Digestive diseases
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Since sorafenib, a multikinase inhibitor targeting angiogenesis of hepatocellular carcinoma (HCC), demonstrated survival benefits in recent clinical trials, it has changed the treatment paradigm and become the standard first-line treatment for patients with advanced HCC. However, disease stabilization with sorafenib lasts a few months, possibly due to the development of resistance, and thus the survival advantage was modest, even in patients with preserved liver function. Furthermore, there is currently no biomarker for monitoring the response or resistance to sorafenib. ⋯ Third, the actual benefits of sorafenib to patients with advanced liver dysfunction should be clarified and a more effective strategy for targeted therapy needs to be developed, for example, using a combination of targeted agents acting on different pathways or different levels of a key pathway. Finally, sorafenib could be used with other treatment modalities, such as local ablation or transarterial chemoembolization, to synergize efficacy. Based on the successful introduction of sorafenib, future studies should focus on plans to further improve the outcome of HCC patients by overcoming resistance and maximizing the efficacy of molecularly targeted therapy.
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Helicobacter pylori induces an inflammatory immune response in the gastric mucosa. The degree of gastric mucosal inflammation and its topographic distribution are key factors in the diversity of H. pylori-related complications. Here we summarize substantial evidence reported in the literature concerning the impact of H. pylori density on gastric inflammation, the development of severe complications, and its relation to H. pylori suppression therapy. ⋯ The influence of H. pylori density reduction on the improvement of gastric mucosal changes was observed in studies using 'clearance' therapies. Mucosal agents provoke a significant, but not persistent, reduction in gastritis activity. Treatments suppressing the density and virulence of H. pylori could become strategies to prevent H. pylori-associated disease in the future.
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In chronic pancreatitis over a course of years to decades, pancreatic parenchyma is gradually lost and pain is gradually decreasing as signs and symptoms of malabsorption appear. Appearance of calcifications is a late sign and in many cases coincides with appearance of steatorrhea. Decreasing output of insulin and glucagon results in diabetes mellitus, which is characterized by a high risk of hypoglycemias ('brittle' diabetes). ⋯ Using such preparations, most patients will reduce their steatorrhea to <15 g fat per day during supplementation of 25,000-40,000 IU of lipase per meal, but in selected cases larger doses may be needed, depending on size of the meal and severity of the disease. Efficacy of enzyme replacement therapy is influenced by denaturation of lipase by gastric acid, improper timing of enzymes, coexisting small-intestinal mucosal disease, rapid intestinal transit and effects of diabetes. This review focuses on pathophysiology, diagnosis and treatment of pancreatic steatorrhea.
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Growing evidence suggests that gastrointestinal immune activation may affect intestinal function and sensory perception, which contribute to symptom generation in patients with irritable bowel syndrome (IBS). The identification of higher counts of immunocytes (e.g. T cells and mast cells), mucosal and systemic immune activation, and increased mucosal permeability in patients with IBS has stimulated interest in the potential development of therapeutic approaches aimed at targeting the immune system and inflammation. ⋯ Nevertheless, the exact mechanism through which this drug affects immune activation in the intestine of patients with IBS remains unknown. There is a need for further studies to prove the efficacy of mesalazine for IBS. Further studies aimed at assessing the role of aminosalicylates and other approaches with potential anti-inflammatory activity, including probiotics, non-absorbable antibiotics, histamine receptor antagonists and protease inhibitors on IBS symptoms or pathophysiology are now warranted.
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There are few diseases whose incidence varies as greatly worldwide as that of diverticulosis. Its prevalence is largely age-dependent: the disease is uncommon in those under the age of 40, the prevalence of which is estimated at approximately 5%; this increases to 65% in those > or =65 years of age. Of patients with diverticula, 80-85% remain asymptomatic, while, for unknown reasons, only three-fourths of the remaining 15-20% of patients develop symptomatic diverticular disease. ⋯ Predictive factors for severe diverticulitis are sex, obesity, immunodeficiency and old age. Surgery for acute complications of diverticular disease of the sigmoid colon carries significant rates of morbidity and mortality, the latter of which occurs predominantly in cases of severe comorbidity. Postoperative mortality and morbidity are to a large extent driven by patient-related factors.