogenesis.

12.
World J Gastroenterol ; 24(26): 2833-2843, 2018 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-30018478

RESUMO

Colorectal cancer (CRC) is the third most common cancer and second leading cause of cancer-related death in the United States. Colonoscopy is widely preferred for CRC screening and is the most commonly used method in the United States. Adequate bowel preparation is essential for successful colonoscopy CRC screening. However, up to one-quarter of colonoscopies are associated with inadequate bowel preparation, which may result in reduced polyp and adenoma detection rates, unsuccessful screens, and an increased likelihood of repeat procedure. In addition, standardized criteria and assessment scales for bowel preparation quality are lacking. While several bowel preparation quality scales are referred to in the literature, these differ greatly in grading methodology and categorization criteria. Published reliability and validity data are available for five bowel preparation quality assessment scales, which vary in several key attributes. However, clinicians and researchers continue to use a variety of bowel preparation quality measures, including nonvalidated scales, leading to potential confusion and difficulty when comparing quality results among clinicians and across clinical trials. Optimal clinical criteria for bowel preparation quality remain controversial. The use of validated bowel preparation quality scales with stringent but simple scoring criteria would help clarify clinical trial data as well as the performance of colonoscopy in clinical practice related to quality measurements.


Assuntos
Catárticos/administração & dosagem , Colonoscopia/métodos , Neoplasias Colorretais/diagnóstico por imagem , Detecção Precoce de Câncer/métodos , Garantia da Qualidade dos Cuidados de Saúde/normas , Colonoscopia/normas , Detecção Precoce de Câncer/normas , Reações Falso-Negativas , Humanos , Guias de Prática Clínica como Assunto , Garantia da Qualidade dos Cuidados de Saúde/métodos
13.
Clin Gastroenterol Hepatol ; 16(3): 357-369.e10, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28826680

RESUMO

BACKGROUND & AIMS: Some features of patients are associated with inadequate bowel preparation, which reduces the effectiveness of colonoscopy examination. We performed a systematic review and meta-analysis of the association between patients' sociodemographic characteristics, health conditions, and medications with inadequate bowel preparation. METHODS: We searched the PubMed, Scopus, and Cochrane Review databases for randomized controlled trials cohort (prospective and retrospective), case-control, and cross-sectional studies published through March 2016. We collected information on study design, study population, and bowel preparation. For each factor, we obtained the odds ratio (OR) for inadequate bowel preparation. We conducted the meta-analyses using the random-effects approach and investigated any identified heterogeneity and publication bias via graphical methods, stratification, and meta-regression. RESULTS: We performed a meta-analysis of 67 studies, comprising 75,818 patients. The estimated pooled OR for inadequate bowel preparation was small for sociodemographic characteristics: 1.14 for age, and 1.23 for male sex (excluding studies in Asia, which had substantial heterogeneity and publication bias), and 1.49 for low education. The effect of high body mass index differed significantly in studies with mostly female patients (OR, 1.05) vs those with mostly male patients (OR, 1.30) (P = .013 for the difference). ORs for constipation and cirrhosis were heterogeneous; adjusted ORs were larger than unadjusted ORs (1.97 vs 1.29 for constipation and 3.41 vs 1.36 for cirrhosis). Diabetes (OR, 1.79), hypertension (OR, 1.25), stroke or dementia (OR, 2.09), and opioid use (OR, 1.70) were associated with inadequate bowel preparation. History of abdominal surgery (OR, 0.99) did not associate with inadequate bowel preparation. Use of tricyclic antidepressants had a larger effect on risk of inadequate bowel preparation in studies of mostly female patients (OR, 2.62) than studies of mostly male patients (OR, 1.42) (P = .085 for the difference). CONCLUSIONS: In a systematic review and meta-analysis, we found no single patient-related factor to be solely associated with inadequate bowel preparation. Health conditions and use of some medications appear to be stronger predictors than sociodemographic characteristics.


