RESUMO
DESCRIPTION: Exocrine pancreatic insufficiency (EPI) is a disorder caused by the failure of the pancreas to deliver a minimum/threshold level of specific pancreatic digestive enzymes to the intestine, leading to the maldigestion of nutrients and macronutrients, resulting in their variable deficiencies. EPI is frequently underdiagnosed and, as a result, patients are often not treated appropriately. There is an urgent need to increase awareness of and treatment for this condition. The aim of this American Gastroenterological Association (AGA) Clinical Practice Update Expert Review was to provide Best Practice Advice on the epidemiology, evaluation, and management of EPI. METHODS: This Expert Review was commissioned and approved by the American Gastroenterological Association (AGA) Institute Clinical Practice Updates Committee (CPUC) and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership, and underwent internal peer review by the CPUC and external peer review through standard procedures of Gastroenterology. These Best Practice Advice statements were drawn from a review of the published literature and from expert opinion. Because systematic reviews were not performed, these Best Practice Advice statements do not carry formal ratings regarding the quality of evidence or strength of the presented considerations. Best Practice Advice Statements BEST PRACTICE ADVICE 1: EPI should be suspected in patients with high-risk clinical conditions, such as chronic pancreatitis, relapsing acute pancreatitis, pancreatic ductal adenocarcinoma, cystic fibrosis, and previous pancreatic surgery. BEST PRACTICE ADVICE 2: EPI should be considered in patients with moderate-risk clinical conditions, such as duodenal diseases, including celiac and Crohn's disease; previous intestinal surgery; longstanding diabetes mellitus; and hypersecretory states (eg, Zollinger-Ellison syndrome). BEST PRACTICE ADVICE 3: Clinical features of EPI include steatorrhea with or without diarrhea, weight loss, bloating, excessive flatulence, fat-soluble vitamin deficiencies, and protein-calorie malnutrition. BEST PRACTICE ADVICE 4: Fecal elastase test is the most appropriate initial test and must be performed on a semi-solid or solid stool specimen. A fecal elastase level <100 µg/g of stool provides good evidence of EPI, and levels of 100-200 µg/g are indeterminate for EPI. BEST PRACTICE ADVICE 5: Fecal elastase testing can be performed while on pancreatic enzyme replacement therapy. BEST PRACTICE ADVICE 6: Fecal fat testing is rarely needed and must be performed when on a high-fat diet. Quantitative testing is generally not practical for routine clinical use. BEST PRACTICE ADVICE 7: Response to a therapeutic trial of pancreatic enzymes is unreliable for EPI diagnosis. BEST PRACTICE ADVICE 8: Cross-sectional imaging methods (computed tomography scan, magnetic resonance imaging, and endoscopic ultrasound) cannot identify EPI, although they play an important role in the diagnosis of benign and malignant pancreatic disease. BEST PRACTICE ADVICE 9: Breath tests and direct pancreatic function tests hold promise, but are not widely available in the United States. BEST PRACTICE ADVICE 10: Once EPI is diagnosed, treatment with pancreatic enzyme replacement therapy (PERT) is required. If EPI is left untreated, it will result in complications related to fat malabsorption and malnutrition, having a negative impact on quality of life. BEST PRACTICE ADVICE 11: PERT formulations are all derived from porcine sources and are equally effective at equivalent doses. There is a need for H2 or proton pump inhibitor therapy with non-enteric-coated preparations. BEST PRACTICE ADVICE 12: PERT should be taken during the meal, with the initial treatment of at least 40,000 USP units of lipase during each meal in adults and one-half of that with snacks. The subsequent dosage can be adjusted based on the meal size and fat content. BEST PRACTICE ADVICE 13: Routine supplementation and monitoring of fat-soluble vitamin levels are appropriate. Dietary modifications include a low-moderate fat diet with frequent smaller meals and avoiding very-low-fat diets. BEST PRACTICE ADVICE 14: Measures of successful treatment with PERT include reduction in steatorrhea and associated gastrointestinal symptoms; a gain of weight, muscle mass, and muscle function; and improvement in fat-soluble vitamin levels. BEST PRACTICE ADVICE 15: EPI should be monitored and baseline measurements of nutritional status should be obtained (body mass index, quality-of-life measure, and fat-soluble vitamin levels). A baseline dual-energy x-ray absorptiometry scan should be obtained and repeated every 1-2 years.
