Prognostic analysis of patients with gastrointestinal stromal tumors: a single unit experience with surgical treatment of primary disease / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Gastrointestinal stromal tumor (GIST), the most common type of mesenchymal tumors of the gastrointestinal tract, is a recently recognized tumor. The biological behavior of GIST is highly variable. Surgical resection remains the major treatment for GIST. In this study we retrospectively analyzed our surgical experience with 181 GIST patients to determine the effects of the treatment and the pathological features and prognosis factors of these GIST patients.</p><p><b>METHODS</b>The clinicopathological features and follow-up data of the 181 patients with GIST who had received surgical resection between January 1999 and December 2007 at Ren Ji Hospital were retrospectively reviewed. Immunohistochemical stains including CD117 (KIT), CD34, and other markers were used. Tumor size, mitotic index and other pathological parameters were recorded. According to the consensus of NIH risk-group stratification system based on maximum tumor size and mitotic index (per 50 high power field), tumors were classified into very-low-risk group (15 tumors, 8.3%), low-risk group (48, 26.5%), intermediate-risk group (52, 28.7%) and high-risk group (66, 36.5%). Prognostic factors were analyzed by Cox analysis including age, sex, tumor size, tumor site, mitotic index, NIH categories and surgical procedures.</p><p><b>RESULTS</b>One hundred and seven (59.1%) of the 181 tumors were located in the stomach, 51 (28.2%) in the small intestine, 9 (5.0%) in the colon and rectum, and 14 (7.7%) in other sites including the omentum and mesentery. The median age of the patients was 58 (range, 24-84) years, and 102 patients (56.4%) were male. Tumor size ranged from 0.5 to 30 cm, while the mean size was 7.02 cm. Metastasis was found in 7 patients. One hundred and seventy-six (97.2%) of the 181 patients underwent radical resection, and among them 26 patients received extensive resection with the adjacent organ adherent to the tumors. The positive rate for the KIT protein (CD117) in immunostaining was 94.5% (171/181), while that for CD34 was 86.2% (156/181). The 1-, 3-, and 5-year survival rates of the 181 patients were estimated to be 95.2%, 87.9% and 78.5%, respectively. There was a significant difference in age, tumor size, tumor site, mitotic index, NIH categories, and presence or absence of multivisceral resection (P<0.05). But there was no significant difference in sex between the groups. Cox hazard proportional model revealed that advanced clinical stage and large tumor size contributed to worse prognosis. The patients who were treated with imatinib because of recurrence and metastasis or high recurrence risk showed stable disease.</p><p><b>CONCLUSIONS</b>Surgical resection is the gold standard of treatment for primary GIST. NIH categorization is simple and effective to evaluate GIST behavior and prognosis. Targeted therapy such as imatinib, a KIT tyrosine kinase inhibitor, may play an important role in the treatment of GIST.</p>

Study of loss of heterozygosity at 9p21 and P16 expression in gastrointestinal stromal tumors / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To evaluate the impact of loss of heterozygosity (LOH) at chromosome 9p21 and P16(INK4A)(CDKN2A) expression on the prognosis of gastrointestinal stromal tumor (GIST).</p><p><b>METHODS</b>A total of 51 cases with GISTs were characterized by immunohistochemistry and evaluated for LOH at 9p21 by microsatellite analysis in 4 markers(D9S1751, D9S1846, D9S942 and D9S1748). Associations of LOH at 9p21 and P16(INK4A) expression encoded by CDKN2A with clinicopathological parameters and prognosis in GISTs were analyzed.</p><p><b>RESULTS</b>The frequency of 9p21 LOH was 37.0% (10/27) at D9S1751, 37.5%(12/32) at D9S1846, 42.1%(16/38) at D9S942 and 24.2%(8/33) at D9S1748. The overall frequency of LOH at 9p21 was 63.3%(31/49). In 21 samples of 51 GISTs(41.2%), P16 expression was not detected. Loss of P16 expression was 60%(12/20) in high risk group and 23.5%(4/17) in very low and low risk groups(P<0.05). The 5-year overall survival rate of p16-negative patients was 70.8%, while in P16-positive patients it was 92.0%(P<0.05).</p><p><b>CONCLUSIONS</b>LOH at 9p21 is a frequent event in GIST. Loss of CDKN2A gene at 9p21 may contribute to the progression and malignant transformation of GIST. P16 expression in GIST is associated with prognosis.</p>