Assuntos
Colonoscopia/métodos , Cuidados Pré-Operatórios/métodos , Qualidade da Assistência à Saúde , Adulto , Idoso , Ásia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
14.
Cancer Prev Res (Phila) ; 10(6): 345-354, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28396341

RESUMO

Guanylate cyclase C (GUCY2C) is a tumor-suppressing receptor silenced by loss of expression of its luminocrine hormones guanylin and uroguanylin early in colorectal carcinogenesis. This observation suggests oral replacement with a GUCY2C agonist may be an effective targeted chemoprevention agent. Linaclotide is an FDA-approved oral GUCY2C agonist formulated for gastric release, inducing fluid secretion into the small bowel to treat chronic idiopathic constipation. The ability of oral linaclotide to induce a pharmacodynamic response in epithelial cells of the colorectum in humans remains undefined. Here, we demonstrate that administration of 0.87 mg of oral linaclotide daily for 7 days to healthy volunteers, after oral colon preparation with polyethylene glycol solution (MoviPrep), activates GUCY2C, resulting in accumulation of its product cyclic (c)GMP in epithelial cells of the cecum, transverse colon, and distal rectum. GUCY2C activation by oral linaclotide was associated with homeostatic signaling, including phosphorylation of vasodilator-stimulated phosphoprotein and inhibition of proliferation quantified by reduced Ki67-positive epithelial cells. In the absence of the complete oral colonoscopy preparation, linaclotide did not alter cGMP production in epithelial cells of the colorectum, demonstrating that there was an effect related to the laxative preparation. These data show that the current FDA-approved formulation of oral linaclotide developed for small-bowel delivery to treat chronic idiopathic constipation is inadequate for reliably regulating GUCY2C in the colorectum to prevent tumorigenesis. The study results highlight the importance of developing a novel GUCY2C agonist formulated for release and activity targeted to the large intestine for colorectal cancer prevention. Cancer Prev Res; 10(6); 345-54. ©2017 AACR.


Assuntos
Colo/efeitos dos fármacos , Neoplasias Colorretais/prevenção & controle , Agonistas da Guanilil Ciclase C/farmacologia , Peptídeos/farmacologia , Receptores de Enterotoxina/metabolismo , Reto/efeitos dos fármacos , Administração Oral , Animais , Moléculas de Adesão Celular/metabolismo , Colo/diagnóstico por imagem , Colonoscopia , GMP Cíclico/metabolismo , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Hormônios Gastrointestinais/metabolismo , Agonistas da Guanilil Ciclase C/uso terapêutico , Voluntários Saudáveis , Humanos , Antígeno Ki-67/metabolismo , Proteínas dos Microfilamentos/metabolismo , Peptídeos Natriuréticos/metabolismo , Peptídeos/uso terapêutico , Fosfoproteínas/metabolismo , Fosforilação , Polietilenoglicóis/farmacologia , Reto/diagnóstico por imagem
15.
Endosc Int Open ; 5(4): E253-E260, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28382323

RESUMO

Background and study aims Dietary restrictions are integral to colonoscopy preparation and impact patient satisfaction. Utilizing split-dose, lower-volume polyethylene glycol 3350-electrolyte solution (PEG-ELS), this study compared colon preparation adequacy of a low-residue diet to clear liquids using a validated grading scale. Patients and methods This was a prospective, randomized, single-blinded, single-center non-inferiority study evaluating diet the day prior to outpatient colonoscopy. Subjects were randomized to a Low-Residue diet for breakfast and lunch, or Clears only. All subjects received split dose PEG-ELS. The primary endpoint was preparation adequacy using the Boston Bowel Preparation Scale (BBPS), with adequate defined as a score > 5. Secondary endpoints included mean BBPS scores for the entire colon and individual segments, satisfaction, adverse events, polyp and adenoma detection rates, and impact on sleep and daily activities. Results Final analysis included 140 subjects, 72 assigned to Clears and 68 to Low-Residue. The Low-Residue diet was non-inferior to Clears (risk difference = - 5.08 %, P = 0.04) after adjusting for age. Mean colon cleansing scores were not significantly different overall and for individual colonic segments. Satisfaction with the Low-Residue diet was significantly greater (P = 0.01). The adenoma detection rate was not statistically significantly different between study groups, but the number of adenomas detected was significantly greater with Clears (P = 0.01). Adverse events and impact on sleep and activities did not differ significantly between diet arms. Conclusions A low-residue diet for breakfast and lunch the day prior to colonoscopy was non-inferior to clear liquids alone for achieving adequate colon cleansing when using split dose PEG-ELS.

