Volume 73 - 2010 - Fasc.3 - Reviews
Usefulness of thiopurine methyltransferase and thiopurine metabolite analysis in clinical practice in patients with inflammatory bowel diseases
Thiopurines (TP) are widely used in the management of inflam- matory bowel diseases. Side-effects and inefficacy are a major con- cern as they lead to withdrawal of the drug. Tools investigating TP metabolism are useful to avoid inadequate cessation of TP thera- py. TP metabolism is complex and many enzymes are involved. Among them, Thiopurine methyltransferase (TPMT) is the only one routinely measured by pheno- or genotyping. In this review, the rationale for TPMT and thiopurine metabolites, 6-thioguanine nucleotides and 6-methylmercaptopurine, determination in clini- cal practice is discussed, specifically in case of thiopurine failure and recommendations are given about their interpretation and potential dose optimization of TP drugs. (Acta gastroenterolog. belg., 2010, 73, 331-335).
Gastrointestinal stromal tumors: Review on morphology, molecular pathology, diagnostics, prognosis and treatment options
Gastrointestinal stromal tumors (GISTs) are the most common non-epithelial mesenchymal tumors of the gastrointestinal tract. GISTs represent a specific group of mesenchymal tumors with uncertain biological behaviors. These tumors are assumed to orig- inate from progenitor cells, usually unable to self-regenerate, which differentiate towards Cajal cells. Apart from common GISTs that occur predominantly in adulthood, a heterogeneous group of tumors has been described that are morphologically iden- tical with GIST, but have a specific clinical presentation and bio- logical properties.
Approximately 30% of newly diagnosed GISTs are malignant or have a high potential for malignancy. Currently, GISTs are rou- tinely identified with histological, immunohistochemical, and molecular genetic assays. However, clinical diagnoses, particular- ly of small or intramural GISTs, might be difficult. The most use- ful techniques for imaging and monitoring disease progression are endoscopic examinations and fused PET/CT imaging. Surgical treatment is the first-line treatment and the only method that might lead to full remission in patients with a primary GIST. There is currently no consensus on the issues of whether to per- form resections in patients with positive margins or resections of metastases. Endoscopic resection could represent a relatively sim- ple and less aggressive alternative as compared to traditional surgery in the treatment of small sized GISTs. Biological therapy with imatinib mesylate is recommended for patients with newly diagnosed, locally advanced, inoperable, or metastasizing gas- trointestinal GISTs that express the c-KIT protein. Treatment may reduce a primary tumor to a size small enough for surgical excision. Current research is focusing on the development of new therapies for the treatment of advanced disease and/or disease prophylaxis. (Acta gastroenterol. belg., 2010, 73, 349-359).
Functional Dyspepsia : still a serious challenge for medical practitioners and new drug investigators ? A Belgian, French, German and Hungarian opinion
The diagnosis of Functional Dyspepsia is based on the identifi- cation of long term specific symptoms and the absence of organic lesions. Many pathophysiological mechanisms are intricate and, at least, partially responsible for the syndrome. Widely accepted technical procedures for the identification of these mechanisms are missing. The final etiopathology is not yet established. The rela- tionship between symptoms and putative mechanisms is unclear. At the moment of the prescription, the physician faces a real ther- apeutic gap. Moreover, Functional Dyspepsia is an evolving area of study and knowledge has to be updated regularly. As a result, con- sultations for Functional Dyspepsia are usually very challenging and patients look desperately for medical support. It is likely that this disease is both under-diagnosed and under-treated. Classi- fying patients into symptomatic subgroups is a promising approach proposed by Rome III. It is assumed that these sub- groups are based on different pathophysiological mechanisms, and may allow for more specific therapeutic approaches. However the assessment of the symptomatic profiles of patients is time-consum- ing. It is also a risky process, because the Rome III subgroups have yet to be validated. There are currently no translations of the def- initions in the different European languages. Interviews of the patients are biased by cultural, educational and subjective factors. Identification of suitable subjects for clinical trials is uneasy for the same reasons and can explain several recent Research and Development (R&D) failures. Therefore, there is a need for an updated, step by step approach, a real diagnostic algorithm of the consultation including the use of simple, clear, universal and cross- cultural validated tools, as word-figure questionnaires, designed to establish the symptomatic profiles of the patients. (Acta gastroen- terol. belg., 2010, 73, 360-365.