Reviews in gastroenterological disorders最新文献

Medical options for Crohn's disease are expanding at an unprecedented rate. The anti-tumor necrosis factor-a (TNF-a) agents infliximab, adalimumab, and certolizumab pegol have proven efficacy for induction and maintenance of remission among patients with moderate to severe Crohn's disease. Anti-TNF therapy has also been successful in reducing the need for corticosteroids, closing fistulas, healing colonic mucosa, and reducing the number of hospitalizations and surgeries. With these tools, the goal of therapy in Crohn's disease may change from the management of symptoms to a change in the natural history of the disease.

Diarrhea continues to be a prevalent symptom in patients with inflammatory bowel disease (IBD), requiring a wide differential diagnosis to define the pathophysiologic mechanisms in individual patients. It is essential that physicians properly evaluate complaints of diarrhea by assessing both patient symptoms and potential physiologic impacts on fluid and electrolyte status. Underlying mechanisms of diarrhea with IBD are the location, extent, and severity of inflammation; malabsorption; altered motility; and iatrogenic causes such as medications, diet, and antibiotic-associated colitis (eg, Clostridium difficile). When treating diarrhea, physicians need to control inflammatory activity using appropriate treatment algorithms. Therapies include aminosalicylates, corticosteroids, immune modifiers, and, most recently, biologic treatment. Other medications, including loperamide, diphenoxylate, codeine sulfate, and tinctures of opium, slow motility and increase the absorption of fluids and nutrients. For iatrogenic issues, medications that cause diarrhea should be withdrawn and individual diets modified. Not all diarrheas in the IBD patient are the same; therefore, it is essential to tailor therapies according to presumed etiologies. Antidiarrheal agents are not recommended in extremely ill patients and those with known hypersensitivity or evidence of obstruction or colonic dilation, fever, or abdominal tenderness. Concomitant use of loperamide with diphenoxylate and atropine should be avoided in early pregnancy.

Maximizing therapy for the patient with symptomatic gastroesophageal reflux disease (GERD) and optimizing efficacy of available agents in the difficult or refractory patient requires an understanding of antisecretory pharmacology and pharmacodynamics. Recent studies raise issues related to potential side effects of proton pump inhibitors (PPIs). Non-acid reflux and its potential association with symptoms must be considered in the management of refractory patients. Medical therapy of GERD is discussed, emphasizing optimizing antisecretory therapy, reviewing recent studies addressing potential side effects of PPIs and options for treatment of non-acid reflux.

Functional bowel disorders (FBDs) such as chronic constipation and irritable bowel syndrome-constipation predominant (IBS-C) often share symptoms, but thanks to advances such as the Rome III criteria, diagnosis of these conditions in the absence of alarm features can be relatively straightforward. Empiric treatment is recommended for most patients, with diagnostic testing reserved for those with alarm symptoms. Most current therapies for constipation are indicated for patients with occasional symptoms, with only lubiprostone and tegaserod (restricted) indicated for chronic constipation. Therapies for IBS-C also are limited. However, ongoing research provides promise for improved outcomes in patients with FBDs.

The evaluation and management of diarrhea can be a challenging problem for primary care physicians. The differential diagnosis is large and the multiplicity of diagnostic tests makes the evaluation complex. A strategy of taking a thorough history and performing simple objective tests can make the diagnostic process easier. This strategy will often lead to a specific diagnosis that can be treated specifically. When a diagnosis is not proven, however, diarrhea can be managed symptomatically with antidiarrheals such as loperamide. Such an approach improves the quality of life of patients with diarrhea and may mitigate associated symptoms, such as fecal incontinence.

Acute hepatitis A and acute hepatitis B are associated with significant morbidity, time away from work or usual activities, substantial cost to the healthcare system, and some mortality. Despite the availability of vaccines against hepatitis B and hepatitis A since 1981 and 1995, respectively, and a combined hepatitis A and B vaccine since 2001, immunization rates against these vaccine-preventable diseases are appallingly low. In particular, several groups of adults, such as men who have sex with men, heterosexuals with multiple partners, injection drug users, persons with human immunodeficiency virus infection, travelers to endemic areas, and persons with chronic liver disease, are at particularly high risk for acute hepatitis A and B or for a more severe illness or a higher rate of chronicity in the case of hepatitis B. Studies have confirmed that hepatitis A and hepatitis B vaccines are safe and immunogenic in patients in these populations, although patients with more advanced disease may respond less well. These observations have led to the recommendation that patients falling into the above risk groups undergo hepatitis A and B vaccination early in the natural history of their underlying risk behavior or diseases. Vaccination rates are low in clinical practice, and public health and educational programs are needed to overcome barriers to facilitate timely implementation of these recommendations. The use of a combined vaccination, possibly using an accelerated administration schedule, provides convenience and may increase compliance.

Although the success rates of endoscopic retrograde cholangiopancreatography (ERCP) in accessing the bile and pancreatic ducts are quite high, failure to achieve duct access still occurs. Options in these cases have traditionally included percutaneous access or open surgical intervention. A combination percutaneous and endoscopic approach (ie, rendezvous procedure) is often used in cases of failed biliary cannulation by ERCP and occasionally for pancreatic duct access. However, this technique often results in complications and is hampered by the difficulty in coordinating schedules between interventional radiologists and endoscopists and the lack of predictability of failed ERCP access. Several groups have described the use of endoscopic ultrasonography (EUS) in accessing the ducts in cases of failed ERCP. This technique has the potential to substantially reduce the need for a percutaneous or surgical approach in many cases. This article reviews the nonsurgical methods for accessing the biliary and pancreatic ducts after failure of ERCP as well as the current status and possible future applications of EUS-assisted drainage techniques.

It is expected that within a few months, there will be commercially available in the United States a total of 3 biologic agents with inhibition of tumor necrosis factor-a (TNF-a) as the primary mechanism of action: infliximab, adalimumab, and certolizumab pegol. The primary efficacy data for each of these agents are reviewed. All 3 agents appear to be efficacious for both induction and maintenance of remission in Crohn's disease. There are no trials comparing these agents, but one can infer from available data that they have broadly similar efficacy. Adverse events associated with anti-TNF-a therapy, including infection, infusion reactions, autoimmunity, risk of malignancy, and neurologic events, are reviewed.

The current Crohn's disease treatment algorithm involves a "step-up" approach in which conventional medications such as corticosteroids are given first and anti-tumor necrosis factor-a (TNF-a) agents are reserved for refractory cases. Although this approach may seem to be cost-efficient, recent studies have shown that "top-down" therapy using anti-TNF-a agents in newly diagnosed patients improves long-term rates of mucosal healing, a therapeutic endpoint that correlates with reduced hospitalizations and surgeries, thereby reducing overall costs and enhancing patients' quality of life. Another reason the step-up approach has been favored over the top-down is concern about side effects; however, a multivariate logistic regression analysis of patients treated with or without infliximab showed no differences in mortality, serious infections, or malignancies between the 2 groups. Moreover, newer anti-TNF-a agents, such as adalimumab and certolizumab pegol, have the potential to reduce the risk of immunogenicity and the associated infusion reactions and loss of response, as well as reducing autoimmunity associated with infliximab therapy. The potential advantages of "reversing" our current therapeutic pyramid/algorithm for the treatment of Crohn's disease include early disease stabilization and disease modification, minimization of complications such as strictures and fistulae that lead to the need for surgery, reduction of postoperative recurrence, and avoidance of the ubiquitous complications of corticosteroid therapy.