CEA levels in peritoneal washings from gastric cancer patients as a prognostic guide

Carcinoembryonic antigen (CEA) levels were determined in the peritoneal washings from 44 patients with gastric cancer to evaluate the usefulness for a predictor of postsurgical prognosis. Seventeen of the 21 patients (80.9%) with serosal invasion showed elevated levels of CEA, whereas most of the patients with no serosal invasion (22/23) showed low levels of CEA and did not develop peritoneal metastasis. All patients with positive cytology showed elevated levels of CEA in the peritoneal washings. Therefore, CEA levels in the peritoneal washings could be an adjunctive tool for predicting the postsurgical prognosis in gastric cancer.     

CEA mRNA,CEA蛋白及细胞学检测胃癌腹腔液中游离癌细胞的初步 …

目的 比较腹腔冲洗液中ＣＥＡ ｍＲＮＡ、ＣＥＡ蛋白和细胞学检测游离癌细胞及预测腹膜转移的应用价值。方法 术中收集４３例胃癌和１０例胃良性病变的腹水或腹腔冲洗液，分别采用ＲＴ－ＰＣＲ方法检测检测腹腔液中游离癌细胞ＣＥＡ ｍＲＮＡ表达，放射免疫检测上清液中ＣＥＡ蛋白含量（ｐ－ＣＥＡ），同时做腹腔冲细胞学（ｐｅｒｉｔｏｎｅａｌ ｌａｖａｇｅ ｃｙｔｏｌｏｇｙ，ＰＬＣ）检查，结果 ＣＥＡ ｍＲＮＡ表达阳性     

Prognostic significance of tumor markers in peritoneal lavage in advanced gastric cancer

OBJECTIVE: Predicting peritoneal dissemination of cancer is very difficult whatever method of examination is used. Recently, a cytological examination of peritoneal lavage has been shown to be a feasible measure to predict an early state of peritoneal seeding. The predictive value of the levels of tumor markers in peritoneal lavage for peritoneal metastasis from gastric carcinoma was thus studied. METHODS: In 229 patients gastric cancer tumor markers, CEA, CA 125, and CA 19-9, in peritoneal lavage were intraoperatively evaluated using a chemiluminescent enzyme immunoassay. RESULTS: CEA in peritoneal lavage at a cutoff level of 0.5 ng/ml showed overall a higher sensitivity of 75.8% at a specificity of 90.8% for a diagnosis of peritoneal dissemination including cytologically positive peritoneal lavage [CY(+)] than CA 125 or CA 19-9 in peritoneal lavage. The CEA level in peritoneal lavage as well as both serosal invasion and the CA 125 level in peritoneal lavage were significant factors for the prediction of peritoneal dissemination including CY(+) with a relative risk of 6.6, 14.1 and 9.4. In patients undergoing curative operations, the recurrence rate for peritoneal dissemination and liver metastasis in cases with CEA levels in peritoneal lavage of > or = 0.5 ng/ml was significantly higher than that in cases with CEA levels of < 0.5 ng/ml (p < 0.0001, p < 0.002). CONCLUSIONS: These finding suggest that the CEA level in peritoneal lavage is thus considered to be a predictor of peritoneal dissemination including CY(+).     

CEA mRNA、CEA蛋白及细胞学检测胃癌腹腔液中游离癌细胞的初步评价

目的　比较腹腔冲洗液中CEAmRNA、CEA蛋白和细胞学检测游离癌细胞及预测腹膜转移的应用价值。方法　术中收集 43例胃癌和 10例胃良性病变的腹水或腹腔冲洗液 ,分别采用RT PCR方法测定腹腔液中游离癌细胞CEAmRNA表达 ,放射免疫检测上清液中CEA蛋白含量 (p CEA) ,同时做腹腔冲洗细胞学 (peritoneallavagecytology ,PLC)检查。结果　CEAmRNA表达阳性率 (5 6 .3% )明显高于p CEA (38.1% )或PLC (33.0 % ,P <0 .0 5～ 0 .0 1)。CEAmRNA表达量随侵袭深度、病期进展而增加 (P <0 .0 5 ) ,因大体类型、浆膜类型不同 ,其阳性表达级别差异有显著性 (P <0 .0 5 )。结论　三种方法均适用于胃癌腹腔脱落癌细胞的诊断或腹膜转移的预测 ,但对微量癌细胞检出的灵敏性 ,以RT PCR方法为优。     

