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>

Value of preoperative barium contrast examination for the diagnosis and operative planning in gastric cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the value of preoperative barium contrast examination for the diagnosis and operative planning in gastric cancer.</p><p><b>METHODS</b>Clinical data of 229 gastric cancer patients were analyzed retrospectively. Lesions were divided into three parts: the cardiac, the body, and the antrum. The diagnostic accuracy of localization and the extent of tumor between gastroscopy alone and gastroscopy plus barium contrast were compared with the results of surgical findings.</p><p><b>RESULTS</b>The diagnostic accuracy of localization and the extent of tumor for gastroscopy in the cardiac, the body and the antrum cancers were 100% and 78.4%, 94.6% and 86.5%, 98.1% and 84.6%, respectively, while for gastroscopy plus barium contrast were 100% and 84.8%, 100% and 91.9%, 99.0% and 90.4%, respectively. The diagnostic accuracy of both the localization and the extent of tumor were not significantly different between gastroscopy alone and gastroscopy plus barium contrast (P>0.05). Diagnostic accuracy of the length of esophagus infiltrated by cardiac cancer in gastroscopy was 60.6%, while in gastroscopy plus barium contrast was 90.9%, which was significantly different (P<0.05). Gastroscopy plus barium contrast was more accurate in predicting the possibility of thoracotomy in cardiac cancer infiltrating the lower esophagus.</p><p><b>CONCLUSIONS</b>It is necessary to perform preoperative barium contrast examination in cardiac cancer patients, so as to identify whether the lower esophagus is infiltrated and to measure the length of lesion, which can provide evidences for making a decision of thoracotomy. For gastric body and antrum cancer, there is no indication for barium contrast examination if gastroscopy findings are satisfied.</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>

Status and clinical analysis of c-kit and PDGFRA mutations in the gastrointestinal stromal tumors / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the status of c-kit and PDGFRA mutations in the gastrointestinal stromal tumors (GIST) and explore the relationship between the mutations and the clinical features.</p><p><b>METHODS</b>One hundred and forty-one cases were evaluated for the presence of c-kit and PDGFRA mutations. Exon 9,11,13, 17 of c-kit and exon 12, 18 of PDGFRA were analyzed by PCR amplification and direct sequencing. The relations of clinical features and mutational status were analyzed with statistical tools in this study.</p><p><b>RESULTS</b>Among the 141 GISTs, c-kit mutations were identified in 76.6% (108/141): 70.2% (99/141) involving exon 11, 5.7% (8/141) involving exon 9, 0.7% (1/141) involving exon 13 and no mutation detected in exon 17. The gene mutations were mostly heterogeneous. The c-kit exon 11 mutational format included deletion (65.7%), point mutation (24.2%) and insert duplications(10.1%).The mutations clustered in the classic "hot spot" at the 5' end of the exon mostly heterogeneous and the second "hot spot" were internal tandem duplications (ITD) at the 3' end of the exon. PDGFRA mutations were totally identified in 12.1%(4/33) of no-c-kit-mutation GISTs and 40%(4/10) of CD117-negative GISTs: all involving exon 18 with the mutations D842V. With the analysis between clinical features and mutation status, the significant difference of gene mutation rate in the different primary tumor organs (chi(2)=7.229, P=0.027, chi(2)=7.000,P=0.03) and no significant differences between the groups of age,gender,tumor size,mitotic rate,grade of malignant potential were found.</p><p><b>CONCLUSION</b>Most GISTs have the c-kit or PDGFRA gene mutation. There are significant difference between mutation and primary tumor organ.</p>

Epidemiological study on an outbreak caused by E. coli O157:H7 in Jiangsu province / 中华流行病学杂志

<p><b>OBJECTIVE</b>To carry out epidemiological study on an outbreak caused by E. coli O157:H7 infection in Jiangsu province in 1999.</p><p><b>METHODS</b>Epidemiological, microbiological and moleculebiological methods were used to find out the source, route of transmission and risk factors.</p><p><b>RESULTS</b>95 severe O157:H7 infected patients with acute renal failure in 9 counties and districts of 2 municipalities were reported in Jiangsu province, 1999 while 83 of the patients died with a death rate of 87.37%. Most patients were seen in mid or late June. The ratio of male to female was 1 to 1.44 and 88.42% of the patients were over 50 years old. 38 patients occurred in 2000 with 34 deaths. Major factors contributing to the outbreak would include without drinking tap water, eating leftover food, poor sanitary status in kitchen, not washing hands before meal and after bowl movement. 2 strain of O157:H7 was isolated from severe patients and 3 from diarrhea cases. Carrier rate among animals was up to 9.62% and 99.41% of the strains carried toxic gene. Strains isolated from feces of patients and animals belonged to the same colonies.</p><p><b>CONCLUSION</b>This outbreak was severe which caused by O157:H7 and was first seen in China, which was closely related to the high carrier rate of O157:H7 in animals and to the positive rate of high toxic gene of the strains. There were various routes of transmission and the main factors of infection would include poor personal health habits and poor sanitation of the household.</p>