Oncogenic signaling mechanisms in imatinib-resistant gastrointestinal stromal tumor / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To characterize oncogenic KIT signaling mechanisms in gastrointestinal stromal tumor(GIST), and to determine which signaling pathway might be of potential relevance to imatinib acquired resistance.</p><p><b>METHODS</b>The mutations of KIT and PDGFRa gene were evaluated and KIT downstream signaling profiles were evaluated in 8 specimen from 5 GIST patients who were evaluated treated between 2003 and 2008 in our hospital. Biochemical inhibition of the expression of related proteins in Ras/Raf/MAPK and PI3-K/AKT pathways, such as KIT, mitogen-activated protein kinase(MAPK),mammalian target of rapamycin(MTOR), AKT, Proliferating cell nuclear antigen (PCNA) and BCL-2, were determined by Western blotting for protein activation.</p><p><b>RESULTS</b>Three cases who showed response to imatinib carried primary mutations in KIT gene, with 2 cases possessing mutation in exon 11, 1 case in exon 13. One case with imatinib-resistance developed KIT secondary mutation, but all the cases had no PDGFRa mutation. p-KIT and p-AKT expressions were higher in the samples of imatinib-resistant GIST than those of imatinib-responsive GIST. Total KIT, MAPK, p-MAPK, p-MTOR expressions were strong and comparable in all varied GISTs, which had no significant difference between imatinib-resistant and imatinib-responsive samples. PCNA and BCL-2 expression varied in samples of different therapy cycles and different location.</p><p><b>CONCLUSIONS</b>Ras/Raf/MAPK and PI3-K/AKT/MTOR pathways are essential to GIST pathogenesis. The KIT secondary mutation and PI3-K/AKT/MTOR pathway are particularly relevant for therapeutic targeting in imatinib-resistant GIST.</p>

Clinicopathological and prognostic analysis of 23 poorly differentiated neuroendocrine carcinomas of the stomach / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To evaluate the clinicopathological characteristics and prognosis of poorly differentiated neuroendocrine carcinoma of the stomach.</p><p><b>METHODS</b>Twenty-three poorly differentiated neuroendocrine carcinomas of the stomach were treated in the Department of Abdominal Surgery at the Cancer Hospital, Fudan University between January 1996 and December 2007. Clinicopathological characteristics and survival data were analyzed.</p><p><b>RESULTS</b>Poorly differentiated neuroendocrine carcinomas of the stomach accounted for 0.52% of all the gastric carcinomas. The tumor occurred more often in males (18 of 23), older patients (mean age of 62 years), upper third of the stomach (16 of 24,one patient had more than one lesion) with large size (mean diameter of 6.8 cm). TNM stages were as follows: stage II in 3 patients, stage III in 12, and stage IIII in 8. Thirteen patients underwent curative resection, while 8 underwent palliative resection and 2 others underwent exploratory laparotomy with biopsy. Of the 21 surgical resection specimens, vascular invasion was found in 18 patients (85.7%), perineural invasion in 16 patients (76.2%), and regional lymph node metastasis in 17 patients (81.0%). Follow up time ranged from 3 to 63 months. Mean overall survival time was 17.7 months. The 1-year, 2-year, and 5-year survival rates were 47.8%, 19.1%, and 4.3%, respectively. Statistically significant differences in survival curves were observed which were related to tumor staging and surgery type, but not related to gender, age, tumor location, or diameter.</p><p><b>CONCLUSIONS</b>Poorly differentiated neuroendocrine carcinomas of the stomach are rare and with poor prognosis. Tumor stage and surgical type have potential impact on survival.</p>

Synchronous or metachronous primary cancers of other organs in 74 patients with gastric cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To study the incidence, clinicopathological characteristics, diagnosis, treatment, and prognosis of synchronous or metachronous primary cancers in patients with gastric cancer.</p><p><b>METHODS</b>Clinical data of 4426 patients with gastric cancer in our hospital from 1996 to 2007 were reviewed.</p><p><b>RESULTS</b>Seventy-four (1.7%) patients had synchronous or metachronous primary cancer of other organ, of whom 10 were synchronous and 64 were metachronous. Colorectal cancer was the most common type of primary cancer in other organs (43.8%), followed by breast cancer (16.3%). The mean time interval between gastric cancer and metachronous primary cancer was 82.2 (3-354) months. The mean age at the diagnosis of gastric cancer was 61.2 (33-84) years. The 5-year overall survival rate was 42.3%. The 5-year survival rates in patients with synchronous cancer, pre-metachronous cancer or post-metachronous cancer were 15.2%, 42.9% and 51.3%, respectively. Causes of death were primary cancers of other organ in 11 patients, gastric cancer in 24, and renal failure in 1 patient.</p><p><b>CONCLUSIONS</b>Primary cancer of other organ should be considered in the management of gastric cancer. Aggressive treatment should be used for the second primary cancer. Gastric cancer is the main cause of death in these patients.</p>

Surgical treatment for patients with advanced gastrointestinal stromal tumor after targeted therapy / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To explore the role of surgery and its long-term outcome in patients with advanced gastrointestinal stromal tumor(GIST) treated with imatinib preoperatively.</p><p><b>METHODS</b>Thirteen patients receiving imatinib therapy preoperatively, were retrospectively assessed for completeness of surgical resection and for disease-free and overall survival after resection.</p><p><b>RESULTS</b>Thirteen patients, including 3 patients with locally advanced primary GIST and 10 patients with recurrent or metastatic GIST, underwent surgery after preoperative treatment with imatinib. Complete resections were accomplished in 4 of the 5 responsive disease(RD) patients, and in 1 of the 8 progression disease(PD) patients (38.5%). The progression-free survival(PFS) time for patients with RD and PD were 24.8 months and 2.8 months respectively. The difference of PFS between patients with RD and those with PD was significant(P<0.01). Median overall survival(OS) was not reached in both patients with RD and PD. The difference of OS between patients with RD and those with PD was not significant(P>0.05).</p><p><b>CONCLUSION</b>Surgical intervention following imatinib is feasible and can be considered for patients with advanced GIST responsive to imatinib.</p>