16.
World J Gastroenterol ; 23(48): 8615-8625, 2017 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-29358870

RESUMO

AIM: To assess the cleansing efficacy and safety of a new Colon capsule endoscopy (CCE) bowel preparation regimen. METHODS: This was a multicenter, prospective, randomized, controlled study comparing two CCE regimens. Subjects were asymptomatic and average risk for colorectal cancer. The second generation CCE system (PillCam® COLON 2; Medtronic, Yoqneam, Israel) was utilized. Preparation regimens differed in the 1st and 2nd boosts with the Study regimen using oral sulfate solution (89 mL) with diatrizoate meglumine and diatrizoate sodium solution ("diatrizoate solution") (boost 1 = 60 mL, boost 2 = 30 mL) and the Control regimen oral sulfate solution (89 mL) alone. The primary outcome was overall and segmental colon cleansing. Secondary outcomes included safety, polyp detection, colonic transit, CCE completion and capsule excretion ≤ 12 h. RESULTS: Both regimens had similar cleansing efficacy for the whole colon (Adequate: Study = 75.9%, Control = 77.3%; P = 0.88) and individual segments. In the Study group, CCE completion was superior (Study = 90.9%, Control = 76.9%; P = 0.048) and colonic transit was more often < 40 min (Study = 21.8%, Control = 4%; P = 0.0073). More Study regimen subjects experienced adverse events (Study = 19.4%, Control = 3.4%; P = 0.0061), and this difference did not appear related to diatrizoate solution. Adverse events were primarily gastrointestinal in nature and no serious adverse events related either to the bowel preparation regimen or the capsule were observed. There was a trend toward higher polyp detection with the Study regimen, but this did not achieve statistical significance for any size category. Mean transit time through the entire gastrointestinal tract, from ingestion to excretion, was shorter with the Study regimen while mean colonic transit times were similar for both study groups. CONCLUSION: A CCE bowel preparation regimen using oral sulfate solution and diatrizoate solution as a boost agent is effective, safe, and achieved superior CCE completion.


Assuntos
Endoscopia por Cápsula/métodos , Catárticos/administração & dosagem , Colo/efeitos dos fármacos , Pólipos do Colo/diagnóstico por imagem , Colonoscopia/métodos , Administração Oral , Idoso , Endoscopia por Cápsula/efeitos adversos , Catárticos/efeitos adversos , Colo/diagnóstico por imagem , Colonoscopia/efeitos adversos , Diatrizoato/administração & dosagem , Diatrizoato/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios/efeitos adversos , Cuidados Pré-Operatórios/métodos , Estudos Prospectivos , Sulfatos/administração & dosagem , Sulfatos/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
17.
ACG Case Rep J ; 2(4): 221-3, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26203445

RESUMO

Colonoscopy is a valuable diagnostic and therapeutic procedure. Colonic perforation is a serious complication of colonoscopy that must be promptly recognized to limit morbidity and mortality. We present a 69-year-old woman who, during colonoscopy, had a perforation secondary to barotrauma of a long-standing ileocolonic anastomosis proximal to the point of colonoscopic intubation. To our knowledge, this is the first case report of a perforation of a well-established anastomosis proximal to the point of endoscope intubation during colonoscopy.

18.
Ann Gastroenterol ; 28(2): 236-240, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25831067

RESUMO

BACKGROUND: Celiac disease is an immune-mediated small bowel disorder that develops in genetically susceptible individuals upon exposure to dietary gluten. Celiac disease could have extra-intestinal manifestations that affect women's reproductive health. The aim of this study was to investigate fertility and outcomes of pregnancy among women with celiac disease. METHODS: In a retrospective cohort study, we analyzed information collected from patients at a tertiary care celiac center and from members of 2 national celiac disease awareness organizations. Women without celiac disease were used as controls. Women completed an anonymous online survey, answering 43 questions about menstrual history, fertility, and outcomes of pregnancy (329 with small bowel biopsy-confirmed celiac disease and 641 controls). RESULTS: Of the 970 women included in the study, 733 (75.6%) reported that they had been pregnant at some point; there was no significant difference between women with celiac disease (n=245/329, 74.5%) and controls (488/641, 76.1%; P=0.57). However, fewer women with celiac disease than controls (79.6% vs. 84.8%) gave birth following 1 or more pregnancies (P=0.03). Women with celiac disease had higher percentages of spontaneous abortion than controls (50.6% vs. 40.6%; P=0.01), and of premature delivery (23.6% vs. 15.9% among controls; P=0.02). The mean age at menarche was higher in the celiac disease group (12.7 years) than controls (12.4 years; P=0.01). CONCLUSIONS: In a retrospective cohort analysis examining reproductive features of women with celiac disease, we associated celiac disease with significant increases in spontaneous abortion, premature delivery, and later age of menarche.

