Best practice & research. Clinical gastroenterology
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Colorectal cancer is one of the most frequent cancers in the world, especially in occidental countries. The primary curative therapy is surgical resection of the tumour. Within the last 15 years, appropriately powered prospective randomized trials have demonstrated that adjuvant post-operative chemotherapy should be the standard treatment for stage III cancers (node-positive disease). 5-Fluorouracil(5FU)/levamisole was used in the early 1990s but has now been replaced by 5FU/leucovorin. ⋯ In an attempt to define groups of stage II cases that may benefit from adjuvant chemotherapy, considerable efforts have been made to determine molecular genetic factors (tumour-ploidy and mutations or alterations in oncogenes and tumour-suppressor genes). Regional therapy (particularly portal vein infusion) is one of the other therapeutic strategies still considered to be investigational. Current clinical trials are evaluating the role of non-fluorinated pyrimidine agents in an adjuvant setting.
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Best Pract Res Clin Gastroenterol · Dec 2001
ReviewDrug metabolism and drug interactions in the elderly.
In the elderly concomitant use of several drugs (polypharmacy) is very common. Thus, the risk for drug interactions might be increased in this population. Since most drugs are hepatically eliminated by various metabolic pathways, liver function has to be considered as an additional factor modifying drug response. ⋯ The most important metabolic drug-drug interactions are independent of the age of the patients. However, since elderly patients consume a greater proportional share of drugs, they represent a population at risk for interactions. Awareness of this clinical problem may help to diminish those risks.
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The potential for cyclo-oxygenase inhibition in cancer prevention and treatment is founded on epidemiology (reduction of colorectal cancer in aspirin users), animal experiments and molecular genetics. Trials using the NSAID sulindac also reduced the number of polyps in patients with familial adenomatous polyposis, but the well-known gastrointestinal toxic effects of aspirin and NSAIDs have discouraged the exploitation of their antineoplastic potential. ⋯ Recently a non-cyclo-oxygenase effect of COX-2 inhibitors, which combines the PPARdelta and the APC tumour suppressor activity, was also demonstrated. The selective COX-2 inhibitor celecoxib has been approved by the FDA for adjuvant treatment of familial adenomatous polyposis, and a large number of prevention and treatment trials of colorectal and other common cancers (prostate and breast cancer) have been started.
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Best Pract Res Clin Gastroenterol · Oct 2001
ReviewPrevention and treatment of gastrointestinal symptoms and complications due to NSAIDs.
The mechanisms by which aspirin(ASA) and non-steroidal anti-inflammatory drugs (NSAIDs) cause gastrointestinal symptoms are poorly understood. They probably arise from several causes, including direct and indirect mucosal injury, exacerbation of underlying peptic ulcer disease or non-ulcer dyspepsia, exacerbation of Helicobacter pylori gastritis, and possibly motility disorders. No single form of therapy has been generally successful. ⋯ Most other low-risk patients may not need any special care. Co-morbid conditions have a major impact on outcome of NSAID therapy. Morbidity or even death attributable solely to NSAIDs is probably small in normal patients, and requires little in the way of prophylaxis.
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Best Pract Res Clin Gastroenterol · Aug 2001
ReviewSclerosing cholangitis in the paediatric patient.
Sclerosing cholangitis in childhood is a heterogeneous condition, which has different aetiologies. Sclerosing cholangitis may be inherited and diagnosed in the neonatal period (neonatal sclerosing cholangitis); it may present later with features of autoimmunity (autoimmune sclerosing cholangitis); or it may be associated with a variety of disorders, including Langerhans cell histiocytosis, immunodeficiency, psoriasis, cystic fibrosis, reticulum cell sarcoma and sickle cell anaemia. ⋯ The initiating events and possible pathogenic mechanisms differ in the various forms of sclerosing cholangitis and are still obscure. Treatment and prognosis depend on the type of sclerosing cholangitis present.