Surgical treatment of patients with gastric carcinoma and duodenal invasion

We retrospectively examined the extent of invasion of gastric cancer with duodenal involvement in order to design pertinent surgical procedures that may lead to a better prognosis. Examinations were made on excised tissues from 650 patients who underwent gastrectomy for adenocarcinoma in the gastric antrum. In 95 patients, the cancer cells extended to beyond the pyloric ring. Spread into the duodenum was limited to within 2 cm in 76% of the patients and to within 3 cm in 81%. In addition to high rates of metastasis in group 1 and 2 lymph nodes, some group 3 lymph nodes also were involved, and more frequently so in cases with duodenal invasion than in those without such invasion (P < 0.01). The 5-year survival rate for patients with duodenal invasion was 35.4% when a curative resection was done. For patients with advanced adenocarcinoma with duodenal invasion, gastrectomy with resection of 3–4 cm of the duodenum and dissection of group 1, 2, and 3 lymph nodes were recommended.     

Increased expression of cyclooxygenase-2 protein in human gastric carcinoma.

Gastric adenocarcinoma is one of the most common malignancies in the world, and yet little is known about its molecular process of development and progression. Recent studies have suggested that ingestion of nonsteroid anti-inflammatory drugs reduces the risk of colon cancer, presumably by inhibiting the cyclooxygenase (COX) enzyme. COX-2, one isoform of the COX enzyme, is the rate-limiting enzyme in prostaglandin synthesis, and the function of this enzyme is thought to relate to inflammatory processes and carcinogenesis. To understand the role of COX enzyme in gastric cancer, we measured COX-2 expression in 104 human gastric carcinoma tissues by immunohistochemical analysis. We obtained tissue specimens from 104 surgically resected gastric adenocarcinoma patients. We performed immunohistochemical stain for human COX-2 with polyclonal antibody in gastric carcinoma. After curative resection and extensive lymph node dissection, all patients received adjuvant chemotherapy containing 5-fluorouracil. Expression of COX-2 showed cytoplasmic staining, not only in cancer cells but also in precancerous lesions such as metaplastic and adenomatous cells. We confirmed up-regulation of COX-2 in gastric cancer tissues compared with normal paired mucosa using Western blot analysis. There was no correlation between clinicopathological characteristics of gastric cancer patients and intensity of COX-2 protein expression. This study indicates that COX-2 protein over-expression may contribute to an early event of gastric cancer development, and it further suggests that selective inhibition of COX-2 may provide a chemopreventive effect against gastric carcinogenesis.     

Relationship between area of serosal invasion and prognosis in patients with gastric carcinoma

We examined the relationship between the spatial extent of invasion of the gastric serosa in patients with gastric carcinoma and their postoperative 5-year survival rate. At the time of surgical resection of gastric cancer, intraperitoneal free cancer cells were detected by lavage of the Douglas cavity in 135 of 309 (44%) patients with gross evidence of serosal invasion. Examination of the relationship between the presence of intraperitoneal free cancer cells and serosal area invaded by the tumor revealed that only 22% of cases with an area of serosal invasion 10 cm2 or less were positive for free cancer cells, but such cells were found in 72% of cases with an area of serosal invasion greater than 20 cm2. The 5-year survival rate was 31% in patients with an area of serosal invasion of less than 10 cm2, whereas the rate was only 8% in patients with an area of serosal invasion greater than 20 cm2. Not only the presence of serosal invasion by a tumor but also the spatial extent of the invasion are significant factors that influence the prognosis of patients with gastric carcinoma.     

贲门癌组织环氧合酶-2的表达与血管生成的关系

目的：探讨环氧合酶-2（cyclooxygenase-2，Cox-2）在贲门癌组织的表达及其与肿瘤血管生成的关系。方法：采用免疫组织化学法检测贲门癌手术切除标本46例和癌旁正常黏膜21例中的Cox-2表达情况，采用抗CD34抗体标记微血管内皮细胞，计算徽血管密度（microvascular density，MVD）。统计学分析Cox-2表达以及MVD与贲门癌主要临床病理特征的相关性。结果：贲门癌组织Cox-2阳性表达率和MVD值分别为80．4％、31．95&#177;3．87，显著高于癌旁正常黏膜的14．3％、16．28&#177;1．55（P〈0．01）。Cox-2的表达以及MVD值与肿瘤临床TNM分期和淋巴结转移密切相关。Spearman等级相关分析表明，MVD与Cox-2表达呈显著正相关。结论：Cox-2异常表达及其诱导的血管生成在贲门癌的侵袭和淋巴结转移中起着重要作用．     

