胃肠道间质瘤概念课件

胃肠道间质瘤概念,胃肠道间质瘤（Gastrointestinal Stromal Tumors, GIST）是一类起源于胃肠道间叶组织的肿瘤，占消化道间叶肿瘤的大部分。Mazur 等于1983 年首次提出了胃肠道间质肿瘤这个概念。,发病率及发病部位,Gastrointestinal stromal tumours (GISTs) represent 0.1-3% of gastrointestinal malignancies and 80% of gastrointestinal mesenchymal tumours The prevalence of the disease is estimated at 11 to 20 cases per million of population 1、2、3.,Sixty percent of GISTs present in the stomach, 30% in the small intestine, 5% in the colon and rectum and 5% in the oesophagus About 140 new cases are recognized in Greece every year; the mean age of diagnosis is 60 years and the male to female ratio approximately 1.4:1 4.,GIST的症状、体征,The delayed diagnosis of stromal tumours, due to the lack of specific symptoms, results in 25% of patients presenting with metastatic disease. It often takes up to 6 months from the onset of initial symptoms to reach a diagnosis 5.,The most frequent manifestations of the disease include gastrointestinal haemorrhage, fatigue due to chronic anaemia, loss of appetite, weight loss, vom-iting, the presence of a palpable mass, and non-spe-cific abdominal pain. These symptoms appear due to displacement, rather than infiltration of nearby structures. A combination of symptoms is present in over 5% of patients 6、7,病理诊断基因诊断,The kit protein is expressed in 90-95% of GISTs. This protein represents a transmembrane receptor that acts like a tyrosine kinase. In 5-10% of GISTs, mutations in Platelet-Derived Growth Factor Recep-tor (PDGFR and PDHFR) are present that are mutually exclusive to the KIT mutations, while some GISTs have no detectable mutations in either receptor (wild-type GISTs) 8,9.,The expression ofCD34 is more frequent in gastric GISTs (85%), while it is positive in only 50% of GISTs that arise from the small intestine 10. CD34 is universally expressed in oesophageal GISTs. Another recently recognized marker is cyclooxygenase 2 (COX-2) At least 80% of GISTs express this protein 11,病理图示,The majority of stromal tumours (70%) consist of spindle cells, 20% are made up of epithelioid cells and the rest present with mixed morphology,CT and EUS,Computed tomography (CT) and endoscopic ultrasound (EUS) have contributed significantly to the diagnosis of GISTs. Computed tomography repre-sents the best imaging modality for tumours 5 cm, while EUS is most useful in identifying tumours 2 cm that are difficult to appreciate in gastroscopy or colonoscopy due to the normal appearance of the mucosa 12,GIST的治疗,Population studies from USA and Sweden, even before the imatinib era, reported a 50-60% rate of patients with localized disease at the time of diag-nosis and more than 95% R0 excision of the tumour 13、14.,GISTs have certain attributes that define the surgical management. First of all, GISTs metastasize to the liver and the peritoneal surfaces; however, the regional lymph nodes are spared. Furthermore, the stromal tumours expand extramurally.,Also, GISTs tend to displace rather than infiltrate adjacent structures. Finally, GISTs are fragile tumours, and if they rupture during their manipulation, there is an increased risk of peritoneal seeding. It should also be noted that an intra-peritoneal rupture of GISTs is of the same prognostic significance as a non-R0 excision of the tumour 15.,those patients with metastatic or relapse of the disease, neoadjuvant therapy is often a prerequisite for an attempted R0 excision. As a matter of fact, these patients in the preimatinib era demonstrated a mean survival of 12 months 16.,药物治疗,Imatinib is a pow-erful inhibitor of the tyrosine kinase. Its results are impressive, with reports of disease control