Analysis of clinicopathology and prognosis in 181 patients with gastrointestinal stromal tumors / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the therapeutic experience of gastrointestinal stromal tumors (GIST) and to analyze the pathological features and prognostic factors of GIST.</p><p><b>METHODS</b>The clinicopathological and follow-up data of 181 patients with GIST admitted in Renji Hospital between January 1999 and December 2007 were analyzed retrospectively. All the cases were grouped according to Fletcher's risk scheme. Life table and COX regression model were used to evaluate the prognostic factors.</p><p><b>RESULTS</b>Out of 181 tumors, 107(59.1%) were located in stomach, 51 (28.2%) in intestine and 23(12.7%) in colorectum or other sites. Distant metastases,including liver metastases were found in 7 patients intraoperatively. Tumor size ranged from 0.5 to 30 cm with the mean of 7.02 cm. The positive rate of CD117 was 94.5% (171/181) and that of CD34 was 86.2% (156/181). One hundred and seventy-six patients underwent complete resections, including multi-organ resections in 26 patients. The other patients underwent palliative operations. The 1-, 3- and 5-year overall survival rates of 181 patients were 95.2%, 87.9% and 78.5% respectively. Univariate analysis revealed age, tumor size, primary organ of tumor, mitotic count, Fletcher's classification and multi-organ resection were associated with survival rate. No significant difference of sex was existed among groups. COX hazard proportional model revealed that advanced stage and large tumor size indicated worse prognosis. Eight patients with high risk of recurrence and 3 patients with recurrence and metastasis were stable after receiving imatinib therapy.</p><p><b>CONCLUSIONS</b>The diagnosis of GIST depends on endoscope and CT. Fletcher's classification is simple and effective to evaluate GIST behavior and prognosis. Surgical resection is still the main therapy for GIST and targeted therapy will play a more important role for prognosis in the future.</p>

A clinicopathological study on 107 cases with gastrointestinal stromal tumors / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the clinical pathological characteristics and prognosis of gastrointestinal stromal tumors (GISTs).</p><p><b>METHODS</b>One hundred and seven cases, admitted to our hospital from Apr. 1996 to Oct. 2005, were detected by Envision immunohistochemical method and diagnosed as GISTs. Their pathological features, immunohistochemical phenotypes, clinical manifestations and imaging findings were analyzed.</p><p><b>RESULTS</b>Of the 107 GISTs, 107 cases were positive for vimentin (107/107, 100%), 107 cases were positive for CD117 (107/107, 100%), 89 cases were positive for CD34 (89/107, 83.2%), 14 cases were positive for SMA (14/107, 13.1%), 10 cases were positive for desmin (10/107, 9.3%), 22 cases were positive for S-100 (22/87, 20.6%) and 15 cases were positive for NSE (15/107, 14.0%). Among all the GISTs, 73 cases occurred in stomach (68.2%), 28 in small intestine (26.2%), 1 in colon (0.9%) and 5 occurred in other position including mesentery, omentum, and retroperitoneum (4.7%). Fifteen cases were diagnosed as very low grade (14.0%), 25 cases as low grade (23.4%), 33 cases as low malignancy (30.8%) and 34 cases as high malignancy (31.8%). The follow-up was obtained successfully in 89 cases (83.2%). Fourteen cases (13.1%) were confirmed to have recurrences or metastases by review and medical records.</p><p><b>CONCLUSIONS</b>The diagnosis of GIST depends on pathological observation and immunohistochemical study. CD117 is a sensitive marker for the diagnosis of GIST. Surgical resection is the choice for treating GIST. Extended resection, even combined resection of involved organs, is required for malignant GIST.</p>

Clinicopathological analysis of 34 cases of primary small intestine lymphoma / 上海第二医科大学学报

Objective To analyse the clinicopathological features of primary small intestine lymphoma(PSIL), and explore the relationship between clinical stage,histological findings,therapeutic modality and prognosis. Methods The clinical data of 34 cases of PSIL were collected,the pathohistological features and results of immunohistochemical examinations were obtained,and the follow-up findings were adopted for comprehensive analysis. Results Among these 34 cases of PSIL,abdominal pain or discomfort,gastrointestinal bleeding and abdominal mass were the predominant symptoms.PSIL mainly involved ileum,especially the bottom of ileum and ileocecal area.Among the 26 patients with follow-up for more than one year,the 1-year survival rate was significantly higher in patients without tumor perforation than those with tumor perforation(76.2% vs 20.0%)(P

Regulatory effects of tuberculin on growth and apoptosis of liver cancer and lung cancer cell lines / 上海第二医科大学学报

Objective To investigate the regulatory effects of tuberculin on growth and apoptosis of liver cancer and lung cancer cell lines. Methods HePG2(liver cancer) and A549(lung cancer) cell lines were treated with TB supernatant(TB-SN) with different concentrations. Cell viability was detected by using LIVE/DEAD Viability/Cytotoxicity cell kits including specific fluorescence primer,and cell apoptosis was detected by Vybrant apoptosis assay. Results After treatment with 5% TB-SN for 5 d,cell apoptosis was significantly increased in HePG2 and A549 cell lines.Cell growth of HePG2 and A549 cell lines was inhibited after treatment with TB-SN. Conclusion Tuberculin can induce cell apoptosis and inhibit cell growth of liver cancer and lung cancer cell lines.