胃癌组织中环氧合酶-2表达及其与P-gp表达相关性的研究

目的 :探讨环氧合酶 2 (COX 2 )蛋白在胃癌组织中的表达 ,并探讨COX 2对P糖蛋白 (P gp)表达的影响。方法 :应用免疫组织化学方法检测 4 8例胃癌及 10例正常胃组织中COX 2蛋白与P gp蛋白的表达。结果 :正常胃组织中未见COX 2表达 ,胃癌组织中COX 2阳性率为 6 0 .4 % (2 9/ 4 8) ,其阳性表达与肿瘤的TNM分期及淋巴结转移相关 (P <0 .0 5 )。COX 2阳性组中P gp表达阳性率为 82 .8% (2 4 / 2 9) ,而COX 2阴性组P gp同时阴性率 6 3.2 %(12 / 19) ,两者有高度正相关性 ,相关系数r=0 .4 70 (P <0 .0 1)。结论 :COX 2蛋白的表达参与胃癌的发生及恶性进展 ,并可能干预P gp表达 ,参与对肿瘤的多药耐药 (MDR)的调节作用     

环氧化酶-2的表达与胃癌浸润转移的关系

目的　探讨环氧化酶 - 2 (cyclooxygenase- 2 ,COX- 2 )在胃癌组织中的表达与胃癌浸润转移的关系。方法　采用免疫组化 S- P法检测 4 5例胃癌手术切除标本 COX- 2的阳性表达。结果　胃癌组织 COX- 2的阳性表达率(77.8% )明显高于癌旁组织 (33.3% ,P<0 .0 1)。有局部淋巴结转移者 COX- 2的阳性表达率明显高于无转移者 (分别为 86 .1%和 4 4 .4 % ,P<0 .0 5 ) ;浸润达浆膜层者明显高于未达浆膜层者 (分别为 87.9%和 5 0 .0 % ,P<0 .0 5 ) ; 、 期胃癌组织明显高于 、 期 (分别为 90 .9%和 4 1.7% ,P<0 .0 5 )。结论　 COX- 2与胃癌的发生有关 ,COX- 2的表达在胃癌浸润和转移过程中显示重要作用     

Expression of cyclooxygenase-2 and matrix metalloproteinase-9 in gastric carcinoma and its correlation with angiogenesis

OBJECTIVE: To investigate the expression of cyclooxygenase (COX)-2 and matrix metalloproteinase (MMP)-9 in gastric carcinomas, and to correlate this expression with clinicopathological parameters and angiogenesis. METHODS: Ninety-six resected tumor specimens from patients with gastric carcinoma were obtained, and 30 corresponding paracancerous normal tissues were randomly selected as a control. Immunohistochemical staining was used for detecting the expression of COX-2 and MMP-9. Monoclonal antibody against CD34 was used for displaying vascular endothelial cells, and microvascular density (MVD) was calculated by counting of CD34-positive vascular endothelial cells. RESULTS: The positive expression rates of COX-2, MMP-9 and MVD in the cancerous tissue were 80.2%, 74.0%, and 32.5 +/- 8.3, respectively, which were significantly higher than those in the normal tissue (P < 0.01). COX-2, MMP-9 expression rates and MVD in the patients with stages III and IV were 91.4%, 84.5% and 34.9 +/- 8.7, respectively, which were significantly higher than those in the patients with stages I and II (P < 0.01). In addition, the Spearman rank correlation test showed that tumor MVD was closely associated with COX-2 (r = 0.311, P < 0.01) and MMP-9 (r = 0.349, P < 0.01) expressions. CONCLUSIONS: Overexpression of COX-2 and MMP-9 is related to tumor invasion and lymph node metastasis in the gastric carcinoma. These results provide evidence that COX-2 contribute to gastric cancer development by promoting MMP-9 expression and angiogenesis.     

血清bFGF和MMP-2与鼻咽癌浸润转移的相关性

目的 探讨碱性成纤维细胞生长因子(bFGF)、基质金属蛋白酶-2(MMP-2)与鼻咽癌浸润转移的相关性.方法 采用酶联免疫吸附试验(ELISA)方法分别检测63例鼻咽癌患者放疗前后及20例健康体检者血清中bFGF、MMP-2水平,比较2个指标的表达水平与鼻咽癌放疗前后及放疗前临床特征间的关系.结果 鼻咽癌患者放疗前血清bFGF、MMP-2表达水平分别明显高于健康体检者(P＜0.01),也明显高于同组患者放疗后血清bFGF、MMP-2表达水平(P＜0.01),鼻咽癌患者放疗后血清bFGF、MMP-2表达水平虽比健康体检者高,但差异无统计学意义(P＞0.05).鼻咽癌患者放疗前血清bFGF、MMP-2表达水平随临床分期、淋巴结转移、远处转移而增加.鼻咽癌患者放疗前血清bFGF、MMP-2表达水平呈正相关(r=0.8748,P＜0.01).结论 血清bFGF、MMP-2表达水平在一定程度上反映鼻咽癌发生、发展、浸润转移情况,联合检测bFGF、MMP-2具有协同评估作用,对鼻咽癌的浸润转移的预测具有重要参考价值.     