RESUMO
BACKGROUND: Most incidental gastric polyps identified during upper endoscopy are considered low-risk. However, current guidelines recommend sampling all gastric polyps for histopathologic analysis. We aimed to devise a simple narrow-band imaging (NBI) classification to reduce the need for routine biopsies of low-risk gastric polyps. METHODS: Pairs of NBI and white-light images were collected from 73 gastric polyps for which concurrent histopathologic diagnosis was available. A diagnostic accuracy cohort study was performed. Two blinded endoscopists independently analysed NBI features of each polyp for color, vessel pattern, surface pattern, and any combinations thereof to develop a classification scheme to differentiate low-risk polyps (fundic-gland or hyperplastic) from high-risk polyps (adenomatous or adenocarcinoma) and fundic-gland polyps (FGPs) from non-FGPs. RESULTS: An isolated lacy vessel pattern and a homogenous absence of surface pattern successfully differentiated low-risk from high-risk gastric polyps. Combining both descriptors into a single algorithm resulted in a negative predictive value (NPV) of 100% [95% confidence interval (CI): 100%-100%], positive predictive value (PPV) of 13.7% (95% CI: 2.6-24.8), sensitivity of 100% (95% CI: 100%-100%), and specificity of 53.7% (95% CI: 45.3%-62.0%) for high-risk polyps. This would reduce the number of polyps requiring biopsy by 50%, while still capturing all high-risk polyps. Regarding FGPs, using a rule not to biopsy polyps with isolated lacy vessels resulted in a 94.9% NPV (95% CI: 89.2%-100%), 63.2% PPV (95% CI: 47.2%-79.2%), 94.8% sensitivity (95% CI: 89.5%-100%), and 63.6% specificity (95% CI: 51.3%-76.0%) for non-FGPs. CONCLUSION: In this derivation cohort study, NBI is helpful for differentiating between high-risk and low-risk gastric polyps, thereby reducing the need for routine sampling of low-risk polyps. These results need to be validated in a separate test population.
RESUMO
Patients with inflammatory bowel disease (IBD) have a higher risk of developing colitis-associated dysplastic lesions. Surveil-lance colonoscopy with endoscopic imaging techniques such as chromoendoscopy has been suggested. However, complex dysplastic lesions of larger size, challenging location behind folds, and nonpolypoid morphology defy standard polypectomy techniques and require advanced management with endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD). When technically feasible for visible dysplasia with distinct margins, these endoscopic procedures have replaced the traditional approach of surgical management. Recent guidelines support careful endoscopic inspection of the colonic mucosa with high-definition colonoscopes and the application of imaging techniques such as chromoendoscopy to enhance lesion detection and characterization as well as to help determine whether endoscopic management is an effective alternative to colectomy. Endoscopic resection techniques such as EMR and ESD have become key modalities in the management of endoscopically resectable dysplasia in patients with IBD.
RESUMO
Over the past 2 decades, biological therapy with monoclonal antibodies targeting tumor necrosis factor-α has become a cornerstone of treatment of patients with inflammatory bowel disease. Although clinically effective, the biological therapies remain expensive, and their availability and utilization have been at times limited due to their high costs. Biosimilars are biological products similar to but not identical to the original biological agent or "reference biologic," also called "originator biologic." It is hoped that the use of biosimilars might enable these agents to become more available and, thus, decrease further expenditures related to the use of the original reference agents such as infliximab and adalimumab. In this study, we review the currently available evidence and shortcomings of these data supporting the use of biosimilars for the treatment of patients with inflammatory bowel disease, including their efficacy and safety as related to initiating therapy with biosimilar agents or switching between reference and biosimilar biologic agents.
Assuntos
Medicamentos Biossimilares/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Adalimumab/economia , Adalimumab/uso terapêutico , Medicamentos Biossimilares/economia , Custos de Medicamentos , Substituição de Medicamentos , Gastos em Saúde , Acessibilidade aos Serviços de Saúde , Humanos , Infliximab/economia , Infliximab/uso terapêuticoRESUMO
Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, can be effectively monitored with the use of endoscopy. The additional application of small field imaging technology such as confocal laser endomicroscopy CLE during ongoing endoscopic evaluation has led to real-time visualization of mucosal abnormalities and thus in vivo histology. The endomicroscopy (CLE) can improve IBD endoscopic evaluation by identifying seemingly normal-appearing mucosa, assessing the function of the intestinal barrier of the epithelium and vascular permeability, and by characterizing any mucosal lesions, including dysplastic lesions. CLE used during conventional endoscopy could especially facilitate the evaluation of mucosal healing in IBD. In addition, future developments in molecular imaging in IBD may optimize therapeutic approaches by identifying mucosal targets for therapy and determining the reasons for lack of response to specific therapy or subsequent loss of the response.
