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Abstract
Gastrointestinal stromal tumours(GISTs)represent the most common mesenchymal neoplasms of the GIT. With an annual incidence of 11-14 per 106, they form 0.1%-3.0% of gastrointestinal malignant tumors (Kim et al., 2005).
GIST occurring in the familial form is autosomal dominant.(Goettschet al., 2005). Stromal tumors were referred to as smooth muscle neoplasms of GIT but immunohistochemistry (IHC) demostrated that these tumors lacked features of smooth muscle differentiation and, while some had markers of neuronal differentiation, some had neither.(Joensuu et al., 2006).
Only 70% of the patients with GIST are symptomatic, while 20% are asymptomatic and the tumors are detected incidentally, 10% of the lesions are detected only at autopsy. Symptoms and signs are not disease specific, they are related more to the site of the tumor. Bleeding (30%-40%) comprises the most common symptom after vague abdominal discomfort (60%-70%). Bleeding is attributed to the erosion into the GIT lumen. Bleeding occurring into the peritoneal cavity due to a ruptured GIST can lead to acute abdominal pain presenting as a surgical emergency. Bleeding into the GI tract lumen, causing hematemesis, melena or anemia, is usually more chronic on presentation. Most of the patients present with vague symptoms, such as nausea, vomiting,
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abdominal discomfort, weight loss or early satiety. Symptoms are usually site specific, these include dysphagia in the esophagus, biliary obstruction around The ampulla of Vater or even intussusception of the small bowel (Goettsch et al., 2005).
GIST usually has an exophytic growth and the common intra-operative appearance is that of a mass attached to the stomach, projecting into the abdominal cavity and displacing other organs. Mucosal ulceration may be present at the summit of the lesion in 50% of cases. On gross appearance they are smooth gray and white tumors which are well circumscribed, usually with a pseudocapsule. A small area of hemorrhage or cystic degeneration and necrosis may be visible (Beham et al., 2012).
Due to the vague presentation of GIST, initial diagnosis can be delayed. Imaging in the form of contrast enhanced computed tomography (CECT) is the modality of choice; it is used to characterize the lesion, evaluate its extent, and assess the presence or absence of metastasis at the initial staging workup. CECT is also used for monitoring response to therapy and performing follow-up surveillance of recurrence (Stamatakos et al., 2009).
Endoscopic ultrasound (EUS) has been used in the diagnosis of GIST; it assesses the depth of invasion and is useful in obtaining a tissue sample. Preoperative
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percutaneous biopsy should not be used because of a significant risk of tumor rupture or dissemination (Fletcheret al., 2002).
The efficacy of EUS guided fine needle aspiration (EUS-FNA) has been pointed out in several studies and the reported accuracy is 80%-85%. A clear role for EUS guided Trucut biopsy has yet to be defined, given the inconsistent results in providing adequate tissue yield. However, at present, EUS-FNA should be considered the procedure of choice to secure a tissue diagnosis of GIST (Stamatakos et al., 2009).
EUS features of a high grade GIST include irregular extra-luminal borders, heterogeneous echo patterns, presence of cystic spaces and echogenic foci (Shah et al., 2009).
EUS-FNA biopsy of the primary site is preferred over percutaneous biopsy as it reduces the risk of tumor hemorrhage and intra-abdominal tumor dissemination (Sepe et al., 2009).
Tumors which are less than 2 cm in the widest dimension are defined as small GIST. They are usually discovered incidentally on endoscopy. If these lesions are symptomatic, complete surgical resection is recommended.
Small asymptomatic gastric GISTs (less than 2 cm) with no high-risk EUS features can be managed
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conservatively with endoscopic surveillance at 6 to 12 month intervals (Demetri et al.,2010).
Surgery is the primary treatment of choice in localized or potentially resectable GIST. It is imperative to avoid tumor rupture. The tumors are fragile and should be handled with care, with an aim to achieve complete gross resection of the tumor with an intact pseudocapsule.
Lymphadenectomy is not required as GISTs have a low incidence of nodal metastases (Demetri et al.,2010)
Although prospective trials are lacking, small series and retrospective analyses have shown low recurrence rates, shorter hospital stay and low morbidity with a laparoscopic approach. It has been recommended for selected GISTs present in favorable anatomic locations like the anterior wall of the stomach, jejunum and ileum. The same surgical principles as open surgery are applicable in laparoscopic surgery for GIST (Demetri et al.; 2010). Endoscopic resection of small GISTs is more controversial due to the risks of positive margins, tumor spillage and intact specimen retrieval (Demetri et al.,2010).
Surgery is the primary treatment for all tumors which can be resected without significant morbidity. If this is not the case, then preoperative imatinib should be considered. Imatinib mesylate is a tyrosine kinase inhibitor its structure mimics adenosine triphosphate (ATP) and it binds
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competitively to the ATP binding site of the target kinases. This prevents substrate phosphorylation and signaling, thereby inhibiting proliferation and survival (Stamatakos et al., 2009).
Imatinib is effective in reducing the size of the tumor prior to resection, increasing the likelihood of negative margins without significant morbidity. Before starting a patient on neoadjuvant imatinib, a baseline CECT is recommended. The optimal duration of pre-operative therapy is yet unknown. In patients responding to therapy, imatinib is continued until maximal response (defined as no further improvement between 2 successive CT scans). This can be as long as 6-12 months but it is not always necessary to wait for a maximal response prior to surgery. Surgery is recommended when the tumor appears to have downsized to a point where complete resection can be achieved without significant morbidity. Imatinib should be stopped just before surgery and resumed as soon as the patient is able to tolerate oral medications, regardless of the surgical margins. The recommended dose is 400 mg/d, with dose escalation to 800 mg/d advised in cases of documented mutations in KIT exon 9 (Wang et al., 2012).
In patients who have not received preoperative imatinib and have undergone complete resection, imatinib has been found to be beneficial if continued for 36 months,
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especially in patients with an intermediate or high risk of recurrence (Demetri et al.,2010).
Imatinib has a very high likelihood of clinical benefit and a positive response in patients with documented unresectable GIST. Imatinib is indicated when primary resection would carry the risk of severe postoperative functional deficit (Dematteo et al., 2009).
There is a survival benefit of cytoreductive surgery following preoperative imatinib in patients responding to preoperative imatinib (Mussi et al., 2010)