Prognostic role of cyclooxygenase-2 in neoadjuvant-treated patients with squamous cell carcinoma of the esophagus

Based on our previous demonstration that elevated cyclooxygenase-2 (COX-2) expression is a prognostic factor for reduced survival in patients with adenocarcinoma of the esophagus, the aim of our study was to analyze the role of COX-2 expression in esophageal squamous cell carcinoma. We analyzed COX-2 protein expression from 117 consecutive patients by immunohistochemistry using a COX-2 specific monoclonal antibody. Eighty-one patients had not received any therapy before surgery whereas 36 patients received neoadjuvant chemotherapy as part of a randomized controlled trial. In the patients who received no chemotherapy, COX-2 expression was low in 75% and high in 25% of the specimens. In this patient group, high COX-2 expression associated with distal location of the tumor (p = 0.02), but did not correlate with any other clinicopathological parameter tested, including overall survival. In the patient group who received neoadjuvant chemotherapy, postoperative COX-2 expression was low in 69% and high in 31%. Interestingly, in this patient group low COX-2 expression correlated with development of distant metastases (p = 0.03) and to reduced overall survival (p = 0.02). Our results show that the prognostic significance of COX-2 depends on the histological type of esophageal carcinoma and preoperative treatment of the patient. In conclusion, COX-2 is not a prognostic marker in squamous cell carcinoma of the esophagus, but low COX-2 expression is associated with poor prognosis in the neoadjuvant-treated patients.     

Selective cyclooxygenase-2 inhibitor downregulates the paracrine epithelial-mesenchymal interactions of growth in scirrhous gastric carcinoma

The importance of cancer-mesenchymal interactions in the aggressive behavior of scirrhous gastric cancer is supported by experimental and clinical evidences. We have previously reported that gastric fibroblasts secretion of keratinocyte growth factor (KGF) underline the remarkable proliferation of scirrhous gastric cancer cells. Cyclooxygenase-2 (COX-2) is not only expressed in cancer cells, but also in interstitial fibroblasts in gastric carcinoma. To clarify the mechanisms responsible for the antiproliferation effect of COX-2 inhibitors, effect of COX-2 inhibitor on the paracrine epithelial-mesenchymal interactions of growth was examined. Scirrhous gastric cancer cell line, OCUM-2M, gastric fibroblasts, NF-21, and COX-2 inhibitor, JTE-522, were used. Growth-interaction was examined by calculating the number of cancer cells or by measuring [(3)H] thymidine incorporation of cancer cells. Effect of JTE-522 on KGF expression from NF-21 cells and OCUM-2M cells was analyzed by ELISA and RT-PCR. The conditioned medium from gastric fibroblasts significantly stimulated the growth of scirrhous gastric cancer cells. JTE-522 at the concentrations of 10(-5) and 10(-6) M significantly decreased the growth-stimulating activity of gastric fibroblasts. JTE-522 reduced the expression of KGF mRNA and the production of KGF from gastric fibroblasts. Oral administration of JTE-522 significantly decreased the size of xenografted tumor coinoculated with OCUM-2M cells and NF-21 cells in nude mice. JTE-522 decreased COX-2 expression and Ki67 labeling index within the coinoculated tumor. These findings suggested that a selective COX-2 inhibitor, JTE-522, downregulates KGF production from gastric fibroblasts, resulting in the inhibition of paracrine epithelial-mesenchymal interactions of proliferation between scirrhous gastric cancer cells and gastric fibroblasts.     

Submucosal invasion in gastric carcinoma of the fundic area

Gastric carcinoma of the undifferentiated type in the fundic gland area has a higher tendency for submucosal invasion than carcinoma located in the pyloric gland area. To investigate whether a similar tendency is present also in a cancerous focus, we studied 147 patients with early gastric carcinomas with submucosal invasion. Out of 27 undifferentiated carcinomas located in the intermediate zone, 20 (54%) showed peripheral submucosal invasion; in 16(80%) of these, the invasion was located near or in the fundic gland area. These results indicate that submucosal invasion is more likely to occur towards the fundic area.     