Effectiveness of continuous hyperthermic peritoneal perfusion for the peritoneal dissemination of gastric cancer

We investigated the effectiveness of continuous hyperthermic peritoneal perfusion (CHPP) for the peritoneal dissemination of gastric cancer. A total 124 patients with advanced gastric cancer were enrolled in this study. Prophylactic CHPP (P-CHPP) was performed in 45 patients who had macroscopic serosal invasion without peritoneal dissemination, and 79 patients without CHPP were a control group. Therapeutic CHPP (T-CHPP) was performed in 21 patients with peritoneal dissemination, and 52 patients without CHPP were a control group. There was no significant difference in 5 year survival between patients treated and not treated with P-CHPP. Univariate analysis showed that location of tumor, tumor diameter, and lymph node metastasis influenced prognosis, but there was no prognostic factor in the Cox proportional regression hazard model. There was no significant difference in 5-year survival between patients treated and not treated with T-CHPP. Univariate analysis showed that degree of peritoneal dissemination and adjuvant chemotherapy influenced prognosis, and the Cox proportional regression hazard model showed that the macroscopic types and degree of peritoneal dissemination affected prognosis. In the patients with CHPP, the incidences of respiratory failure and renal failure were each statistically greater than in the patients undergoing CHPP.     

胃癌腹腔灌洗液CEA测定的临床意义

检测50例胃癌和10例胃良性病变腹腔灌洗液CEA及脱落细胞，CEA临界值定为115ng/g蛋白。结果：胃癌腹膜种植、侵及装膜、未侵及浆膜，CEA阳性率分别为88．9％、55．8％、13．3％。三者差异显著（P＜0.01）。CEA阳性组2年1存率（29．2％），显著低于阴性组（88．5％）（P＜0．05）。提示腹腔灌洗液CEA检测比脱落细胞检查更准确、敏感，是判断腹膜隐性播散和预后的一种好方法。     

大肠癌腹腔CEA测定的临床意义

目的：为了探讨如何早期发现腹腔内隐匿性播散。方法：应用放射免疫法检测60例大肠癌的腹腔CEA与血清CEA值，CEA临界值定为15ng/ml。结果：大肠癌腹膜播散，浸润浆膜、未侵入浆膜，腹腔CEA阳性率分别为81．8%、54．5%、22．2%。三者差异显著（P＜0．01）。CEA阳性组2年生存率（29．1%）显著低于阴性组（88．9%）（P＜0．01）。结论：腹膜CEA检测比血清CEA检测更准确敏感，是判断腹腔内播散和预后的一种好方法。     

A novel rapid colorimetric assay of carcinoembryonic antigen levels in the abdominal cavity to detect peritoneal micrometastasis during gastric cancer surgery

We showed that the carcinoembryonic antigen (CEA) level in a peritoneal washing is an indicator of the postoperative survival of gastric cancer patients. On the premise that the polyvinylidine difluoride membrane adsorbs a fixed quantity of protein, this study was designed to produce a rapid, colorimetric, semi-quantitative assay of peritoneal CEA levels by using anti-CEA antibodies. At the time of laparotomy, peritoneal washings were collected from 60 gastric cancer patients, and CEA levels were determined by our assay and by an enzyme immunoassay (EIA) method. The accuracy of our method corresponded with the results of the EIA method. All the cases with high levels of CEA in the peritoneal washings showed positive color changes. Our new assay had no relation to protein concentrations of the samples. The assay makes use of diluted peritoneal washings without adaptation by protein concentration. The measurement can be completed in the operating room within 30 min. As a result, this assay can detect peritoneal microdissemination easily during surgery, and it can be used as an indication of intraoperative chemotherapy against peritoneal micrometastasis.     

