Reviews in gastroenterological disorders最新文献

Although diarrhea is a common complaint, its evaluation and treatment can be challenging. Appropriately defining and classifying diarrhea provide the framework for approaching diagnostic and therapeutic options. Diarrhea can be defined based on frequency, consistency, and/or weight, and classified as acute or chronic with specific clinical characteristics and stool appearance. Colonoscopy is the most common diagnostic tool used in the evaluation of patients with chronic diarrhea. Other evaluation strategies include timed stool collections, evaluation of inflammatory markers, and hydrogen breath tests. A focused workup of chronic diarrhea may yield a specific diagnosis, including diarrhea-predominant IBS (dIBS), functional diarrhea, diabetic diarrhea, bile acid-induced diarrhea, and microscopic colitis. Ideally, therapeutic decisions are specifically tailored to target the underlying pathophysiology, including, for example, gluten restriction for celiac disease, rotating antibiotics for small bowel bacterial overgrowth, budesonide therapy for collagenous colitis, and loperamide for treatment of functional diarrhea. It is also important to assess the role of diet and medications in chronic diarrhea. However, if no specific causes are identified following workup, empiric therapy with simple opiate antidiarrheals such as loperamide may be effective. If this proves unsuccessful, the use of more potent agents, including codeine and opium, may be considered.

The best known guidelines for colorectal cancer screening in the United States are those of the US Multisociety Task Force on Colorectal Cancer, the American Cancer Society, the United States Preventive Services Task Force, the American College of Gastroenterology, and the American Society of Gastrointestinal Endoscopy. Screening is currently endorsed for both average-risk and high-risk persons by all guideline groups. Some guidelines offer a menu of options for average-risk persons, from which patients and physicians can select according to their perceptions and values regarding effectiveness, risk, and upfront costs. The alternative approach of colonoscopy as the preferred strategy simplifies discussions with patients and better reflects current trends in procedure use in the United States. For patients who refuse invasive testing, fecal occult blood testing is available. Quantitative fecal immunochemical tests offer promise for improved performance compared with guaiac testing. Radiographic screening has declined, although double contrast barium enema still remains an option in some guidelines. Computed tomographic colonography remains under active consideration but is not yet endorsed by any of the guidelines. High risk is still based primarily on family history, and the guidelines are fairly consistent in adjusting screening modality and intervals according to family history.

Irritable bowel syndrome (IBS) is a difficult disease to treat because of its ill-defined triggers, variable clinical course, and unpredictable myriad of symptoms of varying severity. Both doctors and patients are frustrated by the insidious nature of IBS--a nonlethal disorder that destroys lives, relationships, and careers. Traditional therapies are sometimes effective in mild disease but are often self-limiting because they focus primarily on individual symptoms. A combination of lifestyle and diet modifications, pharmacologic agents, and therapeutic interventions is usually necessary to address the multiple symptoms characteristic of IBS. One of the major advancements in the treatment of patients with IBS has been the development of US Food and Drug Administration--approved serotonergic therapeutics that specifically target the underlying causes of IBS and provide multisymptom relief by improving gastrointestinal function. Although they are controversial, alternative treatment approaches that target normalization of intestinal bacterial microflora may be helpful for some patients in whom intestinal bacterial overgrowth is present. Patients who have co-existing pelvic floor dysfunction may benefit from physical therapy. Overall, treatment approaches for IBS should address multisymptom relief and improvement of overall patient well-being.

Natalizumab is a humanized monoclonal antibody that is produced in murine myeloma cells. It functions in the body as an antagonist of integrin heterodimers that contain the a4 integrin subunit. These heterodimers include a4b1 integrin and a4b7 integrin, which are expressed on the surface of most leukocytes. When natalizumab binds to the a4-subunit of the integrin, it prevents the a4-mediated adhesion of the leukocytes to their counter-receptor(s) (eg, vascular cell adhesion molecule-1 and mucosal addressin cell adhesion molecule-1), thus preventing transmigration of the leukocytes across the endothelium and into the inflamed parenchymal tissue. Clinical trials with natalizumab for the treatment of the relapsing forms of multiple sclerosis have found the drug is capable of delaying the accumulation of physical disability and reducing the frequency of clinical exacerbations. Clinical trials of natalizumab for the treatment of Crohn's disease have found the drug, alone or in combination with infliximab, is effective in improving clinical response and remission rates as well as health-related quality of life in patients with Crohn's disease who have not been able to achieve remission with infliximab therapy alone. Like all drugs, natalizumab is not without risks. The drug was temporarily withdrawn from the market because of 3 reported cases of progressive multifocal leukoencephalopathy. Subsequent evaluations determined that the risk of this severe, but rare, adverse reaction did not justify keeping the drug off the market. When natalizumab was reintroduced, however, a closed prescribing and distribution program (Tysabri Outreach Unified Commitment to Health [TOUCH]) was also introduced. This program requires all patients prescribed natalizumab to be enrolled in and to receive their medication through the TOUCH system. Any serious adverse reactions must be reported to the TOUCH and MedWatch systems.

Advances in fecal and serum inflammatory biomarkers, endoscopy, and radiology have led to a rapid expansion of modalities for diagnosis and disease activity assessment of Crohn's disease. Although no test is recognized as the most accurate for assessing disease activity, ileocolonoscopy remains the single test that may approach the gold standard for clinical diagnosis. Serum C-reactive protein concentrations have been shown to correlate reasonably well with clinical, endoscopic, and radiologic measures of disease activity, and they appear to have prognostic value in certain settings. Fecal markers of inflammation, such as lactoferrin and calprotectin, are relatively noninvasive ways to determine disease activity and predict clinical relapse. Capsule endoscopy allows visual inspection of previously inaccessible areas of the small intestine and may serve as a useful tool for patients with suspected small bowel involvement but negative results on conventional testing. Computed tomographic (CT) enterography, which entails ingestion of a large volume of a neutral or negative contrast agent and scanning protocols that take advantage of the differences in contrast between the lumen and the bowel wall, appears to be more sensitive than small bowel follow-through for detecting small bowel Crohn's disease and provides extraluminal information. Magnetic resonance enterography employs principles similar to those of CT enterography without exposure to ionizing radiation, and early results are encouraging. We are beginning to accumulate evidence that treatment based on objective measures such as mucosal healing might affect long-term outcomes, but prospective trials of objective marker-directed therapy are required to confirm this hypothesis.

Although infliximab continues to make an important contribution to the management of Crohn's disease, its use includes several clinical challenges, including loss of response, loss of tolerability due to acute and delayed infusion reactions, and the need for intravenous administration by a health care provider. Newer anti-tumor necrosis factor-a agents such as certolizumab pegol and adalimumab have been shown in clinical trials to have similar efficacy as infliximab, without the acute and delayed infusion reactions. Further information is needed about infliximab, certolizumab pegol, and adalimumab so we can understand the relationships among these 3 agents in terms of antibody formation, drug concentration, dosing (episodic vs systematic maintenance), concomitant immunosuppressive therapy, and efficacy.