Assuntos
Endoscopia Gastrointestinal/métodos , Doenças Inflamatórias Intestinais/diagnóstico , Microscopia Confocal/métodos , Animais , Estudos de Avaliação como Assunto , HumanosRESUMO
BACKGROUND: Many patients with ulcerative colitis (UC) fear the potential side effects of immunosuppressive therapies. However, those with medically refractory disease often require total proctocolectomy (TPC) with a permanent ostomy or pouch, which may reduce quality of life. Prior studies have identified TPC predictors; however, no clinically useful prognostic tools exist to guide shared therapeutic decision-making. We therefore sought to develop a prediction tool of future TPC risk in UC patients. METHODS: In this retrospective study, clinic charts of UC patients were reviewed from January 1, 2017, to December 31, 2017. Cases had TPC performed for refractory UC after January 1, 2008. Controls had no prior UC surgery. Clinical data were assessed 1-12 months preceding TPC or clinic visit for cases and controls, respectively. We randomly selected two-thirds of patients to develop a TPC prediction model using multivariable logistic regression. One-third was reserved for model validation. RESULTS: We identified 115 cases and 325 controls. TPC predictors included albumin, 9-point Mayo score >5, Mayo endoscopic subscore >1, and corticosteroid use within 6 months. The areas under the receiver operating characteristic curve for the multivariable model were 0.94 (95% confidence interval [CI], 0.92-0.95) and 0.92 (95% CI, 0.89-0.95) for the test and validation cohorts, respectively. The validation cohort demonstrated a significant difference in calculated probability distributions between patients who did and did not have TPC (P < 0.01). We incorporated our model into a web-based application to allow convenient calculation of a patient's TPC risk. CONCLUSIONS: We created a user-friendly tool to assess TPC risk in UC. Prospective assessment will determine its utility for shared therapeutic decision-making.
Assuntos
Colectomia/mortalidade , Colite Ulcerativa/patologia , Modelos Teóricos , Complicações Pós-Operatórias , Índice de Gravidade de Doença , Adulto , Colite Ulcerativa/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Valor Preditivo dos Testes , Qualidade de Vida , Curva ROC , Estudos RetrospectivosRESUMO
Helicobacter pylori infection is widely spread all over the world. The prevalence of H. pylori infection in the world varies and depends on numerous factors such as age, ethnicity, geographical and socioeconomic status. Humans have been in a symbiotic relationship with this bacterium for thousands of years. However 10-20% of people infected with H. pylori are likely to develop gastroduodenal diseases such as peptic ulcer disease, iron deficiency anemia, gastric mucosal atrophy, metaplasia, dysplasia, MALT lymphoma, or gastric adenocarcinoma. Most of these diseases develop as the infection progresses and they are likely to occur later in life among the elderly. In the following years, the use of modern molecular techniques has led to the discovery of new Helicobacter strains and their genotypic differentiation. Newly discovered Helicobacter microorganisms can colonize human gastrointestinal tract and bile ducts. This article summarizes the distinct features of H. pylori infection in children including its prevalence, clinical manifestation, indications for treatment and recommended schemes of eradication.
Assuntos
Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori , Criança , Infecções por Helicobacter/complicações , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/epidemiologia , Humanos , PrevalênciaRESUMO
There are currently two validated endoscopic indices for evaluation of Crohn's disease (CD), the Crohn's disease Endoscopic Index of Severity (CDEIS) and the Simple Endoscopic Score for Crohn's disease (SES-CD). The study by Khanna et al. evaluated the responsiveness of the SES-CD and CDEIS using data from a trial of adalimumab. The study used appropriate statistical methods to quantify responsiveness of the indices as assessed by blinded central readers. The SES-CD demonstrated numerically greater responsiveness to a treatment of known efficacy, suggestive that the SES-CD is more efficient outcome measure than the CDEIS. Removal of stenosis as an index item and adjusting for observed segments did not improve responsiveness. In the future, the implementation of the SES-CD into daily clinical practice may become a practical tool used by gastroenterologists when caring for patients with Crohn's disease. Further studies analyzing the responsiveness of the indices in combination with clinical and patients' driven outcomes are expected prior to the indices' use in "prime time".