检测胃癌患者腹腔冲洗液中癌胚抗原mRNA和细胞角蛋白20 mRNA的临床意义

目的探讨采用巢式逆转录聚合酶链反应(RT-PCR)检测胃癌患者腹腔冲洗液中癌胚抗原(CEA)mRNA和细胞角蛋白20(CK-20)mRNA的临床价值。方法收集80例胃癌患者和10例胃良性病变患者的腹腔冲洗液或腹水,常规行HE染色细胞学检查,采用巢式RT-PCR方法检测腹腔冲洗液中CEA mRNA和CK-20 mRNA的表达,并以人胃癌细胞株SGC-7901作为阳性对照。结果80例胃癌患者腹腔冲洗液中CEA mRNA的阳性表达率为52.5%(42/80),CK-20 mRNA的阳性表达率为57.5%(46/80),CEA mRNA和CK-20 mRNA的联合检测阳性率为70.0%(56/80),皆高于腹腔冲洗液细胞学(PLC)检查的27.5%(22/80,P<0.05),且22例PLC检查阳性患者的CEA mRNA和CK-20 mRNA检测结果均为阳性。CEA mRNA和CK-20 mRNA的阳性率与淋巴结转移和TNM分期明显相关(P<0.05)。结论巢式RT-PCR检测胃癌患者腹腔冲洗液中CEA和CK-20基因,可以提高腹腔内游离癌细胞(IFCCs)的检测灵敏度和特异度,对于早期诊断胃癌腹膜微转移有一定的临床价值,可为手术方式选择及术中、术后化疗提供依据。     

Type IV collagen levels are elevated in the serum of patients with peritoneal dissemination of gastric cancer

Type III procollagen (amino-terminal propeptide of procollagen type III) and type IV collagen are considered to be reliable serum markers for monitoring the progression of liver fibrosis. The peritoneal dissemination of gastric cancer is also characterised by abundant collagen deposition in the peritoneum. The present study was performed to investigate the potential of serum type III procollagen and IV collagen as biomarkers for peritoneal dissemination in gastric cancer. The study population consisted of 117 patients with gastric cancer: 32 patients had peritoneal dissemination which was pathologically diagnosed by laparotomy or laparoscopic examination, while 85 patients (45/40, early/advanced gastric cancer) had no peritoneal dissemination. We measured the serum levels of type III procollagen and type IV collagen in comparison to the commonly accepted tumor markers carcinoembryonic (CEA), carbohydrate antigen (CA)19-9 and CA125. The median type III procollagen levels showed no significant differences between the two groups, whereas the median type IV collagen levels were significantly (201 ng/ml) higher in patients with than in those without peritoneal dissemination (early/advanced gastric cancer, 124/136 ng/ml) (P<0.05). In receiver operating characteristic (ROC) curve analysis, type IV collagen had the largest area under the curve (0.83), followed by CA125 (0.72), CA19-9 (0.64), CEA (0.59) and type III procollagen (0.48). Type IV collagen was an independent marker (P<0.0001, odds ratio 15.7) for predicting peritoneal dissemination along with CA125 (P=0.0086, odds ratio 9.4) based on multivariate logistic regression. In conclusion, serum type IV collagen levels may be significant in the early detection and management of patients with peritoneal dissemination of gastric cancer.     

Quantitative molecular diagnosis of peritoneal lavage fluid for prediction of peritoneal recurrence in gastric cancer