in 70-85%of patients with advanced disease (mean survival 36 months, mean survival without progress of the dis-ease 24 months) 17.,A total response was recorded in 4-5% of these patients and a reduction in the size of the tumour 50% in 47-67% of these patients af-ter 9 to 13 months of follow-up 52,53. Stromal tumours respond to classic chemotherapeutic agents in only 5% of the patients 18.,GIST的预后,The prognosis of a patient with a stromal tumour is dependant on the size of the tumour as well as its number of mitoses. Tumours 10 cm in size with 5 mitoses per high-powered field (HPF) tend to recur, metastasize more frequently and are related with poor results. These characteristics are observed in 20-30% of patients with GISTs. Other prognostic factors include the location of the tumour, the R0 excision of the tumour and the mutations of the c-kit gene 19.,Other prognostic factors include the location of the tumour, the R0 excision of the tumour and the mutations of the c-kit gene 20.,文章内容出处,1. Burkill GJ, Badran M, Al-Muderis O, Meirion Thomas J, Jud- son IR, Fischer C, Moskovic EC. Malignant gastrointestinal stromal tumor: distribution, imaging features, and pattern of metastatic spread. Radiology 2003; 226: 527-532 2. Duffaud F, Blay JY. Gastrointestinal stromal tumors: biology and treatment. Oncology 2003; 65: 187-197 3. DeMatteo RP, Lewis JJ, Leung D, Mudan SS, Woodruff JM, Brennan MF. Two hundred gastrointestinal stromal tumors. Re- currence patterns and prognostic factors for survival. Ann Surg 2000; 231: 51-58 4. Goettsch WG, Bos SD, Breekveldt Postma N, Casparie M, Her- ings RM, Hogendoorn PC. Incidence of gastrointestinal stromal tumors is underestimated: results of a nation-wide study. Eur J Cancer 2005; 41: 2868-2872 5. Kosmadakis N, Visvardis EE, Kartsaklis P, Tsimara M, et al. The role of surgery in the management of gastrointestinal stromal tumors (GISTs) in the era of imatinib mesylate effectiveness. Surg Oncol 2005; 14: 75-84,6. Nishida T, Hirota S. Biological and clinical review of stromal tumors in the gastrointestinal tract. Histology and Histopathology 2000; 15: 1293-1301 7. Robson ME, Glogowski E, Sommer G, Antonescu CR, Nafa K, et al. Pleomorphic characteristics of a germ-like KIT mutation in a large kindred with gastrointestinal stromal tumors, hyperpigmentation, and dysphagia. Clinical Cancer Res 2004; 10: 1250-1254 8. Hirota S, Nishida T, Isozaki K, et al. Gain-offunction mutation at the extracellular domain of KIT in gastrointestinal stromal tu-mors. J Pathol 2001; 193: 50510 9. Heinrich MC, Corless CL, Duensing A, et al. PDGFRA activating mutations in gastrointestinal stromal tumors. Science 2003; 299: 708-710,10. Rudolph P, Chiaravalli AM, PauserU, et al. Gastrointestinal mesenchymal tumors-immunophenotypic classification and survival analysis. Virchows Arch 2002; 441: 238-248 11. Stewart AE, Heslin MH, Arch J, et al. Cyclooxygenase-2 expression and clinical outcome in gastrointestinal stromal tumors. J Gastrointest Surg 2006; 10: 315-319 12. Kochhar R, Manoharan P, Leahy M, Taylor MB. Imaging in gastrointestinal stromal tumors: current status and future directions. Clin Radiol 2010; 65: 584-592 13. Tran T, Davila JA, El-Serag HB. The epidemiology of malignant gastrointestinal stromal tumors: an analysis of 1458 cases from 1992 to 2000. Am J Gastroenterol 2005; 100: 162-168 14. Nilsson B, Bumming P, Meis-Kindblom JM, Oden A, Dortok A, Gustavsson B et al. Gastrointestinal stromal tumors: the incidence, prevalence, clinical course and prognostication in the preimatinib mesylate era. Cancer 2005; 103: 821-829,15. DeMatteo RP, Lewis JJ, Leung D