Assuntos
Adalimumab/administração & dosagem , Doença de Crohn , Endoscopia Gastrointestinal/métodos , Projetos de Pesquisa/normas , Anti-Inflamatórios/administração & dosagem , Doença de Crohn/diagnóstico , Doença de Crohn/tratamento farmacológico , Monitoramento de Medicamentos/métodos , Monitoramento de Medicamentos/estatística & dados numéricos , Humanos , Índice de Gravidade de DoençaRESUMO
Chromoendoscopy pertains to image-enhanced endoscopic techniques such as dye-based chromoendoscopy and electronic chromoendoscopy using narrow-band imaging, flexible spectral imaging color enhancement, and i-scan. Dye-based chromoendoscopy has been demonstrated to improve colorectal dysplasia detection in high-risk patients with long-term inflammatory bowel disease, and electronic chromoendoscopy techniques have been shown to improve characterization of diminutive colorectal lesions, allowing for optical diagnosis during a colonoscopy examination. This article reviews endoscopic imaging using chromoendoscopy techniques for colorectal dysplasia evaluation.
RESUMO
Endoscopy is an essential tool for effective care of patients with inflammatory bowel disease (IBD), including Crohn disease and ulcerative colitis. The newest endoscopic small-field imaging technologies with confocal endomicroscopy have allowed real-time imaging of gastrointestinal mucosal during ongoing endoscopic evaluation and in vivo histology. Thus, endomicroscopy has a potential to further enhance the endoscopic evaluation of IBD. Advances in molecular in vivo imaging in IBD may be used not only to better understand the pathophysiology of IBD but also to guide optimized therapy and thus to allow a personalized, new approach to the IBD management.
Assuntos
Endoscopia Gastrointestinal/métodos , Doenças Inflamatórias Intestinais/patologia , Mucosa Intestinal/patologia , Microscopia Confocal/métodos , HumanosAssuntos
Colite/diagnóstico , Doença de Crohn/diagnóstico , Colite Ulcerativa , Humanos , HiperplasiaRESUMO
Endoscopy has become an essential tool for effective management of patients with inflammatory bowel disease, including Crohn's disease and ulcerative colitis. The endoscopic management of inflammatory bowel disease ranges from diagnosing the disease, assessing the disease's extent, and activity to monitor the responses to various medical therapies with assessment of mucosal healing, serving as a predictor of disease course and response to therapy to finally treating the disease's complications. In general, the use of endoscopic scoring systems has been recommended for assessing the activity of the disease, and the prognosis and efficacy of medical treatment. However, many of currently available endoscopic scoring systems are often too complicated for their routine use in clinical practice, lacking adequate interobserver agreement and formal validation. In this review, we will discuss how we should be assessing and documenting endoscopies in inflammatory bowel disease patients and incorporating standard scoring systems into patients' care.
Assuntos
Endoscopia Gastrointestinal/normas , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/terapia , Avaliação de Processos em Cuidados de Saúde/normas , Índice de Gravidade de Doença , Padrão de Cuidado , Gerenciamento Clínico , Progressão da Doença , Endoscopia Gastrointestinal/métodos , Humanos , PrognósticoRESUMO
OPINION STATEMENT: Patients with ulcerative colitis (UC) and Crohn's disease (CD) colitis are at significantly higher risk for the development of colitis-associated colorectal cancer (CAC), a risk associated with increased duration and extent of disease [1]. CAC in patients with ulcerative colitis and Crohn's colitis arises from dysplastic tissue in the background of mucosal inflammatory changes. Regular surveillance by colonoscopy is a recommended cancer prevention strategy endorsed by the US and European GI societies [2-4]. Until recently, random sampling of the mucosa throughout the colon has been the mainstay of this conventional surveillance. This requires multiple biopsies to be taken and processed, a practice which is time consuming, expensive, and has a low diagnostic yield. The growth pattern of dysplastic tissue is often multifocal and diffuse, and thus, its detection may not be optimal with the use of traditional white light colonoscopy. According to recent studies, most dysplastic lesions appear to be visible to careful endoscopic inspection [5-7]. Thus, the approach focusing on targeted biopsies of any mucosal abnormalities instead of only random biopsies has been advocated [8]. In addition, the detection and further delineation of any mucosal abnormalities are thought to be improved by the application of dyes that highlight more subtle abnormalities known as chromoendoscopy (CE) as well as a new generation endoscopic system with high-definition white light endoscopy (HDWL). The application of CE in patients with long-term UC was deemed to be beneficial based upon the results of previous clinical trials comparing CE with standard definition white light endoscopy (SDWL) [9â¢, 10â¢]. However, there are limited data available comparing CE with the currently broadly used high-definition colonoscopies (HDWL) [11â¢, 12â¢, 13â¢]. High-definition (HD) endoscopy uses a high-definition monitor and a high-resolution CCD (charge-coupled device) providing images of substantially higher resolution than standard video endoscopy. Thus, HDWL colonoscopy may be an alternative to CE in IBD surveillance without the need for the extra time and required experience with CE. Further longitudinal studies are necessary to determine the ultimate advantage of chromoendoscopy or lack of the advantages of chromoendoscopy over that of high-definition colonoscopy in detection of dysplasia. Once lesions are identified by HDWL and CE, they can be further evaluated with evolving technologies to perform in vivo microscopy. Small-field technologies such as confocal endomicroscopy (CLE) permit in vivo microscopic assessment of the colonic mucosa. This evolving technology can be utilized in combination with HDWL and CE in selected cases to further define the lesions and assess their histology, and thus, facilitate real-time in vivo diagnosis and decisions regarding resection of lesions. Further studies to determine the applicability of these newer enhanced technologies in evaluation of dysplasia in routine clinical practice are needed.