We developed a quantitative multiple-marker RT-PCR assay for sensitive detection of free cancer cells in the peritoneal cavity and examined the significance of this molecular diagnostic technique for detection and prediction of peritoneal dissemination in patients with gastric cancer. Preoperative peritoneal lavage fluid samples obtained from 129 patients with gastric cancer were subjected to RT-PCR assay with primers specific for carcinoembryonic antigen (CEA) and cytokeratin-20 (CK-20), and conventional cytological examination with Papanicolaou staining. The multi-marker RT-PCR assay was positive in 59 of 129 (46%) gastric cancer patients, whereas conventional cytology was positive in only 9 of 129 (7%) patients. Thirty-two of 129 (22%) patients suffered disease recurrence after surgery. Twenty-one of these patients were confirmed to have had peritoneal recurrence. Although conventional cytology was positive on peritoneal washes in only 9 patients, the RT-PCR assay was positive in 20 of these 21 patients. Furthermore, in cases with negative cytology, patients with PCR-positive findings in peritoneal lavage fluid had a significantly poorer prognosis than those with negative PCR, mainly because of peritoneal recurrence. Our results suggest that the multiplex RT-PCR assay for CEA and CK-20 was highly sensitive for detection and might be useful for prediction of peritoneal dissemination in gastric cancer.     

Prognostic value of carcinoembryonic antigen, CA 19-9 and CA 72-4 in gastric carcinoma.

The prognostic value of preoperative serum levels of carcinoembryonic antigen (CEA), CA 19-9 and CA 72-4 tumor markers was investigated in patients with gastric cancer. Eighty-two patients who underwent surgical resection of gastric cancer were entered in the study. Correlation analyses showed that CA 72-4 was more frequently positive in patients with advanced tumors (p = 0.04), lymph node invasion (p = 0.02), liver metastasis (p = 0.02) and peritoneal involvement (p = 0.03). CA 19-9 was more frequently positive in patients with advanced tumors (p = 0.01) and with serosal (p = 0.04), lymph node (p = 0.008) and peritoneal involvement (p = 0.02). CEA was more frequently positive in patients with liver metastasis (p = 0.03). Low 3-year cumulative survival was significantly associated with elevated serum levels of CA 72-4 (p = 0.004), CA 19-9 (p = 0.001) and CEA (p < 0.001). Age, tumor stage and CA 72-4 provided prognostic information in the multivariate analysis. Patients with elevated serum levels of CA 72-4 showed a 4.2 times higher risk of death than patients with low levels of the marker. Our results suggest that CA 72-4 has prognostic value in gastric cancer, and patients with a high preoperative serum level of CA 72-4 have a greater risk of death due to gastric cancer.     

Correlation of peritoneal dissemination and integrin alpha 3 expression in gastric cancer

To clarify the interrelationship between alpha 3 integrin, subunit/E-cadherin expression and peritoneal dissemination in gastric cancer, alpha 3 integrin subunit and E-cadherin expression gas were immunohistochemically examined and were correlated with clinicopathologic parameters. Among 150 primary gastric cancers, alpha 3 integrin subunit and E-cadherin were strongly expressed in 96 (65%) and 88 (59%) tumors, respectively. Integrin alpha 3 expression was closely associated with peritoneal dissemiantion, but there was no relationship between integrin alpha 3 expression and histologic type, nodal status, macroscopic type or wall invasion. Furthermore, 22 (84%) of 26 tumors which recurred in peritoneum overexpressed integrin alpha 3 expression in primary tumors. All seven peritoneal foci obtained from peritoneal dissemination expressed integrin alpha 3 expression despite no integrin alpha 3 expression in two of these 7 primary tumors. Reduced E-cadherin expression in primary tumors was intimately associated with large tumor size (>6 cm), nodal involvement, peritoneal dissemination and positive serosal invasion. Peritoneal dissemination was most frequently found in the tumors with positive integrin alpha 3 expression and reduced E-cadherin expression. Patients with these type of tumor [E-cadherin expression (-), and integrin alpha 3 subunit (+)] showed the poorest prognosis as compared with the other groups of patients. These results indicate that upregulation of integrin alpha 3 expression and down regulation of E-cadherin might have an important role in the formation of peritoneal dissemination. These tumors have characteristics of easy detachment from the serosal surface via downregulation of E-cadherin and strong adhesion capacity to the peritoneum via up-regulation of integrin alpha 3 expression. The immunohisto-chemical combination analysis of E-cadherin and integrin alpha 3 expression on the primary gastric cancer may be a good screening method to predict peritoneal recurrence.