Serum antioxidative vitamin levels and lipid peroxidation in gastric carcinoma patients

Serum antioxidative vitamin levels and lipid peroxidation in gastric cancer patients were compared with values for age-matched healthy subjects. Blood samples were collected from the stomach of cancer patients scheduled for surgical removal of their tumor. Serum ascorbic acid, alpha-tocopherol, beta-carotene, and retinol in serum were determined by high-performance liquid chromatography, and malondialdehyde levels were analyzed spectrophotometrically. General health characteristics and taste preference for spicy and/or salty food were assessed by a self-administered questionnaire. Significant decreases in serum ascorbic acid and beta carotene were observed in stomach cancer patient as compared to the control group. The levels of ascorbic acid in patients with gastric carcinoma were less than one-fifth of the control. Beta carotene and alpha-tocopherol levels in the serum of the cancer patients were significantly decreased compared to the control group, but there were no differences in retinol between the groups. Serum malondialdehyde levels were significantly higher in the cancer patients than in controls. The levels of ascorbic acid and alpha-tocopherol tend to be lower in the patient with a preference for spicy and salty food than in others without the preference. Our results demonstrate that a correlation existed between the levels of serum ascorbic acid and beta carotene, alpha-tocopherol and lipid peroxidation in gastric carcinoma.     

COX-2、VEGF在胃癌中的表达及其预后意义

目的 :研究COX 2、VEGF表达对胃癌的预后意义。方法 :收集我院 1990～ 1999年早、中期胃癌 2 81例 ,对有完整存档蜡块资料的 2 32例进行免疫组织化学染色。检测COX 2、VEGF及MVD在胃癌组织中的表达 ,并分析其预后意义。结果 :胃癌组织中COX 2、VEGF阳性表达的MVD值均显著高于COX 2、VEGF阴性表达者(P <0 0 1) ;COX 2、VEGF阳性表达及MVD值与胃癌淋巴结转移、血管浸润均密切相关 (P <0 0 1) ;COX 2、VEGF阳性表达者五年生存率明显低于阴性者 (P <0 0 1)。多因素分析显示 ,VEGF表达、淋巴结转移、COX 2表达、浸润深度、血管浸润均为胃癌独立的预后因素。结论 :COX 2、VEGF在胃癌组织呈过度表达状态 ,与胃癌的生长和浸润转移关系密切 ,可以作为反映胃癌生物学行为和判断预后的有效指标。     

进展期胃癌组织中COX-2表达与树突状细胞浸润的相关性研究

目的:探讨环氧化酶-2(cyclooxygen-ase-2,COX-2)在进展期胃癌中的表达及其与树突状细胞(dendritic cells,DCs)浸润关系的临床意义。方法:收集我院接受胃癌根治标本31例,采用免疫组织化学SP法检测COX-2表达及其与DCs浸润程度的关系。结果:COX-2在胃癌中的表达率为67.74%(21/31),对照组为19.35(6/31),两者比较差异有统计学意义,P=0.000;淋巴结转移组COX-2表达率为91.67%,无淋巴结转移组COX-2表达率为52.63%,两者比较差异有统计学意义,P=0.046。淋巴结转移组DCs的浸润数量为9.50±2.28,无淋巴结转移组DCs的浸润数量为7.53±2.14,两者比较差异有统计学意义,P=0.021。而与胃癌患者的年龄、肿瘤的大小、浸润深度和肿瘤的分化无关,P>0.05;DCs低浸润组的COX-2阳性表达率为88.24%,DCs高浸润组的COX-2阳性表达率为42.86%,两者差异有统计学意义,P=0.018。结论:胃癌中COX-2表达与DCs浸润与胃癌的预后有关,并且两者之间有一定的相关性。     

胃癌组织中COX-2蛋白的表达研究

目的:探讨胃癌组织中环氧化酶-2(cyclooxygenase-2,COX-2)蛋白的表达及其与胃癌临床病理参数间的关系.方法:应用免疫组化Envision法检测手术切除的85例胃癌标本中COX-2蛋白的表达.结果:COX-2蛋白在85例胃癌标本中阳性表达率为81.2%(69/85).COX-2蛋白表达与患者的性别、年龄、肿瘤生长部位、分化程度、淋巴结转移及神经是否侵犯无明显相关性(P＞0.05).COX-2蛋白表达与肿瘤大小、Lauren分型、侵犯深度、脉管受侵及肿瘤病理分期显著相关(P＜0.05).结论:COX-2蛋白的表达与胃癌发生、发展、侵袭、转移等相关,可作为反应胃癌生物学行为的指标之一.