RESUMO
Confocal laser endomicroscopy (CLE) is a rapidly emerging tool in endoscopic imaging allowing in-vivo microscopy of examined gastrointestinal mucosa. This review will discuss the most recent advances of confocal laser endomicroscopy in the diagnosis of intestinal neoplasia and inflammatory conditions.
Assuntos
Doenças Inflamatórias Intestinais/diagnóstico , Neoplasias Intestinais/diagnóstico , Microscopia Confocal/métodos , HumanosRESUMO
PURPOSE OF REVIEW: Ulcerative colitis is a chronic inflammatory disease of the colon of unknown cause that is characterized by alternating intervals of active and inactive disease in 80-90% of patients. The primary goal of treatment is to induce and maintain remission using therapy tailored to the individual patient. The purpose of this review was to describe the management of ulcerative colitis with emphasis on the use of anti-tumor necrosis factor (TNF) agents. RECENT FINDINGS: Recent research has shown that new anti-TNF agents, adalimumab (ADA) and golimumab, are effective in induction of remission and maintenance of remission in patients with extensive ulcerative colitis. In a recent study, infliximab was found to have comparable efficacy to cyclosporine in treatment of acute severe refractory to corticosteroids ulcerative colitis. SUMMARY: Anti-TNF therapy should be initiated in patients with acute severe refractory to corticosteroids ulcerative colitis and in patients with moderate-to-severe ulcerative colitis who are not responsive to conventional treatment with aminosalicylates, corticosteroids and immune modulators. Alternatives to infliximab are ADA and golimumab. Future research is needed to further assess the long-term efficacy and safety of ADA and golimumab in ulcerative colitis.
Assuntos
Colite Ulcerativa/tratamento farmacológico , Fármacos Gastrointestinais/uso terapêutico , Imunossupressores/uso terapêutico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Anti-Inflamatórios não Esteroides/uso terapêutico , Azatioprina/uso terapêutico , Ciclosporina/uso terapêutico , Glucocorticoides/uso terapêutico , Humanos , Mercaptopurina/uso terapêutico , Mesalamina/uso terapêuticoRESUMO
INTRODUCTION: The currently available medications for treatment of Crohn's disease (CD) include aminosalicylates, corticosteroids, antibiotics, immunomodulators and biologic agents (infliximab, certolizumab pegol, adalimumab and natalizumab). These agents target the immune and inflammatory pathways of CD, while there is a shortage of agents that target the barrier functions of the gut that are impaired in CD. Glucagon-like peptide 2 is an enterogastrone with strong trophic effects on the intestinal mucosa. Teduglutide , the analog of glucagon-like peptide has been already approved by the US Food and Drug Administration as a treatment of short bowel syndrome. This review discusses the potential use of teduglutide in patients with CD. AREAS COVERED: As there has been only one randomized placebo controlled trial of teduglutide in CD, there is a shortage of data regarding the efficacy of this agent in CD. The literature search was performed using Medline database with the use of the following key words: teduglutide, glucagon-like peptide-2, CD and inflammatory bowel disease. EXPERT OPINION: Based on available data, it can be concluded that this agent seems to be a promising medication in CD and further trials are required to define the place of teduglutide in treatment of CD.