Analysis of 4 cases of sclerosing angiomatoid nodular transformation of spleen / 上海第二医科大学学报

Objective To investigate the clinicopathologic features,diagnosis,differential diagnosis and treatment of sclerosing angiomatoid nodular transformation(SANT). Methods The clinical data,pathologic characteristics,immunophenotype and postoperative follow-up of SANT were analysed. Results There were no specific findings in the clinical manifestations of the 4 cases of SANT.Grossly,the cut surface of the masses was gray-white and vague nodularity was observed.Microscopically,it was characterized by the multinodular angiomatoid appearance in a fibrosclerotic stroma.The nodules were composed of slit-like,sinusoid-like vascular spaces and were interspersed with a population of spindly or ovoid cells.It was revealed by immunohistochemistry that the expression of CD34 in some vessels' endothelial cells was positive,and CD8 was negative.While in another vessels' endothelial cells,CD8 was positive and CD34 was negative.The expression of SMA,Actin,Vimentin,Collage IV and CD68 was positive in all of the 4 cases,while that of CD21,Desmin and NSE was negative.No relapse or metastasis was found during the follow-up.Conclusion SANT is a rarely encountered benign lesion of the spleen,which should be distinguished from the malignant tumor of the spleen.The diagnosis counts on the pathologic and immunohistochemical findings.It could be cured by splenectomy with a favourable prognosis.

Expressions of NOS and NOS mRNA in the Lung of Rats with Hepatopulmonary Syndrome / 上海第二医科大学学报

Objective To investigate the expressions of nitric oxide synthase (NOS) protein and mRNA in the lung of rats with hepatopulmonary syndrome. Methods Male Sprague-Dawley rats were divided into four groups: sham operation (SO), intrahepatic portal hypertension (IHPH), prehepatic portal hypertension (PHPH) and portasymstimic shunt (PCS). Two weeks after preparation of rat models, the following measurements were performed: arterial blood gas analysis; the concentrations of NO in lungs; in situ hybridization of ecNOS and iNOS mRNA expressions in lung tissue sections with digoxin-labeled ecNOS and iNOS oligonucleotide probes; expressions of ecNOS and iNOS proteins by immunohistochemisty; image and semiquantitative analysis of the expressions of ecNOS, iNOS and their mRNA. Results PaO_ 2 was (73.85?6.51) mmHg in IHPH rats, significantly lower than that in PHPH, PCS and SO rats97.39? 1.33, 95.23?2.22 and (99.05?0.75)mmHg, respectively.The level of lung NO of IHPH was(19.78?5.33)?mol per gram of protein,much higher than that of PHPH, PCS and SO 13.21?3.99,13.89?3.16 and (8.71?1.68)?mol per gram of protein,respectively. In capillary endothelia, positive expressions of ecNOS mRNA and ecNOS protein in IHPH(4.96?0.82,4.11?0.28) were significantly higher than those of PHPH (1.81? 0.39, 1.63?0.18), PCS (1.88?0.53,1.83?0.16)and SO(1.19?0.32,0.98?0.20). Conclusion The expressions of NOS protein and mRNA in the lung of rats with hepatopulmonary syndrome were increased, and the level of lung NO was elevated, which seems to play an important role in the pathogenesis of hepatopulmonary syndrome.

Analysis of Comparative Genomic Hybridization in Pleomorphic Xanthoastrocytoma / 上海第二医科大学学报

Objective To detect genetic alterations in pleomorphic xanthoastrocytoma (PXA), and to investigate the mechanism of development of this neoplasm. Methods Three patients with PXA were studied. Comparative genomic hybridization (CGH) was performed to study chromosomal imbalances in PXA. Using immunohistochemical analysis, the expression of EGFR was detected in PXA. Results Using CGH analysis, genetic imbalance was detected on at least one chromosome for each case. One patient revealed multiple genetic alterations, including gains of 2p14-pter, 4p15-pter, 7p21-qter, 11q24-qter, 12 and 15q14-qter,as well as losses of 8p11.2-pter, 9p11-p23, 10p12-pter, and 13q14-qter. This patient experienced tumor recurrence and died one year later. Gain on Chromosome 7 and loss on Chromosome 8p were demonstrated in 2 of the 3 patients. Immunohistochemically, no EGFR positive reaction was found in all cases. Conclusion Detection of genetic alterations is very important in understanding the pathogenesis of PXA.