الفهرس 
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Abstract
Although gastrointestinal stromal tumor (GIST) is generally regarded as a rare tumor, it represents the most common mesenchymal neoplasms of gastrointestinal tract. They account for <1% of all GI tumors. The estimated annual incidence is about 1.5 per 100, 000. In the past, these tumors were presumed to have elements of smooth muscle origin, so they were classified as leiomyomas, leiomyosarcomas and leiomyoblastomas.
GISTs can arise anywhere along the gastrointestinal tract but the most common primary sites for these neoplasms are the stomach, followed by the small intestine, and to a much lesser degree the colon and rectum. GISTs are believed to arise from the interstitial cells of Cajal (ICC), the pacemaker cells of the gut, or from interstitial mesenchymal precursor stem cells. GISTs most commonly result from activating mutations in one of the receptor protein tyrosine kinases: KIT (CD117) or platelet-derived growth factor receptor alpha (PDGFRA).
GIST has been reported in all age groups, in¬cluding newborn infants. However, it is extremely rare in patients younger than 30 years. Over 90% of GISTs occur in adults over 40 years old, in a median age of 63 years. The incidence between the sexes is the same, although a recent study reported that there is a slight predominance of males.
GISTs are associated with a broad range of pre-sentations. Many are identified clinically because they cause symptoms and some are identified at au¬topsy. Small GISTs that are smaller than 2 cm usu¬ally do not produce any symptoms and are detected incidentally during abdominal exploration, endos¬copy, or radiologic imaging. The symptoms & signs are not disease specific and as a consequence, about 50% of GISTs have already metastases at the time of diagnosis. The clinical signs & symptoms are usually related to the presence of a mass or bleeding.
The most common clinical presentation of GIST is gastrointestinal bleeding. Acute abdomen due to tumour rupture, obstruction, appendicitis-like pain, early satiety, bloating or fatigue related to anaemia can occur. Aggressive tumours generally metastasize to the liver or disseminate throughout the abdomen, and they rarely metastasize to lymph nodes or spread outside of the abdominal cavity.
GISTs have an uncertain clinical behavior ranging from benign to frankly malignant, making the outcome totally unpredictable. Multiple parameters have been considered as predictors of malignancy. At present, size, mitotic count, & site appear to be the most useful predictors of the malignant behavior.
Treatment options for GIST vary based on whether the tumor is local or metastatic, unresectable or accessible through surgery. For localized lesions that are deemed surgically resectable, surgical resection is the gold standard therapy. Its goal is complete resection of the disease with avoidance of tumor rupture. Tumor size determines the survival and not the negative microscopic surgical margin.
The treatment of choice for primary GISTs remains complete surgical resection when possible. Until a few years ago, the available treatment options for recurrent or unresectable tumors were very limited. However, the US Food and Drug Administration has approved the use of imatinib mesylate for the treatment of recurrent and/or metastatic GISTs after several reports showed smaller and fewer metastases in 54%, and stable disease in 28%, of treated patients. Imatinib is an oral tyrosine kinase inhibitor that has dramatically changed GIST therapy. This drug inhibits the KIT and PDGFR tyrosine kinases as well as other members of the type III group of tyrosine kinases. However, after the introduction of molecular targeted therapy with Imatinib, treatment of metastatic or recurrent GISTs is more effective and the survival rate has improved impressively.
Multiple novel tyrosine kinase inhibitors may be potentially useful for the treatment of imatinib-resistant GISTs as they interfere with KIT and PDGFRA receptors or with the downstream-signalling proteins. Sunitinib was approved for the treatment of imatinib-resistant GIST or imatinib intolerant patients. Other candidate tyrosine kinase inhibitors are being tested, including Nilotinib, Dasatinib, Sorafenib, Masitinib, Vatalanib and Motesanib.