19.
J Gastroenterol Hepatol Res ; 4(12): 1838-1843, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28164022

RESUMO

AIM: Screening first-degree relatives of celiac disease (CD) patients offers an opportunity to diagnose CD in a high-risk population.This study aims to determine how frequently CD patients receive a physician-issued recommendation for first-degree relative screening. MATERIALS AND METHODS: A 12-question survey assessing whether CD patients receive a physician recommendation to screen first-degree relatives for CD, and the impact of such a recommendation, was validated with outpatients in a university gastroenterology practice ("University"). The 12-question survey was then distributed online to members of a celiac organization - the National Foundation for Celiac Awareness ("NFCA"). Results were collected over 3 months. Univariate analysis was used to compare cohort means and assess the association between demographic and diagnostic factors and first-degree relative screening recommendations. RESULTS: 87 University patients participated in the validation phase. Test-retest reliability of 4 key survey questions was high (Kappa coefficient > 0.80). The main analyses were based on data from 677 NFCA and 82 University respondents. Respondents were predominantly female, with a mean age of 45 years. Significantly more University patients received a recommendation for screening (78% vs 44%, p < 0.001). Ninety-eight percent receiving a screening recommendation (both groups) discussed this with family members, leading to CD screening (University 71%, NFCA 79%) and, ultimately, a CD diagnosis (University 18%, NFCA 27%). CONCLUSIONS: Physicians of CD patients often do not recommend screening first-degree family members. The high clinical impact of this recommendation suggests that greater physician compliance with screening may increase the diagnosis of CD in high risk individuals.

20.
J Clin Gastroenterol ; 49(4): 313-9, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25494362

RESUMO

GOAL: To determine whether Excellent bowel cleansing is superior to Good for the detection of adenomas. BACKGROUND: High quality colonoscopy requires Adequate bowel preparation. However, it is unknown whether adenoma detection differs between subcategories of Adequate cleansing. STUDY: We utilized a retrospective, cross-sectional study design to obtain data about patients undergoing colonoscopy at a single university center between August 31, 2011 and September 1, 2012. Primary outcome was adenoma detection rate (ADR), the percentage of patients with ≥1 adenoma. Secondary outcomes included adenomas per colonoscopy, adenoma distribution (proximal vs. distal), and detection of advanced adenomas, sessile serrated polyps (SSP), and cancer. RESULTS: The electronic medical record of 5113 consecutive colonoscopies with Good or Excellent preparation was queried for preparation quality, colonoscopy indication, demographics, medical history, and history of adenoma and colon cancer. Exclusion criteria were age below 18 years, inflammatory bowel disease, or familial polyposis. Adenoma detection was not superior with Excellent cleansing as compared with Good for ADR [respectively, 26% vs. 29%, odds ratio 0.97 (0.85, 1.11), P=0.618] or adenomas per colonoscopy [respectively, 0.437 vs. 0.499, incidence rate ratio (IRR) 0.98 (0.90, 1.07), P=0.705]. Excellent cleansing demonstrated superior detection of SSPs [IRR 1.66 (1.14, 2.40), P=0.008] and advanced adenomas [IRR 1.37 (1.09, 1.72), P=0.007] but not colon cancer [odds ratio 0.286 (0.083, 0.985), P=0.0474]. CONCLUSIONS: ADR is not significantly different between the Adequate subcategories of Excellent and Good. However, Excellent cleansing is associated with superior detection of advanced adenomas and SSPs. If confirmed, achieving an Excellent preparation may improve colonoscopy performance in the proximal colon where SSPs primarily occur.


Assuntos
Adenoma/diagnóstico , Catárticos/normas , Colonoscopia/normas , Neoplasias Colorretais/diagnóstico , Idoso , Pólipos do Colo/diagnóstico , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Estudos Retrospectivos
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